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 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 to induce cardiac sensitization in experimental screening studies in dogs; only the highest concentration tested--300,000 ppm--elicited a cardiac sensitization response. In an initial 4-week nose-only inhalation study, male and female rats were exposed 6 hr/day, 5 days/week at concentrations of 0, 2000, 10,000, or 40,000 ppm. Females showed no evidence of toxicity at any exposure level; male rats did exhibit degenerative changes only in the tests at all exposure levels. However, because of exposure system irregularities, which resulted in excessive temperature conditions and stress in the HFC-143a-exposed groups, the study was repeated in male rats exposed by whole-body inhalation. In this repeat study no toxicity was observed at < or = 40,000 ppm. Moreover, a subsequent 90-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 no evidence of toxicity at any exposure concentration. The results of the second 4-week and the 90-day studies using whole-body exposures indicate that the findings from the first 4-week study were related to the stress induced by excessive temperatures and nose-only restraint. Therefore, the no-observed-effect level (NOEL) for rats repeatedly exposed up to 90 days was considered to be 40,000 ppm. In developmental toxicity studies with rats and rabbits, an increase in visceral variations or skeletal malformations was observed, respectively, at HFC-143a 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 litter in the control versus 6.8-16.8% for historical control values), the lack of a clear dose-response relationship, and the lack of other developmental effects, these findings were not considered related to HFC-143a exposure. In addition, results from genotoxicity studies (Ames, chromosomal aberration with human lymphocytes, mouse micronucleus) demonstrated that HFC-143a was not mutagenic.
Brock
W J
WJ
E. I. du Pont de Nemours & Co., Haskell Laboratory, Newark, Delaware 19714, USA.
Trochimowicz
H J
HJ
Farr
C H
CH
Millischer
R J
RJ
Rusch
G M
GM
D000014:Abnormalities, Drug-Induced; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D018675:Toxicity Tests
D006845:Hydrocarbons, Fluorinated; D009153:Mutagens; C104768:1,1,1-trifluoroethane