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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
60 mg/kg bw/day
Additional information

In accordance with the OECD guideline on combined repeated dose and reproductive/developmental toxicity screening test, 2-propanol, 1,1,1,3,3,3-hexafluoro- (PHF) was studied for oral toxicity in rats at doses of 0, 10, 60, and 300 mg/kg/day.

At 300 mg/kg, the mean estrous cycle was prolonged to 6 days in 4 dams and the mean estrous cycle in this group was significantly prolonged. The copulation index was 83.3% (10/12 animals) at 300 mg/kg while other groups were all 100 % (12/12 animals). During the gestation period, none of the dams completed the delivery on day 22 of gestation and one of them showed dystosia as it delivered on day 25 of gestation. The gestation length was prolonged in this group. These changes were suspected to be caused by anesthetic action of the test substance. In numbers of corpora lutea, implantations, and offspring, although they were comparable to the control values, number of live offspring and delivery index decreased.

There were no significant differences between the test substance-treated groups and control group in number of days until copulation, incidence of females without the estrous cycle, fertility index, implantation index, numbers of corpora lutea and implantation, gestation index, and number of offspring.

As for the reproductive toxicity of PHF, the NOEL and NOAEL for parental animals were judged to be 60 mg/kg/day, since prolonged estrous cycle and gestation length, decreased copulation index and delivery index in dams were noted in the 300 mg/kg group.

 


Short description of key information:
In accordance with the OECD guideline on combined repeated dose and reproductive/developmental toxicity screening test, 2-propanol, 1,1,1,3,3,3-hexafluoro- (PHF) was studied for oral toxicity in rats at doses of 0, 10, 60, and 300 mg/kg/day. In the parental animals, abnormalities in the reproductive function, parturition, and maternal behavior due to deterioration of the health condition were noted.

Effects on developmental toxicity

Description of key information
In accordance with the OECD guideline on combined repeated dose and reproductive/developmental toxicity screening test, 2-propanol, 1,1,1,3,3,3-hexafluoro- (PHF) was studied for oral toxicity in rats at doses of 0, 10, 60, and 300 mg/kg/day. In the offspring, generalized edema and/or protruding tongue, blackish and/or dark reddish abnormal contents in the intestine, decreases in number of live offspring, body weight, and viability index were observed.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
60 mg/kg bw/day
Additional information

In accordance with the OECD guideline on combined repeated dose and reproductive/developmental toxicity screening test, 2-propanol, 1,1,1,3,3,3-hexafluoro- (PHF) was studied for oral toxicity in rats at doses of 0, 10, 60, and 300 mg/kg/day.

In offspring at 300 mg/kg, among fetuses or dead offsprings of 3 dams including the dead dam during the gestation period, generalized edema and protruding tongue were observed in 20 fetuses/offsprings and in 22 fetuses/offsprings, respectively. In this group, increased pleural fluid was observed in 3 offsprings. Blackish and/or dark reddish abnormal contents in the intestine were observed in 6 offsprings. Since it is reported that ethanol similar to a monohydric alcohol (C3) of PHF affected the offspring’s intestines by embryonic exposure, this change was suspected to be test substance effects. At 300 mg/kg, in addition to total litter loss in 3 dams including the above mentioned dystosia, the number of dead offsprings increased until 4 days after birth. Consequently, the number of live offspring and viability index on day 4 decreased. For these changes, the anesthetic action of the test substance was likely to work on the maternal behavior. Moreover, although the body weight at birth was comparable to that of the control group in both sexes, the variability index and body weight on day 4 decreased.

There were no significant differences between the test substance-treated groups and control group in number of offspring.

As for the developmental toxicity of PHF, the NOEL and NOAEL for offspring were judged to be 60 mg/kg/day, since generalized edema and protruding tongue, blackish and/or dark reddish abnormal contents in the intestine, decreases in number of live offspring, body weight, and viability index in offspring were noted in the 300 mg/kg group.

Justification for classification or non-classification

In the parental animals, abnormalities in the reproductive function, parturition, and in the offspring, generalized edema and/or protruding tongue were observed in this combined repeated dose and reproductive/developmental toxicity screening study. These changes were suspected to be caused by anesthetic action in maternal animals of the test substance. However, the evidence is not sufficiently convincing to secondary toxic effects of test substance. Therefore, PHF is classified into Category 2 for fertility or developmental effects.