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Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

In a well-conducted two-generation reproduction study (Dow Chemical Company, 1985; Hayes et al., 1988), groups of 30 male and 30 female F344 rats were exposed to 0, 30, 100, 300 ppm (0, 70, 240 and 710 mg/m3) propylene oxide vapour, whole body, for 6 hours/day, 5 days/week for 14 weeks prior to mating performed according to GLP and similar to OECD guideline 416.

After weaning, 30 F1 pups/sex/group were similarly exposed to propylene oxide for 17 weeks and then mated to produce F2. Reproductive parameters examined included fertility, litter size, neonatal growth and survival. All adults and weanlings were examined for gross and microscopic lesions.

No deaths occurred, and there were no treatment-related alterations in demeanour or physical appearance in any of the animals during the pre-mating periods. Toxicity was evident as reduced body weight gain in F0 (8%) and F1 (16%) rats at 300 ppm, however there was no evidence of treatment-related adverse effect on fertility in F0 or F1 matings. Growth and survival of F1 and F2 offspring was not adversely affected by exposure of either generation of parents at any dose.

Mating and conception were not significantly affected in either F0 or F1 matings. Litter size was not adversely affected. Detailed pathology examination of adults and weanlings revealed no changes considered attributable to propylene oxide exposure. The results indicate that inhalation exposure to levels up to 300 ppm over two generations did not produce any adverse effect on reproductive function.


Short description of key information:
No adverse effects on fertility were found in a two-generation study (GLP and similar to OECD guideline 416) in which groups of 30 male and 30 female F344 rats were exposed to 0, 70, 240 and 710 mg/m3, propylene oxide vapour, whole body, for 6 hours/day, 5 days/week for 14 weeks prior to mating. The NOAEC for reproductive toxicity is 710 mg/m3.

Effects on developmental toxicity

Description of key information
No selectivbe adverse effects on development were noted in the developmental toxicity study in both rats and rabbits. Propylene oxide was administered by inhalation route at dose levels up to 500 ppm on gestation days 6 to 15. Based on these data, propylene oxide is considered to be not a developmental toxicant. 
Additional information

International Research and Development Corporation (1987)(Harris et al., 1989) investigated the potential developmental toxicity of propylene oxide by inhalation. Groups of 25 female F344 rats were exposed, whole-body, to 0, 100, 300, and 500 ppm (0, 237, 711 and 1,188 mg/m3) for 6 hours/day, on gestation days 6-15 inclusive. Caesarean sections were conducted on day 20 of gestation and the foetuses were removed and examined.

All foetuses were examined externally. No maternal deaths occurred, but mean maternal body weight gain was significantly lower over the period of exposure in darns receiving 500 ppm propylene oxide, compared to controls. Even so, no evidence of embryotoxicity or fetotoxicity was seen. Mean numbers of corpora lutea, implantations, viable foetuses, and post-implantation losses, were all comparable among the treatment groups and controls. The increased incidence of seventh cervical ribs was considered to be associated with maternal toxicity at the high-exposure level.The NOEC for developmental toxicity in rats is 300 ppm.

  

Developmental toxicity was also examined in rabbits (Hardin, 1983), a study performed similar to OECD guideline 414. Twenty three to 30 female New Zealand White rabbits were exposed in a dynamic inhalation chamber to 500 ppm (1,188 mg/m3) propylene oxide vapour. All rabbits were sacrificed and examined on day 30 of gestation. Rabbit foetuses were examined for external defects and visceral abnormality. The NOAEC for developmental effects in rabbits is >500ppm. No evidence of embryo or fetal toxicity or of developmental defects was detected in the propylene oxide exposed rabbits.

Justification for classification or non-classification

Based on the absence of specific adverse effects on reproduction and development in the absence of parental toxicity in the available 2-generation study and the developmental toxicity studies, propylene oxide does not have to be classified for reproductive and developmental toxicity in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008- 9th ATP 19 July 2016.