[X] CLOSEMAIN MENU

[X] CLOSEIN THIS SECTION

photo

Pesticide-Induced Diseases: Asthma / Respiratory Effects

Asthma  Respiratory Disease Lung Cancer

In the U.S., over 25 million people live with asthma, over 14 million individuals live with COPD, and millions of individuals live with lung cancer. The increasing rate of respiratory pathology, since the 1980s, demonstrates a need for better environmental policies and protocols surrounding contaminants like pesticides. Exposure to pesticides increases incidents of respiratory pathologies (i.e., asthma, lung cancer, and chronic obstructive pulmonary disease [COPD]—or chronic bronchitis). The respiratory system is essential to human survival, regulating gas exchange (oxygen-carbon dioxide) in the body to balance acid and base tissue cells for normal function. However, damage to the respiratory system can cause a plethora of issues—from asthma and bronchitis to oxidative stress that triggers the development of extra-respiratory manifestations like rheumatoid arthritis and cardiovascular disease. Therefore, the rise in respiratory illnesses over the last three decades years is highly concerning, especially as research fails to identify an exact cause for the increase in respiratory disease cases.

Asthma 

Asthma is a serious chronic disorder, and in some cases life-threatening disease, of the lungs characterized by recurrent attacks of bronchial constriction, which cause breathlessness, wheezing, and coughing. Researchers have found that pesticide exposure can induce a poisoning effect linked to asthma. Low-income populations, people of color, and children living in inner cities experience disproportionately high morbidity and mortality due to asthma. According to the National Institutes of Health’s National Institute of Allergy and Infectious Disease, African Americans are four to six times more likely than whites to die from asthma. Therefore, any time our policies allow regulators to permit uses of pesticides with known asthma effects, which is done daily, a disproportionate impact is felt in the African-American community. Among other policies, this toxics policy contributes to a cycle of poverty, as asthma is the leading cause of school absenteeism due to chronic illness. Learn more about pesticides and asthma.

  • Influence of pesticides on respiratory pathology – a literature review
    Pesticides are widely employed in agriculture, and the food industry is forced to combat the pests and diseases they cause. Respiratory pathology is related to occupational exposure to pesticides. Impairment of pulmonary function was observed among people professionally exposed to pesticides. Because of the marked use of pesticides in agriculture during the last 20 years, there has been a significant increase in respiratory problems within the population, not only among people who come in direct contact with them, but even in the case of manipulators. The aim is a review of the literature of the past 10 years on the correlation between occupational exposure to pesticides and respiratory pathology. Electronic search in ‘Pub Med’ and ‘Web of Science’ was performed in September 2019 to find papers regarding the above-investigated aspects. Abstracts and full-text articles containing the targeted subject were included. Reviews and studies about the influence of pesticides on other pathologies than respiratory were excluded. After applying the inclusion and exclusion criteria, eligible full-text articles were identified. Exposure to pesticides is highly correlated with respiratory pathologies (asthma, COPD, lung cancer). Contact with these substances can occur at any time in the production, transport, preparation or application of the treatments. Numerous studies documented the association between exposure to pesticides, and therefore the increased incidence of respiratory, cardiovascular and renal diseases, as well as the aging phenomenon.
    [Tarmure, S., Alexescu, T.G., Orasan, O., Negrean, V., Sitar-Taut, A.V., Coste, S.C. and Todea, D.A., 2020. Annals of Agricultural and Environmental Medicine: AAEM, 27(2), pp.194-200.]
  • 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.]
  • "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.]
  • Asthma associated with pesticide exposure among women in rural Western Cape of South Africa.
    Few studies have investigated asthma and pesticides among women farm workers in developing countries.
    A cross-sectional study was conducted to investigate the association between pesticides and asthma among rural women (n = 211). Outcome measurements included respiratory symptoms (European Community Respiratory Health Survey questionnaire), immunological status (Phadiatop, serum IgE to mite allergens) and lower airway inflammation (fractional exhaled nitric oxide (FeNO) levels). Exposure variables included self-reported pesticide exposure and whole blood cholinesterase (ChE). The prevalence of ocular-nasal symptoms (ONS), doctor-diagnosed asthma and current asthma was 24%, 11%, and 6% respectively. ONS was positively associated with re-entering a sprayed field. Asthma symptom score was associated with low ChE. Participants with high FeNO (>50 ppb) also had an elevated odds of having low ChE. Pesticide exposure among women farm workers is associated with increased risk of ocular nasal symptoms and an elevated asthma symptom score.
    [Ndlovu V, Dalvie MA, Jeebhay MF. 2014. Am J Ind Med. 57(12):1331-43.]
  • Exacerbation of symptoms in agricultural pesticide applicators with asthma.
    Study investigated whether exacerbation of symptoms is associated with farming exposures among agricultural pesticide applicators with asthma.Participants were pesticide applicators with active asthma (wheezing and breathing problems in past 12 months) who completed enrollment questionnaires for the Agricultural Health Study (AHS). Exacerbation of asthma was defined as having visited a hospital emergency room or doctor for an episode of wheezing or whistling in the past 12 months. Exposures of interest were using 36 specific pesticides in the past 12 months and conducting various agricultural activities.The 926 AHS adult pesticide applicators with active asthma included 202 (22%) with exacerbation. Inverse associations with exacerbation were observed for two herbicides [glyphosate and paraquat] and several agricultural activities (repairing engines, grinding metal, driving diesel tractors, and performing veterinary procedures). Only asthma cases with allergies (i.e., doctor-diagnosed hay fever or eczema, 46%) had positive exacerbation-pesticide associations, with OR = 2.1 for the herbicide pendimethalin and OR = 10.2 for the insecticide aldicarb.The inverse associations with two pesticides and specific farm activities are consistent with the possibility that asthma cases prone to exacerbation may avoid exposures that trigger symptoms. Although limited by small sample size and a cross-sectional design, our study suggests that use of specific pesticides may contribute to exacerbation of asthma among individuals with allergies.
    [Henneberger PK, Liang X, London SJ, et al.2014. Int Arch Occup Environ Health. 87(4):423-32.]
  • Pesticides and Asthma: Challenges for Epidemiology
    Associations between pesticide exposure and asthma in children, adults, and occupational groups have been reported, but these have not yet been shown to be causal and the biological explanation tying the two remains unclear – it could lie in the mechanisms such as irritation, inflammation, immunosuppression, endocrine disruption, or a combination of these. So far, it is also unknown how pesticides interact with genes that increase susceptibility to asthma.This revies explores the relationship between pesticides and asthma. The present body of evidence is clearly insufficient to draw conclusions about the effect pesticide use has on asthma. It is uncertain whether pesticides cause asthma or act as triggers for asthma exacerbation or both.The main limitations of the current evidence are the outcome definition and the exposure assessment. With larger and preferably prospective studies and better asthma definition and exposure assessment, it will be easier to evaluate the association between individual pesticide exposure and asthma, and additionally it will be possible to identify gene–pesticide interactions. The identification and parameterization of these interactions will mean a big step forward in the understanding of the biological pathways that link pesticide exposure to asthma development and asthma exacerbation.
    [Amaral, A. 2014. Front Public Health.2:6]
  • Pesticide use, immunologic conditions, and risk of non-Hodgkin lymphoma in Canadian men in six provinces.
    Pesticide exposures and immune suppression have been independently associated with the risk of non-Hodgkin lymphoma (NHL), but their joint effect has not been well explored. Data from a case-control study of men from six Canadian provinces were used to evaluate the potential effect modification of asthma, allergies, or asthma and allergies and hay fever combined on NHL risk. Incident NHL cases (n = 513) diagnosed between 1991 and 1994 were recruited from provincial cancer registries and hospitalization records and compared to 1,506 controls. Subjects with asthma, allergies, or hay fever had non-significantly elevated risks of NHL associated with use of MCPA (OR = 2.67) compared to subjects without any of these conditions (OR = 0.81). Conversely, those with asthma, allergies, or hay fever who reported use of malathion had lower risks of NHL (OR = 1.25) versus subjects with none of these conditions (OR = 2.44). Similar effects were observed for asthma and allergies evaluated individually. Although there were some leads regarding effect modification by these immunologic conditions on the association between pesticide use and NHL, small numbers, measurement error and possible recall bias limit interpretation of these results.
    [Pahwa M, Harris SA, Hohenadel K, McLaughlin JR, et al.2012.Int J Cancer. 131(11):2650-9.]
  • Gene-Environment Interactions and Airway Disease in Children
    Asthma is the most common chronic disease of childhood in the United States, affecting nearly 6.5 million children. The prevalence and severity of childhood asthma have continued to increase over the past 2 decades, despite major advances in the recognition and treatment of this condition. Representing a heterogeneous collection of airway diseases, asthma has multiple pathologic processes resulting from the interactions of genetic susceptibility and environmental exposures. Preventing and treating airway disease in children will require new research approaches to understanding these complex interactions.
    [Schwartz, D. 2009. Pediatrics.123, Supplement 3:S151 -S159]
  • Pesticides and Atopic and Nonatopic Asthma among Farm Women in the Agricultural Health Study
    Studying 25,814 farm women in the Agricultural Health Study, authors used self-reported history of doctor-diagnosed asthma with or without eczema and/or hay fever to create two case groups: patients with atopic asthma and those with nonatopic asthma. Growing up on a farm (61% of all farm women) was protective for atopic asthma and, to a lesser extent, for nonatopic asthma. Pesticide use was almost exclusively associated with atopic asthma. Any use of pesticides on the farm was associated only with atopic asthma. This association with pesticides was strongest among women who had grown up on a farm. Women who grew up on farms and did not apply pesticides had the lowest overall risk of atopic asthma compared with women who neither grew up on farms nor applied pesticides. A total of 7 of 16 insecticides, 2 of 11 herbicides, and 1 of 4 fungicides were significantly associated with atopic asthma; only permethrin use on crops was associated with nonatopic asthma.
    [Hoppin, J.et al. 2008. American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 11-18]
  • Atopy, exposure to pesticides and risk of non-Hodgkin lymphoma
    Although the Australian population based case control study did not find a clear connection with asthma and pesticide exposure and NHL, it did find an increased risk of NHL with occupational pesticide exposure and a history of asthma as well as with occupational pesticide exposure an no history of asthma.
    [Vajdic, C.M., et al. 2007. Int J Cancer 120(10):2271-2274]
  • Asthma's Impact on Children and Adolescents
    Low-income populations, minorities, and children living in inner cities experience disproportionately high morbidity and mortality due to asthma.
    [Centers for Disease Control and Prevention, National Center for Environmental Health. 2005]
  • Summary health statistics for U.S. children: National Health Interview Survey, 2003.
    This report presents both age-adjusted and unadjusted statistics from the 2003 National Health Interview Survey (NHIS) on selected health measures for children under 18 years of age, classified by sex, age, race, Hispanic origin, family structure, parent's education, family income, poverty status, health insurance coverage, place of residence, region, and current health status. The topics covered are asthma, allergies, learning disability, Attention Deficit Hyperactivity Disorder (ADHD), use of prescription medication, respondent-assessed health status, school-loss days, usual place of health care, time since last contact with a health care professional, unmet dental needs, time since last dental contact, and selected measures of health care access. In 2003, most U.S. children under 18 years of age had excellent or very good health (83%). However, 10% of children had no health insurance coverage, and 5% of children had no usual place of health care. Thirteen percent of children had ever been diagnosed with asthma. An estimated 8% of children 3-17 years of age had a learning disability, and an estimated 6% of children had ADHD.
    [Centers for Disease Control and Prevention. 2005. Vital and Health Statistics 10 (223)]
  • Asthma and the environment: Connecting the dots
    Report explores the rapid increase in asthma rates in recent years which cannot be explained by genetic causes alone, as genetic changes require many generations for population-wide effects to occur, and because asthma rates are increasing among people without a family history of asthma and allergies.
    [Solomon, G., EH Humphreys, and MD Miller. 2004. Contemporary Pediatrics 21: 73]
  • Asthma Prevalence and Control Characteristics by Race/Ethnicity - United States, 2002
    To assess asthma prevalence and asthma-control characteristics among racial/ethnic populations, CDC analyzed 2002 data from the Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the results of that analysis, which indicated that among the estimated 16 million (7.5%) U.S. adults with asthma, self-reported current asthma prevalence among racial/ethnic minority populations ranged from 3.1% to 14.5%, compared with 7.6% among whites.
    [Centers for Disease Control and Prevention. 2004. Morbidity and Mortality Weekly Report. 53(07);145-148]
  • 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]
  • Health impacts of pesticide exposure in a cohort of outdoor workers.
    We compared mortality of 1,999 outdoor staff working as part of an insecticide application program during 1935-1996 with that of 1,984 outdoor workers not occupationally exposed to insecticides, and with the Australian population. Surviving subjects also completed a morbidity questionnaire. Mortality was significantly higher in both exposed and control subjects compared with the Australian population. The major cause was mortality from smoking-related diseases. Mortality was also significantly increased in exposed subjects for a number of conditions that do not appear to be the result of smoking patterns. Compared with the general Australian population, mortality over the total study period was increased for asthma [standardized mortality ratio (SMR) = 3.45; 95% confidence interval (CI), 1.39-7.10] and for diabetes (SMR = 3.57; 95% CI, 1.16-8.32 for subjects working < 5 years). Mortality from pancreatic cancer was more frequent in subjects exposed to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (SMR = 5.27; 95% CI, 1.09-15.40 for subjects working < 3 years). Compared with the control population, mortality from leukemia was increased in subjects working with more modern chemicals (standardized incidence ratio = 20.90; 95% CI, 1.54-284.41 for myeloid leukemia in the highest exposure group). There was also an increase in self-reported chronic illness and asthma, and lower neuropsychologic functioning scores among surviving exposed subjects when compared with controls. Diabetes was reported more commonly by subjects reporting occupational use of herbicides. These findings lend weight to other studies suggesting an association between adverse health effects and exposure to pesticides.
    [Beard, J., et al. 2003. Environmental Health Perspectives 111(5):724-730]
  • Occupational asthma from fungicides fluazinam and chlorothalonil.
    Authors report two cases of occupational asthma caused by sensitisation to powdered fungicides fluazinam and chlorothalonil, from the same fungicide formulation plant. Both developed work related lower respiratory symptoms after a latent interval of asymptomatic exposure. The diagnosis in each case was confirmed with a serial peak flow record in the workplace followed by specific inhalation tests. These fungicides are known to cause dermatitis; this report indicates that these compounds can induce specific immunological reactions in the airways as well as skin.
    [Draper, A, P Cullinan, C Campbell, et al. 2003. Occup Environ Med 60: 76-77]
  • Asthma the Breathtaking Disease
    In the last 20 years, asthma rates have soared to epidemic levels. Johns Hopkins Bloomberg School Of Public Health researchers investigate the food we eat, the air we breathe, and the way our bodies work for clues to better asthma treatment and prevention.
    [Field, M. 2002. The Magazine of Johns Hopkins Bloomberg School Of Public Health]
  • Hazardous air pollutants and asthma
    Asthma has a high prevalence in the United States, and persons with asthma may be at added risk from the adverse effects of hazardous air pollutants (HAPs). Complex mixtures (fine particulate matter and tobacco smoke) have been associated with respiratory symptoms and hospital admissions for asthma. The toxic ingredients of these mixtures are HAPs, but whether ambient HAP exposures can induce asthma remains unclear. Certain HAPs are occupational asthmagens, whereas others may act as adjuncts during sensitization. HAPs may exacerbate asthma because, once sensitized, individuals can respond to remarkably low concentrations, and irritants lower the bronchoconstrictive threshold to respiratory antigens. Adverse responses after ambient exposures to complex mixtures often occur at concentrations below those producing effects in controlled human exposures to a single compound. In addition, certain HAPs that have been associated with asthma in occupational settings may interact with criteria pollutants in ambient air to exacerbate asthma. Based on these observations and past experience with 188 HAPs, a list of 19 compounds that could have the highest impact on the induction or exacerbation of asthma was developed. Nine additional compounds were identified that might exacerbate asthma based on their irritancy, respirability, or ability to react with biological macromolecules. Although the ambient levels of these 28 compounds are largely unknown, estimated exposures from emissions inventories and limited air monitoring suggest that aldehydes (especially acrolein and formaldehyde) and metals (especially nickel and chromium compounds) may have possible health risk indices sufficient for additional attention. Recommendations for research are presented regarding exposure monitoring and evaluation of biologic mechanisms controlling how these substances induce and exacerbate asthma.
    [Leikauf, GD. 2002. Environmental Health Perspectives 110 (Suppl 4): 505-526]
  • Asthma to tetramethrin.
    Case report of occupational asthma following exposure to tetramethrin.
    [Vandenplas, O, JP Delwiche, J Auverdin, et al. 2000. Allergy 55: 418-419]
  • Fatal asthma in a child after use of an animal shampoo containing pyrethrin
    This case suggests that physicians should also be alert to formulations marketed as pyrethrin. Pesticides of this class are being used with increasing frequency in homes and are easily available to the public. Manufacturers are not required by the Environmental Protection Agency to state on the label that the pyrethrum formulations are allergens. The possibility of an acute allergic reaction occurring from the use of any currently marketed pyrethrum insecticide should be considered in any case of respiratory or dermal allergy of unknown cause.
    [Wagner, SL. 2000. West J Med 173: 86-87]
  • Is the increase in asthma prevalence occurring in children without a family history of atopy?
    Study investigated the familial associations of asthma and atopic disease in a population in which the prevalence of asthma and atopy is increasing. The prevalence of reported asthma (22.5%), eczema (24%) and hayfever (20%) in the children was high but similar to previous studies in this population. Asthma was reported in 20.8% of children of parents without a history of asthma and 18% of children of parents without any history of atopic disease. In children of parents without a family history of atopic disease suggests that much of the increase in asthma prevalence is occurring in children without a significant genetic predisposition. Childhood asthma developing in what would previously have been regarded as low risk families may differ in its aetiology from classical atopic asthma.
    [Christie GL, McDougall CM, Helms PJ. 1998. Is the increase in asthma prevalence occurring in children without a family history of atopy? Scott Med J. 43 (6): 180-182]
  • Asthmatic reactions to a commonly used aerosol insect killer.
    Seven patients with asthma and a history of chest tightness on exposure to aerosol insecticide sprays were studied. Under controlled conditions, objective measures of airways narrowing were taken before and after exposure to an aerosol insect killer (Mortein Pressure Pak). Chest tightness described as asthma was produced in all seven subjects, but only one showed a greater than 20% fall in FEV1, compared to baseline values. A further two subjects showed small changes in the maximum mid-expiratory flow rate. No changes were observed in the subjects' sensitivity to inhaled histamine before, and 24 hours after, exposure to the insecticide. Thus, exposure to a commonly used household insecticide spray produced marked symptoms in all subjects, but objective evidence of airways obstruction was present in only three, and no changes in bronchial reactivity to inhaled histamine occurred in any of the subjects
    [Newton JG and Breslin AB.1983. Med J Aust.1(8):378-80]

Respiratory Diseases

  • Glyphosate poisoning - a case report
    Glyphosate is the most commonly used broad-spectrum, non-selective herbicide in the world. The toxicity is supposed to be due to uncoupling of oxidative phosphorylation and the surfactant polyoxyethylene amine (POEA)- mediated cardiotoxicity. Clinical features of this herbicide poisoning are varied, ranging from asymptomatic to even death. There is no antidote and aggressive supportive therapy is the mainstay of treatment for glyphosate poisoning. We present a 69-year-old female patient with suicidal consumption of around 500 ml of Glycel®. Initially, gastric lavage was done and intravenous fluids were given. Within two hours of presentation, the patient developed respiratory distress needing intubation, hypotension needing vasopressor support, and severe lactic acidosis. She also developed acute respiratory distress syndrome, hypokalemia, hypernatremia, and aspiration pneumonia. Our patient was critically ill with multiple poor prognostic factors, but with timely aggressive supportive management, the patient gradually recovered.
    [Kunapareddy, T. and Kalisetty, S., 2021. Journal of Postgraduate Medicine.]
  • Influence of pesticides on respiratory pathology – a literature review
    Pesticides are widely employed in agriculture, and the food industry is forced to combat the pests and diseases they cause. Respiratory pathology is related to occupational exposure to pesticides. Impairment of pulmonary function was observed among people professionally exposed to pesticides. Because of the marked use of pesticides in agriculture during the last 20 years, there has been a significant increase in respiratory problems within the population, not only among people who come in direct contact with them, but even in the case of manipulators. The aim is a review of the literature of the past 10 years on the correlation between occupational exposure to pesticides and respiratory pathology. Electronic search in ‘Pub Med’ and ‘Web of Science’ was performed in September 2019 to find papers regarding the above-investigated aspects. Abstracts and full-text articles containing the targeted subject were included. Reviews and studies about the influence of pesticides on other pathologies than respiratory were excluded. After applying the inclusion and exclusion criteria, eligible full-text articles were identified. Exposure to pesticides is highly correlated with respiratory pathologies (asthma, COPD, lung cancer). Contact with these substances can occur at any time in the production, transport, preparation or application of the treatments. Numerous studies documented the association between exposure to pesticides, and therefore the increased incidence of respiratory, cardiovascular and renal diseases, as well as the aging phenomenon.
    [Tarmure, S., Alexescu, T.G., Orasan, O., Negrean, V., Sitar-Taut, A.V., Coste, S.C. and Todea, D.A., 2020. Annals of Agricultural and Environmental Medicine: AAEM, 27(2), pp.194-200.]
  • The herbicide paraquat-induced molecular mechanisms in the development of acute lung injury and lung fibrosis
    The herbicide paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridylium dichloride) is a highly toxic organic heterocyclic herbicide that has been widely used in agricultural settings. Since its commercial introduction in the early 1960s, numerous cases of fatal PQ poisonings attributed to accidental and/or intentional ingestion of PQ concentrated formulations have been reported. The clinical manifestations of the respiratory system during the acute phase of PQ poisoning mainly include acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), followed by pulmonary fibrosis in a later phase. The focus of this review is to summarize the most recent publications related to PQ-induced lung toxicity as well as the underlying molecular mechanisms for PQ-mediated pathologic processes. Growing sets of data from in vitro and in vivo models have demonstrated the involvement of the PQ in regulating lung oxidative stress, inflammatory response, epigenetics, apoptosis, autophagy, and the progression of lung fibrosis. The article also summarizes novel therapeutic avenues based on a literature review, which can be explored as potential means to combat PQ-induced lung toxicity. Finally, we also presented clinical studies on the association of PQ exposure with the incidence of lung injury and pulmonary fibrosis.
    [Subbiah, R. and Tiwari, R.R., 2020. Critical Reviews in Toxicology, pp.1-97.]
  • The Organophosphorus Pesticide Chlorpyrifos Induces Sex-Specific Airway Hyperreactivity in Adult Rats.
    Occupational and environmental exposures to organophosphorus pesticides (OPs) are associated with increased incidence of asthma and other pulmonary diseases. While the canonical mechanism of OP neurotoxicity is inhibition of acetylcholinesterase (AChE), it was previously reported that the OP chlorpyrifos (CPF) causes airway hyperreactivity (AHR) in guinea pigs at levels that do not inhibit lung or brain AChE. The guinea pig is considered to have inherently hyperresponsive airways, thus, cross-species validation is needed to confirm relevance to humans. Additionally, sex differences in asthma incidence have been demonstrated in the human population, but whether OP-induced AHR is sex-dependent has not been systematically studied in a preclinical model. In this study, eight-week old male and female Sprague Dawley rats were administered CPF at doses causing comparable AChE inhibition in whole lung homogenate (30 mg/kg in males, 7 mg/kg in females, sc) prior to assessing pulmonary mechanics in response to electrical stimulation of the vagus nerves at 24 h, 48 h, 72 h, 7 d or 14 d post-exposure in males, and 24 h or 7 d post-exposure in females. CPF significantly potentiated vagally-induced airway resistance and tissue elastance at 7 d post-exposure in males, and at 24 h and 7 d post-exposure in females. These effects occurred independent of significant AChE inhibition in cerebellum, blood, trachealis, or isolated airway, suggesting that AChE-independent OP-induced airway hyperreactivity is a cross-species phenomenon. These findings have significant implications for assessing the risk posed by CPF, and potentially other OPs, to human health and safety.
    [Shaffo FC, Grodzki AC, Schelegle ES, Lein PJ. 2018. Toxicol Sci. doi: 10.1093/toxsci/kfy158.]
  • Exposure to pesticides and the associated human health effects.
    Pesticides are used widely to control weeds and insect infestation in agricultural fields and various pests and disease carriers (e.g., mosquitoes, ticks, rats, and mice) in houses, offices, malls, and streets. As the modes of action for pesticides are not species-specific, concerns have been raised about environmental risks associated with their exposure through various routes (e.g., residues in food and drinking water). Although such hazards range from short-term (e.g., skin and eye irritation, headaches, dizziness, and nausea) to chronic impacts (e.g., cancer, asthma, and diabetes), their risks are difficult to elucidate due to the involvement of various factors (e.g., period and level of exposure, type of pesticide (regarding toxicity and persistence), and the environmental characteristics of the affected areas). There are no groups in the human population that are completely unexposed to pesticides while most diseases are multi-causal to add considerable complexity to public health assessments. Hence, development of eco-friendly pesticide alternatives (e.g., EcoSMART) and Integrated Pest Management (IPM) techniques is desirable to reduce the impacts of pesticides. This paper was hence organized to present a comprehensive review on pesticides with respect to their types, environmental distribution, routes of exposure, and health impacts.
    [Kim KH, Kabir E, Jahan SA. 2017. Sci Total Environ. 575:525-535.]
  • Occupational exposure to pesticides are associated with fixed airflow obstruction in middle-age.
    Population-based studies have found evidence of a relationship between occupational exposures and Chronic Obstructive Pulmonary Disease (COPD), but these studies are limited by the use of prebronchodilator spirometry. Establishing this link using postbronchodilator is critical, because occupational exposures are a modifiable risk factor for COPD.This study investigated the associations between occupational exposures and fixed airflow obstruction using postbronchodilator spirometry. One thousand three hundred and thirty-five participants were included from 2002 to 2008 follow-up of the Tasmanian Longitudinal Health Study (TAHS). Spirometry was performed and lifetime work history calendars were used to collect occupational history. ALOHA plus Job Exposure Matrix was used to assign occupational exposure, and defined as ever exposed and cumulative exposure unit (EU)-years. Fixed airflow obstruction was defined by postbronchodilator FEV1/FVC <0.7 and the lower limit of normal (LLN). Ever exposure to biological dust (relative risk (RR)=1.58, 95% CI 1.01 to 2.48), pesticides (RR=1.74,95% CI 1.00 to 3.07) and herbicides (RR=2.09,95% CI 1.18 to 3.70) were associated with fixed airflow obstruction. Cumulative EU-years to all pesticides (RR=1.11,95% CI 1.00 to 1.25) and herbicides (RR=1.15,95% CI 1.00 to 1.32) were also associated with fixed airflow obstruction. In addition, all pesticides exposure was consistently associated with chronic bronchitis and symptoms that are consistent with airflow obstruction. Pesticides and herbicides exposures were associated with fixed airflow obstruction and chronic bronchitis. Biological dust exposure was also associated with fixed airflow obstruction in non-asthmatics. Minimising occupational exposure to these agents may help to reduce the burden of COPD.
    [Alif SM, Dharmage SC, Benke G, Dennekamp M, et al. 2017. Thorax. pii: thoraxjnl-2016-209665]
  • Pesticides are Associated with Allergic and Non-Allergic Wheeze among Male Farmers
    Growing evidence suggests that pesticide use may contribute to respiratory symptoms. We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers. Using the 2005–2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by ≥ 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever (n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever (n = 3,939, 18%); men without wheeze were the referent. In models evaluating current use of specific pesticides, 19 pesticides were significantly associated (p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure–response models with up to five exposure categories, we saw evidence of an exposure–response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin. These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects.
    [Hoppin J.A., Umbach D.M., Long S., London S.J., Henneberger P.K., Blair A., Alavanja M., Beane Freeman L.E., Sandler D.P. 2017. 125:535–543; http://dx.doi.org/10.1289/EHP315]
  • 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]
  • 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.]
  • Early-life exposure to organophosphate pesticides and pediatric respiratory symptoms in the CHAMACOS cohort.
    Authors investigated the relationship between early-life exposure to OPs and respiratory outcomes.Participants included 359 mothers and children from the CHAMACOS birth cohort. Dialkyl phosphate (DAP) metabolites of OP pesticides, specifically diethyl (DE) and dimethyl (DM) phosphate metabolites, were measured in urine from mothers twice during pregnancy (mean = 13 and 26 weeks gestation) and from children five times during childhood (0.5-5 years). Mothers reported their child's respiratory symptoms at 5 and 7 years of age. Higher prenatal DAP concentrations, particularly DE, were nonsignificantly associated with respiratory symptoms in the previous 12 months at 5 or 7 years of age. This association was strongest with total DAP and DE from the second half of pregnancy. Childhood DAP, DE, and DM concentrations were associated with respiratory symptoms and exercise-induced coughing in the previous 12 months at 5 or 7 years of age. Early-life exposure to OP pesticides was associated with respiratory symptoms consistent with possible asthma in childhood.
    [Raanan R, Harley KG, Balmes JR, et al. 2015. Environ Health Perspect. 123(2):179-85.]
  • Asthma associated with pesticide exposure among women in rural Western Cape of South Africa.
    Few studies have investigated asthma and pesticides among women farm workers in developing countries.
    A cross-sectional study was conducted to investigate the association between pesticides and asthma among rural women (n = 211). Outcome measurements included respiratory symptoms (European Community Respiratory Health Survey questionnaire), immunological status (Phadiatop, serum IgE to mite allergens) and lower airway inflammation (fractional exhaled nitric oxide (FeNO) levels). Exposure variables included self-reported pesticide exposure and whole blood cholinesterase (ChE). The prevalence of ocular-nasal symptoms (ONS), doctor-diagnosed asthma and current asthma was 24%, 11%, and 6% respectively. ONS was positively associated with re-entering a sprayed field. Asthma symptom score was associated with low ChE. Participants with high FeNO (>50 ppb) also had an elevated odds of having low ChE. Pesticide exposure among women farm workers is associated with increased risk of ocular nasal symptoms and an elevated asthma symptom score.
    [Ndlovu V, Dalvie MA, Jeebhay MF. 2014. Am J Ind Med. 57(12):1331-43.]
  • Levels and sources of volatile organic compounds in homes of children with asthma.
    This study characterizes VOC levels in 126 homes of children with asthma in Detroit, Michigan, USA. The total target VOC concentration ranged from 14 to 2274 μg/m(3); 56 VOCs were quantified; and d-limonene, toluene, p, m-xylene, and ethyl acetate had the highest concentrations. Based on the potential for adverse health effects, priority VOCs included naphthalene, benzene, 1,4-dichlorobenzene, isopropylbenzene, ethylbenzene, styrene, chloroform, 1,2-dichloroethane, tetrachloroethene, and trichloroethylene. Concentrations varied mostly due to between-residence and seasonal variation. Identified emission sources included cigarette smoking, solvent-related emissions, renovations, household products, and pesticides. The effect of nearby traffic on indoor VOC levels was not distinguished. While concentrations in the Detroit homes were lower than levels found in other North American studies, many homes had elevated VOC levels, including compounds that are known health hazards. Thus, the identification and control of VOC sources are important and prudent, especially for vulnerable individuals. The most important sources included cigarette smoking, vehicle-related emissions, building renovation, solvents, household products, and pesticides.
    [Chin JY, Godwin C, Parker E, et al. 2014. Indoor Air. 24(4):403-15.]
  • The association of respiratory symptoms and indoor housing conditions among migrant farmworkers in eastern North Carolina.
    Farm labor housing has been described as among the worst in the nation, oftentimes with poor and unsanitary indoor living conditions. The objective of this study was to evaluate the association between indoor environmental risk factors and respiratory health among migrant farmworker occupants (N = 352) living in employer-provided housing. A cross-sectional sample of adult Latino male farm laborers were administered a questionnaire to identify the prevalence of major respiratory symptoms. Self-reported and independent observations were made to evaluate environmental respiratory risk factors and indoor housing conditions, including but not limited to, the presence of cockroaches, rodents, pesticides, and visible signs of mold. Spirometry was performed to evaluate lung function using FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity), and FEV1 /FVC ratio. Bivariate analysis was applied to evaluate associations between respiratory symptoms and selected indoor environmental risk factors. Findings for respiratory health included prevalence of wheeze (11.4%), coughing up phlegm (17.3%), tightness of chest (16.8%), and runny or stuffy nose (34.4%). Respiratory risks identified inside the dwellings included the use of pesticides or bug sprays for cockroaches (31.5%), rat or mouse poison (19.5%), visible signs of water damage in the bathroom (22.5%), and mold in the sleeping room (11.1%). Spirometry values were normal for most occupants, although statistically significant associations were found between mold and coughing up phlegm when not having a cold (P = .0262); presence of mold and asthma (P = .0084); pesticides used in the home and tightness of chest (P = .0001); and use of tobacco and coughing up phlegm (P = .0131). Although causal inference can be difficult to establish from a cross-sectional study, findings from this study represents suggestive evidence that indoor environmental risk factors may be contributory factors for respiratory health problems among this vulnerable workgroup population.
    [Kearney GD, Chatterjee AB, Talton J, et al. 2014. J Agromedicine. 19(4):395-405.]
  • Prenatal exposure to pesticide ingredient piperonyl butoxide and childhood cough in an urban cohort.
    A previous study from the authors reports that airborne concentrations of cis-permethrin, but not trans-permethrin, measured during pregnancy in an inner city pediatric cohort was associated with cough by age 5. However, the effect of subsequent exposures to both permethrins during early childhood, and to piperonyl butoxide (PBO, a synergist for residential pyrethroid insecticides) remains to be elucidated. This study hypothesized that prenatal and age 5-6 year measures of PBO and permethrins would be associated with cough at age 5-6 years in this cohort. Further, the authors explored the associations between these pesticide measures and wheeze, asthma, seroatopy, and fractional exhaled nitric oxide (FeNO).PBO and permethrins were measured in personal air during the third trimester of pregnancy and indoor residential air at age 5-6 years (n=224). Health outcome questionnaires were administered to the mothers of 5-6 year old children. Indoor allergen specific and total immunoglobulin (Ig) E production was measured from sera collected at age 5, and FeNO was measured at 5-6 years.Noninfectious cough was reported among 14% of children at age 5-6 years. Measures of prenatal PBO, but not age 5-6 year PBO or permethrins, increased the odds of cough. No significant associations were found for other measured health outcomes.Authors conclude prenatal PBO exposure was associated with childhood cough. It is unclear whether the observed effect is due mainly to PBO itself or residential pyrethroids of which PBO is an indicator.
    [Liu B, Jung KH, Horton MK, et al. 2012. Environ Int. 48:156-61.]
  • Rhinitis associated with pesticide exposure among commercial pesticide applicators in the Agricultural Health Study
    To investigate the association between current rhinitis and pesticide use, authors used data from 2245 Iowa commercial pesticide applicators in the Agricultural Health Study. 74% of commercial pesticide applicators reported at least one episode of rhinitis in the past year (current rhinitis). Five pesticides used in the past year were significantly positively associated with current rhinitis: the herbicides 2,4-D, glyphosate and petroleum oil, the insecticide diazinon and the fungicide benomyl. The association for 2,4-D and glyphosate was limited to individuals who used both in the past year (OR 1.42, 95% CI 1.14 to 1.77). Both petroleum oil and diazinon showed consistent evidence of an association with rhinitis, based on both current use and exposure–response models.
    [R E Slager, J A Poole, T D LeVan, et al. 2009. Occup Environ Med 2009 66: 718-724]
  • Respiratory symptoms in children and exposure to pesticides
    A cross­sectional study was performed on children from a randomly selected sample of Lebanese public schools. Exposure to pesticides was evaluated by a standardised questionnaire and a residential exposure score, and respiratory symptoms were assessed. A chronic respiratory disease was reported in 407 (12.4%) out of 3,291 children. The baseline difference in mean age was small but statistically significant. Any exposure to pesticides, including residential, para­occupational and domestic, was associated with respiratory disease and chronic respiratory symptoms (chronic phlegm, chronic wheezing, ever wheezing), except for chronic cough.
    [Salameh, PR, I Baldi, P Brochard, et al. 2003. European Respiratory Journal 22: 507-512]
  • Chemical predictors of wheeze among farmer pesticide applicators in the Agricultural Health Study.
    Using the Agricultural Health Study, a large cohort of certified pesticide applicators in Iowa and North Carolina, authors explored the association between wheeze and pesticide use in the past year. Self-administered questionnaires contained items on 40 currently used pesticides and pesticide application practices. A total of 20,468 applicators, ranging in age from 16 to 88 years, provided complete information; 19% reported wheezing in the past year. The herbicides, atrazine and alachlor, but not 2,4-D, were associated with wheeze. Atrazine had a significant dose-response trend with participants applying atrazine more than 20 days/year.These associations, though small, suggest an independent role for specific pesticides in respiratory symptoms of farmers.
    [Hoppin, JA, DM Umbach, SJ London, et al. 2002. M J Respir Crit Care Med 165: 683-689]
  • Identifying and managing adverse environmental health effects: Pesticides.
    Pesticide exposure can cause many different health effects, from acute problems such as dermatitis and asthma exacerbation to chronic problems such as chronic obstructive pulmonary disease and cancer. The resulting clinical presentations are undifferentiated, and specific knowledge of the links to environmental exposures is often required for effective diagnosis. In this article we illustrate the use of the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Drugs and Diet), a history-taking tool that assists physicians in quickly identifying possible environmental exposures. We also provide clinical information on the epidemiology, clinical presentations, treatment and prevention of pesticide exposures.
    [Sanborn, MD, D Cole, A Abelsohn, and E Weir. May 28 2002. CMAJ 166 (11): 1431-1436]
  • Exposures of children to organophosphate pesticides and their potential adverse health effects.
    Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children's exposure to pesticides and other environmental agents, and thereby reduce the incidence of environmentally related disease.
    [Eskanazi, B, A Bradman, and R Castorina. 1999. Environmental Health Perspectives 107(Suppl 3): 409-419]
  • Five office workers inadvertently exposed to cypermethrin
    Five cases of poisoning by cypermethrin, a pyrethroid pesticide, are presented. The chemical was inadvertently introduced to the air-conditioning ducts and the patients inhaled it. Exposed patients experienced shortness of breath, nausea, headaches, and irritability. The exposure was compounded by repeated entry into the contaminated area and slow referral to a physician experienced in pesticide exposures.
    [Lessenger JE. 1992. J Toxicol Environ Health 35: 261-267]
  • Indoor spraying with the pyrethroid insecticide lambda-cyhalothrin: effects on spraymen and inhabitants of sprayed houses.
    In March 1990 a study was carried out in the village of Kicheba, United Republic of Tanzania, in which the pyrethroid insecticide lambda-cyhalothrin was sprayed on all the internal surfaces of houses and other shelters at a coverage of about 25 mg of active ingredient per m2. All the spraymen complained at least once of symptoms that were related to exposure to lambda-cyhalothrin, the commonest being itching and burning of the face, and nose or throat irritation frequently accompanied by sneezing or coughing. Facial symptoms occurred on non-protected areas only. The number of subjects affected and the duration of their facial symptoms were proportional to the amount of compound sprayed.
    [Moretto A. 1991.Bull WHO 69 (5): 591-594]
  • Occupational exposure to some synthetic pyrethroids (permethrin and fenvalerate).
    In a two-step study on exposure control method for occupational handling of permethrin was developed. Air sampling on a filter can be used in case of exposure to permethrin in powder form. The detection limit is 0.001 mg/m3. If biological sampling is used, the acid metabolite moiety in the urine must be monitored. However, the uptake after exposure to permethrin in forestry was too low, and no urine concentration could be found. The detection limit is 0.1 microgram/ml. Six persons in a plant nursery and six planters were studied in this way. Interviews were conducted with 139 planters. Irritative symptoms form the skin and upper respiratory tract were reported in 73% for fenvalerate, 63% for permethrin (trans/cis 75/25) and 33% for permethrin (trans/cis 60/40).
    [Kolmodin-Hedman, B, A Swensson, and M Akerblom. 1982. Arch Toxicol 50: 27-33]
  • Insecticides: household use and respiratory impairment
    An early study done in the 1960s in Hawaii shows that frequent household use of insecticides is correlated with an increased prevalence of respiratory disorders, including asthma and chronic bronchitis. The majority of the household pesticides used were insect sprays for mosquitoes, flies, and cockroaches
    [Weiner, BP, and RM Worth. 1969. Hawaii Medical Journal 28 (4): 283-285]

Lung Cancer

  • Influence of pesticides on respiratory pathology – a literature review
    Pesticides are widely employed in agriculture, and the food industry is forced to combat the pests and diseases they cause. Respiratory pathology is related to occupational exposure to pesticides. Impairment of pulmonary function was observed among people professionally exposed to pesticides. Because of the marked use of pesticides in agriculture during the last 20 years, there has been a significant increase in respiratory problems within the population, not only among people who come in direct contact with them, but even in the case of manipulators. The aim is a review of the literature of the past 10 years on the correlation between occupational exposure to pesticides and respiratory pathology. Electronic search in ‘Pub Med’ and ‘Web of Science’ was performed in September 2019 to find papers regarding the above-investigated aspects. Abstracts and full-text articles containing the targeted subject were included. Reviews and studies about the influence of pesticides on other pathologies than respiratory were excluded. After applying the inclusion and exclusion criteria, eligible full-text articles were identified. Exposure to pesticides is highly correlated with respiratory pathologies (asthma, COPD, lung cancer). Contact with these substances can occur at any time in the production, transport, preparation or application of the treatments. Numerous studies documented the association between exposure to pesticides, and therefore the increased incidence of respiratory, cardiovascular and renal diseases, as well as the aging phenomenon.
    [Tarmure, S., Alexescu, T.G., Orasan, O., Negrean, V., Sitar-Taut, A.V., Coste, S.C. and Todea, D.A., 2020. Annals of Agricultural and Environmental Medicine: AAEM, 27(2), pp.194-200.]
  • Pesticide exposure and lung cancer risk: A case-control study in Nakhon Sawan, Thailand
    Pesticide exposure might increase risk of lung cancer. The purpose of this study was to investigate the association between the historical use of pesticides commonly found in Thailand, and lung cancer. This case-control study compared a lifetime pesticide exposure of 233 lung cancer cases, and 447 healthy neighbours matched for gender, and age (±5 years). Data on demographic, pesticide exposure and other related factors were collected using a face-to-face interview questionnaire. Associations between lung cancer and types of pesticides as well as individual pesticides were analyzed using logistic regression adjusted for gender (male, female), age (≤54, 55-64, 65-74, ≥75), cigarette smoking ( never smoked, smoked < 109,500, smoked ≥ 109,500), occupation (farmer, non-farmer), cooking fumes exposure (yes, no), and exposure to air pollution (yes, no). It was found that lung cancer was positively associated with lifetime use of herbicides, insecticides, and fungicides. Compared to people in the lowest quartile of number of days using the herbicides and insecticides, those in a higher quartile had an elevated risk of lung cancer, with odds ratio (OR) between 3.31 (95% confidence interval (CI) 1.49–7.34), and 12.58 (95% CI 5.70-27.75) (p < 0.001). For fungicides, only the most exposed group had a significant risk (OR = 4.25; 95% CI 1.23-14.72). For individual pesticides, those presenting a significant association with lung cancer were dieldrin (OR = 2.56; 95% CI 1.36-4.81), chlorpyrifos (OR = 3.29; 95 % CI 1.93-5.61), and carbofuran (OR = 2.10; 95% CI 1.28-3.42). The results showed that lung cancer among Thai people in Nakhon Sawan province is associated with previous pesticide use. This finding was consistent with previous studies in other parts of the world. Further study should focus on identifying more individual compounds that may cause lung cancer, as well as other types of cancer.
    [Kangkhetkron, T. and Juntarawijit, C., 2020. F1000Research, 9(492), p.492.]
  • Occupational Exposure to Pesticides and the Incidence of Lung Cancer in the Agricultural Health Study.
    Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between several pesticides and lung cancer incidence.We evaluated use of 43 pesticides and 654 lung cancer cases after 10 years of additional follow-up in the AHS, a prospective cohort study comprising 57,310 pesticide applicators from Iowa and North Carolina.Information about lifetime pesticide use and other factors was ascertained at enrollment (1993-1997) and updated with a follow-up questionnaire (1999-2005). Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI: 0.98, 2.31), dieldrin (1.93; 95% CI: 0.70, 5.30), and chlorimuron ethyl (1.74; 95% CI: 1.02, 2.96), although monotonic exposure-response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days (p = 0.049) and borderline for lifetime days (p = 0.073). None of the remaining pesticides evaluated was associated with lung cancer incidence.These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted.
    [Bonner MR1, Freeman LE, Hoppin JA, Koutros S, Sandler DP, et al. 2017. Environ Health Perspect. 125(4):544-551.]
  • Chronic exposure to chlorophenol related compounds in the pesticide production workplace and lung cancer: a meta-analysis.
    Chlorophenols (CPs) and related phenoxyacetic acids (PAs) are pesticide groups contaminated with highly toxic 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) during production. PAs and CPs exposure is associated with risk of cancer, but the situation regarding lung cancer has not been clearly defined. Study is a meta-analysis of published researches to evaluate relationship between chronic exposure to PAs and CPs in pesticide production workplaces and the risk of lung cancer.Five papers with six reports were included in the final analysis. The standardized mortality rate for lung cancer from the random model was 1.18 with moderate heterogeneity. Publication bias was not found for included studies in meta-analysis (p=0.9).Our findings has strengthen the evidence of lung cancer from chronic exposure to chlorophenol related compounds (PAs, CPs).
    [Zendehdel R, Tayefeh-Rahimian R, Kabir A. 2014. Asian Pac J Cancer Prev. 15(13):5149-53.]
  • Risk factors for lung cancer in the Pakistani population.
    In this retrospective case-control study, 400 cases and 800 controls were enrolled from different hospitals of all provinces of Pakistan. Information about socio-demographic, occupational, lifestyle and dietary variables was extracted by questionnaire from all subjects. Strong associations were observed for smoking (OR=9.4), pesticide exposure (OR=5.1), exposure to diesel exhaust (OR=3.1). Other associated factors observed were family history (OR=2.0) wood dust (OR=1.9), asbestos exposure(OR=1.5). Strongest dose-response relationships were observed for smoking , pesticide exposure and exposure to diesel exhaust.
    [Luqman M, Javed MM, Daud S, Raheem N, et al. 2014. Asian Pac J Cancer Prev. 15(7):3035-9.]
  • TP53 gene mutations of lung cancer patients inupper northern Thailand and environmental risk factors
    A study that evaluated the risk factors that influence TP53 gene mutation (which is observed in about 40-70% of lung cancer tissues) in lung cancer patients finds that these mutations are induced by exposure to substances other than tocacoo smoke, possibly pesticide exposure.
    [Bumroongkit, K., et al. 2008. Cancer Genet Cytogenet 185(1):20-27.]
  • Cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study
    Dicamba is an herbicide commonly applied to crops in the United States and abroad. We evaluated cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in North Carolina and Iowa. Detailed pesticide exposure information was obtained through a self-administered questionnaire completed from 1993 to 1997. Cancer incidence was followed through 31 December 2002 by linkage to state cancer registries. We used Poisson regression to estimate rate ratios and 95% confidence intervals for cancer subtypes by tertiles of dicamba exposure. Two dicamba exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days (lifetime days × intensity score). A total of 41,969 applicators were included in the analysis, and 22,036 (52.5%) reported ever using dicamba. Exposure was not associated with overall cancer incidence nor were there strong associations with any specific type of cancer. When the reference group comprised low-exposed applicators, we observed a positive trend in risk between lifetime exposure days and lung cancer (p = 0.02), but none of the individual point estimates was significantly elevated. We also observed significant trends of increasing risk for colon cancer for both lifetime exposure days and intensity-weighted lifetime days, although these results are largely due to elevated risk at the highest exposure level. There was no apparent risk for non-Hodgkin lymphoma. Although associations between exposure and lung and colon cancer were observed, we did not find clear evidence for an association between dicamba exposure and cancer risk.
    [Samanic, C., et al. 2006. Environ Health Perspect 114(10):1521-1526.]
  • Cancer incidence among pesticide applicators exposed to metolachlor in the Agricultural Health Study
    Metolachlor is one of the most widely used herbicides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to metolachlor in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 50,193 pesticide applicators were included. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered enrollment questionnaires completed between 1993 and 1997; average length of follow-up was 7.33 years. Two metolachlor exposure metrics were used : (i) lifetime days personally mixed or applied metolachlor and (ii) intensity-weighted lifetime days (lifetime days x an intensity level). Poisson regression analysis was used to estimate relative risks (RR) and 95% confidence intervals (95%CI) for cancer subtypes by tertiles of metolachlor exposure. No clear risk for any cancer subtype was found for exposure to metolachlor. A significantly decreased RR was found for prostate cancer in the highest category of lifetime days exposure (RR = 0.59; 95%CI, 0.39-0.89) and in the second highest category of intensity-weighted lifetime days exposure (RR = 0.66; 95%CI, 0.45-0.97); however, the test for trend was not significant for either exposure metric. A nonsignificantly increased risk was found for lung cancer with lifetime days exposure in the highest category (RR = 2.37; 95%CI, 0.97-5.82, p-trend = 0.03) but not with intensity-weighted lifetime days. Given the widespread use of metolachlor and the frequent detection of metolachlor in both surface and ground water, future analyses of the AHS will allow further examination of long-term health effects, including lung cancer and the less common cancers.
    [Rusiecki, J.A., et al. 2006. Int J Cancer 118(12):3118-3123.]
  • Cancer incidence among male pesticide applicators in the Agricultural Health Study cohort exposed to diazinon
    Little is known about the potential carcinogenicity associated with routine application of diazinon, a common organophosphate insecticide. The authors explored a possible association of diazinon exposure with cancer risk in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina enrolled in 1993-1997. A total of 23,106 male applicators provided information in a self-administered questionnaire. Among 4,961 applicators who reported using diazinon, 301 incident cancer cases were diagnosed during the follow-up period ending December 2002 compared with 968 cases among 18,145 participants who reported no use. Poisson regression was used to calculate rate ratios and 95% confidence intervals. Two quantitative exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days, a measure that incorporates probability of pesticide exposure with lifetime pesticide application frequency. When lifetime exposure days were used, increased risks for the highest tertile of exposure and significant tests for trend for lung cancer and leukemia were observed. No other cancer site showed an association with diazinon for the highest tertile of exposure. Because these results were based on small numbers, additional analyses are necessary as more cases accrue to clarify whether diazinon is associated with cancer risk in humans.
    [Beane Freeman, L.E., et al. 2005. American Journal of Epidemiology 162(11):1070-1079]
  • Parental occupational exposures and Ewing’s sarcoma
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with a twofold increase risk for lung cancer for both males and females (OR 2.01 males; 2.63 females).
    [Moore, L.E., et al. 2005. Int J Cancer 114(3):472-478.]
  • Cancer Incidence Among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health Study
    Chlorpyrifos is one of the most widely used insecticides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 54 383 pesticide applicators were included in this analysis. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed at the time of enrollment (December 1993–December 1997). Poisson regression analysis was used to evaluate the association between chlorpyrifos exposure and cancer incidence after adjustment for potential confounders. All statistical tests were two-sided. A total of 2070 incident malignant neoplasms were diagnosed through 2001. The rate ratio for all cancers combined among chlorpyrifos-exposed applicators compared with nonexposed applicators was 0.97 (95% confidence interval = 0.87 to 1.08). For most cancers analyzed, there was no evidence of an exposure–response relationship. However, the incidence of lung cancer was statistically significantly associated with both chlorpyrifos lifetime exposure-days ( Ptrend = .002) and chlorpyrifos intensity-weighted exposure-days ( Ptrend = .036). After adjustment for other pesticide exposures and demographic factors, individuals in the highest quartile of chlorpyrifos lifetime exposure-days (>56 days) had a relative risk of lung cancer 2.18 (95% confidence interval = 1.31 to 3.64) times that of those with no chlorpyrifos exposure. Our findings suggest an association between chlorpyrifos use and incidence of lung cancer that deserves further evaluation.
    [Lee WJ, et al. 2004. J Natl Cancer Inst. 96(23):1781-9.]
  • Pesticides and lung cancer risk in the Agricultural Health Study Cohort
    Four agricultural pesticides are associated with a significant excess lung cancer risk in the Agricultural Health Study cohort.
    [Alavanja, M.C.R., et al. 2004. American Journal of Epidemiology 160(9):876-885.]
  • Cohort mortality and nested case-control study of lung cancer among structural pest control workers in Florida (United States)
    A previous report on the mortality of this cohort of Florida (United States) pest control workers found the risk of lung cancer was positively associated with the number of years licensed. An additional follow-up (1977–82) of this male cohort confirmed the excess (SMR=1.4) and the rising risk with increasing number of years licensed (SMR=2.2 among workers employed more than 20 years). A nested case-control study was undertaken to determine the effects of smoking and the type of pesticide exposure on lung cancer risk. Occupational histories and other data were obtained on 65 deceased lung cancer cases, 122 deceased controls, and 172 living controls. Interviews were conducted with next-of-kin regardless of the vital status of the subject. Odds ratios (OR) were adjusted by age and smoking. Adjustments for diet and other occupations had no effect on risk estimates and were not included in the final model. Using information from licensing records, ORs for lung cancer were greater for workers first licensed before age 40 (OR=2.4, 95 percent confidence interval [CI]=1.0–5.9 with deceased controls) and increased from 1.4 (CI=0.7–3.0) for subjects licensed 10–19 years to 2.1 (CI=0.8–5.5) for subjects licensed 20 or more years. Using living controls, an association with duration of employment was observed when years of licensure were lagged five years, but was not observed in unlagged analyses. Using information from the questionnaire, the risk of lung cancer was greater among those who worked as pest control operators than non-pest control workers. Although numbers were typically small, lung cancer risk among pest control operators was associated with reported exposure to carbamates, organophosphates, and phenoxyacetic acids and more specifically with diazinon, DDT, carbaryl, and propoxur. These results further suggest that pesticides may play a role in lung cancer risk and underscore the need for research that focuses on specific chemicals.
    [Pesatori, A.C., et al. 1994. Cancer Causes and Control 5:310-318.]
  • Occupational risk factors for lung cancer among nonsmoking women: a case-control study in Missouri (United States)
    A population-based, case-control study of nonsmokers finds elevated risk among women exposed to pesticides (OR 2.4) for lung cancer.
    [Brownson, R.C., et al. 1993. Cancer Causes Control 4(5):449-454.]
  • Lung cancer and other causes of death among licensed pesticide applicators.
    A cohort study of causes of death among licensed pesticide applicators in Florida finds excess deaths due to lung cancer. Although individuals’ tobacco use was not available, a 1983 study of causes of death among licensed pesticide applicators in Florida finds excess deaths due to cancer of the lungs and that the risk increased with the number of years licensed. Mortality is shown to be greatest for those first licensed before age 40 than among those individuals licensed after age 40.
    [Blair, A., et al. 1983. J Natl Cancer Inst 71(1):31-37]
  • Increased risk of lung cancer in pesticide-exposed male agricultural workers
    A 1981 study of male German agricultural workers exposed to pesticides finds a dose-effect relationship between duration of employment and lung cancer mortality.
    [Barthel, E. 1981. J Toxicol Environ Health 8(5-6):1027-1040.]