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Pesticide-Induced Diseases: Body Burden

Most people are unaware that they carry chemical compounds in their bodies. Chemical 'Body Burden' refers to the accumulation of synthetic chemicals found in pesticides, cosmetics, industrial solvents, heavy metals, etc in our bodies. At any given time, hundreds of chemicals can be found in blood, urine, breast milk and even umbilical cord blood. Many of these chemicals enter our bodies through the foods we eat or drink, products we put on our skin and air we breathe. Before birth, people normally carry a body burden inherited from their mothers. Scientists believe the typical human being hosts close to 500 chemicals in various compartments in the body, mostly in fatty tissue. Many chemicals are broken down in our bodies and their metabolites are eliminated, but others linger in our bodies for a lifetime and can increase our risk for certain diseases such as cancer and Parkinson's disease.

Over the past decade, agencies like the Center for Disease Control and Prevention (CDC) have been tracking chemical burden in the general public by analyzing blood and urine. Termed "biomonitoring," it is considered to be the most health-relevant assessment of exposure because they "measure the amount of the chemical that actually gets into people, not the amount that may get into people." Since 2001, CDC releases its "National Report on Human Exposure to Environmental Chemicals" which documents the environmental chemical exposure in the U.S. population.

Jump to: Breast MilkFarmworkers and Farmworker Children • GMOs • Infants/ChildrenObesityOxidative StressSkin Reactions/Diseases • Urine and Other Compartments • Wildlife

Breast Milk

  • Levels of persistent organic pollutants in breast milk of Maya women in Yucatan, Mexico.
    In this study, 24 breast milk samples, obtained from rural Maya women, from municipalities of Yucatan, Mexico, were analyzed for organochlorine pesticide (OCP) residues by gas chromatography. Recent studies have shown that Maya communities have a poor perception about the proper usage and handling of OCP. The karstic soil in this area has a high vulnerability to groundwater pollution by the use of OCP in agriculture and livestock activities. The impact of the ecosystem on human health is much more critical due to the prevailing poverty and a very low educational level of these communities. About 30% of the Maya population consumes water directly from contaminated wells and sinkholes, resulting in a chronic exposure to OCP. The samples served to identify and quantify high levels of OCP residues (18.43 mg/kg of heptachlor epoxide and 1.92 mg/kg of endrin in the metropolitan zone; 2.10 mg/kg of dieldrin, 0.117 mg/kg of endosulfan II, 0.103 mg/kg of heptachlor, 0.178 mg/kg of endrin, and 0.127 mg/kg of endrin aldehyde in the main agricultural zone and on the west coast). The detected levels of OCP residues are a major concern and represent a potential risk to women and children in the region. This could be associated with the high rates of cervical uterine and breast cancer mortality in Yucatan. Thus, regulations on the usage of OCP and their enforcement are necessary, and it is important to establish a yearly monitoring program for OCP residues in breast milk and groundwater, as well as to implement health promotion programs for women in particular and the general population in general.
    [Polanco Rodríguez ÁG, Inmaculada Riba López M, Angel DelValls Casillas T, et al. Environ Monit Assess.189(2):59. ]
  • Levels of persistent organic pollutants in breast milk of Maya women in Yucatan, Mexico.
    In this study, 24 breast milk samples, obtained from rural Maya women, from municipalities of Yucatan, Mexico, were analyzed for organochlorine pesticide (OCP) residues by gas chromatography. Recent studies have shown that Maya communities have a poor perception about the proper usage and handling of OCP. The karstic soil in this area has a high vulnerability to groundwater pollution by the use of OCP in agriculture and livestock activities. The impact of the ecosystem on human health is much more critical due to the prevailing poverty and a very low educational level of these communities. About 30% of the Maya population consumes water directly from contaminated wells and sinkholes, resulting in a chronic exposure to OCP. The samples served to identify and quantify high levels of OCP residues (18.43 mg/kg of heptachlor epoxide and 1.92 mg/kg of endrin in the metropolitan zone; 2.10 mg/kg of dieldrin, 0.117 mg/kg of endosulfan II, 0.103 mg/kg of heptachlor, 0.178 mg/kg of endrin, and 0.127 mg/kg of endrin aldehyde in the main agricultural zone and on the west coast). The detected levels of OCP residues are a major concern and represent a potential risk to women and children in the region. This could be associated with the high rates of cervical uterine and breast cancer mortality in Yucatan. Thus, regulations on the usage of OCP and their enforcement are necessary, and it is important to establish a yearly monitoring program for OCP residues in breast milk and groundwater, as well as to implement health promotion programs for women in particular and the general population in general.
    [Polanco Rodríguez ÁG, Inmaculada Riba López M, Angel DelValls Casillas T, et al. 2017. Environ Monit Assess. 189(2):59]
  • Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human breast milk and associated health risks to nursing infants in Northern Tanzania
    This is the first study to report organochlorines (OCs), including chlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human milk from Tanzania. The main aims of this study were to assess the level of contamination and the possible health risks related to OC exposure in nursing infants from the Northern parts of Tanzania. Ninety-five healthy mother-infant couples attending Mount Meru Regional Referral Hospital (MMRRH), Arusha, Tanzania, were assessed for associations between maternal/infant characteristics, i.e. mother's age, BMI, gestational weight gain, occupation, residence and fetal growth parameters and breast milk levels of OCPs, such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, dieldrin and PCBs. p,p'-DDE and p,p'-DDT were detected in 100% and 75% of the breast milk samples, respectively, and ranged between 24 and 2400ng/g lipid weight (lw) and
    [Müller MH, Polder A, Brynildsrud OB, Karimi M, et al. 2017. Environ Res. 154:425-434]
  • Persistent Environmental Toxicants in Breast Milk and Rapid Infant Growth.
    Many environmental toxicants are passed to infants in utero and through breast milk. Exposure to toxicants during the perinatal period can alter growth patterns, impairing growth or increasing obesity risk. Previous studies have focused on only a few toxicants at a time, which may confound results. We investigated levels of 26 toxicants in breast milk and their associations with rapid infant growth, a risk factor for later obesity.We used data from the Norwegian HUMIS study, a multi-center cohort of 2,606 mothers and newborns enrolled between 2002 and 2008. Milk samples collected 1 month after delivery from a subset of 789 women oversampled by overweight were analyzed for toxicants including polychlorinated biphenyls (PCBs), heavy metals, and pesticides. Growth was defined as change in weight-for-age z-score between 0 and 6 months among the HUMIS population, and rapid growth was defined as change in z-score above 0.67. We used a Bayesian variable selection method to determine the exposures that most explained variation in the outcome. Identified toxicants were included in logistic and linear regression models to estimate associations with growth, adjusting for maternal age, smoking, education, pre-pregnancy body mass index (BMI), gestational weight gain, parity, child sex, cumulative breastfeeding, birth weight, gestational age, and preterm status.Of 789 infants, 19.2% displayed rapid growth. The median maternal age was 29.6 years, and the median pre-pregnancy BMI was 24.0 kg/m2, with 45.3% of mothers overweight or obese. Rapid growers were more likely to be firstborn. Hexachlorobenzene, β-hexachlorocyclohexane (β-HCH), and PCB-74 were identified in the variable selection method. An interquartile range (IQR) increase in β-HCH exposure was associated with a lower odds of rapid growth (OR 0.63, 95% CI 0.42-0.94). Newborns exposed to high levels of β-HCH showed reduced infant growth (β = -0.03, 95% CI -0.05 to -0.01 for IQR increase in breast milk concentration). No other significant associations were found. Our results suggest that early life β-HCH exposure may be linked to slowed growth. Further research is warranted on the potential mechanism behind this association and the longer-term metabolic effects of perinatal β-HCH exposure.
    [Criswell R, Lenters V, Mandal S, Stigum H, et al. 2017. Ann Nutr Metab. 70(3):210-216. ]
  • Biological monitoring of Persistent Organic Pollutants in human milk in Israel.
    The Stockholm Convention on Persistent Organic Pollutants (POPs) aims to eliminate or restrict the production and use of POPs around the globe. Human milk, with a relatively high fat content is a preferred matrix for the monitoring of exposure. Breast milk was collected from 52 primipara women, aged 23-35, living in Israel for the last 10 years who gave birth to singleton full term healthy infants. Out of over 50 Persistent Organic Pollutants listed in the analysis, 16, including aldrin, endrin, parlar and mirex were not found at detectable levels in the Israeli pooled sample. For the indicator compounds found at detectable levels, most were lower than those reported in European countries. Since 1982, levels of POPs contamination as measured in breast milk have declined significantly. This is likely due to restrictions on agricultural, industrial, and other uses of many POPs in Israel.
    [Wasser J, Berman T, Lerner-Geva L, et al 2015. Chemosphere. 137:185-91.]
  • Organochlorine pesticide residues in breast milk and maternal psychopathologies and infant growth from suburban area of Ankara, Turkey
    Authors aimed to determine the levels of organochlorine pesticides (OCPs) in the breast milk; to assess the effect of detectable OCPs on maternal-infant characteristics and; to evaluate the relation between OCPs and the maternal psychopathologies [Brief Symptom Inventory (BSI), Postpartum Bonding Questionnaire (PBQ), Mother-to-Infant Bonding Scale (MIBS) and Edinburgh Postnatal Depression Scale (EPDS)] and infant growth. DDT, beta-hexachlorocyclohexane (HCH), aldrin and heptachlor were detected in 89.3, 70.7, 58.7 and 34.7 % of the samples, respectively. Mothers with low monthly family income had detectable DDTs less frequently. The frequencies of detectable heptachlor epoxide were significantly higher in mothers with gestational nausea. Anaemic mothers had more frequently detectable alpha-HCH. Z scores of head circumference were inversely correlated with beta-HCH and DDT levels. The heptachlor epoxide levels were positively correlated with PBQ, MIBS and indexes of BSI. No relation was detected between EPDS and OCPs. Further studies are needed for changes in maternal psychopathologies.
    [Yalçın SS, Örün E, Yalçın S, Aykut O. 2015. Int J Environ Health Res.25(4):364-72.]
  • Organochlorine pesticides and their metabolites in human breast milk from Shanghai, China.
    This study recruited 142 pregnant mothers in 2011-2012 in Shanghai, China, and their breast milk samples were collected during lactation and analyzed for 27 OCP compounds. Detection rates were in a range of 65.5 to 100 %. In particular, metabolites of 2,2-bis(chlorophenyl)-1,1,1-trichloroethane (DDT) such as 2-chloro-1,1-bis(4-chlorophenyl)ethylene (DDMU), 2,2-bis(4-chlorophenyl)ethanol (DDOH), bis(4-chlorophenyl)ketone (DBP), and 4,4'-dichlorodiphenylmethane (DDM) were detected in most milk samples. DDTs, hexachlorobenzene (HCB), and hexachlorocyclohexane (HCH) were dominant OCPs with mean levels of 316, 49.8, and 41.5 ng/g lipid content, respectively, whereas levels of methoxychlor, ∑Drins, ∑Heptachlor, ∑Chlordane, and ∑Endosulfan were fairly low (0.87-5.6 ng/g lipid content). ∑OCPs in this study were much lower than those in human breast milk samples collected in 2002 and 2007. Consumption of higher amounts of fish was associated with higher milk levels of OCPs. Specific OCP patterns in breast milk samples from migrant mothers in Shanghai reflected features of OCP production, use, and exposure in their home provinces.
    [Lu D, Wang D, Ni R, Lin Y, et al. 2015. Environ Sci Pollut Res Int. 22(12):9293-306.]
  • Organochlorine pesticides residue in breast milk: a systematic review.
    This study was conducted to review and compile the results of the studies undertaken in the world which surveyed the organochlorine pesticides residue in breast milk. Thirty articles published between 1980 and 2013 were selected and reviewed.The majority of the reviewed articles indicated the presence of two or more organochlorine pesticides in the collected samples of breast milk. Based on the reviewed studies, dichlorodiphenyltrichloroethane (DDT) had the highest level of concentration in the collected samples of breast milk. Moreover, there was a statistically significant positive correlation between mother's age, her multiparty and concentration of chlorinated pesticides in breast milk.
    [Pirsaheb M, Limoee M, Namdari F, Khamutian R. 2015. Med J Islam Repub Iran. 29:228.]
  • Perinatal exposure to chlordecone, thyroid hormone status and neurodevelopment in infants: the Timoun cohort study in Guadeloupe (French West Indies).
    Aim of the study was to evaluate the impact of perinatal exposure to chlordecone on the thyroid hormone system of a sample of infants from the Timoun mother-child cohort in Guadeloupe and their further neurodevelopment.Chlordecone was measured in cord blood and breast milk samples. Thyroid stimulating hormone (TSH), free tri-iodothyronine (FT3), free thyroxine (FT4) were determined in child blood at 3 months (n=111). Cord chlordecone was associated with an increase in TSH in boys, whereas postnatal exposure was associated with a decrease in FT3 overall, and in FT4 among girls. Higher TSH level at 3 months was positively associated with the ASQ score of fine motor development at 18 months among boys, but TSH did not modify the association between prenatal chlordecone exposure and poorer ASQ fine motor score.
    [Cordier S, Bouquet E, Warembourg C, Massart C, et al. 2015. Environ Res. 138:271-8]
  • Persistent organic pollutants in matched breast milk and infant faeces samples
    To determine whether measuring POPs in faeces might reflect blood concentration during infancy, authors measured the concentrations of a range of POPs (i.e. polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs)) in a pilot study using matched breast milk and infant faecal samples obtained from ten mother–child pairs. All infants were breast fed, with 8 of them also receiving solid food at the time of faecal sampling. In this small dataset faecal concentrations are strongly associated with milk concentrations. Different sources (external or internal) of exposure appeared to directly influence faecal concentrations of different chemicals based on different inter-individual variability in the faeces-to-milk concentration ratio Rfm. Overall, the matrix of faeces as an external measure of internal exposure in infants looks promising for some chemicals and is worth assessing further in larger datasets.
    [Chen Y, Wang X, Li Y, Toms LM, Gallen M, et al. 2015. Chemosphere. 118:309-14.]
  • Estimated infant intake of persistent organic pollutants through breast milk in New Zealand.
    Study aimed to estimate average infant daily intake of chlorinated persistent organic pollutants (POPs) through the consumption of breast milk in New Zealand.Breast milk of 39 first-time mothers aged 20-30 years was collected during 2007-2010 and analysed for persistent organic pollutants including dioxin-like compounds and organochlorine pesticides. Of all POPs quantified, the EDI of DDT (principally in the form of its metabolite p,p'-DDE) was the highest (1.6 mcg/kg/day), and above the tolerable daily intake (TDI) of 0.5 mcg/kg/day. The mean EDI for dioxin-like compounds (including PCDD/Fs and PCBs) was 19.7 pg TEQ(toxic equivalency)/kg/day, which is among the lowest reported worldwide, yet above the TDI of 1 pg TEQ/kg/day. The EDI of HCH, HCB, dieldrin, heptachlor and mirex were 32.9, 37.9, 39.4, 2.0, and 0.9 ng/kg/day respectively, all of which were below the current TDI. Age of the mother was positively associated with higher EDIs for the infant, particularly for total-TEQ and total-DDT.Infant daily intakes of chlorinated POPs through breast milk estimated for New Zealand are low or average by international comparison, and 5 times lower than 25 years ago. Future breast milk monitoring will determine whether this diminishing trend is continuing as well as providing monitoring information on other POPs.
    ['t Mannetje A, Coakley J, Bridgen P, et al. 2014. N Z Med J. 127(1401):56-68.]
  • Monitoring of pesticide residues in human breast milk from Punjab, India and its correlation with health associated parameters.
    This study was undertaken to determine the present status of pesticide residues in breast milk from Punjab. A total of 127 breast milk samples were analyzed and pesticide residues were detected in 25 % of the milk samples. Residues of cyfluthrin, fenvalerate, cypermethrin, profenophos, γ-HCH, β-HCH, chlorpyriphos, monocrotophos, p,p' DDE and phosalone were detected with mean levels of 63.04, 11.69, 3.63, 2.66, 2.64, 2.29, 1.91, 1.63, 0.56 and 0.29 ng g(-1), respectively. Cyfluthrin was leading pesticide detected in breast milk contributing 31.28 % to the total residue load. It was observed that the residue levels were decreasing with increase in parity and age of mother and cyfluthrin had highest mean concentration of 90.63 ng g(-1) in the first parity and 21.11 ng g(-1) in youngest age group. Residue levels were higher in urban population than the rural population although, statistically non-significant difference was found between the two (p > 0.05).
    [Sharma A, Gill JP, Bedi JS, Pooni PA. 2014. Bull Environ Contam Toxicol.93(4):465-71.]
  • Organochlorine pesticide levels in breast milk in Guerrero, Mexico.
    Human breast milk samples were collected from 171 mothers who were residents from Guerrero, Mexico. Median concentrations (mg/kg on fat basis) for the following pesticides were: HCB, 0.009; β-HCH, 0.004; pp'DDE, 0.760; op'DDT, 0.016; pp'DDT, 0.045; and Σ-DDT, 0.833. These values are lower than in other States in Mexico, and in some countries where the use of these pesticides was banned more than 30 years ago. Differences were found in HCB, pp'DDE and pp'DDT concentrations in groups divided according to age. The older age groups had higher concentrations, except for the comparison between groups 21-23/24-28 years, which were 0.913 and 0.530 mg/kg of pp'DDE, respectively. Given the restrictions on use, a greater decrease in organochlorine pesticide levels in human milk is expected in a few years.
    [Chávez-Almazán LA1, Diaz-Ortiz J, Alarcón-Romero M, et al. 2014. Bull Environ Contam Toxicol.93(3):294-8.]
  • Polychlorinated biphenyls and organochlorine pesticides in human milk samples from two regions in Croatia.
    Study analyzed 20 polychlorinated biphenyls (PCBs) and seven organochlorine pesticides (OCPs) in milk samples collected during 2009-2011 from primiparae living in two different regions in Croatia. p,p'-DDE is the dominant organochlorine pesticide. α-HCH/γ-HCH and p,p'-DDE/p,p'-DDT ratios indicate that there is fresh input of γ-HCH in investigated population on both locations, while this is not applicable to p,p'-DDT. The PCB profile was dominated by higher chlorinated congeners. Non-ortho PCB congeners which have the highest TEF values were not detected in any of individual samples. Toxic equivalents for mono-ortho substituted PCB congeners indicated higher exposure to toxic PCBs in Zadar, but estimated daily intakes for both locations indicate that infants consuming mother's milk are not at risk of adverse effects caused by PCBs and OCPs.
    [Klinčić D, Herceg Romanić S, Matek Sarić M, et al. 2014. Environ Toxicol Pharmacol. 37(2):543-52]
  • Contamination of polychlorinated biphenyls and organochlorine pesticides in breast milk in Korea: time-course variation, influencing factors, and exposure assessment.
    Breast milk is a noninvasive specimen to assess maternal and infant exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). In this study, 206 breast milk samples were collected from 87 participants during lactation, at <7, 15, 30, or 90 days postpartum in four cities in Korea. The total concentrations of PCBs (ΣPCB) and OCPs (ΣOCP) ranged from <LOQ to 84.0 (median: 12.1) ng g(-1) lipid weight and from <LOQ to 559 (median: 144) ng g(-1) lipid weight, respectively. The residue levels of these contaminants measured in the study were relatively lower than those reported for European, African and Asian populations. Within a month postpartum typically after day seven the levels of ΣPCB and ΣOCP significantly increased. Some OCP compounds were correlated with maternal age, BMI, parity, and delivery mode. Certain types of dietary habits such as seafood and noodle consumption were significantly associated with ΣPCB and ΣOCP. The estimated daily intakes (EDIs) of ΣPCB and ΣOCP were 45.2-127 ng kg(-1) bw day(-1) and 625-1259 ng kg(-1) bw day(-1) during lactation, respectively, which are lower than the threshold values proposed by the US EPA and Health Canada. The exposure of Korean infants to chlordanes via breast milk had a potential health risk which deserves further investigation.
    [Lee S, Kim S, Lee HK, Lee IS, et al. 2013. Chemosphere.93(8):1578-85.]
  • Cognitive, visual, and motor development of 7-month-old Guadeloupean infants exposed to chlordecone.
    The insecticide chlordecone was extensively used in the French West Indies to control banana root borer. Its persistence in soils has led to the widespread pollution of the environment, and human beings are still exposed to this chemical. Chlordecone has been shown to impair neurological and behavioural functions in rodents when exposed gestationally or neonatally.The aim of the study was to evaluate the impact of prenatal and postnatal exposure to chlordecone on the cognitive, visual, and motor development of 7-month-old infants from Guadeloupe. Infants were tested at 7 months. Visual recognition memory and processing speed were assessed. Samples of cord blood and breast milk at 3 months were analyzed for chlordecone concentrations. Postnatal exposure was determined through breast feeding and frequency of contaminated food consumption by the infants. Cord chlordecone concentrations in tertiles were associated with reduced novelty preference on the FTII in the highly exposed group. Postnatal exposure through contaminated food consumption was marginally related to reduced novelty preference and longer processing speed. Detectable levels of chlordecone in cord blood were associated with higher risk of obtaining low scores on the fine motor development scale.These results suggest that pre- and postnatal low chronic exposure to chlordecone is associated with negative effects on cognitive and motor development during infancy.
    [Dallaire R, Muckle G, Rouget F, et al. 2012. Environ Res. 118:79-85]
  • Estimation of human body concentrations of DDT from indoor residual spraying for malaria control.
    Inhabitants of dwellings treated with DDT for indoor residual spraying show high DDT levels in blood and breast milk. This is of concern since mothers transfer lipid-soluble contaminants such as DDT via breastfeeding to their children. Focusing on DDT use in South Africa, authors employ a pharmacokinetic model to estimate DDT levels in human lipid tissue over the lifetime of an individual to determine the amount of DDT transferred to children during breastfeeding, and to identify the dominant DDT uptake routes. In particular, the effects of breastfeeding duration, parity, and mother's age on DDT concentrations of mother and infant are investigated. Model results show that primiparous mothers have greater DDT concentrations than multiparous mothers, which causes higher DDT exposure of first-born children. DDT in the body mainly originates from diet. Generally, modeled DDT levels reproduce levels found in South African biomonitoring data within a factor of 3.
    [Gyalpo T, Fritsche L, Bouwman H, Bornman R, et al. 2012. Environ Pollut. 169:235-41]
  • Fifteen years of monitoring of POPs in the breast milk, Czech Republic, 1994-2009: trends and factors.
    The breast milk has been recommended to carry out as a monitoring tool for effectiveness evaluation of the Stockholm Convention on Persistent Organic Pollutants (POPs). Polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloro-ethane (DDT) and its metabolites (DDX), hexachlorbenzene (HCB) and isomers of hexachlocyklohexane (HCHs) have been monitored in the breast milk of nursing mothers in the Czech Republic since 1994 as a part of The Environmental Health Monitoring System. The human milk samples (4,753 samples) were analysed for a number of chlorinated organic chemicals including PCBs and selected chlorinated pesticides (OCPs, HCB, HCHs, DDX). The long-term data indicates a continuation of a decreasing trend of POPs concentrations on breast milk. The higher BMI was associated with higher amounts of HCB and lower amounts of higher chlorinated PCBs. The results confirm the effectiveness of restrictions of POPs usage in the Czech Republic. This ongoing long-term study is very useful tool for parametric effectiveness evaluation of Stockholm Convention.
    [Mikeš O, Cupr P, Kohút L, Krsková A, Cerná M. 2012. Environ Sci Pollut Res Int. 19(6):1936-43.]
  • Pyrethroids in human breast milk: occurrence and nursing daily intake estimation.
    There is an assumption that pyrethroid pesticides are converted to non-toxic metabolites by hydrolysis in mammals. However, some recent works have shown their bioaccumulation in human breast milk collected in areas where pyrethroids have been widely used for agriculture or malaria control. In this work, thirteen pyrethroids have been studied in human breast milk samples coming from areas without pyrethroid use for malaria control, such as Brazil, Colombia and Spain. The concentrations of pyrethroids ranged from 1.45 to 24.2 ng g⁻¹ lw. Cypermethrin, λ-cyhalothrin, permethrin and esfenvalerate/fenvalerate were present in all the studied samples. The composition of pyrethroid mixture depended on the country of origin of the samples, bifenthrin being the most abundant in Brazilian samples, λ-cyhalothrin in Colombian and permethrin in Spanish ones. When the pyrethroid concentrations were confronted against the number of gestations, an exponential decay was observed. Moreover, a time trend study was carried out in Brazil, where additional archived pool samples were analyzed, corresponding to years when pyrethroids were applied for dengue epidemic control. In these cases, total pyrethroid levels reached up to 128 ng g⁻¹ lw, and concentrations decreased when massive use was not allowed. Finally, daily intake estimation of nursing infants was calculated in each country and compared to acceptable WHO levels. The estimated daily intakes for nursing infants were always below the acceptable daily intake levels, nevertheless in certain samples the detected concentrations were very close to the maximum acceptable levels.
    [Corcellas C, Feo ML, Torres JP, et al. 2012. Environ Int. 47:17-22.]
  • A pilot study of pesticides and PCBs in the breast milk of women residing in urban and agricultural communities of California.
    In this pilot study authors developed a multiresidue laboratory method to measure non-persistent and persistent pesticides and polychlorinated biphenyl (PCB) congeners in human milk samples from women residing in the agricultural region of Salinas, CA (n = 13) and the urban San Francisco Bay Area, CA (n = 21). Samples were collected from 2002-2007. Median concentrations in pg g(-1) milk among urban and agricultural women, respectively were reported for: chlorpyrifos (24.5 and 28.0), cis-permethrin (81.9 and 103), trans-permethrin (93.1 and 176), hexachlorobenzene (191 and 223), β-hexachlorocyclohexane (220 and 443), o,p'-DDT (36.6 and 62.4), p,p'-DDT,(107 and 102), o,p'-DDE (5.65 and 5.17), p,p'-DDE (3170 and 3490), dacthal (2.79 and 3.43), PCB 118 (92.8 and 17.0), PCB 138 (183 and 38.2), PCB 153 (242 and 43.6) and PCB 180 (239 and 683). Among urban women, median concentrations were 4.02 and 4.32 pg g(-1) milk for chlorpyrifos-methyl and propoxur, respectively. These results suggest that neonates and young children may be exposed to persistent and non-persistent pesticides and PCBs via breast milk.
    [Weldon RH, Barr DB, Trujillo C, et al. 2011. J Environ Monit. 13(11):3136-44.]
  • Concentration of DDT compounds in breast milk from African women (Manhiça, Mozambique) at the early stages of domestic indoor spraying with this insecticide.
    Breast milk concentrations of 4,4'-DDT and its related compounds were studied in samples collected in 2002 and 2006 from two populations of mothers in Manhiça, Mozambique. The 2006 samples were obtained several months after implementation of indoor residual spraying (IRS) with DDT for malaria vector control in dwellings and those from 2002 were taken as reference prior to DDT use. A significant increase in 4,4'-DDT and its main metabolite, 4,4'-DDE, was observed between the 2002 (median values 2.4 and 0.9 ng/ml, respectively) and the 2006 samples (7.3 and 2.6 ng/ml, respectively, p<0.001 and 0.019, respectively). This observation identifies higher body burden intakes of these compounds in pregnant women already in these initial stages of the IRS program. The increase in both 4,4'-DDT and 4,4'-DDE suggest a rapid transformation of DDT into DDE after incorporation of the insecticide residues. The median baseline concentrations in breast milk in 2002 were low, and the median concentrations in 2006 (280 ng/g lipid) were still lower than in other world populations. However, the observed increases were not uniform and in some individuals high values (5100 ng/g lipid) were determined. Significant differences were found between the concentrations of DDT and related compounds in breast milk according to parity, with higher concentrations in primiparae than multiparae women. These differences overcome the age effect in DDT accumulation between the two groups and evidence that women transfer a significant proportion of their body burden of DDT and its metabolites to their infants.
    [Manaca MN, Grimalt JO, Sunyer J, Mandomando I, et al. 2011. Chemosphere. 85(3):307-14.]
  • Long-term biomonitoring of polychlorinated biphenyls and organochlorine pesticides in human milk from mothers living in northern Germany
    Polychlorinated biphenyls (PCBs) and organochlorine pesticides are persistent organic pollutants that have a widespread distribution in the environment. Human biomonitoring is a suitable tool to assess the burden of humans with these substances. Over a time span of 8 years, a free analysis of their milk was offered to lactating mothers residing in the state of Lower Saxony, Germany. The human milk was analyzed for a number of organic chemicals including polychlorinated biphenyls (PCBs), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), hexachlorobenzene (HCB) and ß-hexachlorocyclohexane (ß-HCH). Factors that may influence these levels were investigated using a questionnaire. In total, 4314 samples were collected in the years 1999–2006 and analyzed for their content of these persistent organic pollutants (POPs). A clear downward trend of median total PCB, DDT, ß-HCH and HCB values in all participants and also in different selected subgroups could be observed. There were reductions between 40.9% and 47.1% compared to the year 1999. Among other influencing factors, median concentrations of total PCB, DDT, ß-HCH and HCB showed a clear rise with increasing age of mothers whereas an increasing number of breastfed infants per mother led to a decrease. We conclude that the known declining trend of important xenobiotic substances in human milk of German mothers has continued.
    [Zietz, B.P., et al. 2008. International Journal of Hygiene and Environmental Health 211(5-6): 624-638]
  • From mother to child: Investigation of prenatal and postnatal exposure to persistent bioaccumulating toxicants using breast milk and placenta biomonitoring
    The exposure levels of placenta and paired breast milk samples to selected organochlorine compounds and pesticides from Danish and Finnish samples have been investigated. p,p'-DDE is the dominant pollutant, ß-HCH, hexachlorobenzene, endosulfan-I, dieldrin, oxychlordane, cis-heptachlor epoxide and p,p'-DDT being the other major constituents. Their concentrations are linearly correlated between milk and placenta in similar patterns for Danish and Finnish samples. Milk samples have higher levels of these pollutants than placenta on lipid base. However, the apparently not correlated compounds, such as a-HCH, pentachlorobenzene, pentachloroanisole and methoxychlor, are generally accumulated more in placenta, which may suggest a tissue specific metabolic activity. Thus, depending on the compound of interest, biomonitoring may be done in placenta only or in both matrices.
    [Shen, H., et al. 2007. Chemosphere67(9): S256-S262]
  • Risk assessment of triclosan [Irgasan] in human breast milk.
    Sixty two unselected samples of human milk from Breast Milk Banks in California and Texas have been analysed for triclosan; the concentration ranged from 0 to 2100 microg/kg lipid. A risk assessment of triclosan in human milk has been made, based on a conservative calculation of exposure of neonates and experimental toxicity test results. The maximum exposure of babies via breast milk calculated using very conservative additive assumptions is approximately 7.4 microg/kg/d. The 'Margin of Exposure' between the NOAEL and that calculated in breast fed babies is approximately 6760-fold. It is concluded that there is no evidence to indicate that the presence of a miniscule amount of triclosan in breast milk presents a risk to babies.
    [Dayan AD. 2007. Food Chem Toxicol. 45(1):125-9]
  • Environmental Contaminants in Breast Milk
    Toxic environmental contaminants can be transferred from mother to infant via breastfeeding. Persistent organic pollutants (POPs) are a family of lipophilic stable chemicals that bioaccumulate in adipose tissue and create a lasting toxic body burden. Breastfeeding provides a significant source of exposure to POPs early in human life, the effects of which are unknown, and is the subject of a growing body of research. Despite the possibility of harm from environmental contaminants in breast milk, breastfeeding is still recommended as the best infant feeding method. This article reviews what is known about POPs in breast milk and their effect on infant development to inform clinicians about the issue, provide recommendations for practice, and promote environmental and public health policies that reduce human exposure to harmful pollutants.
    [Nickerson, K. 2006. Journal of Midwifery & Women's Health, 51(1):26–34]
  • Persistent Pesticides in Human Breast Milk and Cryptorchidism
    Prenatal exposure to some pesticides can adversely affect male reproductive health in animals. Study investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children. 62 milk samples from mothers of cryptorchid boys and 68 from mothers of healthy boys were selected. Eight organochlorine pesticides were measurable in all samples for cases/controls: p,p'-DDE, ß-HCH, HCB, a –endosulfan, oxychlordane, p,p'-DDT, dieldrin, cis-HE. Seventeen of 21 organochlorine pesticides were measured in higher median concentrations in case milk than in control milk. Apart from trans-chlordane, there were no significant differences between cryptorchid and healthy boys for individual chemicals. However, combined statistical analysis of the eight most abundant persistent pesticides showed that pesticide levels in breast milk were significantly higher in boys with cryptorchidism. The association between congenital cryptorchidism and some persistent pesticides in breast milk as a proxy for maternal exposure suggests that testicular descent in the fetus may be adversely affected.
    [Damgaard, I et al. 2006. Environ Health Perspect; 114(7): 1133–1138]
  • Human Breast Milk and Xenoestrogen Exposure: A Possible Impact on Human Health
    Human milk is the best natural and optimal food for neonates with several immunologic, developmental and practical advantages throughout childhood. Although the World Health Organization strongly supports breastfeeding, it recognizes the potential health risks posed by the presence of environmental toxicants in breast milk. Contamination of human milk is widespread and due to decades of inadequately controlled pollution by toxicants, persistent pesticides or chemical solvents. These chemicals tend to degrade slowly in the environment, to bioaccumulate in the food chain and to have long half-lives in humans. Many of these environmental pollutants have estrogen-like activities and, thus they are called environmental estrogen disruptors or xenoestrogens. Certain adverse health and reproductive outcomes are attributed to these chemicals in laboratory animals and in wildlife as well as in humans. Here, authors review available data from breast milk monitoring studies suggesting the environmental chemicals that may affect child health through breastfeeding.
    [Massart, F, Harrell, J,C., Federico, G. and Saggese, G.2005. Journal of Perinatology, 25: 282–288]
  • Breastfeeding, exposure to organochlorine compounds, and neurodevelopment in infants.
    Exposure to organochlorine compounds (OCs) occurs both in utero and through breastfeeding. Levels of hexachlorobenzene (HCB) found in the cord serum of newborns from a population located in the vicinity of an electrochemical factory in Spain were among the highest ever reported. This study looked at the association between exposure to OCs and breastfeeding on neurodevelopment in the 1-year-old infants of this population. A birth cohort including 92 mother-infant pairs was recruited between 1997 and 1999 in 5 neighboring villages. The mental and psychomotor development of each infant was assessed at 13 months. OCs were measured in cord serum. Dichlorodiphenyl dichloroethylene (p,p'DDE) cord serum levels were negatively associated with both mental and psychomotor development. For each doubling of a dose of p,p'DDE, study found a resultant decrease of 3.50 points on the mental scale and 4.01 points on the psychomotor scale. Long-term breastfeeding was associated with better performance on both the mental and motor scales. Short-term breastfed infants with higher p,p'DDE levels in cord serum were associated with the lowest scores on both the mental and the psychomotor scales. Prenatal exposure to p,p'DDE was associated with a delay in mental and psychomotor development at 13 months. No association was found for exposure to HCB. Long-term breastfeeding was found to be beneficial to neurodevelopment, potentially counterbalancing the impact of exposure to these chemicals through breast milk.
    [Ribas-Fitó N, Cardo E, Sala M, et al. 2003. Pediatrics.111(5 Pt 1):e580-5.]
  • Chemical contaminants in breast milk: time trends and regional variability
    In this paper the authors review available data on levels of organochlorine pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs), polybrominated diphenyl ethers (PBDEs), metals, and solvents in breast milk. Over the past few decades, levels of the organochlorine pesticides, PCBs, and dioxins have declined in breast milk in countries where these chemicals have been banned or otherwise regulated. In contrast, the levels of PBDEs are rising. Diet is a major factor that influences breast milk levels of persistent organic pollutants, with patterns in fish consumption playing a particularly significant role. Authors conclude, improved global breast milk monitoring programs would allow for more consistent data on trends over time, detection of new xenobiotics in breast milk, and identification of disproportionately exposed populations.
    [Solomon GM, Weiss PM. 2002. Environ Health Perspect.;110(6):A339-47]
  • Triclosan, a commonly used bactericide found in human milk and in the aquatic environment in Sweden.
    High levels of the commonly used, effective bactericide triclosan was found in three out of five randomly selected human milk samples. It was also found in the bile of fish exposed to municipal wastewater and in wild living fish from the receiving waters of the three wastewater treatment plants.
    [Adolfsson-Erici M, Pettersson M, Parkkonen J, Sturve J. 2002. Chemosphere. 46(9-10):1485-9]
  • Pesticides and breast cancer risk: a review of DDT, DDE, and dieldrin.
    There has been interest in evaluating what role environmental chemicals, especially those with evidence of being hormonally active agents, play in breast cancer risk. Organochlorine pesticides have received the most attention because of their persistence in the environment, ability to concentrate up the food chain, continued detection in the food supply and breast milk, and ability to be stored in the adipose tissue of animals and humans. Although several early descriptive studies and a cohort study identified a strong positive association with breast cancer risk and adipose or blood levels of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) and/or its metabolite dichlorodiphenyldichloroethylene (DDE), most of the more recent case—control and nested case—control studies have not supported this association. In this review author discusses these findings and explores how exposure to different forms of DDT with varying estrogenicities may have affected the results of these studies. Author also address how other factors influence the interpretation of the studies on DDT, DDE, and breast cancer risk. These include the effect of analytic methods, dietary factors, menopausal status, use of different types of control populations, lactation history, estrogen receptor status, ethnic/racial subgroups, breast tumor characteristics, and polymorphisms
    [Snedeker, S, M. 2001. Environ Health Perspect; 109(Suppl 1): 35–47]
  • Maternal body burden of organochlorine pesticides and dioxins
    This study investigated the body burden of organochlorine pesticides and dioxins in Japanese women. 125 milk samples were collected from 41 mothers in 1994, 42 in 1995, and 42 in 1996. Dieldrin, heptachor epoxide, oxychlordane, trans-chlordane, and cis-chlordane were detected at lower average levels. Dioxins were detected in all samples. Levels of the analytes also significantly increased depending on mother's age.
    [Nakagawa R, Hirakawa H, Iida T, Matsueda T, Nagayama J. 1999. J AOAC Int.;82(3):716-24]
  • Human milk as a bioindicator for body burden of PCDDs, PCDFs, organochlorine pesticides, and PCBs.
    Researchers collected samples on a voluntary basis from nursing mothers and analyzed them for polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). More than 1400 individual milk samples have been analyzed for organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). The 2 yr investigations revealed somewhat lower levels compared to former years. This might be an indication that the efforts undertaken to minimize dioxin emissions and to shut down known sources have already had an effect on the body burden of humans. Although mostly banned for a considerable period of time now, some lipophilic persistent pesticides such as DDT, dieldrin, hexachlorobenzene (HCB), and hexachlorocyclohexanes (HCH) can still be found in human milk.
    [Fürst P, Fürst C, Wilmers K. 1994. Environ Health Perspect.;102 Suppl 1:187-93]

Farmworkers and Farmworker Children

  • Assessment of Risk Factors for Health Disparities among Latina Farm Workers

    Latina farm workers may experience a unique intersection of social and environmental factors that are known to affect health and well-being. The disadvantages inherent in their gender, race and social class may be compounded by their immigration status, rural location and the hazards of farm work. We propose to identify the most critical risk factors for poor health facing this underserved and understudied population. Our study uses a mixed-methods approach that combines qualitative data from focus groups (n=3 groups of 10 participants each) and semi-structured interviews (n=15) with quantitative and qualitative survey data (n=100) and biological monitoring (n=45). The study includes six domains of inquiry: sociodemographics, food security and food access, housing conditions, social isolation, access to medical care and occupational hazards. Urinary biomonitoring is used to assess exposure to common agricultural pesticides. All study participants identify as Latina or Hispanic and, among those recruited to date (n=25), range in ages from 25 to 71 and report an average of 12 years working in agriculture. While sample and data collection is in progress, preliminary analysis indicate that these participants spend an average of 7.5 months per year employed in agricultural work.Participants report working with a range of crops common in Southern Idaho, including onions, sugarbeets, peas, corn, grapes, and hops. More than 25% of the study participants report that their employers do not provide water, cups and hand washing facilities on a daily basis. Participants report use of backpack and air blast sprayers, and approximately one-third report receiving training from their employers on the use of pesticides. This research will assess the prevalence of social and environmental risk factors among Latina farm workers using an interdisciplinary approach that combines surveys, in-depth interviews and focus groups, biological monitoring and field observations.


    [Curl, C., Meierotto, L. and Som, R., 2019. Research & Practice, 12(5). ]
  • Hearing Loss in Agricultural Workers Exposed to Pesticides and Noise
    Agricultural workers who have concurrent exposure to pesticides and noise are at increased risk of hearing loss. We recruited 163 Thai conventional and 172 organic farmers to answer our questionnaires about personal demographics, agricultural activities, and pesticide and agricultural machinery use. This information was used to calculate the years of conventional (pesticide use) farming and the years of agricultural noise exposure, and to estimate semiquantitative metrics for pesticide exposure (cumulative intensity score-years) and cumulative noise exposure (dB(A)-years) for each conventional farmer. All participants underwent pure tone audiometric testing. The mean hearing threshold in the low-frequency band (0.5–2 kHz) and high-frequency band (3–6 kHz) were used for analysis. Years involved in conventional farming and years using agricultural machinery were associated with an increase in the average hearing threshold for the high-frequency band after controlling for age, ever exposed to industrial noise and cigarette smoking. The highest category of cumulative insecticide exposure (score-years), cumulative organophosphates exposure (score-years) and cumulative noise exposure (dB(A)-years) were also associated with an increased high-frequency band hearing threshold among conventional farmers. Results from the full cohort and the subcohort of conventional farmers support each other and the hypothesis that pesticide and noise have an additive effect on hearing, since no model interactions were significant.
    [Choochouy, N., Kongtip, P., Chantanakul, S., Nankongnab, N., Sujirarat, D. and Woskie, S.R., 2019. Annals of work exposures and health, 63(7), pp.707-718.]
  • Literature review: dermal monitoring data for pesticide exposure assessment of farm workers.
    A systematic literature search was performed on eight online databases. Two screening phases with predetermined criteria identified the qualifying literature. Standard information and dermal pesticide monitoring data were recorded and summarized from each qualifying study to assess its usefulness for future pesticide exposure assessment. A total of 31 farm studies qualified for review; task information was used to standardize all farm job(s) evaluated into 5 job groups: operators, applicators, mixer-loaders, field workers, and flaggers. When attempting to compare dermal exposure levels between studies, two types of variation were identified: (1) variation in study focus and reporting and 2) variation in exposure levels. The former variation type prevented exposure level comparisons between studies. Within studies, exposure levels were compared across body parts to identify that which had the highest measured exposure and to determine if results were similar in other studies that evaluated the same farm job. Using studies that measured exposure for multiple farm jobs, within study comparisons of total body exposure were performed to evaluate work factors. Future dermal pesticide exposure monitoring studies should standardize reporting procedures, as suggested in this review, to allow for more extensive dermal data comparisons. Body parts with highest measured levels of dermal exposure were identified by farm job, along with work factors to be further investigated as potential dermal pesticide exposure determinants for farm workers.
    [Garzia NA, Spinelli JJ, Gotay CC, Teschke K. 2018. J Agromedicine. 23(3):187-214.]
  • A longitudinal study of atrazine and 2,4-D exposure and oxidative stress markers among iowa corn farmers.
    Reactive oxygen species, potentially formed through environmental exposures, can overwhelm an organism's antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases. Pesticide exposures have been shown to cause oxidative stress in vivo. Study utilized a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to the widely used herbicides atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. 225 urine samples were collected during five agricultural time periods (pre-planting, planting, growing, harvest, off-season) for 30 farmers who applied pesticides occupationally and 10 controls who did not; all were non-smoking men ages 40-60. Atrazine mercapturate (atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2'-deoxyguanosine [8-OHdG], and 8-isoprostaglandin-F2α [8-isoPGF]) were measured in urine. Farmers had higher urinary atrazine mercapturate and 2,4-D levels compared with controls. In regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (β = 0.066, 95%CI = 0.008-0.124) and 8-isoPGF (β = 0.088, 95%CI = 0.004-0.172). 2,4-D may be associated with oxidative stress because of modest increases in 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation, with recent 2,4-D exposure. Future studies should investigate the role of 2,4-D-induced oxidative stress in the pathogenesis of human diseases.
    [Lerro CC, Beane Freeman LE, Portengen L, Kang D, et al. 2017. Environ Mol Mutagen. 58(1):30-38.]
  • Central nervous system tumors and agricultural exposures in the prospective cohort AGRICAN.
    Studies in farmers suggest a possible role of pesticides in the occurrence of Central Nervous System (CNS) tumors but scientific evidence is still insufficient. Using data from the French prospective agricultural cohort AGRICAN (Agriculture & Cancer), authors investigated the associations between exposure of farmers and pesticide users to various kinds of crops and animal farming and the incidence of CNS tumors, overall and by subtypes. Over the 2005-2007, 181,842 participants completed the enrollment questionnaire that collected a complete job calendar with lifetime history of farming types. Associations were estimated using proportional hazards models with age as underlying timescale. During a 5.2 years average follow-up, 273 incident cases of CNS tumors occurred, including 126 gliomas and 87 meningiomas. Analyses showed several increased risks of CNS tumors in farmers, especially in pesticide users (hazard ratio = 1.96; 95% confidence interval: 1.11-3.47). Associations varied with tumor subtypes and kinds of crop and animal farming. The main increases in risk were observed for meningiomas in pig farmers and in farmers growing sunflowers, beets and potatoes and for gliomas in farmers growing grasslands. In most cases, more pronounced risk excesses were observed among pesticide applicators. 
    [Piel C, Pouchieu C, Tual S, Migault L., et al. 2017. Int J Cancer. doi: 10.1002/ijc.30879. ]
  • Longitudinal assessment of occupational determinants of chlorpyrifos exposure in adolescent pesticide workers in Egypt.
    Chlorpyrifos (CPF) is an organophosphourus insecticide applied to cotton fields by adolescents employed by the Egyptian Ministry of Agriculture. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) is a biomarker of CPF exposure that has substantial variability among these applicators. In order to identify predictors of CPF exposure, we conducted a longitudinal study of 43 adolescent pesticide applicators in Egypt from April 2010 to January 2011 in Egypt. Urinary TCPy was quantified at 25 time-points, prior to, during, and following application. We used log-linear regression and a best subset selection approach to identify the exposure determinants that were most predictive of cumulative TCPy and participants' highest TCPy values (peak exposure). Applicators had cumulative urinary TCPy levels ranging from 167 to 49,8208μg/g creatinine. Total hours applying CPF (semi-partial r2=0.32), and total hours in the field applying other pesticides (semi-partial r2=0.08) were the strongest predictors of cumulative TCPy. Applicators had peak urinary TCPy levels ranging from 4 to 5715μg/g creatinine. The amount of time applying pesticides prior to blood draw was the strongest predictor of peak TCPy (semi-partial r2=0.30). We also observed evidence that wearing clean clothes to work was associated with lower longitudinal TCPy. Our results suggest there is an opportunity for targeted interventions, particularly related to hygiene or implementation of personal protective equipment usage to reduce CPF exposure among adolescent pesticide workers
    [Callahan CL, Hamad LA, Olson JR, Ismail AA, et al. 2017. Int J Hyg Environ Health. 220(8):1356-1362]
  • Occurrence of commonly used pesticides in personal air samples and their associated health risk among paddy farmers.
    This study aims to determine the concentrations of commonly used pesticides (azoxystrobin, buprofezin, chlorantraniliprole, difenoconazole, fipronil, imidacloprid, isoprothiolane, pretilachlor, propiconazole, pymetrozine, tebuconazole, tricyclazole, and trifloxystrobin) in personal air samples and their associated health risks among paddy farmers. Eighty-three farmers from Tangjung Karang, Selangor were involved in this study. A solid sorbent tube was attached to the farmer's breathing zone with a clip, and an air pump was fastened to the belt to collect personal air samples. Pesticides collected in the XAD-2 resin were extracted with acetone, centrifuged, concentrated via nitrogen blowdown and reconstituted with 1mL of 3:1 ultrapure water/HPLC-grade methanol solution. The target compounds were detected with a maximum concentration reaching up to 462.5ngm-3 (fipronil). The hazard quotient (HQ) was less than 1 and the hazard index (HI) value was 3.86×10-3, indicating that the risk of pesticides related diseases was not significant. The lifetime cancer risk (LCR) for pymetrozine was at an acceptable level (LCR<10-6) with 4.10×10-8. The results reported in this study can be beneficial in terms of risk management within the agricultural community.
    [Hamsan , Ho YB, Zaidon SZ, et al. 2017. Sci Total Environ. 603-604:381-389. ]
  • Pesticides: Perceived Threat and Protective Behaviors Among Latino Farmworkers.
    The purpose of this study was to assess the knowledge and beliefs of 72 Latino farmworkers in North Carolina about the threat of health effects of pesticides, including cancer. It sought to explore relationships between threat perceptions and pesticide protective behaviors observed in the field. Utilizing stepwise multiple regression, the authors found that years worked in agriculture in the United States was associated with decreased use of protective clothing. Pesticide protective behaviors in the field may be improved by utilizing moderately experienced farmworkers (less 10 years) as lay advisors to reinforce training.
    [Walton AL, LePrevost C, Wong B, et al. 2017. J Agromedicine. 22(2):140-147.]
  • Association between Parkinson's Disease and Cigarette Smoking, Rural Living, Well-Water Consumption, Farming and Pesticide Use: Systematic Review and Meta-Analysis.
    Bradford Hill's viewpoints were used to conduct a weight-of-the-evidence assessment of the association between Parkinson's disease (PD) and rural living, farming and pesticide use. The results were compared with an assessment based upon meta-analysis. For comparison, we also evaluated the association between PD and cigarette smoking as a "positive control" because a strong inverse association has been described consistently in the literature. PubMed was searched systematically to identify all published epidemiological studies that evaluated associations between Parkinson's disease (PD) and cigarette smoking, rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides, or paraquat. There was a consistent inverse (negative) association between current cigarette smoking and PD risk. In contrast, associations between PD and rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides or paraquat were less consistent when assessed quantitatively or qualitatively. The weight of the evidence and meta-analysis support the conclusion that there is a causal relationship between PD risk and cigarette smoking, or some unknown factor correlated with cigarette smoking. There may be risk factors associated with rural living, farming, pesticide use or well-water consumption that are causally related to PD, but the studies to date have not identified such factors. To overcome the limitations of research in this area, future studies will have to better characterize the onset of PD and its relationship to rural living, farming and exposure to pesticides.
    [Breckenridge CB, Berry C, Chang ET, et al. 2016. PLoS One.11(4):e0151841]
  • Prostate cancer risk among French farmers in the AGRICAN cohort.
    Prostate cancer is one of the most frequent cancers among men worldwide. Its etiology is largely unknown, but an increased risk has been repeatedly observed among farmers. Our aim was to identify occupational risk factors for prostate cancer among farmers in the prospective cohort study AGRICAN.Data on lifetime agricultural exposures (type of crops, livestock and tasks including pesticide use, re-entry and harvesting) were collected from the enrolment questionnaire. During the period from enrolment (2005-2007) to 31 December 2009, 1672 incident prostate cancers were identified. We found an increased risk for cattle breeders using insecticides [HR 1.20, 95% confidence interval (95% CI) 1.01-1.42] with a significant dose-response relationship with number of cattle treated (P for trend 0.01). A dose-response relationship was also observed with the number of hogs (P for trend 0.06). We found an excess of prostate cancer risk among people involved in grassland activities, mainly in haymaking (HR 1.18, 95% CI 1.02-1.36). Pesticide use and harvesting among fruit growers were associated with an elevated prostate cancer risk, with a two-fold increased risk for the largest area. For potato and tobacco producers, an elevated prostate cancer risk was observed for almost all tasks, suggesting a link with pesticide exposure since all of them potentially involved pesticide exposure.Our analysis suggests that the risk of prostate cancer is increased in several farming activities (cattle and hog breeding, grassland and fruit-growing) and for some tasks including pesticide use.
    [Lemarchand C, Tual S, Boulanger M, Levêque-Morlais N, et al. 2016. Scand J Work Environ Health. 42(2):144-52.]
  • "Where they (live, work and) spray": pesticide exposure, childhood asthma and environmental justice among Mexican-American farmworkers
    Asthma prevalence is reportedly low for children of Mexican descent compared with other ethnic groups and Latino subgroups. The results of this exploratory ethnographic research among children of farmworkers in California dramatically suggest otherwise. Little work has been reported employing photovoice, a community-based participatory research method, to study childhood exposure to pesticides. A rich narrative about perceptions of pesticide exposure emerged from the ethnographic interviews. Thematic analysis yielded beliefs about the relationship between air quality and childhood asthma. The findings suggest that childhood asthma should be reviewed within the context of local levels of environmental exposure and the principles of environmental justice.
    [Schwartz NA, von Glascoe CA, Torres V, et al. 2015. Health Place. 32:83-92.]
  • EPA's proposed Worker Protection Standard and the burdens of the past.
    This review considers the proposed revisions' likelihood of addressing historical gaps in farmworker protection. The proposal was compared to the existing Worker Protection Standard, and key aspects were analyzed in relation to existing science on farm labor hazards, as well as historic occupational health, labor and immigration policy. US law historically has left farm workers largely unprotected. These exclusions and delays have been tolerated in part thanks to the myth of the independent family farmer, but more significant is the stingy nativism that presumes to benefit from immigrant labor without assuming any responsibility to protect the humans who provide it. Key aspects of the proposed revision include stronger protections against drift and re-entry exposures, better information provision and training, and increased protections for workers under 16 years. The proposed changes represent an improvement over existing legislation, but do not go far enough. The revision should be strengthened along lines suggested by farm workers themselves, and other labor laws must also be amended to give the men, women, and children who work in the fields of this country full rights and protections.
    [Bohme SR. 2015. Int J Occup Environ Health. 37(1):161-5]
  • Farmworker Housing in the United States and Its Impact on Health.
    Farmworkers in the United States occupy a range of housing, including both on- and off-farm family and communal dwellings. As the farmworker population is becoming more settled, housing needs are changing. Existing regulations designed originally for grower-supplied migrant housing may need to be expanded. Much of farmworker housing is in poor condition, and likely linked to negative mental and physical health outcomes of residents because of exposures to crowding; mold, mildew, and other allergens; pesticides; and structural deficiencies. The existing research literature, both on housing conditions and their associations with farmworker health, is sparse, and large areas of the country and significant domains of health are omitted. This paper reviews this literature and formulates research and policy recommendations for addressing these deficiencies.
    [Quandt SA, Brooke C, Fagan K, Howe A, et al. 2015. New Solut. 25(3):263-86.]
  • Home-based community health worker intervention to reduce pesticide exposures to farmworkers' children: A randomized-controlled trial.
    Authors conducted a randomized-controlled trial of a home-based intervention to reduce pesticide exposures to farmworkers' children in Monterey County, California (n=116 families). Measurements of organophosphate (OP) insecticide metabolites in child urine (n=106) and pesticides in home floor wipes (n=103) were collected before and after the intervention. Median child urinary dialkyl phosphate (DAP) metabolite levels were slightly lower among the intervention group children at follow-up compared with baseline, albeit nonsignificantly. DAP metabolite levels in the control group children were markedly higher at follow-up compared with baseline. In adjusted models, intervention participation was associated with a 51% decrease in total DAP metabolite levels. Carbaryl, chlorpyrifos, cypermethrin, dacthal, diazinon, malathion, and trans-permethrin were commonly detected in the floor wipes. In adjusted models, intervention participation was significantly associated with a 37% decrease in trans-permethrin floor wipe levels in homes, but not OP or other agricultural pesticides. In summary, intervention group children had slightly reduced pesticide exposures, whereas child exposures were higher among the control group. Additional intervention studies evaluating methods to reduce pesticide exposures to farmworker families and children are needed.
    [Salvatore AL, Castorina R, Camacho J, et al. 2015. J Expo Sci Environ Epidemiol. 25(6):608-15]
  • Perceptions of housing conditions among migrant farmworkers and their families: implications for health, safety and social policy.
    This study used qualitative descriptive data and directed content analysis to analyse semi-structured interviews and photographs that were data elements of a larger community-based participatory research study designed to document housing quality and health among North Carolina farmworkers.Specific problems described by the participants include exposure to pesticides, safety issues, pests, water supply and air quality, temperature and moisture.This study describes migrant farmworkers' perceptions of housing quality and numerous potential impacts on health and safety. Research, social policy and practice-based implications derived from this research could serve to improve the health status of these individuals and their families. This study suggests there is much room for sustained advocacy and action, given that many of the farmworkers' descriptions and photographs depicted housing conditions below accepted standards of living. Access to adequate and safe employer-provided housing for migrant farmworkers should be considered a basic human right.
    [Keim-Malpass J, Spears Johnson CR, Quandt SA, Arcury TA. 2015. Rural Remote Health. 15:3076]
  • Amyotrophic Lateral Sclerosis and Agricultural Environments: A Systematic Review
    The aim of this study was to examine the relationship between the risk of amyotrophic lateral sclerosis (ALS) and exposure to rural environments. Studies were identified through OVID MEDLINE and EMBASE search up to September 2013 using as keywords rural residence, farmers, and pesticide exposure. Twenty-two studies were included for this meta-analysis. Summary odds ratios (ORs) were calculated using random effect model by type of exposure index, and subgroup analyses were conducted according to study design, gender, region, case ascertainment, and exposure assessment. The risk of ALS was significantly increased with pesticide exposure (OR, 1.44; 95% CI, 1.22-1.70) and with farmers (OR, 1.42; 95% CI, 1.17-1.73), but was not significant with rural residence (OR, 1.25; 95% CI, 0.84-1.87). The risk estimates for subgroup analysis between pesticide exposure and ALS indicated a significant positive association with men (OR, 1.96), and in studies using El Escorial criteria for ALS definition (OR, 1.63) and expert judgment for pesticide exposure (OR, 2.04) as well. No significant publication bias was observed. Our findings support the association of pesticide exposure and an increased risk for ALS, stressing that the use of more specific exposure information resulted in more significant associations.
    [Kang, H., Cha, E.S., Choi, G.J. and Lee, W.J., 2014. Journal of Korean medical science, 29(12), pp.1610-1617.]
  • Assessing the effectiveness of the Pesticides and Farmworker Health Toolkit: a curriculum for enhancing farmworkers' understanding of pesticide safety concepts
    The crop-specific Pesticides and Farmworker Health Toolkit (Toolkit) is a pesticide safety and health curriculum designed to communicate to farmworkers pesticide hazards commonly found in their working environments and to address Worker Protection Standard (WPS) pesticide training criteria for agricultural workers. The goal of this preliminary study was to test evaluation items for measuring knowledge increases among farmworkers and to assess the effectiveness of the Toolkit in improving farmworkers' knowledge of key WPS and risk communication concepts when the Toolkit lesson was delivered by trained trainers in the field. After receiving training on the curriculum, four participating trainers provided lessons using the Toolkit as part of their regular training responsibilities and orally administered a pre- and post-lesson evaluation instrument to 20 farmworker volunteers who were generally representative of the national farmworker population. Farmworker knowledge of pesticide safety messages significantly increased after participation in the lesson. Further, items with visual alternatives were found to be most useful in discriminating between more and less knowledgeable farmworkers. The pilot study suggests that the Pesticides and Farmworker Health Toolkit is an effective, research-based pesticide safety and health intervention for the at-risk farmworker population and identifies a testing format appropriate for evaluating the Toolkit and other similar interventions for farmworkers in the field.
    [LePrevost CE, Storm JF, Asuaje CR, Arellano C, Cope WG. 2014. J Agromedicine. 19(2):96-102.]
  • Lifetime and current pesticide exposure among Latino farmworkers in comparison to other Latino immigrants.
    This analysis documents lifetime and current pesticide exposure of North Carolina Latino migrant farmworkers, with comparison to non-farmworker Latino immigrants.During May to October 2012, 235 Latino farmworkers and 212 Latino non-farmworkers completed interviews with items to construct measures of lifetime, current residential and occupational pesticide exposure.Farmworkers experience levels of lifetime and residential pesticide exposure that are consistently greater than among non-farmworkers. Farmworkers report a large number of occupational pesticide exposures. Lifetime exposure and current residential pesticide exposure are related to social determinants. Education is inversely related to lifetime pesticide exposure for farmworkers and non-farmworkers; farmworkers with H-2A visas report greater residential pesticide exposure than those without H-2A visas. Occupational safety policy needs to consider these patterns of lifetime exposure when setting standards. Health care providers should be aware of the lifetime and current exposure of this vulnerable population.
    [Arcury TA, Nguyen HT, Summers P, Talton JW, et al. 2014. Am J Ind Med. 57(7):776-87]
  • Macro-activity patterns of farmworker and non-farmworker children living in an agricultural community.
    Children of farmworkers have significantly higher exposure to pesticides than do other children living in the same agricultural communities, but there is limited information about how and where older farmworker children (>6) spend their time and how their activities might influence the risk of pesticide exposure. Using data from the Community Based Participatory Research Study for Healthy Kids, study compared activity patterns recorded over 7 days during two agricultural seasons (pre thinning and thinning) between farmworker and non-farmworker children aged 6-12 years old living in Eastern Washington State. Study observed substantial differences in child activity patterns between the two seasons. The children in this sample spent more time outdoors and were more likely to engage in behaviors, such as playing in the fields and accompanying their parents to work in the fields during the high-spray thinning season. There were some differences in activities and behaviors between farmworker and non-farmworker children during the thinning season.
    [Shepherd-Banigan M, Ulrich A, Thompson B. 2014. Environ Res. 132:176-81]
  • Pesticide exposures to migrant farmworkers in Eastern NC: detection of metabolites in farmworker urine associated with housing violations and camp characteristics.
    The purpose of this paper is to present and evaluate descriptively bivariate associations between urinary metabolites of pesticides and herbicides and migrant camp conditions, violations, and personal worker behaviors at home for farmworkers who do not apply pesticides.Authors studied 183 migrant farmworker camps in eastern North Carolina in 2010. Cockroaches and bathroom violations were predictive of increased exposure to pyrethroids and cyfluthrin/chlorpyrifos, respectively. Changing and storing clothing and shoes in sleeping rooms increased the number of detects for the diazinon metabolite.Farmworkers had exposures to multiple chemicals. No single housing domain was identified as critical to mitigating housing-related exposure; specific attention should be paid to changing and storing soiled clothing in sleeping rooms, and insect infestations.
    [Raymer JH, Studabaker WB, Gardner M, Talton J, et al. 2014. Am J Ind Med. 57(3):323-37.]
  • Pesticides present in migrant farmworker housing in North Carolina
    This analysis (1) describes the presence of organophosphorous (OP) and pyrethroid pesticides in North Carolina migrant farmworker houses, and (2) delineates associations of farmworker camp characteristics with pesticide detection and concentration.In 2010, 186 migrant farmworkers camps in NC were recruited and pesticide wipe samples for 176 houses were analyzed. OPs were found in 166 of 176 houses (average of 2.4/house); pyrethroids were found in 171 houses (average of 4.3/house). The number of different OPs detected in each camp and concentrations of these OPs were not associated with camp and housing characteristics. The number of different pyrethroids detected in each camp and concentrations of these pyrethroids were associated with camps having residents with H2-A visas, a posted North Carolina Department of Labor Certificate of Inspection, no barracks, fewer residents, no bedroom weather protection or floor violations, and no roaches.Farmworkers are exposed to pesticides where they live. Policy on removing pesticides from farmworker houses is needed. Reducing pesticides in farmworker houses will reduce one health risk confronted by this vulnerable population.
    [Arcury TA, Lu C, Chen H, Quandt SA. 2014. Am J Ind Med. 57(3):312-22.]
  • Safety and injury characteristics of youth farmworkers in North Carolina: a pilot study.
    The primary aim for this analysis is to describe the personal characteristics, work characteristics, occupational safety behaviors, and occupational injuries of North Carolina youth farmworkers. Participants included males (62.1%) and females (37.9%), with 26.4% aged 10-13 years, 39.1% 14-15 years, and 34.5% 16-17 years. The majority (78.2%) were born in the United States. Most worked in tobacco (46.0%), sweet potatoes (28.7%), and berries (28.7%). Three quarters wore a hat, and 63.2% wore gloves while working. Five (5.7%) had received pesticide use training in the past year. Over half reported a musculoskeletal injury (54.0%), a traumatic injury (60.9%), or a dermatological injury (72.4%) in the last year. Six of the injuries led to medical treatment, and 10 resulted in missed school or work. Farmworker youth in North Carolina are at times not treated fairly when they work, occupational safety behaviors are limited (increasing exposure to pesticides and other environmental hazards), and they commonly experience injuries. Research on the occupational exposures and health experienced by youth farmworkers is needed to inform policy. Changes in policy are warranted to improve the safety of youth farmworkers.
    [Arcury TA, Rodriguez G, Kearney GD, et al. 2014. J Agromedicine. 19(4):354-63.]
  • Pesticide risk perception and biomarkers of exposure in Florida female farmworkers.
    Study compared workplace characteristics, workplace behaviors, and the health beliefs of female farmworkers of childbearing age with actual biomarkers of exposure to organophosphate pesticides and to the fungicide mancozeb.Hispanic and Haitian farmworkers between the ages of 18 and 40 years working in nursery or fernery operations were recruited to participate in a cross-sectional survey, examining demographics, work practices, work-related hygiene, and pesticide exposure beliefs.Women in nurseries worried less frequently about the effects of pesticides on their health than those in fernery operations. In summary, organophosphate and ethylenethiourea levels in nursery workers were significantly higher than levels in fernery workers and the control group.Results showed that perceived pesticide exposure did not correspond to actual metabolite levels within differing agricultural subpopulations.
    [Runkle JD, Tovar-Aguilar JA, Economos E, et al.2013. J Occup Environ Med. 55(11):1286-92.]
  • Relative pesticide and exposure route contribution to aggregate and cumulative dose in young farmworker children.
    The Child-Specific Aggregate Cumulative Human Exposure and Dose (CACHED) framework integrates micro-level activity time series with mechanistic exposure equations, environmental concentration distributions, and physiologically-based pharmacokinetic components to estimate exposure for multiple routes and chemicals. CACHED was utilized to quantify cumulative and aggregate exposure and dose estimates for a population of young farmworker children and to evaluate the model for chlorpyrifos and diazinon. Micro-activities of farmworker children collected concurrently with residential measurements of pesticides were used in the CACHED framework to simulate 115,000 exposure scenarios and quantify cumulative and aggregate exposure and dose estimates. Modeled metabolite urine concentrations were not statistically different than concentrations measured in the urine of children, indicating that CACHED can provide realistic biomarker estimates. Analysis of the relative contribution of exposure route and pesticide indicates that in general, chlorpyrifos non-dietary ingestion exposure accounts for the largest dose, confirming the importance of the micro-activity approach. The risk metrics computed from the 115,000 simulations, indicate that greater than 95% of these scenarios might pose a risk to children's health from aggregate chlorpyrifos exposure. The variability observed in the route and pesticide contributions to urine biomarker levels demonstrate the importance of accounting for aggregate and cumulative exposure in establishing pesticide residue tolerances in food.
    [Beamer PI, Canales RA, Ferguson AC, et al. 2012. Int J Environ Res Public Health. 9(1):73-96.]
  • Acute Pesticide Illnesses Associated with Off-Target Pesticide Drift from Agricultural Applications — 11 States, 1998–2006
    A study by the Centers for Disease Control and Prevention's (CDC) National Institute for Occupational Safety and Health (NIOSH) and state agency partners finds that pesticide drift from conventional, chemical-intensive farming has poisoned thousands of farmworkers and rural residents in recent years. According to the authors, agricultural workers and residents in agricultural regions were found to have the highest rate of pesticide poisoning from drift exposure, and soil fumigations were a major hazard causing large drift incidents. Daily News
    [Lee, SJ. et al. 2011. Environ Health Perspect. 119:1162–1169]
  • ganophosphate pesticide exposure and residential proximity to nearby fields: evidence for the drift pathway.
    Residential proximity to pesticide-treated farmland is an important pesticide exposure pathway. In-person interviews and biological samples were collected from 100 farmworker and 100 non-farmworker adults and children living in Eastern Washington State. Study examined the relationship of residential proximity to farmland to urinary metabolite concentrations of dimethylphosphate (DMTP) and levels of pesticide residues in house dust.DMTP concentrations were higher in farmworkers than non-farmworkers and in farmworker children than non-farmworker children. Compared to non-farmworker households, farmworker households had higher levels of azinphos-methyl and phosmet. Overall, a 20% reduction in DMTP concentration was observed per mile increase in distance from farmland.
    [Coronado GD, Holte S, Vigoren E, Griffith WC, et al. 2011. J Occup Environ Med. 53(8):884-91.]
  • Pesticides in house dust from urban and farmworker households in California: an observational measurement study.
    Authors conducted a study in low-income homes from urban and agricultural communities to: characterize and compare house dust levels of agricultural and residential-use pesticides; evaluate the correlation of pesticide concentrations in samples collected several days apart; examine whether concentrations of pesticides phased-out for residential uses, but still used in agriculture (i.e., chlorpyrifos and diazinon) have declined in homes in the agricultural community; and estimate resident children's pesticide exposures via inadvertent dust ingestion.In 2006, reserchers collected up to two dust samples 5-8 days apart from each of 13 urban homes in Oakland, California and 15 farmworker homes in Salinas, California, an agricultural community (54 samples total). More than half of the households reported applying pesticides indoors. Analytes frequently detected in both locations included chlorpyrifos, diazinon, permethrin, allethrin, cypermethrin, and piperonyl butoxide. Chlorthal-dimethyl was detected solely in farmworker homes, suggesting contamination due to regional agricultural use. Additionally, diazinon and chlorpyrifos concentrations in Salinas farmworker homes were 40-80% lower than concentrations reported in samples from Salinas farmworker homes studied between 2000-2002, suggesting a temporal reduction after their residential phase-out. Finally, estimated non-dietary pesticide intake for resident children did not exceed current U.S. Environmental Protection Agency's (U.S. EPA) recommended chronic reference doses (RfDs).Study concludes low-income children are potentially exposed to a mixture of pesticides as a result of poorer housing quality. Historical or current pesticide use indoors is likely to contribute to ongoing exposures. Agricultural pesticide use may also contribute to additional exposures to some pesticides in rural areas. The frequent pesticide use reported and high detection of several home-use pesticides in house dust suggests that families would benefit from integrated pest management strategies to control pests and minimize current and future exposures.
    [Quirós-Alcalá L, Bradman A, Nishioka M, et al. 2011. Environ Health. 10:19.]
  • Repeated pesticide exposure among North Carolina migrant and seasonal farmworkers
    Data were collected from 196 farmworkers four times at monthly intervals in 2007. Urine samples were tested for 12 pesticide urinary metabolites. Farmworkers had at least one detection for many pesticide urinary metabolites; for example, 84.2% had at least one detection for acephate, 88.8% for 3,5,6-trichloro-2-pyridinol. Most farmworkers had multiple detections for specific metabolites.
    [Arcury, T. et al. 2010. Am. J. Ind. Med. 53:802–813]
  • A case-control study of farming and prostate cancer in African-American and Caucasian men
    A population-based case-control study in South Carolina finds farming is associated with increase risk of prostate cancer in Caucasians (OR 1.8) but not African-Americans. The study also finds that farmers who mixed or applied pesticides have a greater risk (OR 1.6); and, the increased risk is found only for those farming less than 5 years. The authors conclude that the racial difference in the association between farming and prostate cancer may be explained by different farming activities or different gene–environment interactions by race.
    [Meyer, T.E., et al. 2007. Occup Environ Med 64(3):155-160.]
  • Agreement of pesticide biomarkers between morning void and 24-h urine samples from farmers and their children
    In pesticide biomonitoring studies, researchers typically collect either single voids or daily (24-h) urine samples. Collection of 24-h urine samples is considered the "gold-standard", but this method places a high burden on study volunteers, requires greater resources, and may result in misclassification of exposure or underestimation of dose due to noncompliance with urine collection protocols. To evaluate the potential measurement error introduced by single void samples, we present an analysis of exposure and dose for two commonly used pesticides based on single morning void (MV) and 24-h urine collections in farmers and farm children. The agreement between the MV concentration and its corresponding 24-h concentration was analyzed using simple graphical and statistical techniques and risk assessment methodology. A consistent bias towards overprediction of pesticide concentration was found among the MVs, likely in large part due to the pharmacokinetic time course of the analytes in urine. These results suggest that the use of single voids can either over- or under-estimate daily exposure if recent pesticide applications have occurred. This held true for both farmers as well as farm children, who were not directly exposed to the applications. As a result, single void samples influenced the number of children exposed to chlorpyrifos whose daily dose estimates were above levels of toxicologic significance. In populations where fluctuations in pesticide exposure are expected (e.g., farm families), the pharmacokinetics of the pesticide and the timing of exposure events and urine collection must be understood when relying on single voids as a surrogate for longer time-frames of exposure.
    [Scher, D. et al. 2007, J. Exposure Science and Environmental Epidemiology; 17, 350–357]
  • Agricultural exposures and gastric cancer risk in Hispanic farm workers in California
    Occupation in the citrus industry (OR 2.88) and in areas with high 2,4-D use (OR 1.85) and use of acaricide propargite (OR 2.86) or trifluralin (OR 1.69) are associated with gastric cancer.
    [Mills, P.K., and Yang, R.C. 2007. Environ Res 104(2):282-289.]
  • Pesticides and their metabolites in the homes and urine of farmworker children living in the Salinas Valley, CA.
    In support of planning efforts for the National Children's Study, authors conducted a study to test field methods for characterizing pesticide exposures to 20 farmworker children aged 5-27 months old living in the Salinas Valley of Monterey County, California. Study tested methods for collecting house dust, indoor and outdoor air, dislodgeable residues from surfaces and toys, residues on clothing (sock and union suits), food, as well as spot and overnight diaper urine samples. Authors measured 29 common agricultural and home use pesticides in multiple exposure media samples. A subset of organophosphorus (OP), organochlorine (OC) and pyrethroid pesticides were measured in food. Urine samples were also analyzed. Pesticides were detected more frequently in house dust, surface wipes, and clothing than other media, with chlorpyrifos, diazinon, chlorthal-dimethyl, and cis- and trans-permethrin detected in 90% to 100% of samples. Levels of four of these five pesticides were positively correlated among the house dust, sock, and union suit samples. Pesticide loading on socks and union suits was higher for the group of 10 toddlers compared to the 10 younger crawling children. Several OP pesticides, as well as 4,4'-DDE, atrazine, and dieldrin were detected in the food samples. Future uses of these data include the development of pesticide exposure models and risk assessment.
    [Bradman A, Whitaker D, Quirós L, Castorina R, et al. 2007. J Expo Sci Environ Epidemiol;17(4):331-49]
  • Association of in utero organochlorine pesticide exposure and fetal growth and length of gestation in an agricultural population.
    Although substantial evidence exists for the fetal toxicity of organochlorines in animals, information on human reproductive effects is conflicting. Study investigated whether infants' length of gestation, birth weight, and crown-heel length were associated with maternal serum levels of 11 different organochlorine pesticides: p,p -dichlorodiphenyltrichloroethane (p,p -DDT), p,p -dichlorodiphenyldichloroethylene (p,p -DDE), o,p -dichlorodiphenyltrichloroethane (o,p -DDT), hexachlorobenzene (HCB), gamma-hexachlorocyclohexane (gamma-HCCH), gamma-hexachlorocyclohexane (gamma-HCCH), dieldrin, heptachlor epoxide, oxychlordane, trans-nonachlor, and mirex. Our subjects were a birth cohort of 385 low-income Latinas living in the Salinas Valley, an agricultural community in California. Results found no adverse associations between maternal serum organochlorine levels and birth weight or crown-heel length. Decreased length of gestation with increasing levels of lipid-adjusted HCB was found. Study did not find reductions in gestational duration associated with any of the other organochlorine pesticides. Study's finding of decreased length of gestation related to HCB does not seem to have had clinical implications for this population, given its relatively low rate of preterm delivery (6.5%).
    [Fenster L, Eskenazi B, Anderson M, Bradman A. 2006. Environ Health Perspect. 114(4):597-602]
  • Biomonitoring of exposure in farmworker studies
    Although biomonitoring has been used in many occupational and environmental health and exposure studies, we are only beginning to understand the complexities and uncertainties involved with the biomonitoring process--from study design, to sample collection, to chemical analysis--and with interpreting the resulting data. Author presents an overview of concepts that should be considered when using biomonitoring or biomonitoring data, assess the current status of biomonitoring, and detail potential advancements in the field that may improve our ability to both collect and interpret biomonitoring data. Author also discusses issues such as the appropriateness of biomonitoring for a given study, the sampling time frame, temporal variability in biological measurements to nonpersistent chemicals, and the complex issues surrounding data interpretation. In addition, we provide recommendations to improve the utility of biomonitoring in farmworker studies.
    [Barr DB, et al. 2006. Environ Health Perspect.;114(6):936-42]
  • Cancer incidence among farmers exposed to lindane while sheep dipping
    The objective of this study was to determine whether site-specific cancer incidence among farmers exposed to the insecticide lindane (g-hexachlorocyclohexane) while dipping sheep differs from that of the general population in Iceland.Cohorts of 7882 men and 429 women, who, according to records on sheep dipping, were sheep owners, were followed from 1962 to 2003 in the Cancer Registry for cancer incidence.For men the standardized incidence ratio (SIR) for all cancer sites was 0.79, with a 95% confidence interval (95% CI) of 0.76-0.83. For both the men and the women a significantly increased risk for lip cancer was found, with SIR of 1.50 (95% CI 1.08-2.04) and 9.09 (95% CI 1.02-32.82), respectively. Cancer of the lip was the only cancer type in significant excess among both genders, and the stomach cancer rates were near unity, but, in previous studies on Icelandic farmers, an increase had been found for stomach cancer. The site-specific cancer incidence for sheep-dipping farmers did not differ substantially from that of the general population.
    [Rafnsson V. 2006. Scand J Work Environ Health. 32(3):185-9.]
  • Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino mothers and newborns.
    Recent studies have demonstrated widespread pesticide exposures in pregnant women and in children. Plasma paraoxonase 1 (PON1) plays an important role in detoxification of various organophosphates. The goals of this study were to examine in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort of Latina mothers and their newborns living in the Salinas Valley, California, the frequencies of five PON1 polymorphisms in the coding region (192QR and 55LM) and the promoter region (-162AG, -909CG, and -108CT) and to determine their associations with PON1 plasma levels [phenylacetate arylesterase (AREase) ] and enzyme activities of paraoxonase (POase) and chlorpyrifos oxonase (CPOase) . Authors found that PON1-909, PON1-108, and PON1(192) had an equal frequency (0.5) of both alleles, whereas PON1-162 and PON1(55) had lower variant allele frequencies (0.2) . Nearly complete linkage disequilibrium was observed among coding and promoter polymorphisms (p < 0.001) , except PON1(192) and PON1-162 (p > 0.4) . Children's PON1 plasma levels (AREase ranged from 4.3 to 110.7 U/mL) were 4-fold lower than their mothers' (19.8 to 281.4 U/mL) . POase and CPOase activities were approximately 3-fold lower in newborns than in mothers. The genetic contribution to PON1 enzyme variability was higher in newborns (R2 = 25.1% by genotype and 26.3% by haplotype) than in mothers (R2 = 8.1 and 8.8%, respectively) . However, haplotypes and genotypes were comparable in predicting PON1 plasma levels in mothers and newborns. Most of the newborn children and some pregnant women in this Latino cohort may have elevated susceptibility to organophosphate toxicity because of their PON1192 genotype and low PON1 plasma levels.
    [Holland N, Furlong C, Bastaki M, et al. 2006. Environ Health Perspect. 114(7):985-91]
  • Biologic monitoring to characterize organophosphorus pesticide exposure among children and workers: an analysis of recent studies in Washington State.
    Study examined findings from five organophosphorus pesticide biomonitoring studies conducted in Washington State between 1994 and 1999 and compared urinary dimethylthiophosphate (DMTP) concentrations for all study groups and composite dimethyl alkylphosphate (DMAP) concentrations for selected groups. Children of pesticide applicators had substantially higher metabolite levels than did Seattle children and farmworker children. Metabolite levels of children living in agricultural communities were elevated during periods of crop spraying. Median DMTP concentrations for Seattle children and farmworker children did not differ significantly; however, the DMAP concentrations were higher for Seattle children than for farmworker children. DMTP concentrations of U.S. children 6-11 years of age (1999-2000 National Health and Nutrition Examination Survey population) were higher than those of Seattle children and farmworker children. DMTP concentrations for workers actively engaged in apple thinning were 50 times higher than DMTP concentrations for farmworkers sampled outside of peak exposure periods. Study concludes that workers who have direct contact with pesticides should continue to be the focus of public health interventions and that elevated child exposures in agricultural communities may occur during active crop-spraying periods and from living with a pesticide applicator. Timing of sample collection is critical for the proper interpretation of pesticide biomarkers excreted relatively soon after exposure. Authors surmise that differences in dietary exposure can explain the similar exposures observed among farmworker children, children living in the Seattle metropolitan area, and children sampled nationally.
    [Fenske RA, Lu C, Curl CL, Shirai JH, Kissel JC. 2005. Environ Health Perspect.;113(11):1651-7]
  • Urinary and hand wipe pesticide levels among farmers and nonfarmers in Iowa
    In the spring and summer of 2001, as part of a larger study investigating farm family pesticide exposure and home contamination in Iowa, urine and hand wipe samples were collected from 24 male farmers and 23 male nonfarmer controls. The samples were analyzed for the parent compound or metabolites of six commonly used agricultural pesticides: alachlor, atrazine, acetochlor, metolachlor, 2,4-dichlorophenoxyacetic acid (2,4-D) and chlorpyrifos. For atrazine, acetochlor, metolachlor and 2,4-D, farmers who reported applying the pesticide had significantly higher urinary metabolite levels than nonfarmers, farmers who did not apply the pesticide, and farmers who had the pesticide commercially applied. Generally, there were no differences in urinary pesticide metabolite levels between nonfarmers, farmers who did not apply the pesticide, and farmers who had the pesticide commercially applied. Among farmers who reported applying 2,4-D themselves, time since application, amount of pesticide applied, and the number of acres to which the pesticide was applied were marginally associated with 2,4-D urine levels. Among farmers who reported applying atrazine themselves, time since application and farm size were marginally associated with atrazine mercapturate urine levels. Farmers who reported using a closed cab to apply these pesticides had higher urinary pesticide metabolite levels, although the difference was not statistically significant. Farmers who reported using closed cabs tended to use more pesticides. The majority of the hand wipe samples were nondetectable. However, detection of atrazine in the hand wipes was significantly associated with urinary levels of atrazine above the median.
    [Curwin, B. et al. 2005. J of Exposure Analysis and Environmental Epidemiology 15, 500–508]
  • Cancer risk and parental pesticide application in children of Agricultural Health Study participants.
    Parental exposure to pesticides may contribute to childhood cancer risk. Through the Agricultural Health Study, a prospective study of pesticide applicators in Iowa and North Carolina, we examined childhood cancer risk and associations with parental pesticide application. Identifying information for 17,357 children of Iowa pesticide applicators was provided by parents via questionnaires (1993-1997) and matched against the Iowa Cancer Registry. Fifty incident childhood cancers were identified (1975-1998). Risk of all childhood cancers combined was increased [standardized incidence ratio (SIR) = 1.36; 95% confidence interval (CI), 1.03-1.79]. Risk of all lymphomas combined was also increased (SIR = 2.18; 95% CI, 1.13-4.19), as was risk of Hodgkin's lymphoma (SIR = 2.56; 95% CI, 1.06-6.14). We used logistic regression to explore associations between self-reported parental pesticide application practices and childhood cancer risk. No association was detected between frequency of parental pesticide application and childhood cancer risk. An increased risk of cancer was detected among children whose fathers did not use chemically resistant gloves [odds ratio (OR) = 1.98; 95% CI, 1.05-3.76] compared with children whose fathers used gloves. Of 16 specific pesticides used by fathers prenatally, ORs were increased for aldrin (OR = 2.66), dichlorvos (OR = 2.06), and ethyl dipropylthiocarbamate (OR = 1.91). However, these results were based on small numbers and not supported by prior biologic evidence. Identification of excess lymphoma risk suggests that farm exposures including pesticides may play a role in the etiology of childhood lymphoma.
    [Flower, K., et al. 2004. Environmental Health Perspectives 112:631-635]
  • Arrested Development: A study on the Human Health Impacts of Pesticides
    A study found a strong link between pesticide exposure and cognitive abilities among farmers' children in India. The study revealed serious mental development disorders that ranged from severely impaired analytical abilities, motor skills, concentration and memory among the children in the chemical-intensive cotton belts of India (A 2004 study reveals serious mental development disorders that range from severely impaired analytical abilities, motor skills, concentration and memory among the children in the chemical-intensive cotton belts of India.
    [Kuruganti, K. 2003. Greenpeace. Bangalore India.]
  • Children's Exposure to Chlorpyrifos and Parathion in an Agricultural Community in Central Washington State
    Authors measured two diethyl organophosphorus (OP) pesticides--chlorpyrifos and parathion--in residences, and their metabolic by-products, in the urine of children 6 years old or younger in a central Washington State agricultural community. Median chlorpyrifos house dust concentrations were highest for the 49 applicator homes (0.4 microg/g), followed by the 12 farm-worker homes (0.3 microg/g) and the 14 nonagricultural reference homes (0.1 microg/g); authors observed a similar pattern for parathion in house dust. Chlorpyrifos was measurable in the house dust of all homes, whereas parathion in only 41% of the homes was found. Child urinary metabolite concentrations did not differ across parental occupational classifications. Homes in close proximity (200 ft/60 m) to pesticide-treated farmland had higher chlorpyrifos (p = 0.01) and parathion (p = 0.014) house dust concentrations than did homes farther away, but this effect was not reflected in the urinary metabolite data. Use of OP pesticides in the garden was associated with an increase in TCPy concentrations in children's urine. Parathion concentrations in house dust decreased 10-fold from 1992 to 1995, consistent with the discontinued use of this product in the region in the early 1990s.
    [Fenske, R.A., Lu, C, Barr, D, and Needham, L. 2002. Environ Health Perspect. 11(5):: 549–553]
  • Evaluation of take-home organophosphorus pesticide exposure among agricultural workers and their children.
    Researchers analyzed organophosphorus pesticide exposure in 218 farm worker households in agricultural communities in Washington State to investigate the take-home pathway of pesticide exposure and to establish baseline exposure levels for a community intervention project. House dust samples were collected from within the homes, and vehicle dust samples were collected from the vehicles used by the farm workers to commute to and from work. Urine samples were obtained from a farm worker and a young child in each household. Dust samples were analyzed for six pesticides, and urine samples were analyzed for five dialkylphosphate (DAP) metabolites. Azinphosmethyl was detected in higher concentrations than the other pesticides. Dimethyl DAP metabolite concentrations were higher than diethyl DAP metabolite concentrations in both child and adult urine. Azinphosmethyl concentrations in house dust and vehicle dust from the same household were significantly associated. Dimethyl DAP levels in child and adult urine from the same household were also significantly associated, and this association remained when the values were creatinine adjusted. The results of this work support the hypothesis that the take-home exposure pathway contributes to residential pesticide contamination in agricultural homes where young children are present.
    [Curl CL, Fenske RA, Kissel JC, et al. 2002. Environ Health Perspect;110(12):A787-92]
  • An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population.
    The Ontario Farm Family Health Study collected data by questionnaire on the identity and timing of pesticide use on the farm, lifestyle factors, and a complete reproductive history from the farm operator and eligible couples living on the farm. A total of 2,110 women provided information on 3,936 pregnancies, including 395 spontaneous abortions. To explore critical windows of exposure and target sites for toxicity, authors examined exposures separately for preconception (3 months before and up to month of conception) and postconception (first trimester) windows and for early (< 12 weeks) and late (12-19 weeks) spontaneous abortions. They observed moderate increases in risk of early abortions for preconception exposures to phenoxy acetic acid herbicides, triazines, and any herbicide. For late abortions, preconception exposure to glyphosate, thiocarbamates, and the miscellaneous class of pesticides was associated with elevated risks. This study shows that timing of exposure and restricting analyses to more homogeneous endpoints are important in characterizing the reproductive toxicity of pesticides.
    [Arbuckle,TE, Lin, Z and Mery, LS. 2001. Environ Health Perspect. 109(8): 851–857.]
  • Biological monitoring survey of organophosphorus pesticide exposure among pre-school children in the Seattle metropolitan area
    In this study we assessed organophosphorus (OP) pesticide exposure among children living in two Seattle metropolitan area communities by measuring urinary metabolites, and identified possible exposure risk factors through a parental interview. We recruited children in clinic and outpatient waiting rooms. We obtained spot urine samples in the spring and fall of 1998 from 110 children ages 2-5 years, from 96 households. We analyzed urine samples for six dialkylphosphate (DAP) compounds, the common metabolites of the OP pesticides. Through parental interviews we gathered demographic and residential pesticide use data. At least one of the DAP metabolites was measured in 99% of the children, and the two predominant metabolites (DMTP and DETP) were measured in 70-75% of the children. We found no significant differences in DAP concentrations related to season, community, sex, age, family income, or housing type. Median concentrations of dimethyl and diethyl DAPs were 0.11 and 0.04 micromol/L, respectively (all children). Concentrations were significantly higher in children whose parents reported pesticide use in the garden (0.19 vs. 0.09 micromol/L for dimethyl metabolites, p = 0.05; 0.04 vs. 0.03 micromol/L for diethyl metabolites, p = 0.02), but were not different based on reported pet treatment or indoor residential use. Nearly all children in this study had measurable levels of OP pesticide metabolites. Some of this exposure was likely due to diet. Garden pesticide use was associated with elevated metabolite levels. It is unlikely that these exposure levels would cause acute intoxication, but the long-term health effects of such exposures are unknown. We recommend that OP pesticide use be avoided in areas where children are likely to play.
    [Lu C, Knutson DE, Fisker-Andersen J, Fenske RA. 2001. Environ Health Perspect;109(3):299-303]
  • Agricultural work and the risk of Parkinson's disease in Denmark, 1981-1993
    This study examined the possible association between agricultural and horticultural work and the subsequent morbidity of Parkinson's disease. A high risk of Parkinson's disease was found for the men and women in agriculture and horticulture (134 cases, SHR 132, 95% CI 111-156). Statistically significantly high risks were found for farmers (79 cases, SHR 130, 95% CI 103-163) and for all men in agriculture and horticulture (109 cases, SHR 134, 95% CI 109-162).
    [Tuchsen, F., et al. 2000. Scand J Work Environ Health 26(4):359-362]
  • Biological monitoring of organophosphorus pesticide exposure among children of agricultural workers in central Washington State.
    Children up to 6 years of age who lived with pesticide applicators were monitored for increased risk of pesticide exposure: 48 pesticide applicator and 14 reference families were recruited from an agricultural region of Washington State in June 1995. A total of 160 spot urine samples were collected from 88 children, including repeated measures 3-7 days apart. Dimethylthiophosphate (DMTP) was the dominant metabolite and levels were significantly higher in applicator children than in reference children, with median concentrations of 0.021 and 0.005 microg/ml, respectively; maximum concentrations were 0.44 and 0.10 microg/ml, respectively. Percentages of detectable samples were 47% for applicator children and 27% for reference children. A marginally significant trend of increasing concentration was observed with decreasing age among applicator children, and younger children within these families had significantly higher concentrations when compared to their older siblings. Applicator children living less than 200 feet from an orchard were associated with higher frequency of detectable DMTP levels than nonproximal applicator children. These results indicate that applicator children experienced higher organophosphorus pesticide exposures than did reference children in the same community and that proximity to spraying is an important contributor to such exposures. Trends related to age suggest that child activity is an important variable for exposure. It is unlikely that any of the observed exposures posed a hazard of acute intoxication. This study points to the need for a more detailed understanding of pesticide exposure pathways for children of agricultural workers.
    [Loewenherz C, Fenske RA, Simcox NJ, Bellamy G, Kalman D. 1997. Environ Health Perspect.;105(12):1344-53]
  • Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.
    In this study of cancer in offspring we demonstrate that factors linked to horticulture and use of pesticides are associated with cancer at an early age, whereas factors in animal husbandry, in particular poultry farming, are associated with cancers in later childhood and young adulthood. Incident cancer was investigated in offspring born in 1952-1991 to parents identified as farm holders in agricultural censuses in Norway in 1969-1989. In the follow-up of 323,292 offspring for 5.7 million person-years, 1,275 incident cancers were identified in the Cancer Registry for 1965-1991. The standardized incidence for all cancers was equal to the total rural population of Norway, but cohort subjects had an excess incidence of nervous-system tumours and testicular cancers in certain regions and strata of time that could imply that specific risk factors were of importance. Classification of exposure indicators was based on information given at the agricultural censuses. Risk factors were found for brain tumours, in particular non-astrocytic neuroepithelial tumours: for all ages, pig farming tripled the risk [rate ratio (RR), 3.11; 95% confidence interval (CI), 1.89-5.13]; indicators of pesticide use had an independent effect of the same magnitude in a dose-response fashion, strongest in children aged 0 to 14 years (RR, 3.37; 95% CI, 1.63-6.94). Horticulture and pesticide indicators were associated with all cancers at ages 0 to 4 years, Wilms' tumour, non-Hodgkin's lymphoma, eye cancer and neuroblastoma. Chicken farming was associated with some common cancers of adolescence, and was strongest for osteosarcoma and mixed cellular type of Hodgkin's disease. The main problem in this large cohort study is the crude exposure indicators available; the resulting misclassification is likely to bias any true association towards unity.
    [Kristensen, P., et al. 1996. Int J Cancer 65(1):39-50]
  • Pesticides in household dust and soil: exposure pathways for children of agricultural families.
    Child of agriculture families are likely to be exposed to agricultural chemicals, even if they are not involved in farm activities. This study was designed to determine whether such children are exposed to higher levels of pesticides than children whose parents are not involved in agriculture and whose homes are not close to farms. Household dust and soil samples were collected in children's play areas from 59 residences in eastern Washington State (26 farming, 22 farmworker, and 11 nonfarming families). The majority of the farm families lived within 200 feet of an operating apple or pear orchard, whereas all reference homes were located at least a quarter of a mile from an orchard. Four organophosphorous (OP) insecticides commonly used on tree fruit were targeted for analysis: azinphosmethyl, chlorpyrifos, parathion, and phosmet. Pesticide concentrations in household dust were significantly higher than in soil for all groups. OP levels for farmer/farm-worker families ranged from nondetectable to 930 ng/g in soil (0.93 ppm) and from nondetectable to 17,000 ng/g in dust (17 ppm); all four OP compounds were found in 62% of household dust samples, and two-thirds of the farm homes contained at least one OP above 1000 ng/g.These results demonstrate that children of agricultural families have a higher potential for exposure to OP pesticides than children of nonfarm families in this region. Children's total and cumulative exposure to this pesticide class from household dust, soil, and other sources warrants further investigation.
    [Simcox N.J., Fenske, R.A, Wolz. S.A, Lee, I.C, and Kalman, D.A. 1995. Environ Health Perspect. 103(12):1126-34.]
  • A case-control study of brain gliomas and occupational exposure to chemical carcinogens: the risk to farmers.
    A case control study shows an increased risk for brain gliomas for farmers who reported the use of pesticides and fertilizers (RR 1.6) with a significant increased risk for those that used insecticides and fungicides (RR 2.0).
    [Musicco, M., et al. 1988. American Journal of Epidemiology 128(4):778-785]

GMOs

  • Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada
    Study analyzed blood samples for 39 nonpregnant women and 30 pregnant woman and their fetuses and finds pesticides associated with genetically engineered (GE) foods are present in maternal, fetal and nonpregnant women's blood. Baccillus thuringiensis (Bt) was detected in 93% of maternal blood samples, 80% of fetal blood samples and 69% of the nonpregnant women's blood. Glufosinate was detected in 18% of nonpregnant women's blood but not detected in maternal and fetal blood. It's metabolite, 3-mehtylphosphinicopropionic acid (3-MPPA), however, was detected in 100% of maternal and umbilical cord blood samples and in 67 % of the nonpregnant women's blood. Visit the Genetic Engineering page and Daily News.
    [Aris A, Leblanc S. Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada. Reprod Toxicol (2011)]

Infants/Children

  • Agricultural crop density in the municipalities of France and incidence of childhood leukemia: An ecological study
    Pesticide exposure is suspected to play a role in the etiology of childhood leukemia (AL). Various sources of exposure have been explored, but few studies have investigated the risk of childhood AL in relation to residential exposure to agricultural pesticides. Since around 50% of France is agricultural land, with marked pesticide use, France is a suitable location to investigate for an association. We aimed to analyze the association between the agricultural crop density in the municipalities of France and the incidence of childhood AL between 1990 and 2014. 11,487 cases of AL diagnosed in children aged 0–14 years were registered by the French National Registry of Childhood Hematological Malignancies over 1990–2014. National agricultural census data for 1990, 2000 and 2010 were used to estimate the densities of the most common crops in France. The incidence of AL was estimated in the 35,512 municipalities, by age and gender, and 3 observation periods, and expressed as the standardized incidence ratio (SIR). We observed a moderate log-linear association between viticulture density and the incidence of AL, with a 3% increase in SIR for a 10% increase in viticulture density (SIRR = 1.03; 95%CI [1.00–1.06]). The association remained for lymphoblastic AL but not for myeloid AL. The association was stable after stratification by geographic area, age and period, and after adjustment on UV radiation and a French deprivation index. No consistent association was observed for other crop types. This nationwide study shows a moderate increase in incidence of childhood AL in municipalities where viticulture is common. Future individual studies are needed to know whether this observation is confirmed and related to particular use of pesticides.
    [Coste, A., Goujon, S., Faure, L., Hémon, D. and Clavel, J., 2020. Environmental Research, p.109517.]
  • Environmental Exposures Related to Parental Habits in the Perinatal Period and the Risk of Wilms' Tumor in Children
    Wilms' tumor is the most frequently diagnosed renal tumor in children. Little is known about its etiology. The aim of this study was to investigate the potential role of specific exposures related to parental habits such as parental smoking, maternal alcohol consumption and the use of household pesticides during pregnancy. The ESTELLE study was a nationwide case-control study that included 117 Wilms' tumor cases and 1100 control children from the general French population, frequency-matched by age and gender. Unconditional logistic regression was used to estimate odds ratios and 95 % confidence intervals. After controlling for matching variables and potential confounders, the maternal use of any type of pesticide during pregnancy was associated with the risk of Wilms' tumor in children (OR 1.6 [95 % CI 1.1-2.3]). Insecticides were the most commonly reported type of pesticide and there was a positive association with their use (OR 1.7 [95 % CI 1.1-2.6]. The association was stronger when they were used more often than once a month (OR 1.9 [95 % CI 1.2-3.0]. Neither maternal smoking during pregnancy nor paternal smoking during preconception/pregnancy was associated with a risk of Wilms' tumor (ORs 1.1[95 % CI 0.7-1.8] and 1.1 [95 % CI 0.7-1.7], respectively). No association was observed with maternal alcohol intake during pregnancy (OR 1.2 [95 % CI 0.8-2.0]). Our findings suggest an association between the maternal use of household pesticides during pregnancy and the risk of Wilms' tumor.
    [Rios, P., Bauer, H., Schleiermacher, G., Pasqualini, C., Boulanger, C., Thebaud, E., Gandemer, V., Pellier, I., Verschuur, A., Sudour-Bonnange, H. and Coulomb-l'Hermine, A., 2020. Cancer Epidemiology, 66, p.101706.]
  • Prenatal pesticide exposure and childhood leukemia – A California statewide case-control study
    A number of epidemiologic studies with a variety of exposure assessment approaches have implicated pesticides as risk factors for childhood cancers. Here we explore the association of pesticide exposure in pregnancy and early childhood with childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) utilizing land use and pesticide use data in a sophisticated GIS tool. We identified cancer cases less than 6 years of age from the California Cancer Registry and cancer-free controls from birth certificates. Analyses were restricted to those living in rural areas and born 1998–2011, resulting in 162 cases of childhood leukemia and 9,805 controls. Possible carcinogens were selected from the Environmental Protection Agency's classifications and pesticide use was collected from the California Department of Pesticide Regulation's (CDPR) Pesticide Use Reporting (PUR) system and linked to land-use surveys. Exposures for subjects were assessed using a 4000m buffer around the geocoded residential addresses at birth. Unconditional logistic and hierarchical regression models were used to assess individual pesticide and pesticide class associations. We observed elevated risks for ALL with exposure to any carcinogenic pesticide (adjusted Odds Ratio (aOR): 2.83, 95% CI: 1.67–4.82), diuron (Single-pesticide model, adjusted (OR): 2.38, 95% CI: 1.57–3.60), phosmet (OR: 2.10, 95% CI: 1.46–3.02), kresoxim-methyl (OR: 1.77, 95% CI: 1.14–2.75), and propanil (OR: 2.58, 95% CI: 1.44–4.63). Analyses based on chemical classes showed elevated risks for the group of 2,6-dinitroanilines (OR: 2.50, 95% CI: 1.56–3.99), anilides (OR: 2.16, 95% CI: 1.38–3.36), and ureas (OR: 2.18, 95% CI: 1.42–3.34). Our findings suggest that in rural areas of California exposure to certain pesticides or pesticide classes during pregnancy due to residential proximity to agricultural applications may increase the risk of childhood ALL and AML. Future studies into the mechanisms of carcinogenicity of these pesticides may be beneficial.
    [Park, A.S., Ritz, B., Yu, F., Cockburn, M. and Heck, J.E., 2020. International journal of hygiene and environmental health, 226, p.113486.]
  • Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study
    Data from California state mandated Pesticide Use Reporting were integrated into a geographic information system tool to estimate prenatal and infant exposures to pesticides (measured as pounds of pesticides applied per acre/month within 2000 m from the maternal residence). 11 high use pesticides were selected for examination a priori according to previous evidence of neurodevelopmental toxicity in vivo or in vitro (exposure defined as ever v never for each pesticide during specific developmental periods). Risk of autism spectrum disorder was associated with prenatal exposure to glyphosate (odds ratio 1.16, 95% confidence interval 1.06 to 1.27), chlorpyrifos (1.13, 1.05 to 1.23), diazinon (1.11, 1.01 to 1.21), malathion (1.11, 1.01 to 1.22), avermectin (1.12, 1.04 to 1.22), and permethrin (1.10, 1.01 to 1.20). For autism spectrum disorder with intellectual disability, estimated odds ratios were higher (by about 30%) for prenatal exposure to glyphosate (1.33, 1.05 to 1.69), chlorpyrifos (1.27, 1.04 to 1.56), diazinon (1.41, 1.15 to 1.73), permethrin (1.46, 1.20 to 1.78), methyl bromide (1.33, 1.07 to 1.64), and myclobutanil (1.32, 1.09 to 1.60); exposure in the first year of life increased the odds for the disorder with comorbid intellectual disability by up to 50% for some pesticide substances. 
    [von Ehrenstein, et al. 2019. BMJ 2019;364:l962 ]
  • A Pilot Study Evaluating Organochlorine and Organophosphate Pesticide Exposure in Children and Adolescents of Mexican Descent Residing in Hidalgo County, Texas.
    Children and adolescents of Mexican descent residing in Hidalgo County (TX) were evaluated for exposure to organochlorine (OC) and organophosphate (OP) pesticides. A convenience sample of 60 participants enrolled in our pilot study. The lipid-adjusted serum concentrations of nine OC metabolites and creatinine-adjusted urinary concentrations of six OP metabolites were measured and compared with data from the Centers for Disease Control and Prevention's Fourth Report on Human Exposure to Environmental Chemicals. Descriptive statistics were used to summarize the concentration levels for each metabolite. Study participants were aged 5-18 years. For most of the OC and OP metabolites, our findings showed that participants had concentration levels within the distributional range of the national data. However, notable outlying levels (greater than the 95th percentile in the Fourth Report) were identified for the following OC metabolites: gamma-hexachlorocyclohexane, p,p'-dichlorodiphenyldichloroethene, and p,p'-dichlorodiphenyltrichloroethane. Among the children aged 5-11 years, one child had an outlying value for the OP metabolite: dimethylphosphate. Our findings on the levels of OC and OP pesticide exposure enhances the credibility of national estimates, and can serve as baselines for children and adolescents of Mexican descent residing in Lower Rio Grande Valley. Furthermore, our study contributes to the lacunae of knowledge regarding environmental exposures and presses further investigation of outlying OC and OP exposure levels.
    [Hernandez M, Hernández-Valero MA, García-Prieto C, et al. 2018. J Immigr Minor Health. doi: 10.1007/s10903-018-0791-9.]
  • Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study
    Glyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length. Urine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length. The mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5-7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths. This is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized.
    [Parvez S, Gerona RR, Proctor C, Friesen M, Ashby JL, Reiter JL, Lui Z, Winchester PD. 2018. Environ Health. 17(1):23. doi: 10.1186/s12940-018-0367-0.]
  • Organophosphate and Pyrethroid Pesticide Exposures Measured before Conception and Associations with Time to Pregnancy in Chinese Couples Enrolled in the Shanghai Birth Cohort.
    Pesticides have been associated with reproductive disorders, but there is limited research on pesticide exposures and human fertility. We aimed to investigate the effects of preconception exposure to pesticides on time to pregnancy (TTP) and on infertility in a general population of couples planning to become pregnant in Shanghai, China. A total of 615 women who were planning a pregnancy were enrolled before conception and were prospectively followed for 1 y to observe their TTP. Preconception pesticide exposures were assessed by measuring urinary metabolites of organophosphates (OPs) and pyrethroids (PYRs). Fecundability odds ratios (FORs) and odds ratios (ORs) of infertility were estimated using Cox and logistic regression models, respectively. All analyses were repeated after restricting the sample to nulliparous women (n=569). After adjusting for age, prepregnancy BMI, current smoking, education, annual household income, age at menarche, and two items from the Perceived Stress Scale (PSS-10), women in the highest quartile of diethylthiophosphate (DETP; an OP metabolite) had significantly longer TTP [adjusted FOR=0.68 (95% CI: 0.51, 0.92)] and increased infertility [adjusted OR=2.17 (95% CI: 1.19, 3.93)] compared with women in the lowest quartile. The highest versus lowest quartile of 3-phenoxybenzoic acid (3PBA; a PYR metabolite) was associated with longer TTP and infertility, with significant associations in nulliparous women [adjusted FOR=0.72 (95% CI: 0.53, 0.98); adjusted OR for infertility=2.03 (95% CI: 1.10, 3.74)].Our study provides some of the first evidence that preconception OP and PYR exposures are associated with decreased fertility in Chinese couples. Given that OPs and PYRs are rapidly metabolized in humans, more studies are needed to confirm our findings. 
    [Hu Y, Ji L, Zhang Y, Shi R, Han W, Tse LA, et al. 2018. Environ Health Perspect. 126(7):077001]
  • Prenatal organophosphate insecticide exposure and infant sensory function.
    Occupational studies suggest that exposure to organophosphate insecticides (OPs) can lead to vision or hearing loss. Yet the effects of early-life exposure on visual and auditory function are unknown. Here we examined associations between prenatal OP exposure and grating visual acuity (VA) and auditory brainstem response (ABR) during infancy. 30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Grating visual acuity (VA) (n = 179-200) and auditory brainstem response (ABR) (n = 139-183) were assessed at 6 weeks, 9 months, and 18 months. Outcomes included VA score, ABR wave V latency and central conduction time, and head circumference (HC). Associations between sensory outcomes during infancy and cord OPs were examined using linear mixed models. Prenatal chlorpyrifos exposure was associated with lower 9-month grating VA scores; scores were 0.64 (95% CI: -1.22, -0.06) points lower for exposed versus unexposed infants (p = 0.03). The OPs examined were not associated with infant ABR latencies, but chlorpyrifos and phorate were both significantly inversely associated with HC at 9 months; HCs were 0.41 (95% CI: 0.75, 0.6) cm and 0.44 (95% CI: 0.88, 0.1) cm smaller for chlorpyrifos (p = 0.02) and phorate (p = 0.04), respectively.We found deficits in grating VA and HC in 9-month-old infants with prenatal exposure to chlorpyrifos. The clinical significance of these small but statistically significant deficits is unclear. However, the disruption of visual or auditory pathway maturation in infancy could potentially negatively affect downstream cognitive development.
    [Silver MK, Shao J, Ji C, Zhu B, Xu L, Li M, et al. 2018. Int J Hyg Environ Health. pii: S1438-4639(17)30563-1.]
  • A task-based assessment of parental occupational exposure to pesticides and childhood acute lymphoblastic leukemia.
    Associations between parental occupational pesticide exposure and childhood acute lymphoblastic leukemia (ALL) vary across studies, likely due to different exposure assessment methodologies. This study assessed parental occupational pesticide exposure from the year before pregnancy to the child's third year of life for 669 children diagnosed with ALL and 1021 controls. Authors conducted expert rating using task-based job modules (JM) to estimate exposure to pesticides among farmer workers, gardeners, agricultural packers, and pesticide applicators. Compared to complete JMs, partial JMs and JEM led to 3.1% and 9.4% of parents with pesticide exposure misclassified, respectively. Misclassification was similar in cases and controls. Using complete JMs, we observed an increased risk of ALL for paternal occupational exposure to any pesticides (OR=1.7; 95% CI=1.2, 2.5), with higher risks reported for pesticides to treat nut crops (OR=4.5; 95% CI=0.9, 23.0), and for children diagnosed before five years of age (OR=2.3; 95% CI: 1.3, 4.1). Exposure misclassification from JEM attenuated these associations by about 57%. Maternal occupational pesticide exposure before and after birth was not associated with ALL. The risk of ALL was elevated in young children with paternal occupational pesticide exposure during the perinatal period, using more detailed occupational information for exposure classification.
    [Gunier RB, Kang A, Hammond SK, Reinier K, et al. 2017. Environ Res. 156:57-62.]
  • Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: the PELAGIE mother-child cohort.
    The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds.The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Increased prenatal cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3-phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans-DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03).The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age.
    [Viel JF, Rouget F, Warembourg C, Monfort C, et al. 2017. Occup Environ Med. 74(4):275-281.]
  • Biomonitoring of Danish school children and mothers including biomarkers of PBDE and glyphosate.
    The Danish part of the large European Human biomonitoring pilot project Demonstration of a study to Coordinate and Perform Human biomonitoring on a European Scale (DEMOCOPHES) investigated the urine, hair and blood concentrations of 66 different environmental chemicals in a group of 145 Danish school children aged 6-11 years and their mothers from rural and urban areas in autumn 2011. Some - but not all - results were published; however, the concurrence of the chemicals has not been assessed. The measured concentrations of polybrominated diphenyl ethers (PBDEs) and glyphosate is assessed to complete the investigation of all 66 chemicals in DEMOCOPHES. The concentrations of PBDEs were measured in plasma samples of 143 mothers and 116 children. Glyphosate was measured in a subsample of 27 urine samples. Previously assessed chemicals were polychlorinated biphenyls (PCBs), and polyfluoroalkyl substances (PFASs) analyzed in blood samples, mercury analyzed in hair, and phthalate metabolites, parabens, phenols, cadmium, paracetamol and cotinine analyzed in urine samples. Differences in concentrations between mothers and children were assessed, and the associations between the concentrations of the different environmental chemicals. investigated by correlation analysis. PBDE47 was found in relatively high levels compared with previous Danish results in both mothers and children, with a significantly higher level in the children compared to their mothers. Glyphosate in concentrations around 1 ng/mL was detected in all 27 samples. The analyzed environmental exposures seem to follow a pattern where chemicals within the same classes are strongly correlated and where children and mothers are exposed to the same chemicals.The correlations between the measured environmental chemicals indicate that a specific exposure pattern may exist, where people who are highly exposed to one class of environmental chemicals also may be highly exposed to certain other classes. As some of the compounds were measured in higher levels in children compared to mothers, increased focus also on the exposure in young children is recommended. For more detailed investigation of specific exposure sources more studies with increased power and detailed questionnaires should be developed.
    [Knudsen LE, Hansen PW, Mizrak S, Hansen HK, Mørck TA, et al. 2017. Rev Environ Health. 32(3):279-290]
  • Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder.
    Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800μg (median). Mothers' addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. High FA intake (≥800μg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800μg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed.
    [Schmidt RJ, Kogan V, Shelton JF, Delwiche L, Hansen RL, et al. 2017. Environ Health Perspect. 125(9):097007.]
  • Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk-an exploratory study
    Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that epigenetics might be involved. The aim of the present study was therefore to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children.Whole blood DNA methylation patterns in 48 children (6-11 years of age), whose mothers were occupationally unexposed or exposed to pesticides early in pregnancy, were determined by Illumina 450 K methylation arrays.A specific methylation profile was observed in prenatally pesticide exposed children carrying the PON1 192R-allele. Differentially methylated genes were enriched in several neuroendocrine signaling pathways including dopamine-DARPP32 feedback (appetite, reward pathways), corticotrophin releasing hormone signaling, nNOS, neuregulin signaling, mTOR signaling, and type II diabetes mellitus signaling. Furthermore, we were able to identify possible candidate genes which mediated the associations between pesticide exposure and increased leptin level, body fat percentage, and difference in BMI Z score between birth and school age.DNA methylation may be an underlying mechanism explaining an adverse cardio-metabolic health profile in children carrying the PON1 192R-allele and prenatally exposed to pesticides.
    [Declerck K, Remy S, Wohlfahrt-Veje C, Main KM, et al. 2017. Clin Epigenetics. 9:35. ]
  • Persistent Environmental Toxicants in Breast Milk and Rapid Infant Growth.
    Many environmental toxicants are passed to infants in utero and through breast milk. Exposure to toxicants during the perinatal period can alter growth patterns, impairing growth or increasing obesity risk. Previous studies have focused on only a few toxicants at a time, which may confound results. We investigated levels of 26 toxicants in breast milk and their associations with rapid infant growth, a risk factor for later obesity.We used data from the Norwegian HUMIS study, a multi-center cohort of 2,606 mothers and newborns enrolled between 2002 and 2008. Milk samples collected 1 month after delivery from a subset of 789 women oversampled by overweight were analyzed for toxicants including polychlorinated biphenyls (PCBs), heavy metals, and pesticides. Growth was defined as change in weight-for-age z-score between 0 and 6 months among the HUMIS population, and rapid growth was defined as change in z-score above 0.67. We used a Bayesian variable selection method to determine the exposures that most explained variation in the outcome. Identified toxicants were included in logistic and linear regression models to estimate associations with growth, adjusting for maternal age, smoking, education, pre-pregnancy body mass index (BMI), gestational weight gain, parity, child sex, cumulative breastfeeding, birth weight, gestational age, and preterm status.Of 789 infants, 19.2% displayed rapid growth. The median maternal age was 29.6 years, and the median pre-pregnancy BMI was 24.0 kg/m2, with 45.3% of mothers overweight or obese. Rapid growers were more likely to be firstborn. Hexachlorobenzene, β-hexachlorocyclohexane (β-HCH), and PCB-74 were identified in the variable selection method. An interquartile range (IQR) increase in β-HCH exposure was associated with a lower odds of rapid growth (OR 0.63, 95% CI 0.42-0.94). Newborns exposed to high levels of β-HCH showed reduced infant growth (β = -0.03, 95% CI -0.05 to -0.01 for IQR increase in breast milk concentration). No other significant associations were found. Our results suggest that early life β-HCH exposure may be linked to slowed growth. Further research is warranted on the potential mechanism behind this association and the longer-term metabolic effects of perinatal β-HCH exposure.
    [Criswell R, Lenters V, Mandal S, Stigum H, et al. 2017. Ann Nutr Metab. 70(3):210-216. ]
  • Prenatal and postnatal exposure to organophosphate pesticides and childhood neurodevelopment in Shandong, China.
    Although studies in laboratory animals demonstrate neurodevelopmental deficits caused by prenatal or postnatal organophosphate pesticide (OP) exposure, there is limited evidence on effects induced by not only prenatal but also postnatal exposure of children to OPs. We measured diethylphosphate (DE), dimethylphosphate (DM), and total dialkylphosphate (DAP) metabolites in maternal and child urine at 12 and 24months of age and examined their relationship with developmental quotients (DQs) in 12-month-old infants and 24-month-old children in Shandong, China.The median concentrations of total DAP metabolites (DAPs) in child urine [371.97nmol/g creatinine (12-month-old infants), 538.64nmol/g creatinine (24-month-old children)] were higher than those in maternal urine (352.67nmol/g creatinine). Prenatal OP exposure was negatively associated with 24-month-old children's DQs, especially among boys. A 10-fold increase in prenatal DEs and DAPs was associated with a 2.59- and 2.49-point decrease in social domain DQ scores in 24-month-old children (n=262), respectively. However, positive association of postnatal exposure to OPs and 24-month-old children's DQs was observed (n=237). Neither prenatal nor postnatal exposure to OPs was related to 12-month-old infants' DQs.These data suggested that prenatal OP exposure could adversely affect children's neurodevelopment at 24months of age, especially among boys. The prenatal period might be a critical window of OP exposure. In view of the positive association with postnatal OP exposure, it is necessary to interpret findings with caution.
    [Wang Y, Zhang Y, Ji L, Hu Y, et al. 2017. Environ Int. 108:119-126.]
  • Residential Pesticide Exposures in Pregnancy and the Risk of Sporadic Retinoblastoma: A Report From the Children's Oncology Group.
    Study examined whether parental pesticide exposure contributes to the development of sporadic retinoblastoma. Data were collected by a large multicenter study of sporadic retinoblastoma in which parents of 99 unilateral and 56 bilateral age-matched case-control pairs were interviewed by telephone. Unilateral retinoblastoma was associated with parental insecticide use (odds ratio [OR], 2.8; confidence interval [CI], 1.1-6.7) and the use of professional lawn or landscape services (OR, 2.8; CI, 1.0-8.2). For bilateral disease study observed large point estimates for several exposures but the small number of cases rendered these results uninformative (ie, resulted in wide confidence intervals). Whether parents used the pesticide inside vs outside the home did not appear to modify risk estimates for unilateral retinoblastoma (OR, 2.5; CI, 0.9-7.0 vs OR, 2.5; CI, 1.0-6.5), nor did the type, frequency, timing related to pregnancy, or applicator of pesticide used influence estimates to an appreciable degree for disease. Results suggest that parental pesticide exposure before or during pregnancy may play a role in the development of childhood retinoblastoma. Retrospectively collected exposure data introduces the possibility of recall bias; therefore, results should be interpreted cautiously until additional studies are conducted.
    [Omidakhsh N, Ganguly A, Bunin GR, et al. 2017. Am J Ophthalmol. 176:166-173]
  • Residential proximity to agricultural fumigant use and IQ, attention and hyperactivity in 7-year old children
    Our objective was to examine the relationship between residential proximity to agricultural fumigant use and neurodevelopment in 7-year old children. Participants were living in the agricultural Salinas Valley, California and enrolled in the Center for the Health Assessment of Mothers and Children Of Salinas (CHAMACOS) study. We administered the Wechsler Intelligence Scale for Children (4th Edition) to assess cognition and the Behavioral Assessment System for Children (2nd Edition) to assess behavior. We estimated agricultural fumigant use within 3, 5 and 8km of residences during pregnancy and from birth to age 7 using California's Pesticide Use Report data. We evaluated the association between prenatal (n = 285) and postnatal (n = 255) residential proximity to agricultural use of methyl bromide, chloropicrin, metam sodium and 1,3-dichloropropene with neurodevelopment. We observed decreases of 2.6 points (95% Confidence Interval (CI): -5.2, 0.0) and 2.4 points (95% CI: -4.7, -0.2) in Full-Scale intelligence quotient for each ten-fold increase in methyl bromide and chloropicrin use within 8km of the child's residences from birth to 7-years of age, respectively. There were no associations between residential proximity to use of other fumigants and cognition or proximity to use of any fumigant and hyperactivity or attention problems. These findings should be explored in larger studies.
    [Gunier RB, Bradman A, Castorina R, Holland NT, et al. 2017. Environ Res. 158:358-365]
  • Adverse Associations of both Prenatal and Postnatal Exposure to Organophosphorous Pesticides with Infant Neurodevelopment in an Agricultural Area of Jiangsu Province, China.
    Prenatal exposure to organophosphorous (OP) pesticides has been found to be associated with adverse effects on child neurodevelopment, but evidence on potential effects induced by both prenatal and postnatal OP exposure in infants is limited.Our aim was to investigate the associations of both prenatal and postnatal OP exposure with birth outcomes and infant neurodevelopment.Exposure to OP in 310 mother-infant pairs was assessed by measuring dimethylphosphate (DM), diethylphosphate (DE), and total dialkylphosphate (DAP) metabolites in urines from pregnant women and their children at 2 years of age. The Gesell Developmental Schedules was administered to examine neurodevelopment of 2-year-old children.Based on the Gesell Developmental Schedules, the proportions of children with developmental delays were < 6%. Adverse associations between head circumference at birth and prenatal OP exposure were demonstrated. Both prenatal and postnatal OP exposure was significantly associated with increased risk of being developmentally delayed. Specifically, odds ratio (OR) value for prenatal DEs was 9.75 (95% CI: 1.28, 73.98, p = 0.028) in the adaptive area, whereas in the social area, OR values for postnatal DEs and DAPs were 9.56 (95% CI: 1.59, 57.57, p = 0.014) and 12.00 (95% CI: 1.23, 117.37, p = 0.033), respectively. Adverse associations were observed only in boys, not in girls.Both prenatal and postnatal OP exposure may adversely affect the neurodevelopment of infants living in the agricultural area. The present study adds to the accumulating evidence on associations of prenatal and postnatal OP exposure with infant neurodevelopment.
    [Liu P, Wu C, Chang X, Qi X, Zheng M, Zhou Z. 2016. Environ Health Perspect. 124(10):1637-1643.]
  • Agricultural crop exposure and risk of childhood cancer: new findings from a case-control study in Spain.
    Childhood cancer is the main cause of disease-related death in children in Spain. Although little is known about the etiology, environmental factors are potential explanations for a fraction of the cases. Previous studies have shown pesticides to be associated with childhood cancer. The difficulty of collecting personal environmental exposure data is an important limitation; this lack of information about pesticides motivates the development of new methods to subrogate this exposure. We developed a crop exposure index based on geographic information to study the relationship between exposure to different types of crops and risk of childhood tumors.We conducted a population-based case-control study of childhood cancer covering 3350 cases and 20,365 controls in two Spanish regions. We found excess of risk among children living in the proximity of crops. For total crops our results showed excesses of risk for almost all diagnostic groups and increasing risk with increasing crop index value. Analyses by region and individual type of crop also showed excess of risk.The results suggest that living in the proximity of cultivated land could be a risk factor for several types of cancer in children.
    [Gómez-Barroso D, García-Pérez J, López-Abente G, et al. 2016. Int J Health Geogr. 15(1):18]
  • An Observational Study to Evaluate Associations Between Low-Level Gestational Exposure to Organophosphate Pesticides and Cognition During Early Childhood.
    Prenatal exposure to organophosphate pesticides, which is ubiquitous, may be detrimental to neurological development. We examined 327 mother/infant pairs in Cincinnati, Ohio, between 2003 and 2006 to determine associations between prenatal exposure to organophosphate pesticides and neurodevelopment. Twice during pregnancy urinary concentrations of 6 common dialkylphosphates, nonspecific metabolites of organophosphate pesticides, were measured. Aggregate concentrations of diethylphosphates, dimethylphosphates, and total dialkylphosphates were calculated. Bayley Scales of Infant Development, Second Edition-Mental and Psychomotor Developmental indices were administered at ages 1, 2, and 3 years, the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, at age 4, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at age 5. Mothers with higher urinary total dialkylphosphate concentrations reported higher levels of socioeconomic status and increased fresh fruit and vegetable intake. We found no associations between prenatal exposure to organophosphate pesticides and cognition at 1-5 years of age. In our cohort, exposure to organophosphate pesticides during pregnancy was not associated with cognition during early childhood. It is possible that a higher socioeconomic status and healthier diet may protect the fetus from potential adverse associations with gestational organophosphate pesticide exposure, or that dietary exposure to the metabolites is innocuous and not an ideal measure of exposure to the parent compound.
    [Donauer S, Altaye M, Xu Y, Sucharew H, et al. 2016. Am J Epidemiol. 184(5):410-8. ]
  • Effect of Prenatal Exposure to Pesticides on Children's Health.
    The aim of this study was to summarize the current state of knowledge on pesticide-related fertility problems and disadventeges of childrens due to prenatal pesticides exposure. Available literature was analyzed. Due to the extent of the issue, the study focuses on epidemiological studies conducted in humans, despite evidence from in vitro and animal studies. It seems certain that exposure to harmful chemicals is one of the factors that may cause a decline in fertility and problems with conceiving, whereas exposure during pregnancy can impair foetal development. Prenatal exposure may also result in the occurrence of childhood cancer and neurobehavioral disorders. The meaning of the project is to summarize the role of pesticides in the process of reproduction. This applies especially to people working in agriculture, since they might be occupationally exposed to pesticides.
    [Matysiak M, Kruszewski M, Jodlowska-Jedrych B, Kapka-Skrzypczak L. 2016. J Environ Pathol Toxicol Oncol. 35(4):375-386.]
  • Environmental pollutants and child health-A review of recent concerns
    In recent years, many new studies have evaluated associations between environmental pollutants and child health. This review aims to provide a broad summary of this literature, comparing the state of epidemiological evidence for the effects of a wide range of environmental contaminants (air pollutants, heavy metals, organochlorine compounds, perfluoroalkyl substances, polybrominated diphenyl ethers, pesticides, phthalates and bisphenol A) on child health outcomes. The review addresses effects on foetal growth and prematurity, neurodevelopment, respiratory and immune health, and childhood growth and obesity. Findings of recent prospective studies and meta-analyses have corroborated previous good evidence, often at lower exposure levels, for effects on foetal growth of air pollution and polychlorinated biphenyls (PCBs), for neurotoxic effects of lead, methylmercury, PCBs and organophosphate pesticides, and for respiratory health effects of air pollution. Moderate evidence has emerged for a potential role of environmental pollutants in attention deficit hyperactivity disorder and autism (lead, PCBs, air pollution), respiratory and immune health (dichlorodiphenyldichloroethylene - DDE - and PCBs), and obesity (DDE). In addition, there is now moderate evidence that certain chemicals of relatively recent concern may be associated with adverse child health outcomes, specifically perfluorooctanoate and foetal growth, and polybrominated diphenyl ethers and neurodevelopment. For other chemicals of recent concern, such as phthalates and bisphenol A, the literature is characterised by large inconsistencies preventing strong conclusions. In conclusion, since most of the recent literature evaluates common exposures in the general population, and not particularly high exposure situations, this accumulating body of evidence suggests that the unborn and young child require more protection than is currently provided. Large, coordinated research efforts are needed to improve understanding of long-term effects of complex chemical mixtures.
    [Vrijheid M, Casas M, Gascon M, Valvi D, Nieuwenhuijsen M. 2016. Int J Hyg Environ Health. 219(4-5):331-42]
  • Exposure to pyrethroid pesticides and the risk of childhood brain tumors in East China
    Pesticide exposure is hypothesized as one of the risk factors for the development of childhood brain tumors (CBT). This hospital-based case-control study evaluated the association of pyrethroid pesticide exposure with the risk for CBT in a children population in East China. In total, 161 CBT cases and 170 controls were recruited from 2 children's medical centers in Shanghai (Xinhua Hospital and Shanghai Children's Medical Center) between September 2012 and June 2015. The cases and controls were matched for age, sex, and province of residence. Pyrethroid pesticide exposure was evaluated by urinalysis of 3 nonspecific metabolites of pyrethroids (cis-DCCA, trans-DCCA, and 3-PBA) using gas chromatography-mass spectrometry (GC-MS) detection and by administering a questionnaire. Unconditional logistic regression showed that trans-DCCA, 3-PBA, and total metabolites (sum of the 3 metabolites) were positively associated with the increased risk of CBT. Children in the highest quartile had a nearly 3-fold increased risk of CBT compared with those in the lowest quartile after adjusting for confounding factors (trans-DCCA, odds ratio (OR) = 2.58, 95% confidence interval (CI), 1.38-4.80, p = 0.003; 3-PBA, OR = 3.26, 95% CI, 1.73-6.14, p < 0.0001; total metabolites, OR = 3.60, 95% CI, 1.87-6.93, p < 0.0001). We also found that exposure to both mosquitocide and cockroach killer was related to the increased risk of CBT (mosquitocide, OR = 1.68, 95% CI, 1.06-2.67, p = 0.027; cockroach killer, OR = 1.83, 95% CI, 1.13-2.95, p = 0.013). These findings indicate that exposure to pyrethroid pesticides might be associated with increased risk of CBT. Prospective cohort studies with larger sample sizes are required to confirm this conclusion
    [Chen S, Gu S, Wang Y, Yao Y, et al. 2016. Environ Pollut. 218:1128-1134.]
  • Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children.
    Attention-deficit/hyperactivity disorder (ADHD) is male predominated, and the etiology of this disorder remains unclear. Past studies have assessed the association of low-level organophosphate pesticide exposure with childhood ADHD cross-sectionally and prospectively. However, the results have been inconsistent. A first case-control study was performed to investigate the relationship between organophosphate pesticide exposure and ADHD with adjusted covariates. We recruited 97 doctor-diagnosed ADHD cases and 110 non-ADHD controls who were 4-15 years of age. Exposure was assessed using urinary levels of dialkylphosphate metabolites, which are biomarkers of OP pesticide exposure. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. The sociodemographics and lifestyles of the children and of the mothers during pregnancy were collected using a questionnaire. The blood lead levels of both groups were similar (1.57 ± 0.73 vs. 1.73 ± 0.77 μg/dL, p = 0.15). Significant urinary concentration differences in one of the six dialkylphosphate metabolites, dimethylphosphate (DMP), were found between ADHD and control subjects (322.92 ± 315.68 vs. 224.37 ± 156.58 nmol/g cr., p < 0.01). A dose-response relationship was found between urinary concentrations of DMP and ADHD in both crude and adjusted analyses (p for trend<0.05). Children with higher urinary DMP concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD. We report a dose-response relationship between child DMP levels and ADHD. Organophosphate pesticide exposure may have deleterious effects on children's neurodevelopment, particularly the development of ADHD.
    [Yu CJ, Du JC, Chiou HC, Chung MY, et al. 2016. Andrology. 4(4):695-705.]
  • Negative Role of the Environmental Endocrine Disruptors in the Human Neurodevelopment
    The endocrine disruptors (EDs) are able to influence the endocrine system, mimicking or antagonizing hormonal molecules. They are bio-persistent for their degradation resistance in the environment. Our research group has investigated by gas chromatography-mass spectrometry (GC-MS) the EDs presence in 35 brain samples, coming from 27 cases of sudden intrauterine unexplained death syndrome (SIUDS) and 8 cases of sudden infant death syndrome (SIDS), collected by centralization in the last year (2015). More in detail, a mixture of 25 EDs has been subjected to analytical procedure, following standard protocols. Among the target analytes, some organochlorine pesticides, that is α-chlordane, γ-chlordane, heptachlor, p,p-DDE, p,p-DDT, and the two most commonly used organophosphorus pesticides (OPPs), chlorpyrifos and chlorfenvinfos, have been found in seven and three samples, respectively. The analytical procedure used to detect the presence of environmental EDs in cortex samples has been successfully implemented on SIUDS and SIDS victims. The environmental EDs have been found to be able to overcome the placental barrier, reaching also the basal ganglia assigned to the control of the vital functions. This finding, related to the OPPs bio-persistence, implies a conceptual redefinition of the fetal-placental and fetal blood-brain barriers: not real safety barriers but simply time-deferral mechanisms of absorption.
    [Roncati L, Termopoli V, Pusiol T. 2016. Front Neurol. 7:143.]
  • Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community.
    Exposure to pesticides has been suggested as a risk factor for childhood leukemia, but definitive evidence on this relation and the specific pesticides involved is still not clear.We carried out a population-based case-control study in a Northern Italy community to assess the possible relation between passive exposure to agricultural pesticides and risk of acute childhood leukemia.We assessed passive pesticide exposure of 111 childhood leukemia cases and 444 matched controls by determining density and type of agricultural land use within a 100-m radius buffer around children's homes. We focused on four common crop types, arable, orchard, vineyard and vegetable, characterized by the use of specific pesticides that are potentially involved in childhood induced leukemia. The use of these pesticides was validated within the present study. We computed the odds ratios (OR) of the disease and their 95% confidence intervals (CI) according to type and density of crops around the children's homes, also taking into account traffic pollution and high-voltage power line magnetic field exposure. Childhood leukemia risk did not increase in relation with any of the crop types with the exception of arable crops, characterized by the use of 2.4-D, MCPA, glyphosate, dicamba, triazine and cypermethrin. The very few children (n=11) residing close to arable crops had an OR for childhood leukemia of 2.04 (95% CI 0.50-8.35), and such excess risk was further enhanced among children aged
    [Malagoli C, Costanzini S, Heck JE, Malavolti M, et al. 2016. Int J Hyg Environ Health. 219(8):742-748.]
  • Pesticide exposure and neurodevelopment in children aged 6-9 years from Talamanca, Costa Rica.
    Certain pesticides may affect children's neurodevelopment. We assessed whether pesticide exposure was associated with impaired neurobehavioral outcomes in children aged 6-9 years. We conducted a cross-sectional study in 140 children living near banana plantations and plantain farms in the Talamanca County, Costa Rica and assessed their neurobehavioral performance. Exposure was determined by analyzing urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy), mancozeb (ethylenethiourea, ETU), and pyrethroids (3-phenoxybenzoic acid, 3-PBA). Repeated urine samples were obtained for 36 children. We estimated associations of pesticide concentrations with neurobehavioral outcomes using multivariable linear and logistic regression models. Median (25th-75th percentiles) TCPy, ETU, and 3-PBA concentrations were 1.4 (.7-3.1), 1.2 (.7-3.0), and .8 (.5-1.5) μg/L, respectively. Intraclass correlation coefficients (ICC) ranged between .32 and .67. After adjustment for potential confounders, higher urinary TCPy concentrations were associated with poorer working memory in boys (n = 59) (β per 10-fold increase in TCPy concentrations = -7.5, 95% CI: -14.4, -.7); poorer visual motor coordination (β = -1.4, 95% CI: -2.7, -.1); increased prevalence of parent-reported cognitive problems/inattention (adjusted OR per 10-fold increase in urinary concentrations = 5.8, 95% CI: 1.6, 22.9), oppositional disorders (aOR = 3.9, 95% CI: 1.0, 16.0), and ADHD (aOR = 6.8, 95% CI: 1.8, 28.6), and; decreased ability to discriminate colors (aOR = 6.6, 95% CI: 1.6, 30.3; the higher the score the worse). Higher ETU concentrations were associated with poorer verbal learning outcomes (β = -7.0, 95% CI: -12.7, -1.3). Higher 3-PBA concentrations were associated with poorer processing speed scores, particularly in girls (β = -8.8, 95% CI: -16.1, -1.4). Our findings indicate that children living near banana and plantain plantations are exposed to pesticides that may affect their neurodevelopment, which for certain domains may differ between boys and girls. We recommend the implementation of measures to reduce pesticide exposure in children living nearby banana plantations.
    [van Wendel de Joode B, Mora AM, Lindh CH, et al. 2016. Cortex. 85:137-150. ]
  • Potential role of organochlorine pesticides in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders: A review.
    Organochlorine pesticides (OCPs) are persistent and bioaccumulative environmental contaminants with potential neurotoxic effects. The growing body of evidence has demonstrated that prenatal exposure to organochlorines (OCs) is associated with impairment of neuropsychological development. The hypothesis is consistent with recent studies emphasizing the correlation of environmental as well as genetic factors to the pathophysiology of neurodevelopmental and neurobehavioral defects. It has been suggested that maternal exposure to OCPs results in impaired motor and cognitive development in newborns and infants. Moreover, in utero exposure to these compounds contributes to the etiology of autism. Although impaired neurodevelopment occurs through prenatal exposure to OCs, breastfeeding causes postnatal toxicity in the infants. Parkinson's disease (PD) is another neurological disorder, which has been associated with exposure to OCs, leading to α-synuclein accumulation and depletion of dopaminergic neurons. The study aimed to review the potential association between pre- and post-natal exposure to OCs and impaired neurodevelopmental processes during pregnancy and neuropsychological diseases such as PD, behavioral alterations, seizures and autism.
    [Saeedi Saravi SS, Dehpour AR. 2016. Life Sci.145:255-64.]
  • Prenatal exposure to multiple pesticides is associated with auditory brainstem response at 9months in a cohort study of Chinese infants
    Pesticides are associated with poorer neurodevelopmental outcomes, but little is known about the effects on sensory functioning.Auditory brainstem response (ABR) and pesticide data were available for 27 healthy, full-term 9-month-old infants participating in a larger study of early iron deficiency and neurodevelopment. Cord blood was analyzed by gas chromatography-mass spectrometry for levels of 20 common pesticides. The ABR forward-masking condition consisted of a click stimulus (masker) delivered via ear canal transducers followed by an identical stimulus delayed by 8, 16, or 64 milliseconds (ms). ABR peak latencies were evaluated as a function of masker-stimulus time interval. Shorter wave latencies reflect faster neural conduction, more mature auditory pathways, and greater degree of myelination. Linear regression models were used to evaluate associations between total number of pesticides detected and ABR outcomes. We considered an additive or synergistic effect of poor iron status by stratifying our analysis by newborn ferritin (based on median split).Infants in the sample were highly exposed to pesticides; a mean of 4.1 pesticides were detected (range 0-9). ABR Wave V latency and central conduction time (CCT) were associated with the number of pesticides detected in cord blood for the 64ms and non-masker conditions. A similar pattern seen for CCT from the 8ms and 16ms conditions, although statistical significance was not reached. Increased pesticide exposure was associated with longer latency. The relation between number of pesticides detected in cord blood and CCT depended on the infant's cord blood ferritin level. Specifically, the relation was present in the lower cord blood ferritin group but not the higher cord blood ferritin group.ABR processing was slower in infants with greater prenatal pesticide exposure, indicating impaired neuromaturation. Infants with lower cord blood ferritin appeared to be more sensitive to the effects of prenatal pesticide exposure on ABR latency delay, suggesting an additive or multiplicative effect.
    [Sturza J, Silver MK, Xu L, Li M, et al. 2016. Environ Int.92-93:478-85.]
  • Prenatal Organophosphorus Pesticide Exposure and Child Neurodevelopment at 24 Months: An Analysis of Four Birth Cohorts.
    Organophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001.We conducted a pooled analysis of four birth cohorts (children's centers; n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months. Using general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (ΣDAP), diethyl (ΣDEP), and dimethylphosphate (ΣDMP) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype.There was significant heterogeneity in the center-specific estimates of association for ΣDAP and ΣDMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ΣDAP (p = 0.06) and ΣDMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ΣDAP (β = -4.17; 95% CI: -7.00, -1.33) and ΣDMP (β = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (β per 10-fold increase in ΣDAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative associations of ΣDAP and ΣDEP with the 24-month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics. Data pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution because of significant heterogeneity in associations by center, race/ethnicity, and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure.
    [Engel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, et al. 2016. Environ Health Perspect. 124(6):822-30]
  • Prenatal Triclosan Exposure and Anthropometric Measures Including Anogenital Distance in Danish Infants.
    Prenatal triclosan exposure is associated with reduced head circumference, a trait linked to cognitive impairment.
    [Lassen et al. 2016. Environmental Health Perspectives doi: 10.1289/ehp.1409637.]
  • Research Review: Environmental exposures, neurodevelopment, and child mental health - new paradigms for the study of brain and behavioral effects.
    Environmental exposures play a critical role in the genesis of some child mental health problems.We open with a discussion of children's vulnerability to neurotoxic substances, changes in the distribution of toxic exposures, and cooccurrence of social and physical exposures. We address trends in prevalence of mental health disorders, and approaches to the definition of disorders that are sensitive to the subtle effects of toxic exposures. We suggest broadening outcomes to include dimensional measures of autism spectrum disorders, attention-deficit hyperactivity disorder, and child learning capacity, as well as direct assessment of brain function.We consider the impact of two important exposures on children's mental health: lead and pesticides. We argue that longitudinal research designs may capture the cascading effects of exposures across biological systems and the full-range of neuropsychological endpoints. Neuroimaging is a valuable tool for observing brain maturation under varying environmental conditions. A dimensional approach to measurement may be sensitive to subtle subclinical toxic effects, permitting the development of exposure-related profiles and testing of complex functional relationships between brain and behavior. Questions about the neurotoxic effects of chemicals become more pressing when viewed through the lens of environmental justice.Reduction in the burden of child mental health disorders will require longitudinal study of neurotoxic exposures, incorporating dimensional approaches to outcome assessment, and measures of brain function. Research that seeks to identify links between toxic exposures and mental health outcomes has enormous public health and societal value.
    [Rauh VA, Margolis AE. 2016. J Child Psychol Psychiatry. 57(7):775-93.]
  • Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children.
    Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity.We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression.Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = -3.0; 95% Confidence Interval (CI) = (-5.6, -0.3)], Perceptual Reasoning [β = -4.0; (-7.6, -0.4)], and Working Memory [β = -2.8; (-5.6, -0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory.Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age.
    [Rowe C, Gunier R, Bradman A, Harley KG, et al. 2016. Environ Res.150:128-37.]
  • Chronic adverse effects of long-term exposure of children to dichlorodiphenyltrichloroethane (DDT) through indoor residual spraying: A systematic review.
    Malaria remains a significant public health problem in endemic regions of the world, most especially in sub-Saharan Africa. As part of the global efforts to control malaria, dichlorodiphenyltrichloroethane (DDT), a cheap and effective chemical, was endorsed by the World Health Organization for use in indoor residual spraying (IRS). However, in the light of evidence on the acute toxicity of DDT, concerns have grown about the safety or the possible chronic health effects from the continued use of this persistent chemical, generating much debate and research efforts over the years. The purpose of this study was to identify, appraise and synthesise evidence about the chronic adverse effects of long-term exposure to DDT in children, 0-18 years, in zones where IRS is practised, in order to contribute to informing policy decisions.Twenty-seven electronic databases were systematically searched using pre-defined inclusion/exclusion criteria. Two were trial registers while 25 others indexed studies of various designs. Only nine studies met the inclusion/exclusion criteria out of 3281 hits generated. Five of the studies are of high quality while four are of moderate quality. For the three studies on neurodevelopment, evidence suggestive of negative impact of DDT was found. For the three studies on endocrine/congenital disorders, ambivalent evidence existed. In the case of the immunity-related outcome, there was growing but insufficient evidence of negative effect. The only study on survival outcome was inconclusive. Empirically, insufficient evidence exists with regard to the chronic adverse effects of long-term exposure of children to DDT through IRS. Considering the dearth of studies and the fact that many adverse effects might take much longer time to manifest, inferences drawn are weak. It would therefore require a series of well-coordinated observational studies done in the context of IRS to adequately address this evidence gap in the future.
    [Osunkentan AO, Evans D. 2015. Rural Remote Health.15(2):2889.]
  • Elucidating the Links Between Endocrine Disruptors and Neurodevelopment
    Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes.
    [Schug TT, Blawas AM, Gray K, et al. 2015. Endocrinology. 156(6):1941-51.]
  • Organic Compounds Detected in Deciduous Teeth: A Replication Study from Children with Autism in Two Samples
    Biological samples are an important part of investigating toxic exposures and disease outcomes. However, blood, urine, saliva, or hair can only reflect relatively recent exposures. Alternatively, deciduous teeth have served as a biomarker of early developmental exposure to heavy metals, but little has been done to assess organic toxic exposures such as pesticides, plastics, or medications. The purpose of our study was to determine if organic chemicals previously detected in a sample of typically developing children could be detected in teeth from a sample of children with autism. Eighty-three deciduous teeth from children with autism spectrum disorders (ASD) were chosen from our tooth repository. Organic compounds were assessed using liquid chromatography tandem mass spectrometry and gas chromatography methods. Consistent with a prior report from Camann et al., (2013), we have demonstrated that specific semivolatile organic chemicals relevant to autism etiology can be detected in deciduous teeth. This report provides evidence that teeth can be useful biomarkers of early life exposure for use in epidemiologic case-control studies seeking to identify differential unbiased exposures during development between those with and without specific disorders such as autism.
    [Palmer RF, Heilbrun L, Camann D, Yau A, et al. 2015. J Environ Public Health. 2015:862414.]
  • Pre- and postnatal exposures to pesticides and neurodevelopmental effects in children living in agricultural communities from South-Eastern Spain.
    Childrens exposure to neurotoxic compounds poses a major problem to public health because oftheir actively developing brain that makes them highly vulnerable. However, limited information is available on neuropsychological effects in children associated with pre- and postnatal exposures to pesticides.Study's aim was to evaluate the association between current and pre- and postnatal exposures to pesticides and their effects on neurodevelopment in children aged 6–11 years living in agricultural communities from South-Eastern Spain.An ambispective study was conducted on 305 children aged 6–11 years randomly selected from public schools of the study area. Current exposure to organophosphate pesticides was assessed measuring children's urinary levels of dialkylphosphates (DAPs). Both prenatal and postnatal residential exposure to pesticides was estimated by developing a geographical information system (GIS) technology-based index that integrated distance-weighted measure of agricultural surface, time-series of crop areas per municipality and year, and land-use maps. Neuropsychological performance was evaluated with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV).Greater urinary DAP levels were associated with a poorer performance on intelligence quotient and verbal comprehension domain, with effects being more prominent in boys than in girls. The influence of an increase in 10 ha per year in crop surface around the child's residence during the postnatal period was associated with decreased intelligence quotient, processing speed and verbal comprehension scores. As regards prenatal exposure to pesticides, a poor processing speed performance was observed. These effects were also more prominent in boys than in girls.Our results suggest that postnatal exposure to pesticides can negatively affect children's neuropsychological performance. Prenatal exposure was weakly associated to neurodevelopment impairment.
    [González-Alzaga B, Hernández AF, Rodríguez-Barranco M, et al. 2015. Environ Int. 85:229-37. ]
  • Prenatal DDT and DDE exposure and child IQ in the CHAMACOS cohort.
    Although banned in most countries, dichlorodiphenyl-trichloroethane (DDT) continues to be used for vector control in some malaria endemic areas. Previous findings from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study found increased prenatal levels of DDT and its breakdown product dichlorodiphenyl-dichloroethylene (DDE) to be associated with altered neurodevelopment in children at 1 and 2years of age. In this study, we combined the measured maternal DDT/E concentrations during pregnancy obtained for the prospective birth cohort with predicted prenatal DDT and DDE levels estimated for a retrospective birth cohort. Using generalized estimating equation (GEE) and linear regression models, we evaluated the relationship of prenatal maternal DDT and DDE serum concentrations with children's cognition at ages 7 and 10.5years as assessed using the Full Scale Intelligence Quotient (IQ) and 4 subtest scores (Working Memory, Perceptual Reasoning, Verbal Comprehension, and Processing Speed) of the Wechsler Intelligence Scale for Children (WISC). In GEE analyses incorporating both age 7 and 10.5 scores (n=619), we found prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales (p-value>0.05). In linear regression analyses assessing each time point separately, prenatal DDT levels were inversely associated with Processing Speed at age 7years (n=316), but prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales at age 10.5years (n=595). We found evidence for effect modification by sex. In girls, but not boys, prenatal DDE levels were inversely associated with Full Scale IQ and Processing Speed at age 7years. We conclude that prenatal DDT levels may be associated with delayed Processing Speed in children at age 7years and the relationship between prenatal DDE levels and children's cognitive development may be modified by sex, with girls being more adversely affected.
    [Gaspar FW, Harley KG, Kogut K, Chevrier J, et al. 2015. Environ Int. 85:206-12]
  • Prenatal exposure to the organophosphate pesticide chlorpyrifos and childhood tremor.
    The organophosphate insecticide chlorpyrifos (CPF), widely used for agricultural purposes, has been linked to neurodevelopmental deficits. Possible motor effects at low to moderate levels of exposure have not been evaluated.Prenatal exposure to CPF was measured in umbilical cord blood in a sample of 263 inner-city minority children, who were followed prospectively. At approximately 11 years of age (mean age 10.9 ± 0.85 years, range=9.0-13.9), during a neuropsychological assessment, children were asked to draw Archimedes spirals. These were rated by a senior neurologist specializing in movement disorders who was blind to CPF exposure level.Compared to all other children, those with prenatal CPF exposure in the upper quartile range (n=43) were more likely to exhibit mild or mild to moderate tremor (≥ 1) in either arm (p=0.03), both arms (p=0.02), the dominant arm (p=0.01), and the non-dominant arm (p=0.055). Logistic regression analyses showed significant CPF effects on tremor in both arms, either arm, the dominant arm (p-values <0.05), and the non-dominant arm (p=0.06), after adjustment for sex, age at testing, ethnicity, and medication. Prenatal CPF exposure is associated with tremor in middle childhood, which may be a sign of the insecticide's effects on nervous system function.
    [Rauh VA, Garcia WE, Whyatt RM, Horton MK, et al. 2015. Neurotoxicology. 51:80-6. ]
  • Pyrethroid insecticide exposure and cognitive developmental disabilities in children: The PELAGIE mother-child cohort.
    Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment. The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend=0.04 and P-trend<0.01, respectively) and with working memory scores (P-trend=0.05 and P-trend<0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA). Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance.
    [Viel JF, Warembourg C, Le Maner-Idrissi G, Lacroix A, et al. 2015. Environ Int. 82:69-75.]
  • Chemical exposure early in life and the neurodevelopment of children--an overview of current epidemiological evidence
    A number of chemicals have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. This article aims at evaluating the impact of exposure to several chemicals including: organophosphate, organochlorine pesticides, polychlorinated biphenyls (PCBs), mercury and lead on the neurodevelopment of children by reviewing the most recent published literature, and answer the question whether any progress has been made in the epidemiology of the neurodevelopment of children induced by exposure to those chemicals. The result of the presented studies show that exposure to the above-mentioned chemicals may impair the neurodevelopment of children. Neonates exposed to organophosphate pesticides demonstrated a higher proportion of abnormal reflexes, and young children had more attention problems. Exposure to organochlorine pesticides in children was associated with alertness, quality of alert responsiveness, cost of attention and other potential attention associated measures. Because the neurotoxicants may cross the placenta and the fetal brain, exposure consideration regarding the reduction of exposure to those chemicals should be implemented.
    [Jurewicz J, Polańska K, Hanke W. 2013. Ann Agric Environ Med. 20(3):465-86]
  • Prenatal exposure to environmental contaminants and behavioural problems at age 7-8years
    Animal studies showed that the developing brain is particularly sensitive to chemical exposure. Human studies carried out in areas with high exposures have proven neurodevelopmental disorders in relation to e.g. lead and PCBs. Whether these chemicals are associated with behavioural problems in childhood at current environmental levels is not well known. Therefore, we assessed the association between prenatal exposure to lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE and behavioural problems in 7-8year old children. Prenatal exposure data were obtained from the Flemish mother-new-born cohort. Lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE were analysed in cord blood. When the child reached 7-8years, 270 mothers completed the Strengths and Difficulties Questionnaire assessing their children's behavioural health. We found that doubling the prenatal lead exposure (cord blood lead levels) was associated with a 3.43 times higher risk for hyperactivity in both boys and girls. In addition, total difficulties were 5.08 times more likely in the highest tertile for prenatal lead exposure compared to the lowest tertile. In girls, total difficulties were 4.92 more likely when doubling cord blood p,p'-DDE, whereas no significant association was found in boys. Further, we noted in boys a 1.53 times higher risk for emotional problems when doubling cord blood cadmium, whereas no significant association was found in girls. These results indicate that the presence of environmental contaminants influences the mental health of the next generation.
    [Sioen I, Den Hond E, Nelen V, Van de Mieroop E, et al. 2013. Environ Int. 59:225-31.]
  • Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory?
    In the current paper, the authors expanded the previous work on CPF to investigate how additional biological and social environmental factors might create or explain differential neurodevelopmental susceptibility, focusing on main and moderating effects of the quality of the home environment (HOME) and child sex. The study evaluate how the quality of the home environment (specifically, parental nurturance and environmental stimulation) and child sex interact with the adverse effects of prenatal CPF exposure on working memory at child age 7years. Results found a borderline significant interaction between prenatal exposure to CPF and child sex suggesting males experience a greater decrement in working memory than females following prenatal CPF exposure. In addition, a borderline interaction between parental nurturance and child sex was detected suggesting that, in terms of working memory, males benefit more from a nurturing environment than females. This is the first investigation into factors that may inform an intervention strategy to reduce or reverse the cognitive deficits resulting from prenatal CPF exposure.
    [Horton, M.K., L.G. Kahn, F. Perera, D.B. Barr and V. Rauh. 2012. Neurotoxicology and Teratology. 34(5):534-41]
  • Dioxin Exposure and Age of Pubertal Onset among Russian Boys

    Animal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations. We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region. Between 2003 and 2005, 499 boys 8–9 years of age were enrolled in a longitudinal study in Chapaevsk, Russia. Pubertal onset [stage 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 mL] was assessed annually between ages 8 and 12 years. Serum levels at enrollment were analyzed by the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. We used Cox proportional hazards models to assess age at pubertal onset as a function of exposure adjusted for potential confounders. We conducted sensitivity analyses excluding boys with pubertal onset at enrollment. The median (range) total serum TEQ concentration was 21 (4–175) pg/g lipid, approximately three times higher than values in European children. At enrollment, boys were generally healthy and normal weight (mean body mass index, 15.9 kg/m2), with 30% having entered puberty by G2+ and 14% by TV criteria. Higher dioxin TEQs were associated with later pubertal onset by TV (hazard ratio = 0.68, 95% confidence interval, 0.49–0.95 for the highest compared with the lowest quartile). Similar associations were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin concentrations for TV but not G2+. Results were robust to sensitivity analyses. Findings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation.
    [Korrick, S.A., Lee, M., Williams, P., et al. 2011. Environ Health Perspect. 119 (9):1339–1344.]

  • Chlorpyrifos Exposure and Urban Residential Environment Characteristics as Determinants of Early Childhood Neurodevelopment

    We evaluated whether neighborhood characteristics correlated with early neurodevelopment and whether these characteristics confounded the previously reported association between exposure to chlorpyrifos (an organophosphate insecticide) and neurodevelopment. We obtained prenatal addresses, chlorpyrifos exposure data, and 36-month Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores for a birth cohort in New York City (born 1998–2002). We used data from the 2000 US Census to estimate measures of physical infrastructure, socioeconomic status, crowding, demographic composition, and linguistic isolation for 1-kilometer network areas around each child's prenatal address. Generalized estimating equations were adjusted for demographics, maternal education and IQ, prenatal exposure to tobacco smoke, caretaking environment quality, and building dilapidation. Of 266 children included as participants, 47% were male, 59% were Dominican, and 41% were African American. For each standard deviation higher in neighborhood percent poverty, the PDI score was 2.6 points lower (95% confidence interval [CI] = −3.7, −1.5), and the MDI score was 1.7 points lower (95% CI = −2.6, −0.8). Neighborhood-level confounding of the chlorpyrifos-neurodevelopment association was not apparent. Neighborhood context and chlorpyrifos exposure were independently associated with neurodevelopment, thus providing distinct opportunities for health promotion.
    [Lovasi , G. et al. 2010. Am J Public Health. AJPH.2009.168419v1]

  • Dietary Intake and Its Contribution to Longitudinal Organophosphorus Pesticide Exposure in Urban/suburban Children.
    Study assessed young urban/suburban children's longitudinal exposure to OP pesticides in the Children's Pesticide Exposure Study (CPES).Twenty-three children 3-11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003-2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. Study measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons. By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to non-detected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. Study also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year. The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children.
    [Lu C, Barr DB, Pearson MA, Waller LA. 2008. Environ Health Perspect. 216(4):537-42.]
  • Childhood cancer in Texas counties with moderate to intense agricultural activity
    With few established risk factors, cancer remains the second leading cause of death for children in the U.S. Agricultural pesticide use is one of many suspected factors that may contribute to the etiology of childhood cancer. This study tests the hypothesis that birth in Texas counties with moderate to intense agricultural activity increases childhood cancer risk. This case-control study analyzed 6974 cases and controls ages 0 to 14, identified through the Texas Cancer Registry and Texas birth records, respectively. Exposure data were obtained from the Census of Agriculture. Percent cropland in the county of birth and total county-specific pesticide exposure incorporating the EPA's carcinogenicity classification served as surrogates for pesticide exposure. Cancer sites examined include: all cancers, leukemia, lymphoma, CNS tumors, and several specific subsites. Elevated, although not statistically significant, ORs for the association between birth in counties with > or =50% cropland were produced for all CNS tumors (OR = 1.3, 95% CI = 0.9-1.8), astrocytoma (OR = 1.4, 95% CI = 0.8-2.2), and PNET (OR = 1.3, 95% CI = 0.7-2.5). A similar pattern was not observed using the index of total county-specific pesticide exposure. Although imprecise, these exposure assessment methods represent novel applications of agricultural census data. Although a pattern of increased risk was observed between percent cropland and CNS tumors, this study's results do not support an association between birth in Texas counties with moderate to intense agricultural activity and childhood cancer. Due to study limitations, such an association should not be ruled out. Future research should incorporate individual-level data from various sources to increase precision and decrease misclassification in the exposure assessment.
    [Walker, K.M., et al. 2007. J Agric Saf Health 13(1):9-24.]
  • Developmental exposure to pesticides zineb and/or endosulfan renders the nigrostriatal dopamine system more susceptible to these environmental chemicals later in life.
    The purpose of this study was to test the hypothesis that exposure to pesticides such as endosulfan and/or zineb during critical periods of postnatal development could result in neuronal dysfunction and enhance the impact of these pesticides during exposure as adults. Mice exposed to these pesticides as juveniles and re-exposed at 8 months of age had significantly altered striatum and brain cortex neurotransmitter levels. Thus, mice re-exposed during adulthood to zineb, endosulfan and their mixtures showed a significantly depleted striatal dopamine levels, to 22, 16 and 35% of control, respectively. Acetylcholinesterase activity in the cerebral cortex was significantly increased in all pesticide treated groups (rho< or =0.05) upon repeated exposure, and pesticide mixture treatment also significantly increased levels of normal and aggregated alpha-synuclein. Collectively, these findings support our hypothesis that exposure to pesticides such as endosulfan and zineb during critical periods of postnatal development contributes to neurotransmitter changes upon re-challenge in adulthood.
    [Jia, Z., et al. 2007. Neurotoxicology 28(4):727-735]
  • A Longitudinal Approach to Assessing Urban and Suburban Children's Exposure to Pyrethroid Pesticides
    Researchers conducted a longitudinal study to assess the exposure of 23 elementary school-age children to pyrethroid pesticides, using urinary pyrethroid metabolites as exposure biomarkers. Most of the children's conventional diets were substituted with organic food items for 5 consecutive days and two daily spot urine samples wrer collected, throughout the 15-day study period. Yrine samples for five common pyrethroid metabolites were analyzed. Authors found an association between the parents' self-reported pyrethroid use in the residential environment and elevated pyrethroid metabolite levels found in their children's urine. Children were also exposed to pyrethroids through their conventional diets, although the magnitude was smaller than for the residential exposure. Children's ages appear to be significantly associated with pyrethroids exposure, which is likely attributed to the use of pyrethroids around the premises or in the facilities where older children engaged in the outdoor activities. Study concludes that residential pesticide use represents the most important risk factor for children's exposure to pyrethroid insecticides. Because of the wide use of pyrethroids in the United States, the findings of this study are important for both children's pesticide exposure assessment and environmental public health.
    [Lu C, Barr DB, Pearson M, Bartell S, Bravo R.. 2006. Environ Health Perspect. 114(9):1419-23.]
  • Early-Life Environmental Risk Factors for Asthma: Findings from the Children's Health Study
    To investigate further whether the timing of such experiences and exposures is associated with the occurrence of asthma by 5 years of age, authors conducted a prevalence case-control study nested within the Children's Health Study, a population-based study of > 4,000 school-aged children in 12 southern California communities. Asthma diagnosis before 5 years of age was associated with exposures in the first year of life to wood or oil smoke, soot, or exhaust , cockroaches , herbicides, pesticides, and farm crops, farm dust, or farm animals. The ORs for herbicide, pesticide, farm animal, and crops were largest among children with early-onset persistent asthma. The risk of asthma decreased with an increasing number of siblings. Day care attendance within the first 4 months of life was positively associated with early-onset transient wheezing.
    [Salam, MT, YF Li, B Langholz, and FD Gilliland. 2004. Environmental Health Perspectives 112 (6): 760-765]
  • Antibiotic Resistance: What is the Impact of Agricultural Uses of Antibiotics on Children’s Health?
    Antimicrobial resistance has reached crisis stage in human medicine. The rapid acceleration of multidrug-resistant bacteria in the past 2 decades has overtaken new drug development, and patients and clinicians are faced with the prospect of untreatable infections. Although much of the problem stems from overuse and misuse of antimicrobial agents in human medicine, large-scale use of antimicrobials in agriculture also contributes to the crisis. Agricultural uses of antibiotics produce environmental exposures in a variety of reservoirs, which select for resistant microbes and microbial genes. This article presents the major lines of evidence documenting the risks to human health of some of the agricultural uses of antimicrobials. A brief review of the microbiologic antecedents of resistance is followed by a discussion of agricultural uses of antimicrobials and a targeted review of the literature, which provides the background knowledge and evidence necessary for pediatricians and other clinicians to be informed and to advocate for judicious use of antimicrobials in all sectors.
    [K.M. Shea, 2003. Pediatrics 2003;112:253–258.]
  • An Anthropological Approach to the Evaluation of Preschool Children Exposed to Pesticides in Mexico
    In a comparative study in Mexico, children exposed to pesticides demonstrated decreases in stamina, coordination, memory, and the ability to draw familiar subjects.
    [Guillette, E., et al. 1998. Environmental Health Perspectives, 106(6):347-353.]
  • Childhood cancer and paternal employment in agriculture: the role of pesticides
    Previous studies have suggested that the offspring of men potentially exposed to pesticides at work may be at increased risk of kidney cancer (Wilms' tumour), brain tumours, Ewing's bone sarcoma and acute leukaemia. This paper examines the association between potential occupational exposure of fathers to pesticides and offspring's death from cancer in a large national database. Records for 167703 childhood deaths occurring during 1959-63, 1970-78 and 1979-90 in England and Wales have been analysed. Among the offspring of men with potential occupational exposure to pesticides there were 5270 deaths, of which 449 were due to cancer. Associations were assessed using proportional mortality ratios (PMRs), with adjustment for age, year of death and paternal social class. Of the childhood cancers previously linked with potential paternal occupational exposure to pesticides, the only statistically significant excess was for kidney cancer (PMR=1.59, 95% CI=1.18-2.15, based on 42 deaths). Although these results offer some support for the suggestion that paternal occupational exposure to pesticides may be related to the subsequent development of kidney cancer in offspring, other explanations cannot be excluded. In the light of the findings presented here and elsewhere, further, more detailed, research into the nature of this relationship is warranted.
    [Fear, N.T., et al. 1998. Br J Cancer 77(5):825-829.]

Obesity

  • Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology
    Ancestral environmental exposures to a variety of factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. One of the most widely used agricultural pesticides worldwide is the herbicide glyphosate (N-(phosphonomethyl)glycine), commonly known as Roundup. There are an increasing number of conflicting reports regarding the direct exposure toxicity (risk) of glyphosate, but no rigorous investigations on the generational actions. The current study using a transient exposure of gestating F0 generation female rats found negligible impacts of glyphosate on the directly exposed F0 generation, or F1 generation offspring pathology. In contrast, dramatic increases in pathologies in the F2 generation grand-offspring, and F3 transgenerational great-grand-offspring were observed. The transgenerational pathologies observed include prostate disease, obesity, kidney disease, ovarian disease, and parturition (birth) abnormalities. Epigenetic analysis of the F1, F2 and F3 generation sperm identified differential DNA methylation regions (DMRs). A number of DMR associated genes were identified and previously shown to be involved in pathologies. Therefore, we propose glyphosate can induce the transgenerational inheritance of disease and germline (e.g. sperm) epimutations. Observations suggest the generational toxicology of glyphosate needs to be considered in the disease etiology of future generations.
    [Kubsad, D., Nilsson, E.E., King, S.E., Sadler-Riggleman, I., Beck, D. and Skinner, M.K., 2019. Scientific reports, 9(1), pp.1-17.]
  • Chronic chlorpyrifos exposure elicits diet-specific effects on metabolism and the gut microbiome in rats.
    Chlorpyrifos is a commonly-used pesticide which was reported to interfere with hormone signaling and metabolism, however, little is known about its effect on gut microbiota. In this study, adult male rats fed a normal (NF) or high fat (HF) diet were exposed to 0.3 or 3.0 mg chlorpyrifos/kg bodyweight/day or vehicle alone for 9 weeks. Effects on bodyweight, serum levels of glucose, lipid, cytokines, and gut microbiome community structure were measured. The effects of chlorpyrifos on metabolism were dose- and diet-dependent, with NF-fed rats administered the low dose showing the largest metabolic changes. NF-fed rats exposed to chlorpyrifos exhibited a pro-obesity phenotype compared with their controls, whereas there was no difference in pro-obesity phenotype between HF-fed groups. Chlorpyrifos exposure significantly reduced serum insulin, C-peptide, and amylin concentrations in NF- and HF-fed rats, leaving serum glucose and lipid profiles unaffected. Chlorpyrifos exposure also significantly altered gut microbiota composition, including the abundance of opportunistic pathogens, short chain fatty acid-producing bacteria and other bacteria previously associated with obese and diabetic phenotypes. The abundance of bacteria associated with neurotoxicity and islet injury was also significantly increased by chlorpyrifos. Our results suggest risk assessments for chlorpyrifos exposure should consider other effects in addition to neurotoxicity.
    [Fang B, Li JW, Zhang M, Ren FZ, Pang GF. 2018. Food Chem Toxicol. 111:144-152]
  • Increased levels of persistent organic pollutants in serum one year after a great weight loss in humans: Are the levels exceeding health based guideline values?
    With the growing prevalence of obesity, an increased number of bariatric surgeries are being performed. Lipophilic persistent organic pollutants (POPs) are stored in adipose tissue, and an increased release of lipophilic POPs into the blood circulation may occur following rapid weight loss such as after bariatric surgery.To evaluate and compare POP levels in serum before and after bariatric surgery, and to assess if the POP levels exceeded health based guideline values, with particular focus on women of childbearing age (WCBA). Serum samples from 63 patients before and one year after bariatric surgery were analysed for organochlorine pesticides (OCPs); polychlorinated biphenyls (PCBs); and brominated flame retardants (BFRs).
    Mean weight loss one year after surgery was 32.1kg. The levels of all the analysed POPs in serum increased during the study period. Median levels of dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzen (HCB) and PCB-153 increased from 90.2ng/g lipid weight (lw) to 158.5ng/glw, from 21.1ng/glw to 36.4ng/glw and from 48.7ng/glw to 71.5ng/glw, respectively. The highest percentage increase was observed for PCB -138, with 83.1%. BFRs were detected in low sample numbers and at low levels. Guideline values for ΣPCB6 in serum were exceeded for 5% of the participants. Weight loss after bariatric surgery resulted in increases of POPs levels in serum between 46.7%-83.1%. Guideline values for ΣPCB6 in serum were exceeded for 5% of the participants. For WCBA, the possible transfer of comparable levels to infants warrants further attention.
    [Jansen A, Polder A, Müller MHB, et al. 2018. Sci Total Environ. 622-623:1317-1326. ]
  • Association between organic food consumption and metabolic syndrome: cross-sectional results from the NutriNet-Santé study.
    Metabolic syndrome (MetS), a multicomponent condition, is a cardiovascular disease predictor. Although exposure to agricultural pesticides has been suggested as a potential contributor to the rising rates of obesity, type 2 diabetes, and other features of metabolic disorders, no studies have focused on the association between consumption of organic food (produced without synthetic pesticides) and MetS. We aimed to investigate the cross-sectional association between organic food consumption and MetS in French adults to determine whether it would be worth conducting further studies, particularly large prospective and randomised trials.A total of 8174 participants from the NutriNet-Santé study who attended a clinical visit and completed an organic food frequency questionnaire were included in this cross-sectional analysis.Higher organic food consumption was negatively associated with the prevalence of MetS: adjusted prevalence ratio was 0.69 (95% CI 0.61, 0.78) when comparing the third tertile of proportion of organic food in the diet with the first one (p value <0.0001). Higher consumption of organic plant-based foods was also related to a lower probability of having MetS. In addition, when stratifying by lifestyle factors (nutritional quality of the diet, smoking status, and physical activity), a significant negative association was detected in each subgroup (p values <0.05), except among smokers. Our results showed that a higher organic food consumption was associated with a lower probability of having MetS. Additional prospective studies and randomised trials are required to ascertain the relationship between organic food consumption and metabolic disorders.
    [Baudry J, Lelong H, Adriouch S, Julia C, et al. 2017. Eur J Nutr. doi: 10.1007/s00394-017-1520-1. ]
  • Diet and contaminants: driving the rise to obesity epidemics?
    The obesity epidemic is spreading worldwide without reversal trend and despite specific policies oriented to dietary habits and lifestyle, which seem to have modest effects. Genetic factors only partly explain the rise, whereas environmental factors seem to play a key role, mainly by gene-environment interactions through epigenetic mechanisms. A number of animal and human studies point to maternal diet, intestinal microbiota and chemicals introduced as contaminants with food, all factors able to increase the risk of obesity. Widely diffused toxics (mainly BPA, phthalates, pesticides) are able to promote obesity in children and adults, mainly by acting on the differentiation pathway linking multipotent stromal stem cell to mature adipocyte, modulating epigenetic factors and influencing a series of mechanisms finally leading to altered dietary habits, increased adipocyte formation and fat storage. Furthermore, the adipose tissue is an important target for several chemicals (mainly POPs) which represent a threat to metabolic health. In conclusion, besides excessive individual energy intake and inadequate lifestyle, other broadly diffused and modifiable factors (mainly ingestion of toxic chemicals with food) seem to have a critical role in the rapid epidemiological growing of obesity, also considering trans-generational transmission of risk and later development of obesity due to exposure during early life. Further studies are needed, to better assess interactions between cumulative effects of toxic food contaminants and modification of diet and lifestyle, and to verify the efficacy of primary prevention strategies acting on all these factors and potentially able to reverse the continuous rising of the obesity epidemic.
    [Di Ciaula A, Portincasa P. 2017. Curr Med Chem. doi: 10.2174/0929867324666170518095736]
  • Early-life chemical exposures and risk of metabolic syndrome.
    The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS) have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood) may have a more profound effect on life-long risk of obesity and MetS. This narrative review explores the evidence linking early-life exposure to a suite of chemicals that are common contaminants associated with food production (pesticides; imidacloprid, chlorpyrifos, and glyphosate) and processing (acrylamide), in addition to chemicals ubiquitously found in our household goods (brominated flame retardants) and drinking water (heavy metals) and changes in key pathways important for the development of MetS and obesity.
    [De Long NE, Holloway AC. 2017. Diabetes Metab Syndr Obes. 10:101-109. ]
  • Endocrine Disruptors and Obesity
    The purpose of this review was to summarise current evidence that some environmental chemicals may be able to interfere in the endocrine regulation of energy metabolism and adipose tissue structure. Recent findings demonstrate that such endocrine-disrupting chemicals, termed "obesogens", can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and as ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing the retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer.
    [Darbre PD. 2017. Curr Obes Rep. 6(1):18-27]
  • Environmental endocrine disruptors: New diabetogens?
    The prevalence of type-2 diabetes has dramatically increased worldwide during the last few decades. While lifestyle factors (sedentariness, noxious food), together with genetic susceptibility, are well-known actors, there is accumulating evidence suggesting that endocrine disrupting chemicals (EDCs) may also play a pathophysiological role in the occurrence of metabolic diseases. Both experimental and epidemiological evidence support a role for early and chronic exposure to low doses of chemical pollutants with endocrine and metabolic disrupting effects. Most are present in the food chain and accumulate in the fat mass after absorption. In rodents, bisphenol A stimulates synthesis and secretion of pancreatic β cells and disturbs insulin signaling in liver, muscle and adipose tissue through epigenetic changes leading to insulin resistance and β cell impairment. In humans, epidemiological reports show statistical link between exposure to pesticides, polychlorinated bisphenyls, bisphenol A, phthalates, dioxins or aromatic polycyclic hydrocarbides or heavy metals and DT2 after acute accidental releases or early in life and/or chronic, low doses exposure. More prospective, longitudinal studies are needed to determine the importance of such environmental risk factors.
    [Fénichel P, Chevalier N. 2017. C R Biol. pii: S1631-0691(17)30124-5]
  • Facts and Fallacies in the Debate on Glyphosate Toxicity.
    The safety profile of the herbicide glyphosate and its commercial formulations is controversial. Reviews have been published by individuals who are consultants and employees of companies commercializing glyphosate-based herbicides in support of glyphosate's reapproval by regulatory agencies. These authors conclude that glyphosate is safe at levels below regulatory permissible limits. In contrast, reviews conducted by academic scientists independent of industry report toxic effects below regulatory limits, as well as shortcomings of the current regulatory evaluation of risks associated with glyphosate exposures. Two authors in particular (Samsel and Seneff) have published a series of commentaries proposing that long-term exposure to glyphosate is responsible for many chronic diseases (including cancers, diabetes, neuropathies, obesity, asthma, infections, osteoporosis, infertility, and birth defects). The aim of this review is to examine the evidential basis for these claimed negative health effects and the mechanisms that are alleged to be at their basis. We found that these authors inappropriately employ a deductive reasoning approach based on syllogism. We found that their conclusions are not supported by the available scientific evidence. Thus, the mechanisms and vast range of conditions proposed to result from glyphosate toxicity presented by Samsel and Seneff in their commentaries are at best unsubstantiated theories, speculations, or simply incorrect. This misrepresentation of glyphosate's toxicity misleads the public, the scientific community, and regulators. Although evidence exists that glyphosate-based herbicides are toxic below regulatory set safety limits, the arguments of Samsel and Seneff largely serve to distract rather than to give a rational direction to much needed future research investigating the toxicity of these pesticides, especially at levels of ingestion that are typical for human populations.
    [Mesnage R, Antoniou MN. 2017. Front Public Health. 5:316]
  • Imidacloprid Promotes High Fat Diet-Induced Adiposity in Female C57BL/6J Mice and Enhances Adipogenesis in 3T3-L1 Adipocytes via the AMPKα-Mediated Pathway.
    Imidacloprid, a neonicotinoid insecticide, was previously reported to enhance adipogenesis and resulted in insulin resistance in cell culture models. It was also reported to promote high fat diet-induced obesity and insulin resistance in male C57BL/6J mice. Thus, the goal of the present study was to determine the effects of imidacloprid and dietary fat interaction on the development of adiposity and insulin resistance in female C57BL/6J mice. Mice were fed with a low (4% w/w) or high fat (20% w/w) diet containing imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) for 12 weeks. Mice fed with imidacloprid (0.6 mg/kg bw/day) significantly enhanced high fat diet-induced weight gain and adiposity. Treatment with imidacloprid significantly increased serum insulin levels with high fat diet without effects on other markers of glucose homeostasis. AMPKα activation was significantly inhibited by 0.6 and 6 mg imidacloprid/kg bw/day in white adipose tissue. Moreover, AMPKα activation with 5-aminoimidazole-4-carboxamide ribonucleotide abolished the effects of imidacloprid (10 μM) on enhanced adipogenesis in 3T3-L1 adipocytes. N-Acetyl cysteine also partially reversed the effects of imidacloprid on reduced phosphorylation of protein kinase B (AKT) in C2C12 myotubes. These results indicate that imidacloprid may potentiate high fat diet-induced adiposity in female C57BL/6J mice and enhance adipogenesis in 3T3-L1 adipocytes via the AMPKα-mediated pathway. Imidacloprid might also influence glucose homeostasis partially by inducing cellular oxidative stress in C2C12 myotubes.
    [Sun Q, Qi W, Xiao X, Yang SH, et al. 2017. J Agric Food Chem. 65(31):6572-6581]
  • Metabolic syndrome is associated with exposure to organochlorine pesticides in Anniston, AL, United States.
    The Anniston Community Health Survey, a cross-sectional study, was undertaken in 2005-2007 to study environmental exposure to polychlorinated biphenyl (PCB) and organochlorine (OC) pesticides and health outcomes among residents of Anniston, AL, United States. The examination of potential risks between these pollutants and metabolic syndrome, a cluster of cardiovascular risk factors (i.e., hypertension, central obesity, dyslipidemia and dysglycemia) was the focus of this analysis. Participants were 548 adults who completed the survey and a clinic visit, were free of diabetes, and had a serum sample for clinical laboratory parameters as well as PCB and OC pesticide concentrations. Associations between summed concentrations of 35 PCB congeners and 9 individual pesticides and metabolic syndrome were examined using generalized linear modeling and logistic regression; odds ratios (OR) and 95% confidence intervals (CI) are reported. Pollutants were evaluated as quintiles and as log transformations of continuous serum concentrations. Participants were mostly female (68%) with a mean age (SD) of 53.6 (16.2) years. The racial distribution was 56% white and 44% African American; 49% met the criteria for metabolic syndrome. In unadjusted logistic regression, statistically significant and positive associations across the majority of quintiles were noted for seven individually modeled pesticides (p,p'-DDT, p,p'-DDE, HCB, β-HCCH, oxychlor, tNONA, Mirex). Following adjustment for covariables (i.e., age, sex, race, education, marital status, current smoking, alcohol consumption, positive family history of diabetes or cardiovascular disease, liver disease, BMI), significant elevations in risk were noted for p,p'-DDT across multiple quintiles (range of ORs 1.61 to 2.36), for tNONA (range of ORs 1.62-2.80) and for p,p'-DDE [OR (95% CI)] of 2.73 (1.09-6.88) in the highest quintile relative to the first. Significant trends were observed in adjusted logistic models for log10 HCB [OR=6.15 (1.66-22.88)], log10 oxychlor [OR=2.09 (1.07-4.07)] and log10 tNONA [3.19 (1.45-7.00)]. Summed PCB concentrations were significantly and positively associated with metabolic syndrome only in unadjusted models; adjustment resulted in attenuation of the ORs in both the quintile and log-transformed models. In conclusion, several OC pesticides were found to have significant associations with metabolic syndrome in the Anniston study population while no association was observed for PCBs.
    [Rosenbaum PF, Weinstock RS, Silverstone AE, et al. 2017. Environ Int. 108:11-21]
  • Persistent Environmental Toxicants in Breast Milk and Rapid Infant Growth.
    Many environmental toxicants are passed to infants in utero and through breast milk. Exposure to toxicants during the perinatal period can alter growth patterns, impairing growth or increasing obesity risk. Previous studies have focused on only a few toxicants at a time, which may confound results. We investigated levels of 26 toxicants in breast milk and their associations with rapid infant growth, a risk factor for later obesity.We used data from the Norwegian HUMIS study, a multi-center cohort of 2,606 mothers and newborns enrolled between 2002 and 2008. Milk samples collected 1 month after delivery from a subset of 789 women oversampled by overweight were analyzed for toxicants including polychlorinated biphenyls (PCBs), heavy metals, and pesticides. Growth was defined as change in weight-for-age z-score between 0 and 6 months among the HUMIS population, and rapid growth was defined as change in z-score above 0.67. We used a Bayesian variable selection method to determine the exposures that most explained variation in the outcome. Identified toxicants were included in logistic and linear regression models to estimate associations with growth, adjusting for maternal age, smoking, education, pre-pregnancy body mass index (BMI), gestational weight gain, parity, child sex, cumulative breastfeeding, birth weight, gestational age, and preterm status.Of 789 infants, 19.2% displayed rapid growth. The median maternal age was 29.6 years, and the median pre-pregnancy BMI was 24.0 kg/m2, with 45.3% of mothers overweight or obese. Rapid growers were more likely to be firstborn. Hexachlorobenzene, β-hexachlorocyclohexane (β-HCH), and PCB-74 were identified in the variable selection method. An interquartile range (IQR) increase in β-HCH exposure was associated with a lower odds of rapid growth (OR 0.63, 95% CI 0.42-0.94). Newborns exposed to high levels of β-HCH showed reduced infant growth (β = -0.03, 95% CI -0.05 to -0.01 for IQR increase in breast milk concentration). No other significant associations were found. Our results suggest that early life β-HCH exposure may be linked to slowed growth. Further research is warranted on the potential mechanism behind this association and the longer-term metabolic effects of perinatal β-HCH exposure.
    [Criswell R, Lenters V, Mandal S, Stigum H, et al. 2017. Ann Nutr Metab. 70(3):210-216. ]
  • Persistent Environmental Toxicants in Breast Milk and Rapid Infant Growth.
    Many environmental toxicants are passed to infants in utero and through breast milk. Exposure to toxicants during the perinatal period can alter growth patterns, impairing growth or increasing obesity risk. Previous studies have focused on only a few toxicants at a time, which may confound results. We investigated levels of 26 toxicants in breast milk and their associations with rapid infant growth, a risk factor for later obesity.We used data from the Norwegian HUMIS study, a multi-center cohort of 2,606 mothers and newborns enrolled between 2002 and 2008. Milk samples collected 1 month after delivery from a subset of 789 women oversampled by overweight were analyzed for toxicants including polychlorinated biphenyls (PCBs), heavy metals, and pesticides. Growth was defined as change in weight-for-age z-score between 0 and 6 months among the HUMIS population, and rapid growth was defined as change in z-score above 0.67. We used a Bayesian variable selection method to determine the exposures that most explained variation in the outcome. Identified toxicants were included in logistic and linear regression models to estimate associations with growth, adjusting for maternal age, smoking, education, pre-pregnancy body mass index (BMI), gestational weight gain, parity, child sex, cumulative breastfeeding, birth weight, gestational age, and preterm status.Of 789 infants, 19.2% displayed rapid growth. The median maternal age was 29.6 years, and the median pre-pregnancy BMI was 24.0 kg/m2, with 45.3% of mothers overweight or obese. Rapid growers were more likely to be firstborn. Hexachlorobenzene, β-hexachlorocyclohexane (β-HCH), and PCB-74 were identified in the variable selection method. An interquartile range (IQR) increase in β-HCH exposure was associated with a lower odds of rapid growth (OR 0.63, 95% CI 0.42-0.94). Newborns exposed to high levels of β-HCH showed reduced infant growth (β = -0.03, 95% CI -0.05 to -0.01 for IQR increase in breast milk concentration). No other significant associations were found. Our results suggest that early life β-HCH exposure may be linked to slowed growth. Further research is warranted on the potential mechanism behind this association and the longer-term metabolic effects of perinatal β-HCH exposure.
    [Criswell R, Lenters V, Mandal S, Stigum H, et al. 2017. Ann Nutr Metab. 70(3):210-216. ]
  • Potential contribution of insecticide exposure and development of obesity and type 2 diabetes.
    The introduction of insecticides has greatly improved agricultural productivity and human nutrition; however, the wide use of insecticides has also sparked growing concern over their health impacts. Increased rate of cancers, neurodegenerative disorders, reproductive dysfunction, birth defects, respiratory diseases, cardiovascular diseases and aging have been linked with insecticide exposure. Meanwhile, a growing body of evidence is suggesting that exposure to insecticides can also potentiate the risk of obesity and type 2 diabetes. This review summarizes the relationship between insecticide exposure and development of obesity and type 2 diabetes using epidemiological and rodent animal studies, including potential mechanisms. The evidence as a whole suggests that exposure to insecticides is linked to increased risk of obesity and type 2 diabetes.
    [Xiao X, Clark JM2, Park Y. 2017. Food Chem Toxicol. 105:456-474]
  • Understanding Epigenetic Effects of Endocrine Disrupting Chemicals: from Mechanisms to Novel Test Methods.
    Endocrine disrupting chemicals (EDCs) are man-made chemicals that interfere with hormonal signalling pathways. They are used in, e.g., production of common household materials, in resin-based medical supplies, pesticides. Thus, they are environmentally ubiquitous and humans and wildlife are exposed to them on a daily basis. Early life exposure to EDCs has been associated with later life adversities such as obesity, diabetes and cancer. Mechanisms underlying such associations are unknown but are likely to be mediated by epigenetic changes induced by EDCs. Epigenetics is the study of changes in gene function that are heritable but do not entail a change in DNA sequence. EDCs have been shown to affect epigenetic marks such as DNA methylation and histone modifications. The scope of this article is to review today's knowledge about mechanisms involved in EDC-induced epigenetic changes and to discuss how this knowledge could be used for designing novel methods addressing epigenetic effects of EDCs.
    [Alavian-Ghavanini A, Rüegg J. 2017. Basic Clin Pharmacol Toxicol. doi: 10.1111/bcpt.12878.]
  • Glyphosate pathways to modern diseases V: Amino acid analogue of glycine in diverse proteins
    Glyphosate, a synthetic amino acid and analogue of glycine, is the most widely used biocide on the planet. Its presence in food for human consumption and animal feed is ubiquitous. Epidemiological studies have revealed a strong correlation between the increasing incidence in the United States of a large number of chronic diseases and the increased use of glyphosate herbicide on corn, soy and wheat crops. Glyphosate, acting as a glycine analogue, may be mistakenly incorporated into peptides during protein synthesis. A deep search of the research literature has revealed a number of protein classes that depend on conserved glycine residues for proper function. Glycine, the smallest amino acid, has unique properties that support flexibility and the ability to anchor to the plasma membrane or the cytoskeleton. Glyphosate substitution for conserved glycines can easily explain a link with diabetes, obesity, asthma, chronic obstructive pulmonary disease (COPD), pulmonary edema, adrenal insufficiency, hypothyroidism, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, prion diseases, lupus, mitochondrial disease, nonHodgkin’s lymphoma, neural tube defects, infertility, hypertension, glaucoma, osteoporosis, fatty liver disease and kidney failure. The correlation data together with the direct biological evidence make a compelling case for glyphosate action as a glycine analogue to account for much of glyphosate’s toxicity. Glufosinate, an analogue of glutamate, likely exhibits an analogous toxicity mechanism. There is an urgent need to find an effective and economical way to grow crops without the use of glyphosate and glufosinate as herbicides.
    [Samsel, A. and Seneff, S., 2016. J Biol Phys Chem, 16(6), pp.9-46.]
  • Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice.
    Increasing evidence links the widespread exposure to organophosphate (OP) pesticides to the global epidemics of type 2 diabetes and obesity. Recent data highlighted gene×environment interactions: mice expressing the human apolipoprotein E3 (apoE3) isoform were more prone to develop obesity than those expressing apoE2 or apoE4 upon dietary challenge with chlorpyrifos (CPF), the most used OP worldwide. Study aimed to further explore the contribution of the APOE3 genotype on the emergence of obesity and related metabolic dysfunctions upon subchronic exposure to CPF. Seven-month-old targeted replacement apoE3 and C57BL/6N male mice were orally exposed to CPF at 0 or 2mg/kg body weight/day for 8 consecutive weeks. CPF exposure generally increased food ingestion, glucose and total cholesterol concentrations, and tended to elevate acyl ghrelin levels. Nonetheless, excess weight gain and increased leptin levels were inherent to apoE3 mice. Moreover, the propensity towards a diabetic profile was markedly higher in these animals than in C57BL/6N, as they showed a higher homeostatic model assessment for insulin resistance index and higher insulin levels. Although both genotypes were metabolically affected by CPF, the results of the present investigation revealed that apoE3 mice were the most vulnerable to developing obesity and related disturbances following CPF administration through the diet. Since the APOE3 genotype is the most prevalent worldwide, current findings have particular implications for human health.
    [Peris-Sampedro F, Cabré M, Basaure P, Reverte I, et al. 2015. Environ Res. 142:169-76]
  • EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals.
    The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.
    [Gore AC, Chappell VA, Fenton SE, Flaws JA, et al. 2015. Endocr Rev. 36(6):E1-E150.]
  • Inflammatory and cardiometabolic risk on obesity: role of environmental xenoestrogens.
    The objective of the study was to investigate the levels of xenoestrogens (XEs) in plasma and adipose tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing bariatric surgery and their cardiometabolic impact in an obese state.Authors evaluated XE levels in plasma and visceral and subcutaneous AT samples of Portuguese obese (body mass index ≥ 35 kg/m(2)) women undergoing bariatric surgery. Association with metabolic parameters and 10-year cardiovascular disease risk was assessed. Data show that XEs are pervasive in this obese population. Distribution of individual and concentration of total XEs differed between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation was different between pre- and postmenopausal women. Significant associations between XE levels and metabolic and inflammatory parameters were found. In premenopausal women, XEs in plasma seem to be a predictor of 10-year cardiovascular disease risk.
    [Teixeira D, Pestana D, Santos C, Correia-Sá L, et al. 2015. J Clin Endocrinol Metab. 100(5):1792-801]
  • Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.
    Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity.The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU.An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change.The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 in 2010 with associated costs of €24.6 million. A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200-56 400) with associated costs of €835 million (sensitivity analysis: €835 million-16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion.
    [Legler J, Fletcher T, Govarts E, Porta M, et al. 2015. J Clin Endocrinol Metab. 100(4):1278-88.]
  • Association of urinary phenols with increased body weight measures and obesity in children and adolescents.
    To examine the association of urinary levels of the environmental phenol pesticides 2,5-dichlorophenol, 2,4-dichlorophenol, and triclosan with body weight outcomes in children and adolescent participants in the National Health and Nutrition Examination Survey 2007-2010. Study found a statistically significant positive association between both 2,5-dichlorophenol and 2,4-dichlorophenol with BMI z-score, WC, and obesity in children and adolescents. After stratification by age, the significant associations remained only in adolescents (ages 12-19). No associations were found between triclosan and any of the body weight outcomes.
    [Buser MC, Murray HE, Scinicariello F. 2014. J Pediatr. 165(4):744-9.]
  • Prenatal exposure to dichlorodiphenyltrichloroethane and obesity at 9 years of age in the CHAMACOS study cohort.
    In-utero exposure to endocrine-disrupting compounds, including dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenylethylene (DDE), has been hypothesized to increase the risk of obesity later in life. Authors examined the associations of maternal serum concentrations of DDT and DDE during pregnancy with body mass index, obesity, waist circumference, and percentage of body fat in 9-year-old children (n = 261) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal birth cohort study in the Salinas Valley, California (2000-2010).Study found associations between prenatal exposure to DDT and DDE and several measures of obesity at 9 years of age in boys but not in girls. For example, among boys, 10-fold increases in prenatal DDT and DDE concentrations were associated with increased odds of becoming overweight or obese (for o,p'-DDT, adjusted odds ratio (OR) = 2.5, for p,p'-DDT, adjusted OR = 2.1, and for p,p'-DDE, adjusted OR = 1.97). The difference by sex persisted after considering pubertal status. These results provide support for the chemical obesogen hypothesis.
    [Warner M, Wesselink A, Harley KG, Bradman A, et al. 2014. Am J Epidemiol. 179(11):1312-22.]
  • Infant antibiotic exposures and early-life body mass.
    Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6–14 months, 15–23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.
    [Trasande, L., Blustein, J., Liu, M., Corwin, E., Cox, L.M. and Blaser, M.J., 2013. International journal of obesity, 37(1), p.16.]
  • Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity
    Researchers gave neonatal rats chlorpyrifos, diazinon or parathion in doses devoid of any acute signs of toxicity, straddling the threshold for barely-detectable cholinesterase inhibition. Organophosphate exposure during a critical developmental window altered the trajectory of hepatic adenylyl cyclase/cyclic AMP signaling, culminating in hyperresponsiveness to gluconeogenic stimuli. Consequently, the animals developed metabolic dysfunction resembling prediabetes. When the organophosphate-exposed animals consumed a high fat diet in adulthood, metabolic defects were exacerbated and animals gained excess weight compared to unexposed rats on the same diet. At the same time, the high fat diet ameliorated many of the central synaptic defects caused by organophosphate exposure, pointing to nonpharmacologic therapeutic interventions to offset neurodevelopmental abnormalities, as well as toward fostering dietary choices favoring high fat intake. These studies show how common insecticides may contribute to the increased worldwide incidence of obesity and diabetes.
    [Slotkin, T.A. 2011. Reproductive Toxicology. 31: 297–301.]
  • Low dose organochlorine pesticides and polychlorinated biphenyls predict obesity, dyslipidemia, and insulin resistance among people free of diabetes
    The current study examined if low dose POPs predicted future adiposity, dyslipidemia, and insulin resistance among controls without diabetes in that study. 90 controls were diabetes-free during 20 years follow-up. They were a stratified random sample, enriched with overweight and obese persons. POPs measured in 1987-88 (year 2) sera included 8 organochlorine (OC) pesticides, 22 polychlorinated biphenyls (PCBs), and 1 polybrominated biphenyl (PBB). Body mass index (BMI), triglycerides, HDL-cholesterol, LDL-cholesterol, and homeostasis model assessment value for insulin resistance (HOMA-IR) were study outcomes at 2005-06 (year 20). Parallel to prediction of type 2 diabetes, many statistically significant associations of POPs with dysmetabolic conditions appeared at low dose, forming inverted U-shaped dose-response relations. Among OC pesticides, p,p'-DDE most consistently predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 after adjusting for baseline values. Simultaneous exposure to various POPs in the general population may contribute to development of obesity, dyslipidemia, and insulin resistance, common precursors of type 2 diabetes and cardiovascular diseases. Although obesity is a primary cause of these metabolic abnormalities, POPs exposure may contribute to excess adiposity and other features of dysmetabolism.
    [Lee, D.H., Steffes, M., Sjödin, A., et al. 2011. PLoS ONE. 6: e15977.]
  • The association between urinary concentrations of dichlorophenol pesticides and obesity in children
    This study was conducted to assess the association of exposure to environmental pesticides with childhood obesity.A total of 6770 subjects aged 6-19 years were selected from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey (NHANES). Exposure to environmental pesticides was determined based on the concentrations of pesticide residues in urine. A dose-dependent increase in prevalence of obesity was observed in the groups with inter-quartile urinary concentrations of 2,5-dichlorophenol (2,5-DCP). There was a significant association between urinary 2,5-DCP levels and childhood obesity. However, urinary concentrations of 2,4-dichlorophenol were not shown to be significantly associated with childhood obesity. This study suggests a possible relationship between exposure to 2,5-DCP and obesity in children.
    [Twum, C. and Wei. Y. 2011. Reviews on Environ Health.26(3): 215–219.]
  • Obesity and Persistent Organic Pollutants: Possible Obesogenic Effect of Organochlorine Pesticides and Polychlorinated Biphenyls
    This study aims to assess the associations between serum levels of persistent organic pollutants (POPs) and the prevalence of obesity in a cohort of obese and lean adult men and women. POP serum samples were investigated cross-sectionally in 98 obese and 47 lean participants, aged ≥18 years. Serum samples were analyzed for the presence of polychlorinated biphenyl (PCB) congeners and for the organochlorine pesticides, dichloro-diphenyl-dichloroethylene (pp-DDE), and β-hexachlorocyclohexane (βHCH). Authors established a significant negative correlation between BMI, waist, fat mass percentage, total and subcutaneous abdominal adipose tissue, and serum levels of PCB and the sumPCBs. For βHCH, authors demonstrated a positive correlation with BMI, waist, fat mass percentage, and total and subcutaneous abdominal adipose tissue. A strong correlation was established between all POP serum levels and age. Combined, these results suggest that the diabetogenic effect of low-dose exposure to POPs might be more complicated than a simple obesogenic effect.
    [Dirinck, E., Jorens,P., Covaci, A., Geens, T., et al. 2010. Obesity. 19: 709–714.]

Oxidative Stress

  • Cellular injury leading to oxidative stress in acute poisoning with potassium permanganate/oxalic acid, paraquat, and glyphosate surfactant herbicide
    Previous studies on human acute kidney injury (AKI) following poisoning with potassium permanganate/oxalic acid (KMnO4/H2C2O4), paraquat, and glyphosate surfactant herbicide (GPSH) have shown rapid and large increases in serum creatinine (sCr) that cannot be entirely explained by direct nephrotoxicity. One plausible mechanism for a rapid increase in sCr is oxidative stress. Thus, we aimed to explore biomarkers of oxidative stress, cellular injury, and their relationship with sCr, after acute KMnO4/H2C2O4, paraquat, and GPSH poisonings. Serum biomarkers [sCr, creatine (sCn), cystatin C (sCysC)] and urinary biomarkers [cytochrome C (CytoC), 8-isoprostane (8-IsoPs)] were evaluated in 105 patients [H2C2O4/KMnO4 (N = 57), paraquat, (N = 21), GPSH (N = 27)] recruited to a multicenter cohort study. We used area under the receiver operating characteristics curve (AUC-ROC) to quantify the extent of prediction of moderate to severe AKI (acute kidney injury network stage 2/3 (AKIN2/3)). Patients with AKIN2/3 showed increased levels of CytoC. Early high CytoC predicted AKIN2/3 in poisoning with KMnO4/H2C2O4 (AUC-ROC4-8h: 0.81), paraquat (AUC-ROC4-8h: 1.00), and GPSH (AUC-ROC4-8h: 0.91). 8-Isoprostane levels were not significantly elevated. Reduced sCn and increased sCr/sCn ratios were observed for 48 h post KMnO4/H2C2O4 ingestion. Paraquat exhibited a similar pattern (N = 11), however only 3 were included in our study. Increased CytoC suggests there is mitochondrial injury coupled with energy depletion. The increased sCr within 24 h could be due to increased conversion of cellular creatine to creatinine during the process of adenosine triphosphate (ATP) generation and then efflux from cells. Later increases of sCr are more likely to represent a true decrease in kidney function.
    [Wijerathna, T.M., Mohamed, F., Gawarammana, I.B., Wunnapuk, K., Dissanayake, D.M., Shihana, F. and Buckley, N.A., 2020. Environmental toxicology and pharmacology, 80, p.103510.]
  • Low doses of the neonicotinoid insecticide imidacloprid induce ROS triggering neurological and metabolic impairments in Drosophila
    Declining insect population sizes are provoking grave concern around the world as insects play essential roles in food production and ecosystems. Environmental contamination by intense insecticide usage is consistently proposed as a significant contributor, among other threats. Many studies have demonstrated impacts of low doses of insecticides on insect behavior, but have not elucidated links to insecticidal activity at the molecular and cellular levels. Here, the histological, physiological, and behavioral impacts of imidacloprid are investigated in Drosophila melanogaster, an experimental organism exposed to insecticides in the field. We show that oxidative stress is a key factor in the mode of action of this insecticide at low doses. Imidacloprid produces an enduring flux of Ca2+ into neurons and a rapid increase in levels of reactive oxygen species (ROS) in the larval brain. It affects mitochondrial function, energy levels, the lipid environment, and transcriptomic profiles. Use of RNAi to induce ROS production in the brain recapitulates insecticide-induced phenotypes in the metabolic tissues, indicating that a signal from neurons is responsible. Chronic low level exposures in adults lead to mitochondrial dysfunction, severe damage to glial cells, and impaired vision. The potent antioxidant, N-acetylcysteine amide (NACA), reduces the severity of a number of the imidacloprid-induced phenotypes, indicating a causal role for oxidative stress. Given that other insecticides are known to generate oxidative stress, this research has wider implications. The systemic impairment of several key biological functions, including vision, reported here would reduce the resilience of insects facing other environmental challenges.
    [Martelli, F., Zhongyuan, Z., Wang, J., Wong, C.O., Karagas, N.E., Roessner, U., Rupasinghe, T., Venkatachalam, K., Perry, T., Bellen, H.J. and Batterham, P., 2020. Proceedings of the National Academy of Sciences, 117(41), pp.25840-25850.]
  • Environmental concentrations of triclosan activate cellular defence mechanism and generate cytotoxicity on zebrafish (Danio rerio) embryos.
    Triclosan (TCS, 5‑chloro‑2‑(2,4‑dichlorophenoxy) phenol) is becoming a major surface waters pollutant worldwide at concentrations ranging from ng L−1 to μg L−1. Up to now, the adverse effects on aquatic organisms have been investigated at concentrations higher than the environmental ones, and the pathways underlying the observed toxicity are still not completely understood. Therefore, the aim of this study was to investigate the toxic effects of TCS at environmental concentrations on zebrafish embryos up to 120 hours post fertilization (hpf). The experimental design was planned considering both the quantity and the exposure time for the effects on the embryos, exposing them to two different concentrations (0.1 μg L−1, 1 μg L−1) of TCS, for 24 h (from 96 to 120 hpf) and for 120 h (from 0 to 120 hpf). A suite of biomarkers was applied to measure the induction of embryos defence system, the possible increase of oxidative stress and the DNA damage. We measured the activity of glutathione‑S‑transferase (GST), P‑glycoprotein efflux and ethoxyresorufin‑o‑deethylase (EROD), the level of ROS, the oxidative damage through the Protein Carbonyl Content (PCC) and the activity of antioxidant enzymes. The genetic damage was evaluated through DNA Diffusion Assay, Micronucleus test (MN test), and Comet test. The results showed a clear response of embryos defence mechanism, through the induction of P-gp efflux functionality and the activity of detoxifying/antioxidant enzymes, preventing the onset of oxidative damage. Moreover, the significant increase of cell necrosis highlighted a strong cytotoxic potential for TCS. The overall results obtained with environmental concentrations and both exposure time, underline the critical risk associated to the presence of TCS in the aquatic environment.
    [Parenti, CC et al. 2018. Science of the Total Environment 650 (2019): 1752-1758.]
  • Bifenthrin-induced neurotoxicity in rats: involvement of oxidative stress.
    Extensive use of synthetic pyrethroids has resulted in serious human health issues. Induction of oxidative stress is an important mechanism of action of most pesticides including pyrethroids. In the present study, we have elucidated the possible role of oxidative stress in bifenthrin-induced neurotoxicity. Adult male Wistar rats were administered bifenthrin (3.5 and 7 mg per kg body weight p.o.) for 30 days. Behavioral studies were conducted on a set of randomly selected rats from each treatment group after completion of treatment. Neurochemical parameters were assessed 24 h after the last dose was administered. The selected behavioral and neurochemical endpoints were also assessed 15 days after cessation of exposure to reveal whether the neurobehavioral changes produced by bifenthrin were temporary or permanent. Deficits in motor activity, motor incoordination, and cognitive impairment were observed after exposure to bifenthrin. Levels of biogenic amines viz. dopamine (DA) and its metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), epinephrine (EPN), norepinephrine (NE), and serotonin (5-HT) altered in the frontal cortex, corpus striatum, and hippocampus of bifenthrin-treated rats. A decrease in the activity of acetylcholinesterase (AChE) occurred in all regions of the brain. Both doses of bifenthrin significantly induced lipid peroxidation (LPO) and increased protein carbonyl levels in the frontal cortex, corpus striatum, and hippocampus of rats. The activities of antioxidant enzymes, i.e. catalase, superoxide dismutase, and glutathione peroxidase, were also suppressed in all selected regions of the brain. A trend of recovery was, however, observed in all the behavioral and neurochemical endpoints 15 days after withdrawal of exposure. Oxidative stress seems to play an important role in bifenthrin-induced neurotoxicity. Our study suggests that long-term exposure to these compounds can produce detrimental effects.
    [Syed F, Awasthi KK, Chandravanshi LP, et al 2017. Toxicol Res (Camb). 7(1):48-58.]
  • Effects of melatonin in rats in the initial third stage of pregnancy exposed to sub-lethal doses of herbicides.
    Exposure to the herbicides Paraquat (PQ) and Roundup® may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the reproductive system. This study evaluated the possible changes in reproductive parameters and hepatic, as well as its prevention by simultaneous application of melatonin.Thirty-five female rats at the age of 3 months were divided into seven groups: three groups exposed to sub-lethal doses of the herbicides PQ (50mg/kg) and Roundup® (500mg/kg) (n=5, G2, G3 and G4); three groups exposed to herbicides and simultaneous treatment with 10mg/kg of Melatonin (n=5, G5, G6 and G7) and control group (n=5, G1) from the first to the seventh day of pregnancy. On the seventh day of pregnancy, the rats were anesthetized and euthanized, followed by laparotomy to remove their reproductive tissues and liver. Body and ovary weights were taken and the number of implantation sites, corpora lutea, preimplantation losses, implantation rates were counted and histopathology of the implantation sites, morphometry of the surface and glandular epithelia of endometrium and hepatic oxidative stress were undertaken.The present study shows the decrease in body and ovary weight, decrease in the number of implantation sites, implantation rate, in the total number of corpora lutea and increase of preimplantation percentages were observed when compared to the G1. The histopathological analysis of the implantation sites showed a disorder of the cytotrophoblast and cell degeneration within the blastocyst cavity in Fig. 4. Morphometry revealed a reduction in surface and glandular epithelia and in the diameter of the endometrial glands (Table 2; p>0.05 ANOVA/Tukey), whereas in liver, serum levels of thiobarbituric acid reactive substances (TBARS) were found to be significantly elevated (Fig. 2; p>0.001; p>0.05 ANOVA/Tukey), and serum level of reduced glutathione (GSH) was significantly lower (Fig. 3; p>0.001 ANOVA/Tukey). However, treatments with melatonin exhibited improvements in reproductive parameters, as well as reduced lesions in the implantation sites  and in serum levels TBARS, serum levels GSH.These results reveal that melatonin is a protective agent against experimentally induced maternal/embryo toxicity with herbicides and favoring normalization of reproductive parameters and hepatic.
    [Almeida LL, Teixeira ÁAC, Soares AF, Cunha FMD, et al. Acta Histochem. 119(3):220-227.]
  • Early life exposure to permethrin: a progressive animal model of Parkinson's disease.
    Oxidative stress, alpha-synuclein changes, mitochondrial complex I defects and dopamine loss, observed in the striatum of rats exposed to the pesticide permethrin in early life, could represent neuropathological hallmarks of Parkinson's disease (PD). Nevertheless, an animal model of PD should also fulfill criteria of face and predictive validities. This study was designed to: 1) verify dopaminergic status in the striatum and substantia nigra pars compacta; 2) recognize non-motor symptoms; 3) investigate the time-course development of motor disabilities; 4) assess L-Dopa effectiveness on motor symptoms in rats previously exposed to permethrin in early life. The permethrin-treated group received 34mg/kg daily of permethrin from postnatal day 6 to 21, whereas the age-matched control group was administered with the vehicle only. At adolescent age, the permethrin-treated group showed decreased levels of dopamine in the striatum, loss of dopaminergic neurons in the substantia nigra pars compacta and cognitive impairments. Motor coordination defects appeared at adult age (150days old) in permethrin-treated rats on rotarod and beam walking tasks, whereas no differences between the treated and control groups were detected on the foot print task. Predictive validity was evaluated by testing the ability of L-Dopa (5, 10 or 15mg/kg, os) to restore the postural instability in permethrin-treated rats (150days old) tested in a beam walking task. The results revealed full reversal of motor deficits starting from 10mg/kg of L-Dopa. The overall results indicate that this animal model replicates the progressive, time-dependent nature of the neurodegenerative process in Parkinson's disease.
    [Nasuti C, Brunori G, Eusepi P, Marinelli L, et al. 2016. J Pharmacol Toxicol Methods. 83:80-86.]
  • Combined effects of repeated administration of Bretmont Wipeout (glyphosate) and Ultrazin (atrazine) on testosterone, oxidative stress and sperm quality of Wistar rats.
    The potential toxicity resulting from the possible interactions of the herbicides, Ultrazin (atrazine, ATZ) and Bretmont Wipeout (glyphosate, GLY) is not completely known. This study evaluated reproductive- and hepato-toxicity in rats co-exposed to ATZ and GLY.Six weeks old male rats were exposed by gavage three times per week to ATZ (12.5 mg/kg) or GLY (5 mg/kg) alone or in combination (12.5 mg/kg ATZ + 5 mg/kg GLY).ATZ and GLY impaired sperm quality but GLY has more adverse effect on sperm quality than ATZ. Testosterone level, sperm motility, sperm counts, live/dead ratio and the weight of the epididymis were lower in the GLY group compared to the ATZ group by 57%, 33%, 20%, 22% and 41% and higher by 109%, 76.7%, 39.6%, 32.3% and 100% respectively in the combine-exposure group (ATZ + GLY) compared to the GLY group. Oxidative stress and histopathological changes were also noticeable in the liver but not in the testis of GLY-treated animals, and the observed effects were more remarkable in the GLY group than the ATZ or the combined-exposure group. The combined effects of the active ingredients on testosterone level, sperm count and hepatic malondialdehyde (MDA) levels were also similar as when the commercial formulations were used. Study finds antagonistic interactions between the two toxicants on the toxicity endpoints investigated in this study and these effects are due to the active ingredients of both herbicides in the commercial formulations.
    [Abarikwu SO, Akiri OF, et al. 2015. Toxicol Mech Methods.25(1):70-80.]
  • Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids.
    Pyrethroids are a class of insecticides involved in different neurological disorders. They cross the blood-brain barrier and exert their effect on dopaminergic system, contributing to the burden of oxidative stress in Parkinson's disease through several pathways. The aim of this study was to evaluate the effect of neonatal exposition to permethrin and cypermethrin (1/10 of DL(50)) in rats from the eighth to the fifteenth day of life. Open-field studies showed increased spontaneous locomotor activity in the groups treated with permethrin and the one treated with cypermethrin, while a higher number of center entries and time spent in the center was observed for the cypermethrin-treated group. Lower dopamine and higher homovanillic acid levels were measured in the striatum from both treated groups. A reduction of blood glutathione peroxidase content was measured, while no change in blood superoxide dismutase was observed. Carbonyl group formation increased in striatum, but not in erythrocytes. Lipid peroxidation occurred in erythrocytes, but not in striatum. No changes in fluidity at different depths of plasma membrane were measured in striatum or erythrocytes. The activation of monocyte NADPH oxidase by phorbol esters (PMA) shows that superoxide anion production was reduced in the pyrethroid-treated groups compared to the control group. Study suggests that neonatal exposition to permethrin or cypermethrin induces long-lasting effects after developmental exposure giving changes in open-field behaviors, striatal monoamine level, and increased oxidative stress. Although the action of pyrethroids on various target cells is different, a preferential interaction with the extracellular side of plasma membrane proteins can be observed.
    [Nasuti C, Gabbianelli R, Falcioni ML, et al.2007. Toxicology. 229(3):194-205.]

Skin Reactions/Diseases

  • Filaggrin Polymorphisms and the Uptake of Chemicals through the Skin—A Human Experimental Study
    The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals. The objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype. We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects’ urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis. Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20–22 repeats) and high FLG CNV (23–24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUC(0–40h)">AUC(040h)AUC(0–40h)) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUC(0–40h)">AUC(040h)AUC(0–40h)) for pyrimethanil than wt carriers with low and high CNV, respectively. We conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals
    [Liljedahl, E.R., Johanson, G., de Paula, H. K., Faniband, M., Assarsson, E., Littorin, M., Engfeldt, M., Lidén, C., Julander, A., Wahlberg, K., Lindh, C., Broberg, K., 2021. Environmental Health Perspectives. ]
  • Dermatologic reactions to disinfectant use during the COVID-19 pandemic
    Infection preventive practice of using disinfectants against SARS-CoV-2 has become the new normal due to the COVID-19 pandemic. Although disinfectants may not be applied directly to the human body, it remains at high risk of exposure including close skin contact on disinfected surfaces or during handling. This dermal contact, on a regular basis, can induce hazardous skin reactions like irritation, inflammation, and burning in severe conditions. Disinfectants are germicide chemicals that can penetrate the skin and create skin reactions that are usually regarded as irritant and allergic contact dermatitis. More importantly, disinfectants can react with skin components (proteins and lipids) to facilitate their skin penetration and disrupt the skin barrier function. Whereas the antimicrobial actions of disinfectants are well understood, much less is known regarding their dermatologic reactions, including but not limited to irritation and hypersensitivity. We reviewed the skin reactions created by those disinfectants against SARS-CoV-2 approved by the European Chemical Agency and the US Environmental Protection Agency.
    [Goh, C.F., Ming, L.C. and Wong, L.C., 2020. Clinics in Dermatology.]
  • Literature review: dermal monitoring data for pesticide exposure assessment of farm workers.
    A systematic literature search was performed on eight online databases. Two screening phases with predetermined criteria identified the qualifying literature. Standard information and dermal pesticide monitoring data were recorded and summarized from each qualifying study to assess its usefulness for future pesticide exposure assessment. A total of 31 farm studies qualified for review; task information was used to standardize all farm job(s) evaluated into 5 job groups: operators, applicators, mixer-loaders, field workers, and flaggers. When attempting to compare dermal exposure levels between studies, two types of variation were identified: (1) variation in study focus and reporting and 2) variation in exposure levels. The former variation type prevented exposure level comparisons between studies. Within studies, exposure levels were compared across body parts to identify that which had the highest measured exposure and to determine if results were similar in other studies that evaluated the same farm job. Using studies that measured exposure for multiple farm jobs, within study comparisons of total body exposure were performed to evaluate work factors. Future dermal pesticide exposure monitoring studies should standardize reporting procedures, as suggested in this review, to allow for more extensive dermal data comparisons. Body parts with highest measured levels of dermal exposure were identified by farm job, along with work factors to be further investigated as potential dermal pesticide exposure determinants for farm workers.
    [Garzia NA, Spinelli JJ, Gotay CC, Teschke K. 2018. J Agromedicine. 23(3):187-214.]

Urine and Other Compartments

  • Association of urinary metabolites of organophosphate and pyrethroid insecticides, and phenoxy herbicides with endometriosis
    Endometriosis is a hormone-responsive gynecologic disease, signifying its connotations across a woman’s life span. Previous studies suggested that endocrine disrupting chemicals were risk factors for endometriosis. Nevertheless, little is known on exposure to organophosphate, pyrethroid and phenoxy acid pesticides on endometriosis diagnosis. In this study, we determined the concentrations of 11 pesticides, metabolites of organophosphate and pyrethroid insecticides, and phenoxy herbicides, in urine collected from 619 reproductive-age women in Utah and California, using liquid chromatography-tandem mass spectrometry. The association of urinary concentrations of pesticides with an increase in the odds of endometriosis diagnosis was examined in 594 women who underwent laparoscopy/laparotomy (operative cohort: n = 471) or pelvic magnetic resonance imaging (population cohort: n = 123), during 2007–2009. 2-Isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), malathion dicarboxylic acid (MDA), para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPY), 3-phenoxybenzoic acid (3-PBA), and 2,4-dichlorophenoxyacetic acid (2,4-D) were detected in ≥95% of the urine samples analyzed. Urinary concentrations of IMPY, MDA, PNP, 3-PBA and 2,4-D tended to be higher in younger, non-Hispanic black, nulliparous and less affluent women. IMPY was the most dominant compound in urine followed by PNP and TCPY. When women in the 4th quartile of IMPY and the 2nd quartile of TCPY concentrations (μg/g creatinine) were compared with women in the 1st quartile, the odds ratios (ORs) for diagnosis of endometriosis increased significantly in unadjusted models (IMPY OR = 1.89, 95% confidence interval (Cl) = 1.12–3.20; TCPY OR = 1.65, 95% Cl = 1.02–2.69) for the operative (n = 471) and entire data set (n = 594), respectively. Our results suggest that exposure to elevated concentrations of diazinon (the parent compound of IMPY) and chlorpyrifos and chlorpyrifos-methyl (parent compounds of TCPY) may be associated with endometriosis.
    [Li, A.J., Chen, Z., Lin, T.C., Louis, G.M.B. and Kannan, K., 2020. Environment International, 136, p.105456.]
  • Exposure to organophosphorus insecticides and increased risks of health and cancer in US women
    Results of this paper provide evidence that chronic long-term exposure to organophosphorus insecticides poses a significantly higher health risk for US women than for men, based on dialkylphosphate biomarker data from NHANES cycles 2003-2012. The risk of cardiovascular disease for female non-smokers aged 60-85 years in the highest dimethylthiophosphate (DMTP) urinary concentration quartile is 3.0 (odds ratio, OD = 3.0, 95%CI 1.4-6.4) times higher than that in the lowest quartile. Women with higher urinary DMTP concentrations also have significantly higher risk of asthma at the ages 6-39 years and an apparently higher risk of chronic bronchitis at the ages 60-85. Overall cancer risk is significantly higher for female non-smokers aged 60-85 years in the higher urinary DMTP quartiles (OD = 2.7, 95% CI 1.3-5.9). Increasing risks of breast cancer for female smokers and prostate cancer for male smokers aged 60-85 years with higher exposure to organophosphorus insecticides in the US are also significant.
    [Sun, H., Sun, M.L. and Barr, D.B., 2020. Environmental Toxicology and Pharmacology, 80, p.103474.]
  • Organic diet intervention significantly reduces urinary glyphosate levels in U.S. children and adults
    A growing set of studies show that an organic diet is associated with reduced levels of urinary pesticide analytes. However, with the exception of one pilot study of two individuals, diet intervention studies to date have not analyzed glyphosate, the most commonly used herbicide in the United States and globally. To investigate the impact of an organic diet intervention on levels of glyphosate and its main metabolite, AMPA (aminomethyl phosphonic acid), in urine collected from adults and children. We analyzed urine samples from four racially and geographically diverse families in the United States for five days on a completely non-organic diet and for five days on a completely organic diet (n = 16 participants and a total of 158 urine samples). Mean urinary glyphosate levels for all subjects decreased 70.93% (95% CI -77.96, −61.65, p<0.010) while mean AMPA levels decreased by 76.71% (95% CI -81.54, −70.62, p < 0.010) within six days on an organic diet. Similar decreases in urinary levels of glyphosate and AMPA were observed when data for adults were examined alone, 71.59% (95% CI -82.87, −52.86, p < 0.01) and 83.53% (95% CI -88.42, −76.56, p < 0.01) and when data for children were examined alone, 70.85% (95% CI -78.52, −60.42, p < 0.01) and 69.85% (95% CI -77.56, −59.48, p < 0.01). An organic diet was associated with significantly reduced urinary levels of glyphosate and AMPA. The reduction in glyphosate and AMPA levels was rapid, dropping to baseline within three days. This study demonstrates that diet is a primary source of glyphosate exposure and that shifting to an organic diet is an effective way to reduce body burden of glyphosate and its main metabolite, AMPA. This research adds to a growing body of literature indicating that an organic diet may reduce exposure to a range of pesticides in children and adults.
    [Fagan, J., Bohlen, L., Patton, S. and Klein, K., 2020. Environmental Research, 189, p.109898.]
  • Profiles of urinary neonicotinoids and dialkylphosphates in populations in nine countries
    The application of neonicotinoid insecticides (neonics) has increased dramatically as a replacement for organophosphate pesticides (OPs) in recent years. Nevertheless, little is known about human exposure to these pesticides in various countries. In this study, concentrations of 14 neonics and six dialkylphosphate metabolites (DAPs) were determined simultaneously in 566 urine samples collected from nine countries during 2010-2014. The highest sum concentration of 14 neonics was found in urine from Vietnam (median: 12.2 ng/mL) whereas that of six DAPs was from China (18.4 ng/mL). The median concentrations of ∑6 DAPs were twice higher than those of ∑14 neonics across the nine countries, which suggested a greater exposure to OPs than neonics. The overall pattern of urinary pesticide concentrations was similar among the nine countries with dimethylphosphate (DMP) and dimethylthiophosphate (DMTP) accounting for 51-89% of the total pesticide concentrations. Differences in urinary pesticide concentrations between genders (female and male), age groups (≤20, 21-49, and ≥50 years), and regions (cities of Shanghai, Guangzhou and Qiqihar) were examined. Total daily exposure doses to OPs were highest in China (515 μg/day) with 15% of the samples exceeding the U.S. Environmental Protection Agency's reference dose for chlorpyrifos (18 μg/day). This is the first study to establish baseline levels of OP and neonics exposure in general populations across nine countries.
    [Li, A.J. and Kannan, K., 2020. Environment International, 145, p.106120.]
  • Association Between Exposure to Pyrethroid Insecticides and Risk of All-Cause and Cause-Specific Mortality in the General US Adult Population
    Widespread exposure to pyrethroid insecticides has been reported among the general population in the United States and worldwide. However, little is known about the association of pyrethroid. To examine the association of pyrethroid exposure with all-cause and cause-specific mortality among adults in the United States. The national representative cohort included 2116 adults aged 20 years and older who participated in the US National Health and Nutrition Examination Survey conducted from 1999 to 2002 and provided urine samples for pyrethroid metabolite measurements. Participants were linked to mortality data from the survey date through December 31, 2015. Data were analyzed from May to August 2019. Urinary levels of 3-phenoxybenzoic acid, a general pyrethroid metabolite and commonly used biomarker for pyrethroid exposure, were determined by using high-performance liquid chromatography coupled with electrospray chemical ionization and tandem mass spectrometry. Mortality from all causes, cardiovascular disease, and cancer. This cohort study of 2116 adults comprised 1145 women (weighted proportion, 51.6%) and 971 men (weighted, 48.4%), with a weighted mean (SE) age of 42.6 (0.5) years; 958 participants (weighted, 68.4%) were of non-Hispanic white ancestry, 646 (weighted, 14.7%) of Hispanic ancestry, 419 (weighted, 11.3%) of non-Hispanic black ancestry, and 93 (weighted, 5.6%) of other ancestry. During a median of 14.4 years (range, 0.1-16.8 years) of observation, 246 deaths occurred, including 41 associated with cardiovascular disease and 52 associated with cancer. Participants with higher urinary 3-phenoxybenzoic acid levels were at a higher risk of death during the follow-up period, with death occurring in 8.5% (unweighted, 75 of 709), 10.2% (unweighted, 81 of 701), and 11.9% (unweighted, 90 of 706) of participants across increasing tertiles of urinary 3-phenoxybenzoic acid levels. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and urinary creatinine levels, the hazard ratios for all-cause mortality, cardiovascular disease mortality, and cancer mortality among participants with the highest tertile compared with those with the lowest tertile of urinary 3-phenoxybenzoic acid levels were 1.56 (95% CI, 1.08-2.26), 3.00 (95% CI, 1.02-8.80), and 0.91 (95% CI, 0.31-2.72), respectively. In this nationally representative sample of US adults, environmental exposure to pyrethroid insecticides was associated with an increased risk of all-cause and cardiovascular disease mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.
    [Bao, W., Liu, B., Simonsen, D.W. and Lehmler, H.J., 2019. JAMA Internal Medicine. 180(3):367-374.]
  • Association between urinary triclosan with bone mass density and osteoporosis in the US adult women, 2005-2010.
    Laboratory studies have demonstrated that Triclosan (TCS) could result in significant interstitial collagen accumulation and an increase in trabecular bone. However, little is known about the relationship between TCS exposure and human bone health. We used 2005-2010 National Health and Nutrition Examination Survey data to examine the association between urinary TCS concentrations with BMD and osteoporosis in the US adult women (age ≥20 years). After inclusion and exclusion, 1,848 women were finally analyzed. After adjustment for other covariates, we observed significant associations between tertile 3 of TCS concentration and lower BMD in regions of total femur (β=-0.016, 95% CI=-0.032, -0.000), intertrochanter (β=-0.022, 95% CI=-0.042, -0.002), and lumbar spine (β=-0.014, 95% CI=-0.029, 0.001), respectively, relative to tertile 1. Compared with women at tertile 1, those at tertile 3 were more likely to have increased osteoporosis prevalence in intertrochanter [odd ratio (OR)=2.464, 95% CI = 1.190, 5.105]. This is the first epidemiological study to investigate the association between urinary TCS concentration with BMD and osteoporosis in the US adult women. We found urinary TCS concentration was negatively associated with BMD and was positively associated with the prevalence of osteoporosis. The evidence was stronger in postmenopausal women than in premenopausal women. Future prospective studies are needed to validate the findings.
    [Cai, S., Zhu, J., Sun, L., Fan, C., Zhong, Y., Shen, Q. and Li, Y., 2019. The Journal of Clinical Endocrinology & Metabolism.]
  • Characterising glyphosate exposures among amenity horticulturists using multiple spot urine samples.
    Glyphosate has recently received much public attention following its 'Group 2A - probably carcinogenic to humans' classification from the International Agency for Research on Cancer. Despite the widespread use of glyphosate, there is limited data on potential exposures during common occupational uses. The study aimed to characterize occupational exposures to glyphosate among amenity horticulturists through the collection and analysis of urine samples following pesticide application. The impact of work practices on personal exposure, as well as suitability of collecting multiple spot urine samples as a sampling strategy for the assessment of occupational exposure for glyphosate were also examined.A minimum of three spot urine samples were collected per work task; before the work task began, after the work task completion and the following first morning void. Peak urine glyphosate concentrations measured for work tasks were 2.5, 1.9, 1.9 and 7.4 μg L-1 (arithmetic mean, geometric mean, median and maximum value, respectively). Concentrations were highest in samples taken up to 3 h after completing the work task. Regression analysis showed that workers who sprayed the day before the sampling task had higher glyphosate concentrations in pre-task samples than those who did not spray the day before (p < 0.01). Similarly, workers who took breaks during the work task had higher peak urinary glyphosate concentrations (p < 0.01). The multivariate mixed-effect model showed that the following first-morning void samples were approximately a factor 0.7 lower than post-task values. Occupational exposures to glyphosate among amenity horticulturalists are greater than those reported in environmental studies and comparable with previously reported agricultural studies. A suitable sampling strategy for occupational exposures to glyphosate is the collection of a spot urine sample up to 3 h after completing the application of a glyphosate-based pesticide product, which provides a reliable marker of peak exposure.
    [Connolly A, Basinas I, Jones K, Galea KS, et al. 2018. Int J Hyg Environ Health. 221(7):1012-1022]
  • Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study
    Glyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length. Urine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length. The mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5-7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths. This is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized.
    [Parvez S, Gerona RR, Proctor C, Friesen M, Ashby JL, Reiter JL, Lui Z, Winchester PD. 2018. Environ Health. 17(1):23. doi: 10.1186/s12940-018-0367-0.]
  • Glyphosate in German adults - Time trend (2001 to 2015) of human exposure to a widely used herbicide.
    The broadband herbicide glyphosate (N-[phosphonomethyl]-glycine) and its main metabolite aminomethylphosphonic acid (AMPA) were analyzed by GC-MS-MS in 24h-urine samples cryo-archived by the German Environmental Specimen Bank (ESB). Samples collected in 2001, 2003, 2005, 2007, 2009, 2011, 2012, 2013, 2014, and 2015 were chosen for this retrospective analysis. All urine samples had been provided by 20 to 29 years old individuals living in Greifswald, a city in north-eastern Germany. Out of the 399 analyzed urine samples, 127 (=31.8%) contained glyphosate concentrations at or above the limit of quantification (LOQ) of 0.1μg/L. For AMPA this was the case for 160 (=40.1%) samples. The fraction of glyphosate levels at or above LOQ peaked in 2012 (57.5%) and 2013 (56.4%) after having discontinuously increased from 10.0% in 2001. Quantification rates were lower again in 2014 and 2015 with 32.5% and 40.0%, respectively. The overall trend for quantifiable AMPA levels was similar. Glyphosate and AMPA concentrations in urine were statistically significantly correlated (spearman rank correlation coefficient=0.506, p≤0.001). Urinary glyphosate and AMPA levels tended to be higher in males. The possible reduction in exposure since 2013 indicated by ESB data may be due to changes in glyphosate application in agricultural practice. The ESB will continue monitoring internal exposures to glyphosate and AMPA for following up the time trend, elucidating inter-individual differences, and contributing to the ongoing debate on the further regulation of glyphosate-based pesticides.
    [Conrad A, Schröter-Kermani C, Hoppe HW, Rüther M, Pieper S, Kolossa-Gehring M. 2017. Int J Hyg Environ Health. 220(1):8-16]
  • Glyphosate Residues in Groundwater, Drinking Water and Urine of Subsistence Farmers from Intensive Agriculture Localities: A Survey in Hopelchén, Campeche, Mexico
    The use of pesticides in Mexican agriculture creates an interest in learning about the presence of these substances in different environmental matrices. Glyphosate (GLY) is an herbicide widely used in the state of Campeche, located in the Mayan zone in the western Yucatan peninsula. Despite the fact that GLY is considered a non-toxic pesticide to humans, its presence in water bodies through spillage, runoff, and leaching are a risk to human health or biota that inhabit these ecosystems. In the present study, glyphosate residues were determined in groundwater, bottled drinking water, and the urine of subsistence farmers from various localities of the Hopelchén municipality in Campeche. Determination of GLY was carried out using Enzyme-Linked Immunosorbent Assay (ELISA). The highest concentrations of GLY were observed in the groundwater (1.42 μg/L) of Ich-Ek and urine (0.47 μg/L) samples of subsistence farmers from the Francisco J. Mújica communities. The glyphosate concentrations in groundwater and bottled drinking water indicate an exposure and excessive use of glyphosate in these agricultural communities. This is one of the first studies that reports glyphosate concentration levels in human urine and bottled drinking water in México and in the groundwater in the Yucatan Peninsula as part of a prospective pilot study, to which a follow-up will be performed to monitor this trend over time.
    [Rendon-von Osten J, Dzul-Caamal R. 2017. Int J Environ Res Public Health. 14(6). pii: E595.]
  • Longitudinal assessment of occupational determinants of chlorpyrifos exposure in adolescent pesticide workers in Egypt.
    Chlorpyrifos (CPF) is an organophosphourus insecticide applied to cotton fields by adolescents employed by the Egyptian Ministry of Agriculture. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) is a biomarker of CPF exposure that has substantial variability among these applicators. In order to identify predictors of CPF exposure, we conducted a longitudinal study of 43 adolescent pesticide applicators in Egypt from April 2010 to January 2011 in Egypt. Urinary TCPy was quantified at 25 time-points, prior to, during, and following application. We used log-linear regression and a best subset selection approach to identify the exposure determinants that were most predictive of cumulative TCPy and participants' highest TCPy values (peak exposure). Applicators had cumulative urinary TCPy levels ranging from 167 to 49,8208μg/g creatinine. Total hours applying CPF (semi-partial r2=0.32), and total hours in the field applying other pesticides (semi-partial r2=0.08) were the strongest predictors of cumulative TCPy. Applicators had peak urinary TCPy levels ranging from 4 to 5715μg/g creatinine. The amount of time applying pesticides prior to blood draw was the strongest predictor of peak TCPy (semi-partial r2=0.30). We also observed evidence that wearing clean clothes to work was associated with lower longitudinal TCPy. Our results suggest there is an opportunity for targeted interventions, particularly related to hygiene or implementation of personal protective equipment usage to reduce CPF exposure among adolescent pesticide workers
    [Callahan CL, Hamad LA, Olson JR, Ismail AA, et al. 2017. Int J Hyg Environ Health. 220(8):1356-1362]
  • Urinary Concentrations of Insecticide and Herbicide Metabolites among Pregnant Women in Rural Ghana: A Pilot Study.
    Use of pesticides by households in rural Ghana is common for residential pest control, agricultural use, and for the reduction of vectors carrying disease. However, few data are available about exposure to pesticides among this population. Our objective was to quantify urinary concentrations of metabolites of organophosphate (OP), pyrethroid, and select herbicides during pregnancy, and to explore exposure determinants. In 2014, 17 pregnant women from rural Ghana were surveyed about household pesticide use and provided weekly first morning urine voids during three visits (n = 51 samples). A total of 90.1% (46/51) of samples had detectable OP metabolites [geometric mean, GM (95% CI): 3,5,6-trichloro-2-pyridinol 0.54 µg/L (0.36-0.81), para-nitrophenol 0.71 µg/L (0.51-1.00)], 75.5% (37/49) had detectable pyrethroid metabolites [GM: 3-phenoxybenzoic acid 0.23 µg/L (0.17, 0.32)], and 70.5% (36/51) had detectable 2,4-dichlorophenoxyacetic acid levels, a herbicide [GM: 0.46 µg/L (0.29-0.73)]. Concentrations of para-nitrophenol and 2,4-dichlorophenoxyacetic acid in Ghanaian pregnant women appear higher when compared to nonpregnant reproductive-aged women in a reference U.S.
    [Wylie BJ, Ae-Ngibise KA, Boamah EA, Mujtaba M, et al. Int J Environ Res Public Health. 14(4). pii: E354.]
  • An Observational Study to Evaluate Associations Between Low-Level Gestational Exposure to Organophosphate Pesticides and Cognition During Early Childhood.
    Prenatal exposure to organophosphate pesticides, which is ubiquitous, may be detrimental to neurological development. We examined 327 mother/infant pairs in Cincinnati, Ohio, between 2003 and 2006 to determine associations between prenatal exposure to organophosphate pesticides and neurodevelopment. Twice during pregnancy urinary concentrations of 6 common dialkylphosphates, nonspecific metabolites of organophosphate pesticides, were measured. Aggregate concentrations of diethylphosphates, dimethylphosphates, and total dialkylphosphates were calculated. Bayley Scales of Infant Development, Second Edition-Mental and Psychomotor Developmental indices were administered at ages 1, 2, and 3 years, the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, at age 4, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at age 5. Mothers with higher urinary total dialkylphosphate concentrations reported higher levels of socioeconomic status and increased fresh fruit and vegetable intake. We found no associations between prenatal exposure to organophosphate pesticides and cognition at 1-5 years of age. In our cohort, exposure to organophosphate pesticides during pregnancy was not associated with cognition during early childhood. It is possible that a higher socioeconomic status and healthier diet may protect the fetus from potential adverse associations with gestational organophosphate pesticide exposure, or that dietary exposure to the metabolites is innocuous and not an ideal measure of exposure to the parent compound.
    [Donauer S, Altaye M, Xu Y, Sucharew H, et al. 2016. Am J Epidemiol. 184(5):410-8. ]
  • Determinants of urinary concentrations of dialkyl phosphates among pregnant women in Canada - Results from the MIREC study
    Organophosphate (OP) insecticides are commonly used in agriculture. Their use decreased in recent years as they were gradually replaced by other pesticides, but some OPs are still among the insecticides most used in Canada. Exposure to elevated levels of OPs during pregnancy has been associated with adverse birth outcomes and poorer neurodevelopment in children. The objective of the present study was to examine the relationship between the concentrations of OP pesticides urinary dialkyl phosphate (DAP) metabolites and various factors that are potential sources of exposure or determinants of DAP levels. In the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, six DAPs were measured in 1st trimester urine samples of 1884 pregnant women living in Canada. They were grouped into sums of dimethyl alkyl phosphates (DMAP) and diethyl alkyl phosphates (DEAP) for statistical analysis. We found that 93% of women had at least one DAP detected in their urine. Geometric means (GM) of specific gravity-corrected levels for urine dilution were 59 (95% CI 56-62) and 21 (95% CI 20-22) nmol/L for DMAP and DEAP, respectively. The following characteristics were significantly associated with higher urinary concentrations of DMAP or DEAP: higher education, nulliparous, normal pre-pregnancy body mass index, non-smoker, not fasting at sampling, winter season at sampling, and early and late day collection times. Dietary items that were significantly related with higher urinary concentrations included higher intake of citrus fruits, apple juice, sweet peppers, tomatoes, beans and dry peas, soy and rice beverages, whole grain bread, white wine and green and herbal teas. This study indicates that exposure to these compounds is quasi-ubiquitous. The factors associated with greater DAP levels identified here could be useful to regulatory agencies for risk analysis and management. However, some exposure misclassification might occur due to the single DAP measurement available, and to the presence of preformed DAPs in the environment.
    [Sokoloff K, Fraser W, Arbuckle TE, et al. 2016. Environ Int. 94:133-40.]
  • Association of pyrethroid pesticide exposure with attention-deficit/hyperactivity disorder in a nationally representative sample of U.S. children.
    Study examined the association between pyrethroid pesticide exposure and ADHD in a nationally representative sample of US children, and tested whether this association differs by sex. Data are from 8-15 year old participants (N = 687) in the 2001-2002 National Health and Nutrition Examination Survey. Children with urinary 3-PBA above the limit of detection (LOD) were twice as likely to have ADHD compared with those below the LOD. Hyperactive-impulsive symptoms increased by 50 % for every 10-fold increase in 3-PBA levels; effects on inattention were not significant. Authors observed possible sex-specific effects: pyrethroid biomarkers were associated with increased odds of an ADHD diagnosis and number of ADHD symptoms for boys but not girls. Results found an association between increasing pyrethroid pesticide exposure and ADHD which may be stronger for hyperactive-impulsive symptoms compared to inattention and in boys compared to girls.
    [Wagner-Schuman M, Richardson JR, Auinger P, et al. 2015. Environ Health.14:44.]
  • Comparison of residents' pesticide exposure with predictions obtained using the UK regulatory exposure assessment approach.
    The UK regulatory methods currently used for estimating residents' potential pesticide exposure were assessed to determine whether they provide sufficiently conservative estimates. A non-random sample of 149 residents living within 100 m of fields where pesticides were sprayed provided first morning void urine samples one and/or two days after spraying. Using farmers' spray information, regulatory exposure assessment (REA) models were applied to estimate potential pesticide intake among residents, with a toxicokinetic (TK) model used to estimate urinary biomarker concentrations in the mornings of the two days following the spray. These were compared with actual measured urinary biomarker concentrations obtained following the spray applications. The study focused on five pesticides (cypermethrin, penconazole, captan, chlorpyrifos and chlormequat). All measured cypermethrin urinary biomarker levels were lower than the REA-predicted concentrations. Over 98% and 97% of the measured urinary biomarker concentrations for penconazole and captan respectively were lower than the REA-predicted exposures. Although a number of the chlorpyrifos and chlormequat spray-related urinary biomarker concentrations were greater than the predictions, investigation of the background urinary biomarker concentrations suggests these were not significantly different from the levels expected had no pesticide spraying occurred. The majority of measured concentrations being well below the REA-predicted concentrations indicate that, in these cases, the REA is sufficiently conservative.
    [Galea KS, MacCalman L, Jones K, Cocker J, et al. 2015. Regul Toxicol Pharmacol.73(2):634-43.]
  • Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land
    This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing ≤100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1-2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 μg/g creatinine). Overall, study observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population.
    [Galea KS, MacCalman L, Jones K, Cocker J, et al. 2015. J Expo Sci Environ Epidemiol. 25(6):623-31.]
  • Association of urinary phenols with increased body weight measures and obesity in children and adolescents.
    To examine the association of urinary levels of the environmental phenol pesticides 2,5-dichlorophenol, 2,4-dichlorophenol, and triclosan with body weight outcomes in children and adolescent participants in the National Health and Nutrition Examination Survey 2007-2010. Study found a statistically significant positive association between both 2,5-dichlorophenol and 2,4-dichlorophenol with BMI z-score, WC, and obesity in children and adolescents. After stratification by age, the significant associations remained only in adolescents (ages 12-19). No associations were found between triclosan and any of the body weight outcomes.
    [Buser MC, Murray HE, Scinicariello F. 2014. J Pediatr. 165(4):744-9.]
  • Biomonitoring of dialkylphosphate metabolites (DAPs) in urine and hair samples of sprayers and rural residents of Crete, Greece.
    The aim of this study was to evaluate the exposure of rural residents (control group) and occupational exposed population group of sprayers to organophosphorus pesticides (OPs) by measuring their non-specific dialkylphosphate metabolites (DAPs) in hair and in urine samples. All subjects (n=120) were residents of the municipality of Ierapetra, an area of intensive cultivation in Crete, Greece.The determined OPs metabolites were DMP, DEP, DETP and DEDTP. The detection rates of DMP, DEP and DETP for both control and sprayers groups were high in both matrices, ranging from 91% to 100%. DEDTP was detected only in 9% of sprayers hair samples, while its detection rates in urine samples ranged from 83% to 90% for both population groups. Data analysis revealed significantly higher sumDAPs levels in urine of sprayers than in the urine of control group and this is justified since sampling occurred during spraying periods. SumDAPs levels in hair samples of the sprayers were also significantly higher than in the hair of control group, confirming the long-term exposure to OPs. SumDAPs found levels in urine and hair samples of subjects were significantly correlated. Study confirmed the elevated levels of DAPs in hair and urine samples in occupationally exposed group of sprayers in comparison to control group, even detected levels were similar in logarithmic scale.
    [Kokkinaki A, Kokkinakis M, Kavvalakis MP, Tzatzarakis MN, et al. 2014. Environ Res. 134:181-7.]
  • Trends in long term exposure to propoxur and pyrethroids in young children in the Philippines.
    Ongoing pesticide exposure has to be monitored in the study of long term outcome of pesticide adverse effects since changes in the type and amount of exposure can influence outcome. The aim of this paper is to describe the trend in long term pesticide exposure in children through the analysis of pesticides in their hair. As part of an NIH study on the long term effects of pesticide exposure in young children, ongoing exposure to pesticides was determined by the analysis of children's hair for propoxur and pyrethroids at 2, 4 and 6 years of age.There were significant changes in the prevalence and concentration of propoxur and pyrethroids in children's hair at 2, 4 and 6 years of age. At ages 2 and 4 years, the prevalence of propoxur exposure increased from 12.4% to 24.1% but dramatically decreased to 1.7% at 6 years. For bioallethrin, the prevalence of exposure steadily increased from 2 years to 4 years and to 6 years. Exposure to transfluthrin significantly increased from 4 years to 6 years. Between 4 and 6 years, there was a higher median concentration of propoxur at 4 compared to 6 years and for transfluthrin and bioallethrin, at 6 compared to 4 years.Changes in the prevalence and concentration of exposure to propoxur and pyrethroids in children at 2, 4 and 6 years of age are related to the progress in ambulation of young children and to changes in the formulation of home spray pesticides. Thus, periodic monitoring of pesticide exposure is necessary when studying the long term effects of pesticide exposure in the neurodevelopment of young children.
    [Ostrea EM Jr, Villanueva-Uy E, Bielawski D, et al. 2014. Environ Res. 131:13-6.]
  • Uptake and elimination of permethrin related to the use of permethrin treated clothing for forestry workers.
    Wearing of permethrin treated clothing usually implicates an uptake of permethrin by the user. Aim of study was to examine the kinetics of internal permethrin exposure in volunteers during and after a single 8h-use of treated clothing as well as factors potentially influencing permethrin uptake. 28 male volunteers (age: 20-34 years) were equipped with permethrin treated jackets and pants from two different suppliers. The clothing was worn for 8h, simulating differing external conditions, including comfort conditions as well as conditions of increased temperature and humidity without and with additional physical workload. Internal permethrin exposure was monitored by determination of permethrin metabolites (DCCA and 3-PBA) in a set of 12 urine samples, covering a period of 504 h from the beginning of the wearing interval. Time-concentration curves showed an increase of internal exposure associated with wearing of the clothing (individual maximum: 109.5 μg/L) followed by a first-order like decay (mean half-life: 38.5 h). Metabolite excretion was affected by the make of clothing, which could be explained by differing permethrin contents of the garment. Furthermore, internal exposure increased with increasing temperature/humidity and additional physical workload. Assuming dermal uptake of permethrin, this may be ascribed to an alteration of the barrier function of the skin.
    [Rossbach B, Niemietz A, Kegel P, Letzel S. 2014. Toxicol Lett. 231(2):147-53.]
  • Urinary biomarkers of exposure to insecticides, herbicides, and one insect repellent among pregnant women in Puerto Rico.
    Authors measured urinary concentrations of the insect repellent N-N-diethyl-meta-toluamide (DEET) and two of its metabolites [3-diethyl-carbamoyl benzoic acid (DCBA) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB)], four pyrethroid insecticide metabolites [4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA); 3-phenoxybenzoic acid (3-PBA); trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA); and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA)], and two chlorophenoxy herbicides [2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)] in 54 pregnant women from Puerto Rico at three separate time points (20 ± 2 weeks, 24 ± 2 weeks, and 28 ± 2 weeks of gestation). Results found that 95th percentile urinary concentrations of DEET, 3-PBA, trans-DCCA, and 2,4-D were lower than women of reproductive age on the U.S. mainland, whereas 95th percentile urinary concentrations of 4-F-3-PBA, cis-DBCA, and 2,4,5-T were similar. DCBA, the only urinary biomarker detected in >50% of the samples, showed fair to good reproducibility across pregnancy (intraclass correlation coefficient: 0.60). Women were more likely to have greater urinary concentrations of pesticide biomarkers if they were less educated (DCBA and trans-DCCA), unemployed (DHMB), or married (2,4-D), had consumed collards or spinach in past 48-hr (2,4-D) or had been using insect repellent since becoming pregnant (DCBA), or were involved with residential applications of pesticides (trans-DCCA).
    [Lewis RC, Cantonwine DE, Anzalota Del Toro LV, Calafat AM, et al. 2014. Environ Health. 13:97]
  • Environmental exposure to pyrethroids and sperm sex chromosome disomy: a cross-sectional study.
    This study investigated whether environmental exposure to pyrethroids was associated with altered frequency of sperm sex chromosome disomy in adult men. A sample of 75 subjects recruited through a Massachusetts infertility clinic provided urine and semen samples. Individual exposures were measured as urinary concentrations of three pyrethroid metabolites ((3-phenoxybenzoic acid (3PBA), cis- and trans- 3-(2,2-Dichlorovinyl)-1-methylcyclopropane-1,2-dicarboxylic acid (CDCCA and TDCCA)). Multiprobe fluorescence in situ hybridization for chromosomes X, Y, and 18 was used to determine XX, YY, XY, 1818, and total sex chromosome disomy in sperm nuclei. Poisson regression analysis was used to examine the association between aneuploidy rates and pyrethroid metabolites while adjusting for covariates. Between 25-56% of the sample were above the limit of detection (LOD) for the pyrethroid metabolites. All sex chromosome disomies were increased by 7-30% when comparing men with CDCCA and TDCCA levels above the LOD to those below the LOD. For 3PBA, compared to those below the LOD, those above the LOD had YY18 disomy rates 1.28 times higher whereas a reduced rate was seen for XY18 and total disomy, and no association was seen for XX18 and 1818. Findings suggest that urinary concentrations of CDCCA and TDCCA above the LOD were associated with increased rates of aneuploidy. However the findings for 3BPA were not consistent.
    [Young HA, Meeker JD, Martenies SE, et al. 2013. Environ Health. 12(1):111]
  • Environmental Chemicals in Pregnant Women in the US: NHANES 2003-2004.
    Study analyzed biomonitoring data from the National Health and Nutritional Examination Survey (NHANES) to characterize both individual and multiple chemical exposures in U.S. pregnant women. Data for 163 chemical analytes in 12 chemical classes for subsamples of 268 pregnant women from NHANES 2003-2004, a nationally representative sample of the U.S. population, were analyzed. The percent of pregnant women with detectable levels of an individual chemical ranged from 0 to 100 percent. Certain PCBs, organochlorine pesticides, PFCs, phenols, PBDEs, phthalates, polycyclic aromatic hydrocarbons (PAHs) and perchlorate were detected in 99 to 100% of pregnant women. The median number of detected chemicals by chemical class ranged from 4 (out of 12 PFCs) to 9 (out of 13 phthalates). Across chemical classes, median number ranged from 8 (out of 17 chemical analytes) to 50 (out of 71 chemical analytes). Generally, levels in pregnant women were similar or lower than levels in non-pregnant women, adjustment for covariates tended to increase levels in pregnant women compared to non-pregnant women. Authors conlude, pregnant women in the U.S. are exposed to multiple chemicals. Further efforts are warranted to understand sources of exposure and implications for policy-making.
    [Woodruff TJ, Zota AR, Schwartz JM. 2011. Environ Health Perspect. doi: 10.1289/ehp.1002727]
  • Estrogenic and androgenic activities in total plasma measured with reporter-gene bioassays: Relevant exposure measures for endocrine disruptors in epidemiologic studies?
    The objective of this study was to explore the effects of a variety of sources of potential endocrine disruptors on estrogenic and androgenic activities in total plasma measured by Chemically Activated LUciferase gene eXpression (CALUX®). Plasma samples and interview data on sources of potential endocrine disruptors were collected from 108 men with different exposures profiles. Mean differences (beta) in 17ß-estradiol equivalents (EEQs) and dihydrotestosterone equivalents (AEQs) between exposure groups were estimated using general linear models. Mean plasma AEQs and EEQs were 9.1×10(-1)ng/ml and 12.0pg/ml, respectively. Elevated AEQs were found in smokers and heavy drinkers, and in men occupationally exposed to disinfectants or welding/soldering fumes. Occupational exposure to pesticides, disinfectants, and exhaust fumes seemed to be associated with increased plasma EEQs: 1.5 (-0.2-3.2)pg/ml, 2.1 (0.2-3.9)pg/ml, and 2.9 (0.6-5.2)pg/ml, respectively. Moderate to high plasma dioxin levels, measured in a subgroup by the dioxin-responsive CALUX®, were accompanied by a 20% increase in AEQs. Although the results are not yet readily interpretable, they indicate that these measurements can be valuable for epidemiologic studies on endocrine disruptors and give direction for further research.
    [Brouwers MM et al. 2011. Environ Int.;37(3):557-64]
  • Halogenated POPs and PAHs in Blood Plasma of Hong Kong Residents
    The objective of this study was to quantify organic chlorinated pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs) in blood plasma collected from 111 healthy residents in Hong Kong to assess the levels of these pollutants in the general population during the period of March to April, 2008. Naphthalene, phenanthrene, p,p'-DDE, PCB-180, and PBDE-47 were detected in 100% of the participants. Females had significantly greater concentrations of acenaphthylene (female: 93.3 ng/g lipid; male: 39.8, p < 0.05), anthracene (22.3; 15.3, p < 0.05), fluoranthene (138; 125, p < 0.05), p,p'-DDE, p,p'-DDT, PCB-183, BDE-99 than males. Blood of smokers contained significantly greater (p < 0.05) concentrations of acenaphthene, benzo(a)pyrene, p,p'-DDE, p,p'-DDT, PCB-138, BDE-47, and BDE-99 than did blood of nonsmokers. Positive correlations were found between concentrations of each class of pollutant, with respect to seafood diet habit, Body Mass Index (BMI), and age. Concentrations of HCHs and DDTs in blood plasma of healthy Hong Kong residents were greater than those of other countries, and it was found that smoking, consumption of a seafood diet, BMI, and age could influence concentrations in human blood.
    [Qin YY, et al. 2011. Environ Sci Technol. [Epub ahead of print]
  • Lower birth weight and increased body fat at school age in children prenatally exposed to modern pesticides: a prospective study
    In this prospective study of 247 children born by women working in greenhouses in early pregnancy, 168 were categorized as prenatally exposed to pesticides. At three months and at 6 to 11 years of age the children underwent a clinical examination and blood sampling for analysis. Body fat percentage was also calculated. Compared to unexposed children birth weight and weight for gestational age were lower in the highly exposed children and medium exposed children. Exposed children had significantly larger increase in BMI Z-score from birth to school age and highly exposed children had 15.8% larger skin folds and higher body fat percentage. If prenatally exposed to both pesticides and maternal smoking, the sum of four skin folds was 46.9% and body fat percentage 29.1% higher.
    [Wohlfahrt-Veje, C., K. Main, I. Schmidt, M. Boas, T. Jensen, P. Grandjean, et al. 2011. Environ Health.10:79.]
  • Peripheral precocious puberty in a 4-month-old girl: role of pesticides?
    A 4-month-old girl presented with sexual development, including breast enlargement, menstruation, uterine length of 69mm at ultrasonography, and dramatically high estrogen bioactivity, but no growth acceleration, pubic hair, pelvis masses or adrenal tumors. Gas chromatography with an electron capture detector and mass spectrometry detected pesticides (p,p-DDD, p,p-DDT, lindane and endosulfan sulpfate) in plasma from the infant, the mother, and the 38-year-old father, who reported a dramatic decrease in libido, and in soil samples from their farm. The precocious sexual development was probably caused by the estrogen activity of the environmental contamination by tons of pesticides stored in the family farm.
    [Gaspari L, Paris FO, Jeandel C, Sultan C. 2011. Gynecol Endocrinol. doi:10.3109/09513590.2010.526666]
  • Pesticide exposure among pregnant women in Jerusalem, Israel: results of a pilot study
    Authors measured urinary concentrations of organophosphorus (OP) insecticide metabolites and plasma concentrations of OP and other pesticides in 20 pregnant women, recruited in Jerusalem, Israel in 2006, and collected questionnaire data on demographic factors and consumer habits from these women. Study compared creatinine-adjusted OP pesticide metabolite concentrations, as well as plasma pesticide concentrations, with other populations of pregnant women. Creatinine-adjusted total dimethyl (DM) metabolite concentrations were between 4 and 6 times higher in this population compared to other populations of pregnant women in the United States while total diethyl (DE) metabolite concentrations were lower. Dimethylphosphate (DMP) was detected in 74% of the urine samples whereas dimethylthiophosphate (DMTP) was detected in 90% of the urine samples. The carbamate bendiocarb was detected in 89% of the plasma samples, while the OP insecticide chlorpyrifos was detected in 42% of the samples. Mean plasma concentrations of bendiocarb and chlorpyrifos in our sample were 4.4 and 3.9 times higher, respectively, than that of an urban minority cohort from New York City. Twelve women (63%) reported using some form of household pest control during their pregnancy and five (26%) reported using household pest control during the past month. Women with a graduate degree had significantly higher geometric mean concentrations of total urinary DM metabolite concentrations compared to other women. It is unclear why total DM metabolites concentrations were much higher in this population compared to other populations of pregnant women in the United States and Netherlands.
    [Berman T et al. 2011. Environ Int.;37(1):198-203]
  • Assessing Children's Dietary Pesticide Exposure: Direct Measurement of Pesticide Residues in 24-hr Duplicate Food Samples
    Researchers measured pesticide residues in 24-hr duplicate food samples collected from a group of 46 young children participating in the Children's Pesticide Exposure Study (CPES). Samples of all conventional fruits, vegetables, and fruit juices equal to the quantity consumed by their children, similarly prewashed/ prepared, and from the same source or batch. Individual or composite food items were analyzed for organophosphate (OP) and pyrethroid insecticide residues. Auhors found 14% or 5% of those food samples contained at least one OP or pyrethroid insecticide, respectively. We measured a total of 11 OP insecticides, at levels ranging from 1 to 387 ng/g, and three pyrethroid insecticides, at levels ranging from 2 to 1,133 ng/g, in children's food samples. The frequent consumption of food commodities with episodic presence of pesticide residues that are suspected to cause developmental and neurological effects in young children supports the need for further mitigation.
    [Lu C, Schenck FJ, Pearson MA, Wong JW.2010. Environ Health Perspect.118(11):1625-30.]
  • Attention-Deficit/Hyperactivity Disorder and Urinary Metabolites of Organophosphate Pesticides

    The goal was to examine the association between urinary concentrations of dialkyl phosphate metabolites of organophosphates and attention-deficit/hyperactivity disorder (ADHD) in children 8 to 15 years of age. Cross-sectional data from the National Health and Nutrition Examination Survey (2000–2004) were available for 1139 children, who were representative of the general US population. A structured interview with a parent was used to ascertain ADHD diagnostic status, on the basis of slightly modified criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. One hundred nineteen children met the diagnostic criteria for ADHD. Children with higher urinary dialkyl phosphate concentrations, especially dimethyl alkylphosphate (DMAP) concentrations, were more likely to be diagnosed as having ADHD. A 10-fold increase in DMAP concentration was associated with an odds ratio of 1.55 (95% confidence interval: 1.14–2.10), with adjustment for gender, age, race/ethnicity, poverty/income ratio, fasting duration, and urinary creatinine concentration. For the most-commonly detected DMAP metabolite, dimethyl thiophosphate, children with levels higher than the median of detectable concentrations had twice the odds of ADHD (adjusted odds ratio: 1.93 [95% confidence interval: 1.23–3.02]), compared with children with undetectable levels. These findings support the hypothesis that organophosphate exposure, at levels common among US children, may contribute to ADHD prevalence. Prospective studies are needed to establish whether this association is causal.


    [Bouchard, M. et al. 2010. Pediatrics (doi:10.1542/peds.2009-3058)]
  • Biomonitoring data for 2,4-dichlorophenoxyacetic acid in the United States and Canada: interpretation in a public health risk assessment context using Biomonitoring Equivalents
     Several extensive studies of exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) using urinary concentrations in samples from the general population, farm applicators, and farm family members are now available. Reference doses (RfDs) exist for 2,4-D, and Biomonitoring Equivalents (BEs; concentrations in urine or plasma that are consistent with those RfDs) for 2,4-D have recently been derived and published. We reviewed the available biomonitoring data for 2,4-D from the United States and Canada and compared them with BE values to draw conclusions regarding the margin of safety for 2,4-D exposures within each population group. Data on urinary 2,4-D excretion in general and target populations from recent published studies are tabulated and the derivation of BE values for 2,4-D summarized. The biomonitoring data indicate margins of safety (ratio of BE value to biomarker concentration) of approximately 200 at the central tendency and 50 at the extremes in the general population. Median exposures for applicators and their family members during periods of use appear to be well within acute exposure guidance values. Biomonitoring data from these studies indicate that current exposures to 2,4-D are below applicable exposure guidance values. This review demonstrates the value of biomonitoring data in assessing population exposures in the context of existing risk assessments using the BE approach. Risk managers can use this approach to integrate the available biomonitoring data into an overall assessment of current risk management practices for 2,4-D.
    [Aylward LL et al. 2010. Environ Health Perspect. 118(2):177-81]
  • Pesticide concentrations in maternal and umbilical cord sera and their relation to birth outcomes in a population of pregnant women and newborns in New Jersey
    Study evaluated in utero exposures to pesticides by measuring maternal and cord serum biomarkers in a New Jersey cohort of pregnant women and the birth outcomes of their neonates. Authors evaluated the following pesticide compounds in both maternal and umbilical cord sera: chlorpyrifos, diazinon, carbofuran, chlorothalonil, dacthal, metolachlor, trifluralin and diethyl-m-toluamide (DEET). Of these compounds, chlorpyrifos, carbofuran, chlorothalonil, trifluralin, metolachlor and DEET were the pesticides most frequently detected in the serum samples. High (≥75th percentile) metolachlor concentrations in cord blood were related to birth weight. An increase in abdominal circumference with increasing cord dichloran concentrations was also observed. These observations suggest that in utero exposures to certain pesticides may alter birth outcomes.
    [Barr, D. et al. 2010. Sci Total Environ. 408(4):790-5]
  • Plasma organochlorine levels and risk of non-Hodgkin lymphoma in the Nurses' Health Study
    Numerous studies have reported positive associations of environmental exposure to polychlorinated biphenyls (PCB) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with the risk of non-Hodgkin lymphoma (NHL). In a case-control study nested within the Nurses' Health Study, a prospective cohort of U.S. women, we measured concentrations of PCBs and p,p'-DDE in blood samples from 145 women diagnosed with NHL at least 6 months after blood draw and 290 age- and race-matched controls. We used conditional logistic regression to estimate the odds ratios and 95% confidence intervals for each quartile of exposure relative to the lowest quartile. We also evaluated these associations for major histologic subtypes of NHL. There was no consistent evidence of an association of p,p'-DDE, total PCBs, immunotoxic, or individual PCB congeners with risk of NHL. These results do not support the hypothesis of a positive association between PCB exposure and development of NHL.
    [Laden F et al. 2010. Cancer Epidemiol Biomarkers Prev.19(5):1381-4]
  • Urinary concentrations of metabolites of pyrethroid insecticides in the general U.S. population: National Health and Nutrition Examination Survey 1999-2002
    The objective was to assess human exposure via biomonitoring to pyrethroid insecticides in a representative sample of the general U.S. population >or= 6 years of age. Researchers measured five urinary metabolites of pyrethroid insecticides in 5,046 samples collected as a part of the 1999-2002 National Health and Nutrition Examination Survey (NHANES). Results detected 3-phenoxybenzoic acid (3PBA), a metabolite common to many pyrethroid insecticides, in more than 70% of the samples. Non-Hispanic blacks had significantly higher 3PBA concentrations than did non-Hispanic whites and Mexican Americans in the 2001-2002 survey period and in the combined 4-year survey periods but not in the 1999-2000 survey period. Children had significantly higher concentrations of 3PBA than did adolescents in both NHANES periods and than adults in NHANES 1999-2000. Cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid were highly correlated with each other and with 3PBA, suggesting that urinary 3PBA was derived primarily from exposure to permethrin, cypermethrin, or their degradates. Study concludes pyrethroid insecticide exposure in the U.S. population is widespread, and the presence of its metabolites in the urine of U.S. residents indicates that children may have higher exposures than adolescents and adults.
    [Barr DB, et al. 2010. Environ Health Perspect.;118(6):742-8]
  • Evaluating cumulative organophosphorus pesticide body burden of children: a national case study
    Biomonitoring is a valuable tool for identifying exposures to chemicals that pose potential harm to human health. However, to date there has been little published on ways to evaluate the relative public health significance of biomonitoring data for different chemicals and even less on cumulative assessment of multiple chemicals. The objectives of this study were to develop a methodology for a health risk interpretation of biomonitoring data and to apply it using NHANES 1999-2002 body burden data fororganophosphorus (OP) pesticides. OP pesticides present a particularly challenging case given the nonspecificity of manymetabolites monitored through NHANES. Study back-calculates OP pesticide exposures from urinary metabolite data and compares cumulative dose estimates with available toxicity information for a common mechanism of action (brain cholinesterase inhibition) using data from U.S. EPA. Results suggest that approximately 40% of children in the United States may have had insufficient margins of exposure (MOEs) for neurological impacts from cumulative exposures to OP pesticides (MOE less than 1000). Limitations include uncertainty related to assumptions about likely precursor pesticide compounds of the urinary metabolites, sources of exposure, and intraindividual and temporal variability.
    [Payne-Sturges D, Cohen J, Castorina R, Axelrad DA, Woodruff TJ. 2009. Environ Sci Technol. 15;43(20):7924-30]
  • Genotoxic biomonitoring of agricultural workers exposed to pesticides in the north of Sinaloa State, Mexico
    Genotoxic damage was evaluated in 70 agricultural workers, 25 women and 45 men, exposed to pesticides in Las Grullas, Ahome, Sinaloa, Mexico, with an average of 7 years of exposure. The effect was detected through the sister chromatid exchanges (SCE) in lymphocytes of peripheral blood and micronuclei (MN) and other nuclear anomalies (NA) in buccal exfoliated cells. Also, the influence on cellular proliferation kinetics (CPK) was studied by means of the replication index (RI) and the cytotoxic effect was examined with the mitotic index (MI). The non-exposed group consisted of 70 other persons, 21 women and 47 men from the city of Los Mochis, Sinaloa, Mexico. Significant differences between the exposed and the non-exposed groups were observed in SCE, CPK, MI, MN and NA. Analysis of variance revealed that age, gender, smoking and alcohol consumption did not have a significant effect on genetic damage. However, there was a correlation between exposure time to pesticides and SCE frequency. These results could have been due to the exposure of workers to pesticides containing different chemical compounds. This study afforded valuable data to estimate the possible risk to health associated with pesticide exposure.
    [Martínez-Valenzuela C. et al. 2009. Environ Int;35(8):1155-9]
  • Organochlorine and heavy metals in newborns: results from the Flemish Environment and Health Survey (FLEHS 2002-2006)
    To collect regional information on internal levels of pollutants in humans in Flanders, 1196 mother-child pairs were systematically recruited in 2002-2003 via 25 maternities across Flanders. Cd, Pb, PCB congeners, p,p'-DDE - a key metabolite of DDT- and hexachlorobenzene (HCB) were measured in cord blood or plasma. Cd was detected in 64% of the samples. p,p'-DDE and Pb were measurable in nearly all samples. The individual PCB congeners could be detected in 40 to 81% of the newborns. HCB and dioxin-like compounds were above detection limit in more than 75% of the samples. Age and smoking habits of the mothers, did not influence the cord blood Pb and Cd levels. The organochlorines increased 4 to 9% per year of the mother's age. Mothers had 2.6% less PCBs in cord blood for each unit increase in pre-pregnancy BMI. Season of delivery, breastfeeding previous children or consumption of local dairy products, were minor determinants. Up to 20% of the variability in organochlorine concentrations was explained by residence area. It was concluded that the place of birth in Flanders is an important determinant of the load of pollutants measured at the start of life. This underlines the validity of human biomonitoring on (relatively) small geographical scale.
    [Koppen G et al. 2009. Environ Int.;35(7):1015-22]
  • Arsenic Exposure and Prevalence of Type 2 Diabetes in US Adults
    Using National Health and Nutrition Examination Survey (NHANES) data, this study investigates the association of arsenic exposure, as measured in urine, with the prevalence of type 2 diabetes in a representative sample of US adults. Common sources of inorganic arsenic exposure include dietary exposure, drinking water pollution, and contamination associated with arsenic wood preservatives such as sawdust, smoke, direct contact, and hazardous waste sites. After adjustment for diabetes risk factors and markers of seafood intake, participants with type 2 diabetes had a 26% higher level of total arsenic (95% confidence interval [CI], 2.0%-56.0%) than participants without type 2 diabetes.
    [Navas-Acien, Ana, et al. 2008. JAMA. 300(7):814-822]
  • Biomonitoring of exposure to pesticides
    Many biomonitoring methods have employed analytical techniques such as chromatography and mass spectrometry to accurately measure urinary metabolites or blood body burdens of several classes of pesticides. The pesticides assessed include the banned organochlorine pesticides, the more modern organophosphorus, carbamate, and pyrethroid insecticides along with a variety of herbicides including phenoxyacetic acids and triazines. These methods are capable of detecting concentrations in biological samples resulting from occupational exposures to pesticides, and in some instances, general background exposures from residential or dietary exposures. These data have been used for a variety of applications. They have documented the pervasiveness of pesticide exposures, have allowed us to determine the primary predictors of exposure in certain populations, have helped us to identify the most important pathways of exposure, and have helped us to better understand any potential risks associated with exposures. In addition, these methods have helped us to document poisoning cases and identify etiologic agents in crisis situations. This review discusses the methods that have been employed over the last 40 years and how these methods have addressed critical public health questions.
    [Barr, D. 2008. Journal of Chemical Health and Safety 15(6):20-29]
  • Dietary Intake and Its Contribution to Longitudinal Organophosphorus Pesticide Exposure in Urban/suburban Children.
    Study assessed young urban/suburban children's longitudinal exposure to OP pesticides in the Children's Pesticide Exposure Study (CPES).Twenty-three children 3-11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003-2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. Study measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons. By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to non-detected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. Study also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year. The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children.
    [Lu C, Barr DB, Pearson MA, Waller LA. 2008. Environ Health Perspect. 216(4):537-42.]
  • Environmental chemicals in people: challenges in interpreting biomonitoring information.
    Biomonitoring, the measurement of chemicals in blood, urine, and other tissues or fluids, is becoming an increasingly common tool in the study of human exposure to environmental chemicals and the potential health effects of those chemicals. The National Health and Nutrition Examination Survey (NHANES) now includes biomonitoring data for hundreds of chemicals as well as information on other health and demographic endpoints for thousands of individuals in the United States. The NHANES databases provide valuable information for deriving reference ranges and trend information and can be used for hypothesis-generating analyses, but they cannot be used to establish causal relationships between environmental chemicals and health effects. This commentary examines issues unique to the use of such databases and the interpretation of biomonitoring-based epidemiological studies.
    [LaKind JS, Barraj L, Tran N, Aylward LL. 2008. J Environ Health ;70(9):61-4]
  • The influence of age and gender on triclosan concentrations in Australian human blood serum.
    Recent in vitro and in vivo studies indicate that triclosan might exert adverse effects in humans. triclosan has previously been shown to be present in human plasma and milk at concentrations that are well correlated to the use of personal care products containing triclosan. In this study authors investigated the influence of age, gender, and the region of residence on triclosan concentrations in pooled samples of Australian human blood serum. The results showed no influence of region of residence on the concentrations of triclosan. There was a small but significant influence of age and gender on the serum triclosan concentrations, which were higher in males than in females, and highest in the group of 31-45 year old males and females. However, overall there was a lack of pronounced differences in the triclosan concentrations within the dataset, which suggests that the exposure to triclosan among different groups of the Australian population is relatively homogenous. A selection of the dataset was compared with previous measurements of triclosan concentrations in human plasma from Sweden, where the use of triclosan is expected to be low due to consumer advisories. The triclosan concentrations were a factor of 2 higher in Australian serum than in Swedish plasma.
    [Allmyr M, et al. 2008. Sci Total Environ. ;393(1):162-7]
  • Urinary concentrations of triclosan in the U.S. population: 2003-2004.
    This study was designed to assess exposure to triclosan in a representative sample > or = 6 years of age of the U.S. general population from the 2003-2004 National Health and Nutrition Examination Survey (NHANES). Study analyzed 2,517 urine samples and detected concentrations of total (free plus conjugated) triclosan in 74.6% of samples at concentrations of 2.4-3,790 microg/L. Concentrations of triclosan were higher in people in the high household income than in people in low and medium income categories. In about three-quarters of urine samples analyzed as part of NHANES 2003-2004, we detected concentrations of triclosan. Concentrations differed by age and socioeconomic status but not by race/ethnicity and sex. Specifically, the concentrations of triclosan appeared to be highest during the third decade of life and among people with the highest household incomes.
    [Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. 2008. Environ Health Perspect ;116(3):303-7]
  • Agreement of pesticide biomarkers between morning void and 24-h urine samples from farmers and their children
    In pesticide biomonitoring studies, researchers typically collect either single voids or daily (24-h) urine samples. Collection of 24-h urine samples is considered the "gold-standard", but this method places a high burden on study volunteers, requires greater resources, and may result in misclassification of exposure or underestimation of dose due to noncompliance with urine collection protocols. To evaluate the potential measurement error introduced by single void samples, we present an analysis of exposure and dose for two commonly used pesticides based on single morning void (MV) and 24-h urine collections in farmers and farm children. The agreement between the MV concentration and its corresponding 24-h concentration was analyzed using simple graphical and statistical techniques and risk assessment methodology. A consistent bias towards overprediction of pesticide concentration was found among the MVs, likely in large part due to the pharmacokinetic time course of the analytes in urine. These results suggest that the use of single voids can either over- or under-estimate daily exposure if recent pesticide applications have occurred. This held true for both farmers as well as farm children, who were not directly exposed to the applications. As a result, single void samples influenced the number of children exposed to chlorpyrifos whose daily dose estimates were above levels of toxicologic significance. In populations where fluctuations in pesticide exposure are expected (e.g., farm families), the pharmacokinetics of the pesticide and the timing of exposure events and urine collection must be understood when relying on single voids as a surrogate for longer time-frames of exposure.
    [Scher, D. et al. 2007, J. Exposure Science and Environmental Epidemiology; 17, 350–357]
  • Merging Models and Biomonitoring Data to Characterize Sources and Pathways of Human Exposure to Organophosphorus Pesticides in the Salinas Valley of California
    The study population is the CHAMACOS cohort of almost 600 pregnant Latina women in the Salinas Valley region. Study uses model estimates of organophosphate (OP) intake and urinary dialkylphosphate (DAP) metabolite excretion to develop premises about relative contributions from different exposure sources and pathways. Researchers evaluated these premises by comparing the magnitude and variation of DAPs in the CHAMACOS cohort with those of the whole U.S. population using data from the National Health and Nutrition Examination Survey (NHANES). This comparison supports the premise that diet is the common and dominant exposure pathway in both populations. Biomarker comparisons and model results support the observation that, relative to NHANES, the CHAMACOS population has a statistically significant added intake of OP pesticides with low inter-individual variability. Authors attribute the magnitude and small variance of this intake to residential nondietary exposures from local agricultural OP uses. These results show that mass-balance models can estimate exposures for OP pesticides within the range measured by biological monitoring.
    [McKone, T. et al. 2007. Environ. Sci. Technol. 41 (9): 3233–3240]
  • Pesticides and Childhood Cancer: An Update of Zahm and Ward's 1998 Review
    Children are exposed to pesticides through a number of sources, including residential and agricultural applications. Parental occupational exposure to pesticides is also a concern because exposures occurring during pregnancy and carry-home residues also contribute to children's cumulative burden. A number of epidemiological studies consistently reported increased risks between pesticide exposures and childhood leukemia, brain cancer, neuroblastoma, non-Hodgkin's lymphoma, Wilms' tumor, and Ewing's sarcoma. An extensive review of these studies was published in 1998 (Zahm & Ward, 1998). Fifteen case-control studies, 4 cohort studies, and 2 ecological studies have been published since this review, and 15 of these 21 studies reported statistically significant increased risks between either childhood pesticide exposure or parental occupational exposure and childhood cancer. Therefore, one can confidently state that there is at least some association between pesticide exposure and childhood cancer. However, an unambiguous mechanistic cause-and-effect relationship between pesticide exposure and childhood cancer was not demonstrated in these studies, and modifying factors such as genetic predisposition, rarely considered in the reviewed studies, likely play an important role.
    [Infante-Rivard C, Weichenthal S. 2007. J Toxicol Environ Health B Crit Rev. 10(1-2):81-99.]
  • A Longitudinal Approach to Assessing Urban and Suburban Children's Exposure to Pyrethroid Pesticides
    Researchers conducted a longitudinal study to assess the exposure of 23 elementary school-age children to pyrethroid pesticides, using urinary pyrethroid metabolites as exposure biomarkers. Most of the children's conventional diets were substituted with organic food items for 5 consecutive days and two daily spot urine samples wrer collected, throughout the 15-day study period. Yrine samples for five common pyrethroid metabolites were analyzed. Authors found an association between the parents' self-reported pyrethroid use in the residential environment and elevated pyrethroid metabolite levels found in their children's urine. Children were also exposed to pyrethroids through their conventional diets, although the magnitude was smaller than for the residential exposure. Children's ages appear to be significantly associated with pyrethroids exposure, which is likely attributed to the use of pyrethroids around the premises or in the facilities where older children engaged in the outdoor activities. Study concludes that residential pesticide use represents the most important risk factor for children's exposure to pyrethroid insecticides. Because of the wide use of pyrethroids in the United States, the findings of this study are important for both children's pesticide exposure assessment and environmental public health.
    [Lu C, Barr DB, Pearson M, Bartell S, Bravo R.. 2006. Environ Health Perspect. 114(9):1419-23.]
  • Effects of processing on pesticide residues in peaches intended for baby food.
    Peaches containing added residues of chlorpyrifos-methyl, fenitrothion, procymidone and vinclozolin were used for simulated industrial processing in the manufacture of baby food puree. Residues were determined in raw material, in intermediate products at crucial steps of the processing procedure and in final products. The results of the study were interpreted with respect to enforcement of the stringent Maximum Residue Limit (MRL) of 0.01 mg kg-1 established by the European Commission (EC) for any pesticide in baby food. Peeling was identified as the most effective procedure in reducing residues. Thermal treatment (concentration and sterilisation) substantially reduced organophosphate (chlorpyrifos-methyl, fenitrothion) residues, whereas procymidone and vinclozolin residue levels were increased in peach puree.
    [Balinova AM, Mladenova RI, Shtereva DD. 2006. Food Addit Contam.23(9):895-901]
  • Potential Uses of Biomonitoring Data: A Case Study Using the Organophosphorus Pesticides Chlorpyrifos and Malathion
    Biologic monitoring has been widely used to assess exposures, susceptibility, and effects of chlorpyrifos and malathion. For biomonitoring of exposure, chlorpyrifos and malathion have been measured in blood, but most typically their urinary metabolites have been measured. Although many biologic monitoring data have been generated and published on these chemicals, their interpretation is not straightforward. For example, exposure to environmental degradates of chlorpyrifos and malathion may potentially increase f urinary metabolite levels, thus leading to overestimation of exposure. Also, the temporal nature of the exposures makes the evaluation of both exposure and effects difficult. Authors present an overview of the current biomonitoring and other relevant data available on exposure to chlorpyrifos and malathion and the use of these data in various environmental public health applications.
    [Barr, D, B. and Angerer, J. 2006. Environ Health Perspect; 114(11): 1763–1769]
  • Reference values for metabolites of pyrethroid and organophosphorous insecticides in urine for human biomonitoring in environmental medicine
    With reliable and sensitive analytical methods for detecting metabolites of organophosphorous and pyrethroid insecticides in urinary specimens of the general population several studies have been published on internal exposure to these insecticides of the population in Germany. In Germany, reference values for environmental pollutants related to the population are established continuously by the Human Biomonitoring Commission of the German Federal Environmental Agency, preferably based on data gained by representative studies. Since there is a need for reference values to characterise the population's exposure to organophosphates and pyrethroids, and since there are different studies available from Germany that agree quite well with data from other industrialised countries, the Commission has derived reference values from the available data, though none of the studies had fulfilled criteria on representativity. Reference values for metabolites of organophosphorous acids are as follows: DMP 135 µg/l, DMTP 160 µg/l and DEP 16 µg/l and for metabolites of pyrethroids: cis-Cl2CA 1 µg/l, trans-Cl2CA 2 µg/l and 3-PBA 2 µg/l. As the volume-related concentrations of organophosphate and pyrethroid metabolites show no significant age-dependence, the reference values derived are not age-stratified. Though based merely on statistical and not on toxicological data, levels analysed above the reference levels, when reliably measured (verified several times), should prompt environmental health practitioners to search for sources, within the bounds of proportionality. In addition to accidental poisoning, possible sources include indoor contamination following improper pest control operations in homes as well as in pets and food products contaminated by these pesticides.
    [Heudorf, U., Butte, W., Schulz, C., and Angerer. J. 2006. International Journal of Hygiene and Environmental Health, 209(3):293-299]
  • Triclosan in plasma and milk from Swedish nursing mothers and their exposure via personal care products
    In this study, plasma and milk were sampled from 36 mothers and analyzed for triclosan. Scrutinization of the women's personal care products revealed that nine of the mothers used toothpaste, deodorant or soap containing triclosan. Triclosan and/or its metabolites were omnipresent in the analyzed plasma and milk. The concentrations were higher in both plasma and milk from the mothers who used personal care products containing triclosan than in the mothers who did not. This demonstrated that personal care products containing triclosan were the dominant, but not the only, source of systemic exposure to triclosan. The concentrations were significantly higher in plasma than in milk, indicating that infant exposure to triclosan via breast milk is much less than the dose in the mother.
    [Allmyr M, Adolfsson-Erici M, McLachlan MS, Sandborgh-Englund G. 2006. Sci Total Environ.;372(1):87-93]
  • Biologic monitoring to characterize organophosphorus pesticide exposure among children and workers: an analysis of recent studies in Washington State.
    Study examined findings from five organophosphorus pesticide biomonitoring studies conducted in Washington State between 1994 and 1999 and compared urinary dimethylthiophosphate (DMTP) concentrations for all study groups and composite dimethyl alkylphosphate (DMAP) concentrations for selected groups. Children of pesticide applicators had substantially higher metabolite levels than did Seattle children and farmworker children. Metabolite levels of children living in agricultural communities were elevated during periods of crop spraying. Median DMTP concentrations for Seattle children and farmworker children did not differ significantly; however, the DMAP concentrations were higher for Seattle children than for farmworker children. DMTP concentrations of U.S. children 6-11 years of age (1999-2000 National Health and Nutrition Examination Survey population) were higher than those of Seattle children and farmworker children. DMTP concentrations for workers actively engaged in apple thinning were 50 times higher than DMTP concentrations for farmworkers sampled outside of peak exposure periods. Study concludes that workers who have direct contact with pesticides should continue to be the focus of public health interventions and that elevated child exposures in agricultural communities may occur during active crop-spraying periods and from living with a pesticide applicator. Timing of sample collection is critical for the proper interpretation of pesticide biomarkers excreted relatively soon after exposure. Authors surmise that differences in dietary exposure can explain the similar exposures observed among farmworker children, children living in the Seattle metropolitan area, and children sampled nationally.
    [Fenske RA, Lu C, Curl CL, Shirai JH, Kissel JC. 2005. Environ Health Perspect.;113(11):1651-7]
  • Biomonitoring: is body burden relevant to public health?
    Biomonitoring is the study of the presence and concentration of chemicals in humans usually by the measurement of blood, urine or breath (exhaled air). Properly conducted, these data provide a picture of the amount of a chemical or agent actually absorbed into the body for a specific period of time. This review provides a history of biomonitoring, as well as the limitations and potential benefits of these studies. Examples of the proper and possibly improper use of biomonitoring and the impact made on our society are provided. Reasons for having comprehensive national biomonitoring programs are summarized, along with the societal benefits and risks. A brief discussion of the history of the NHANES program and select results from the 2005 Report are presented. By 2010, it has been predicted that the Centers for Disease Control (CDC) will be monitoring nearly 1000 chemicals in persons from all regions of the nation. The measurement of chemicals and biomarkers has revolutionized the field of exposure assessment. Overall, we recommend an approach of careful interpretation, understanding that the data obtained are useful for establishing baseline information about exposure, rather than equating detection with risk. We present suggestions for contextualizing biomonitoring results in order to provide the public with the tools to distinguish genuine health risks from trivial ones.
    [Paustenbach D and Galbraith D. 2005. Regul Toxicol Pharmacol. 44(3):249-6]
  • Glyphosate biomonitoring for farmers and their families: results from the Farm Family Exposure Study.
    Glyphosate is the active ingredient in Roundup agricultural herbicides and other herbicide formulations that are widely used for agricultural, forestry, and residential weed control. As part of the Farm Family Exposure Study, we evaluated urinary glyphosate concentrations for 48 farmers, their spouses, and their 79 children (4-18 years of age). We evaluated 24-hr composite urine samples for each family member the day before, the day of, and for 3 days after a glyphosate application. Sixty percent of farmers had detectable levels of glyphosate in their urine on the day of application. The geometric mean (GM) concentration was 3 ppb, the maximum value was 233 ppb, and the highest estimated systemic dose was 0.004 mg/kg. Farmers who did not use rubber gloves had higher GM urinary concentrations than did other farmers (10 ppb vs. 2.0 ppb). For spouses, 4% had detectable levels in their urine on the day of application. Their maximum value was 3 ppb. For children, 12% had detectable glyphosate in their urine on the day of application, with a maximum concentration of 29 ppb. All but one of the children with detectable concentrations had helped with the application or were present during herbicide mixing, loading, or application. None of the systemic doses estimated in this study approached the U.S. Environmental Protection Agency reference dose for glyphosate of 2 mg/kg/day. Nonetheless, it is advisable to minimize exposure to pesticides, and this study did identify specific practices that could be modified to reduce the potential for exposure.
    [Acquavella, J, F. et al. 2004. Environ Health Perspect; 112(3): 321–326]
  • Genotoxicity of pesticides: a review of human biomonitoring studies
    Pesticides have been considered potential chemical mutagens: experimental data revealed that various agrochemical ingredients possess mutagenic properties inducing mutations, chromosomal alterations or DNA damage. Biological monitoring provides a useful tool to estimate the genetic risk deriving from an integrated exposure to a complex mixture of chemicals. Studies available in scientific literature have essentially focused on cytogenetic end-points to evaluate the potential genotoxicity of pesticides in occupationally exposed populations, including pesticide manufacturing workers, pesticide applicators, floriculturists and farm workers. A positive association between occupational exposure to complex pesticide mixtures and the presence of chromosomal aberrations (CA), sister-chromatid exchanges (SCE) and micronuclei (MN) has been detected in the majority of the studies, although a number of these failed to detect cytogenetic damage. Conflicting results from cytogenetic studies reflect the heterogeneity of the groups studied with regard to chemicals used and exposure conditions. Genetic damage associated with pesticides occurs in human populations subject to high exposure levels due to intensive use, misuse or failure of control measures. The majority of studies on cytogenetic biomarkers in pesticide-exposed workers have indicated some dose-dependent effects, with increasing duration or intensity of exposure. Chromosomal damage induced by pesticides appears to have been transient in acute or discontinuous exposure, but cumulative in continuous exposure to complex agrochemical mixtures.
    [Bolognesi, C. 2003. Mutation Research/Reviews in Mutation Research, 543(3): 251-272]
  • Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: a validation study.
    Authors collected 100 amniotic fluid samples slated for disposal and evaluated analytical methods to measure organophosphate and carbamate pesticides and metabolites, synthetic pyrethroid metabolites, herbicides, and chlorinated phenolic compounds. The following six phenols were detected (detection frequency): 1- and 2-naphthol (70%), 2,5-dichlorophenol (55%), carbofuranphenol (5%), ortho-phenylphenol (30%), and pentachlorophenol (15%). The organophosphate metabolites diethylphosphate and dimethylphosphate were detected in two (10%) samples, and dimethylthiophosphate was detected in one (5%) sample. These levels are low compared with levels reported in urine, blood, and meconium in other studies, but indicate direct exposures to the young fetus, possibly during critical periods of development. Results of this pilot study suggest that amniotic fluid offers a unique opportunity to investigate fetal exposures and health risks.
    [Bradman,A., Barr, D, Claus Henn, B, Drumheller, T, Curry, C. and Eskenazi, B. 2003. Environ Health Perspect. 111(14): 1779–1782.]
  • Organophosphorus Pesticide Exposure of Urban and Suburban Preschool Children with Organic and Conventional Diets.
    Study assessed organophosphorus (OP) pesticide exposure from diet by biological monitoring among Seattle, Washington, preschool children. Parents kept food diaries for 3 days before urine collection, and they distinguished organic and conventional foods based on label information. Children were then classified as having consumed either organic or conventional diets based on analysis of the diary data. Residential pesticide use was also recorded for each home. 24-hr urine samples were collected from 18 children with organic diets and 21 children with conventional diets and analyzed for five OP pesticide metabolites. Results found significantly higher median concentrations of total dimethyl alkylphosphate metabolites than total diethyl alkylphosphate metabolites. The median total dimethyl metabolite concentration was approximately six times higher for children with conventional diets than for children with organic diets. The dose estimates suggest that consumption of organic fruits, vegetables, and juice can reduce children's exposure levels from above to below the U.S. Environmental Protection Agency's current guidelines, thereby shifting exposures from a range of uncertain risk to a range of negligible risk. Consumption of organic produce appears to provide a relatively simple way for parents to reduce their children's exposure to OP pesticides.
    [Curl, C, Fenske, R, and Elgethun, K. 2003. Environ Health Perspect. 111(3): 377–382.]
  • The importance of diet on exposure to and effects of persistent organic pollutants on human health in the Arctic
    Authors describe the importance of diet on exposure to and possible health effects of persistent organic pollutants (POPs) in the Arctic. Minor decreases in POPs and minor increases in Hg levels in Arctic populations in Greenland, Eastern Russia, Western Alaska and Eastern Canada are likely to occur by the year 2010 and major decreases in both POPs and Hg levels in these same populations by 2030. Levels of POPs and metals in populations in the Faeroe Islands and the Scandinavian countries are already reasonably low and are only likely to decline marginally by 2030. To improve understanding of the health effects associated with exposure to contaminants in the Arctic, authors recommend that circumpolar epidemiological studies should be implemented on a larger scale. MeHg- and POPs-related effects are still the key issues. However, the role of newly discovered contaminants, such as PBDEs (polybrominated diphenyl ethers) and PCNs (polychlorinated naphthalenes), should be investigated, as well as a more nuanced view on human dietary exposure to xenobiotics.
    [Odland JO, Deutch B, Hansen JC, Burkow IC. 2003. Acta Paediatr ;92(11):1255-66]
  • Analytical methods for biological monitoring of exposure to pesticides: a review
    Synthetic pesticides have been used since in the early to mid twentieth century. In the US alone, over 800 pesticide active ingredients are formulated in about 21 000 different commercial products. Although many public health benefits have been realized by the use of pesticides, their potential impact on the environment and public health is substantial. For risk assessment studies, exposure assessment is an integral component, which has unfortunately, often been weak or missing. In the past several decades, researchers have proposed to fill these missing data gaps using biological monitoring of specific markers related to exposures. In this paper, authors present a review of existing analytical methodology for the biological monitoring of exposure to pesticides. They also present a critical assessment of the existing methodology and explore areas in which more research is needed.
    [Barr, D and Needham, L. 2002. Journal of Chromatography B 778 (1-2); 5-29]
  • Biological monitoring survey of organophosphorus pesticide exposure among pre-school children in the Seattle metropolitan area
    In this study we assessed organophosphorus (OP) pesticide exposure among children living in two Seattle metropolitan area communities by measuring urinary metabolites, and identified possible exposure risk factors through a parental interview. We recruited children in clinic and outpatient waiting rooms. We obtained spot urine samples in the spring and fall of 1998 from 110 children ages 2-5 years, from 96 households. We analyzed urine samples for six dialkylphosphate (DAP) compounds, the common metabolites of the OP pesticides. Through parental interviews we gathered demographic and residential pesticide use data. At least one of the DAP metabolites was measured in 99% of the children, and the two predominant metabolites (DMTP and DETP) were measured in 70-75% of the children. We found no significant differences in DAP concentrations related to season, community, sex, age, family income, or housing type. Median concentrations of dimethyl and diethyl DAPs were 0.11 and 0.04 micromol/L, respectively (all children). Concentrations were significantly higher in children whose parents reported pesticide use in the garden (0.19 vs. 0.09 micromol/L for dimethyl metabolites, p = 0.05; 0.04 vs. 0.03 micromol/L for diethyl metabolites, p = 0.02), but were not different based on reported pet treatment or indoor residential use. Nearly all children in this study had measurable levels of OP pesticide metabolites. Some of this exposure was likely due to diet. Garden pesticide use was associated with elevated metabolite levels. It is unlikely that these exposure levels would cause acute intoxication, but the long-term health effects of such exposures are unknown. We recommend that OP pesticide use be avoided in areas where children are likely to play.
    [Lu C, Knutson DE, Fisker-Andersen J, Fenske RA. 2001. Environ Health Perspect;109(3):299-303]
  • Biomonitoring of persons exposed to insecticides used in residences
    Pesticides used indoors inevitably result in some unintentional and unavoidable exposures of residents. Measured dosages of residents are well below toxic levels. Exposures are substantially less and occur over a longer time than suggested by unvalidated estimates derived from previous extreme, conservative default assumptions based solely on environmental residues. Human chlorpyrifos exposures were monitored following three different types of applications: fogger, broadcast, and crack-and-crevice. Persistence of total residue on carpet was substantially greater than the persistence of transferable residue. Low-level exposures of family members persisted for periods of weeks to a month after pesticide use. Although few children who resided with their parents in pest-protected homes have been monitored, they eliminated more biomarker than their parents on a kg body weight-day basis when absorbed dosages were derived from spot urine specimens corrected for volume by an age-specific creatinine correction. Ultimately environmental residues may become useful elements of predictive residential exposure models, but their potential contribution to indirect exposure assessments must include careful determination of residue availability for contact transfer to clothing or skin and biological validation. Experimental and situational monitoring of exposed persons is essential for meaningful and responsible predictive resident exposure model building.
    [Krieger, R.I., Bernard, C.E., Dinoff, T.M., Ross J.H. and Williams R.L. 2001. Ann Occup Hyg, 45 (suppl 1): S143-S153. doi: 10.1093/annhyg/45.suppl_1.S143]
  • Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study.
    Experimental data have linked exposure to prenatal organophosphates to adverse neurocognitive sequalae. However, epidemiologic research has been hampered by lack of reliable dosimeters. Existing biomarkers reflect short-term exposure only. Measurements of pesticides in postpartum meconium may yield a longer-term dosimeter of prenatal exposure. As the initial step in biomarker validation, this research determined background levels, detection limits, and stabilities of six organophosphate metabolites in meconium: diethylphosphate (DEP), diethylthiophosphate (DETP), diethyldithiophosphate (DEDTP), dimethylphosphate (DMP), dimethylthiophosphate (DMTP), and dimethyldithiophosphate (DMDTP). The meconium was collected from 20 newborns at New York Presbyterian Hospital; analyses were undertaken at the Centers for Disease Control and Prevention (CDC). DEP was detected in 19/20 samples and DETP was detected in 20/20. DMP and DEDTP were each detected in 1/20 (at 16 and 1.8 microg/g, respectively). DMTP and DMDTP were not detected. Levels were similar to those seen in adult urine in population-based research. Results indicate that measurements of organophosphate metabolites in meconium have promise as biomarkers of prenatal exposure. Further research is needed to determine the time frame of exposure represented by pesticide levels in meconium and to evaluate the dose-response relationship.
    [Whyatt, RM and Barr, DB. 2001. Environ Health Perspect. 109(4): 417–420]
  • Potential exposure and health risks of infants following indoor residential pesticide applications.
    The current study was conducted in two apartments and examines the accumulation of the pesticide chlorpyrifos in childrens' toys after the time suggested for reentry after application. It has been established for the first time that a semivolatile pesticide will accumulate on and in toys and other sorbant surfaces in a home via a two-phase physical process that continues for at least 2 weeks postapplication. A summation of the above for a 3-6-year-old child yielded an estimated nondietary total dose of 208 microg/kg/day. Potential exposure from the inhalation pathway was negligible, while dermal and nondietary oral doses from playing with toys contributed to 39 and 61% of the total dose, respectively. If children with high frequency mouthing behavior are considered as candidates for acute exposure to chlorpyrifos residues, the estimated acute dose could be as high as 356 microg/kg/day. The above information should be used to determine if current procedures for postapplication reentry are sufficient and to evaluate the need for procedures to store frequently used household toys, pillows, and other sorbant objects during insecticidal application.
    [Gurunathan, S., M. Robson, N. Freeman, B. Buckley, A. et al.1998. Environ Health Perspec.t. 106(1): 9–16]
  • Biomonitoring for Pesticide Exposure
    The biological monitoring of pesticide residues and metabolites is becoming increasingly important in the surveillance of occupationally and environmentally exposed individuals. Detection of these compounds in the body indicates that an exposure has occurred; that the pesticide is bioavailable, having been absorbed; and that a dose to critical tissues may have been incurred. Biomarker methods such as for adducted proteins or nucleic acids are being investigated for some pesticides. However, the chemical analyses of readily sampled matrices, such as urine and blood, for parent compound and/or metabolite(s) remain the standard tools of the trade. Methods are becoming more sensitive as advances are made in analytical instrumentation systems. Immunochemical methods are being developed and emphasized for screening purposes, as well as for an enhanced sensitivity and the potential to detect parent compound and multiple metabolites through selective cross-reactivity. When initiating the biomonitoring component of an exposure assessment for pesticides an array of decisions must be made, primarily based on what is known about the metabolism of the pesticide of interest. Detectability of pesticide exposure depends upon selecting the most appropriate biological matrix, the dominant analyte(s) in that matrix, and the timing of sample collection relative to exposure. Useful analytical results are dependent on proper handling and storage of biological samples, as well as the availability of sensitive analytical methods. These factors, currently known biomonitoring approaches, and the results of selected recent biomonitoring studies are presented.
    [Nauman, C.H. et al. 1993. Biomarkers of Human Exposure to Pesticides Chapter 1, pp 1–19 ACS Symposium Series, Vol. 542]
  • Pesticides in the Diets of Infants and Children
    Groundbreaking report presents the findings on a committee charged with responsibility for examining scientific and policy issues faced by government agencies, particularly EPA, in regulating pesticide residues in foods consumed by infants and children. Specifically, the committee was asked to examine the adequacy of current risk assessment policies and methods; to assess information on the dietary intakes of infants and children; to evaluate data on pesticide residues in the food supply; to identify toxicological issues of greatest concern; and to develop relevant research priorities. The committee considered the development of children from the beginning of the last trimester of pregnancy (26 weeks) through 18 years of age, the point when all biological systems have essentially matured.The committee found both quantitative and occasionally qualitative differences in toxicity of pesticides between children and adults; that quantitative differences in toxicity between children and adults are usually less than a factor of approximately 10-fold; and that infants and children differ both qualitatively and quantitatively from adults in their exposure to pesticide residues in foods.
    [National Research Council. 1993. NATIONAL ACADEMY PRESS. Washington, D.C.]
  • Potential exposure and health risks of infants following indoor residential pesticide applications.
    Air and surface chlorpyrifos residues were measured for 24 hours following a 0.5 percent Dursban broadcast application for fleas inside a residence. Two of the three treated rooms were ventilated following application. Maximum air concentrations were measured 3-7 hours post-application. Peak concentrations in the infant breathing zone were 94 micrograms/m3 in the nonventilated room and 61 micrograms/m3 in the ventilated room, and were substantially higher than concentrations in the sitting adult breathing zone. Concentrations of approximately 30 micrograms/m3 were detected in the infant breathing zone 24 hours post-application. Surface residues available through wipe sampling were 0.7-1.6 micrograms/cm2 of carpet on the day of application and 0.3-0.5 micrograms/cm2 24 hours post-application. Estimated total absorbed doses for infants were 0.08-0.16 mg/kg on the day of application and 0.04-0.06 mg/kg the day following application, with dermal absorption representing approximately 68 percent of the totals. These doses are 1.2-5.2 times the human No Observable Effect Level (NOEL). Exposures to cholinesterase inhibiting compounds following properly conducted broadcast applications could result in doses at or above the threshold of toxicological response in infants, and should be minimized through appropriate regulatory policy and public education.
    [Fenske R.A., K. Black, K. Elkner, L. Chorng-Li, M.M. Methner and R. Soto. 1990. Am J Pub Health. 80(6): 689-93.]

Wildlife

  • Birds feeding on tebuconazole treated seeds have reduced breeding output
    Drilled seeds are an important food resource for many farmland birds but may pose a serious risk when treated with pesticides. Most compounds currently used as seed treatment in the EU have low acute toxicity but may still affect birds in a sub-chronic or chronic way, especially considering that the sowing season lasts several weeks or months, resulting in a long exposure period for birds. Tebuconazole is a triazole fungicide widely used in agriculture but its toxicity to birds remains largely unknown. Our aim was to test if a realistic scenario of exposure to tebuconazole treated seeds affected the survival and subsequent reproduction of the red-legged partridge (Alectoris rufa). We fed captive partridges with wheat seeds treated with 0%, 20% or 100% of tebuconazole application rate during 25 days in late winter (i.e. tebuconazole dietary doses were approximately 0.2 and 1.1 mg/kg bw/day). We studied treatment effects on the physiology (i.e. body weight, biochemistry, immunology, oxidative stress, coloration) and reproduction of partridges. Exposed birds did not reduce food consumption but presented reduced plasmatic concentrations of lipids (triglycerides at both exposure doses, cholesterol at high dose) and proteins (high dose). The coloration of the eye ring was also reduced in the low dose group. Exposure ended 60 days before the first egg was laid, but still affected reproductive output: hatching rate was reduced by 23% and brood size was 1.5 times smaller in the high dose group compared with controls. No significant reproductive effects were found in the low dose group. Our results point to the need to study the potential endocrine disruption mechanism of this fungicide with lagged effects on reproduction. Risk assessments for tebuconazole use as seed treatment should be revised in light of these reported effects on bird reproduction.
    [Lopez-Antia, A., Ortiz-Santaliestra, M.E., Mougeot, F., Camarero, P.R. and Mateo, R., 2021. Environmental Pollution, 271, p.116292.]
  • Widespread Occurrence of Pesticides in Organically Managed Agricultural Soils-the Ghost of a Conventional Agricultural Past?
    Pesticides are applied in large quantities to agroecosystems worldwide. To date, few studies assessed the occurrence of pesticides in organically managed agricultural soils, and it is unresolved whether these pesticide residues affect soil life. We screened 100 fields under organic and conventional management with an analytical method containing 46 pesticides (16 herbicides, 8 herbicide transformation products, 17 fungicides, seven insecticides). Pesticides were found in all sites, including 40 organic fields. The number of pesticide residues was two times and the concentration nine times higher in conventional compared to organic fields. Pesticide number and concentrations significantly decreased with the duration of organic management. Even after 20 years of organic agriculture, up to 16 different pesticide residues were present. Microbial biomass and specifically the abundance of arbuscular mycorrhizal fungi, a widespread group of beneficial plant symbionts, were significantly negatively linked to the amount of pesticide residues in soil. This indicates that pesticide residues, in addition to abiotic factors such as pH, are a key factor determining microbial soil life in agroecosystems. This comprehensive study demonstrates that pesticides are a hidden reality in agricultural soils, and our results suggest that they have harmful effects on beneficial soil life.
    [Riedo, J., Wettstein, F.E., Rösch, A., Herzog, C., Banerjee, S., Büchi, L., Charles, R., Wächter, D., Martin-Laurent, F., Bucheli, T.D. and Walder, F., 2021. Environmental Science & Technology.]
  • Anthropogenic Contaminants and Histopathological Findings in Stranded Cetaceans in the Southeastern United States, 2012–2018
    Anthropogenic contaminants in the marine environment often biodegrade slowly, bioaccumulate in organisms, and can have deleterious effects on wildlife immunity, health, reproduction, and development. In this study, we evaluated tissue toxicant concentrations and pathology data from 83 odontocetes that stranded in the southeastern United States during 2012–2018. Mass spectrometry was used to analyze blubber samples for five organic toxicants (atrazine, bisphenol-A, diethyl phthalates, nonylphenol monoethoxylate [NPE], triclosan), and liver samples were analyzed for five non-essential elements (arsenic, cadmium, lead, mercury, thallium), six essential elements (cobalt, copper, manganese, iron, selenium, zinc) and one toxicant mixture class (Aroclor1268). Resultant data considerably improve upon the existing knowledge base regarding toxicant concentrations in stranded odontocetes. Toxicant and element concentrations varied based on animal demographic factors including species, sex, age, and location. Samples from bottlenose dolphins had significantly higher average concentrations of lead, manganese, mercury, selenium, thallium, and zinc, and lower average concentrations of NPE, arsenic, cadmium, cobalt, and iron than samples from pygmy sperm whales. In adult female bottlenose dolphins, average arsenic concentrations were significantly higher and iron concentrations were significantly lower than in adult males. Adult bottlenose dolphins had significantly higher average concentrations of lead, mercury, and selenium, and significantly lower average manganese concentrations compared to juveniles. Dolphins that stranded in Florida had significantly higher average concentrations of lead, mercury, and selenium, and lower concentrations of iron than dolphins that stranded in North Carolina. Histopathological data are presented for 72 animals, including microscopic evidence of Campula spp. and Sarcocystis spp. infections, and results of Morbillivirus and Brucella spp. molecular diagnostic testing. Sublethal cellular changes related to toxicant exposure in free-ranging odontocetes may lead to health declines and, in combination with other factors, may contribute to stranding.
    [Page-Karjian, A., Lo, C.F., Ritchie, B., Harms, C.A., Rotstein, D.S., Han, S., Hassan, S.M., Lehner, A.F., Buchweitz, J.P., Thayer, V.G. and Sullivan, J.M., 2020. Frontiers in Marine Science, 7, p.630.]
  • Anthropogenic stressors impact fish sensory development and survival via thyroid disruption
    Larval metamorphosis and recruitment represent critical life-history transitions for most teleost fishes. While the detrimental effects of anthropogenic stressors on the behavior and survival of recruiting fishes are well-documented, the physiological mechanisms that underpin these patterns remain unclear. Here, we use pharmacological treatments to highlight the role that thyroid hormones (TH) play in sensory development and determining anti-predator responses in metamorphosing convict surgeonfish, Acanthurus triostegus. We then show that high doses of a physical stressor (increased temperature of +3 °C) and a chemical stressor (the pesticide chlorpyrifos at 30 µg L−1) induced similar defects by decreasing fish TH levels and affecting their sensory development. Stressor-exposed fish experienced higher predation; however, their ability to avoid predation improved when they received supplemental TH. Our results highlight that two different anthropogenic stressors can affect critical developmental and ecological transitions via the same physiological pathway. This finding provides a unifying mechanism to explain past results and underlines the profound threat anthropogenic stressors pose to fish communities.
    [Besson, M., Feeney, W.E., Moniz, I., François, L., Brooker, R.M., Holzer, G., Metian, M., Roux, N., Laudet, V. and Lecchini, D., 2020. Nature communications, 11(1), pp.1-10.]
  • Assessing Field‐Scale Risks of Foliar Insecticide Applications to Monarch Butterfly (Danaus plexippus) Larvae
    Establishment and maintenance of milkweed plants (Asclepias spp.) in agricultural landscapes of the north central United States are needed to reverse the decline of North America's eastern monarch butterfly (Danaus plexippus) population. Because of a lack of toxicity data, it is unclear how insecticide use may reduce monarch productivity when milkweed habitat is placed near maize and soybean fields. To assess the potential effects of foliar insecticides, acute cuticular and dietary toxicity of 5 representative active ingredients were determined: beta‐cyfluthrin (pyrethroid), chlorantraniliprole (anthranilic diamide), chlorpyrifos (organophosphate), and imidacloprid and thiamethoxam (neonicotinoids). Cuticular median lethal dose values for first instars ranged from 9.2 × 10–3 to 79 μg/g larvae for beta‐cyfluthrin and chlorpyrifos, respectively. Dietary median lethal concentration values for second instars ranged from 8.3 × 10–3 to 8.4 μg/g milkweed leaf for chlorantraniliprole and chlorpyrifos, respectively. To estimate larval mortality rates downwind from treated fields, modeled insecticide exposures to larvae and milkweed leaves were compared to dose–response curves obtained from bioassays with first‐, second‐, third‐, and fifth‐instar larvae. For aerial applications to manage soybean aphids, mortality rates at 60 m downwind were highest for beta‐cyfluthrin and chlorantraniliprole following cuticular and dietary exposure, respectively, and lowest for thiamethoxam. To estimate landscape‐scale risks, field‐scale mortality rates must be considered in the context of spatial and temporal patterns of insecticide use.
    [Krishnan, N., Zhang, Y., Bidne, K.G., Hellmich, R.L., Coats, J.R. and Bradbury, S.P., 2020. Environmental Toxicology and Chemistry, 39(4), pp.923-941.]
  • Cascading effects of insecticides and road salt on wetland communities
    Novel stressors introduced by human activities increasingly threaten freshwater ecosystems. The annual application of more than 2.3 billion kg of pesticide active ingredient and 22 billion kg of road salt has led to the contamination of temperate waterways. While pesticides and road salt are known to cause direct and indirect effects in aquatic communities, their possible interactive effects remain widely unknown. Using outdoor mesocosms, we created wetland communities consisting of zooplankton, phytoplankton, periphyton, and leopard frog (Rana pipiens) tadpoles. We evaluated the toxic effects of six broad-spectrum insecticides from three families (neonicotinoids: thiamethoxam, imidacloprid; organophosphates: chlorpyrifos, malathion; pyrethroids: cypermethrin, permethrin), as well as the potentially interactive effects of four of these insecticides with three concentrations of road salt (NaCl; 44, 160, 1600 Cl- mg/L). Organophosphate exposure decreased zooplankton abundance, elevated phytoplankton biomass, and reduced tadpole mass whereas exposure to neonicotinoids and pyrethroids decreased zooplankton abundance but had no significant effect on phytoplankton abundance or tadpole mass. While organophosphates decreased zooplankton abundance at all salt concentrations, effects on phytoplankton abundance and tadpole mass were dependent upon salt concentration. In contrast, while pyrethroids had no effects in the absence of salt, they decreased zooplankton and phytoplankton density under increased salt concentrations. Our results highlight the importance of multiple-stressor research under natural conditions. As human activities continue to imperil freshwater systems, it is vital to move beyond single-stressor experiments that exclude potentially interactive effects of chemical contaminants.
    [Lewis, J.L., Agostini, G., Jones, D.K. and Relyea, R.A., 2020. Environmental Pollution, p.116006.]
  • Early Life Exposure to Environmentally Relevant Levels of Endocrine Disruptors Drive Multigenerational and Transgenerational Epigenetic Changes in a Fish Model
    The inland silverside, Menidia beryllina, is a euryhaline fish and a model organism in ecotoxicology. We previously showed that exposure to picomolar (ng/L) levels of endocrine disrupting chemicals (EDCs) can cause a variety of effects in M. beryllina, from changes in gene expression to phenotypic alterations. Here we explore the potential for early life exposure to EDCs to modify the epigenome in silversides, with a focus on multi- and transgenerational effects. EDCs included contaminants of emerging concern (the pyrethroid insecticide bifenthrin and the synthetic progestin levonorgestrel), as well as a commonly detected synthetic estrogen (ethinylestradiol), and a synthetic androgen (trenbolone) at exposure levels ranging from 3 to 10 ng/L. In a multigenerational experiment, we exposed parental silversides to EDCs from fertilization until 21 days post hatch (dph). Then we assessed DNA methylation patterns for three generations (F0, F1, and F2) in whole body larval fish using reduced representation bisulfite sequencing (RRBS). We found significant (α = 0.05) differences in promoter and/or gene body methylation in treatment fish relative to controls for all EDCs and all generations indicating that both multigenerational (F1) and transgenerational (F2) effects that were caused by strict inheritance of DNA methylation alterations and the dysregulation of epigenetic control mechanisms. Using gene ontology and pathway analyses, we found enrichment in biological processes and pathways representative of growth and development, immune function, reproduction, pigmentation, epigenetic regulation, stress response and repair (including pathways important in carcinogenesis). Further, we found that a subset of potentially EDC responsive genes (EDCRGs) were differentially methylated across all treatments and generations and included hormone receptors, genes involved in steroidogenesis, prostaglandin synthesis, sexual development, DNA methylation, protein metabolism and synthesis, cell signaling, and neurodevelopment. The analysis of EDCRGs provided additional evidence that differential methylation is inherited by the offspring of EDC-treated animals, sometimes in the F2 generation that was never exposed. These findings show that low, environmentally relevant levels of EDCs can cause altered methylation in genes that are functionally relevant to impaired phenotypes documented in EDC-exposed animals and that EDC exposure has the potential to affect epigenetic regulation in future generations of fish that have never been exposed.
    [Major, K.M., DeCourten, B.M., Li, J., Britton, M., Settles, M.L., Mehinto, A.C., Connon, R.E. and Brander, S.M., 2020. Frontiers in Marine Science, 7, p.471.]
  • Human practices promote presence and abundance of disease-transmitting mosquito species
    Humans alter the environment at unprecedented rates through habitat destruction, nutrient pollution and the application of agrochemicals. This has recently been proposed to act as a potentially significant driver of pathogen-carrying mosquito species (disease vectors) that pose a health risk to humans and livestock. Here, we use a unique set of locations along a large geographical gradient to show that landscapes disturbed by a variety of anthropogenic stressors are consistently associated with vector-dominated mosquito communities for a wide range of human and livestock infections. This strongly suggests that human alterations to the environment promote the presence and abundance of disease vectors across large spatial extents. As such, it warrants further studies aimed at unravelling mechanisms underlying vector prevalence in mosquito communities, and opens up new opportunities for preventative action and predictive modelling of vector borne disease risks in relation to degradation of natural ecosystems.
    [Schrama, M., Hunting, E.R., Beechler, B.R., Guarido, M.M., Govender, D., Nijland, W., van‘t Zelfde, M., Venter, M., van Bodegom, P.M. and Gorsich, E.E., 2020. Scientific reports, 10(1), pp.1-6.]
  • Long-term effects of neonicotinoid insecticides on ants
    The widespread prophylactic usage of neonicotinoid insecticides has a clear impact on non-target organisms. However, the possible effects of long-term exposure on soil-dwelling organisms are still poorly understood especially for social insects with long-living queens. Here, we show that effects of chronic exposure to the neonicotinoid thiamethoxam on black garden ant colonies, Lasius niger, become visible before the second overwintering. Queens and workers differed in the residue-ratio of thiamethoxam to its metabolite clothianidin, suggesting that queens may have a superior detoxification system. Even though thiamethoxam did not affect queen mortality, neonicotinoid-exposed colonies showed a reduced number of workers and larvae indicating a trade-off between detoxification and fertility. Since colony size is a key for fitness, our data suggest long-term impacts of neonicotinoids on these organisms. This should be accounted for in future environmental and ecological risk assessments of neonicotinoid applications to prevent irreparable damages to ecosystems.
    [Schläppi, D., Kettler, N., Straub, L., Glauser, G. and Neumann, P., 2020. Communications biology, 3(1), pp.1-9.]
  • Long-term maternal exposure to atrazine in the drinking water reduces penis length in the tammar wallaby Macropus eugenii
    Marsupials are experiencing devastating population declines across Australia. Exposure to environmental endocrine disruptors, through ingestion of contaminated resources in the environment, could be contributing to this decline. Atrazine (ATZ), a widely used herbicide in Australia, is an endocrine disruptor with the ability to cause reproductive abnormalities in a diverse range of vertebrates. We exposed adult female wallabies (Macropus eugenii) to drinking water containing ATZ (450 p.p.m) throughout pregnancy, parturition and lactation. We assessed the outcome of this exposure to the reproductive development of their young by assessing gonad and phallus development. Both these organs are especially sensitive to perturbations in the hormonal environment during development. Although no gross abnormalities were seen in gonad structure, exposure to ATZ did alter the expression of genes required for normal testis function. Furthermore, long-term exposure to ATZ resulted in a significant reduction in penis length. These results demonstrate that ATZ exposure during gestation and lactation can significantly affect the development of male young by affecting virilisation. Given the known vulnerability of macropodid marsupials to endocrine disruption, as well as their overlapping distribution with agricultural areas, these data raise major concerns for the use of pesticides in areas with fragile marsupial populations.
    [Cook, L.E., Chen, Y., Renfree, M.B. and Pask, A.J., 2020. Reproduction, Fertility and Development, 32(13), pp.1168-1168.]
  • Low doses of the neonicotinoid insecticide imidacloprid induce ROS triggering neurological and metabolic impairments in Drosophila
    Declining insect population sizes are provoking grave concern around the world as insects play essential roles in food production and ecosystems. Environmental contamination by intense insecticide usage is consistently proposed as a significant contributor, among other threats. Many studies have demonstrated impacts of low doses of insecticides on insect behavior, but have not elucidated links to insecticidal activity at the molecular and cellular levels. Here, the histological, physiological, and behavioral impacts of imidacloprid are investigated in Drosophila melanogaster, an experimental organism exposed to insecticides in the field. We show that oxidative stress is a key factor in the mode of action of this insecticide at low doses. Imidacloprid produces an enduring flux of Ca2+ into neurons and a rapid increase in levels of reactive oxygen species (ROS) in the larval brain. It affects mitochondrial function, energy levels, the lipid environment, and transcriptomic profiles. Use of RNAi to induce ROS production in the brain recapitulates insecticide-induced phenotypes in the metabolic tissues, indicating that a signal from neurons is responsible. Chronic low level exposures in adults lead to mitochondrial dysfunction, severe damage to glial cells, and impaired vision. The potent antioxidant, N-acetylcysteine amide (NACA), reduces the severity of a number of the imidacloprid-induced phenotypes, indicating a causal role for oxidative stress. Given that other insecticides are known to generate oxidative stress, this research has wider implications. The systemic impairment of several key biological functions, including vision, reported here would reduce the resilience of insects facing other environmental challenges.
    [Martelli, F., Zhongyuan, Z., Wang, J., Wong, C.O., Karagas, N.E., Roessner, U., Rupasinghe, T., Venkatachalam, K., Perry, T., Bellen, H.J. and Batterham, P., 2020. Proceedings of the National Academy of Sciences, 117(41), pp.25840-25850.]
  • Massive use of disinfectants against COVID-19 poses potential risks to urban wildlife

    Globally, massive disinfectants are used to contain the rapid spread of COVID-19. Applying massive disinfectants pose a significant threat to urban environment and wildlife. Policies are required to minimize the adverse effects on wildlife due to overuse of disinfectants.
    [Nabi, G., Wang, Y., Hao, Y., Khan, S., Wu, Y. and Li, D., 2020. Environmental Research, 188, p.109916.]

  • Micronucleus Test Reveals Genotoxic Effects in Bats Associated with Agricultural Activity
    Bats play a vital role in our ecosystems and economies as natural pest‐control agents, seed dispersers, and pollinators. Agricultural intensification, however, can impact bats foraging near crops, affecting the ecosystem services they provide. Exposure to pesticides, for example, may induce chromosome breakage or missegregation that can result in micronucleus formation. Detection of micronuclei is a simple, inexpensive, and relatively minimally invasive technique commonly used to evaluate chemical genotoxicity but rarely applied to assess wildlife genotoxic effects. We evaluated the suitability of the micronucleus test as a biomarker of genotoxicity for biomonitoring field studies in bats. We collected blood samples from insectivorous bats roosting in caves surrounded by different levels of disturbance (agriculture, human settlements) in Colima and Jalisco, west central Mexico. Then, we examined the frequency of micronucleus inclusions in erythrocytes using differentially stained blood smears. Bats from caves surrounded by proportionately more (53%) land used for agriculture and irrigated year‐round had higher micronucleus frequency than bats from a less disturbed site (15% agriculture). We conclude that the micronucleus test is a sensitive method to evaluate genotoxic effects in free‐ranging bats and could provide a useful biomarker for evaluating risk of exposure in wild populations. Environ Toxicol Chem 2021;40:202–207.
    [Sandoval‐Herrera, N., Castillo, J.P., Montalvo, L.G.H. and Welch, K.C., 2020. Environmental Toxicology and Chemistry.]
  • Roundup causes embryonic development failure and alters metabolic pathways and gut microbiota functionality in non-target species
    Research around the weedkiller Roundup is among the most contentious of the twenty-first century. Scientists have provided inconclusive evidence that the weedkiller causes cancer and other life-threatening diseases, while industry-paid research reports that the weedkiller has no adverse effect on humans or animals. Much of the controversial evidence on Roundup is rooted in the approach used to determine safe use of chemicals, defined by outdated toxicity tests. We apply a system biology approach to the biomedical and ecological model species Daphnia to quantify the impact of glyphosate and of its commercial formula, Roundup, on fitness, genome-wide transcription and gut microbiota, taking full advantage of clonal reproduction in Daphnia. We then apply machine learning-based statistical analysis to identify and prioritize correlations between genome-wide transcriptional and microbiota changes. We demonstrate that chronic exposure to ecologically relevant concentrations of glyphosate and Roundup at the approved regulatory threshold for drinking water in the US induce embryonic developmental failure, induce significant DNA damage (genotoxicity), and interfere with signaling. Furthermore, chronic exposure to the weedkiller alters the gut microbiota functionality and composition interfering with carbon and fat metabolism, as well as homeostasis. Using the “Reactome,” we identify conserved pathways across the Tree of Life, which are potential targets for Roundup in other species, including liver metabolism, inflammation pathways, and collagen degradation, responsible for the repair of wounds and tissue remodeling. Our results show that chronic exposure to concentrations of Roundup and glyphosate at the approved regulatory threshold for drinking water causes embryonic development failure and alteration of key metabolic functions via direct effect on the host molecular processes and indirect effect on the gut microbiota. The ecological model species Daphnia occupies a central position in the food web of aquatic ecosystems, being the preferred food of small vertebrates and invertebrates as well as a grazer of algae and bacteria. The impact of the weedkiller on this keystone species has cascading effects on aquatic food webs, affecting their ability to deliver critical ecosystem services.
    [Suppa, A., Kvist, J., Li, X., Dhandapani, V., Almulla, H., Tian, A.Y., Kissane, S., Zhou, J., Perotti, A., Mangelson, H. and Langford, K., 2020. Microbiome, 8(1), pp.1-15.]
  • The Combined Algae Test for the Evaluation of Mixture Toxicity in Environmental Samples
    The combined algae test is a 96-well plate-based algal toxicity assay with the green algae Raphidocelis subcapitata that combines inhibition of 24-h population growth rate with inhibition of photosynthesis detected after 2 and 24 h with pulse-amplitude modulated (PAM) fluorometry using a Maxi-Imaging PAM. The combined algae test has been in use for more than a decade but has had limitations due to incompatibilities of the measurements of the 2 biological endpoints on the same microtiter plates. These limitations could be overcome by increasing growth rates and doubling times on black, clear-bottom 96-well plates by application of dichromatic red/blue light-emitting diode illumination. Different robotic dosing approaches and additional data evaluation methods helped to further expand the applicability domain of the assay. The combined algae test differentiates between nonspecifically acting compounds and photosynthesis inhibitors, such as photosystem II (PSII) herbicides. The PSII herbicides acted immediately on photosynthesis and showed growth rate inhibition at higher concentrations. If growth was a similar or more sensitive endpoint than photosynthesis inhibition, this was an indication that the tested chemical acted nonspecifically or that a mixture or a water sample was dominated by chemicals other than PSII herbicides acting on algal growth. We fingerprinted the effects of 45 chemicals on photosynthesis inhibition and growth rate and related the effects of the single compounds to designed mixtures of these chemicals detected in water samples and to the effects directly measured in water samples. Most of the observed effects in the water samples could be explained by known photosystem II inhibitors such as triazines and phenylurea herbicides. The improved setup of the combined algae test gave results consistent with those of the previous method but has lower costs, higher throughput, and higher precision.
    [Glauch, L. and Escher, B.I., 2020. Environmental Toxicology and Chemistry, 39(12), pp.2496-2508.]
  • Dysbiosis and early mortality in zebrafish larvae exposed to subclinical concentrations of streptomycin.
    Exposure to low concentrations of antibiotics found in aquatic environments can increase susceptibility to infection in adult fish due to microbiome disruption. However, little is known regarding the effect of antibiotic pollution on fish larvae. Here, we show that exposure to streptomycin, a common antibiotic used in medicine and aquaculture, disrupts the normal composition of zebrafish larvae microbiomes, significantly reducing the microbial diversity found in the fish. Exposure to streptomycin also significantly increased early mortality among fish larvae, causing full mortality within a few days of exposure at 10 μg/mL. Finally, we found that subclinical concentrations of streptomycin also increased the abundance of class 1 integrons, an integrase-dependent genetic system associated to the horizontal transfer of antibiotic resistance genes, in the larvae microbiomes. These results suggest that even low concentrations of streptomycin associated with environmental pollution could impact fish populations and lead to the creation of antibiotic resistance reservoirs.
    [Pindling, S., Azulai, D., Zheng, B., Dahan, D. and Perron, G.G., 2018. FEMS microbiology letters, 365(18), p.fny188.]
  • Environmental concentrations of triclosan activate cellular defence mechanism and generate cytotoxicity on zebrafish (Danio rerio) embryos.
    Triclosan (TCS, 5‑chloro‑2‑(2,4‑dichlorophenoxy) phenol) is becoming a major surface waters pollutant worldwide at concentrations ranging from ng L−1 to μg L−1. Up to now, the adverse effects on aquatic organisms have been investigated at concentrations higher than the environmental ones, and the pathways underlying the observed toxicity are still not completely understood. Therefore, the aim of this study was to investigate the toxic effects of TCS at environmental concentrations on zebrafish embryos up to 120 hours post fertilization (hpf). The experimental design was planned considering both the quantity and the exposure time for the effects on the embryos, exposing them to two different concentrations (0.1 μg L−1, 1 μg L−1) of TCS, for 24 h (from 96 to 120 hpf) and for 120 h (from 0 to 120 hpf). A suite of biomarkers was applied to measure the induction of embryos defence system, the possible increase of oxidative stress and the DNA damage. We measured the activity of glutathione‑S‑transferase (GST), P‑glycoprotein efflux and ethoxyresorufin‑o‑deethylase (EROD), the level of ROS, the oxidative damage through the Protein Carbonyl Content (PCC) and the activity of antioxidant enzymes. The genetic damage was evaluated through DNA Diffusion Assay, Micronucleus test (MN test), and Comet test. The results showed a clear response of embryos defence mechanism, through the induction of P-gp efflux functionality and the activity of detoxifying/antioxidant enzymes, preventing the onset of oxidative damage. Moreover, the significant increase of cell necrosis highlighted a strong cytotoxic potential for TCS. The overall results obtained with environmental concentrations and both exposure time, underline the critical risk associated to the presence of TCS in the aquatic environment.
    [Parenti, CC et al. 2018. Science of the Total Environment 650 (2019): 1752-1758.]
  • Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines.
    It has been reported that oxidative stress may be induced by pesticides and it could be the cause of health alteration mediated by pollutants exposure. The present investigation was designed to identify the pathway involved in chlorpyrifos (CPF)-inhibited cell proliferation in MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, authors determined if CPF-induced oxidative stress is related to alterations in antioxidant defense system. The molecular mechanisms underlying in the cell proliferation inhibition produced by the pesticide were also looked at. Study demonstrates that CPF (50 μM) induces redox imbalance altering the antioxidant defense system in breast cancer cells. The main mechanism involved in the inhibition of cell proliferation induced by CPF is an increment of p-ERK1/2 levels mediated by H2O2 in breast cancer cells. Study concluded that ERK1/2 phosphorylation is subsequent to ROS production induced by CPF but not the inverse.
    [Ventura C, Venturino A, Miret N, et al. 2015. Chemosphere. 120:343-50.]
  • Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines.
    It has been reported that oxidative stress may be induced by pesticides and it could be the cause of health alteration mediated by pollutants exposure. The present investigation was designed to identify the pathway involved in chlorpyrifos (CPF)-inhibited cell proliferation in MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, authors determined if CPF-induced oxidative stress is related to alterations in antioxidant defense system. The molecular mechanisms underlying in the cell proliferation inhibition produced by the pesticide were also looked at. Study demonstrates that CPF (50 μM) induces redox imbalance altering the antioxidant defense system in breast cancer cells. The main mechanism involved in the inhibition of cell proliferation induced by CPF is an increment of p-ERK1/2 levels mediated by H2O2 in breast cancer cells. Study concluded that ERK1/2 phosphorylation is subsequent to ROS production induced by CPF but not the inverse.
    [Ventura C, Venturino A, Miret N, et al. 2015. Chemosphere. 120:343-50.]
  • Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines.
    It has been reported that oxidative stress may be induced by pesticides and it could be the cause of health alteration mediated by pollutants exposure. The present investigation was designed to identify the pathway involved in chlorpyrifos (CPF)-inhibited cell proliferation in MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, authors determined if CPF-induced oxidative stress is related to alterations in antioxidant defense system. The molecular mechanisms underlying in the cell proliferation inhibition produced by the pesticide were also looked at. Study demonstrates that CPF (50 μM) induces redox imbalance altering the antioxidant defense system in breast cancer cells. The main mechanism involved in the inhibition of cell proliferation induced by CPF is an increment of p-ERK1/2 levels mediated by H2O2 in breast cancer cells. Study concluded that ERK1/2 phosphorylation is subsequent to ROS production induced by CPF but not the inverse.
    [Ventura C, Venturino A, Miret N, et al. 2015. Chemosphere. 120:343-50.]
  • Diamondback terrapins as indicator species of persistent organic pollutants: Using Barnegat Bay, New Jersey as a case study
    The diamondback terrapin's (Malaclemys terrapin) wide geographic distribution, long life span, occurrence in a variety of habitats within the saltmarsh ecosystem, predatory foraging behavior, and high site fidelity make it a useful indicator species for contaminant monitoring in estuarine ecosystems. In this study fat biopsies and plasma samples were collected from males and females from two sites within Barnegat Bay, New Jersey, as well as tissues from a gravid female and blue mussels (Mytilus edulis), which are terrapin prey. Samples were analyzed for persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), chlorinated pesticides, and methyl-triclosan. Terrapins from the northern site, Spizzle Creek, closest to influences from industrial areas, had higher POP concentrations for both tissues than terrapins from the less impacted Forsythe National Wildlife Refuge. Sex differences were observed with males having higher contaminant concentrations in fat and females in plasma. PCB patterns in terrapin fat and plasma were comparable to other wildlife. Plasma contaminant concentrations significantly and positively correlated with those in fat. This study addresses several aspects of using the terrapin as an indicator species for POP monitoring: site and sex differences, tissue sampling choices, maternal transfer, and biomagnification.
    [Basile ER, Avery HW, Bien WF, Keller JM. 2011. Chemosphere. 82(1):137-44]
  • Incidence of organochlorine pesticides and the health condition of nestling ospreys (Pandion haliaetus) at Laguna San Ignacio, a pristine area of Baja California Sur, Mexico.
    Researchers identified and quantified organochlorine (OC) pesticide residues in the plasma of 28 osprey (Pandion haliaetus) nestlings from a dense population in Laguna San Ignacio, a pristine area of Baja California Sur, Mexico, during the 2001 breeding season. Sixteen OC pesticides were identified and quantified. a-, ß-, d- and ?-hexachlorocyclohexane, heptaclor, heptachlor epoxide, endosulfan I and II, endosulfan-sulfate, p,p'-DDE, p,p'-DDD, aldrin, dieldrin, endrin, endrin aldehyde, and endrin ketone were the OCs found in the plasma of nestlings, ranging from 0.002 to 6.856 pg/µl (parts per billion). No differences were found in the concentration of pesticides between genders (P > 0.05). In this work, the concentrations detected in the plasma were lower than those reported to be a threat for the species and that affect the survival and reproduction of birds. The presence of OC pesticides in the remote Laguna San Ignacio osprey population is an indication of the ubiquitous nature of these contaminants. OCs are apparently able to travel long distances from their source to the study area. A significant relationship between hemoglobin and mean corpuscular hemoglobin concentrations and OC concentrations were found suggesting that a potential effect on the health of chicks may exist in this osprey population caused by the OC, e.g. anemia. The total proteins were positively correlated with a-BHC, endosulfan I, and p,p'-DDD. It has been suggested that OC also affects competitive interactions and population status over the long term in vertebrate species, and these results could be used as reference information for comparison with other more exposed osprey populations.
    [Rivera-Rodríguez LB, Rodríguez-Estrella R. 2011. Ecotoxicology.;20(1):29-38]
  • Flame retardants and organochlorine pollutants in bald eagle plasma from the Great Lakes region
    Study reports measurements of polybrominated diphenyl ethers and of emerging flame retardants in the plasma of nestling bald eagles sampled from early May to late June of 2005. Concentrations of total PBDEs ranged from 0.35 ng g(-1) ww to 29.3 ng g(-1) ww. Several emerging flame retardants, such as pentabromoethylbenzene (PBEB), hexabromocyclododecanes (HBCDs), and Dechlorane Plus (DP), were detected in these samples. Polychlorinated biphenyls (PCBs) and organochlorine pesticides were also detected at levels close to those previously published. A statistically significant relationship was found between total PBDE concentrations and total PCB and p,p'-DDE concentrations, suggesting that these compounds share a common source, which is most likely the eagle's food.
    [Venier M. et al. 2010. Chemosphere.80(10):1234-40]
  • Partitioning of persistent organic pollutants between blubber and blood of wild bottlenose dolphins: implications for biomonitoring and health
    Biomonitoring surveys of wild cetaceans commonly utilize blubber as a means to assess exposure to persistent organic pollutants (POPs), but the relationship between concentrations in blubber and those in blood, a better indicator of target organ exposure, is poorly understood. To define this relationship, matched blubber and plasma samples (n = 56) were collected from free-ranging bottlenose dolphins (Tursiops truncatus) and analyzed for 61 polychlorinated biphenyl (PCB) congeners, 5 polybrominated diphenyl ether (PBDE) congeners, and 13 organochlorine pesticides (OCPs). With the exception of PCB 209, lipid-normalized concentrations of the major POPs in blubber and plasma were positively and significantly correlated (R(2) = 0.828 to 0.976). Plasma concentrations, however, significantly increased with declining blubber lipid content, suggesting that as lipid is utilized, POPs are mobilized into blood. Compound- and homologue- specific blubber/blood partition coefficients also differed according to lipid content, suggesting POPs are selectively mobilized from blubber. Overall, these results suggest that with the regression parameters derived here, blubber may be used to estimate blood concentrations and vice versa. Additionally, the mobilization of lipid from blubber and concomitant increase in contaminants in blood suggests cetaceans with reduced blubber lipid may be at greater risk for contaminant-associated health effects.
    [Yordy JE, Wells RS, Balmer BC, Schwacke LH, Rowles TK, Kucklick JR. 2010. Environ Sci Technol. 15;44(12):4789-95]
  • Concentrations in bird feathers reflect regional contamination with organic pollutants
    Feathers have recently been shown to be potentially useful non-destructive biomonitoring tools for organic pollutants. However, the suitability of feathers to monitor regional variations in contamination has not been investigated until now. Here concentrations of organic pollutants were compared in feathers of common magpies (Pica pica) between urban and rural areas in Flanders, Belgium. The results showed that concentrations of p,p'-dichlorodiphenyldichloroethylene (DDE) were significantly higher in the rural areas, while polychlorinated biphenyls (PCBs) were significantly more available in an urban environment. This pattern agrees with previous studies using other tissues than feathers as a biomonitoring tool. In addition, differences in PCBs and PBDEs profiles were found with lower halogenated congeners being more prominent in the urban areas in comparison to the rural areas. In summary, feathers seem to reflect regional variations in contamination, which strengthens their usefulness as a non-destructive biomonitor for organic pollutants.
    [Jaspers VL, Covaci A, Deleu P, Eens M. 2009. Sci Total Environ;407(4):1447-51]
  • Chiral organochlorine contaminants in blood and eggs of glaucous gulls (Larus hyperboreus) from the Norwegian Arctic.
    Glaucous gulls (Larus hyperboreus) and their eggs from Svalbard (Norwegian Arctic) have been used as biomonitors of contaminants in the marine environment. In this study, the enantiomer fractions (EFs) of chiral chlordanes and atropisomeric polychlorinated biphenyl (PCB) congeners were determined in the blood plasma of adult male and female glaucous gulls from three breeding colonies in Svalbard. Plasma EFs were similar in magnitude and direction to EFs previously reported in glaucous gulls from other arctic food webs, suggesting overall similarities in the biochemical processes influencing the EFs of bioaccumulated organochlorine (OC) contaminants within the food webs at those locations. Additionally, EFs in yolk of eggs collected concurrently from within the same nesting colonies varied with location, laying date, and OC concentrations, and may be influenced by changes in the local feeding ecology between those colonies. The use of eggs as a valuable and noninvasive means of OC biomonitoring may also extend to enantiomer compositions in glaucous gulls, and perhaps also in other seabird species from arctic regions.
    [Ross MS, Verreault J, Letcher RJ, Gabrielsen GW, Wong CS. 2008. Environ Sci Technol.;42(19):7181-6]
  • Can predatory bird feathers be used as a non-destructive biomonitoring tool of organic pollutants?
    The monitoring of different types of pollutants that are released into the environment, and that present risks for both humans and wildlife have become increasingly important. In this study, authors examined whether feathers of predatory birds can be used as a non-destructive biomonitor of organic pollutants. Study demonstrates that polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and polybrominated diphenyl ethers (PBDEs) are measurable in one single tail feather of common buzzards (Buteo buteo) and that levels in this feather and internal tissues are significantly related to each other. Findings provide the first indication that feathers of predatory birds could be useful in non-destructive biomonitoring of organic pollutants, although further validation may be necessary.
    [Jaspers, V,L. et al. 2006. Biol. Lett. 2, 283-285]
  • Organochlorine chemical residues in fish from the Mississippi River basin, 1995.
    Fish were collected in late 1995 from 34 National Contaminant Biomonitoring Program (NCBP) stations and 13 National Water Quality Assessment Program (NAWQA) stations in the Mississippi River basin (MRB) and in late 1996 from a reference site in West Virginia. Four composite samples, each comprising (nominally) 10 adult common carp (Cyprinus carpio) or black bass (Micropterus spp.) of the same sex, were collected from each site and analyzed for organochlorine chemical residues. At the NCBP stations, which are located on relatively large rivers, concentrations of organochlorine chemical residues were generally lower than when last sampled in the mid-1980s. Residues derived from DDT (primarily p,p'-DDE) were detected at all sites (including the reference site); however, only traces of the parent insecticide (p,p'-DDT) were present, which indicates continued weathering of residual DDT from past use. Nevertheless, concentrations of DDT (as p,p'-DDE) in fish from the cotton-farming regions of the lower MRB were great enough to constitute a hazard to fish-eating wildlife and were especially high at the NAWQA sites on the lower-order rivers and streams of the Mississippi embayment. Mirex was detected at only two sites, both in Louisiana, and toxaphene was found exclusively in the lower MRB. Most cyclodiene pesticides (dieldrin, chlordane, and heptachlor epoxide) were more widespread in their distributions, but concentrations were lower than in the 1980s except at a site on the Mississippi River near Memphis, TN. Concentrations were also somewhat elevated at sites in the Corn Belt. Endrin was detected exclusively at the Memphis site. PCB concentrations generally declined, and residues were detected at only 35% of the stations, mostly in the more industrialized parts of the MRB.
    [Schmitt CJ. 2002. Arch Environ Contam Toxicol.;43(1):81-97]