Comparison of Current-Use Pesticide and Other Toxicant Urinary Metabolite Levels among Pregnant Women in the CHAMACOS Cohort and NHANES

BackgroundWe measured 34 metabolites of current-use pesticides and other precursor compounds in urine samples collected twice during pregnancy from 538 women living in the Salinas Valley of California, a highly agricultural area (1999-2001). Precursors of these metabolites included fungicides, carbamate, organochlorine, organophosphorus (OP), and pyrethroid insecticides, and triazine and chloroacetanilide herbicides. We also measured ethylenethiourea, a metabolite of the ethylene-bisdithiocarbamate fungicides. Repeat measurements of the compounds presented here have not been reported in pregnant women previously. To understand the impact of the women's regional environment on these findings, we compared metabolite concentrations from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) cohort with U.S. national reference data for 342 pregnant women sampled by the National Health and Nutrition Examination Survey (1999-2002).ResultsThe eight metabolites detected in > 50% of samples [2,4-dichlorophenol (2,4-DCP); 2,5-dichlorophenol (2,5-DCP); 1- and 2-naphthol; ortho-phenylphenol (ORTH); para-nitrophenol (PNP); 2,4,6-trichlorophenol (2,4,6-TCP); and 3,4,6-trichloro-2-pyridinol (TCPy)] may be related to home or agricultural pesticide use in the Salinas Valley, household products, and other sources of chlorinated phenols. More than 78% of women in this study had detectable levels of at least one of the OP pesticide-specific metabolites that we measured, and > 30% had two or more. The 95th percentile values of six of the most commonly detected (> 50%) compounds were significantly higher among the CHAMACOS women after controlling for age, race, socioeconomic status, and smoking [(2,4-DCP; 2,5-DCP; ORTH; PNP; 2,4,6-TCP; and TCPy); quantile regression p < 0.05].ConclusionsFindings suggest that the CHAMACOS cohort has an additional burden of precursor pesticide exposure compared with the national sample, possibly from living and/or working in an agricultural area

Developmental Changes in PON1 Enzyme Activity in Young Children and Effects of PON1 Polymorphisms

BackgroundParaoxonase 1 (PON1) is an enzyme that detoxifies activated organophosphorus pesticides (OPs) and is also involved in oxidative stress pathways.ObjectivesPON1 activity in newborns is lower than in adults, but the ontogeny of PON1 activity is poorly characterized in young children. We examined the effects of age and PON1 genotype on enzyme activity in a birth cohort of Mexican-American children.MethodsWe determined three substrate-specific measures of PON1 activity in 1,143 plasma samples collected longitudinally from 458 children at five time points from birth through 7 years of age, and genotyped PON1 polymorphisms at positions 192 and -108 in these children.ResultsContrary to previous reports that PON1 activities plateau by 2 years of age, we observed an age-dependent increase in all three PON1 measures from birth through 7 years of age (p < 0.0001). The PON1(192) genotype significantly modified the effect of age on paraoxonase (POase) activity (p < 0.0001) such that increases in enzyme activity with age were influenced by the number of R alleles in a dose-dependent manner. Children with the PON1(-108CC192RR) diplotype had significantly higher mean PON1 activities and also experienced steeper increases of POase activity over time compared with children with the PON1(-108TT192QQ) diplotype.ConclusionsLower levels of the PON1 enzyme, which is involved in protection against OPs and oxidative stress, persist in young children past 2 years of age through at least 7 years of age. Future policies addressing pesticide exposure in children should take into account that the window of vulnerability to OPs in young children may last beyond infancy

PON1 and Neurodevelopment in Children from the CHAMACOS Study Exposed to Organophosphate Pesticides in Utero

BackgroundParaoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study.ObjectiveWe determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior.MethodsWe measured DAP concentrations in maternal urine during pregnancy, PON1₁₉₂ and PON1₋₁₀₈ genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds' blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD.ResultsChildren with the PON1(-108T) allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. The association between DAPs and MDI scores was strongest in children with PON1(-108T) allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant.ConclusionPON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure