Paraoxonase status and plasma butyrylcholinesterase activity in chlorpyrifos manufacturing workers

Abstract

Chlorpyrifos is an organophosphorus (OP) anticholinesterase insecticide. Paraoxonase (PON1) is an enzyme found in liver and plasma that hydrolyzes a number of OP compounds. PON1 polymorphisms include a glutamine (Q)/arginine (R) substitution at position 192 (PON1 Q192R ) that affects hydrolysis of OP substrates, with the PON1 192Q allotype hydrolyzing chlorpyrifos oxon less efficiently than the PON1 192R allotype, a variation potentially important in determining susceptibility to chlorpyrifos. We studied 53 chlorpyrifos workers and 60 referents during 1 year and estimated chlorpyrifos exposure using industrial hygiene and employment records and excretion of the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol (TCP). Plasma butyrylcholinesterase (BuChE) activity, which may by inhibited by chlorpyrifos exposure, was measured monthly. In addition, plasma samples were assayed for paraoxonase (PONase), diazoxonase (DZOase), and chlorpyrifosoxonase (CPOase) activity to determine PON1 status (inferred genotypes and their functional activity). Linear regression analyses modeled BuChE activity as a function of chlorpyrifos exposure and covariates. We postulated that the level of CPOase activity and the inferred PON1 192 genotype (together reflecting PON1 status) would differ between groups and that PON1 status would modify the models of chlorpyrifos exposure on BuChE activity. Chlorpyrifos workers and referents had a 100-fold difference in cumulative chlorpyrifos exposure. Contrary to our hypotheses, mean CPOase activity was similar in both groups (P ¼ 0.58) and PON1 192Q showed a slight overrepresentation, not an underrepresentation, in the chlorpyrifos group compared with referents (PON1 192QQ , 51% chlorpyrifos, 40% referent; PON 192QR , 43% chlorpyrifos, 40% referent; PON 192RR , 6% chlorpyrifos, 20% referent, P ¼ 0.08). In our models, BuChE activity was significantly inversely associated with measures of interim chlorpyrifos exposure, but the biological effects of chlorpyrifos exposure on BuChE activity were not modified by PON1 inferred genotype or CPOase activity.

In Vitro Age-Dependent Enzymatic Metabolism of Chlorpyrifos and Chlorpyrifos-Oxon in Human Hepatic Microsomes and Chlorpyrifos-Oxon in Plasma

“…Plasma samples contained all functional phenotypes of PON1, and the majority was represented by QQ, the phenotype with the lowest CPFoxon hydrolysis activity. The functional phenotype ratio measured here was similar to those reported previously (Albers et al, 2010;Davis et al, 2009), and adult oxon hydrolysis rates were comparable to what others have reported in the literature .…”

Paraoxonase 1 (PON1) as a genetic determinant of susceptibility to organophosphate toxicity

“…In contrast to these findings, however, in workers involved in the manufacturing of chlorpyrifos and exposed to this OP, the decreased plasma BuChE activity was not associated with low PON1 status (Albers et al 2010). …”

Associations of maternal organophosphate pesticide exposure and PON1 activity with birth outcomes in SAWASDEE birth cohort, Thailand

“…This is consistent with the reported insensitivity of AChE activity to exposures to OP pesticides that are far below lethal levels. A study in workers involved in the manufacturing of chlorpyrifos found that the decreased AChE activity was not associated with low PON1 status (Albers et al 2010). Similarly, a study in agricultural workers observed inhibition of AChE and BChE after chlorpyrifos application but an association of PON1 activity with inhibition was not found (Ellison et al 2012).…”