Studies in rodents indicate that dichlorotrifluoroethane is easily absorbed via the respiratory route and undergoes a biphasic uptake. It is distributed in all organs and is more concentrated in the liver.
About 90% of unchanged dichlorotrifluoroethane was eliminated via the lungs. The rest was metabolised to trifluoroacetic acid which was excreted in the urine. Small amounts of trifluoroacetylated proteins were detected in exposed rats.
Dichlorotrifluoroethane has a low order of acute toxicity. Its oral approximate lethal dose in rats was 9,000 mg/kg; its 4-hour-inhalation LC50 was 200,000 mg/m3 in rats and 178,000 mg/m3 in hamsters. Its dermal LD50p in rats and rabbits was greater than 2,000 mg/kg. The primary effect was a rapidly reversible central nervous depression. After a few minutes exposure it induced prenarcotic effects at 31,300 mg/m3 and anaesthesia at 129,000 mg/m3 in rats.
Liquid dichlorotrifluoroethane did not induce skin irritation in rabbit or skin sensitization in guinea pigs but it caused moderate eye irritation in rabbits.
Repeated inhalation exposure studies in rats exposed 6 h/d, 5 d/wk, for 4 to 13 weeks, to vapour levels of up to 125,000 mg/m3, have resulted in bodyweight decreases and liver weight increases but with minimal adverse histological findings. Dichlorotrifluoroethane was found to cause a marked drop in serum cholesterol, triglyceride and glucose levels at 1,880 mg/m3 and above. Signs of CNS depressing effects were seen during exposure periods above 6,250 mg/m3. However, there was no evidence of neurotoxicity when specific testing for neurobehavioural and nervous tissue histology were performed in a 13-week neurotoxicity study in rats.
Dichlorotrifluoroethane elicited cardiac sensitization to adrenaline in dogs acutely exposed by inhalation at a concentration of 119,000 mg/m3. The no-effect-level was 62,500 mg/m3.
No clear effects were seen in serum steroid hormone and CCK levels in rats and guinea pigs exposed to dichlorotrifluoroethane. In rats dichlorotrifluoroethane produced minimal decreases in testicular luteinizing hormone and testosterone levels under stimulation conditions only. Dichlorotrifluoroethane was found to induce liver peroxisome proliferation in rats. Its proliferating potential is weak and may be due to its metabolism to trifluoroacetic acid.
Dichlorotrifluoroethane was not teratogenic or embryotoxic to rats and rabbits exposed by inhalation at concentrations of 31,300 and 62,500 mg/m3 which induced slight maternal toxicity.
In a two-generation inhalation study conducted with dichlorotrifluoroethane in rats exposed 6 h/d, 7 d/wk at concentrations ranging from 188 to 6,250 mg/m3, there were no effects on mating performance and offspring survival. Growth retardation was observed in pups during nursing at all test concentrations, but normal growth was restored in the post-weaning phase. Dichlorotrifluoethane was inactive in several in vitro studies including a series of Salmonella typhimurium assays, a Saccharomyces cerevisiae assay and a cell transformation assay. It was active only in the human lymphocyte chromosome abberation assay. Dichlorotrifluoroethane was clearly inactive in a series of in viva studies, including mouse micronucleus, rat chromosome abberation and rat unscheduled DNA synthesis. In conclusion, dichlorotrifluoroethane is not genotoxic in viva and therefore does not have toxicologically significant genotoxicity.
Rats were exposed 6 h/d, 5 d/wk for 2 years by inhalation in a lifetime study to concentrations of 1,875; 6,250 and 31,300 mg/m3. Compared to controls, survival was significantly improved in an exposure related pattern in all exposed groups. Significantly depressed bodyweights and levels of serum triglycerides, glucose and cholesterol were observed. Compound-related increased incidences of benign tumours were observed in the liver, testis and pancreas. These tumours were a continuum from hyperplasia and occurred late in life. It is thought that they are related with non-genotoxic mechanisms associated with the peroxisome proliferating potential of dichlorotrifluoroethane or with hormonal disturbances occurring in senescent rats. Considering they occurred late in life and were benign, the relevance of these findings is questionable in terms of a carcinogenic risk to man.
Joint Assessment of Commodity Chemicals No. 33
ECETOC, February 1996