Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Members of the butenes category are not genotoxic. Key bacterial mutation studies (Ames tests) on all isomers (butene, but-1-ene, 2-butene and 2-methylpropene) are provided by Araki (1994) and a key study on 2-butene is provided by Safepharm (1992a). Supporting studies on 2-methylpropene are provided by Cornet et al (1992), NTP (1998) and Shimizu et al et al (1985). In all studies, all category members were not mutagenic in the presence and absence of metabolic activation whilst positive control compounds gave the expected results demonstrating that the studies were robust.

2-Butene has been tested in vitro in a chromosome aberration study (Safepharm 1992b) where it was not clastogenic to rat lymphocytes in vitro in the presence and absence of metabolic activation. 2-Methylpropene also gave negative results in vitro; a micronucleus assay in human lymphocytes (Jorritsma et al 1995) and a mouse lymphoma mutation assay (IRI 1981a) were both negative. In addition, a mammalian cell transformation assay on 2-methylpropene (IRI 1981b) was also negative in the presence and absence of metabolic activation. In all cases, positive control compounds gave the expected results, demonstrating that the studies were robust.

Genotoxicity studies in vivo are provided by a key bone marrow micronucleus assay on 2-methylpropene (Exxon 1990) where mice were exposed to concentrations up to 10,000 ppm (22,948 mg/m3) for 2 days. A statistically significant increase in micronucleus formation in mouse bone marrow was not observed therefore 2-methylpropene was not clastogenic in mouse bone marrow. A peripheral blood micronucleus test was also conducted during a repeat dose toxicity test on 2-methylpropene, where mice were exposed via inhalation for 14 weeks at 500, 1000, 2000, 4000 and 8000 ppm (1147, 4589, 18,359 mg/m3). No increases in the frequency of micronucleated normochromatic erythrocytes were seen in peripheral blood samples in either sex (NTP 1998).

When the overall database on the genotoxicity of all the butene isomers in this category are considered together with the negative carcinogenicity studies on 2-methylpropene in rats and mice there is minimal likely-hood of genotoxicity for any of the category members.

There is no data on the genetic toxicity of the butenes in humans.



Short description of key information:
Members of the butenes category are not mutagenic in vitro or vivo under conditions where positive control compounds gave the expected results. A NOAEC of 10,000 ppm (22,948 mg/m3) (the highest concentration tested) was identified from an in vivo mouse bone marrow micronucleus assay on 2-methylpropene.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Members of the butenes category are not genotoxic and therefore do not warrant classification under Dir 67/548/EEC or GHS/CLP.