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HYDROFLUOROCARBON-404A 64 from the F1 generation (20 litters per group) were raised to maturity. The F1 animals were mated and the pregnant females were killed on day 20 of pregnancy for examination of uterine contents and ovaries. No clinical signs of toxicity were observed in the F0 or F1 generations, nor were there any significant effects on body weights. With regard to breeding performance, no effects were observed on estrous cycles, mating, precoital times, conception, and gestation length in the F0 or F1 generations. No significant changes in the number of live-born pups, sex ratio, and survival postpartum were observed. There was a statistically significant delay in pinnae detachment, eye opening, and startle response in the F1 generation from parents exposed to HFC-134a at 64,400 ppm. However, because the delays were small, they were not considered biologically significant. No exposure-related abnormalities were observed in any of the postmortem examinations of the F0 and F1 generations. In addition, when the uterine contents of pregnant females sacrificed before term were examined, the number of corpora lutea, implants, embryonic deaths, live young, sex ratio, litter weights, and fetal body weights did not differ significantly from controls, and the incidence, type, and distribution of visceral or skeletal abnormalities did not increase. Barton et al. (1994) studied the effects of HFC-134a on testicular endocrine function of male rats. Groups of 25 male rats were exposed daily to HFC-134a at concentrations of 10,000, 30,000, or 100,000 ppm for 11 weeks before mating, during mating, and after mating for a total exposure duration of 18 weeks. Nose-only exposure was given for the first 9 weeks and then whole- body exposure for the remainder of the study. At 16 weeks, the basal level of luteinizing hormone (LH) was high in all groups, including the control group. No intergroup differences were observed when these animals were stimulated with luteinizing-hormone releasing hormone. When the testes from exposed animals were incubated with human chorionic gonadotrophin, there was a small increase in testosterone secretion and biosynthesis with a concomitant rise in progesterone secretion in the 100,000-ppm group but not in the lower- concentration groups. There were no changes in androgen biosynthesis, and levels of 17-hydroxyprogesterone, androstenedione, and estradiol were not significantly different from control levels. Genotoxicity Numerous in vitro and in vivo genotoxicity tests were performed with
