Zachariah Guerrette

Abstract:

Exposure biomonitoring of organophosphate (OP) pesticides is a common practice to protect the health of agricultural workers. However, few studies have examined the association between markers of exposure and cholinesterase inhibition, the standard marker of effect, for these compounds or how genetic variation in the metabolic pathways responsible for the activation and detoxification of OP pesticides affects these associations. We evaluated the potential for pesticide exposure and cholinesterase inhibition levels of apple orchard farmworkers and their children in relation to non-farmworker households in the same region. We tested the hypothesis that 1.) OP pesticide exposure biomarkers were predictive of the inhibition of cholinesterase enzymes and 2.) genetic variants for metabolizing genes, including paraoxonase-1 (PON1) and cytochrome P-450s (CYP450s) altered this association. Higher levels of azinphos methyl in blood and dimethylphosphate urinary metabolites were observed in farmworkers adults and children during periods of pesticide application (thinning season) compared to non-farmworkers. Levels of azinphos methyl in blood were significantly associated with higher levels of dimethyl phosphate metabolites in urine. Significant associations between concentrations of these exposure biomarkers and levels of cholinesterase inhibition were observed during the thinning season. We observed no significant modification of these observations when incorporating PON1 phenotypic and genotypic information into our models in accordance with predictions from in vivo data. However, when considering quantification of exposure via urinary metabolites, we found significant modification of the exposure/effect relationship by genetic variants for a number of CYP450 enzymes. These observations suggest that significant differences in the level of activation or detoxification of OP pesticides occur between individuals differing in genotype of certain CYP450s responsible for this metabolism. Despite not directly handling pesticides, individuals working in apple orchards during periods of the pesticide application and their children are exposed to OP pesticides and can experience cholinesterase inhibition. Furthermore, the risk of cholinesterase inhibition appears to be greater in individuals with certain genetic backgrounds. This information illustrates the significance of individual susceptibility and the metabolism of specific OP pesticides for cumulative risk assessments of these compounds.