Propyloxirane

Endpoint summary

Additional information

In vitro:

The mutagenic potential of n-Pentenoxide-1,2 was analyzed similar to OECD guideline 471 in the bacterial Ames test (control with E. coli or S. typhimurium TA 102 strain is missing). The test item was applied up to the highest concentration of 5000 µg/plate. No changes in bacterial cell growth was observed in the strains TA98 and TA1537. However, a slight increase in revertant colonies was observed in the TA100 S. typhimurium (1.6 -fold increase without and 1.7 -fold increase with metabolic activation at the highest concentration; no changes at lower concentration) and a significant dose-dependent increase in the TA1535 strain (2.3 -fold without and 2 -fold with metabolic activation at 5000 µg/plate). These results indicate that n-Pentenoxide-1,2 is weakly mutagenic in the Ames test under the applied experimental conditions. According to this result, the mutagenic potential of n-Pentenoxide-1,2 was investigated in the Luria and Delbrück's fluctuation test using Klebsiella pneumoniae as test organism. The test item was dissolved in DMSO and subsequently added to Broth which was inoculated with a mutant of Klebsiella pneumoniae requiring uracil and proline for growth. If an increase of the mutation rate compared to the spontaneous mutation rate by 1.5 or more was observed, the test substance was considered to be mutagenic. Increased mutation rates as compared to the control were observed following incubation with 86 mg/l (2.3 -fold), 172 mg/L (2.6 -fold) and 430 mg/l (3.2 -fold) of the test item. Hence, n-Pentenoxide-1,2 also showed a mutagenic potential in this test.

Apart from n-Pentenoxide-1,2, 1,2 -Butenoxide did also show a mutagenic potential in a variety of in vitro studies. In particular, 1,2 -Butenoxide showed a weakly mutagenic effect in the Ames test (OECD guideline 471) when tested in concentrations ranging from 20 - 7500 ug/plate with and without S-9 mix in all Salmonalle typhimurium strains analysed (TA1535, 1537, 98 and 100; BASF, 1989). Furthermore, Anderson et al. (1990) reported a positive result for the chromosome aberration test with Chinese hamster ovary cell with and without S-9 mix at the highest dose of 1,2 -Butenoxide (500 ug/ml). Moreover, McGregor et al. (1987) found a positive result for 1,2 -Butenoxide with and without S-9 mix in a mammalian gene mutation assay with mouse lymphoma L5178Y cells. These results further support the validity of a read-across between these two epoxides, suggesting that both compounds possess an in vitro mutagenic capacity.

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) and 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-Butenoxide, 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 vivo:

In vivo results for n-Pentenoxide-1,2 are not available. However, as mentioned above, the in vivo mutagenic potential can be derived from experimental data of the closely related 1,2 -Butenoxide, for which negative results have been reported in an chromosome aberration assay (OECD guideline 475). The test substance was given via inhalation (7 single exposures for 5 consecutive days) to male and female rats at concentrations of 250 and 1000 ppm (NIOSH, 1981). Furthermore, in a dominant-lethal test (NIOSH, 1981) according to OECD guideline 478, 1,2 -Butenoxide had no identifiable effect on male rats when given in doses of 250 and 1000 ppm via inhalation (vapor). These data suggest that even though 1,2 -Butenoxide and n-Pentenoxide-1,2 have mutagenic capacity in vitro, they lack clastogenic activity in vivo.

1,2 -Butenoxide is legally classified as cancer category 2 according to Regulation (EC) 1272/2008, but lacks classification for genetic toxicity. Accordingly, n-Pentenoxide-1,2 will follow also be classified as potential carcinogen (cancer Cat 2), but no label will be used concerning genotoxicity.

Short description of key information:
mutagenic in bacteria (BASF AG, 1989; Ames test (OECD471); Voogd et al, Luri and Delbruecks fluctuation test, 1981)

Read-across to 1,2-Butenoxide: negative in vivo results in the chromosome aberration test (OECD475) and dominant lethal test (OECD478; NIOSH, 1981)

Endpoint Conclusion:

Justification for classification or non-classification

The mutagenic effects found in vitro could not be confirmed in in vivo studies for 1,2 -Butenoxide, a stuctural analog of n-Pentenoxid-1,2; gonadic tissues are not affected. These results indicate that the test substance is unlikely to exert systemic effects, but rather induces local genetic alterations. Hence, classification is not warranted according to Directive 67/548/EEC and Regulation (EC) 1272/2008 (CLP).