Exposure of Male Farmers and Nonfarmers to Neonicotinoid Pesticides in the South-West and Littoral Regions of Cameroon: A Comparative Study.

Pesticides, especially the newly developed neonicotinoids, are increasingly used in many countries around the world, including Cameroon, to control pests involved in crop destruction or disease transmission. Unfortunately, the pesticides also pose tremendous environmental problems because a predominant amount of their residues enter environmental matrices to affect other nontargeted species including humans. This therefore calls for continuous biomonitoring of these insecticides in human populations. The present study sought to assess the neonicotinoid insecticide exposures in two agrarian regions of Cameroon, the South-West region and Littoral region. The study involved 188 men, including 125 farmers and 63 nonfarmers. Spot urine samples were obtained from these subjects and subjected to liquid chromatographic-tandem mass spectrometric analysis for concentrations of neonicotinoid compounds, including acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, nitenpyram, thiamethoxam, and N-dm-acetamiprid. Neonicotinoid compounds were detected in all study participants, and residues of all the screened pesticides were detected among participants. N-dm-Acetamiprid and imidacloprid were the most prevalent among the subjects (100.0% and 93.1%, respectively), whereas nitenpyram was less common (3.2%). The median values of imidacloprid and total urinary neonicotinoid concentrations were elevated among farmers (0.258 vs. 0.126 µg/L and 0.829 vs. 0.312 µg/L, respectively). Altogether the findings showed that both the farmer and nonfarmer study populations of Cameroon were exposed to multiple residues of neonicotinoids, with relatively higher levels of pesticides generally recorded among farmers. Although exposure levels of the neonicotinoids were generally lower than their respective reference doses, these results warrant further research on the health risk evaluation of multiple residues of the pesticides and reinforcement of control measures to minimize the exposure risks, especially among farmers. Environ Toxicol Chem 2024;43:952-964. © 2024 SETAC.

Association of pesticide exposure with neurobehavioral outcomes among avocado farmworkers in Mexico.

BACKGROUND AND AIM: To date, few studies have focused on the health effects of pesticide exposure among avocado farmworkers. We examined the association of exposure to insecticides, fungicides, and herbicides with cognitive and mental health outcomes among these avocado workers from Michoacan, Mexico. MATERIALS AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We collected data on self-reported pesticide use during the 12 months prior to the baseline survey and estimated annual exposure-intensity scores (EIS) using a semi-quantitative exposure algorithm. We calculated specific gravity adjusted average concentrations of 12 insecticide, fungicide, or herbicide metabolites measured in urine samples collected during two study visits (8-10 weeks apart). We assessed participants' cognitive function and psychological distress using the NIH Toolbox Cognition Battery and the Brief Symptom Inventory 18 (BSI-18), respectively. We examined individual associations of EIS and urinary pesticide metabolites with neurobehavioral outcomes using generalized linear regression models. We also implemented Bayesian Weighted Quantile Sum (BWQS) regression to evaluate the association between a pesticide metabolite mixture and neurobehavioral outcomes. RESULTS: In individual models, after adjusting for multiple comparisons, higher concentrations of hydroxy-tebuconazole (OH-TEB, metabolite of fungicide tebuconazole) were associated with higher anxiety (IRR per two-fold increase in concentrations = 1.26, 95% CI:1.08, 1.48) and Global Severity Index (GSI) (IRR = 1.89, 95% CI:1.36, 2.75) scores, whereas higher concentrations of 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) were associated with lower GSI scores (IRR = 0.69, 95% CI: 0.56, 0.85). In BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with higher anxiety (IRR = 1.72, 95% CrI: 1.12, 2.55), depression (IRR = 4.60, 95% CrI: 2.19, 9.43), and GSI (IRR = 1.99, 95% CrI: 1.39, 2.79) scores. OH-TEB and hydroxy-thiabendazole (metabolite of fungicide thiabendazole) combined contributed 54%, 40%, and 54% to the mixture effect in the anxiety symptoms, depression symptoms, and overall psychological distress models, respectively. CONCLUSIONS: We found that exposure to tebuconazole and thiabendazole, fungicides whose effects have been rarely studied in humans, may be associated with increased psychological distress among avocado farmworkers. We also observed that exposure to chlorpyrifos may be associated with decreased psychological distress.

Dietary Predictors of Urinary Biomarkers of Pyrethroids in the General Population - A Scoping Review.

BACKGROUND: Pyrethroid pesticides are ubiquitous environmental contaminants, contributing to chronic and potentially harmful exposure among the general population. Although studies have measured pesticide residues on agricultural products, the link between food intake and concentrations of pyrethroid biomarkers in urine remains unclear. OBJECTIVE: This scoping review aims to analyze peer-reviewed publications investigating dietary predictors of pyrethroid exposure through urinary biomarkers. We assess existing evidence, identify research gaps, and highlight current limitations. METHODS: We conducted a comprehensive search using PubMed and Google Scholar. Eligible studies examined associations between diets, food items or dietary components, and measured urinary pyrethroid biomarkers. No geographical restriction was applied to our search. Results were summarized in themes referring to study characteristics, relevant outcomes, biomarker measurement, dietary assessment and statistical analyses. RESULTS: We identified 20 relevant articles. Most studies presented evidence on associations between the consumption of organic diets or food items and reduced concentrations of 3-phenobenzoic acid metabolites in urine. There was less evidence for diet affecting other pyrethroid-specific biomarkers. Dietary assessment methodologies and recall periods varied, as did the number and timing of urine collections. Many studies did not control for potential alternative pyrethroid sources, exposure to other pesticides, or demographic and socioeconomic characteristics. CONCLUSION: Researchers should consider standardized dietary assessment, chemical analyses of foods consumed, adequate recall time, and food preparation methods. Consistency in biomarker measurement, including urine collection time and corrections for specific gravity or creatinine, is needed. Ensuring the validity of such studies also requires larger samples and appropriate control for confounders.

Prenatal and childhood exposure to organophosphate pesticides and functional brain imaging in young adults.

BACKGROUND: Early life exposure to organophosphate (OP) pesticides has been linked with poorer neurodevelopment from infancy to adolescence. In our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort, we previously reported that residential proximity to OP use during pregnancy was associated with altered cortical activation using functional near infrared spectroscopy (fNIRS) in a small subset (n = 95) of participants at age 16 years. METHODS: We administered fNIRS to 291 CHAMACOS young adults at the 18-year visit. Using covariate-adjusted regression models, we estimated associations of prenatal and childhood urinary dialkylphosphates (DAPs), non-specific OP metabolites, with cortical activation in the frontal, temporal, and parietal regions of the brain during tasks of executive function and semantic language. RESULTS: There were some suggestive associations for prenatal DAPs with altered activation patterns in both the inferior frontal and inferior parietal lobes of the left hemisphere during a task of cognitive flexibility (ß per ten-fold increase in DAPs = 3.37; 95% CI: -0.02, 6.77 and ß = 3.43; 95% CI: 0.64, 6.22, respectively) and the inferior and superior frontal pole/dorsolateral prefrontal cortex of the right hemisphere during the letter retrieval working memory task (ß = -3.10; 95% CI: -6.43, 0.22 and ß = -3.67; 95% CI: -7.94, 0.59, respectively). We did not observe alterations in cortical activation with prenatal DAPs during a semantic language task or with childhood DAPs during any task. DISCUSSION: We observed associations of prenatal OP concentrations with mild alterations in cortical activation during tasks of executive function. Associations with childhood exposure were null. This is reasonably consistent with studies of prenatal OPs and neuropsychological measures of attention and executive function found in CHAMACOS and other birth cohorts.

Association of urinary organophosphate metabolites with adult asthma patients: a cross-sectional population-based study.

Human health is adversely affected by exposure to organophosphate (OP) pesticides. This study aims to investigate the correlation between urinary OP metabolites and the prevalence of asthma. In cross-sectional studies, data from the National Health and Nutrition Examination Survey (NHANES) projects conducted between 2003-2008, 2011-2012, and 2015-2018 were analyzed. Multiple logistic regressions and restricted cubic spline (RCS) regressions were utilized to examine the relationship between four urinary OP metabolites, namely dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl phosphorothioate (DMTP), and diethyl phosphorothioate (DETP), and the prevalence of asthma. Additionally, quantile g-computation (QG-C) regression was employed to evaluate the association between urinary OP metabolites (both individual and combined exposures) and asthma prevalence. The results showed that a total of 9316 adults, including 1298 participants with asthma, were included in the analysis. The median age of the participants was 47.37 years, and 50.27% were female. In the comprehensive model, the third tertile of DMP and DEP exhibited a positive association with asthma prevalence compared to the first tertile (odds ratio [95% confidence interval]: 1.26 [1.01-1.57], Ptrend = 0.036; and 1.25 [1.07-1.51], Ptrend = 0.008, respectively). Moreover, a linear relationship was observed between DMP, DEP, and asthma prevalence (P for nonlinearity = 0.320 and 0.553, respectively). The QG-C regression revealed a positive association between the mixture of urinary OP metabolites and asthma prevalence (OR = 1.04 [1.01-1.07], P = 0.025), with DEP contributing the most substantial effect (weight = 0.564). Our findings suggest that exposure to OP pesticides is associated with an increased prevalence of asthma, with DEP demonstrating the strongest impact.

Exposure of the general French population to herbicides, pyrethroids, organophosphates, organochlorines, and carbamate pesticides in 2014-2016: Results from the Esteban study.

Esteban is a nationwide cross-sectional study conducted in France in 2014-2016, including 2503 adults aged 18-74 years old and 1104 children aged 6-17 years old, as part of the French Human Biomonitoring programme. The present paper describes the biological levels of five families of pesticides analysed on random sub-samples of 900 adults and 500 children for urine concentrations, and 759 adults and 255 children for serum concentrations, and the determinants of exposure. Organophosphates, carbamates and herbicides were measured in urine by UPLC-MS/MS; chlorophenols and pyrethroids were measured in urine by GC-MS/MS; specific organochlorines were measured in serum by GC-HRMS. Multivariate analyses were performed to identify the determinants of exposure using a generalized linear model. Pyrethroid metabolites were quantified in 99% of adults and children, with the exeption of F-PBA, which was quantified in 31% of adults and 27% of children, respectively. Carbamates and some specific organophosphates were barely or not quantified. DMTP was quantified in 82% of adults and 93% of children, and γ-HCH (lindane) was quantified in almost 50% of adults and children. Concentration levels of pesticide biomarkers were consistent with comparable international studies, except for ß-HCH, DMTP, and the deltamethrin metabolite Br2CA, whose levels were sometimes higher in France. Household insecticide use and smoking were also associated with higher levels of pyrethroids. All pyrethroids concentration levels were below existing health-based HBM guidance values, HBM-GVsGenPop, except for 3-PBA, for which approximately 1% and 10% of children were above the lower and upper urine threshold values of 22 µg/L and 6.4 µg/L, respectively. Esteban provides a French nationwide description of 70 pesticide biomarkers for the first time in children. It also describes some pesticide biomarkers for the first time in adults, including glyphosate and AMPA. For the latter, urine concentration levels were overall higher in children than in adults. Our results highlight a possible beneficial impact of existing regulations on adult exposure to organochlorine and organophosphate pesticides between 2006 and 2016, as concentration levels decreased over this period.

Residual Dialkyl Phosphate Metabolite Concentrations of Organophosphate Pesticides Among Indian Farmworkers: Implication of Exposure and Hazard Assessment.

OBJECTIVE: Biomonitoring of urinary dialkyl phosphate (DAP) metabolites, a sensitive biomarker to assess pesticides exposure and also to study the impact of the use of personal protective equipment (PPE). METHODS: A preintervention-postintervention study to biomonitor dimethylphosphate, diethylphosphate, diethylthiophosphate, and diethyl-dithiophosphate using liquid chromatography with tandem mass spectrometry among Indian farmworkers (n = 120). RESULTS: Dimethylphosphate was detected in all samples at a mean concentration of 74.91 µg · L -1 (17.616 µg · g -1 creatinine), whereas diethylthiophosphate and diethyl-dithiophosphate were detected in 88% and 82% of samples, respectively, among farmworkers who adopted unsafe pesticide-handling practices. Intervention studies showed a significant reduction in the urinary DAP metabolites detected among the farmworkers using PPE provided to them ( P < 0.01). CONCLUSIONS: Study confirms the exposure to pesticides among farmworkers and highlights the importance of the use of PPE to minimize exposure.

Assessing the impact of coexposure on the measurement of biomarkers of exposure to the pyrethroid lambda-cyhalothrin in agricultural workers.

There are few published data on the impact of combined exposure to multiple pesticides (coexposure) on levels of biomarkers of exposure in workers, which may alter their toxicokinetics and thus the interpretation of biomonitoring data. This study aimed to assess the impact of coexposure to two pesticides with shared metabolism pathways on levels of biomarkers of exposure to pyrethroid pesticides in agricultural workers. The pyrethroid lambda-cyhalothrin (LCT) and the fungicide captan were used as sentinel pesticides, since they are widely sprayed concomitantly in agricultural crops. Eighty-seven (87) workers assigned to different tasks (application, weeding, picking) were recruited. The recruited workers provided two-consecutive 24-h urine collections following an episode of lambda-cyhalothrin application alone or in combination with captan or following tasks in the treated fields, as well as a control collection. Concentrations of lambda-cyhalothrin metabolites - 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-cyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) - were measured in the samples. Potential determinants of exposure established in a previous study, including the task performed and personal factors were documented by questionnaire. Multivariate analyses showed that coexposure did not have a statistically significant effect on the observed urinary levels of 3-PBA (Exp(ß) (95% confidence interval (95% CI)): 0.94 (0.78-1.13)) and CFMP (1.10 (0.93-1.30). The repeated biological measurements ("time variable") - defined as the within-subjects variable - was a significant predictor of observed biological levels of 3-PBA and CFMP; the within-subjects variance (Exp(ß) (95% (95% CI)) for 3-PBA and CFMP was 1.11 (1.09-3.49) and 1.25 (1.20-1.31). Only the main occupational task was associated with urinary levels of 3-PBA and CFMP. Compared to the weeding or picking task, the pesticide application task was associated with higher urinary 3-PBA and CFMP concentrations. In sum, coexposure to agricultural pesticides in the strawberry fields did not increase pyrethroid biomarker concentrations at the exposure levels observed in the studied workers. The study also confirmed previous data suggesting that applicators were more exposed than workers assigned to field tasks such as weeding and picking.

Effect of prenatal exposure to organophosphates and pyrethroid pesticides on neonatal anthropometric measures and gestational age.

Several studies have examined the association between prenatal exposure to organophosphate and pyrethroid pesticides and their impact on foetal growth and newborn anthropometry; however, the available evidence is limited and inconclusive. This study examined whether prenatal organophosphate and pyrethroid pesticide exposure was associated with anthropometric measures at birth (weight, length, head circumference), ponderal index, gestational age, and prematurity in 537 mother-child pairs. These were randomly selected from the 800 pairs participating in the prospective birth cohort GENEIDA (Genetics, early life environmental exposures and infant development in Andalusia). Six non-specific organophosphate metabolites (dialkylphosphates, DAPs), one metabolite relatively specific to chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy) and a common metabolite to several pyrethroids (3-phenoxybenzoic acid, 3-PBA) were measured in maternal urine from the 1st and 3rd pregnancy trimesters. Information on anthropometric measures at birth, gestational age and prematurity was retrieved from medical records. The sum on a molar basis of DAPs with methyl (Æ©DMs) and ethyl (Æ©DEs) moieties and the sum of the 6 DAPs metabolites (Æ©DAPs) was calculated for both trimesters of pregnancy. High urinary levels of dimethyl phosphate (DMP) during the 3rd trimester were associated with a decrease in birth weight (ß = -0.24; 95% CI: 0.41; -0.06) and birth length (ß = -0.20; 95% CI: 0.41; 0.02). Likewise, ΣDMs during 3rd trimester were near-significantly associated with decreased birth weight (ß = -0.18; 95% CI: 0.37; 0.01). In turn, increased urinary TCPy during 1st trimester was associated with a decreased head circumference (ß = -0.31; 95% CI: 0.57; -0.06). Finally, an increase in 3-PBA in the 1st trimester was associated with a decreased gestational age (ß = -0.36 95% CI: 0.65-0.08), whereas increased 3-PBA at 1st and 3rd trimester was associated with prematurity. These results indicate that prenatal exposure to organophosphate and pyrethroid insecticides could affect normal foetal growth, shorten gestational age and alter anthropometric measures at birth.

Pyrethroid and Chlorpyrifos Pesticide Exposure, General Intellectual Abilities, and Executive Functions of School Children from Montevideo, Uruguay.

Children's developing brains are susceptible to pesticides. Less is known about the effect of exposure to chlorpyrifos and pyrethroids on executive functions (EF). We measured urinary 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos, and urinary 3-phenoxybenzoic acid (3-PBA), a general, nonspecific metabolite of pyrethroids in first-grade children from Montevideo, Uruguay (n = 241, age 80.6 ± 6.4 months, 58.1% boys). EFs were assessed with the Intra-dimensional/Extra-dimensional shift (IED), Spatial Span (SSP), and Stockings of Cambridge (SOC) tests from the Cambridge Neuropsychological Test Automated (CANTAB) Battery. General intellectual ability (GIA) was assessed using the Woodcock-Muñoz Cognitive battery. Median (range) urinary TCPy and 3-PBA levels were 16.7 (1.9, 356.9) ng/mg of creatinine and 3.3 (0.3, 110.6) ng/mg of creatinine, respectively. In multivariable generalized linear models, urinary TCPy was inversely associated with postdimensional errors on the IED task ß [95% CI]: -0.11 [-0.17, -0.06]. Urinary 3-PBA was inversely associated with the total number of trials -0.07 [-0.10, -0.04], and the total number of errors -0.12 [-0.18, -0.07] on the IED task. When TCPy and 3-PBA were modeled together, the associations did not differ from single-metabolite models. We found no evidence of effect modification by blood lead level (BLL). Pesticide exposure may affect EF performance in urban children.

Exposure to non-persistent pesticides and sexual maturation of Spanish adolescent males.

BACKGROUND: Several non-persistent pesticides are endocrine disrupting chemicals and may impact on sexual maturation. OBJECTIVE: To examine the association between urinary biomarkers of non-persistent pesticides and sexual maturation in adolescent males in the Environment and Childhood (INMA) Project. METHODS: The metabolites of several pesticides were measured in spot urine samples collected from 201 boys aged 14-17 years, including: 3,5,6-trichloro-2-pyridinol (TCPy), metabolite of chlorpyrifos; 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), metabolite of diazinon; malathion diacid (MDA), metabolite of malathion; diethyl thiophosphate (DETP) and diethyl dithiophosphate, non-specific metabolites of organophosphates; 3-phenoxybenzoic acid (3-PBA) and dimethyl cyclopropane carboxylic acid, metabolites of pyrethroids; 1-naphthol (1-NPL), metabolite of carbaryl; and ethylene thiourea (ETU), metabolite of dithiocarbamate fungicides. Sexual maturation was assessed using Tanner stages, self-reported Pubertal Development Scale, and testicular volume (TV). Multivariate logistic regression was employed to examine associations between urinary pesticide metabolites and the odds of being in Tanner stage 5 of genital development (G5) or pubic hair growth (PH5); stage ≥4 of overall pubertal development, gonadarche, and adrenarche; or having mature TV (≥25 mL). RESULTS: DETP concentrations>75th percentile (P75) were associated with lower odds of being in stage G5 (OR = 0.27; 95% CI = 0.10-0.70), detectable TCPy with lower odds of gonadal stage≥4 (OR = 0.50; 95% CI = 0.26-0.96), and intermediate detectable MDA concentrations (

Associations between prenatal organophosphate pesticide exposure and placental gene networks.

BACKGROUND: Exposure to organophosphate (OP) pesticides during pregnancy has been linked to deficiencies of neurobehavioral development in childhood; however, the molecular mechanisms underlying this association remain elusive. The placenta plays a crucial role in protecting the fetus from environmental insults and safeguarding proper fetal development including neurodevelopment. The aim of our study is to evaluate changes in the placental transcriptome associated with prenatal OP exposure. METHODS: Pregnant farm workers from two agricultural districts in northern Thailand were recruited for the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE) from 2017 to 2019. For 254 participants, we measured maternal urinary concentrations of six nonspecific dialkyl phosphates (DAP) metabolites in early, middle, and late pregnancy. In parallel, we profiled the term placental transcriptome from the same participants using RNA-Sequencing and performed Weighted Gene co-expression Network Analysis (WGCNA). Generalized linear regression modeling was used to examine associations of urinary OP metabolites and placental co-expression module eigenvalues. RESULTS: We identified 21 gene co-expression modules in the placenta. From the six DAP metabolites assayed, diethylphosphate (DEP) and diethylthiophosphate (DETP) were detected in more than 70% of the urine samples. Significant associations between DEP at multiple time points and two specific placental gene modules were observed. The 'black' module, enriched in genes involved in epithelial-to-mesenchymal transition (EMT) and hypoxia, was negatively associated with DEP in early (p = 0.034), and late pregnancies (p = 0.016). The 'lightgreen' module, enriched in genes involved in myogenesis and EMT, was negatively associated with DEP in late pregnancy (p = 0.010). We observed 2 hub genes (CELSR1 and PYCR1) of the 'black' module to be negatively associated with DEP in early and late pregnancies. CONCLUSIONS: Our results suggest that prenatal OP exposure may disrupt placental gene networks in a time-dependent manner. Such transcriptomic effects may lead to down-stream changes in placental function that ultimately affect the developing fetus.

Effects of urinary of organophosphate metabolites on nerve conduction and neurobehavioral performance among farmers in northern Thailand.

Farmers are regarded as a high-risk population for pesticide exposure because of the frequency of their occupational exposure to organophosphate (OP) pesticides. The purposes of this study were 1) to compare urinary OP metabolites, nerve conduction, and neurobehavioral (NB) performance between farmers and a control group, as well as between baseline measurement and after spraying OP pesticides; 2) to investigate the factors associated with increased urinary OP metabolites after spraying OP pesticides; and 3) to investigate the effects of OP metabolites on changes in nerve conduction and NB performance after spraying OP pesticides. This study was conducted with a sample size of 71 farmers and a control group of 26. The findings showed that after spraying OP pesticides total dialkylphosphate (DAP) levels were significantly higher than baseline levels. Multiple linear regression showed that increased urinary OP metabolites among farmers after spraying pesticides were negatively associated with wearing a mask when spraying OP pesticides and positively associated with the number of years of farm work and type of sprayer equipment. The results also showed a positive association between the increased urinary total diethylphosphate (DEP) levels and the decreased amplitude of motor nerve conduction. Furthermore, a positive correlation was observed between increased urinary total DEP and decreased right amplitude of sympathetic skin response (SSR). An increase in urinary total DMP was positively associated with a decrease in raw score and a standard score of visual-motor integration (VMI). Our findings provide evidence that exposure to OP pesticides can cause a deficit in nerve conduction and NB performance in farmers. These findings may contribute to the early detection of neurological disease and inform strategies to prevent damage to the peripheral and central nervous systems.

Detections of organophosphate and pyrethroid insecticide metabolites in urine and sweat obtained from women during infrared sauna and exercise: A pilot crossover study.

Synthetic pesticides such as organophosphates and pyrethroids are commonly used worldwide yet the metabolic and long-term human health effects of these environmental exposures are unclear. Urinary detections of metabolites involving both classes of insecticides have been documented in various global populations. However, reports documenting similar detections in human sweat are sparse. In this study, the concentrations of four insecticide metabolites were measured using liquid chromatography coupled with tandem mass spectrometry in repeated sweat and urine collections (n = 85) from 10 women undergoing three interventions (control, infrared sauna and indoor bicycling) within a single-blinded randomised crossover trial. The Friedman test with post-hoc two-way analysis of variance, the related-samples Wilcoxon signed rank test and the Spearman's rank-order correlation test were used to analyse the results. Organophosphate metabolites were detected in 84.6% (22/26) and pyrethroids in 26.9% (7/26) of the collected sweat samples (pooled per individual, per intervention). Urinary concentrations of three of the four metabolites marginally increased after infrared sauna bathing: 3,5,6-trichloro-2-pyridinol (z = 2.395, p = 0.017); 3-phenoxybenzoic acid (z = 2.599, p = 0.009); and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (z = 2.090, p = 0.037). Urinary 3-phenoxybenzoic acid also increased after exercise (z = 2.073, p = 0.038) and demonstrated the most temporal variability (days to weeks) of any of the urinary metabolites. Definitive sweat/urine correlations were not demonstrated. These results indicate metabolites from organophosphate and pyrethroid pesticides can be detected in human sweat and this raises intriguing questions about perspiration and its role in the metabolism and excretion of synthetic pesticides.

Determinants of organophosphorus pesticide urinary metabolite levels in pregnant women from the CHAMACOS cohort.

Organophosphosphorus pesticides (OPs) are widely used as insecticides in agriculture. Human exposure to OPs has been linked to adverse effects including poorer child neurodevelopment, reduced birth weight, altered serum hormone levels, and reduced semen quality. We measured six OP dialkyl phosphate (DAP) metabolites [three dimethyl alkylphosphates (DMs) and three diethyl alkylphosphates (DEs)] in urine samples collected two times during pregnancy (~13 and ~26 weeks gestation) from 594 women participating in the CHAMACOS birth cohort study and resided in an agricultural community in the United States (U.S.) between 1999 and 2000. Previous studies have shown these women have higher OP exposures compared with the general U.S. population. We examined bivariate associations between prenatal DAP metabolite levels and exposure determinants such as age, season, years living in the US, housing characteristics, fruit and vegetable consumption, occupation and residential proximity to agricultural fields. Final multivariable models indicated that season of urine collection was significantly associated (p < 0.01) with specific gravity-adjusted DM, DE and total DAP metabolites; samples collected in fall and winter had higher concentrations than those collected in spring-summer. Specific gravity-adjusted levels of DM and total DAP metabolites were significantly higher in women who had resided in the U.S. for 5 years or less (p < 0.05). Levels of DM metabolites also increased with daily fruit and vegetable servings (p < 0.01), and levels of DE metabolites were higher in residences with poorer housekeeping quality (p < 0.01) and in mothers that worked in agriculture (p < 0.05). These findings suggest that there are multiple determinants of OP exposure in pregnant women.

Assessment of exposure to pesticide mixtures in five European countries by a harmonized urinary suspect screening approach.

Humans are exposed to a mixture of pesticides through diet as well as through the environment. We conducted a suspect-screening based study to describe the probability of (concomitant) exposure to a set of pesticide profiles in five European countries (Latvia, Hungary, Czech Republic, Spain and the Netherlands). We explored whether living in an agricultural area (compared to living in a peri-urban area), being a a child (compared to being an adult), and the season in which the urine sample was collected had an impact on the probability of detection of pesticides (-metabolites). In total 2088 urine samples were collected from 1050 participants (525 parent-child pairs) and analyzed through harmonized suspect screening by five different laboratories. Fourty pesticide biomarkers (either pesticide metabolites or the parent pesticides as such) relating to 29 pesticides were identified at high levels of confidence in samples across all study sites. Most frequently detected were biomarkers related to the parent pesticides acetamiprid and chlorpropham. Other biomarkers with high detection rates in at least four countries related to the parent pesticides boscalid, fludioxonil, pirimiphos-methyl, pyrimethanil, clothianidin, fluazifop and propamocarb. In 84% of the samples at least two different pesticides were detected. The median number of detected pesticides in the urine samples was 3, and the maximum was 13 pesticides detected in a single sample. The most frequently co-occurring substances were acetamiprid with chlorpropham (in 62 urine samples), and acetamiprid with tebuconazole (30 samples). Some variation in the probability of detection of pesticides (-metabolites) was observed with living in an agricultural area or season of urine sampling, though no consistent patterns were observed. We did observe differences in the probability of detection of a pesticide (metabolite) among children compared to adults, suggesting a different exposure and/or elimination patterns between adults and children. This survey demonstrates the feasibility of conducting a harmonized pan-European sample collection, combined with suspect screening to provide insight in the presence of exposure to pesticide mixtures in the European population, including agricultural areas. Future improvements could come from improved (harmonized) quantification of pesticide levels.

Organophosphate pesticide exposure and biomarkers of liver injury/liver function.

BACKGROUND AND AIMS: There is little epidemiological evidence linking the exposure of organophosphate pesticides (OPs) to liver function or liver injury in the general population. We used data from the National Health and Nutrition Examination Survey 1999-2012 to investigate the relationship of urinary OPs with biomarkers of liver function/liver injury. METHODS: The exposures were the concentrations of urinary OP metabolites (dimethyl phosphate [DMP], dimethyl thiophosphate [DMTP], diethyl phosphate [DEP] and diethyl thiophosphate [DETP]). The health outcomes were biomarkers of liver function/liver injury. The multivariable linear regression model, restricted cubic splines (RCSs) analysis and weighted quantile sum (WQS) regression were used to evaluate the relationship between individual or overall exposure of OPs and outcomes. RESULTS: Regressions of RCSs suggested linear and positive associations of OP metabolites with aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (DMP and DEP) and fibrosis-4 (FIB-4) index (DMP, DEP and DMTP) (all p-non-linear values >.05). However, L-shaped relationships were found between OP metabolites (DMTP and DETP) and blood albumin and total protein (TP) concentrations (both p and non-linear values <.05). The positive associations of urinary DMP, DEP and DMTP with AST/ALT ratio, and with FIB-4 score were more pronounced among non-smokers than smokers, among alcohol drinkers than non-drinkers and among those with a body mass index (BMI) of ≥25 than participants with a BMI of <25. However, most of the interaction p values were more than .05, indicating no significant interactions between covariates and OPs on outcomes mainly including AST/ALT, FIB-4, ALB and TP levels. Finally, the WQS indices were positively associated with AST/ALT ratio (p = .014) and FIB-4 score (p = .002). CONCLUSIONS: Our study added novel evidence that exposures to OPs might be adversely associated with the biomarkers of liver function/liver injury. These findings indicated the potential toxic effect of OP exposures on the human liver.

Higher proportion of agricultural land use around the residence is associated with higher urinary concentrations of AMPA, a glyphosate metabolite.

INTRODUCTION: Pesticides, including herbicides, are widely used for agricultural and sanitary reasons and concerns have been raised about their various health effects. Little research has been done into the extent to which agricultural land use in the residential surroundings contributes to (internal) exposure of pesticides. OBJECTIVES: We investigated the associations between the proportion of agricultural land use around the residence and the exposure to pesticides in adolescents in Flanders (Belgium). MATERIAL AND METHODS: We included 424 adolescents participating in the fourth Flemish Environment and Health Study (FLEHS IV) between 2016 and 2020. The residential address of all participants was geocoded and the proportion of agricultural land use around the residence was estimated in several buffers (300 m, 500 m, 1000 m and 2000 m). The concentrations of the following biomarkers of pesticides were measured in urine and adjusted for the specific gravity: glyphosate and its metabolite, aminomethyl-phosphonic acid (AMPA); 3-phenoxybenzoic acid (3-PBA); 3,5,6-trichloro-2-pyridinol (TCPy) and 2,4-dichlophenoxy-acetic acid (2,4-D). We categorized the pesticide biomarkers in three categories according to the exposure levels and used ordinal logistic regression models adjusted for sex, season and household education to estimate the odds ratio for an increase in an interquartile range (IQR) of proportion of agricultural land use. We also used binary logistic regression models in which the category of highest exposure was compared to the category of lowest exposure. In addition, we explored potential effect modification by sex and season. RESULTS: We found a significant association between the proportion of agricultural land use in a buffer of 2000 m around the residence and the levels of urinary AMPA divided into three categories (OR = 1.35 for an IQR increase in the proportion of agricultural land use around residence; 95% CI: 1.00-1.83). This association was less pronounced and not statistically significant for the other studied pesticides (OR ranging between 0.95 and 1.16). Stratified analysis showed the strongest association of the proportion of agricultural land use within 2000 m buffers for AMPA among boys (OR = 1.89; 95% CI: 1.19-3.04). Results using smaller buffers were comparable, but did not reach statistical significance. CONCLUSION: Our findings suggest that a higher proportion of agricultural land use around the residence might increase exposure to AMPA.

Pesticide exposure and cortical brain activation among farmworkers in Costa Rica.

BACKGROUND: Previous epidemiological studies have reported associations of pesticide exposure with poor cognitive function and behavioral problems. However, these findings have relied primarily on neuropsychological assessments. Questions remain about the neurobiological effects of pesticide exposure, specifically where in the brain pesticides exert their effects and whether compensatory mechanisms in the brain may have masked pesticide-related associations in studies that relied purely on neuropsychological measures. METHODS: We conducted a functional neuroimaging study in 48 farmworkers from Zarcero County, Costa Rica, in 2016. We measured concentrations of 13 insecticide, fungicide, or herbicide metabolites or parent compounds in urine samples collected during two study visits (approximately 3-5 weeks apart). We assessed cortical brain activation in the prefrontal cortex during tasks of working memory, attention, and cognitive flexibility using functional near-infrared spectroscopy (fNIRS). We estimated associations of pesticide exposure with cortical brain activation using multivariable linear regression models adjusted for age and education level. RESULTS: We found that higher concentrations of insecticide metabolites were associated with reduced activation in the prefrontal cortex during a working memory task. For example, 3,5,6-trichloro-2-pyridinol (TCPy; a metabolite of the organophosphate chlorpyrifos) was associated with reduced activation in the left dorsolateral prefrontal cortex (ß = -2.3; 95% CI: -3.9, -0.7 per two-fold increase in TCPy). Similarly, 3-phenoxybenzoic acid (3-PBA; a metabolite of pyrethroid insecticides) was associated with bilateral reduced activation in the dorsolateral prefrontal cortices (ß = -3.1; 95% CI: -5.0, -1.2 and -2.3; 95% CI: -4.5, -0.2 per two-fold increase in 3-PBA for left and right cortices, respectively). These associations were similar, though weaker, for the attention and cognitive flexibility tasks. We observed null associations of fungicide and herbicide biomarker concentrations with cortical brain activation during the three tasks that were administered. CONCLUSION: Our findings suggest that organophosphate and pyrethroid insecticides may impact cortical brain activation in the prefrontal cortex - neural dynamics that could potentially underlie previously reported associations with cognitive and behavioral function. Furthermore, our study demonstrates the feasibility and utility of fNIRS in epidemiological field studies.

An assessment of exposure to several classes of pesticides in pet dogs and cats from New York, United States.

Exposure of pet dogs and cats to pesticides used in and around homes (e.g., lawns and gardens) is a significant health concern. Furthermore, some pesticides are directly used on dogs and cats for flea, lice, and tick control. Despite this, little is known regarding the extent of pesticide exposure in pets. In this study, we determined the concentrations of 30 biomarkers of pesticide exposure in urine collected from dogs and cats in New York State, USA: 6 dialkylphosphate (DAP) metabolites of organophosphates (OPs); 14 neonicotinoids (neonics); 3 specific metabolites of OPs; 5 pyrethroids (PYRs); and 2 phenoxy acids (PAs). The sum median concentrations of these 30 pesticide biomarkers (ΣPesticides) in dog and cat urine were 35.2 and 38.1 ng/mL, respectively. Neonics were the most prevalent in dogs (accounting for 43% of the total concentrations), followed by DAPs (17%), PYRs (16%), OPs (13%), and PAs (∼10%). In cat urine, neonics alone accounted for 83% of the total concentrations. Elevated concentrations of imidacloprid were found in the urine of certain dogs (max: 115 ng/mL) and cats (max: 1090 ng/mL). Some pesticides showed gender- and sampling location- related differences in urinary concentrations. We calculated daily exposure doses of pesticides from the measured urinary concentrations through a reverse dosimetry approach. The estimated daily intakes (DIs) of chlorpyrifos, diazinon, and cypermethrin were above the chronic reference doses (cRfDs) in 22, 76, and 5%, respectively, of dogs. The DIs of chlorpyrifos, parathion, diazinon, and imidacloprid were above the cRfDs in 33, 14, 100, and 29%, respectively, of cats. This study thus provides evidence that pet dogs and cats are exposed to certain pesticides at levels that warrant immediate attention.