PNNL

Abstract

Objective: Evaluate the quantitative relation between measured red blood cell acetylcholinesterase (RBC AChE) and plasma butyrylcholinesterase (BuChE) activities and exposure to chlorpyrifos (CPF) as assessed by measurement of urinary 3,5,6-trichloro-2-pyridinol (TCPy) in a study group of workers occupationally exposed in the manufacture of chlorpyrifos (n=53) and a referent group of chemical manufacturing workers (n=60). Methods: Measures of plasma and red blood cell cholinesterase activity and urinary TCPy concentration collected over a year-long study in CPF-exposed workers and referents were analyzed using linear mixed models to characterize exposure-response relations. Inter- and intra-individual variability in cholinesterase measures in referents were assessed, and Kaplan-Meier survival curves were used to estimate the rate at which subjects experienced 20 percent or greater decreases in serum cholinesterase activity. Results: Urinary TCPy concentrations in CPF workers were substantially elevated compared to referents. Intraindividual variability in ChE activities were substantial, with referents displaying a 17% failure rate in the survival analysis over the course of repeated measures over the year of observation. RBC AChE activity, an early biomarker of effect, was unrelated to urinary TCPy concentration over the entire range of exposure. Plasma BuChE activity, a non-adverse biomarker of exposure, was negatively related to urinary TCPy at urinary TCPy concentrations above 90 µg/g creatinine. Conclusions: Intra-individual variability in measured ChE activities in referents was substantial, suggesting that ongoing monitoring programs may have a substantial rate of false positives. No-effect levels for inhibition of plasma BuChE and RBC AChE of approximately 90 [May Change to 110] and >1,000 µg TCPy/g creatinine, respectively (corresponding to absorbed doses of CPF of approximately 4.5 [May Change to 5] and >50 µg/kg-d, respectively) were identified. These findings are consistent with previous no-effect level determinations for ChE inhibition in humans and suggest a substantial margin of exposure for general population CPF exposure levels.