PAFT : Programme for Alternative Fluorocarbon Toxicity Testing

HCFC-225ca and HCFC-225cb (two isomers of dichloropentafluoropropane) are two of a series of fluorocarbon alternatives being tested by the Programme for Alternative Fluorocarbon Toxicity Testing (PAFT). HCFC-225ca and HCFC-225cb are being considered primarily as alternatives to CFC-113 as a solvent in cleaning applications. The isomers have been commercialized as a 45/55 weight percent mixture of HCFC-225ca and HCFC-225cb. Testing has been conducted on the separate isomers to allow characterization of the toxicity of each isomer and of the mixed isomer products.

Summary of Testing Results HCFC-225ca and HCFC-225cb have low acute oral, dermal and inhalation toxicity. Exposure in the range of 650 to 1,000 ppm with HCFC-225ca produced effects on the liver in rodents, but a minor effect in a primate. Exposures in the range of 1,000 to 5,000 ppm with HCFC-225cb resulted in only marginal effects in rodents or a primate. Neither isomer is genotoxic.

Data from acute toxicity studies demonstrate that HCFC-225ca and HCFC-225cb have very low acute toxicity. Neither isomer causes eye irritation nor dermal toxicity in standardized tests; skin application of both isomers at high doses (2,000 mg/kg body weight) produces no adverse effects. Oral administration of either isomer at high doses (5,000 mg/kg body weight) does not cause any mortality. Therefore, the oral LD50s are greater than 5,000 mg/kg body weight. Both isomers also have very low acute inhalation toxicity as measured by the concentration that causes 50% mortality in experimental animals, the LC50. The 4-hour exposure LC50s for both isomers are approximately 37,000 ppm in rats. Anaesthetic-like effects are observed in rats at high inhalation concentration (greater than 5,000 ppm).

As with many other halocarbons and hydrocarbons, inhalation of HCFC-225ca and HCFC-225cb followed by intravenous injection of epinephrine, which simulates human stress reactions, results in a cardiac sensitization response in experimental screening studies with dogs. This cardiac sensitization response is observed at approximately 15,000 ppm for the mixture of HCFC-225ca/ HCFC-225cb (45/55 weight percent) and 20,000 ppm for HCFC-225cb, which are levels well above expected exposures. By comparison, a cardiac sensitization response is observed with CFC-113 at approximately 5,000 ppm.

In 28-day inhalation studies with rats, the activity and responsiveness of the animals was reduced at exposures of 5,000 ppm or greater for each isomer. Toxicity was otherwise confined to the liver; liver enlargement and induction of peroxisomes was seen following treatment with either of the isomers. HCFC-225ca was more potent than HCFC-225cb in eliciting these liver effects.

To investigate the biological relevance of the liver toxicity to humans, comparative repeated inhalation studies have been conducted with rats, hamsters, guinea pigs and marmosets. In 14- day exposure studies with rats, hamsters and guinea pigs, the liver effects were also observed in rodents, while no such effects were observed in guinea pigs. In the 28-day study with marmosets, exposure to HCFC-225ca at 1,000 ppm caused effects on the liver, such as slight fat deposition associated with changes in serum biochemical parameters. In the same study, exposure to HCFC-225cb at 5,000 ppm caused somnolence during exposure and an increase of cytochrome P-450, indicative of an adaptive response to HCFC-225cb. However, no liver enlargement was seen and virtually no peroxisomal induction was observed with either isomer.

Several genetic studies have also been completed with both isomers. These studies included an Ames assay, in vitro chromosomal aberration with Chinese Hamster Lung (CHL) and human lymphocyte, and in vivo unscheduled DNA synthesis assay. Based on the weight of evidence from all in vitro and in vivo studies, neither isomer is mutagenic. In only one study, which utilized an in vitro culture of human lymphocyte, did HCFC-225ca cause changes in the genetic materials while HCFC-225cb elicited a marginal response. However, the overall evidence from these studies implies that neither isomer is genotoxic.

Pharmacokinetic studies with rats indicated that either isomer found in blood is rapidly eliminated on termination of exposure.

The testing of HCFC-225ca and HCFC-225cb under PAFT IV has been completed. The results are summarized in the sidebar above.

As for all chemicals, PAFT recommends that exposures be kept to a practicable minimum.

September 1995

Last updated October 11, 1996