or food consumption or in clinical observations or post-mortem findings. There were no compound-related developmental effects. The end points evaluated were mean fetal weight, mean litter size, pre- and post-implantation embryo lethality, and fetal malformations and variations.
Genotoxicity
Bentley (1995a) evaluated HFC-236fa (concentrations ranging from 200,000 to 1,000,000 ppm) for clastogenic activity in human lymphocytes in vitro following 3-hr exposures with and without metabolic activations (S9). No increases in the percent of chromosomally abnormal cells occurred at any HFC-236fa concentration evaluated, and no concentration-related trends in chromosomal-aberration induction were observed.
An inhalation micronucleus study was conducted in male and female mice exposed to HFC-236fa at 0, 5,000, 20,000, or 50,000 ppm for 6 hr per day for 2 consecutive days. Bone-marrow smears were prepared approximately 24 and 48 hr after the second exposure (Bentley 1995b). No statistically significant increases in micronucleated polychromatic erythrocytes were observed in any animal at any concentration tested.
HFC-236fa was also evaluated for mutagenicity in Salmonella typhimurium strains TA100, TA1535, TA97, and TA98 and in Escherichia coli WPSuvrA-(pKM101) with and without an exogenous metabolic activation system (S9) (Bentley 1995c). At concentrations tested between 0 and 1,000,000 ppm, no evidence of mutagenic activity was detected in either of two independent trials.
On the basis of the available data, the subcommittee concludes that HFC-236fa is not genotoxic and is unlikely to induce heritable effects in humans
Carcinogenicity
No chronic carcinogenicity exposure studies of HFC-236fa are currently available.
SUMMARY
Studies on the metabolism and disposition of HFC-236fa indicate that HFC-236fa is not metabolized to any significant extent. PB-PK modeling us-
