Nerve agents human exposure studies

The current human estimates for nerve agent vapor and aerosol toxicity are based upon data from animal models. Rodents are popular animal models in that they are readily available, cheap, and convenient to handle. Additionally, there is a great amount of background data on rodents available in the literature for comparison to many biological endpoints. However, nonrodent models are preferred for studies of prophylactic and therapeutic efficacy associated with nerve agent exposure due to the protective buffering impact of relatively high blood carboxylesterase levels in... 

Polyneuropathy, the major neuromuscular manifestation seen after exposure to organophosphate pesticides, has not been reported in humans after exposure to nerve agents. Studies suggest that these agents cause polyneuropathy in animals... 

Note that the presence or absence of miosis does not provide any important prognostic information about the overall response to exposure to an anticholinesterase. Experimental studies in humans have shown that there is significant miosis after exposure to sarin at a Ct of only 5. Visual acuity is commonly affected by low-level vapour exposure to nerve agents. The duration of effect, like that of the pupils, can be variable, with normal vision returning within 2-35 days. The assessment of miosis is considered in Box 7.5. Figure 7.1 shows miosis after a low-level exposure to a nerve agent. 

The only published study of the brain structural effects of nerve agent exposure in a human population focused on longterm changes induced in victims of the 1995 Tokyo subway sarin attack (Yamasue et al, 2007). In this event, which resulted in 12 deaths, approximately 5,500 victims were exposed to sarin, and essentially all patients exhibited typical symptoms of acute intoxication (Lee, 2003 Ohbu et al. 

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