Acute Toxicities of Organophosphates and Carbamates

Abstract

The insecticides of the organophosphorus and carbamate classes are widely used and highly effective pest control agents. Although there are agents within these two classes that have other pesticidal uses, such as fungicidal or herbicidal applications, it is the insecticides (which also have utility as nematocides, acaricides, and helminthicides) that display the greatest neurotoxic properties. Any agent designed to kill pests is of potential danger to nontarget organisms, such as humans, if the molecular target for the pesticide also exists as an important entity in the nontarget organism. Such a common molecular target exists for the organophosphorus and carbamate insecticides. As will be discussed in greater detail below, members of these two insecticidal classes are inhibitors of acetylcholinesterase (AChE). The inhibition of AChE mediates most, if not all, of the clinical signs of toxicity during an acute intoxication. Because of the environmental and metabolic lability of these two classes of agrochemicals, they were important replacements for the persistent and bioaccumulative organochlorine insecticides, which were the predominant agricultural chemicals in the 1950s and 1960s. The use of the organophosphorus insecticides (less accurately but more commonly called organophosphates: OPs) and the carbamates has been an important component in the control of insects in agriculture, buildings, home gardens, and public health since the 1950s. While attempts have been made by the agrochemical industry to improve the pest vs nontarget organism selectivity, and these attempts have frequently been very effective, it remains a fact that some of the agents with high-use patterns are still moderately or highly toxic to mammals (1,2). Because of their intense use, it is inevitable that human exposures will occur, and, despite important safety precautions being in place, some of these exposures are likely to be high level and life-threatening during accidents. This chapter provides a summary of the history, chemistry, metabolism, and mechanism of action of the OPs and carbamates. Further information can be obtained from the following references: Chambers (3), Chambers and Levi (4), Ecobichon (5), Ecobichon and Joy (6), Eto (7), Fest and Schmidt (8), Hayes, (9,10), Heath (11), and Kuhr and Dorough (12).