Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Adequate in vitro and in vivo data available for the butenes category indicates that category members 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 (1985). In all studies, category members were not mutagenic in the presence or absence of metabolic activation; the results from positive control compounds indicate that the assay and metabolic activation system were functioning within the acceptable range.

 

2-Butene was tested in vitro for clastogenic (Safepharm 1992b) and mutagenic (Envigo 2015) properties in the presence or absence of metabolic activation in rat lymphocytes and L5178Y mouse lymphoma cells, respectively. Both studies produced negative results, and metabolic activation had no effect. 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 with 2-methylpropene (IRI 1981b) was also negative in the presence or absence of metabolic activation. In all cases, positive control compounds gave the expected results, demonstrating that the studies were robust.

 

The in vivo genotoxicity of 2-methylpropene was examined in a key bone marrow micronucleus assay (Exxon 1990), in which mice were exposed to concentrations up to 10,000 ppm (22,948 mg/m3) for 2 days. No statistically significant increase in micronucleus formation in the bone marrow was observed; therefore 2-methylpropene was not clastogenic in this assay. A peripheral blood micronucleus test was also conducted during a repeat dose toxicity test with 2-methylpropene, in which 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).

 

Review of the overall database on genotoxicity data for all the butene isomers within this category, together with the negative rat and mouse carcinogenicity studies conducted on 2-methylpropene, indicate that there is minimal likelihood that butenes category members present a genotoxic hazard.


Short description of key information:
Members of the butenes category are not mutagenic in vitro or in 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 conducted 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 GHS/CLP.