CHRONIC TOXICITY, ONCOGENICITY, AND MUTAGENICITY STUDIES WITH CHLOROTETRAFLUOROETHANE (HCFC-124)

The chronic toxicity, oncogenicity, and mutagenicity of chlorotetraflu oroethane (HCFC-124) were evaluated. in the chronic toxicity/oncogenic ity study, male and female rats were exposed to 0 2000 10,000, or 50,0 00 ppm HCFC-124 for 6 hr/day, 5days/week, for 2 years. Body weights we re obtained weekly during the first three months of the study and ever y other week for the remainder of the study. Food consumption was dete rmined weekly. Clinical signs of toxicity were monitored throughout th e study. An ophthalmological examination was performed on all animals prior to study start, and all surviving rats were examined at approxim ately 3 12, and 24 months after study start. Clinical pathology was ev aluated at 3, 6 12, 18, and 24 months. An interim termination was cond ucted at 12 months. All surviving rats were necropsied at 24 months. A complete set of tissues was collected for microscopic examination, an d selected tissues were weighed. There were no compound-related, adver se effects on body weight, food consumption, survival, clinical signs of toxicity, ophthalmoscopically observable ocular lesions, serum horm one concentrations, or clinical pathology parameters at any exposure c oncentration in either male or female rats. Compared to controls, urin e fluoride was increased in males and females at all exposure concentr ations, and plasma fluoride was increased in females at all exposure c oncentrations. Excretion of fluoride represents conversion of the pare nt molecule, and as such is not considered to be an adverse effect The re were no toxicologically significant, compound-related organ weight changes or grass or microscopic findings in male or female rats at any of the exposure concentrations tested. HCFC-124 was not toxic or carc inogenic in rats of either sex after inhalation exposure at concentrat ions of up to 50,000 ppm in this two-year chronic toxicity/oncogenicit y study. After exposure to HCFC-124 for six hours per day, five days p er week, for 24 months, the no-observed-adverse-effect level for male and female rats was 50,000 ppm. HCFC-124 was not mutagenic in Salmonel la typhimurium strains TA1535, TA97, TA98, and TA100 with and without activation when evaluated at concentrations up to 60% HCFC-124 for 48 hours. No evidence of clastogenic activity was observed in cultured hu man lymphocytes at atmospheric concentrations up to 100% HCFC-124 for 3 hours, with and without metabolic activation. In vivo, no micronucle i were induced in mouse bone marrow cells following exposure of mice t o concentrations of 99,000 ppm HCFC-124 6 hours/day for 2 days.