The Neurotoxicity of Cholinesterase-Inhibiting Insecticides: Past and Present Evidence Demonstrating Persistent Effects

Abstract

It is assumed that the primary mechanism of action of carbamate and organophosphate insecticides is the inhibition of an enzyme, acetylcholinesterase (AChE; EC 3.1.1.7). This enzyme normally maintains the proper level of the neurotransmitter acetylcholine in the central and peripheral nervous systems. When AChE activity is depressed due to exposure to cholinesterase-inhibiting insecticides, the ordinarily rapid breakdown of acetylcholine is retarded, causing overstimulation of target cells, which, under extreme conditions, is termed a “cholinergic crisis.” At the present time, these indicators of acute intoxication, that is, cholinesterase inhibition and/or clinical signs of cholinergic overstimulation, are used in the risk assessment process to regulate cholinesterase-inhibiting insecticides. There is, however, accumulating evidence both from epidemiological studies and from experimental laboratory studies that short-term exposure to some cholinesterase-inhibiting insecticides may precipitate long-term adverse effects. Recent experimental studies in our laboratory and in others have demonstrated that a single or short-term exposure to some cholinesterase-inhibiting insecticides may produce behavioral or neurochemical changes lasting for days or months, presumably outlasting the cholinesterase inhibition. This body of amassing evidence should alert those in the scientific and regulatory arenas as to the multifaceted nature of the toxicity profile of cholinesterase-inhibiting insecticides