Dataset Information

Organophosphate pesticide metabolite levels in pre-school children in an agricultural community: within- and between-child variability in a longitudinal study.

ABSTRACT: This study characterized the within- and between-child variability in dimethylthiophosphate (DMTP) levels in the urine of 44 children living in an agricultural community in central Washington State in December 1997 and 1999. The goal of this analysis was to investigate these variability components during periods when organophosphate pesticides were and were not actively applied to orchards in that community. Each child provided between 10 and 26 biweekly urine samples over a 21-month period, and these samples were analyzed for six dialkylphosphate (DAP) metabolites common to organophosphate pesticides, including DMTP. Previous analysis of this dataset found that DAP concentrations were elevated during months when organophosphate pesticides were applied to orchards in this region. The current analysis demonstrates that the within-child component of day-to-day variability was much greater than the between-child component of variability by a factor of 3-7 across the DAP metabolites that were analyzed. Therefore, organophosphate pesticide exposure appeared to vary more than 3 times from day-to-day than from child-to-child. This finding has important implications for epidemiologic and exposure pathways research, since accounting for within-child variability may increase the power of a study and allow for the detection of differences that would not otherwise be possible without an analysis that separates out the within-child variability.

SUBMITTER: Griffith W

PROVIDER: S-EPMC3726011 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Organophosphate pesticide metabolite levels in pre-school children in an agricultural community: within- and between-child variability in a longitudinal study.

Griffith W W Curl C L CL Fenske R A RA Lu C A CA Vigoren E M EM Faustman E M EM

Environmental research 20110602 6

This study characterized the within- and between-child variability in dimethylthiophosphate (DMTP) levels in the urine of 44 children living in an agricultural community in central Washington State in December 1997 and 1999. The goal of this analysis was to investigate these variability components during periods when organophosphate pesticides were and were not actively applied to orchards in that community. Each child provided between 10 and 26 biweekly urine samples over a 21-month period, and ...[more]

PMID: 21636082

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Project description:Organophosphate (OP) pesticides remain widely used in agriculture. Previously, we reported that PON1 genotype was directly associated with neurodevelopment at age two, and that PON1 genotype may increase susceptibility to OP exposure.We examined the relationships of maternal and child PON1 genotype and enzyme activity levels and neurodevelopment at school age and examined their interaction with maternal dialkyl phosphate (DAP) metabolite levels to investigate differential susceptibility to OP-related neurotoxicity.Participants were from the CHAMACOS longitudinal birth cohort of Latino families in an agricultural region of California. We measured DAP metabolites of OP pesticides in maternal and child urine samples, and analyzed PON1192 and PON1-108 genotypes and enzyme activity [arylesterase (ARYase), paraoxonase (POase)] in maternal and child blood. We examined their association with children?s performance on the Conners? Kiddie Continuous Performance Test (K-CPT) at 5 years (n=296) and the Wechsler Intelligence Scale for Children (WISC-IV) at 7 years (n=327).Maternal and child PON1 genotype was not related to performance on K-CPT or WISC, although WISC scores tended to be lowest in children and children of mothers who carried the PON-108TT genotype. Pregnancy ARYase levels were positively associated with all WISC subscales (e.g., 4.0 point increase in Full Scale IQ per standard deviation increase in ARYase, 95% CI=1.6, 6.4), while pregnancy POase levels were positively associated with WISC Processing Speed only. Maternal PON1-108 weakly modified the relationship of maternal DAPS and K-CPT scores (pinteraction=0.21) and WISC verbal IQ (pinteraction=0.71). The association between DAPs and Full-Scale IQ was strongest for children of mothers with lowest-tertile ARYase levels (pinteraction=0.27). This relationship held for both diethyl and dimethyl DAPs and for all subscales of the WISC.We extend our previous findings that PON1 genotype and enzyme levels may be directly related to performance on certain domains of neurodevelopment in school-age children. Lower maternal PON1 enzyme levels during pregnancy may also increase susceptibility of children to neurotoxicity from OP pesticide exposure.

Project description:BackgroundSpot urine samples are often used to assess exposure to organophosphate (OP) pesticides in place of "gold standard" 24-hr samples, which are cumbersome to collect. Assessment of non-persistent chemicals using spot urine samples may result in exposure misclassification that could bias epidemiological analyses towards the null. Few studies have examined the validity of measurements of urinary metabolites in spot samples to estimate daily OP dose or the potential implications of reliance on spot samples for risk assessments.ObjectiveExamine the validity of using first morning void (FMV) and random non-FMV urine samples to estimate cumulative 24-hr OP pesticide dose among children living in an agricultural region.MethodsWe collected urine samples over 7 consecutive days, including two 24-hr samples, from 25 children living in an agricultural community. We used measurements of urinary dialkylphosphate (DAP) metabolites, data on nearby agricultural pesticide applications, and daily dietary intake data to estimate internal dose from exposure to a mixture of OP pesticides according to the U.S. Environmental Protection Agency Cumulative Risk Assessment guidelines. Dose estimates from volume- and creatinine-adjusted same-day FMV and non-FMV spot urine samples were compared to the "gold standard" estimates from 24-hr samples.ResultsNon-FMV samples had relatively weak ability to predict 24-hr dose (R2 = 0.09-0.38 for total DAPs) and tended to underestimate the percentage of samples exceeding regulatory guidelines. Models with FMV samples or the average of an FMV and non-FMV sample were similarly predictive of 24-hr estimates (R2 for DAPs = 0.40-0.68 and 0.40-0.80, respectively, depending on volume adjustment method).ConclusionReliance on non-FMV samples for risk assessments may underestimate daily OP dose and the percentage of children with dose estimates exceeding regulatory guidelines. If 24-hr urine sample collection is infeasible, we recommend future studies prioritize the collection of FMV samples to most accurately characterize OP dose in children.

Project description:BackgroundPrenatal exposure to organophosphate (OP) pesticides has been associated with altered neuronal cell development and behavioral changes in animal offspring. However, the few studies investigating the association between prenatal OP pesticide exposure and neurodevelopmental outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD) and autistic traits in children produced mixed findings.ObjectiveThe objective of the present study was to examine whether maternal urinary concentrations of OP pesticide metabolites are associated with ADHD and autistic traits in children participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands.MethodMaternal concentrations of 6 dialkylphosphates (DAPs) were measured using gas chromatography coupled with tandem mass spectrometry in urine samples collected at <18 weeks, 18-25 weeks, and > 25 weeks of gestation in 784 mother-child pairs. DAP metabolite concentrations were expressed as molar concentrations divided by creatinine levels and log10 transformed. ADHD traits were measured at ages 3, 6, and 10 years using the Child Behavior Checklist (CBCL) (n = 781) and autistic traits were measured at age 6 years using the Social Responsiveness Scale (SRS) (n = 622). First, regression models were fit for the averaged prenatal exposure across pregnancy. Second, we investigated associations for each collection phase separately, and applied a mutually adjusted model in which the effect of prenatal DAP concentrations from each time period on ADHD and autistic traits were jointly estimated. All associations were adjusted for relevant confounders.ResultsMedian DAP metabolite concentration was 309 nmol/g creatinine at <18 weeks, 316 nmol/g creatinine at 18-25 weeks, and 308 nmol/g creatinine at >25 weeks of gestation. Overall, DAP metabolite concentrations were not associated with ADHD traits. For instance, a log10 increase in averaged total DAP concentrations across gestation was not associated with a lower ADHD score (-0.03 per SD 95 CI: -0.28 to 0.23). Similarly, no associations between maternal DAP concentrations and autistic traits were detected.ConclusionsIn this study of maternal urinary DAP metabolite concentrations during pregnancy, we did not observe associations with ADHD and autistic traits in children. These are important null observations because of the relatively high background DAP concentrations across pregnancy, the relatively large sample size, and the 10-year follow-up of the offspring. Given the measurement error inherent in our OP pesticide exposure biomarkers, future studies using more urine samples are needed to accurately measure OP pesticide exposure over pregnancy in relation to ADHD and autistic traits.

Dataset Information

Organophosphate pesticide metabolite levels in pre-school children in an agricultural community: within- and between-child variability in a longitudinal study.

Publications

Organophosphate pesticide metabolite levels in pre-school children in an agricultural community: within- and between-child variability in a longitudinal study.

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