Reproductive toxicity sarin

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 ... 

Agent GB (Sarin). RfDe = 2 x 10 mg kg d". A LOAEL was identified in a 90-d oral study in rats. A total uncertainty factor of 3000 was applied to account for protection of sensitive subpopulations (10), animal-to-human extrapolation (10), LOAEL-to-NOAEL extrapolation (3), extrapolation from a subchronic to chronic exposure (3), and incomplete data base (3). An uncertainty factor of 3 rather than 10 was used to extrapolate from a subchronic to chronic exposure because of the unlikelihood that the LOAEL would have been substantially lower if the exposure had continued for a longer period of time. The LOAEL-to-NOAEL uncertainty factor of 3 was used because the endpoint, cholinesterase inhibition, was not associated with any physical signs of clinical toxicity. A pilot multigeneration reproductive toxicity study on GB was inconclusive however, because the available evidence indicates that organophosphate cholinesterase inhibitors such as GB are not likely to be reproductive toxins, the lack of definitive results was not considered critical. Therefore, a UFd of 3, not the default value of 10, was applied. 

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