Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

The following key genotoxicity studies were identified for n-pentane and/or 2-methylbutane: two in vitro gene mutation studies in bacteria; an in vitro cytogenicity in mammalian cells or micronucleus study; and an in vivo mutagenicity test. Details regarding these studies are presented below.

 

One key and one read-across in vitro gene mutation studies in bacteria were identified, one conducted with 2 -methylbutane and another conducted with n-pentane.   For 2 -methylbutane, strains (TA1535, TA1537, TA98, TA100, and TA1538) ofS. typhimurium exposed to 2 -methylbutane at concentrations of 50, 25, 10, 8, 5, 2, or 1% in the presence and absence of mammalian metabolic activation using a modified standard plate test (Kirwin, 1980).   2 -Methylbutane was not found to be mutagenic at any concentration in both the presence and absence of S9 mix. In a similar read-across study conducted with n-pentane, the same strains ofS. typhimurium exposed to n-pentane in the presence and absence of mammalian metabolic activation (Kirwin, 1980). Like 2 -methylbutane, n-pentane was not found to be mutagenic.

 

An in vitro gene mutation assay in mammalian cells was conducted with n-pentane (Pryzgoda, 1997). In this study, Chinese hamster ovary cells were exposed to n-pentane (97.4% a.i., batch 2036924) at concentrations of 600, 1000, 1100, 1200, 1300, 1400, or 1500 μg/mL, +S9, and 300, 600, 900, 950, 1000, 1050, or 1100 μg/mL, -S9, for 20 hours (initial and confirmatory assay) and 44 hours (confirmatory assay). The test material did not induce any biologically significant increase in chromosome aberrations in cultured CHO cells with or without metabolic activation under the conditions of this study. Positive, vehicle, and non-treated controls performed in an appropriate manner, indicating that the test system could detect both activation-dependent and direct-acting clastogens.

 

In a Crl: CDBR rat bone marrow micronucleus assay, 5 animals/sex/dose were administered n-pentane via inhalation at nominal doses of 0; 5000; 10,000; or 20,000 mg/m3 (Pryzgoda, 1997).  Rats were exposed to either n-pentane or air (control) 6 hours per day, 5 days per week for 13 weeks.  Actual doses received were 5097±97; 10,203±151; and 20,483±734 mg/m3.  n-Pentane did not induce an increase in micronuclei formation at any exposure level when compared to the control group. n-Pentane was tested at an adequate dose because the high dose was half of the lower explosive limit and was the highest dose considered safe to test. The positive control induced the appropriate response.

 

Based on the lack of observed mutagenic effects in in vitro and in vivo studies with 2 -methylbutane or n-pentane, it is concluded that 2 -methylbutane is not mutagenic. Based on these findings, 2 -methylbutane does not meet the EU criteria for classification and labelling (Dangerous Substances Directive 67/548/EEC and CLP EU Regulation 1272/2008) for mutagenicity.


Short description of key information:
A key in vitro gene mutation study in bacteria (OECD 471) was identified for 2-methylbutane. Additionally, the following read-across studies were identified from n-pentane: in vitro gene mutation study in bacteria (OECD 471 and ECC B. 13/14); in vitro cytogenicity in mammalian cells or micronucleus study (EU Method B.10); and other in vivo mutagenicity test (EU Method B.12). All genetic toxicity tests, both in vitro and in vivo, were negative.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

All in vitro genetic toxicity studies (i. e., gene mutation studies in bacteria and cytogenicity studies in mammalian cells) from 2 -methylbutane and n-pentane showed negative results. In vivo mouse micronucleus studies with n-pentane also produced no evidence of mutagenic effects. Based on the weight of evidence, 2 -methylbutane is unlikely to be mutagenic and does not meet the criteria for classification and labelling as described inEU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.