Inhalation fertility and reproduction studies with O,O'-dimethylphosphorodithioate in Sprague-Dawley rats

Groups of 15 male and 35 female Sprague-Dawley rats were exposed to O,O'-dimethylphosphorodithioate (DMPDT) 6 hr/day, 5 days/week for 11 weeks. Initial target concentrations were 0, 4, 25, and 200 mg/m3. However, because of excessive toxicity, the high-exposure level was reduced to 125 mg/m3 after 8 weeks. Exposed males were cohoused with two unexposed females immediately following the exposure period and later mated to an additional two unexposed females following a 16-week recovery period. Exposed females were cohoused with untreated males, and exposures were resumed after mating and continued during gestation. Some females were terminated at midgestation to assess fertility, while others were allowed to deliver their pups. F1 animals were terminated for histological examination or mated to assess fertility. High-exposure level F0 males were infertile after exposures, and there was little or no recovery. The fertility of low-exposure level males was not affected, but equivocal results were obtained at the mid-exposure level. In this study, testicular lesions were observed only in high level F0 males. However, testicular lesions were also noted in a few males exposed to 4 and 25 mg/m3 in a concurrent subchronic toxicity study. Female fertility was apparently unaffected by exposure, and no treatment-related effects were noted in males or females exposed in utero.