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

The acute, subchronic and genetic toxicity of the hydrochlorofluorocarbons HCFC-225ca and HCFC-225cb were evaluated to assist in establishing proper handling guides. In acute inhalation studies, rats were exposed for 4 h to various concentrations of each isomer. Based on the mortality incidence, the LC50 value for HCFC-225cb for males and females (combined) was 36800 ppm. For HCFC-225ca, the LC50 for males and females (combined) was 37300 ppm. Narcotic-like effects, e.g. prostration, incoordination and reduced motor activity, were observed during exposure to either isomer, but these signs were not evident 15 min after termination of exposure. Histopathological examination of the liver revealed an increase in mitotic figures with vacuolation of hepatocytes and fluid-filled, congested hepatic sinusoids. In cardiac sensitization studies, HCFC-225cb induced a cardiac sensitization response at 20000 ppm, with one fatal response, whereas a blend of the two isomers (45% HCFC-225ca/55% HCFC-225cb) produced a cardiac sensitization response at 15000 ppm. In 4-week subchronic inhalation studies, male and female rats were whole-body exposed to HCFC-225cb at concentrations of 0, 1000, 5000 or 15000 ppm for 6 h a day, 5 days per week. Similarly, male and female rats were whole-body exposed to HCFC-225ca concentrations of 0, 50, 500 or 5000 ppm for 6 h a day, 5 days per week. During exposure, narcotic-like and irritant effects were observed. A dose-related decrease in cholesterol and triglycerides was observed in the treated rats, with males being affected more than females. Increases in liver weight were observed in most male and female rats exposed to either isomer. The increase in liver weight was consistent in male rats with microscopic evidence of hepatocyte hypertrophy. Although liver weight was increased in female rats, no hepatocyte enlargement was 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 reverse mutation assay, or clastogenic in the chromosomal aberration assay with Chinese hamster lung cells. Also, neither isomer induced unscheduled DNA synthesis in liver cells. However, both isomers were clastogenic in the chromosomal aberration assay with human lymphocytes in the absence of S-9. No increases in aberrant cells were observed in activated cells exposed to either isomer.

Biodegradation and ecotoxicity of HFCs and HCFCs.

Hydrofluorocarbons (HFCs) and hydrochlorofluorocarbons (HCFCs) are used or developed as substitutes for fully halogenated chlorofluorocarbons. Based on the results of closed-bottle tests, the biodegradation of HFC-32, HCFC-123, HCFC-124, HFC-125, HFC-134a, HCFC-141b, HCFC-225ca, and HCFC-225cb was less than 60% after 28 days and therefore these compounds are considered not readily biodegradable. Standard acute toxicity tests with HCFC-123, HCFC-141b, and HCFC-225ca using algae, water fleas, and fish revealed EC50 values in the range of 17-126 mg/L. EC50 values of HFC-134a ranged between 450-980 mg/L. Fish studies with HCFC-141b and HCFC-225ca revealed bioaccumulation factors of <3 and 15-64, respectively. A study with plants revealed no effect of HCFC-141b on seed germination and growth of wheat (Triticum aestivum), radish (Raphanus sativus), and cress (Lepidium sativum). In conclusion, HFCs and HCFCs are not very toxic to aquatic organisms and terrestrial plants. No evidence for any aerobic biodegradation for most of the HFCs and HCFCs was found.

Four-week repeated inhalation study of HCFC 225ca and HCFC 225cb in the common marmoset.

Four male and three female marmosets in each group were exposed to air only, 1000 ppm of HCFC 225ca or 5000 ppm of HCFC 225cb, for 6 h per day for 28 consecutive days. HCFC 225ca caused a slight reduction in body weight. HCFC 225cb occasionally caused somnolence during exposure and vomiting on the first day of exposure. Clinical chemistry findings included a mild reduction of triglyceride, cholesterol and phospholipid levels and increased GOT level in the HCFC 225ca exposure group. HCFC 225cb also caused a reduction of triglyceride levels in some animals. HCFC 225ca caused a slight increase of hepatic carnitine palmitoyltransferase (CPT) activity while HCFC 225cb slightly increased cyanide-insensitive palmitoyl CoA beta-oxidation (FAOS) activity. In the HCFC 225cb exposure group, an increase in cytochrome P-450 content was also observed. HCFC 225ca caused a fatty change in the hepatic cells. Increased incidence of lipid droplets in the hepatic cells and myelin-like bodies in hepatic cells, Kupffer's cells and hepatic blood vessels were observed electron microscopically in the HCFC 225ca exposure group. A proliferation of smooth endoplasmic reticulum was observed in the HCFC 225cb exposure group. Decreased peroxisome volume density in the HCFC 225ca group, and increased volume density in the HCFC 225cb exposed females were seen. However, organ weight measurement and histopathological examination did not reveal hepatomegaly or hypertrophy with either substance. Although slight changes were noticed in peroxisome volume density and in some of the peroxisomal enzyme activities, the changes related to peroxisome proliferation with HCFC 225ca and 225cb were minimal in marmosets compared to those seen in rats. Histopathological examination and hormonal analysis did not reveal any abnormalities in the pancreas or testes.