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The aim was to study associations between dialkylphosphates (DAPs), organophosphate (OP) metabolites in urine, biomarkers of OP insecticide exposure, and respiratory symptoms among children in upper northern Thailand. We recruited junior high school children in randomly selected schools in four cities (N = 337), with repeated data collection in wet and dry seasons. Urine was collected and analyzed for six OP metabolites, with creatinine adjustment. Total DAP was expressed as sum of DAPs. Data on respiratory symptoms was collected by a standardized questionnaire. Associations were analyzed by multiple logistic regression. Totally 11.3 % lived in farm families. Total DAPs concentration was higher in dry season (p = 0.002) but did not differ between farm and non-farm children. Total DAPs in wet season was associated with current wheeze (p = 0.019), current asthma attacks (p = 0.012) and attacks of breathlessness in last 12 months (p = 0.021). Total DAPs in dry season was associated with current wheeze (p = 0.042), and associations between DAPs and respiratory symptoms were stronger for dimethylphosphate metabolites (DMPs) than for diethylphosphate metabolites (DEPs). DMPs are produced by certain OP pesticides. Biomass burning inside or outside the home, and dampness or mold at home, enhanced the association between total DAPs and attacks of breathlessness. In conclusion, OP pesticide exposure, measured as urinary DAPs, was higher in dry season and similar in farm and non-farm children. OPs exposure, especially to DMP related pesticides, can increase asthmatic symptoms, especially in wet season. Combined exposure to OP and smoke from biomass burning, or dampness and mold, can further increase the prevalence of attacks of breathlessness. There is a need to reduce OP insecticide and biomass smoke exposure among Thai children. Since different pesticides can be used in different seasons, studies on respiratory health effects of OPs pesticide exposure should be done in different seasons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

A toxicokinetic model of the pyrethroid insecticide lambda-cyhalothrin (LCT) was developed to relate absorbed doses to urinary cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (CFMP) metabolite levels used as a biomarker of exposure. The model then served to reconstruct absorbed doses in agricultural workers and their probability of exceeding the EFSA Acceptable occupational Exposure Level (AOEL). The toxicokinetic model was able to reproduce the temporal profiles of CFMP in the urine of operators spraying pesticides using the optimized model parameters (adjusted to human volunteer data). Modeling also showed that simulation of an inadvertent oral exposure mainly was the exposure scenario giving the best fit to CFMP urinary time-course data in applicators. With the dermal model parameters optimized from data in volunteers, simulation of a dermal exposure in applicators did not allow to reproduce the observed peak excretions and urinary metabolite levels; extremely high applied dermal doses would be required but still simulated dermal penetration rate would remain too slow. Simulation of an inhalation exposure allowed to reproduce the observed time-courses, but with unrealistic air concentrations. For applicators with the highest urinary concentrations, there was a probability of exceeding the AOEL at some points during the biomonitoring period [>50% probability of exceeding for 27% of 24-h samples]; for non-applicator workers the probability of exceeding the AOEL value was very low [corresponding value of 5%]. Furthermore, the median [95% CI] estimates of 10 000 Monte Carlo simulations led to a biological reference value corresponding to the AOEL of 116 [113-119] ng/kg bw/d and 7.5 [7.3-7.7] μg/L. Overall, 7% of applicators and 1% of workers performing weeding and strawberry picking had a probability of exceeding this biological reference value. As a next step, it would be interesting to apply these methods to multiple exposure to various contaminants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Côté, Bouchard. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pyrethroids (PYR) are among the most widely used insecticides in households, leading to substantial exposure. Children and adolescents, especially during growth spurts, have a reduced capacity to effectively metabolize these insecticides. The relationship between PYR exposure and asthma in these age groups remains poorly understood, highlighting the need for further research.We used data from the 2007-2014 National Health and Nutrition Examination Survey, which included 1181 children aged 6-11 years and 1258 adolescents aged 12-19 years. The concentration of the PYR metabolite 3-phenoxybenzoic acid (3-PBA) in urine was quantified using solid-phase extraction-high-performance liquid chromatography-heated electrospray ionization tandem mass spectrometry. Asthma was defined based on self-reported doctor diagnoses from the questionnaire. PYR exposure was measured using urine samples collected simultaneously with the questionnaire. We explored the association between PYR exposure and asthma using multiple logistic regression analyses, adjusting for potential confounders.Multiple logistic regression analyses revealed no significant association between PYR exposure and asthma in children and adolescent boys (all P > 0.05). In contrast, PYR exposure was significantly associated with asthma in adolescent girls aged 12-19 years. Specifically, for "ever asthma," the odds ratios (ORs) were 2.49 (95% CI = 1.03-5.97) in the second quartile of PYR exposure and 2.48 (95% CI = 1.04-5.91) in the third quartile, each in comparison to the first quartile. For "current asthma," in comparison to the first quartile, the ORs were 3.99 (95% CI = 1.55-10.26) in the second quartile of PYR exposure, 3.39 (95% CI = 1.32-8.70) in the third quartile, and 2.93 (95% CI = 1.24-6.90) in the fourth quartile.Conclusions:Our study found a significant association between PYR exposure and asthma in adolescent girls, whereas no significant association was observed in children and adolescent boys. These findings suggest potential sex and age differences in susceptibility to PYR exposure. Further research is warranted to confirm these results and elucidate the underlying mechanisms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: Organophosphate pesticides such as malathion are the most widely used pesticides. Despite endocrine-disrupting effects, there is a paucity of information regarding chronic exposure to non-persistent organopesticides such as malathion. The purpose of this study is to describe the exposure burden among U.S. residents as well as possible impacts on fertility., Methods: Population-based data collected by the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2016 were used to perform a retrospective analysis on urinary concentrations of malathion diacid. Samples were assessed from 1703 adult participants, statistically weighted to represent over 231 million individuals. General linear models were used to examine associations between exposure and reproductive health measures among pre-menopausal women., Results: Detectable concentrations of malathion diacid were identified in 16.1 % (n = 254) of samples. Concentrations were higher among women who reported seeing a physician due to difficulties becoming pregnant (P < 0.001; r 2  = 0.12) as well as among women who reported trying for at least a year to become pregnant (P < 0.001; r 2  = 0.06)., Conclusions: Exposure to malathion is associated with a history of reproductive health challenges among women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: China produces and consumes a large amount of neonicotinoids. A non-negligible exposure to neonicotinoids might occur for Chinese pregnant women, but relevant data remain limited., Objective: To investigate the exposure to neonicotinoids by urinary biomonitoring in pregnant women from Wenzhou City, East China., Methods: We selected 432 pregnant women in Wenzhou City in 2022. A total of eight parent neonicotinoids and four metabolites were determined in single spot urine by liquid chromatography coupled to mass spectrometry. Basic characteristics, physical activity, pre-pregnant body mass index, and intake of drinking water and food were investigated by the questionnaire. Health risk was assessed by hazard quotient (HQ) and hazard index (HI) based on human safety thresholds derived from different health endpoints., Results: Neonicotinoids and their metabolites in urine had a detection frequency between 0 % and 80.1 %. At least one neonicotinoid or metabolite was detected in 93.5 % of urine samples. Except for clothianidin (51.2 %) and N-desmethyl-acetamiprid (80.1 %), the detection frequencies of other neonicotinoids and metabolites ranged from 0 % to 43.8 %. The summed concentrations of all neonicotinoids and their metabolites ranged from < LOD to 222.83 μg/g creatinine with the median concentration of 2.58 μg/g creatinine. Maternal age, educational level, occupation, household income, screen time, and pre-pregnant body mass index were associated with detection frequencies or concentrations of neonicotinoids and their metabolites. Pregnant women with higher consumption frequencies of wheat, fresh vegetable, shellfish, fresh milk, and powdered milk had higher detection frequencies of neonicotinoids and their metabolites. Both HQ and HI were less than one., Conclusions: Overall, pregnant women in Wenzhou City showed a notable frequency of exposure to at least one neonicotinoid, although the exposure frequency for each specific neonicotinoid was generally low. Several food items derived from plants and animals were potential exposure sources. A low health risk was found based on current safety thresholds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Pyrethroids are widely used pesticides and are suspected to affect children's neurodevelopment. The characterization of pyrethroid exposure during critical windows of development, such as fetal development and prenatal life, is essential to ensure a better understanding of pyrethroids potential effects within the concept of Developmental Origins of Health and Disease., Objective: The aim of this study was to estimate maternal exposure of French pregnant women from biomonitoring data and simulate maternal and fetal internal concentrations of 3 pyrethroids (permethrin, cypermethrin and deltamethrin) using a multi-substance pregnancy-PBPK (physiologically based pharmacokinetics) model. The estimated maternal exposures were compared to newly proposed toxicological reference values (TRV) children specific also called draft child-specific reference value to assess pyrethroid exposure risk during pregnancy i.e. during the in utero exposure period., Methods: A pregnancy-PBPK model was developed based on an existing adult pyrethroids model. The maternal exposure to each parent compound of pregnant women of the Elfe (French Longitudinal Study since Childhood) cohort was estimated by reverse dosimetry based on urinary biomonitoring data. To identify permethrin and cypermethrin contribution to their common urinary biomarkers of exposure, an exposure ratio based on biomarkers in hair was tested. Finally, exposure estimates were compared to current and draft child-specific reference values derived from rodent prenatal and postnatal exposure studies., Results: The main contributor to maternal pyrethroid diet intake is cis-permethrin. In blood, total internal concentrations main contributor is deltamethrin. In brain, the major contributors to internal pyrethroid exposure are deltamethrin for fetuses and cis-permethrin for mothers. Risk is identified only for permethrin when referring to the draft child-specific reference value. 2.5% of the population exceeded permethrin draft child-specific reference value., Conclusions: A new reverse dosimetry approach using PBPK model combined with human biomonitoring data in urine and hair was proposed to estimate Elfe pregnant population exposure to a pyrethroids mixture with common metabolites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities., Methods: In 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17β-estradiol, and cortisol. We used general linear models to assess linear (β = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (β 2  = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions., Results: The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (β boys  = 5.88% [1.21%, 10.78%], β girls  = 4.10% [-0.02%, 8.39%]), and cortisol (β boys  = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (β 2 boys  = -0.17 (-0.33, -0.003), p = 0.04) and DHEA (β 2 boys  = -0.49 (-0.80, -0.19), p = 0.001) in boys. The neonicotinoid summary score (β boys  = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (β boys  = 3.90% [1.28%, 6.58%]) were positively associated with 17β-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE., Conclusions: We observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17β-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The appropriate use of human biomonitoring data to model population chemical exposures is challenging, especially for rapidly metabolized chemicals, such as agricultural chemicals. The objective of this study is to demonstrate a novel approach integrating model predicted dietary exposures and biomonitoring data to potentially inform regulatory risk assessments. We use lambda-cyhalothrin as a case study, and for the same representative U.S. population in the National Health and Nutrition Examination Survey (NHANES), an integrated exposure and pharmacokinetic model predicted exposures are calibrated to measurements of the urinary metabolite 3-phenoxybenzoic acid (3PBA), using an approximate Bayesian computing (ABC) methodology. We demonstrate that the correlation between modeled urinary 3PBA and the NHANES 3PBA measurements more than doubled as ABC thresholding narrowed the acceptable tolerance range for predicted versus observed urinary measurements. The median predicted urinary concentrations were closer to the median measured value using ABC than using current regulatory Monte Carlo methods.

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., (© 2024 SETAC.)

Organophosphate (OP) insecticides are some of the most abundantly used insecticides, and prenatal exposures have been linked to adverse maternal and child health outcomes. Anogenital distance (AGD) has emerged as an early marker of androgen activity, and later reproductive outcomes, that is sensitive to alteration by environmental chemicals. Here, we examined associations between prenatal exposure to chlorpyrifos, an OP insecticide, with AGD. Pregnant farmworkers were enrolled in the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE; N = 104) between 2017 and 2019 in Northern Thailand. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos, were measured in composited urine samples obtained from each trimester of pregnancy. AGD was measured at 12 months of age. Sex-specific adjusted linear regression models were used to examine associations between average and trimester-specific TCPy levels and AGD. In adjusted models for females and males, increasing TCPy was consistently associated with a modest, non-significant reduction in AGD. Across both strata of sex, associations were greatest in magnitude for trimester 3 (females: β = -2.17, 95 % confidence interval (CI) = -4.99, 0.66; males: β = -3.02, 95 % CI = -6.39, 0.35). In the SAWASDEE study, prenatal chlorpyrifos exposure was not strongly associated with AGD at 12 months of age., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Organophosphates and pyrethroids are two major groups of insecticides used for crop protection worldwide. They are neurotoxicants and exposure during vulnerable windows of brain development may have long-term impact on human neurodevelopment. Only few longitudinal studies have investigated associations between prenatal exposure to these substances and intelligence quotient (IQ) at school age in populations with low, mainly dietary, exposure., Objective: To investigate associations between maternal urinary concentrations of insecticide metabolites at gestational week 28 and IQ in offspring at 7-years of age., Materials and Methods: Data was derived from the Odense Child Cohort (OCC). Metabolites of chlorpyrifos (TCPy) and pyrethroids (3-PBA, cis- and trans-DCCA, 4-F-3PBA, cis-DBCA) were measured in maternal urine collected at gestational week (GW) 28. An abbreviated version of the Danish Wechsler Intelligence Scale for Children fifth edition (WISC-V) consisting of four subtests to estimate full scale IQ (FSIQ) was administered by trained psychologists. Data were analyzed by use of multiple linear regression and adjusted for confounders., Results: 812 mother/child-pairs were included. Median concentrations were 0.21 μg/L for 3-PBA, 1.67 μg/L for TCPy and the mean IQ for children were 99.4. Null association between maternal 3-PBA and child IQ at 7 years was seen, but with trends suggesting an inverse association. There was a significant association for maternal TCPy and child IQ at mid-level exposure. Trans-DCCA above the level of detection (LOD) was also associated with slightly lower child IQ, but the association was also not statistically significant., Conclusions: We found no significant associations between maternal 3-PBA metabolites and child IQ at 7 years, but with trends suggesting an inverse association. A non-significant trend between maternal TCPy exposure and child IQ in 7-year-children was seen even in this low exposed population. Given the widespread exposure and increasing use of insecticides, this should be elaborated in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The extensive global use of neonicotinoid insecticides (NNIs) has led to widespread human exposure, necessitating the development of effective methods for large-scale biomonitoring. However, current methods are inadequate in simultaneously and accurately detecting various NNIs or their metabolites (m-NNIs). In this study, we aimed to establish a robust method using solid-phase extraction (SPE)-ultra high performance liquid chromatography tandem Q-Orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) for the simultaneous determination of 12 NNIs and 6 m-NNIs in human urine. Samples were prepared using Oasis HLB 96 well plate with Isopropanol: methanol (7:3, v/v) as the elution solvent. The target compounds were separated using the Accucore RP-MS column and subsequently analyzed under parallel reaction monitoring mode. NTN32692 (m/z = 255.06433) was confirmed to be the specific metabolite of cycloxaprid for the further detection. Satisfactory recoveries (81.6-122.4 %) of the NNIs and m-NNIs were observed, with intra- (n = 3) and inter-day (n = 9) relative standard deviation (RSD) ranging from 0.8 % to 13.7 % and from 1.1 % to 18.6 %, respectively. Good linearity (R 2  > 0.99) was achieved for all analytes. The limits of detection (LODs) for all target analytes ranged from 0.01 ng/mL to 0.65 ng/mL. This method was applied to urine samples collected from 10 children recruited from an agricultural area in China. Our study provides an effective method to identify and assess human exposure to NNIs and their metabolites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Acetamiprid (ACE) and imidacloprid (IMI) are insecticides of global importance and are used as spray and watering agents for ornamental plants to control biting and sucking insects or as topical medications on pets to remove and control fleas. Human biomonitoring data on ACE and IMI exposures when applying these products are limited. We investigated exposures to ACE and IMI in male volunteers after the domestic application of either an ACE-containing agent or an IMI-containing spot-on medication. Complete and consecutive urine samples were collected for up to 56 h after application. Urine samples were analyzed for ACE, IMI, and their respective metabolites ( N -desmethyl-ACE, IMI-olefin, and sum of 4-/5-hydroxy-IMI) by liquid chromatography-tandem mass spectrometry. Fairly uniform concentrations of N -desmethyl-ACE could be observed before and after orchid treatment, so that an ACE exposure associated with orchid treatment can most likely be excluded. In contrast, after the application of the IMI-containing medication, elevated concentrations of IMI, 4-/5-hydroxy-IMI, and IMI-olefin were quantified in urine samples post-20 h with maximum concentrations of 3.1, 14.9, and 8.0 μg/g creatinine, respectively, well above general background levels. Nevertheless, the IMI intake (10.6 μg/kg bw), calculated from the excreted amounts, was around five times below the current European acceptable daily intake. Based on the case results here, household exposures to ACE and IMI after spray treatment of ornamental plants and anti-flea treatment of dogs can be regarded as low and safe. However, people regularly applying neonicotinoid-containing formulations, such as professional gardeners and employees in animal shelters, should be studied in more detail., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wrobel, Koslitz, Bury, Hayen, Koch, Brüning and Käfferlein.)

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood psychiatric disorder with severe and lifelong impact on mental health and socioeconomic achievements. Environmental factors may play a role in the increasing incidens rates. Previous studies on associations between prenatal and childhood exposure to organophosphate and pyrethroid insecticides and ADHD symptoms have yielded mixed findings., Objectives: To investigate associations between prenatal and childhood exposure to chlorpyrifos and pyrethroids and ADHD symptoms in 5-year-old children from the Odense Child Cohort., Methods: Spot urine samples from pregnant women in gestational week 28 (n = 614) and offspring at 5 years of age (n = 814) were collected and analyzed for the specific metabolite of chlorpyrifos, TCPY (3,5,6-trichloro-2-pyridinol), as well as the generic pyrethroid metabolite, 3-PBA (3-phenoxybenzoic acid). Offspring ADHD symptoms were assessed at age 5 years using the parent reported "ADHD scale" from the "Child Behavior Checklist 1½-5" (n = 1114). Associations between insecticide exposure variables and an ADHD score ≥90th percentile were analyzed using logistic regression for all children and stratified by sex., Results: Most pregnant women had detectable concentrations of 3-PBA (93%) and TCPY (91%) with median concentrations of 0.20 μg/L and 1.62 μg/L, respectively. In children, 3-PBA and TCPY concentrations were detectable in 88% and 82% of the samples, and the median concentrations were 0.17 and 1.16 μg/L. No statistically significant associations were observed between insecticide metabolites and an ADHD score ≥90th percentile at age 5., Conclusion: In this relatively large Danish birth cohort study with mainly low dietary insecticide exposure, we found no statistically significant associations between prenatal or childhood exposure to chlorpyrifos or pyrethroids, and excess ADHD-symptom load, in 5-year-old children. Prospective studies with multiple urine samples across vulnerable windows of neurodevelopment is warranted to improve assessment of safe exposure levels, which is particularly relevant for pyrethroids, since their use is increasing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Chlorpyrifos (CPF) is a widely used organophosphate insecticide that has been linked to detrimental health effects that range from neurological impacts to respiratory disease. The objective of this study was to assess respiratory symptoms associated with CPF exposure throughout the application season. Urine samples were collected from Egyptian adolescent applicators ( n  = 206) and non-applicators ( n  = 72) to assess 3,5,6-trichloro-2-pyridinol (TCPy), a biomarker for CPF exposure, along with spirometry measures to determine lung ventilatory function. Samples were collected over 7 months in 2016. Logistic regression was used to model the odds of reporting wheeze symptoms based on urinary TCPy concentrations while controlling for age and smoking in the household. Ordinal multinomial logistic regression was used to model the percent reference for forced expiratory volume in one second (rFEV 1 ) based on urinary TCPy concentration (µg/g creatinine). Wheezing increased with increasing pesticide exposure (OR = 1.74 (1.32 - 2.31)). There was no statistically significant relationship between rFEV 1 and TCPy concentration. Efforts to reduce pesticide exposure should be implemented to prevent the potential onset or exacerbation of any linked respiratory complications in adolescents.

Background: Neonicotinoids are the most widely used insecticides. Laboratory studies have suggested that neonicotinoids are one potential obesogen, but relevant data are limited in human., Objective: To examine the association between exposure to neonicotinoids and childhood obesity., Methods: We investigated 442 children in Shanghai, East China and measured eight neonicotinoids (thiamethoxam, clothianidin, acetamiprid, imidacloprid, thiacloprid, nitenpyram, dinotefuran, and imidaclothiz) and four metabolites (N-desmethyl-thiamethoxam, N-desmethyl-clothianidin, N-desmethyl-acetamiprid, and 5-OH-imidacloprid) in urine. Body mass index (BMI) and waist circumference (WC) were used to identify general overweight/obesity and central obesity, respectively. Linear and logistic regression models based on generalized estimating equations were used to investigate the associations of urinary neonicotinoids and metabolites with BMI z-score, WC z-score, general overweight/obesity, and central obesity., Results: Children with a positive detection of clothianidin and its metabolite had a marginally higher BMI z-score (regression coefficient (β): 0.08, 95% confidence interval (95% CI): 0.01, 0.14) after adjusted for relevant covariates. After creatinine-adjusted concentration was trichotomized, compared to children with a negative detection, children in the high urinary concentration of acetamiprid and its metabolite had a low BMI z-score (β: -0.19, 95%CI: -0.30, -0.08), children in the medium urinary concentration of neonicotinoids and metabolites other than thiamethoxam, clothianidin, acetamiprid, and their metabolites had a marginally higher BMI z-score (β: 0.25, 95%CI: 0.03, 0.46), a higher WC z-score (β: 0.24, 95%CI: 0.14, 0.33), and a higher odds of central obesity (odds ratio (OR): 2.16, 95% CI: 1.28, 3.63), and children in the medium urinary concentration of all neonicotinoids and metabolites had a higher odds of central obesity (OR: 1.55, 95%CI: 1.04, 2.33). Some associations showed sex- and age- related differences., Conclusion: Urinary neonicotinoids and metabolites were found to be differently associated with obesity-related indexes, which suggested that exposure to neonicotinoids might have a mixed effect on childhood obesity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pyrethroids are commonly used insecticides in Brazil. Gestational and early childhood exposure to pyrethroids has been linked to adverse health effects, including neurodevelopmental delays, behavioral issues, and endocrine disruption. This study evaluated the exposure of pregnant women and their children to pyrethroid insecticides in Rio de Janeiro, Brazil., Methods: Creatinine-adjusted levels of the pyrethroid metabolites 3-phenoxy benzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzyl acid (4-FPBA) were measured in the urine of 142 pregnant women and their children at birth and in the first, third, and 6th months of life., Results: The geometric mean (GM) and 95% confidence interval (95% CI) of 3-PBA and 4-FPBA urinary concentrations in pregnant women were 0.50 (0.37-0.67) and 0.37 (0.05-2.90) ng/mg, detected in 47.2 and 10.6%, respectively. Urinary concentrations of 3-PBA in the children were 0.18 (0.15-0.23) ng/mg at birth, 0.36 (0.08-1.56) ng/mg at 1-month-old, 0.68 (0.36-1.27) ng/mg at 3-month-old, and 1.36 (0.77-2.42) ng/mg at 6-month-old, and the detection rates were respectively 10.8, 9.4, 20.9, and 20.7%., Discussion: This study is one of the few that has evaluated the urinary concentrations of pyrethroids in newborns and children in their 1 st year of life. The results of this study show that children's exposure to pyrethroids significantly increases after birth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Martins, Santos, Moreira, Câmara, Asmus, Rosa, Vineis and Meyer.)

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., Competing Interests: Conflicts of interest: None declared., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

Pesticides are a group of organic compounds used to control weeds or insect infestations in agriculture. Diet is the major route of human exposure to these compounds, which can cause serious health problems, even when the intake occurs at low concentrations. Hence, the consumption of organic food is an appropriate strategy to minimize the exposure to pesticides. A prospective, randomized study was conducted to assess the impact of an organic dietary intervention on the levels of urinary dialkyl phosphates (DAP). A screening of 204 pesticides was also carried out in order to confirm the absence of these compounds in organic food. The analytical results showed that only 20 of the 204 pesticides (9.8 %) had concentrations above the limit of quantification in one or more samples of the organic food consumed by the participants. It is substantially lower than the levels of pesticides found in other studies analysing conventional food, confirming the diet as suitable for the organic dietary intervention. A general reduction of most DAP metabolites in urine was found, being significant (p < 0.05) the decrease of dimethyl phosphate (DMP) (0.49 µg/g creatinine in Day 1 vs. 0.062 µg/g creatinine in Day 6), dimethyl thiophosphate (DMTP) (0.49 µg/g creatinine in Day 1 vs. 0.093 µg/g creatinine in Day 6) and diethyl phosphate (DEP) (0.28 µg/g creatinine in Day 1 vs. 0.12 µg/g creatinine in Day 6). In addition, the molar score for the total dimethyl DAP (ΣMP) and total dialkyl phosphate (ΣDAP) also showed significant differences after changing a conventional diet by an organic diet, being reduced from 0.008 µmol/g to 0.002 µmol/g for ΣMP and from 0.012 µmol/g to 0.003 µmol/g for ΣDAP. To the best of our knowledge, this is the first study that evaluates both the impact of an organic diet in the exposure to DAP and the levels of 204 pesticides in the organic food provided to the participants. In summary, the consumption of organic products decreases the dietary intake of pesticides, thus reducing also the potential adverse effects on human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

High urinary levels of dialkylphosphates (DAPs), which are common structures of organophosphate pesticides (OPs), have been associated with several adverse health outcomes in human biomonitoring studies. Previous studies have indicated that dietary OP exposure and ingestion of environmentally degraded DAP, which is inactive with acetylcholinesterase, can lead to an increase in urinary DAP levels in the general population. However, the specific food sources contributing to the intake of OPs and DAPs have not been identified. In this study, we analyzed the levels of OPs and preformed DAPs in various food items. DAP levels were markedly high in certain fruits, such as persimmon, apple juice, kiwi, and mandarin. In contrast, only moderate levels of OPs were detected in these foods. Furthermore, the levels of OPs and DAPs were positively associated with vegetables, whereas no such association was observed in fruits. Increased consumption of certain fruits presumably leads to a marked increase in urinary DAP levels in individuals despite limited exposure to OPs, resulting in reduced reliability of urinary DAPs as a marker of OP exposure. Therefore, the possible effects of dietary habits and the resulting intake of preformed DAPs should be considered when interpreting biomonitoring data of urinary DAPs. Additionally, DAP levels in most organic foods were much lower than those in conventional foods, suggesting that the reduction in urinary DAPs by organic diet intervention may be mainly attributed to the reduced intake of preformed DAPs rather than reduced exposure to OPs. Therefore, urinary DAP levels may not be suitable indicators for evaluating ingested OP exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 β-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-GVs GenPop , 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that may have influenced the work reported in this paper., (Copyright © 2023 Santé publique France. Published by Elsevier GmbH.. All rights reserved.)

Humans are exposed to neonicotinoid insecticides (NEOs) from various routes. Urine has been widely used to characterize the internal exposure levels of NEOs in humans. However, variable sampling methods can result in highly variable measurements of NEOs, potentially leading to misunderstanding of human exposure. In this study, we collected the first morning voids urine (FMVU), spot urine (SU), and 24 h urine (24hU) samples from 8 healthy adults during 7 consecutive days. The concentration, variability, and reproducibility of six parent NEOs (p-NEOs) and three NEOs metabolites (m-NEOs) were measured. Over 79 % of the urine samples had detectable levels of NEOs. Dinotefuran (DIN) and olefin-imidacloprid (of-IMI) were excreted in the highest concentration of p-NEO and m-NEO, respectively. All of the p-NEOs except thiacloprid (THD) and of-IMI were recommended as biomarkers for biomonitoring studies. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were used to evaluate the temporal variability and reproducibility of urinary NEOs in SU, FMVU and 24hU, respectively. We observed low ICCs ranging from 0.016 to 0.39 for NEOs regardless of the sample types. However, the higher CV and lower ICC values observed in SU samples suggested lower reproducibility compared to FMVU and 24hU samples. Significant correlations of several NEOs between FMVU and 24hU were also observed in the current study. Considering the comparable concentrations and similarity between FMVU and 24hU, our study proposed possible biomarkers and indicated that the potential for FMVU samples to estimate adequately an individual's exposure to NEOs. Therefore, we suggested FMVU as a sampling strategy in future human biomonitoring studies, while multiple samples were recommended to detect exposure over time intervals of weeks or months., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tao Zhang reports financial support was provided by National Natural Science Foundation of China. Tao Zhang reports financial support was provided by Natural Science Foundation of Guangdong Province, China., (Copyright © 2023. Published by Elsevier B.V.)

Background: Neonicotinoid insecticides (NEOs) are emerging synthetic insecticides used in various pest management regimens worldwide. Toxicology studies have indicated the obesogenic potential of NEOs, but their associations with adiposity measures are largely unknown., Objectives: We aimed to assess urinary levels of NEOs/metabolites and their associations with children's adiposity measures, and to further investigate the potential role of oxidative stress., Methods: This study included 380 children who participated in the 7th year's follow-up of the Laizhou Wan Birth Cohort in northern China. Urinary levels of seven NEOs and two metabolites and a biomarker of lipid peroxidation named 8-iso-prostaglandin-F2α (8-iso-PGF2α) were detected. A total of nine indicators of adiposity were measured. Body mass index (BMI) z-score ≥85th percentile was defined as overweight/obesity, and waist-to-height ratio (WHtR) ≥0.5 was considered as abdominal obesity. Multiple linear regression, binary logistic regression and mediation analysis were performed., Results: Six NEOs [imidacloprid (IMI, 99.7%), clothianidin (CLO, 98.9%), dinotefuran (DIN, 97.6%), thiamethoxam (THM, 95.5%), acetamiprid (ACE, 82.9%), thiacloprid (THD, 77.6%)] and two metabolites [N-desmethyl-acetamiprid (N-DMA, 100.0%), 6-chloronicotinic acid (6-CINA, 97.9%)] exhibited high detection rates. Multiple linear regressions showed positive associations of waist circumference with urinary levels of IMI and THM, of WHtR with IMI and THM levels, and of body fat percentage with 6-CINA levels. In contrast, exposure to N-DMA was negatively associated with body fat percentage and fat mass index. Binary logistic regressions further revealed that higher IMI levels were associated with overweight/obesity (OR = 1.556, 95% CI: 1.100, 2.201) and abdominal obesity (OR = 1.478, 95% CI: 1.078, 2.026) in children. 8-iso-PGF2α demonstrated 27.92%, 69.52% and 35.37% mediating effects in the positive associations of IMI, THD and THM with WHtR, respectively. Sex modified the associations of DIN with body fat mass (p int  = 0.032), body fat percentage (p int  = 0.009), fat mass index (p int  = 0.037) and the overweight/obesity rate (p int  = 0.046), with negative associations in girls and nonsignificant positive associations in boys., Conclusions: School-age children in northern China were widely exposed to NEOs/metabolites. Urinary levels of NEOs/metabolites were associated with adiposity measures through the mediating role of 8-iso-PGF2α. These associations were mixed, and a sex-specific effect might exist., Competing Interests: Declaration of competing interest The authors declare that they have no actual competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

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(β) (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(β) (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., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Neonicotinoids and neonicotinoid-like compounds (NNIs) are widely used insecticides and their ubiquitous occurrence in the environment requires methods for exposure assessment in humans. The majority of the NNIs can be divided into 6-chloropyridinyl- and 2-chlorothiazolyl-containing compounds, suggesting the formation of the group-specific metabolites 6-chloronicotinic acid (6-CNA), 2-chloro-1,3-thiazole-5-carboxylic acid (2-CTA), and their respective glycine derivatives (6-CNA-gly, 2-CTA-gly). Here, we developed and validated an analytical method based on gas chromatography coupled to mass spectrometry (GC-MS/MS) to simultaneously analyze these four metabolites in human urine. As analytical standards for the glycine conjugates were not commercially available, we synthesized 6-CNA-gly, 2-CTA-gly, and their 13 C 2 , 15 N-labeled analogs for internal standardization and quantitation by stable isotope dilution. We also ensured chromatographic separation of 6-CNA and its isomer 2-CNA. Enzymatic cleavage during sample preparation was proven unnecessary. The limits of quantitation were between 0.1 (6-CNA) and 0.4 μg/L (2-CTA-gly) and the repeatability was satisfactory (coefficient of variation was <19% over the calibration range). We analyzed 38 spot urine samples from the general population and were able to quantify 6-CNA-gly in 58% of the samples (median 0.2 μg/L). In contrast, no 6-CNA could be detected. The results are in line with well-known metabolic pathways specific in humans, that, compared to rodents, favor the formation and excretion of phase-II-metabolites (glycine derivatives) rather than phase-I metabolites (free carboxylic acids). Nevertheless, the exact source of exposure (i.e., the specific NNI) remains elusive in the general population, may even vary quantitatively between different NNIs, and also might be regional specific based on the respective use of individual NNIs. In sum, we developed a robust and sensitive analytical method for the determination of four group-specific NNI metabolites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 β [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.

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., Competing Interests: Declarations of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Current-use pesticides (CUP) are extensively applied in both agricultural and urban settings. Exposure occurs mainly via the dietary pathway; however, other pathways such as inhalation or skin contact are also important. In this study, urinary levels of 12 CUP metabolites were investigated among 110 parent-child pairs during two seasons of 2020. Metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH) were detected in more than 60% of the samples. Chlorpyrifos metabolite was found at the highest concentration and tebuconazole was detected in almost all samples. CUP urinary metabolite levels were significantly higher in children in comparison to adults, except for tebuconazole, which was similar in both groups. In children, winter samples had significantly higher concentrations of pyrethroid and chlorpyrifos metabolites in comparison to the summer samples, but in adults, only chlorpyrifos metabolite concentrations were higher in the winter. No association between CUP urinary metabolite levels and proximity/surface of agricultural areas around residences was observed. Based on our findings, we suspect that CUP exposure is mainly driven by diet and that the effect of environmental exposure is less significant. Daily Intakes were estimated with three possible scenarios considering the amount of the metabolite excreted in urine and were compared to Acceptable Daily Intake values. Using a realistic scenario, exposure to chlorpyrifos exhibited the highest health risk, but still within a safe level. The Acceptable Daily Intake was exceeded only in one child in the case of cypermethrin. The cumulative risk assessment of pesticide mixtures having an effect on the nervous system, based on the total margin of exposure calculations, did not indicate any risk. The overall risk associated with pesticide exposure in the observed population was low. However, the risk observed using the worst-case scenario suggests the need for continuous evaluation of human exposure to such compounds, especially in children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Organophosphate (OP) pesticides act by inhibiting acetylcholinesterase activity at synaptic junctions and have already been linked with deleterious effects on neurodevelopment, including autism spectrum disorders (ASD)., Objectives: To investigate the association of prenatal exposure to OP pesticides with traits related to ASD in 11-year-old children., Methods: The "Childhood Autism Spectrum Test" (CAST) parent questionnaire was used to screen for autistic traits in 792 children from the French PELAGIE cohort. Prenatal maternal urine samples were collected <19 weeks of gestation in which metabolites of organophosphate insecticides were assessed for 185 of them. Negative binomial regression models were performed to explore the association between the CAST score and 8 groups of urine components, adjusted for potential ASD risk factors., Results: In these urine samples, dialkylphosphates (DAP) were detected most often (>80%), terbufos and its metabolites least often (<10%). No association with ASD was found for DAP, terbufos or its metabolites. Incidence rate ratios (IRRs) increased with maternal urinary diazinon concentrations, from 1.11 (95% CI: 0.87-1.42) to 1.17 (95% CI: 0.94-1.46). Higher CAST scores were statistically significantly associated with the maternal urine samples in which chlorpyrifos or two of its metabolites (chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol) were detected. The IRR for exposure to chlorpyrifos or chlorpyrifos-oxon was 1.27 (95%CI: 1.05-1.52) among all children, and 1.39 (95%CI: 1.07-1.82) among boys., Conclusion: These findings suggest an increase in autistic traits among 11-year-old children in association with prenatal maternal exposure to chlorpyrifos and possibly diazinon. These associations were previously suspected in the literature, in particular for chlorpyrifos. Further work establishing the causal mechanisms behind these risk association is needed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Organophosphate (OP) insecticides represent one of the largest classes of sprayed insecticides in the U.S., and their use has been associated with various adverse health outcomes, including disorders of blood pressure regulation such as hypertension (HTN)., Methods: In a study of 935 adults from the NHANES 2013-2014 cycle, we examined the relationship between systolic and diastolic blood pressure changes and urinary concentrations of three OP insecticides metabolites, including 3,5,6-trichloro-2-pyridinol (TCPy), oxypyrimidine, and para-nitrophenol. These metabolites correspond to the parent compounds chlorpyrifos, diazinon, and methyl parathion, respectively. Weighted, multivariable linear regression analysis while adjusting for potential confounders were used to model the relationship between OP metabolites and blood pressure. Weighted, multivariable logistic regression analysis was used to model the odds of HTN for quartile of metabolites., Results: We observed significant, inverse association between TCPy on systolic blood pressure (β-estimate = -0.16, p < 0.001) and diastolic blood pressure (β-estimate = -0.15, p < 0.001). Analysis with para-nitrophenol revealed a significant, positive association with systolic blood pressure (β-estimate = 0.03, p = 0.02), and an inverse association with diastolic blood pressure (β-estimate = -0.09, p < 0.001). For oxypyrimidine, we observed significant, positive associations between systolic blood pressure (β-estimate = 0.58, p = 0.03) and diastolic blood pressure (β-estimate = 0.31, p < 0.001). Furthermore, we observed significant interactions between TCPy and ethnicity on systolic blood pressure (β-estimate = 1.46, p = 0.0036). Significant interaction terms were observed between oxypyrimidine and ethnicity (β-estimate = -1.73, p < 0.001), as well as oxypyrimidine and BMI (β-estimate = 1.51 p < 0.001) on systolic blood pressure, and between oxypyrimidine and age (β-estimate = 1.96, p = 0.02), race (β-estimate = -3.81 p = 0.004), and BMI on diastolic blood pressure (β-estimate = 0.72, p = 0.02). A significant interaction was observed between para-nitrophenol and BMI for systolic blood pressure (β-estimate = 0.43, p = 0.01), and between para-nitrophenol and ethnicity on diastolic blood pressure (β-estimate = 2.19, p = 0.006). Lastly, we observed a significant association between the odds of HTN and TCPy quartiles (OR = 0.65, 95% CI [0.43,0.99])., Conclusion: Our findings support previous studies suggesting a role for organophosphate insecticides in the etiology of blood pressure dysregulation and HTN. Future studies are warranted to corroborate these findings, evaluate dose-response relationships between organophosphate insecticides and blood pressure, determine clinical significance, and elucidate biological mechanisms underlying this association., (© 2022. The Author(s).)

Background: Previous epidemiological evidence mainly focused on the adverse effects of prenatal exposure to pyrethroid insecticides (PYRs) on respiratory health during childhood. It remains unclear whether the PYR exposures can also impact on children's lung function., Objectives: To explore the potential effects of prenatal PYR exposures on lung function in a population of Chinese children., Methods: This study included 233 mother-child dyads from the Laizhou Wan Birth Cohort (LWBC), Shandong province, northern China, between September 2010 and December 2013. Three metabolites of PYRs [3-phenoxybenzoic acid (3-PBA), and cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans-DCCA)] were measured using gas chromatography-mass spectrometry (GC-MS) in maternal urine samples collected at recruitment. Lung function was assessed with spirometry in children aged 6-8 years. Multivariable linear regression and generalized linear models (GLMs) assessed the associations of prenatal PYR exposures with lung function in children., Results: Among the PYR metabolites, 3-PBA (81.5%) were most frequently detected, followed by trans-DCCA (55.4%) and cis-DCCA (21.9%). The 3-PBA concentration was associated with a 1% decrease in FEV 1 /FVC in the highest quartiles of exposure compared to the lowest quartile, with a potential dose response association (p-trend = 0.085). Our findings provide a suggestive effect modification by sex, with girls being more susceptible than the boys (p-trend = 0.011). However, there were no associations between the trans-DCCA concentration and lung function parameters., Conclusion: Prenatal 3-PBA concentrations were associated with a modest decrease in FEV 1 /FVC among school-aged children, and the association was slightly more pronounced for the girls than for the boys., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Only few studies have compared environmental pesticide air concentrations with specific urinary metabolites to evaluate pathways of exposure. Therefore, we compared pyrimethanil and chlorpyrifos concentrations in air with urinary 4-hydroxypyrimethanil (OHP, metabolite of pyrimethanil) and 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) among pregnant women from the Infant's Environmental Health Study (ISA) in Matina County, Costa Rica., Methods: During pregnancy, we obtained repeat urinary samples from 448 women enrolled in the ISA study. We extrapolated pyrimethanil and chlorpyrifos concentrations measured with passive air samplers (PAS) (n = 48, from 12 schools), across space and time using a Bayesian spatiotemporal model. We subsequently compared these concentrationswith urinary OHP and TCPy in 915 samples from 448 women, usingseparatemixed models andconsidering several covariables., Results: A 10% increase in air pyrimethanil (ng/m 3 ) was associated with a 5.7% (95% confidence interval (CI 4.6, 6.8) increase in OHP (μg/L). Women living further from banana plantations had lower OHP: -0.7% (95% CI -1.2, -0.3) for each 10% increase in distance (meters) as well as women who ate rice and beans ≥15 times a week -23% (95% CI -38, -4). In addition, each 1 ng/m 3 increase in chlorpyrifos in air was associated with a 1.5% (95% CI 0.2, 2.8) increase in TCPy (μg/L), and women working in agriculture tended to have increased TCPy (21%, 95% CI -2, 49)., Conclusion: The Bayesian spatiotemporal models were useful to estimate pyrimethanil and chlorpyrifos air concentrations across space and time. Our results suggest inhalation of pyrimethanil and chlorpyrifos is a pathway of environmental exposure. PAS seems a useful technique to monitor environmental current-use pesticide exposures. For future studies, we recommend increasing the number of locations of environmental air measurements, obtaining all air and urine measurements during the same month, and, ideally, including dermal exposure estimates as well., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Over the past two decades, domestic shipments of glyphosate (Gly), in the form of an ionic salt, have been increasing steadily in Japan. This increase has raising concerns about the effects of chemical exposure on children. The International Agency for Research on Cancer classified Gly as a "probably carcinogenic to humans (Group 2A)" in 2015. The purpose of the current study was to analyze Gly in urine samples of Japanese children to determine temporal changes, seasonal changes, and gender differences., Method: First-morning urine samples were obtained from 50 Japanese children (4-6-year-old) in October of 2006, 2011, and 2015 (total = 150) to investigate the temporal trends in urinary Gly concentrations. Additionally, first-morning urine samples were collected from 3-year-old children in August-September of 2012 (summer; n = 42) and in February of 2013 (winter; n = 42) to investigate the seasonal and gender differences, and the correlations between urinary Gly concentrations and insecticide exposure biomarkers. Urine samples were analyzed to measure for Gly using a liquid chromatography with tandem mass spectrometry (LC-MS/MS)., Results: Detectable Gly concentrations were found in 41% of the 234 children. The 75th percentile and maximum concentrations of urinary Gly were 0.20 and 1.33 μg/L, respectively. The urinary Gly concentration in 2015 was significantly higher than in 2006, suggesting that the Gly exposure levels have been increasing. No seasonal or gender-specific differences in urinary Gly concentrations were observed, and no correlation with insecticide exposure biomarkers was found., Conclusion: This study revealed that Gly exposure trends show an increase between 2006 and 2015, and that season and gender were not the exposure-determining factors. Overall, urinary concentrations of Gly were comparable with studies from other countries., (Copyright © 2022. Published by Elsevier GmbH.)

This study aimed to assess pesticide exposure and its determinants in children aged 5-14 years. Urine samples (n = 953) were collected from 501 participating children living in urban areas (participant n = 300), rural areas but not on a farm (n = 76), and living on a farm (n = 125). The majority provided two samples, one in the high and one in the low spraying season. Information on diet, lifestyle, and demographic factors was collected by questionnaire. Urine was analysed for 20 pesticide biomarkers by GC-MS/MS and LC-MS/MS. Nine analytes were detected in > 80% of samples, including six organophosphate insecticide metabolites (DMP, DMTP, DEP, DETP, TCPy, PNP), two pyrethroid insecticide metabolites (3-PBA, trans-DCCA), and one herbicide (2,4-D). The highest concentration was measured for TCPy (median 13 μg/g creatinine), a metabolite of chlorpyrifos and triclopyr, followed by DMP (11 μg/g) and DMTP (3.7 μg/g). Urine metabolite levels were generally similar or low compared to those reported for other countries, while relatively high for TCPy and pyrethroid metabolites. Living on a farm was associated with higher TCPy levels during the high spray season. Living in rural areas, dog ownership and in-home pest control were associated with higher levels of pyrethroid metabolites. Urinary concentrations of several pesticide metabolites were higher during the low spraying season, possibly due to consumption of imported fruits and vegetables. Organic fruit consumption was not associated with lower urine concentrations, but consumption of organic food other than fruit or vegetables was associated with lower concentrations of TCPy in the high spray season. In conclusion, compared to other countries such as the U.S., New Zealand children had relatively high exposures to chlorpyrifos/triclopyr and pyrethroids. Factors associated with exposure included age, season, area of residence, diet, in-home pest control, and pets., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Since chlorpyrifos (CPF), a major organophosphorus pesticide, is widely used for agricultural and domestic purposes, thus, humans may be exposed to these toxic compounds through multiple sources. In recent years, significant concerns have been raised regarding the deleterious effects of exposure to CPF on human health, especially growing fetus. Therefore, in this study, we aimed to evaluate the health risks of exposure to CPF among pregnant women living in Isfahan province, Iran, using deterministic and probabilistic approaches. The urinary concentration of 3, 5, 6-trichloro-2-pyridinol (TCP), the most common metabolite of CPF, was measured as the biomarker of current exposure to CPF. For this purpose, spot urine samples were taken from 110 pregnant women and the urinary concentrations of TCP were quantified. The estimated daily intake and hazard quotient (HQ) for CPF exposure were measured according to the reference values set by World Health Organization (WHO) and United States Environmental Protection Agency (US EPA) for acute and chronic exposure to CPF. Based on the results, TCP was detected in more than 70% of samples (3.8 ± 2.72 μg/L). The estimated daily intake for some participants was found to be higher than the suggested reference dose by USEPA for chronic exposure to CPF. Furthermore, the HQ>1 was obtained for 20% of the study population in Monte-Carlo analysis using USEPA chronic reference dose, indicating that chronic toxic effects are expected at least for a part of the target population. Based on the findings, proper measures should be taken to reduce the exposure of Iranian pregnant women to CPF and resultant health risks., Competing Interests: The authors have declared that no competing interests exist.

Neonicotinoids are systemic insecticides used since the 1990's , that possess renal tubular toxicity. We conducted a field-based descriptive study in the North Central Dry-zone of Sri Lanka, where chronic kidney disease (CKD) of unknown etiology has been increasing since the 1990's. To elucidate the relationship between renal tubular dysfunctions and urinary neonicotinoids concentrations, we collected spot urine samples from15 CKD patients, 15 family members, and 62 neighbors in 2015, analyzed two renal tubular biomarkers, Cystatin-C and L-FABP, quantified seven neonicotinoids and a metabolite N-desmethyl-acetamiprid by LC-MS/MS; and we investigated their symptoms using a questionnaire. Cystatin-C and L-FABP had a positive correlation (p < 0.001). N-Desmethyl-acetamiprid was detected in 92.4% of the urine samples, followed by dinotefuran (17.4%), thiamethoxam (17.4%), clothianidin (9.8%), thiacloprid and imidacloprid. Dinotefuran and thiacloprid have never been registered in Sri Lanka. In High Cystatin-C group (> 70 μg/gCre, n = 7), higher urinary concentration of dinotefuran (p = 0.009), and in Zero Cystatin-C group (< LOQ, n = 7), higher N-desmethyl-acetamiprid (p = 0.013), dinotefuran (p = 0.049), and thiacloprid (p = 0.035), and more complaints of chest pains, stomachache, skin eruption and diarrhea (p < 0.05) were found than in Normal Cystatin-C group (n = 78). Urinary neonicotinoids may be one of the potential risk factors for renal tubular dysfunction in this area., (© 2021. The Author(s).)

Background: This study aims to establish an in vitro monitoring approach to evaluate the pesticide exposures. We studied the in vitro cytotoxicity of three different body fluids of rats to the respective corresponding tissue-derived cells., Methods: Wistar rats were orally administrated daily with three different doses of chlorpyrifos (1.30, 3.26, and 8.15 mg/kg body weight/day, which is equal to the doses of 1/125, 1/50, and 1/20 LD 50 , respectively) for consecutive 90 days. Blood samples as well as 24-hour urine and fecal samples were collected and processed. Then, urine, serum, and feces samples were used to treat the correspondent cell lines, i.e., T24 bladder cancer cells, Jurkat lymphocytes, and HT-29 colon cancer cells respectively, which derived from the correspondent tissues that could interact with the respective corresponding body fluids in organism. Cell viability was determined by using MTT or trypan blue staining., Results: The results showed that urine, serum, and feces extract of the rats exposed to chlorpyrifos displayed concentration- and time-dependent cytotoxicity to the cell lines. Furthermore, we found that the cytotoxicity of body fluids from the exposed animals was mainly due to the presence of 3, 4, 5-trichloropyrindinol, the major toxic metabolite of chlorpyrifos., Conclusions: These findings indicated that urine, serum, and feces extraction, especially urine, combining with the corresponding tissue-derived cell lines as the in vitro cell models could be used to evaluate the animal exposure to pesticides even at the low dose with no apparent toxicological signs in the animals. Thus, this in vitro approach could be served as complementary methodology to the existing toolbox of biological monitoring of long-term and low-dose exposure to environmental pesticide residues in practice., (© 2021. The Author(s).)

To reduce the exposure of the French West Indies population to the organochlorine insecticide chlordecone (Kepone; CLD), the contamination of currently consumed foodstuffs must be reduced. Depuration of contaminated animals before slaughter could be a strategy to obtain safe animal products. The aim of this study was to characterize and quantify CLD elimination in contaminated ewes during depuration process. Experiments A and B consisted in a single intravenous (i.v.) administration of CLD (n = 5) and CLDOH (chlordecol; n = 3) followed by a 84-d and 3-d depuration period respectively with collection of blood, faeces and urine samples. After CLD administration, CLD and conjugated-CLDOH (CLDOH-C) were quantified in serum and urine and CLD and CLDOH were quantified in faeces. Based on calculations of faecal, urinary and body clearances of CLD and CLDOH-C, faeces appeared as the major route of CLD excretion with 86 % of the CLD administered dose eliminated in faeces, either as CLD (51 %) or as CLDOH (35 %)., (Copyright © 2021. Published by Elsevier B.V.)

Pesticide poisoning is a common occurrence due to their widespread use, easy access and high toxicity even in small concentrations. The most common poisoning fatalities have been observed due to exposure to organophosphates, carbamates and neonicotinoids, thus development of a method for the rapid determination of these compounds in blood and urine is of great importance for clinical and toxicology laboratories. A simple, fast and reliable method was developed for the determination of 9 pesticides in blood and urine using HPLC-MS/MS instrumentation. In order to find the most suitable sample pretreatment technique, three different sample preparation procedures: SPE, protein precipitation and QuEChERS were compared. The final optimized analytical method was fully validated with the values of parameters such as calibration linearity, accuracy, precision, recovery, matrix effect and stability being acceptable. The method proved reliable, accurate, robust and sensitive and was successfully applied for the quantitation of pesticides in three postmortem cases of pesticides poisoning., (Copyright © 2021. Published by Elsevier B.V.)

Results of this paper provide evidence that chronic long-term exposure to organophosphorus insecticides poses a significantly higher health risk for US women than for men, based on dialkylphosphate biomarker data from NHANES cycles 2003-2012. The risk of cardiovascular disease for female non-smokers aged 60-85 years in the highest dimethylthiophosphate (DMTP) urinary concentration quartile is 3.0 (odds ratio, OD = 3.0, 95%CI 1.4-6.4) times higher than that in the lowest quartile. Women with higher urinary DMTP concentrations also have significantly higher risk of asthma at the ages 6-39 years and an apparently higher risk of chronic bronchitis at the ages 60-85. Overall cancer risk is significantly higher for female non-smokers aged 60-85 years in the higher urinary DMTP quartiles (OD = 2.7, 95% CI 1.3-5.9). Increasing risks of breast cancer for female smokers and prostate cancer for male smokers aged 60-85 years with higher exposure to organophosphorus insecticides in the US are also significant., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Neonicotinoid insecticides (neonicotinoids) are widely used, however, they can negatively affect human health. Thus, neonicotinoids and their metabolites in human urine are analyzed globally to assess exposure levels and health risks. To properly assess the exposure levels and health risks, accurate analytical results are a necessity., Objective: This study aims to develop urine certified reference material (CRM), NMIJ CRM 7408-a, for the quantification of neonicotinoids., Method: To develop NMIJ CRM 7408-a, commercially available artificial urine was used as the raw material to which the target neonicotinoids were added. Analyses of neonicotinoids in NMIJ CRM 7408-a were carried out by isotope dilution mass spectrometry (IDMS)., Results: Sample homogeneity was assessed, with the results showing that acetamiprid, clothianidin, thiacloprid, and thiamethoxam exhibited sufficiently homogeneous distributions in the material. The relative uncertainties due to inhomogeneity were 1.2-7.0%. The results obtained from long-term stability assessment indicated that the target neonicotinoids were stable. The relative uncertainties due to instability were 9.4-17.2% (for an expiry date of 21 months). The characterization for providing concentration values was carried out using one (clothianidin and thiacloprid) or two (acetamiprid and thiamethoxam) analytical methods. The certified values of the target neonicotinoids (acetamiprid, clothianidin, thiacloprid, and thiamethoxam) were 0.19-1.38 µg/kg., Conclusions: This is the first frozen artificial urine CRM in which neonicotinoids were quantified by IDMS and will be useful for evaluating the accuracy of analysis and validation of analytical methods for the determination of neonicotinoids in urine., Highlights: NMIJ CRM 7408-a, which has been certified for four neonicotinoids, was developed by NMIJ., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Our study aimed to investigate dietary and non-dietary predictors of exposure to pyrethroids, organophosphates pesticides and 2,4-D herbicide in two cohorts of pregnant women in New York City: 153 women from the Thyroid Disruption and Infant Development (TDID) cohort and 121 from the Sibling/Hermanos Cohort(S/H). Baseline data on predictors were collected from the women at time of recruitment. We used three different modeling strategies to address missing data due to biomarker values below the limit of detection (

Single-spot urine is often used to estimate organophosphorus insecticide (OP) exposure. However, variations of urinary metabolite concentrations during the day are considerable as OP half-lives are short and as diet is their main exposure source. In addition, quality control is indispensable for institutions that analyze these metabolites. This study aimed to clarify (1) adequate frequencies of urine collection for estimating OP exposure and (2) interlaboratory variation in measured concentrations of OP metabolites, dialkylphosphates (DAPs). To quantify intra-individual variations, urine was collected eight times during a period that spanned 5 consecutive days from nine children aged 5-6 years. For interlaboratory variations, 41 spot samples from 14 pregnant women and 13 three-year-old children were used. Intraclass correlation coefficients for the DAPs were moderate but misclassification occurred in > 50% of the surrogate category analyses using single measurements. The misclassification frequency decreased to satisfactory levels when three temporal measurements were conducted. Values of four DAPs measured in the two laboratories correlated well except in the cases of urine samples obtained from two pregnant women. In conclusion, urinary DAPs should be measured from spot urine samples obtained during 3 different days. Sharing matrix-contained standards and quality control samples should minimize interlaboratory variations.

Background: Pyrethroid exposure in the household environment affects children directly via inhalation or dermal exposure. Hand wipes can effectively predict pyrethroid exposure to young children along with the children's activities. The main purpose of this study is to identify the relationship between 3-PBA metabolites, hand wipe sample concentrations and multiple exposure factors, within the population of households with young children in urban Bangkok, Thailand., Methods: Interviews were conducted with the parents of 80 children (aged 2-3 years). Urine was collected to analyze for 3-PBA metabolites and hand wipe samples were collected to analyze for cypermethrin. Both were analyzed by gas chromatography (GC/MS)., Results: A Spearmen's correlation test of the increase of 3-PBA metabolites was significantly associated with an increase in hand wipe samples (cypermethrin) in children (r s = 0.226-0.274, p -value < 0.05). The binary logistic regression test presented an association between exposure factors with 3-PBA metabolite concentration. Gender presented a significant association with 3-PBA metabolites ( p -value = 0.035, OR = 0.326, 95% CI 0.115-0.926), and frequency of bare feet inside the household presented a significant association with 3-PBA metabolites ( p -value < 0.01, OR = 7.072, 95% CI 1.707-29.291). In addition, exposure factors were not significantly associated with wipe sample concentration (cypermethrin) but showed high risk of exposure to young children., Conclusions: Suggestions to reduce the risk from long-term pyrethroid insecticide exposure to children living in households include increased education, awareness, and management., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Environmental factors, including high temperature and humidity, can influence dermal absorption of chemicals. Soldiers can be dermally exposed to permethrin while wearing permethrin-treated uniforms. This study aimed at examining the effects of high temperature and a combined high temperature and humid environment on permethrin absorption compared with ambient conditions when wearing a permethrin-treated uniform. Twenty-seven male enlisted soldiers wore study-issued permethrin-treated army uniforms for 33 consecutive hours in three different environments: 1) simulated high temperature (35°C, 40% relative humidity [rh]) ( n = 10), 2) simulated high temperature and humidity (30°C, 70% rh) ( n = 10), and 3) ambient conditions (13°C, 60% rh) ( n = 7). Spot urine samples, collected at 21 scheduled time points before, during, and after wearing the study uniforms, were analyzed for permethrin exposure biomarkers (3-phenoxybenzoic acid, cis - and trans -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid) and creatinine. Biomarker concentrations were 60-90% higher in the heat and combined heat/humidity groups ( P < 0.001-0.022) than the ambient group. Also, the average daily permethrin dose, calculated 12 hours after removing the treated uniforms, was significantly higher in the heat ( P = 0.01) and the heat/humidity ( P = 0.03) groups than the ambient group. There were no significant differences in biomarker concentrations or computed average daily dose between the heat and the heat/humidity groups. Both hot and combined hot and humid environmental conditions significantly increased permethrin absorption in soldiers wearing permethrin-treated uniforms.

Background and Aim: Metofluthrin, profluthrin, tefluthrin, and transfluthrin are pyrethroid (PYR) insecticides increasingly used to control mosquitoes, flies, and moths in households and public places (hygiene-PYRs). Currently, there is limited data available concerning exposure to these novel hygiene-PYRs. The goal of this study was to monitor exposure to these hygiene-PYRs by analysing their urinary metabolites and to investigate the temporal and seasonal trends in the concentrations of these metabolites., Methods: First morning urine samples were obtained from 50 Japanese children (four-six years old) in October of 2006, 2011, and 2015 (total = 150 children) in order to investigate temporal trends. Additionally, first-morning urine samples were collected from 44 three-year-old children in August-September of 2012 (summer) and in February of 2013 (winter) to investigate seasonal differences. The urinary concentrations of 2,3,5,6-tetrafluorobenzyl alcohol (FB-Al; a specific metabolite of transfluthrin), 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (CH 3 -FB-Al; a common metabolite of tefluthrin and profluthrin), 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (CH 3 OCH 2 -FB-Al; a specific metabolite of metofluthrin), and 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH 2 -FB-Al; a common metabolite of metofluthrin, tefluthrin, and profluthrin) were measured using GC-MS/MS., Results: For the investigated years, rapid increases in the detection rates of the hygiene-PYR metabolites were observed. In 2015, FB-Al was identified in 64% of the samples, CH 3 -FB-Al in 46%, CH 3 OCH 2 -FB-Al in 50%, and HOCH 2 -FB-Al in 83%. Significant increasing trends were found for the concentrations of all hygiene-PYR metabolites from 2006 to 2015 (Jonckheere-Terpstra test, p < 0.001). The concentrations of FB-Al and CH 3 OCH 2 -FB-Al were higher in summer than in winter (Mann Whitney-U test, p < 0.05)., Conclusions: These findings suggest that, in Japanese children, exposure to hygiene-PYRs has increased over the past decade, and that children are exposed to higher levels of hygiene-PYRs in summer than in winter., Competing Interests: Declarations of competing interest None., (Copyright © 2019. Published by Elsevier GmbH.)

Diazinon poisoning is an important issue in occupational, clinical, and forensic toxicology. While sensitive and specific enough to analyse diazinon in biological samples, current methods are time-consuming and too expensive for routine analysis. The aim of this study was therefore to design and validate a simple dispersive liquid-liquid microextraction (DLLME) for the preparation of urine samples to be analysed for diazinon with high performance liquid chromatography with diode-array detector (HPLC-DAD) to establish diazinon exposure and poisoning. To do that, we first identified critical parameters (type and volume of extraction and disperser solvents, pH, surfactant, and salt concentrations) in preliminary experiments and then used central composite design to determine the best experimental conditions for DLLME-HPLC-DAD. For DLLME they were 800 µL of methanol (disperser solvent) and 310 µL of toluene (extraction solvent) injected to the urine sample rapidly via a syringe. The sample was injected into a HPLC-DAD (C18 column, 250×4.6 mm, 5 μm), and the mobile phase was a mixture of acetonitrile and buffer (63:37 v/v, pH 3.2; flow rate: 1 mL/ min). Standard calibration curves for diazinon were linear with the concentration range of 0.5-4 µg/mL, yielding a regression equation Y=0.254X+0.006 with a correlation coefficient of 0.993. The limit of detection and limit of quantification for diazinon were 0.15 µg/mL and 0.45 µg/mL, respectively. The proposed method was accurate, precise, sensitive, and linear over a wide range of diazinon concentrations in urine samples. This method can be employed for diazinon analysis in routine clinical and forensic toxicology settings.