Modeling cholinesterase activity for human dietary risk assessment of carbamate insecticides

Abstract

This article demonstrates statistical models to quantify the interaction between a carbamate insecticide and acetylcholinesterase. Carbamates are a class of chemicals that inhibit the activity of acetylcholinesterase in humans, an enzyme involved in the regulation of the neurotransmitter acetylcholine. Following exposure to a carbamate insecticide, we specifically address (1) if acetylcholinesterase activity recovers to its level of preexposure activity; (2) the level of inhibition of acetylcholinesterase activity; (3) the recovery time of acetylcholinesterase activity to its preexposure level for a typical individual; and (4) the upper percentiles of the recovery time of acetycholinesterase activity across individuals. A nonlinear mixed-effects model is fitted to data from a repeated measures experiment conducted with human volunteers randomly assigned to a control and four dose groups. Repeated measurements were taken prior to exposure and at 1, 2, 4, 6, 8, and 21 hours after exposure to the carbamate aldicarb. It was found that full recovery did occur. Inhibition at 1 hour was estimated with maximum inhibition most likely occurring prior to 1-hour postexposure. In addition, recovery was rapid even for sensitive individuals. Given this information, the potential effect from exposure to a carbamate consumed in the diet during a day can be quantitatively assessed.