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.
Brock
W J
WJ
E.I. du Pont de Nemours & Co., Haskell Laboratory, Newark, DE 19714, USA.
Shin-Ya
S
S
Rusch
G M
GM
Hardy
C J
CJ
Trochimowicz
H J
HJ
D000280:Administration, Inhalation; D000818:Animals; D002478:Cells, Cultured; D017402:Chlorofluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D002784:Cholesterol / Q000097:blood; D006224:Cricetinae; D003412:Cricetulus; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D015386:Hazardous Substances / Q000008:administration & dosage / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D006801:Humans; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D017402:Chlorofluorocarbons; D015386:Hazardous Substances; D014280:Triglycerides; C076684:HCFC 225; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol