2-YEAR INHALATION TOXICITY STUDY IN RATS WITH HYDROCHLOROFLUOROCARBON-123

The potential chronic toxicity and oncogenicity of hydrochlorofluoroca rbon 123 (HCFC-123) was evaluated by exposing male and female rats to 0, 300, 1000, or 5000 ppm HCFC-123 for 6 hr/day, 5 days/week, for 2 ye ars. Clinical pathology was evaluated at 6, 12, 18, and 24 months. An interim termination and measurements of hepatic cell proliferation and beta-oxidation activity were conducted at 12 months. The terminal eut hanization occurred at 24 months. Males and females exposed to 5000 pp m and females exposed to 300 or 1000 ppm had lower body weights and bo dy weight gains. Serum triglyceride and glucose concentrations were si gnificantly decreased at all exposure concentrations in both sexes. Se rum cholesterol was also lower in 300, 1000, and 5000 ppm females and in 5000 ppm males. Alterations in serum protein concentrations occurre d at 300, 1000, and 5000 ppm. Survival was higher in 1000 and 5000 ppm males and females. At 24 months, increased relative liver weight occu rred in 5000 ppm males, and decreased absolute kidney weight occurred in 5000 ppm males and in 1000 and 5000 ppm females. Benign hepatocellu lar adenomas were increased in 5000 ppm males and in all test groups o f females. Hepatic cholangiofibromas were also increased in 5000 ppm f emales. Pancreatic acinar cell adenomas were increased in all test gro ups of males, and acinar cell hyperplasia was increased in the 1000 an d 5000 ppm males and females. Benign testicular interstitial adenomas and focal interstitial cell hyperplasia were also increased in all mal e test groups compared to controls. Diffuse retinal atrophy was increa sed in all male and female test groups, but it was considered to be an indirect compound-related effect. Hepatic beta-oxidation activity (pe roxisome proliferation) was higher in 300, 1000 and 5000 ppm males and 1000 and 5000 ppm females. Compound-related differences in the rate o f hepatic cell proliferation were not observed at any exposure concent ration. Decreased incidences of a variety of age-related lesions occur red at 1000 and 5000 ppm. (C) 1995 Society of Toxicology.