Search the Database

Kidney/Renal Cancer

• 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.]
• Evidence of risks of renal function reduction due to occupational exposure to agrochemicals: A systematic review.
  Agriculture accounts for an important economic activity worldwide and the search for the increased productivity incorporated the use of pesticides in this practice. Such compounds have significant environmental and human health effects, especially for workers exposed to them. Among the main health problems caused by pesticides are the renal alterations, which in more advanced stages comprise an important public health problem. For this reason, this systematic review aimed at gathering evidence of the risk of renal changes induced by occupational exposure to pesticides. The search was made in PubMed, Scopus, Lilacs and Scielo in December 2017, using keywords as pesticides, poisoning, kidney, renal insufficiency. After the application of inclusion criteria, 11 studies were selected. It was possible to gather evidence on the prevalence and risk (3.12-6.71) of renal injury from the occupational exposure of agricultural workers and its association with the exposure to agrichemicals, as organophosphates and herbicides.
  [Prudente IRG, Cruz CL, Nascimento LC, Kaiser CC, Guimarães AG. 2018. Environ Toxicol Pharmacol. 63:21-28]
• Occupational exposures and genetic susceptibility to urinary tract cancers: a systematic review and meta-analysis.
  This study aims to summarize the current knowledge on the relationship between genetic polymorphisms, occupational exposures, and urinary tract cancers. Authors searched MEDLINE, ISI Web of science, and SCOPUS online databases for all articles published in English language up to September 2016. A meta-analysis was performed to provide summary estimates for the association between a certain genetic polymorphism, occupational exposure and bladder cancer (BC) or kidney cancer (KC), when appropriate. Fifteen studies on BC and six on KC were deemed eligible for the review. With regard to BC, an overall odds ratio (OR) of 2.07 [95% confidence interval (CI): 1.38-3.09] for those with GSTM1 and an OR of 2.07 (95% CI: 1.38-3.09) for those with GSTT1 null genotype were reported when exposed to polycyclic aromatic hydrocarbons (PAHs). NAT2 slow genotype carriers had an OR of 3.59 (95% CI: 2.62-4.93) for BC when exposed to aromatic amines and an OR of 2.07 (95% CI: 1.36-3.15) when exposed to PAHs. With regard to KC and pesticide exposure, the meta-analysis reported an OR of 4.38 (95% CI: 2.28-8.41) for GSTM1 present genotype, an OR of 2.59 (95% CI: 1.62-4.15) for GSTT1-present genotype and an OR of 6.51 (95% CI: 2.85-14.89) for combined effects of GSTM1 and GSTT1 active genotypes. This meta-analysis indicates a possible association between the variant genotypes of GSTM1, GSTT1, NAT2 and SULT1A1, occupational exposure to aromatic amines or PAHs, and development of BC. Our results suggest that polymorphisms in GSTM1 and GSTT1 genes could influence the risk for developing KC in individuals occupationally exposed to pesticides.
  [Stojanovic J, Milovanovic S, Pastorino R, et al. 2017. Eur J Cancer Prev. doi: 10.1097/CEJ.0000000000000364]
• Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms.
  This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. Study also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles. Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, it was observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.
  [Karami S, Boffetta P, Rothman N, Hung RJ, Stewart T, et al. 2008. Carcinogenesis. 29(8):1567-71]
• Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
  An ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with moderate to high agriculture activity finds statistically significantly elevated risk for renal carcinoma at moderate agriculture activity (OR 2.3) and at high agriculture activity (OR 3.3). In regards to specific crops grown, the study finds a link between cotton crops and renal carcinomas (OR 6.9).
  [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
• Wilm’s tumor and exposure to residential and occupational hazardous chemicals
  A case-control study by the CDC finds elevated risk for pesticides during pregnancy and during the 2-year period prior to birth.
  [Tsai, J., et al. 2006. Int J Hyg Environ Health 209(1):57-64.]
• Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals.
  Study aimed to investigate the possible interaction between occupational risk factors and genotype for glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in renal cell cancer (RCC).One hundred patients with RCC and 200 outpatient controls were enrolled at Parma University Hospital. The polymorphisms of glutathione S-transferase M1-1 (GSTM1) and T1-1 (GSTT1) were investigated by PCR; occupational history was collected by a structured questionnaire. Subjects with GSTM1 present genotype showed higher risks for RCC, compared to GSTM1 null subjects, if exposed to metals or pesticides. The GSTT1 present genotype also enhanced the risk (about twofold) of RCC among subjects exposed to solvents and pesticides, compared with those GSTT1 null.Results support the hypothesis that GSTM1 and GSTT1 polymorphisms can interact with several occupational exposures to significantly modify the risk of RCC among exposed subjects.
  [Buzio L, De Palma G, Mozzoni P, et al. 2003. Occup Environ Med. 60(10):789-93]
• Occupational risk factors for renal cell cancer. An Italian case-control study.
  “Prolonged” occupational exposures to pesticides is associated with an increased risk for renal cell cancer (OR 2.0).
  [Buzio, L., et al. 2002. Med Lav 93(4):303-309.]
• Renal cell carcinoma and occupational exposure to chemicals in Canada
  An increased risk of renal cell carcinoma in males is associated with exposure to herbicides (1.6 OR) and pesticides (1.8 OR) and in particular a dose-response relationship for herbicides.
  [Hu, J., et al. 2002. Occup Med 52(3):157-164.]
• 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.]
• Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.
  Parental agricultural exposure to pesticides is associated with Wilms’ tumor, as well as other forms of cancer.
  [Kristensen, P., et al. 1996. Int J Cancer 65(1):39-50]
• Parental exposures to pesticides and risk of Wilms’ tumor in Brazil
  Elevated risk is found for farm work involving paternal (3.24 OR) and maternal (128.6 OR) frequent use of pesticides.
  [Sharpe, C.R., et al. 1995. Am J Epidemiol 141(3):210-217.]
• Occupational risk factors for renal-cell carcinoma in Denmark
  Risk of renal-cell carcinoma was found to be associated with employment as a truck driver, exposure to gasoline, other hydrocarbons, and insecticides and herbicides. The risk of renal-cell carcinoma was higher in the lower socioeconomic strata for both the men and the women.
  [Mellemgaard, A., et al. 1994. Scand J Work Environ Health 20(3):160-165.]
• Cancer among farmers in central Italy
  A case-referent study of Italian farmers finds a significantly increased risk of kidney cancer among farmers with greater than 10 years experience and a possible relationship between olives and potato growing and kidney cancer.
  [Forastiere, F, et al. 1993. Scand J Work Environ Health 19(6):382-389.]
• Risk factors for Wilms tumor
  A study examining nonoccupational risk factors for Wilms tumor finds an association with a history of household insect extermination.
  [Olshan, A.F., et al. 1993. Cancer 72(3):938-944.]

Kidney Function/Disease

• Exploring the toxicity of thiamethoxam on aquatic ecosystems: an overarching assessment of biochemical parameters, genotoxicity, fish flesh residues and histological alterations in Nile tilapia
  This study assessed the effect of thiamethoxam on the Nile tilapia (Oreochromis niloticus) under subacute and chronic exposure. The study focused on biochemical markers, genetic damage, pesticide residue levels in fish flesh, and histopathological changes in fish exposed to different concentrations of thiamethoxam (25, 50) for 30 days and (100, 250 mg/L) for 4 days. The study found that prolonged exposure to high doses of thiamethoxam (50 mg/L for 30 days) had significant negative effects on fish health. This exposure led to increased levels of urea and ALT in the blood, indicating potential damage to the kidneys and liver. Additionally, thiamethoxam caused oxidative stress, as evidenced by elevated levels of MDA and upregulated TLR2 gene expression. Thiamethoxam also negatively impacted the fish’s antioxidant defense system. It significantly reduced the expression of key antioxidant genes like ghrelin and catalase, particularly at 250 mg/L for 4 days. The total antioxidant capacity (TAC) and superoxide dismutase (SOD) levels remained relatively stable, except for slight decreases at the highest dose. Thiamethoxam residues were detected in the muscle tissue of fish, with the highest levels found in the 250 mg/L for 4 days. Histological examination revealed severe degenerative changes in the gills and liver tissues of the fish exposed to thiamethoxam, with the severity of the damage increasing with the concentration of the pesticide. In conclusion, cautions must be taken when we use neonicotinoids due to its negative feedback impact on Nile Tilapia fish health and consequently affect humans as a final consumer.
  [Mansour, A. et al. (2025) Exploring the toxicity of thiamethoxam on aquatic ecosystems: an overarching assessment of biochemical parameters, genotoxicity, fish flesh residues and histological alterations in Nile tilapia, Environmental Pollutants and Bioavailability. Available at: https://www.tandfonline.com/doi/full/10.1080/26395940.2025.2493050.]
• Chronic kidney disease from agricultural communities—association and accumulation of hexachlorobenzene, malathion, and parathion pesticides
  Objective
  There is an increasing prevalence of chronic kidney disease (CKD) reported from agricultural communities in tropical climates, and pesticide use has been implicated in its causation. The primary objective of the study was to compare the serum and urine levels of commonly used pesticides in the region, between subjects with CKD and their matched healthy controls.

  Methods
  A list of 150 commonly used pesticides used in the region was prepared and qualitative screening performed on sera from thirty participants. A total of 36 pesticides were identified using gas chromatography tandem mass spectrometry, including 15 organophosphates, 8 organochlorines, and 13 pyrethroids, for further quantitative estimation. Patients with unexplained chronic kidney disease, not requiring dialysis, and matched healthy controls were enrolled, and their clinical characteristics, serum and urine levels of selected pesticides, estimated glomerular filtration rate (eGFR) and urinary pesticide adjusted for urinary creatinine (UPestCR) were measured.

  Results
  The serum levels of certain pesticides from all the three tested groups (organophosphates, organochlorines and pyrethroids) were found to be significantly elevated in patients with CKD than in controls—among organophosphates—malathion (0.43 vs. 0.23 ppb), parathion (4.32 vs. 3.23 ppb), carbophenothion (0.45 vs. 0.10 ppb), and azinphosmethyl (0.45 vs. 0.24 ppb), among organochlorines—chloroneb (1.39 vs. 0.83 ppb), beta HCH (0.29 vs. 0.04 ppb), pp’-DDE (1.08 vs. 0.55 ppb) and among pyrethroids—transfluthrin (1.88 vs. 0.83 ppb), flucythrinate 1 (2.49 vs. 1.42 ppb), and flucythrinate 2 (26.98 vs. 15.68 ppb) ( all with p < 0.0001). UPestCR of many of the tested pesticides were significantly higher in the control group than in the CKD cases. Multivariate regression showed significant association between serum levels of three non-renally eliminated pesticides hexachlorobenzene, malathion, parathion levels, and low eGFR.

  Conclusion
  Serum levels of many commonly used pesticides are increased in patients with unexplained chronic kidney disease when compared to controls. Reduced renal elimination might account for the possible bioaccumulation of these pesticides in these patients with CKD.
  [Verma, J. et al. (2024) Chronic kidney disease from agricultural communities-association and accumulation of hexachlorobenzene, malathion, and parathion pesticides, Toxicology and Environmental Health Sciences. Available at: https://link.springer.com/article/10.1007/s13530-024-00222-y. ]

• Physiological responses of oxidative damage, genotoxicity and hematological parameters of the toxic effect of neonicotinoid-thiamethoxam in Oreochromis niloticus
  The purpose of investigation assessed the impacts of neonicotinoid thiamethoxam (TMX) at sublethal concentrations in hematological profile and renal function of Oreochromis niloticus. In the experiment, fish were exposed to TMX in four groups (0, 50, 100 and 150 ppm) for 7 days. At the end of the experiment, biochemical analysis of blood samples showed that the parameters indicating renal function showed a significant increase in serum enzymes ALT, AST, ALP and metabolites (BUN, urea, uric acid, creatinine and cortisol) concentrations, while albumin concentration decreased in a dose-dependent manner compared to the control group. In parallel with the decrease in Na+, K+ and Ca+2 in blood ion levels, there was a significant decrease in the activity of Na+/K+ ATPase, Ca+2 ATPase and AChE enzyme, levels of GSH and HSP70 in kidney tissue in TMX groups compared to the control group. It was determined that the toxic effect of TMX caused a significant increase in TBARS, PC, 8-OHdG levels, respectively. In conclusion, our study shows that TMX causes dose-dependent toxic effects, with knock-on effects on physiological processes regarding the hematological profile and renal function of O. niloticus.
  [Temiz, Ö., & Kargın, D. (2024). Physiological responses of oxidative damage, genotoxicity and hematological parameters of the toxic effect of neonicotinoid-thiamethoxam in Oreochromis niloticus. Environmental toxicology and pharmacology, 106, 104377. https://doi.org/10.1016/j.etap.2024.104377]
• Toxicological assessment of bromoxynil and 2-methyl-4-chlorophenoxyacetic acid herbicide in combination on Cirrhinus mrigala using multiple biomarker approach
  The widespread application of herbicides raises concerns about their impact on non-target aquatic organisms. This study aimed to evaluate the toxicity of a commercially available herbicide formulation containing Bromoxynil+MCPA (2-Methyl-4-chlorophenoxyacetic acid) on Cirrhinus mrigala (economically significant fish). A total of 210 juvenile fish were subjected to a triplicate experimental setup, with 70 fish allocated to each replicate, exposed to seven different concentrations of herbicide: 0 mg/L, 0.133 mg/L, 0.266 mg/L, 0.4 mg/L, 0.5 mg/L, 0.66 mg/L, and 0.8 mg/L, respectively, for a duration of 96 h. The median lethal concentration (LC50) was determined to be 0.4 mg/L. Significant hematological alterations were observed, including decreases in RBC counts, hemoglobin, hematocrit, and lymphocyte counts, along with an increase in erythrocyte indices. Biochemical analysis revealed elevated levels of neutrophils, WBCs, bilirubin, urea, creatinine, ALT, AST, ALP, and glucose in treated groups. Morphological abnormalities in erythrocytes and histopathological changes in gills, liver, and kidneys were noted. Pathological alterations in gills, liver and kidneys including epithelial cell uplifting, lamellar fusion, hepatolysis, and renal tubule degeneration were observed. Oxidative stress biomarkers such as TBARS (Thiobarbituric Acid Reactive Substance), ROS (Reactive Oxygen Species), and POD (Peroxides) activity increased, while antioxidant enzymatic activities decreased as toxicant doses increased from low to high concentrations. The study reveals that Bromoxynil+MCPA significantly disrupts physiological and hematobiochemical parameters in Cirrhinus mrigala, which highlights the substantial aquatic risks. In conclusion, the herbicide formulation induced significant alterations in various fish biomarkers, emphasizing their pivotal role in assessing the environmental impact of toxicity. This multi-biomarker approach offers valuable insights regarding the toxicological effects, thereby contributing substantially to the comprehensive evaluation of environmental hazards.
  [Afzal, F., Ghaffar, A., Jamil, H., Abbas, G., Tahir, R., & Ataya, F. S. (2024). Toxicological assessment of bromoxynil and 2-methyl-4-chlorophenoxyacetic acid herbicide in combination on Cirrhinus mrigala using multiple biomarker approach. The Science of the total environment, 926, 172019. https://doi.org/10.1016/j.scitotenv.2024.172019]
• Assessment of the impact of glyphosate and 2,4-D herbicides on the kidney injury and transcriptome changes in obese mice fed a Western diet.
  The development of chronic kidney disease has been associated with comorbidities resulting from the consumption of Westernized dietary (WD) patterns, including obesity and other metabolic dysfunctions. Kidneys also have a crucial role in the metabolism and excretion of xenobiotics, including herbicides. There is limited knowledge regarding the simultaneous exposure to WD and glyphosate (glypho) and 2,4-D, the most used herbicides globally. Thus, this study examined whether exposure to glypho and/or 2,4-D, either individually or in mixed, could impact the early effects of WD intake on kidney histology and gene expression in a rodent model. Male C57BL6J mice were fed a WD containing 20% lard, 0.2% cholesterol, 20% sucrose, and high sugar solution with 23.1 and 18.9 g/L of D-fructose and D-glucose for six months. During this period, the mice also received glypho (0.05 or 5 mg/kg/day), 2,4-D (0.02 or 2 mg/kg/day), or a mixture of both (0.05 +0.02, 5 +2 mg/kg/day) via intragastric administration five times per week. The doses were within or below the established regulatory limits. While single or mixed exposures did not alter WD-induced obesity, tubular lipid vacuolation, or increased serum creatinine levels; the exposure to higher doses of the mixture (5 +2) reduced the mesangial matrix area and tubular cell proliferation, while increasing the density of F4/80 macrophages in the renal interstitium. In terms of transcriptomic analysis, the herbicide mixture altered the expression of 415 genes in the kidney, which were found to be associated with immune response processes, particularly those related to phagocyte activity. While discrete, findings indicate that herbicide mixtures, rather than single exposures, might induce minor deleterious effects on the kidneys of obese mice under WD intake.
  [Romualdo, G.R., de Souza, J.L.H., Valente, L.C. and Barbisan, L.F., 2023. Toxicology Letters, 385, pp.1-11.]
• Association of indoor use of pesticides with CKD of unknown origin
  Chronic kidney disease (CKD) is a growing global health problem. Recently, an epidemic of CKD of unknown origin (CKDu), a form of CKD seen mostly in agricultural communities, has been emerged. One of the proposed causes of CKDu is pesticide use in farmers. On the other hand, the research on relation between indoor use of pesticides and CKDu is little. In this study, we aimed to investigate the association between indoor use of pesticide as well as the exposure time with CKDu. This study was done as part of the population-based cohort of Prospective Epidemiological Research Studies in Iran. We used the baseline data of the Zahedan Adult Cohort Study. All subjects with diabetes mellitus and/or hypertension, estimated glomerular filtration rate (eGFR) between 60–89 ml/min/1.73 m2, and unavailable creatinine measurement were excluded. Subjects with an eGFR of less than 60 ml/min/1.73 m2 were defined as having CKDu, and their data were compared with those with an eGFR of more than 90 ml/min/1.73 m2. Data regarding indoor pesticide use and duration of exposure were obtained through a questionnaire. After applying the exclusion criteria, 1079 subjects remained in the study. Female sex, single marital status, low physical activity, triglyceride (TG) levels of more than 150 mg/dl, body mass index (BMI) of more than 25 kg/m2, non-smokers, indoor pesticide use, and high pesticide exposure time were associated with CKDu. The effects of age, female sex, TG levels more than 150 mg/dl, pesticide use (OR 1.36; 95% CI 1.01–1.84), and high exposure time (third tertile of exposure time) compared to non-users (OR 1.64; 95% CI 1.07–2.51) remained significant in multivariable analysis.
  [Alvand, S., Alatab, S., Dalvand, S., Shahraki-Sanavi, F., Kaykhaei, M.A., Shahraki, E., Barar, E., Sepanlou, S.G. and Ansari-Moghaddam, A., 2023. Plos one, 18(7), p.e0277151.]
• Biopesticides as a promising alternative to synthetic pesticides: A case for microbial pesticides, phytopesticides, and nanobiopesticides
  Over the years, synthetic pesticides like herbicides, algicides, miticides, bactericides, fumigants, termiticides, repellents, insecticides, molluscicides, nematicides, and pheromones have been used to improve crop yield. When pesticides are used, the over-application and excess discharge into water bodies during rainfall often lead to death of fish and other aquatic life. Even when the fishes still live, their consumption by humans may lead to the biomagnification of chemicals in the body system and can cause deadly diseases, such as cancer, kidney diseases, diabetes, liver dysfunction, eczema, neurological destruction, cardiovascular diseases, and so on. Equally, synthetic pesticides harm the soil texture, soil microbes, animals, and plants. The dangers associated with the use of synthetic pesticides have necessitated the need for alternative use of organic pesticides (biopesticides), which are cheaper, environment friendly, and sustainable. Biopesticides can be sourced from microbes (e.g., metabolites), plants (e.g., from their exudates, essential oil, and extracts from bark, root, and leaves), and nanoparticles of biological origin (e.g., silver and gold nanoparticles). Unlike synthetic pesticides, microbial pesticides are specific in action, can be easily sourced without the need for expensive chemicals, and are environmentally sustainable without residual effects. Phytopesticides have myriad of phytochemical compounds that make them exhibit various mechanisms of action, likewise, they are not associated with the release of greenhouse gases and are of lesser risks to human health compared to the available synthetic pesticides. Nanobiopesticides have higher pesticidal activity, targeted or controlled release with top-notch biocompatibility and biodegradability. In this review, we examined the different types of pesticides, the merits, and demerits of synthetic pesticides and biopesticides, but more importantly, we x-rayed appropriate and sustainable approaches to improve the acceptability and commercial usage of microbial pesticides, phytopesticides, and nanobiopesticides for plant nutrition, crop protection/yield, animal/human health promotion, and their possible incorporation into the integrated pest management system.
  [Ayilara, M.S. et al. (2023) Biopesticides as a promising alternative to synthetic pesticides: A case for microbial pesticides, phytopesticides, and nanobiopesticides, Frontiers in Microbiology. Available at: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1040901/full. ]
• Glyphosate-induced liver and kidney dysfunction, oxidative stress, immunosuppression in Nile tilapia, but ginger showed a protection role
  The water-borne herbicides are involved in the toxicity of aquatic animals resulting in impaired health status and low productivity. Dietary medicinal herbs present a practical solution to relieve the impacts of herbicides toxicity on the performances of aquatic animals. Herein, we investigated the toxicity of commercial glyphosate-induced oxidative stress, immunosuppression, liver and kidney dysfunction, and the protective role of ginger or ginger nanoparticles in Nile tilapia. Fish were allocated into four groups: the first group presented the control without glyphosate toxicity and ginger feeding, the second group intoxicated with glyphosate at 0.6 mg/L and fed ginger free diet, the third group intoxicated with glyphosate and fed ginger at 2.5 g/kg, and the fourth group intoxicated with glyphosate and fed ginger nanoparticles at 2.5 g/kg. Fish were kept under the experimental conditions for four weeks, and the samples of blood and tissues were collected after 2 and 4 weeks. Markedly, fish exposed to glyphosate showed the highest ALT and AST activities, glucose and cortisol levels, and malondialdehyde levels (MDA) in gills and tissues. While fish in the control and fish intoxicated with glyphosate and fed ginger nanoparticles had the lowest ALT and AST activities, glucose and cortisol levels, and MDA levels after 2 and 4 weeks (P < 0.05). Fish fed dietary ginger had lower ALT and AST activities, glucose and cortisol levels, and MDA levels than the glyphosate intoxicated group after 2 and 4 weeks (P < 0.05). Interestingly, fish-fed ginger nanoparticles showed lower urea and creatinine levels and higher total protein, albumin, and globulin than the glyphosate intoxicated group (P < 0.05) and similar to the control (P > 0.05). Further, fish intoxicated with glyphosate and fed ginger nanoparticles had the highest GSH, lysozyme activity, and immunoglobulin levels after 2 and 4 weeks (P < 0.05). In conclusion, ginger nanoparticles are superior to the standard ginger form in enhancing the antioxidative and immune responses of Nile tilapia exposed to glyphosate.
  [Abdelmagid, A.D., Said, A.M., Abd El-Gawad, E.A. et al. Glyphosate-induced liver and kidney dysfunction, oxidative stress, immunosuppression in Nile tilapia, but ginger showed a protection role. Vet Res Commun 47, 445–455 (2023). https://doi.org/10.1007/s11259-022-09961-0]
• Human serum lipidomics analysis revealed glyphosate may lead to lipid metabolism disorders and health risks
  Glyphosate-based herbicides (GBH) are one of the most widely used pesticides worldwide. Industrial workers in glyphosate-based herbicides manufacture are the populations who experience long-term exposure to high glyphosate levels. The impacts of glyphosate on human health are the important public health problem of great concern. Up to date, the potential adverse effects of glyphosate on humans or other mammals have been reported in multiple studies. However, limited research is available on lipid alternations related to human exposure to glyphosate. In fact, the perturbations in some lipid metabolisms have been found in industrial workers in previous work. This study aims to explore the serum lipidomic characterization and to understand the underlying mechanisms of health risks associated with glyphosate exposure. A nontargeted lipidomics study was conducted to investigate the 391 serum samples from the general population and chemical factory workers. It was demonstrated that glyphosate caused significant perturbations of 115 differentially expressed lipids. The main manifestations were the elevation of circulating diacylglycerols (DG), cholesteryl esters (CE), ceramides (Cer), sphingomyelins (SM), lysophosphatidylethanolamines (LPE) and phosphatidylcholines (PC), and the decrease of ysophosphatidylcholines (LPC), triacylglycerols (TG), fatty acids (FA) and phosphatidylethanolamines (PE). A total of 88 lipids were further screened as potential lipid biomarkers associated closely with glyphosate using partial correlation analysis, and five of which (including PC 16:0/18:2; O, PC 18:0/18:2; O, PC 18:0/20:4; O, PC O-40:9 and CE 18:3) showed excellent superior performance (AUC = 1) to evaluate and monitor health risks due to glyphosate exposure. The present work discovered glyphosate-induced potential health risks, including chronic hepatic and renal dysfunction, atherosclerosis, cardiovascular disease and neurodegenerative diseases from a lipidomic perspective, and could inform the identification of early indicators and interpretation of biological mechanisms to detect health risks of the glyphosate-exposed populations as early as possible.
  [Zhang, F., Zhang, Q., Liu, X., Gao, M., Li, X., Wang, Y., Chang, Y., Zhang, X., Huo, Z., Zhang, L. and Shan, J., 2023. Environment International, 171, p.107682.]
• Pesticides and insulin resistance-related metabolic diseases: Evidences and mechanisms.
  The use of pesticides in the past century has lot helped humankind in improving crops' field and general hygiene level. Nevertheless, there has been countless evidences on the toxic effects of pesticides on the living systems. The link of exposure to pesticides with different human chronic diseases in the context of carcinogenicity, neurotoxicity, developmental toxicity, etc., have been evaluated in various types of studies. There are also some evidences on the link of exposure to pesticides with higher incidence of metabolic diseases associated with insulin resistance like diabetes, obesity, metabolic syndrome, hypertension, polycystic ovary syndrome and chronic kidney diseases. Physiologically, weakening intracellular insulin signaling is considered as a compensatory mechanism for cells to cope with cellular stresses like xenobiotic effects, oxidative stress and inflammatory responses, but it can pathologically lead to a defective cycle with lowered sensitivity of the cells to insulin which happens in metabolic disorders. In this work, the data related to metabolic toxicity of pesticides categorized in the mentioned metabolic diseases with a focus on the effects of pesticides on insulin signaling pathway and the mechanisms of development of insulin resistance will be systematically reviewed and presented.
  [Arab, A. and Mostafalou, S., 2023. Pesticide Biochemistry and Physiology, p.105521.]
• Biochemical and Histological Evaluation of Penoxsulam Herbicide on an Animal Model
  Aims: Many herbicides react to the body system and might effect the activity of hormones in the human body. The present work aims to determine the potential impact of 90 days of repeated exposure to Penoxsulam herbicide by oral gavage on the Liver, Kidney, Thyroid endocrine profile and biochemical stress in the wistar rat model.
  Study design: The primary study was performed to Wistar rats grouped into 6 groups. Four groups were picked for low dose, middle dose, high dose, and high recovery dose, respectively. They were administered the Penoxsulam at dose levels of 100, 300, 500 mg/kg body weight. Similarly, 2 recovery groups were classified as control and recovery control groups, and doses were administered to them only
  through the corn oil (vehicle) via the oral route with the help of a suitable cannula for 90 days.
  Place and Duration of Study: Toxicology department, Shriram Institute for Industrial Research, Delhi (INDIA), July 2020 and June 2021.
  Methodology: In this study, healthy 60 male and 60 female Wistar rats aged 6-8 weeks, weighing 130-190 gm, were used. Before commencing the study, permission from IAEC (Institutional animal ethics committee) was taken for this experiment (CPCSEA).
  Results: This study evaluates significant changes in the body weight of rats; moreover, Penoxsulam elevated the significance level of SGOT, SGPT, BUN, Urea, and Creatinine. No alterations were seen in Hematology parameters and Ophthalmology examination. Also, physiological changes were examined
  after exposure to penoxsulam in rats.
  Conclusion: Therefore, Penoxsulam showed harmful toxic effects on the Kidney and Liver. However, no alteration has been seen in the thyroid profile (T3 triiodothyronine, T4 thyroxine, TSH thyroid-stimulating hormone) of Wistar rats during the experimentation period.
  [Chaurasia, V., Aggarwal, M. and Garg, M. (2022) Biochemical and Histological Evaluation of Penoxsulam Herbicide on an Animal Model, Journal of Pharmaceutical Research International. Available at: https://www.researchgate.net/publication/358594997_Biochemical_and_Histological_Evaluation_of_Penoxsulam_Herbicide_on_an_Animal_Model.]
• Harmful health effects of pesticides used on museum textile artifacts - overview
  The paper discusses the types of fibers contained in the museum textile artifacts and the types of pests and pesticides. Also, the main health problems associated with pesticide exposure are presented. Textile fibers represent an excellent source of food for microbes and insects. The key to the long-term preservation of textiles is by implementing an integrated management program for pest and environmental conditions control. The main types of pesticides are insecticides, herbicides, fungicides, rodenticides, acaricides, and fumigants and a way for classification can be made according to the LD50 (lethal dose) value which evaluates the toxicity of a pesticide. Depending on the LD50 values, pesticides can be very toxic, moderately toxic, slightly toxic, and relatively non-toxic. Exposure to pesticides can occur through 4 four routes: oral, dermal, respiratory, and eye exposure. The main diseases that can be associated with exposure to pesticides are discussed in the paper. In the end, a basic set of precautionary recommendations when handling museum objects that may contain hazardous materials was presented.
  [Tănăsescu, E.C. and Lite, M.C., 2022. Ecotoxicology and Environmental Safety, 247, p.114240.]
• Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: The CaReMe CKD study
  Background
  Digital healthcare systems data could provide insights into the global prevalence of chronic kidney disease (CKD). We designed the CaReMe CKD study to estimate the prevalence, key clinical adverse outcomes and costs of CKD across 11 countries.
  Methods
  Individual-level data of a cohort of 2·4 million contemporaneous CKD patients was obtained from digital healthcare systems in participating countries using a pre-specified common protocol; summarized using random effects meta-analysis. CKD and its stages were defined in accordance with current Kidney Disease: Improving Global Outcomes (KDIGO) criteria. CKD was defined by laboratory values or by a diagnosis code.
  Findings
  The pooled prevalence of possible CKD was 10·0% (95% confidence interval 8.5‒11.4; mean pooled age 75, 53% women, 38% diabetes, 60% using renin-angiotensin-aldosterone system inhibitors). Two out of three CKD patients identified by laboratory criteria did not have a corresponding CKD-specific diagnostic code. Among CKD patients identified by laboratory values, the majority (42%) were in KDIGO stage 3A; and this fraction was fairly consistent across countries. The share with CKD based on urine albumin-creatinine ratio (UACR) alone (KDIGO stages one and two) was 29%, with a substantial heterogeneity between countries. Adverse events were common; 6·5% were hospitalized for CKD or heart failure, and 6·2% died, annually. Costs for renal events and heart failure were consistently higher than costs for atherosclerotic events in CKD patients across all countries.
  Interpretation
  We estimate that CKD is present in one out of ten adults. These individuals experience significant adverse outcomes with associated costs. The prevalence of CKD is underestimated when using diagnostic codes alone. There is considerable public health potential in diagnosing CKD and providing treatments to those currently undiagnosed.
  [Sundström, J. et al. (2022) Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: The Careme CKD study, The Lancet Regional Health Europe. Available at: https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(22)00132-6/fulltext. ]
• Association of Pesticides and Kidney Function among Adults in the US Population 2001–2010
  Chronic kidney disease of unknown cause is prevalent in a range of communities; however, its etiology remains unclear. We examined the association between pesticide exposures and the risk of kidney function loss using four waves of the National Health and Nutrition Examination Survey (NHANES) to identify a pathological pathway. We pooled data from four cross-sectional waves of NHANES, with 41,847 participants in total. Exposure to malathion increased the risk of low kidney function (aOR = 1.26, 95% CI = 1.01–1.56) in the adjusted model. Increased risk of low kidney function was not found among those exposed to 2,4-D (aOR = 0.88, 95% CI = 0.72–1.09), 3,5,6-trichloropyridinol (aOR = 0.96, 95% CI = 0.83–1.12), and 3-PBA (aOR = 1.03, 95% CI = 0.94–1.13). Our findings provide evidence of altered kidney function in people exposed to malathion, highlighting the potential of organophosphate pesticides’ role in renal injury.
  [Wan, E.T., Darssan, D., Karatela, S., Reid, S. and Osborne, N. Int. J. Environ. Res. Public Health.]
• Systemic effects of the pesticide mancozeb - A literature review
  Objective: The purpose of this literature review is to document what has already been scientifically published about the pesticide Mancozeb and its potential systemic complications.

  Materials and methods: Data were collected during the months of July, August and September 2020, from the Medline and PubMed databases, in the Portuguese, English and Spanish, covering articles written in the last 20 years. Twenty-one studies were selected for analysis.

  Results: The results found in this review study, indicate that Mancozeb is potentially damaging to health, appearing as an increase in ethylethiourea (ETU) dosages in most studies.

  Conclusions: About the widespread use of Mancozeb, the studies found show that this fungicide is a potential cause of several health problems, mainly hepatic, renal and genotoxic, demonstrating with an increase in ETU dosages, as well as liver enzymes in most studies, corroborating the idea that the deliberate use of the product can induce potential systemic complications, and is a public health problem.
  [Dall’Agnol, J. (2021) Systemic effects of the pesticide mancozeb - A literature review, European Review for Medical and Pharmacological Sciences. Available at: https://pubmed.ncbi.nlm.nih.gov/34156691/. ]

• Water sources and kidney function: investigating chronic kidney disease of unknown etiology in a prospective study
  A chronic Kidney Disease of unknown etiology (CKDu) has emerged with disproportionately high prevalence across dry lowland agricultural communities globally. Here we present the results of a prospective cohort of 293 patients with CKDu in the endemic region of Wilgamuwa, Sri Lanka, in whom we measured baseline kidney function and undertook quarterly follow up over 2 years. Well water was the primary historic drinking water source in the region, although a majority (68%) of participants reported switching to reverse osmosis water during study follow ups. Participants who reported ever drinking from well water had estimated glomerular filtration rates −6.7 (SD: 2.8) ml/min/1.73 m2 lower than participants who did not drink from well water historically (p = 0.0184) during the study period. Geospatial analysis identifies a cluster within the region where CKDu progression is significantly higher than the surrounding area. Samples of household wells (n = 262) indicated 68% had detectable agrochemical compounds with concentration above global water quality standards. It is expected that the detected contaminants compounds are indicators of poor water quality and that there is likely additional agrochemical exposure including commercial additives that may contribute to CKDu onset and/or progression. Thus, our study finds that well water exposure during a person’s lifetime in this region is associated with kidney function decline and identifies and quantifies putative nephrotoxic agrochemicals above safe drinking water concentrations in these wells.
  [Vlahos, P., Schensul, S.L., Anand, S., Shipley, E., Diyabalanage, S., Hu, C., Ha, T., Staniec, A., Haider, L., Schensul, J.J. and Hewavitharane, P. npj Clean Water, 4(1), pp.1-7.]
• 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.]
• Chronic kidney disease and household behaviors in Sri Lanka: Historical choices of drinking water and agrochemical use
  This paper examines whether there are systematic differences in the historical behaviors of households that are affected and unaffected by chronic kidney disease (CKD) in Sri Lanka pertaining to their water source choices, water treatment practices, and agrochemical use. This analysis is motivated by the Sri Lankan government's largest policy response to this epidemic - to encourage communities to switch from untreated well water to publicly provided alternatives. We use recall methods to elicit information on the drinking water source and treatment choices of households over an 18-year period from 2000-2017. Our analysis is based on a survey of 1497 rural ground-water dependent households in the most CKD-affected areas of the 10 districts of Sri Lanka with the highest prevalence of CKD. Our main findings are that (a) households that have ever used a pump to extract (typically deep) drinking water from a household well are more likely to be affected by CKD; (b) we fail to find a relationship between disease status and households' use of buckets to extract (typically shallow) groundwater from their wells; and (c) those who have ever treated their shallow well water by boiling it are less likely to be affected by CKD. We also find that a greater share of CKD affected households historically used agrochemicals, used wells that were geographically removed from surface water sources, and displayed lower proxies of wealth. The implications of these findings are fourfold. First, since the systematic differences in the historical patterns of water sources and treatments used by CKD affected and non-affected households are modest, the sources of water and the treatment practices themselves may not be the sole risk factors in developing CKD. Second, although we find a negative association between boiling water and the probability of CKD, it is not obvious that a public policy campaign to promote boiling water is an appropriate response. Third, the hydrochemistry of deep and shallow well water needs to be better understood in order to shed light on the positive relationship between deep well water and disease status, and on why boiling shallow but not deep well water is associated with a lower probability of CKD. Fourth, there is a need for a deeper understanding of other risk factors and of the efficacy of preventative programs that provide alternative sources of household drinking water.
  [Balasubramanya, S., Stifel, D., Horbulyk, T. and Kafle, K., 2020. Economics & Human Biology, 37, p.100862.]
• Methyl thiophanate-induced toxicity in liver and kidney of adult rats: a biochemical, molecular and histopathological approach
  The aim of this study was to elucidate the redox effects of Thiophanate methyl (MT) in the rat liver and kidney. Our results showed, after 3 days of MT injection (700 mg/kg), an increase in malondialdehyde (MDA), hydrogen peroxide and advanced oxidation protein products levels. Glutathione peroxidase and superoxide dismutase activities were also remarkably increased in the liver but decrease in the kidney. Glutathione and vitamin C values were significantly reduced. The changes in biochemical parameters were substantiated by histological and molecular data. A smear without ladder formation on agarose gel was shown, indicating random DNA degradation in the liver and the kidney of MT treated rats. The increase in cyclooxygenase-2 gene expression, marker of inflammation, and an increase in genes expression of glutathione peroxidase and superoxide dismutase in liver and their decrease in the kidney were also occurred after MT exposure. These data confirmed the pro-oxidant and genotoxic effects of this fungicide.
  [Feki, A., Ben Saad, H., Jaballi, I., Magne, C., Boudawara, O., Zeghal, K. M., Hakim, A., Ben Ali, Y., & Ben Amara, I. (2017). Methyl thiophanate-induced toxicity in liver and kidney of adult rats: a biochemical, molecular and histopathological approach. Cellular and Molecular Biology, https://doi.org/10.14715/cmb/2017.63.2.4]
• Kidney biomarkers in MCPA-induced acute kidney injury in rats: Reduced clearance enhances early biomarker performance
  For improved early detection and assessment of severe acute kidney damage following accidental or intentional ingestion of the herbicide MCPA, we compared a panel of 14 novel kidney injury biomarkers with plasma creatinine. Male Wistar rats received four different oral doses of MCPA and plasma and urine biomarker levels were measured at 8, 24 and 48 h after MCPA exposure. Diagnostic performances using absolute levels, urine levels normalized to urine creatinine or urinary excretion rate were determined by ROC analysis. Plasma creatinine remained the best early biomarker for predicting histological changes at 48 h. The performance of plasma cystatin C in mirroring kidney function was similar to that of plasma creatinine. While urine concentrations were generally less predictive, normalization by urine creatinine greatly improved the performance of several biomarkers. This may be due to an apparent amplification of the biomarker signal on normalizing to creatinine, in the presence of a declining glomerular filtration rate prior to reaching steady state. Normalized 8 h osteopontin and albumin concentrations outperformed other normalized biomarkers in predicting histological changes at later times. Normalized urinary kidney injury molecule-1 at 48 h also correlated well with the degree of kidney damage.
  [Wunnapuk, K. (2014) Kidney biomarkers in MCPA-induced acute kidney injury in rats: Reduced clearance enhances early biomarker performance, Toxicology Letters. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0378427414000290. ]
• Subacute oral toxicity of combinations of selected synthetic pyrethroids, piperonyl butoxide, and tetramethrin in rats
  In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes. Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days. During the study period, mortality and serious clinical findings were not observed in any animal. However, feed consumptions decreased in groups 1 and 3 (p < 0.05). Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0.05). Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups. Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0.05). The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver. It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.
  [Yavuz O, Aksoy A, Das YK, et al. (2013). Subacute oral toxicity of combinations of selected synthetic pyrethroids, piperonyl butoxide, and tetramethrin in rats. Toxicology and Industrial Health. https://journals.sagepub.com/doi/abs/10.1177/0748233712469651]
• Acute Renal Failure following Penoxsulam poisoning
  Penoxsulam is a fluorinated benzenesulfonamide. It is a herbicide used in dry and wet seeded crops mainly in rice paddies in Sri Lanka. Toxicity following human ingestion has not been reported before. Eye contact with penoxsulam dust or granules may cause slight irritation, although corneal injury is unlikely. Harmful effects are not anticipated from swallowing small amounts. In animal studies, the predominant target organ were the kidney and the urothelium. Due to limited solubility in urine, penoxsulam forms crystals/calculi in the pelvis of the kidney and the lumen of the urinary bladder. Raised blood urea, reduced urine osmolality and increased urine volume were noted as secondary effects. Renal tubular degeneration was also sometimes observed. A treatment-related chronic progressive glomerulonephropathy was observed in male rats. Kidney damage seen in shorter-term studies was generally not exacerbated in longer-term studies.

  Human intoxication with Penoxsulam has not been reported before. We wish to report a patient who developed acute renal failure requiring dialysis. It is important to be aware of the possible renal toxicity of this herbicide.
  [Karunatilake, H. (2011). Acute Renal Failure following Penoxsulam poisoning. Clinical Toxicology, 50(1), 79. https://doi.org/10.3109/15563650.2011.633492]

• Short-term oral and dermal toxicity of MCPA and MCPP
  The herbicides 2-methyl-4-chlorophenoxy acetic acid (MCPA) and 2-(2-methyl-4-chlorophenoxy) propionic acid (MCPP or mecoprop) were tested for 90 days in rats. The compounds were added to the diet at levels of 0, 50, 400 and 3200 ppm. Growth, food intake, mortality, haematology, blood and liver chemistry, organ weights and histopathology were used as criteria.

  The main effects of both compounds were growth retardation and elevated relative kidney weights at levels of 400 ppm and more. The 50 ppm dose level can be considered as a non-toxic-effect level in the 90-day study.

  In subacute dermal studies in rabbits during 3 weels the dosage were 0, 0.5, 1.0 and 2 g MCPA or MCPP per kg body weight. Thereafter followed a recovery period of 2 weeks. Growth, mortality, skin reaction, haematology, organ weights (MCPP) and histopathology were recorded and determined. Both compounds caused slight to moderate erythema at all dose levels, whereas elasticity of the skin was decreased. In both experiments the skin returned to normal during the recovery period. Weight loss was observed at all dose levels. In the MCPA experiments high mortality and histopathological changes in the liver, kidneys, spleen and thymus were recorded at the two highest dose levels. The cause of this could have been either the treatment with MCPA or a dysbacteria infection which developed during the experiment.
  [Verschuuren, H. et al. (1975) Short-term oral and dermal toxicity of MCPA and MCPP, Toxicology. Available at: https://www.sciencedirect.com/science/article/abs/pii/0300483X75900360. ]

Kidney Function/Disease

• Exploring the toxicity of thiamethoxam on aquatic ecosystems: an overarching assessment of biochemical parameters, genotoxicity, fish flesh residues and histological alterations in Nile tilapia
  This study assessed the effect of thiamethoxam on the Nile tilapia (Oreochromis niloticus) under subacute and chronic exposure. The study focused on biochemical markers, genetic damage, pesticide residue levels in fish flesh, and histopathological changes in fish exposed to different concentrations of thiamethoxam (25, 50) for 30 days and (100, 250 mg/L) for 4 days. The study found that prolonged exposure to high doses of thiamethoxam (50 mg/L for 30 days) had significant negative effects on fish health. This exposure led to increased levels of urea and ALT in the blood, indicating potential damage to the kidneys and liver. Additionally, thiamethoxam caused oxidative stress, as evidenced by elevated levels of MDA and upregulated TLR2 gene expression. Thiamethoxam also negatively impacted the fish’s antioxidant defense system. It significantly reduced the expression of key antioxidant genes like ghrelin and catalase, particularly at 250 mg/L for 4 days. The total antioxidant capacity (TAC) and superoxide dismutase (SOD) levels remained relatively stable, except for slight decreases at the highest dose. Thiamethoxam residues were detected in the muscle tissue of fish, with the highest levels found in the 250 mg/L for 4 days. Histological examination revealed severe degenerative changes in the gills and liver tissues of the fish exposed to thiamethoxam, with the severity of the damage increasing with the concentration of the pesticide. In conclusion, cautions must be taken when we use neonicotinoids due to its negative feedback impact on Nile Tilapia fish health and consequently affect humans as a final consumer.
  [Mansour, A. et al. (2025) Exploring the toxicity of thiamethoxam on aquatic ecosystems: an overarching assessment of biochemical parameters, genotoxicity, fish flesh residues and histological alterations in Nile tilapia, Environmental Pollutants and Bioavailability. Available at: https://www.tandfonline.com/doi/full/10.1080/26395940.2025.2493050.]
• Chronic kidney disease from agricultural communities—association and accumulation of hexachlorobenzene, malathion, and parathion pesticides
  Objective
  There is an increasing prevalence of chronic kidney disease (CKD) reported from agricultural communities in tropical climates, and pesticide use has been implicated in its causation. The primary objective of the study was to compare the serum and urine levels of commonly used pesticides in the region, between subjects with CKD and their matched healthy controls.

  Methods
  A list of 150 commonly used pesticides used in the region was prepared and qualitative screening performed on sera from thirty participants. A total of 36 pesticides were identified using gas chromatography tandem mass spectrometry, including 15 organophosphates, 8 organochlorines, and 13 pyrethroids, for further quantitative estimation. Patients with unexplained chronic kidney disease, not requiring dialysis, and matched healthy controls were enrolled, and their clinical characteristics, serum and urine levels of selected pesticides, estimated glomerular filtration rate (eGFR) and urinary pesticide adjusted for urinary creatinine (UPestCR) were measured.

  Results
  The serum levels of certain pesticides from all the three tested groups (organophosphates, organochlorines and pyrethroids) were found to be significantly elevated in patients with CKD than in controls—among organophosphates—malathion (0.43 vs. 0.23 ppb), parathion (4.32 vs. 3.23 ppb), carbophenothion (0.45 vs. 0.10 ppb), and azinphosmethyl (0.45 vs. 0.24 ppb), among organochlorines—chloroneb (1.39 vs. 0.83 ppb), beta HCH (0.29 vs. 0.04 ppb), pp’-DDE (1.08 vs. 0.55 ppb) and among pyrethroids—transfluthrin (1.88 vs. 0.83 ppb), flucythrinate 1 (2.49 vs. 1.42 ppb), and flucythrinate 2 (26.98 vs. 15.68 ppb) ( all with p < 0.0001). UPestCR of many of the tested pesticides were significantly higher in the control group than in the CKD cases. Multivariate regression showed significant association between serum levels of three non-renally eliminated pesticides hexachlorobenzene, malathion, parathion levels, and low eGFR.

  Conclusion
  Serum levels of many commonly used pesticides are increased in patients with unexplained chronic kidney disease when compared to controls. Reduced renal elimination might account for the possible bioaccumulation of these pesticides in these patients with CKD.
  [Verma, J. et al. (2024) Chronic kidney disease from agricultural communities-association and accumulation of hexachlorobenzene, malathion, and parathion pesticides, Toxicology and Environmental Health Sciences. Available at: https://link.springer.com/article/10.1007/s13530-024-00222-y. ]

• Physiological responses of oxidative damage, genotoxicity and hematological parameters of the toxic effect of neonicotinoid-thiamethoxam in Oreochromis niloticus
  The purpose of investigation assessed the impacts of neonicotinoid thiamethoxam (TMX) at sublethal concentrations in hematological profile and renal function of Oreochromis niloticus. In the experiment, fish were exposed to TMX in four groups (0, 50, 100 and 150 ppm) for 7 days. At the end of the experiment, biochemical analysis of blood samples showed that the parameters indicating renal function showed a significant increase in serum enzymes ALT, AST, ALP and metabolites (BUN, urea, uric acid, creatinine and cortisol) concentrations, while albumin concentration decreased in a dose-dependent manner compared to the control group. In parallel with the decrease in Na+, K+ and Ca+2 in blood ion levels, there was a significant decrease in the activity of Na+/K+ ATPase, Ca+2 ATPase and AChE enzyme, levels of GSH and HSP70 in kidney tissue in TMX groups compared to the control group. It was determined that the toxic effect of TMX caused a significant increase in TBARS, PC, 8-OHdG levels, respectively. In conclusion, our study shows that TMX causes dose-dependent toxic effects, with knock-on effects on physiological processes regarding the hematological profile and renal function of O. niloticus.
  [Temiz, Ö., & Kargın, D. (2024). Physiological responses of oxidative damage, genotoxicity and hematological parameters of the toxic effect of neonicotinoid-thiamethoxam in Oreochromis niloticus. Environmental toxicology and pharmacology, 106, 104377. https://doi.org/10.1016/j.etap.2024.104377]
• Toxicological assessment of bromoxynil and 2-methyl-4-chlorophenoxyacetic acid herbicide in combination on Cirrhinus mrigala using multiple biomarker approach
  The widespread application of herbicides raises concerns about their impact on non-target aquatic organisms. This study aimed to evaluate the toxicity of a commercially available herbicide formulation containing Bromoxynil+MCPA (2-Methyl-4-chlorophenoxyacetic acid) on Cirrhinus mrigala (economically significant fish). A total of 210 juvenile fish were subjected to a triplicate experimental setup, with 70 fish allocated to each replicate, exposed to seven different concentrations of herbicide: 0 mg/L, 0.133 mg/L, 0.266 mg/L, 0.4 mg/L, 0.5 mg/L, 0.66 mg/L, and 0.8 mg/L, respectively, for a duration of 96 h. The median lethal concentration (LC50) was determined to be 0.4 mg/L. Significant hematological alterations were observed, including decreases in RBC counts, hemoglobin, hematocrit, and lymphocyte counts, along with an increase in erythrocyte indices. Biochemical analysis revealed elevated levels of neutrophils, WBCs, bilirubin, urea, creatinine, ALT, AST, ALP, and glucose in treated groups. Morphological abnormalities in erythrocytes and histopathological changes in gills, liver, and kidneys were noted. Pathological alterations in gills, liver and kidneys including epithelial cell uplifting, lamellar fusion, hepatolysis, and renal tubule degeneration were observed. Oxidative stress biomarkers such as TBARS (Thiobarbituric Acid Reactive Substance), ROS (Reactive Oxygen Species), and POD (Peroxides) activity increased, while antioxidant enzymatic activities decreased as toxicant doses increased from low to high concentrations. The study reveals that Bromoxynil+MCPA significantly disrupts physiological and hematobiochemical parameters in Cirrhinus mrigala, which highlights the substantial aquatic risks. In conclusion, the herbicide formulation induced significant alterations in various fish biomarkers, emphasizing their pivotal role in assessing the environmental impact of toxicity. This multi-biomarker approach offers valuable insights regarding the toxicological effects, thereby contributing substantially to the comprehensive evaluation of environmental hazards.
  [Afzal, F., Ghaffar, A., Jamil, H., Abbas, G., Tahir, R., & Ataya, F. S. (2024). Toxicological assessment of bromoxynil and 2-methyl-4-chlorophenoxyacetic acid herbicide in combination on Cirrhinus mrigala using multiple biomarker approach. The Science of the total environment, 926, 172019. https://doi.org/10.1016/j.scitotenv.2024.172019]
• Assessment of the impact of glyphosate and 2,4-D herbicides on the kidney injury and transcriptome changes in obese mice fed a Western diet.
  The development of chronic kidney disease has been associated with comorbidities resulting from the consumption of Westernized dietary (WD) patterns, including obesity and other metabolic dysfunctions. Kidneys also have a crucial role in the metabolism and excretion of xenobiotics, including herbicides. There is limited knowledge regarding the simultaneous exposure to WD and glyphosate (glypho) and 2,4-D, the most used herbicides globally. Thus, this study examined whether exposure to glypho and/or 2,4-D, either individually or in mixed, could impact the early effects of WD intake on kidney histology and gene expression in a rodent model. Male C57BL6J mice were fed a WD containing 20% lard, 0.2% cholesterol, 20% sucrose, and high sugar solution with 23.1 and 18.9 g/L of D-fructose and D-glucose for six months. During this period, the mice also received glypho (0.05 or 5 mg/kg/day), 2,4-D (0.02 or 2 mg/kg/day), or a mixture of both (0.05 +0.02, 5 +2 mg/kg/day) via intragastric administration five times per week. The doses were within or below the established regulatory limits. While single or mixed exposures did not alter WD-induced obesity, tubular lipid vacuolation, or increased serum creatinine levels; the exposure to higher doses of the mixture (5 +2) reduced the mesangial matrix area and tubular cell proliferation, while increasing the density of F4/80 macrophages in the renal interstitium. In terms of transcriptomic analysis, the herbicide mixture altered the expression of 415 genes in the kidney, which were found to be associated with immune response processes, particularly those related to phagocyte activity. While discrete, findings indicate that herbicide mixtures, rather than single exposures, might induce minor deleterious effects on the kidneys of obese mice under WD intake.
  [Romualdo, G.R., de Souza, J.L.H., Valente, L.C. and Barbisan, L.F., 2023. Toxicology Letters, 385, pp.1-11.]
• Association of indoor use of pesticides with CKD of unknown origin
  Chronic kidney disease (CKD) is a growing global health problem. Recently, an epidemic of CKD of unknown origin (CKDu), a form of CKD seen mostly in agricultural communities, has been emerged. One of the proposed causes of CKDu is pesticide use in farmers. On the other hand, the research on relation between indoor use of pesticides and CKDu is little. In this study, we aimed to investigate the association between indoor use of pesticide as well as the exposure time with CKDu. This study was done as part of the population-based cohort of Prospective Epidemiological Research Studies in Iran. We used the baseline data of the Zahedan Adult Cohort Study. All subjects with diabetes mellitus and/or hypertension, estimated glomerular filtration rate (eGFR) between 60–89 ml/min/1.73 m2, and unavailable creatinine measurement were excluded. Subjects with an eGFR of less than 60 ml/min/1.73 m2 were defined as having CKDu, and their data were compared with those with an eGFR of more than 90 ml/min/1.73 m2. Data regarding indoor pesticide use and duration of exposure were obtained through a questionnaire. After applying the exclusion criteria, 1079 subjects remained in the study. Female sex, single marital status, low physical activity, triglyceride (TG) levels of more than 150 mg/dl, body mass index (BMI) of more than 25 kg/m2, non-smokers, indoor pesticide use, and high pesticide exposure time were associated with CKDu. The effects of age, female sex, TG levels more than 150 mg/dl, pesticide use (OR 1.36; 95% CI 1.01–1.84), and high exposure time (third tertile of exposure time) compared to non-users (OR 1.64; 95% CI 1.07–2.51) remained significant in multivariable analysis.
  [Alvand, S., Alatab, S., Dalvand, S., Shahraki-Sanavi, F., Kaykhaei, M.A., Shahraki, E., Barar, E., Sepanlou, S.G. and Ansari-Moghaddam, A., 2023. Plos one, 18(7), p.e0277151.]
• Biopesticides as a promising alternative to synthetic pesticides: A case for microbial pesticides, phytopesticides, and nanobiopesticides
  Over the years, synthetic pesticides like herbicides, algicides, miticides, bactericides, fumigants, termiticides, repellents, insecticides, molluscicides, nematicides, and pheromones have been used to improve crop yield. When pesticides are used, the over-application and excess discharge into water bodies during rainfall often lead to death of fish and other aquatic life. Even when the fishes still live, their consumption by humans may lead to the biomagnification of chemicals in the body system and can cause deadly diseases, such as cancer, kidney diseases, diabetes, liver dysfunction, eczema, neurological destruction, cardiovascular diseases, and so on. Equally, synthetic pesticides harm the soil texture, soil microbes, animals, and plants. The dangers associated with the use of synthetic pesticides have necessitated the need for alternative use of organic pesticides (biopesticides), which are cheaper, environment friendly, and sustainable. Biopesticides can be sourced from microbes (e.g., metabolites), plants (e.g., from their exudates, essential oil, and extracts from bark, root, and leaves), and nanoparticles of biological origin (e.g., silver and gold nanoparticles). Unlike synthetic pesticides, microbial pesticides are specific in action, can be easily sourced without the need for expensive chemicals, and are environmentally sustainable without residual effects. Phytopesticides have myriad of phytochemical compounds that make them exhibit various mechanisms of action, likewise, they are not associated with the release of greenhouse gases and are of lesser risks to human health compared to the available synthetic pesticides. Nanobiopesticides have higher pesticidal activity, targeted or controlled release with top-notch biocompatibility and biodegradability. In this review, we examined the different types of pesticides, the merits, and demerits of synthetic pesticides and biopesticides, but more importantly, we x-rayed appropriate and sustainable approaches to improve the acceptability and commercial usage of microbial pesticides, phytopesticides, and nanobiopesticides for plant nutrition, crop protection/yield, animal/human health promotion, and their possible incorporation into the integrated pest management system.
  [Ayilara, M.S. et al. (2023) Biopesticides as a promising alternative to synthetic pesticides: A case for microbial pesticides, phytopesticides, and nanobiopesticides, Frontiers in Microbiology. Available at: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1040901/full. ]
• Glyphosate-induced liver and kidney dysfunction, oxidative stress, immunosuppression in Nile tilapia, but ginger showed a protection role
  The water-borne herbicides are involved in the toxicity of aquatic animals resulting in impaired health status and low productivity. Dietary medicinal herbs present a practical solution to relieve the impacts of herbicides toxicity on the performances of aquatic animals. Herein, we investigated the toxicity of commercial glyphosate-induced oxidative stress, immunosuppression, liver and kidney dysfunction, and the protective role of ginger or ginger nanoparticles in Nile tilapia. Fish were allocated into four groups: the first group presented the control without glyphosate toxicity and ginger feeding, the second group intoxicated with glyphosate at 0.6 mg/L and fed ginger free diet, the third group intoxicated with glyphosate and fed ginger at 2.5 g/kg, and the fourth group intoxicated with glyphosate and fed ginger nanoparticles at 2.5 g/kg. Fish were kept under the experimental conditions for four weeks, and the samples of blood and tissues were collected after 2 and 4 weeks. Markedly, fish exposed to glyphosate showed the highest ALT and AST activities, glucose and cortisol levels, and malondialdehyde levels (MDA) in gills and tissues. While fish in the control and fish intoxicated with glyphosate and fed ginger nanoparticles had the lowest ALT and AST activities, glucose and cortisol levels, and MDA levels after 2 and 4 weeks (P < 0.05). Fish fed dietary ginger had lower ALT and AST activities, glucose and cortisol levels, and MDA levels than the glyphosate intoxicated group after 2 and 4 weeks (P < 0.05). Interestingly, fish-fed ginger nanoparticles showed lower urea and creatinine levels and higher total protein, albumin, and globulin than the glyphosate intoxicated group (P < 0.05) and similar to the control (P > 0.05). Further, fish intoxicated with glyphosate and fed ginger nanoparticles had the highest GSH, lysozyme activity, and immunoglobulin levels after 2 and 4 weeks (P < 0.05). In conclusion, ginger nanoparticles are superior to the standard ginger form in enhancing the antioxidative and immune responses of Nile tilapia exposed to glyphosate.
  [Abdelmagid, A.D., Said, A.M., Abd El-Gawad, E.A. et al. Glyphosate-induced liver and kidney dysfunction, oxidative stress, immunosuppression in Nile tilapia, but ginger showed a protection role. Vet Res Commun 47, 445–455 (2023). https://doi.org/10.1007/s11259-022-09961-0]
• Human serum lipidomics analysis revealed glyphosate may lead to lipid metabolism disorders and health risks
  Glyphosate-based herbicides (GBH) are one of the most widely used pesticides worldwide. Industrial workers in glyphosate-based herbicides manufacture are the populations who experience long-term exposure to high glyphosate levels. The impacts of glyphosate on human health are the important public health problem of great concern. Up to date, the potential adverse effects of glyphosate on humans or other mammals have been reported in multiple studies. However, limited research is available on lipid alternations related to human exposure to glyphosate. In fact, the perturbations in some lipid metabolisms have been found in industrial workers in previous work. This study aims to explore the serum lipidomic characterization and to understand the underlying mechanisms of health risks associated with glyphosate exposure. A nontargeted lipidomics study was conducted to investigate the 391 serum samples from the general population and chemical factory workers. It was demonstrated that glyphosate caused significant perturbations of 115 differentially expressed lipids. The main manifestations were the elevation of circulating diacylglycerols (DG), cholesteryl esters (CE), ceramides (Cer), sphingomyelins (SM), lysophosphatidylethanolamines (LPE) and phosphatidylcholines (PC), and the decrease of ysophosphatidylcholines (LPC), triacylglycerols (TG), fatty acids (FA) and phosphatidylethanolamines (PE). A total of 88 lipids were further screened as potential lipid biomarkers associated closely with glyphosate using partial correlation analysis, and five of which (including PC 16:0/18:2; O, PC 18:0/18:2; O, PC 18:0/20:4; O, PC O-40:9 and CE 18:3) showed excellent superior performance (AUC = 1) to evaluate and monitor health risks due to glyphosate exposure. The present work discovered glyphosate-induced potential health risks, including chronic hepatic and renal dysfunction, atherosclerosis, cardiovascular disease and neurodegenerative diseases from a lipidomic perspective, and could inform the identification of early indicators and interpretation of biological mechanisms to detect health risks of the glyphosate-exposed populations as early as possible.
  [Zhang, F., Zhang, Q., Liu, X., Gao, M., Li, X., Wang, Y., Chang, Y., Zhang, X., Huo, Z., Zhang, L. and Shan, J., 2023. Environment International, 171, p.107682.]
• Pesticides and insulin resistance-related metabolic diseases: Evidences and mechanisms.
  The use of pesticides in the past century has lot helped humankind in improving crops' field and general hygiene level. Nevertheless, there has been countless evidences on the toxic effects of pesticides on the living systems. The link of exposure to pesticides with different human chronic diseases in the context of carcinogenicity, neurotoxicity, developmental toxicity, etc., have been evaluated in various types of studies. There are also some evidences on the link of exposure to pesticides with higher incidence of metabolic diseases associated with insulin resistance like diabetes, obesity, metabolic syndrome, hypertension, polycystic ovary syndrome and chronic kidney diseases. Physiologically, weakening intracellular insulin signaling is considered as a compensatory mechanism for cells to cope with cellular stresses like xenobiotic effects, oxidative stress and inflammatory responses, but it can pathologically lead to a defective cycle with lowered sensitivity of the cells to insulin which happens in metabolic disorders. In this work, the data related to metabolic toxicity of pesticides categorized in the mentioned metabolic diseases with a focus on the effects of pesticides on insulin signaling pathway and the mechanisms of development of insulin resistance will be systematically reviewed and presented.
  [Arab, A. and Mostafalou, S., 2023. Pesticide Biochemistry and Physiology, p.105521.]
• Biochemical and Histological Evaluation of Penoxsulam Herbicide on an Animal Model
  Aims: Many herbicides react to the body system and might effect the activity of hormones in the human body. The present work aims to determine the potential impact of 90 days of repeated exposure to Penoxsulam herbicide by oral gavage on the Liver, Kidney, Thyroid endocrine profile and biochemical stress in the wistar rat model.
  Study design: The primary study was performed to Wistar rats grouped into 6 groups. Four groups were picked for low dose, middle dose, high dose, and high recovery dose, respectively. They were administered the Penoxsulam at dose levels of 100, 300, 500 mg/kg body weight. Similarly, 2 recovery groups were classified as control and recovery control groups, and doses were administered to them only
  through the corn oil (vehicle) via the oral route with the help of a suitable cannula for 90 days.
  Place and Duration of Study: Toxicology department, Shriram Institute for Industrial Research, Delhi (INDIA), July 2020 and June 2021.
  Methodology: In this study, healthy 60 male and 60 female Wistar rats aged 6-8 weeks, weighing 130-190 gm, were used. Before commencing the study, permission from IAEC (Institutional animal ethics committee) was taken for this experiment (CPCSEA).
  Results: This study evaluates significant changes in the body weight of rats; moreover, Penoxsulam elevated the significance level of SGOT, SGPT, BUN, Urea, and Creatinine. No alterations were seen in Hematology parameters and Ophthalmology examination. Also, physiological changes were examined
  after exposure to penoxsulam in rats.
  Conclusion: Therefore, Penoxsulam showed harmful toxic effects on the Kidney and Liver. However, no alteration has been seen in the thyroid profile (T3 triiodothyronine, T4 thyroxine, TSH thyroid-stimulating hormone) of Wistar rats during the experimentation period.
  [Chaurasia, V., Aggarwal, M. and Garg, M. (2022) Biochemical and Histological Evaluation of Penoxsulam Herbicide on an Animal Model, Journal of Pharmaceutical Research International. Available at: https://www.researchgate.net/publication/358594997_Biochemical_and_Histological_Evaluation_of_Penoxsulam_Herbicide_on_an_Animal_Model.]
• Harmful health effects of pesticides used on museum textile artifacts - overview
  The paper discusses the types of fibers contained in the museum textile artifacts and the types of pests and pesticides. Also, the main health problems associated with pesticide exposure are presented. Textile fibers represent an excellent source of food for microbes and insects. The key to the long-term preservation of textiles is by implementing an integrated management program for pest and environmental conditions control. The main types of pesticides are insecticides, herbicides, fungicides, rodenticides, acaricides, and fumigants and a way for classification can be made according to the LD50 (lethal dose) value which evaluates the toxicity of a pesticide. Depending on the LD50 values, pesticides can be very toxic, moderately toxic, slightly toxic, and relatively non-toxic. Exposure to pesticides can occur through 4 four routes: oral, dermal, respiratory, and eye exposure. The main diseases that can be associated with exposure to pesticides are discussed in the paper. In the end, a basic set of precautionary recommendations when handling museum objects that may contain hazardous materials was presented.
  [Tănăsescu, E.C. and Lite, M.C., 2022. Ecotoxicology and Environmental Safety, 247, p.114240.]
• Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: The CaReMe CKD study
  Background
  Digital healthcare systems data could provide insights into the global prevalence of chronic kidney disease (CKD). We designed the CaReMe CKD study to estimate the prevalence, key clinical adverse outcomes and costs of CKD across 11 countries.
  Methods
  Individual-level data of a cohort of 2·4 million contemporaneous CKD patients was obtained from digital healthcare systems in participating countries using a pre-specified common protocol; summarized using random effects meta-analysis. CKD and its stages were defined in accordance with current Kidney Disease: Improving Global Outcomes (KDIGO) criteria. CKD was defined by laboratory values or by a diagnosis code.
  Findings
  The pooled prevalence of possible CKD was 10·0% (95% confidence interval 8.5‒11.4; mean pooled age 75, 53% women, 38% diabetes, 60% using renin-angiotensin-aldosterone system inhibitors). Two out of three CKD patients identified by laboratory criteria did not have a corresponding CKD-specific diagnostic code. Among CKD patients identified by laboratory values, the majority (42%) were in KDIGO stage 3A; and this fraction was fairly consistent across countries. The share with CKD based on urine albumin-creatinine ratio (UACR) alone (KDIGO stages one and two) was 29%, with a substantial heterogeneity between countries. Adverse events were common; 6·5% were hospitalized for CKD or heart failure, and 6·2% died, annually. Costs for renal events and heart failure were consistently higher than costs for atherosclerotic events in CKD patients across all countries.
  Interpretation
  We estimate that CKD is present in one out of ten adults. These individuals experience significant adverse outcomes with associated costs. The prevalence of CKD is underestimated when using diagnostic codes alone. There is considerable public health potential in diagnosing CKD and providing treatments to those currently undiagnosed.
  [Sundström, J. et al. (2022) Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: The Careme CKD study, The Lancet Regional Health Europe. Available at: https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(22)00132-6/fulltext. ]
• Association of Pesticides and Kidney Function among Adults in the US Population 2001–2010
  Chronic kidney disease of unknown cause is prevalent in a range of communities; however, its etiology remains unclear. We examined the association between pesticide exposures and the risk of kidney function loss using four waves of the National Health and Nutrition Examination Survey (NHANES) to identify a pathological pathway. We pooled data from four cross-sectional waves of NHANES, with 41,847 participants in total. Exposure to malathion increased the risk of low kidney function (aOR = 1.26, 95% CI = 1.01–1.56) in the adjusted model. Increased risk of low kidney function was not found among those exposed to 2,4-D (aOR = 0.88, 95% CI = 0.72–1.09), 3,5,6-trichloropyridinol (aOR = 0.96, 95% CI = 0.83–1.12), and 3-PBA (aOR = 1.03, 95% CI = 0.94–1.13). Our findings provide evidence of altered kidney function in people exposed to malathion, highlighting the potential of organophosphate pesticides’ role in renal injury.
  [Wan, E.T., Darssan, D., Karatela, S., Reid, S. and Osborne, N. Int. J. Environ. Res. Public Health.]
• Systemic effects of the pesticide mancozeb - A literature review
  Objective: The purpose of this literature review is to document what has already been scientifically published about the pesticide Mancozeb and its potential systemic complications.

  Materials and methods: Data were collected during the months of July, August and September 2020, from the Medline and PubMed databases, in the Portuguese, English and Spanish, covering articles written in the last 20 years. Twenty-one studies were selected for analysis.

  Results: The results found in this review study, indicate that Mancozeb is potentially damaging to health, appearing as an increase in ethylethiourea (ETU) dosages in most studies.

  Conclusions: About the widespread use of Mancozeb, the studies found show that this fungicide is a potential cause of several health problems, mainly hepatic, renal and genotoxic, demonstrating with an increase in ETU dosages, as well as liver enzymes in most studies, corroborating the idea that the deliberate use of the product can induce potential systemic complications, and is a public health problem.
  [Dall’Agnol, J. (2021) Systemic effects of the pesticide mancozeb - A literature review, European Review for Medical and Pharmacological Sciences. Available at: https://pubmed.ncbi.nlm.nih.gov/34156691/. ]

• Water sources and kidney function: investigating chronic kidney disease of unknown etiology in a prospective study
  A chronic Kidney Disease of unknown etiology (CKDu) has emerged with disproportionately high prevalence across dry lowland agricultural communities globally. Here we present the results of a prospective cohort of 293 patients with CKDu in the endemic region of Wilgamuwa, Sri Lanka, in whom we measured baseline kidney function and undertook quarterly follow up over 2 years. Well water was the primary historic drinking water source in the region, although a majority (68%) of participants reported switching to reverse osmosis water during study follow ups. Participants who reported ever drinking from well water had estimated glomerular filtration rates −6.7 (SD: 2.8) ml/min/1.73 m2 lower than participants who did not drink from well water historically (p = 0.0184) during the study period. Geospatial analysis identifies a cluster within the region where CKDu progression is significantly higher than the surrounding area. Samples of household wells (n = 262) indicated 68% had detectable agrochemical compounds with concentration above global water quality standards. It is expected that the detected contaminants compounds are indicators of poor water quality and that there is likely additional agrochemical exposure including commercial additives that may contribute to CKDu onset and/or progression. Thus, our study finds that well water exposure during a person’s lifetime in this region is associated with kidney function decline and identifies and quantifies putative nephrotoxic agrochemicals above safe drinking water concentrations in these wells.
  [Vlahos, P., Schensul, S.L., Anand, S., Shipley, E., Diyabalanage, S., Hu, C., Ha, T., Staniec, A., Haider, L., Schensul, J.J. and Hewavitharane, P. npj Clean Water, 4(1), pp.1-7.]
• 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.]
• Chronic kidney disease and household behaviors in Sri Lanka: Historical choices of drinking water and agrochemical use
  This paper examines whether there are systematic differences in the historical behaviors of households that are affected and unaffected by chronic kidney disease (CKD) in Sri Lanka pertaining to their water source choices, water treatment practices, and agrochemical use. This analysis is motivated by the Sri Lankan government's largest policy response to this epidemic - to encourage communities to switch from untreated well water to publicly provided alternatives. We use recall methods to elicit information on the drinking water source and treatment choices of households over an 18-year period from 2000-2017. Our analysis is based on a survey of 1497 rural ground-water dependent households in the most CKD-affected areas of the 10 districts of Sri Lanka with the highest prevalence of CKD. Our main findings are that (a) households that have ever used a pump to extract (typically deep) drinking water from a household well are more likely to be affected by CKD; (b) we fail to find a relationship between disease status and households' use of buckets to extract (typically shallow) groundwater from their wells; and (c) those who have ever treated their shallow well water by boiling it are less likely to be affected by CKD. We also find that a greater share of CKD affected households historically used agrochemicals, used wells that were geographically removed from surface water sources, and displayed lower proxies of wealth. The implications of these findings are fourfold. First, since the systematic differences in the historical patterns of water sources and treatments used by CKD affected and non-affected households are modest, the sources of water and the treatment practices themselves may not be the sole risk factors in developing CKD. Second, although we find a negative association between boiling water and the probability of CKD, it is not obvious that a public policy campaign to promote boiling water is an appropriate response. Third, the hydrochemistry of deep and shallow well water needs to be better understood in order to shed light on the positive relationship between deep well water and disease status, and on why boiling shallow but not deep well water is associated with a lower probability of CKD. Fourth, there is a need for a deeper understanding of other risk factors and of the efficacy of preventative programs that provide alternative sources of household drinking water.
  [Balasubramanya, S., Stifel, D., Horbulyk, T. and Kafle, K., 2020. Economics & Human Biology, 37, p.100862.]
• Methyl thiophanate-induced toxicity in liver and kidney of adult rats: a biochemical, molecular and histopathological approach
  The aim of this study was to elucidate the redox effects of Thiophanate methyl (MT) in the rat liver and kidney. Our results showed, after 3 days of MT injection (700 mg/kg), an increase in malondialdehyde (MDA), hydrogen peroxide and advanced oxidation protein products levels. Glutathione peroxidase and superoxide dismutase activities were also remarkably increased in the liver but decrease in the kidney. Glutathione and vitamin C values were significantly reduced. The changes in biochemical parameters were substantiated by histological and molecular data. A smear without ladder formation on agarose gel was shown, indicating random DNA degradation in the liver and the kidney of MT treated rats. The increase in cyclooxygenase-2 gene expression, marker of inflammation, and an increase in genes expression of glutathione peroxidase and superoxide dismutase in liver and their decrease in the kidney were also occurred after MT exposure. These data confirmed the pro-oxidant and genotoxic effects of this fungicide.
  [Feki, A., Ben Saad, H., Jaballi, I., Magne, C., Boudawara, O., Zeghal, K. M., Hakim, A., Ben Ali, Y., & Ben Amara, I. (2017). Methyl thiophanate-induced toxicity in liver and kidney of adult rats: a biochemical, molecular and histopathological approach. Cellular and Molecular Biology, https://doi.org/10.14715/cmb/2017.63.2.4]
• Kidney biomarkers in MCPA-induced acute kidney injury in rats: Reduced clearance enhances early biomarker performance
  For improved early detection and assessment of severe acute kidney damage following accidental or intentional ingestion of the herbicide MCPA, we compared a panel of 14 novel kidney injury biomarkers with plasma creatinine. Male Wistar rats received four different oral doses of MCPA and plasma and urine biomarker levels were measured at 8, 24 and 48 h after MCPA exposure. Diagnostic performances using absolute levels, urine levels normalized to urine creatinine or urinary excretion rate were determined by ROC analysis. Plasma creatinine remained the best early biomarker for predicting histological changes at 48 h. The performance of plasma cystatin C in mirroring kidney function was similar to that of plasma creatinine. While urine concentrations were generally less predictive, normalization by urine creatinine greatly improved the performance of several biomarkers. This may be due to an apparent amplification of the biomarker signal on normalizing to creatinine, in the presence of a declining glomerular filtration rate prior to reaching steady state. Normalized 8 h osteopontin and albumin concentrations outperformed other normalized biomarkers in predicting histological changes at later times. Normalized urinary kidney injury molecule-1 at 48 h also correlated well with the degree of kidney damage.
  [Wunnapuk, K. (2014) Kidney biomarkers in MCPA-induced acute kidney injury in rats: Reduced clearance enhances early biomarker performance, Toxicology Letters. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0378427414000290. ]
• Subacute oral toxicity of combinations of selected synthetic pyrethroids, piperonyl butoxide, and tetramethrin in rats
  In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes. Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days. During the study period, mortality and serious clinical findings were not observed in any animal. However, feed consumptions decreased in groups 1 and 3 (p < 0.05). Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0.05). Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups. Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0.05). The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver. It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.
  [Yavuz O, Aksoy A, Das YK, et al. (2013). Subacute oral toxicity of combinations of selected synthetic pyrethroids, piperonyl butoxide, and tetramethrin in rats. Toxicology and Industrial Health. https://journals.sagepub.com/doi/abs/10.1177/0748233712469651]
• Acute Renal Failure following Penoxsulam poisoning
  Penoxsulam is a fluorinated benzenesulfonamide. It is a herbicide used in dry and wet seeded crops mainly in rice paddies in Sri Lanka. Toxicity following human ingestion has not been reported before. Eye contact with penoxsulam dust or granules may cause slight irritation, although corneal injury is unlikely. Harmful effects are not anticipated from swallowing small amounts. In animal studies, the predominant target organ were the kidney and the urothelium. Due to limited solubility in urine, penoxsulam forms crystals/calculi in the pelvis of the kidney and the lumen of the urinary bladder. Raised blood urea, reduced urine osmolality and increased urine volume were noted as secondary effects. Renal tubular degeneration was also sometimes observed. A treatment-related chronic progressive glomerulonephropathy was observed in male rats. Kidney damage seen in shorter-term studies was generally not exacerbated in longer-term studies.

  Human intoxication with Penoxsulam has not been reported before. We wish to report a patient who developed acute renal failure requiring dialysis. It is important to be aware of the possible renal toxicity of this herbicide.
  [Karunatilake, H. (2011). Acute Renal Failure following Penoxsulam poisoning. Clinical Toxicology, 50(1), 79. https://doi.org/10.3109/15563650.2011.633492]

• Short-term oral and dermal toxicity of MCPA and MCPP
  The herbicides 2-methyl-4-chlorophenoxy acetic acid (MCPA) and 2-(2-methyl-4-chlorophenoxy) propionic acid (MCPP or mecoprop) were tested for 90 days in rats. The compounds were added to the diet at levels of 0, 50, 400 and 3200 ppm. Growth, food intake, mortality, haematology, blood and liver chemistry, organ weights and histopathology were used as criteria.

  The main effects of both compounds were growth retardation and elevated relative kidney weights at levels of 400 ppm and more. The 50 ppm dose level can be considered as a non-toxic-effect level in the 90-day study.

  In subacute dermal studies in rabbits during 3 weels the dosage were 0, 0.5, 1.0 and 2 g MCPA or MCPP per kg body weight. Thereafter followed a recovery period of 2 weeks. Growth, mortality, skin reaction, haematology, organ weights (MCPP) and histopathology were recorded and determined. Both compounds caused slight to moderate erythema at all dose levels, whereas elasticity of the skin was decreased. In both experiments the skin returned to normal during the recovery period. Weight loss was observed at all dose levels. In the MCPA experiments high mortality and histopathological changes in the liver, kidneys, spleen and thymus were recorded at the two highest dose levels. The cause of this could have been either the treatment with MCPA or a dysbacteria infection which developed during the experiment.
  [Verschuuren, H. et al. (1975) Short-term oral and dermal toxicity of MCPA and MCPP, Toxicology. Available at: https://www.sciencedirect.com/science/article/abs/pii/0300483X75900360. ]