An initial preliminary range finding inhalation reproductive toxicity study was conducted to determine effects, if any, on reproduction in Sprague-Dawley rats in a single generation. Both male and female (20/sex/exposure level) rats were exposed to D4 vapor at 70 and 700 ppm six (6) hours per day for twenty eight (28) days prior to mating; a concurrent filtered air control followed a similar regimen. Exposure was then continued throughout a two week mating phase until necropsy (exposure of female rats was temporarily suspended from gestational day 21 through lactation day 4). Pups were exposed following a similar regimen after weaning on postnatal day 21 through postnatal day 28. Following this initial range-finding study, a repeat range-finding study was conducted because the initial results were equivocal, making interpretation difficult. The repeat range-finding study utilized one group of rats exposed to D4 vapor at 700 ppm and two filtered air control groups (221sex). The design of the repeat study was identical to the initial study with the following exceptions: (a) the pups in the F1 generation were euthanized on postnatal day 4 instead of postnatal day 28, (b) testicular and epididymal sperm counts and sperm production rates were measured, and (c) testes, epididymides and ovaries were weighed and examined histologically. In the initial range-finding study, no significant clinical signs of toxicity were noted in D4 exposed males or females. Inhibition in body weight gain and food consumption in the 700 ppm exposed female group was observed. This was particularly evident in the females during gestation. There were no adverse effects in overall reproductive performance in D4 exposed animals (male or female fertility index, pregnancy rate, mating behavior, females with viable pups, gestational period or mean pre-coital intervals). No abnormalities were observed in any of the pups. However, we did observe an apparent reduction in the mean viable litter size (11.6 pups/Iitter) in the 700 ppm exposure group only. While this observation was statistically significant (p<0.01) when compared to concurrent controls, the control group had an atypically high (based on historical control data) mean viable litter size (16.4 pups compared to an historical range of 11.7- 15.9) which was outside the range of normal control data. The mean viable litter size of 11.6 pups/Iitter in the 700 ppm D4 group, approximating the lower end of historical control data for this strain of rat, when coupled with the fact that all other reproductive performance indicators were unaffected by exposure to D4s confounds interpretation of these data.