Pilot: Inhibition of Cholinesterase by Pharmacological and Dietary Agents

(NIOSH 2007-2009) Organo-phosphorus pesticides (OPs) have widespread commercial application in the United States and worldwide, and their primary toxicological effect is associated with inhibition of cholinesterase (ChE). In Washington State, cholinesterase activity is measured in farmworkers expected to have high exposures to OPs, and when depression in cholinesterase activity is observed, remedial actions are undertaken to reduce exposures and protect worker health. However, the cholinesterase assay lacks specificity: there are a number of dietary and pharmacological agents that can depress cholinesterase levels. In the context of the Washington State cholinesterase monitoring rule, this would lead to an incorrect conclusion that the worker had been overexposed to pesticide. This misclassification of exposure confounds epidemiological studies of farmworker health and pesticide exposure, and undermines worker and employer confidence in the cholinesterase monitoring program.

This pilot study measured the effect of quinine and acetaminophen on cholinesterase levels in vivo in humans. Quinine is a known inhibitor of cholinesterase, and the potential for exposure to quinine is high due to its presence as an ingredient in tonic water. Quinine and its analogs are also used medicinally as prophylaxis for malaria and muscle cramping. Acetaminophen (brand names: tylenol, paracetamol) is a common over the counter and prescription medication for pain relief and fever reduction. Acetaminophen is a known hepatotoxin, and has been shown to reduce cholinesterase levels in vitro. Both compounds have been suggested as potential confounders to the use of cholinesterase measurements as a marker for pesticide exposure.

Human volunteers ingested either quinine (singe acute dose) or acetaminophen (3g/day for up to 6 days), and the effect on plasma cholinesterase and acetylcholinesterase was monitored.

2007 to 2009