Urine tcpy as a biomarker of occupational exposure to chlorpyrifos

The organophosphate pesticide, chlorpyrifos, is widely used throughout the world. The aim of this study is to determine the impact of genotype on a urine biomarker in Egyptian agricultural workers that apply chlorpyrifos to cotton fields. Cytochrome P-450 (CYP) 2C19 detoxifies chlorpyrifos to 3,5,6-trichloro-2-pyridinol (TCPy), while CYP2B6 metabolizes chlorpyrifos to the toxic oxon form, which inhibits cholinesterases. Urinary-TCPy is a specific biomarker of exposure to chlorpyrifos and was assessed in agricultural workers in three job-categories (applicators, engineers, technicians) and a reference group. Variations in CYP2B6 and CYP2C19 genotypes were analyzed to determine their influence on urinary-TCPy levels. Saliva samples were collected from 313 workers and genotyped for CYP2B6 and CYP2C19 variants. The workers also provided spot urine samples during 2009 and 2010, which were analyzed for TCPy levels. Job category was highly associated with exposure. Applicators had significantly higher urinary-TCPy levels than other workers across application periods presumably due to extensive dermal exposure from the application process and the lack of personal-protective equipment. Technicians and engineers had similar mean TCPy levels throughout the study-period that were greater than the reference group. CYP2B6*1/*1, CYP2B6*1/*6, and CYP2B6*6/*6 were the most common CYP2B6 genotypes in the Egyptian population, which is similar to other populations. Urinary TCPy excretion (TCPy/g creatinine) was lower among CYP2B6 *6 carriers, which is consistent with the in vitro hepatic metabolism of chlorpyrifos when controlling for genotypes. Together, these findings will better inform studies of neurobehavioral performance in these workers. (Supported by NIEHS grant ES016308)