Wj. Brock et al., ACUTE, SUBCHRONIC, AND DEVELOPMENTAL TOXICITY AND GENOTOXICITY OF 1,1,1-TRIFLUOROETHANE (HFC-143A), Fundamental and applied toxicology, 31(2), 1996, pp. 200-209
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