Toxicity mechanisms, nerve agents

As outlined in the toxicity section above the toxicological mechanism of action of nerve agents is based on the chemical reactivity of the nucleophilic leaving group. Therefore, metabolism in terms of degradation by hydrolysis and binding to proteins determines bioavailability and elimination processes thus regulating toxicity. 

CWAs are represented by any one of a number of chemicals exhibiting a very high toxicity by various mechanisms. The present Handbook exhibits CWAs with structures as simple as carbon monoxide (CO) and as complex as botulinum toxin or ricin proteins. While this chapter could address the development of PBPK models of CWAs in general, the focus will primarily be on the organophosphate (OP)-based nerve agents typically represented by sarin (GB - isopropyl methylfluoro-phosphonate). 

The most important inhibitors of CarbEs are organo-phosphorus insecticides (malathion, parathion, para-oxon, methyl parathion, EPN, and others), nerve agents (DFP, soman, sarin, tabun, and VX) and carbamate insecticides (carbofuran, carbaryl, aldicarb, propoxur, oxamyl, methomyl, and others). Organo-phosphorus toxicants inhibit CarbEs irreversibly by phosphorylation and carbamates inhibit CarbEs reversibly by carbamylation similar to the basic mechanism (i.e., acylation of the active site) ... 

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