Aldicarb, the active ingredient in the insecticide TEMIK, was introduced to the agricultural community over 25 years ago. It has been registered worldwide to control a wide variety of insect, mite, and nematode pests in agriculture. The toxicological research database supporting the registration and use of aldicarb was generated over more than 25 years and contains more than 280 animal studies on 12 species of animals, 2 clinical human trials, and over 20 human monitoring studies. This database, which includes biochemical aspects (metabolism and mode-of-action studies), acute toxicity and special short-term toxicity studies, long-term toxicity studies, and epidemiological observations in humans, serves as the starting point for the evaluation of the risks associated with the acceptance of levels of aldicarb residues in food and drinking water and for the more direct occupational exposure. This article highlights the available toxicological data and reviews worldwide regulation of aldicarb. Included in these discussions is a brief description of the toxicological end point upon which regulatory decisions have been based, namely acetylcholinesterase depression. Aldicarb, the N-methylcarbamic acid ester of 2-methyl-2-(methylthio) propionaldehyde oxime, was the first of a limited group of insecticidal oxime Nmethylcarbamates that have properties distinct from N-methylcarbamates which have a phenolic constituent, instead of the oxime moiety. Aldicarb is highly water-soluble (approximately 6000 ppm), nonvolatile, relatively stable under acidic conditions, and is easily degraded under alkaline conditions. These properties are important determinants of its systemic action in plants and of its problematic environmental behavior. ing acetylcholinesterase in nerve synapses and myoneural junctions. Acetylcholinesterase inhibition by these insecticides involves the formation of an enzymeinhibitor complex followed by the reaction of this inhibitor at the active site of the enzyme, which generates either a carbamoylated or phosphorylated enzyme. Phosphorylated acetylcholinesterase is relatively stable, so that inhibition is virtually irreversible after a phenomenon defined as aging has occurred. However, carbamoylated acetylcholinesterase can be readily, and spontaneously hydrolyzed to regenerate the original form of the active enzyme. Although the carbamoylated enzyme is sufficiently stable to disrupt cholinergic transmission, acetylcholinesterase activity is rapidly regenerated following subacute doses. Repeated subacute dosing with cholinergic N-methylcarbamate insecticides does not lead to cumulative intoxication, based on what is known about the insecticides' mode of action and the general physicochemical properties of the chemical class.While not being readily defined in pharmacokinetic terms, the qualitative and quantitative metabolic pattern of degradation in plants and animals is well known. Aldicarb is quickly oxidized to aldicarb sulfoxide and more slowly to aldicarb sulfone, before undergoing hydrolytic breakdown t...
