Sarin, OPIDN agent

Application of in vitro test methods have become advantageous in specific cases, such as structurally defined compounds and delayed neuropathy, since target cell data and biochemical processes associated in delayed neuropathy are known. Microscopic studies reveal that cases of OPIDN have degeneration of axons followed by demyelination of the nervous system.25,26 Epidemiologic studies have indicated mild impairment of the brainstem, spinal cord, and peripheral nerve functions in Gulf War veterans.27 Such studies are consistent with the spectrum of OPIDN syndrome. The main nerve agents have been shown to inhibit NTE in vitro as well as in vivo. Sarin has been shown to produce delayed neurotoxicity when administered at higher doses in protected hens.25-27... 

GA, a unitary chemical munition, inhibits AChE, the enzyme responsible for the breakdown of the neurotransmitter ACh. When inhaled, its toxicity is half that of sarin. It depresses plasma and RBC-AChE activities significantly in the blood. At 20-25% of red blood cell AChE baseline, the effect of the nerve agent becomes noticeable. There is no evidence of systemic toxicity other than the cholinesterase activity (Parker et al, 1990 Munro et al, 1994). GA has not been shown to produce OPIDN except at extremely high doses. The cardiac effect of GA conforms to OP-caused arrhythmias and AV block. 

Fluorophosphates are also highly toxic and relatively volatile. Sarin and soman are chemical warfare agents. Diisopropyl fluorophosphate (DFP) is often used by biochemists to study serine-active enzymes. Mipafox and DFP cause OPIDN in humans and experimental animals. 

No review of subacute, subchronic, or chronic toxicity of chemical warfare nerve agents would be complete without discussion of the significant paper by Munro et al. that reviewed both animal and human studies of the nerve agents tabun (GA), sarin (GB), and VX. These studies included subacute, subchronic, and chronic toxicity studies in animals. Special attention was paid to the phenomenon of Organophosphorus-Induced Delayed Neuropathy (OPIDN). Reproductive toxicity and carcinogenicity tests were reviewed as well as in vitro studies of mutagenicity. Munro et al. s findings can be summarized as follows ... 

Agriculture has been fortunate to be relatively free of mass outbreaks of OPIDN. The major chemical offender has been the plasticizer and lubricant trl-ortho-cresyl phosphate (TOCP). Contamination of various products with TOCP has paralyzed thousands of people since the turn of the century ( ). OPs in use In agriculture that have been shown to be neuropathic Include the cotton defoliant DEF and the pesticides EPN, haloxon and leptophos (not registered In the US). Neuropathic OPs used experimentally Include DFP and mlpafox one nerve gas (sarin) has been shown to cause OPIDN and there Is evidence another (soman) Is also a delayed neuropathic agent ( ). Recently, Wilson et al. ( ) found that isofenphos (IFF) caused OPIDN In hens. 

---