Animal studies nerve agents toxicity

Human toxicity data for bicyclophosphates have not been published or have not been established. However, available information indicates that under optimum conditions some of the agents are as toxic as nerve agent VX (C01-A016). Based on animal studies, bicyclophosphates are not cumulative and are rapidly eliminated from the body. 

The use of the subchronic rat study for developing an oral RfD for GD is complicated by the fact that rodents have a mnch lower RBC-AChE activity level compared to hnmans (ElUn, 1981, see Table 1). By itself, this could cause rats to be relatively more sensitive than hnmans to anticholinesterase compounds however, the lower RBC-ChE activity may be offset by the presence of aliesterase in rat blood. Aliesterase, which is not present in hnmans (Cohen et al., 1971), is known to bind to and thereby rednce the toxicity of cholinesterase inhibitors (Fonnnm and Sterri, 1981). Other species differences, snch as the rates of aging of the nerve agent-ChE complex, the rates of synthesis of plasma cholinesterase in the liver, and the levels of AChE in various parts of the nervous system (see Ivanov et al., 1993) may also resnlt in differences in species sensitivities. There are insufficient data to determine the relative snsceptibilities of humans and rodents to GD therefore, for the pnrpose of this assessment, the EPA method will be followed which assumes that humans may be as mnch as ten times more sensitive to a chemical than laboratory animals. 

There have been some discrepancies between the results of various studies evaluating the reproductive toxicity of different OP compounds. While decreased libido has been observed in men following acute exposures to both OP nerve agents and insecticides, this reproductive effect is most hkely related to the neurobehavioral effects, such as post-traumatic stress disorder, associated with acute exposures to these chemicals (McDonough and Romano, 2008). Some nerve agents have been associated with post-implantation morbidity and mortahty in laboratory animals (Wismer,... 

Human toxicity data for the Carbamate Nerve Agents has not been published or has not been established. However, based on animal studies, toxicities of some agents appear to be in a range nearly as low as the "V" series Nerve Agents (see Class Index C02). 

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