1-chloro-1,1-difluoroethane

Endpoint summary

Additional information

The results of 4 separate tests conducted on 1-chloro-1,1-difluoroethane vapors indicate that the material produced a mutagenic activity in Salmonella typhimurium TA1535 and TA100 strains with, as well as without metabolic activation by S9 mix rat microsomes. Concentrations as high as 30% or more of the gas in air and a sufficient time exposure (24 hours or more) were generally needed to get positive effects. The increase in revertant colony number over the control values remained small with TA 100 (never more than 3 times of the control value, even with 100% gas exposure – 4100000 mg/m³). With TA1535 values tended to remain low (less than 4 times control value) up to 50% gas exposure (2050000 mg/m³); only the 100% (4100000 mg/m³) concentration exposure gave large excess of revertant colony number over the control (44 times control value).

 

In addition two cell transformation assays were conducted on 1-chloro-1,1 difluoroethane. One was poorly reported and gave a positive result (exposure in liquid phase). The other gave a negative result (exposure in gaseous phase). Overall, it is not possible to derive any firm conclusion about the cell transforming potential of the compound.

 

1-Chloro-1,1- difluoroethane did not demonstrate statistically significant chromosomal aberration activity in a 90 day-inhalation bone marrow cytogenic study in male rats exposed to airborne concentrations ranging from 1000 (4100 mg/m³) to 20000 ppm (82000 mg/m³), 6 hours/day, 5 days/week. A slight, but not statistically significant, increase in the mitotic rate was noted but was not considered to be an exposure-related adverse response. There were no increases in the numbers of chromosome gaps. Increased numbers of chromosome breaks were seen at all exposure levels and were accompanied by an increased incidence of acentric fragments at the 20000 ppm exposure level. These intergroup differences were neither statistically significant nor dose-related.

 

In a dominant lethal assay, male rats were exposed by inhalation to 1-chloro-1,1- difluoroethane at concentrations of 1000, 10000 and 20000 ppm (4100, 41000 and 82000 mg/m³, respectively) for a 15 week-treatment period and subsequently mated with untreated females. The results were considered to show negative dominant lethal mutagenicity.

The genotoxicity picture is common to other 1,1,1 trihaloethanes (i.e. occasional positive Ames test in Salmonella typhimurium TA1535 and TA100 with as well as without metabolic activation, negative in vivo mutagenicity tests, and no induction of malignant tumours in long term rat studies). In conclusion, genotoxicity is not an endpoint of concern for the substance.

Short description of key information:
1-Chloro-1,1- difluoroethane has shown positive effect in the Ames test on Salmonella typhimurium TA 1535 and TA 100 with as well as without metabolic activation (at concentrations as high as 30% or more of the gas in air and a sufficient time exposure (24 hours or more)) and gave equivocal results in cell transformation assays. However 1-chloro- 1,1- difluoroethane has shown two negative in vivo assays in a dominant lethal and in a bone marrow cytogenetic assay in rats exposed during 15 and 13 weeks respectively.
This genotoxicity picture is common to other 1,1,1 trihaloethanes (i.e. occasional positive Ames test in Salmonella typhimurium TA1535 and TA100 with as well as without metabolic activation, negative in vivo mutagenicity tests, and no induction of malignant tumours in long term rat studies).
In conclusion, genotoxicity is not an endpoint of concern for the substance.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on all available data on genotoxicity, classification for genotoxicity for 1-chloro-1,1-difluoroethane is not warranted according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.