Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
731 690 mg/m³
Additional information

No studies assessing the effects of 1,1,1,2,3,3,3 -heptafluoropropane on fertility were available. However, Article 13 of REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such asin vitrotests, QSARs, grouping and read-across.

The use of analogue approach for hydrofluorocarbons is justified and documented in the position paper "Use of read across in the human hazard assessment of hydrofluorocarbons (HFCs)", attached in the endpoint summary in Section 7 of the Technical Dossier (Toxicological information).

A combined fertility and developmental effects study with rats was available on the structurally related substance, 1,1,1,3,3 -pentafluorobutane (HFC 365mfc; TNO, 2001). Groups of 28 male and female rats were exposed to 0, 5000, 15000 and 30000 ppm of the test substance. Males were exposed during a 10 weeks premating period, females were exposed 2 weeks prior to mating 5 days/week, 6 h/day. Afterwards animals were cohabited (one male and one female per cage) for maximum one week of mating, during which they were still exposed 6 h/day. Pregnant females were exposed until day 15 of gestation and sacrificed on day 21. Fetus, placentas and reproductive organs were weighed and fetuses were examined after Caesarian section. The viscera and the skeletons of all fetuses were examined. Males were sacrificed after the mating period and testes and epididymides, including sperm parameters, were examined.

No statistically significant differences between the control group and the exposed groups concerning the number of corpora lutea, implantation sites, live and dead fetuses, early and late resorptions and pre-and post-implantation losses were observed. The sex ratio of the fetuses was comparable amongst all groups. No statistically significant differences in gravid and empty uterus weight, ovary weight, carcass weight and net weight change of females were observed. Also no remarkable findings of the placenta and the mean placenta weight, as well as statistically significant difference in mean anogenital distance were found between the control and exposed groups. Upon fetal examination there were no treatment-related changes in external observations or fetal soft tissues. No statistically significant differences were observed among the control, low-, mid- and high-concentration groups in skeletal malformations and anomalies. Statistically significant differences found in variations, retardation in skeletal ossification and cartilage were considered not to be related to treatment.

Based on the results of the study, NOAEL for reproductive and developmental effects was set at 30000 ppm, corresponding to the highest tested concentration.

In addition, a dominant lethal assay with mice, performed according to the protocol similar to OECD guideline 478 (ICI Central Toxicology Laboratory, 1979) and a reproductive toxicity study with rats (Alexander et al., 1996) on another structural analogue of 1,1,1,2,3,3,3 -heptafluoropropane, 1,1,1,2 -tetrafluoroethane (HFC 134a), were available for assessment. No adverse effects on fertility were noted in the dominant lethal assay in mice exposed to the test substance at concentration levels of 0, 1000, 10000, 50000 ppm for 6 hr/days during 5 days. In the reproductive toxicity study, pregnant female rats (F0 generation) were exposed to to the test substance at concentrations of 0, 2,500, 10,000 and 50,000 ppm from day 17 to 20 of gestation. Exposure recommenced at the same concentrations on day 1 post partum and continued until day 21 post partum. The females were allowed to litter and rear their young (F1 generation). On day 21, 1 male and 1 female F1 pup was retained from each of the 20 litters/group and raised to maturity. The selected F1 rats were mated when they were approximately 84 days old and, on day 20 of pregnancy, the females were terminated to allow the examination of their uterine contents and ovaries. The F1 males were also terminated at this time. No treatment-related effects on reproductive performance, maturation or development of the offspring were reported, resulting in NOAEL of 50000 ppm for effects on fertility.

Finally, gross pathology and histopathology examinations performed in several reproductive organs of males (testes, epididymis and prostate) and females (uterus, ovaries and vagina) in a 90 -day inhalation study in rats exposed up to 731690 mg/m3 HFC 227ea did not reveal any adverse effects (WIL Research Laboratories, 1993a).

In summary, based on the evidence from the available studies on the structural analogues 1,1,1,2 -tetrafluoroethane and 1,1,1,3,3 -pentafluorobutane, 1,1,1,2,3,3,3 -heptafluoroethane is considered to be not toxic for reproduction. The absence of any signs of toxicity to reproductive organs following subchronic exposure to 731690 mg/m3 HFC 227ea further support the conclusion of no concern for possible effects to reproduction.


Short description of key information:
No data on reproductive toxicity of 1,1,1,2,3,3,3-heptafluoropropane were available. However, based on the data from the structurally related substances 1,1,1,3,3-pentafluorobutane and 1,1,1,2-tetrafluoroethane, the substance is considered to be not be toxic to reproduction.

Effects on developmental toxicity

Description of key information
The results of two developmental toxicity studies showed no maternal and developmental toxicity in rats and rabbits up to the highest concentration tested (731690 mg/m3 (105000 ppm)).
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
731 690 mg/m³
Additional information

Two developmental toxicity studies were available, one with rats (WIL Research Laboratories, 1994a) and one with rabbits (WIL Research Laboratories, Inc., 1994b), with exposure concentrations varying from ca. 137000 to 731000 mg/m3 (20000-105000 ppm). At termination, no treatment-related internal findings or organ weight changes were observed in either of the studies up to 731690 mg/m3, the maximum dose tested. In both the rabbit and rat studies, there were no statistically significant differences in the intrauterine growth and survival of foetuses after implantation between the treated and control groups. Parameters evaluated included pre-implantation loss, post-implantation loss, live litter size, foetal sex ratios, foetal body weights and numbers of corpora lutea and implantation sites. Some foetal external, soft tissue and skeletal malformations and variations were observed; however, these observations are commonly observed in the historical control data and appeared at a similar incidence in the concurrent control group, or occurred occasionally. Based on the results of the animal studies, the NOAEL for both maternal and developmental toxicity in rabbits and in rats was 731690 mg/m3 (105000 ppm), 6 hr/day. Therefore, developmental toxicity is not considered an endpoint of concern for the substance.

These studies support the NOAEL of 731690 mg/m3 which will be used for DNEL derivation for repeated dose toxicity.

Justification for classification or non-classification

As no developmental toxicity was observed in developmental toxicity studies with rats and rabbits up to 731.69 mg/L (105000 ppm), classification is not warranted according to EU Directive 67/548/EEC or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.