ACUTE, SUBCHRONIC, AND DEVELOPMENTAL TOXICITY AND GENOTOXICITY OF 1,1,1-TRIFLUOROETHANE (HFC-143A)

The toxicity potential of 1,1,1-trifluoroethane (HFC-143a), a CFC alte rnative, was evaluated in several acute, subchronic, and developmental toxicity studies by the inhalation route and in genotoxicity studies. HFC-143a has a very low acute inhalation toxicity potential as shown by a 4-hr LC50 of >540,000 ppm in rats. HFC-143a has a low potential t o induce cardiac sensitization in experimental screening studies in do gs; only the highest concentration tested-300,000 ppm-elicited a cardi ac sensitization response. Tn an initial 4-week nose-only inhalation s tudy, male and female rats were exposed 6 hr/day, 5 days/week at conce ntrations of 0, 2000, 10,000, or 40,000 ppm. Females showed no evidenc e of toxicity at any exposure level; male rats did exhibit degenerativ e changes only in the testes at all exposure levels. However, because of exposure system irregularities, which resulted in excessive tempera ture conditions and stress in the HFC-143a-exposed groups, the study w as repeated in male rats exposed by whole-body inhalation. In this rep eat study no toxicity was observed at less than or equal to 40,000 ppm . Moreover, a subsequent 90-day whole-body inhalation study in rats ex posed 6 hr/day, 5 days/week at 0, 2000, 10,000, or 40,000 ppm resulted in no evidence of toxicity at any exposure concentration. The results of the second 4-week: and the 90-day studies using whole-body exposur es indicate that the findings from the first 4-week study were related to the stress induced by excessive temperatures and nose-only restrai nt. Therefore, the no-observed-effect level (NOEL) for rats repeatedly exposed up to 90 days was considered to be 90,000 ppm. Tn development al toxicity studies with rats and rabbits, an increase in visceral var iations or skeletal malformations was observed, respectively, at HFC-1 43a concentrations of 2000, 10,000, or 40,000 ppm (rat) or at the low and high concentrations (rabbit). Because of the unusually low control incidence of variations (1.6% per liner in the control versus 6.8-16. 8% for historical control values), the lack of a clear dose-response r elationship, and the lack of other developmental effects, these findin gs were not considered related to HFC-143a exposure. In addition, resu lts from genotoxicity studies (Ames, chromosomal aberration with human lymphocytes, mouse micronucleus) demonstrated that HFC-143a was not m utagenic. (C) 1996 Society of Toxicology