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Association of Organophosphate Pesticide Exposure and a Marker of Asthma Morbidity in an Agricultural Community.

ABSTRACT: Objectives: We explored the short-term impact of pesticide exposure on asthma exacerbation among children with asthma in an agricultural community.Methods: We obtained repeated urine samples from a subset of 16 school-age children with asthma (n = 139 samples) as part of the Aggravating Factors of Asthma in a Rural Environment (AFARE) study cohort. Biomarkers of organophosphate (OP) pesticide exposure (dialkylphosphates (DAPs)), and asthma exacerbation (leukotriene E4 (uLTE4)) were assessed in urine samples. We used generalized estimating equations to examine the association of summed measures of creatinine-adjusted DAPs (total dimethyl alkylphosphate (EDM), total diethyl alkylphosphate (EDE), and total dialkylphosphate pesticides (EDAP)) and uLTE4 concentration, adjusting for multiple confounders, yielding beta-coefficients with 95% CIs.Results: A total of 139 observations were obtained from the 16 children over the study period, the total number of samples per subject ranged from 1 to 12 (median: 10.5). The geometric mean (GM) of creatinine-adjusted EDE, EDM, and EDAP in this population were 81.0, 71.8 and 168.0 nmol/g, respectively. Increase in uLTE4 levels was consistently associated with increased exposures to DAPs (interquartile range in ?g/g): ?_EDE: 8.7 (95%CI: 2.8, 14.6); ?_EDM: 1.1 (0.5, 1.7); ?_EDAP: 4.1 (0.7, 7.5).Conclusion: This study suggests that short-term OP exposure is associated with a higher risk of asthma morbidity, as indicated by increased uLTE4 levels in this cohort of children with asthma in an agricultural community. Additional studies are required to confirm these adverse effects, and explore the mechanisms underlying this relationship.

SUBMITTER: Benka-Coker W

PROVIDER: S-EPMC6875607 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Association of Organophosphate Pesticide Exposure and a Marker of Asthma Morbidity in an Agricultural Community.

Benka-Coker Wande W Loftus Christine C Karr Catherine C Magzamen Sheryl S

Journal of agromedicine 20190525 1

<b>Objectives</b>: We explored the short-term impact of pesticide exposure on asthma exacerbation among children with asthma in an agricultural community.<b>Methods</b>: We obtained repeated urine samples from a subset of 16 school-age children with asthma (n = 139 samples) as part of the Aggravating Factors of Asthma in a Rural Environment (AFARE) study cohort. Biomarkers of organophosphate (OP) pesticide exposure (dialkylphosphates (DAPs)), and asthma exacerbation (leukotriene E4 (uLTE4)) were ...[more]

PMID: 31130077

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Project description:Organophosphate (OP) pesticides are widely used in California for agricultural pest and weed control despite their well-documented adverse health effects among infants, children, and adults. We sought to identify factors affecting urinary OP metabolites among families living in high-exposure communities. Our study included 80 children and adults who lived within 61 m (200 ft) of agricultural fields in the Central Valley of California in January and June 2019, which are pesticide non-spraying and spraying seasons, respectively. We collected one urine sample per participant during each visit to measure dialkyl phosphate (DAP) metabolites; these were coupled with in-person surveys to identify health, household, sociodemographic, pesticide exposure, and occupational risk factors. We used a data-driven, best subsets regression approach to identify key factors that influenced urinary DAPs. Participants were mostly Hispanic/Latino(a) (97.5 %), over half were female (57.5 %), and most households reported having a member who worked in agriculture (70.6 %). Among the 149 urine samples suitable for analysis, DAP metabolites were detected in 48.0 % and 40.5 % of samples during January and June, respectively. Total diethyl alkylphosphates (EDE) were only detected in 4.7 % (n = 7) of samples, but total dimethyl alkylphosphates (EDM) were detected in 41.6 % (n = 62) of samples. No differences were observed in urinary DAP levels by visit month or by occupational exposure to pesticides. Best subsets regression identified several individual- and household-level variables that influenced both urinary EDM and total DAPs: the number of years spent living at the current address, household use of chemical products to control mice/rodents, and seasonal employment status. Among adults only, we identified educational attainment (for total DAPs) and age category (for EDM) as significant factors. Our study found consistent urinary DAP metabolites among participants, regardless of spraying season, and identified potential mitigating factors that members of vulnerable populations can implement to protect their health against OP 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:BackgroundEpidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association.MethodsThe study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1(192) and PON1(-108)) and enzyme activity (paraoxonase and arylesterase). Infant birth weight, head circumference, and gestational age were obtained from medical records.ResultsInfants' PON1 genotype and activity were associated with birth outcome, but mothers' were not. Infants with the susceptible PON1(-108TT) genotype had shorter gestational age (β = -0.5 weeks, 95% Confidence Interval (CI): -0.9, 0.0) and smaller head circumference (β = -0.4 cm, 95% CI: -0.7, 0.0) than those with the PON1(-108CC) genotype. Infants' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON1(-108TT) genotype (p-value(interaction) = 0.09). However, maternal DAP concentrations were associated with larger birth weight (p-value(interaction) = 0.06) and head circumference (p-value(interaction)<0.01) in infants with non-susceptible genotypes.ConclusionsInfants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor contributing to preterm or low birth weight birth.

Project description:BackgroundOrganophosphates (OP) are widely used insecticides that acutely inhibit acetylcholinesterase enzyme activity. There is great interest in improving the understanding of molecular mechanisms related to chronic OP exposure induced toxicity. We aim to elucidate epigenetic changes associated with OP exposure, using untargeted analysis of genome-wide DNA methylation data.MethodsIn a population-based case control study of Parkinson's disease (PD), we assessed ambient OP exposure via residential and workplace proximity to commercial applications. We investigated associations between OP exposure and genome-wide DNA methylation (Illumina 450 k) in 580 blood samples (342 PD patients, 238 controls) and 259 saliva samples (128 patients, 131 controls). To identify differential methylation related to OP exposure, we controlled for age, sex, European ancestry, and PD status; in addition, we stratified by disease status.ResultsWe identified 70 genome-wide significant CpGs, including cg01600516 in ALOX12 (cor = 0.27, p = 1.73E-11) and two CpGs in HLA genes, cg01655658 (cor = -0.24, p = 2.80E-09) in HLA-L (pseudogene) and cg15680603 (cor = 0.20, p = 7.94E-07) in HLA-DPA1. Among the 70 CpGs located in 41 genes, 14 were also differentially methylated in saliva samples. The most overrepresented pathway was the nicotinic acetylcholine receptor signaling pathway (fold enrichment = 15.63, p = 1.01E-03, FDR = 1.64E-01). Expanding to a larger number of genes (CpG p < 5E-04, FDR < 2.25E-01; 1077 CpGs, 662 genes), the most enriched pathway shifted to the muscarinic acetylcholine receptor 1 and 3 signaling pathway (p-value = 5.36E-04, FDR = 4.73E-02). When we stratified by PD status, results were similar. Of the 70 significant CpGs, 63 were detected among both patients and controls and 7 were only associated with OP exposure among patients.ConclusionsThis study finds chronic low-level OP exposure is associated with differential DNA methylation in blood and saliva, both in elderly population controls and PD patients. Our study results suggest that long-term sub-acute OP exposure influences methylation in genes enriched for muscarinic and nicotinic acetylcholine receptor pathways.

Project description:BackgroundPerturbations in fetal growth may have adverse consequences for childhood and later life health. Organophosphate pesticide (OP) exposure has been associated with reduced birth weight at delivery but results are not consistent. We investigated this question by utilizing ultrasound measures of size in utero in combination with measures from delivery.MethodsWithin Generation R, a population-based prospective cohort conducted between 2002 and 2006 in Rotterdam, Netherlands, we measured dialkyl phosphates (DAPs), OP metabolites, in urine samples from early, middle, and late pregnancy and created a subject-specific average to estimate OP exposure ([Formula: see text]). Ultrasound measures of head circumference, femur length, and estimated fetal weight from middle and late pregnancy and delivery measures were converted to standard deviation scores (SDS). Associations with DAP average were examined in linear mixed effects models that included an interaction term between gestational age at measurement and DAP average to investigate whether the relationship differed over time. Windows of vulnerability to exposure were assessed by modeling urinary DAPs from each visit in relation to growth measurements.ResultsA 10-fold increase in average DAPs was associated with a [Formula: see text] SDS decrease in fetal length (95% [Formula: see text], [Formula: see text]) and a [Formula: see text] SDS decrease in estimated fetal weight (95% [Formula: see text], [Formula: see text]) at 20 weeks of gestation. These differences corresponded to 5% and 6% decreases relative to the mean. Effect estimates were greatest in magnitude for DAP concentrations measured early in pregnancy. Associations between average DAPs and growth measures at delivery were positive but not significant for head circumference and length and were null for weight.ConclusionsMaternal urinary DAPs were associated with decreased fetal weight and length measured during mid-pregnancy, but not at delivery. https://doi.org/10.1289/EHP4858.

Dataset Information

Association of Organophosphate Pesticide Exposure and a Marker of Asthma Morbidity in an Agricultural Community.

Publications

Association of Organophosphate Pesticide Exposure and a Marker of Asthma Morbidity in an Agricultural Community.

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