Methylene chloride: two-generation inhalation reproductive study in rats.

Reproductive parameters in Fischer 344 rats were evaluated following inhalation of methylene chloride (MeCl2) for two successive generations. Thirty male and female rats were exposed to 0, 100, 500, or 1500 ppm MeCl2 for 6 hr/day, 5 days/week for 14 weeks and then mated to produce f1 litters. After weaning, 30 randomly selected f1 pups/sex/group were exposed to MeCl2 for 17 weeks and subsequently mated to produce f2 litters. Reproductive parameters examined included fertility, litter size and neonatal growth, and survival. All adults and selected weanlings were examined for grossly visible lesions. Tissues from selected weanlings were examined histopathologically. No adverse effects on reproductive parameters, neonatal survival, or neonatal growth were noted in animals exposed to methylene chloride in either the f0 or f1 generations. Similarly, there were no treatment-related gross pathologic observations in f0 or f1 adults or f1 and f2 weanlings. Histopathologic examination of tissues from f1 and f2 weanlings did not reveal any lesions attributed to methylene chloride. Thus, exposure of rats to concentrations as high as 1500 ppm methylene chloride, which has been shown in a 2-year study to produce treatment-related effects, did not affect any reproductive parameters.