Propyloxirane

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

Short description of key information:
No data on the reproductive toxicity of n-Pentenoxide-1,2 are available. However, for the structural analog 1,2-Butenoxide, no effects on reproduction organs have been noted in a 90-day inhalation study in rats and mice (NTP, 1988; MIller et al 1981; OECD413). Furthermore, negative results were obtained in the dominant lethal assay in male rats (NIOSH, 1981; OECD478) and in developmental toxicity studies (NIOSH, 1981; OECD414). Thus, testing for this endpoint is not necessary

Effects on developmental toxicity

Description of key information

No studies are available for n-Pentenoxide-1,2. However, due to its close structural analogy to 1,2-Butenoxide, a teratology assessment of 1,2-Butenoxide is used to estimate the developmental toxicity of n-Pentenoxide-1,2 (NIOSH, 1981). 
1,2-Butenoxide is not teratogen in rats and rabbits (OECD414, NIOSH, 1981)

Additional information

Justification for read-across to 1,2 -Butenoxide:

No data on carcionogenic potential are available for n-Pentenoxide-1,2. However, a read-across to 1,2-Butenoxide, another member of the epoxide family can be made. The only structural difference between n-Pentenoxid-1,2 and 1,2-Butenoxide is the presence of an additional CH2-group in n-Pentenoxide-1,2. The chemical characteristics between these two substances are quite similar, with 1,2 -Butenoxide being more soluble in water (86.6 g/L vs 23 g/L water solubility), less lipophilic (log Pow=0.68 vs 1.29) and exhibiting a higher vapor pressure (227 hPa vs 70 hPa) as compared with n-Pentenoxide-1,2. It has been shown that the toxicities of epoxides decrease from ethylenoxide to propylenoxide to 1,2 -Butanoxide, suggesting that the toxicity of this reactive group of epoxide chemicals decreases with increasing length of the carbon backbone (Fox et al, 1983; NTP report No 267, 1985). In line with this assumption, the oral LD50 of 1,2-Butenoxide is smaller (900 mg/kg) as compared with n-Pentenoxide-1,2 (1460 mg/kg), further supporting the validity of a read-across from n-Pentenoxide-1,2 to 1,2-Butenoxide, taking into account that this will represent a worst case scenario.

The developmental toxicity of 1,2-Butenoxide was analyzed according to OECD guideline 414 in rats and rabbits at concentration of 250 and 1000 ppm (equals 0.75 and 3 mg/l) using the whole body inhalation chamber (8 hours per day, 7 days per week; day 1-19 of gestation; NIOSH 1981). Furthermore, groups with pregestational exposure of 21 days were analyzed.

No mortality without pregestational exposure (0/38) occurred in rats. High pregestational exposure caused one death (1/42). However, this death was not regarded as substance-related (the surviving animals showed no signs of severe toxicity; no further details are given in the report). Pregestational exposure to 1000 ppm of 1,2-Butenoxide produced a slight, but statistically significant reduction in the body weight of the rats relative to the controls at most time periods. The differences were transient and were not statistically significant at the end of the pregestation exposure. By 7 days of gestational exposure, the rats exposed at the high levels were significantly lighter than the controls, and remained lighter throughout the study. No remarkable changes in food consumption were produced by pregestational or gestational exposure of rats. The exposure did not affect liver, lung and placental weight. Apparently normal corpora lutea were noted in the sections of ovary from each rat. The exposure led to a slightly reduced percentage of sperm-positive rats which were pregnant although no clear dose relationship was seen and the decrease was not statistically significant. The exposure had no statistically significant effect on either the weight or length of the fetuses in rats. Statistically significant differences in the sex ratios were not observed. Pregestational and/or gestational exposure did not have statistically significant effects on any of the measures of reproductive success. Alterations of the nature or incidence of morphologic changes related to exposure were not noted. The NOAEC for maternal toxicity was 1000 ppm (i.e., 3 mg/L air) and the NOAEC for developmental toxicity and teratogenicity also was 1000 ppm (i.e., 3 mg/L air).

Similar to this study with rats, concentrations of 250 and 1000 ppm (i.e., 0.75, 3.0 mg/L air) were given via the inhalation route (vapor) for 7 h/d for 5 d/w to pregnant rabbits from gestation day 1-24 (NIOSH, 1981). Fourteen of 24 (58%) rabbits exposed to 1000 ppm and 1/23 (4.3%) rabbits exposed to 250 ppm died during exposure. Suppurative pneumonia was the usual necropsy finding in rabbits which died during exposure. The exposure did not have a major effect on lung, kidney and placental weights. The exposure led to a reduced percentage of sperm-positive rabbits, based on the results at scheduled sacrifice. Although this might be considered to be influenced by pre-implantation mortality of does, nine of 13 does in the high-dose group which died prior to scheduled sacrifice were pregnant; furthermore, 2/10 remaining rabbits of the high-dose group were sperm-positive. This gives an overall fraction of 11/23 or 48% in the high-dose group as compared to the 42% pregnant rabbits in the air group. The exposure had no statistically significant effect on either the weight or length of the fetuses. The fetuses of the two surviving litters of high dose rabbits were markedly smaller than were those of the control or low dose groups. No differences in live fetuses/litter were recorded in the low dosed group as compared with controls. Statistically significant differences in the sex ratios were not observed. The NOAEC for maternal toxicity was found to be 250 ppm (i.e., 0.75 mg/L air); the NOAEC for teratogenicity was 1000 ppm (i.e., 3 mg/L air).

Justification for classification or non-classification

No indications of reproductive toxicity were seen in repeated dose toxicity studies (vapor inhalation), in the dominant lethal test in vivo and in developmental toxicity studies with 1,2 -Butanoxide, a structural similar compound of n-Pentenoxide-1,2. The available studies on developmental toxicity and teratogenicity for 1,2 -Butanoxide (rat and rabbit) revealed neither developmental toxicity nor teratogenicity. Thus, a classification or labeling of n-Pentenoxide-1,2 according to the EU 67/548/EEC Directive and according to Regulation (EC) 1272/2008 (CLP) is not warranted.