Inhalation toxicity and genotoxicity of hydrochlorofluorocarbon (HCFC)-225ca and HCPC-225cb

The acute, subchronic and genetic toxicity of the hydrochlorofluorocarbons HCFC-225ca and HCFC-225cb were evaluated to assist in establishing proper h andling guides. In acute inhalation studies, rats were exposed for 4h to va rious concentrations of each isomer. Based on the mortality incidence, the Lc,, value for HCFC-225cb for males and females (combined) was 36 800 ppm. For HCFC-225ca, the LC50 for males and females (combined) was 37 300 ppm. N arcotic-like effects, e.g. prostration, incoordination and reduced motor ac tivity, were observed during exposure to either isomer, but these signs wer e not evident 15 min after termination of exposure. Histopathological exami nation of the liver revealed an increase in mitotic figures with vacuolatio n of hepatocytes and fluid-filled, congested hepatic sinusoids. In cardiac sensitization studies, HCFC-225cb induced a cardiac sensitization response at 20 000 ppm, with one fatal response, whereas a blend of the two isomers (45% HCFC-225ca/55% HCFC-225cb) produced a cardiac sensitization response a t 15 000 ppm. In it-week subchronic inhalation studies, male and female rat s were whole-body exposed to HCFC-225cb at concentrations of 0, 1000, 5000 or 15 000 ppm for 6 h a day, 5 days per week. Similarly, male and female ra ts were whole-body exposed to HCFC-225ca concentrations of 0, 50, 500 or 50 00 ppm for 6h a day, 5 days per week. During exposure, narcotic-like and ir ritant effects were observed. A dose-related decrease in cholesterol and tr iglycerides was observed in the treated rats, with males being affected mor e than females. Increases in liver weight were observed in most male and fe male rats exposed to either isomer. The increase in liver weight was consis tent in male rats with microscopic evidence of hepatocyte hypertrophy. Alth ough liver weight was increased in female rats, no hepatocyte enlargement w as observed in treated female rats. Increases in cytochrome P-450 and beta- oxidation activities were also observed in male and female rats exposed to either isomer. Neither of the HCFC-225 isomers was mutagenic in the Ames re verse mutation assay, or clastogenic in the chromosomal aberration assay wi th Chinese hamster lung cells. Also, neither isomer induced unscheduled DNA synthesis in liver cells. However, both isomers were clastogenic in the ch romosomal aberration assay with human lymphocytes in the absence of S-9. No increases in aberrant cells were observed in activated cells exposed to ei ther isomer. Copyright (C) 1999 John Wiley & Sons, Ltd.