Rodents anticholinesterase sensitivity

The use of a rat study for developing an RfD for GA is complicated by the fact that rodents have a much lower RBC-AChE activity level compared to humans (Ellin, 1981). By itself, this could cause rats to be relatively more sensitive than humans to anticholinesterase compounds however, the lower RBC-AChE activity may be offset by the presence of ahesterases in the blood of rats. Aliesterases, which are not found in human blood plasma, are known to bind to and, therefore, reduce the toxicity of GB, and a similar mechanism may operate in the case of GA. Other species differences, such as in the rates of aging of the GA-ChE complex, in the rates of synthesis of plasma-ChE in the liver, and in the levels of AChE in the nervous system (see Ivanov et al., 1993) may also result in difference between species in sensitivity to GA. Data are insufficient to more fuUy evaluate these possibihties. There is httle human acute toxicity data that can be compared with the available rat data however, acute toxicity data for primates in general (see Table 2) suggests that humans are likely to be more sensitive than rats. Therefore, for the purpose of this assessment, the standard EPA method will be followed which assumes that humans can be as much as ten times more sensitive to a chemical than laboratory animals. 

These differences in RBC-ChE activity may affect a species sensitivity to a particular organophosphate compound. At the same time, the relative amonnt of plasma cholinesterase and other compounds in the blood that can bind to the organophosphate agents mnst also be considered. As noted above, rodents, but not humans, have high levels of aliesterases in the blood (Cohen et al., 1971). These compounds may provide rats and mice with a higher level of resistance to anticholinesterase componnds to which they bind, such as GB, but not to others snch as VX (Fonnnm and Sterri, 1981). 

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