Using GxE Approaches to Link Biomarkers of Exposure and Effect for Organophosphate Pesticides in Agricultural Community Households

摘要

Exposure biomonitoring of organophosphate pesticides (OPs) is a common practice to ensure protection of agricultural workers. The University of Washington Center for Child Environmental Health Risks Research collected biological samples from farmworkers and non-farmworkers to investigate potential exposures to OPs during agricultural periods of OP application. A key focus of the study was to identify within and between person variability thus urine samples were collected every two days and were matched with blood samples and AChE measurements from the same time period. Urine samples were assayed for 6 diakyl metabolites of OPs and blood for parent compounds. To estimate the joint distribution of the metabolites and clearance rates, we used MCMC methods in a mixed effects model. Levels of metabolite DMTP in farmworkers were 19 times that of the non-farmworkers. Across all of the farmworkers (fixed effects), the clearance half-life of DMTP had a geometric mean (95% CI) of 3.6 (2.5, 6.0) days compared to the non-farmworkers who showed no clearance. The half-lives for individual farmworkers (random effects) varied between 1.5 days and no clearance. The shorter half-lives were seen in farmworkers who had higher first day concentrations of DMTP and farmworkers with no clearance with those who had lower first day concentrations. These results are consistent with a continuing variable level of occupational exposure of the farmworkers with some of the farmworkers having a higher exposure prior to our collection of urine. The pattern in the non-farmworkers is consistent with exposures to preformed metabolites of OPs through diet and other routes of non-occupational exposure. Our mixed effects model included genotyping data for metabolism genes, and we observed significant differences in the relationship of cytochrome P450 isoforms with exposure (DAP metabolites) and health impacts (AChE inhibition). (Supported by NIH grants P01 ES009601, P30 ES007033 and RD-834514, RD-831709, RD-832733 from USEPA.).