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 alternative, was evaluated in several acute, subchronic,and developmental toxicity studies by the inhalation route andin genotoxicity studies. HFC-143a has a very low acute inhalationtoxicity potential as shown by a 4-hr LC50 of >540,000 ppmin rats. HFC-143a has a low potential to induce cardiac sensitizationin experimental screening studies in dogs; only the highestconcentration tested—300,000 ppm—elicited a cardiacsensitization response. In an initial 4-week nose-only inhalationstudy, male and female rats were exposed 6 hr/day, 5 days/weekat concentrations of 0, 2000, 10,000, or 40,000 ppm. Femalesshowed no evidence of toxicity at any exposure level; male ratsdid exhibit degenerative changes only in the testes at all exposurelevels. However, because of exposure system irregularities,which resulted in excessive temperature conditions and stressin the HFC-143a-exposed groups, the study was repeated in malerats exposed by whole-body inhalation. In this repeat studyno toxicity was observed at 40,000 ppm. Moreover, a subsequent90-day whole-body inhalation study in rats exposed 6 hr/day,5 days/week at 0, 2000, 10,000, or 40,000 ppm resulted in noevidence of toxicity at any exposure concentration. The resultsof the second 4-week and the 90-day studies using whole-bodyexposures indicate that the findings from the first 4-week studywere related to the stress induced by excessive temperaturesand nose-only restraint. Therefore, the no-observed-effect level(NOEL) for rats repeatedly exposed up to 90 days was consideredto be 40,000 ppm. In developmental toxicity studies with ratsand rabbits, an increase in visceral variations or skeletalmalformations was observed, respectively, at HFC-143a concentrationsof 2000, 10,000, or 40,000 ppm (rat) or at the low and highconcentrations (rabbit). Because of the unusually low controlincidence of variations (1.6% per litter in the control versus6.8–16.8% for historical control values), the lack ofa clear dose-response relationship, and the lack of other developmentaleffects, these findings were not considered related to HFC-143aexposure. In adition, results from genotoxicity studies (Ames,chromosomal aberration with human lymphocytes, mouse micronucleus)demonstrated that HFC-143a Was not mutagenic.