3-methoxybutan-1-ol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Non-human information

3 -methoxybutan-1-ol

The key studies for 3-methoxybutan-1-ol are two core genotoxicity assays. In a bacterial reverse mutation test in a range of Salmonella strains (Hoechst, 1992) 3-methoxybutan-1-ol was negative. In an in vitro mammalian cell gene mutation test with L5178Y mouse lymphoma cells (Notox, 2010) 3-methoxybutan-1-ol was also not genotoxic.

3-methoxybutan-1-ol is a simple alkyl structure containing no structural features or chemical groups that alert to likely genotoxic activity when examined with established structure-activity (SAR) considerations (Ashby & Tennant, 1988). On the basis of this SAR evaluation, 3-methoxybutan-1-ol would not be expected to show any significant genotoxic activity. This is consistent with the available data from 3-methoxybutan-1-ol.

Genotoxicity data are available for chemicals that are structurally similar to 3-methoxybutan-1-ol, and contain the same combination of groupings, namely a short-chain alkyl backbone and a methoxy moiety. Data considered relevant to an assessment of 3-methoxybutan-1-ol are summarised below.

3-Methoxy-3-methyl-1-butanol (structural analogue)

3-Methoxy-3-methyl-1-butanol has been examined in the Ames test using both a range of Salmonella strains and an E coli strain (FDSC, Hatano Res. Inst., 2002a). It has also been examined for the ability to cause cytogenetic effects in vitro in CHL cells (FDSC, Hatano Res. Inst., 2002b). 3-Methoxy-3-methyl-1-butanol was negative in both assays.

These data are from a close structural analogue of 3-methoxybutan-1-ol, which contains all the features of 3-methoxybutan-1-ol and only differs in having a single additional methyl group. The negative results support the conclusion that the linear C-4 alcohol moiety in 3-methoxybutan-1-ol, together with the 3-methoxy group, is not genotoxic.

3 -Methoxybutyl acetate (metabolised to 3-methoxybutan-1-ol)

3 -Methoxybutyl acetate was tested in the standard Ames test protocol in both the absence and presence of auxiliary metabolic activation (S9) using Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100.  A range of doses was used up to 5000 µg/plate.  3 -Methoxybutyl acetate was negative in this assay.

n-Butanol (structural analogue)

n-Butanol has been examined in the Ames test in a range of Salmonella strains, including TA102 (McCann et al., 1975; Jung et al., 1992). It has also been examined for the ability to cause cytogenetic effects both in vitro (Lasne et al., 1984) and in vivo (in the mouse bone marrow, as cited in ECETOC, 2003) using the micronucleus endpoint. This endpoint can assess for both chromosomal damage and also numerical changes in chromosomes, i.e. aneuploidy. N-Butanol was negative in the Ames test and also negative in both cytogenetic assays. N-Butanol has also been examined in other assays and these confirm that n-butanol is negative in established assays for evaluating genotoxic activity. The one reported positive result is in a non-standard assay using Aspergillus (Crebelli et al 1989), and the finding is not considered to indicate any significant genotoxic activity for n-butanol, especially in view of the negative findings in mammalian cells in assays that can assess for possible numerical chromosomal changes (in vitro and in vivo micronucleus assays).

These data support the conclusion that the linear C-4 alcohol moiety in 3-methoxybutan-1-ol is not genotoxic.

Butane-1,3 -diol (putative metabolite)

Butane-1,3-diol has been examined for genotoxic activity both in somatic cells in the bone marrow using an in vivo cytogenetic assay and in germ cells using a dominant lethal assay (Hess et al., 1981). It was reported negative in both assays.

These data support the conclusion that the linear C-4 alcohol moiety in 3-methoxybutan-1-ol is not genotoxic. In addition, they indicate that any conversion of 3-methoxybutan-1-ol to butane-1,3-diol would not result in genotoxic activity.

A consideration of these relevant structural analogues provides data that are relevant to an assessment of 3-methoxybutan-1-ol including data in the categories of in vitro gene mutation and cytogenetic activity (including chromosomal damage) and also in vivo cytogenetic activity in both somatic and germ cells. The results for these structural analogues are negative across the range of endpoints and support the available data for 3 -methoxybutan-1 -ol itself that show a lack of genotoxic activity.

There is no human information.

Citation

Ashby J and Tennant RW (1988) Chemical structure, Salmonella mutagenicity and extent of

carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the U.S. NCI/NTP. Mutat Res 204: 17-115. Crebelli R, Conti G, Conti L, Carere A. 1989. A comparative study on ethanol and acetaldehyde as inducers of chromosome malsegregation in Aspergillus nidulans. Mutat. Res. 215: 187 -195

Short description of key information:
Considering the data from 3-methoxybutan-1-ol and 3-methoxybutyl acetate (which is metabolised to 3-methoxybutan-1-ol) together with the data from relevant structural analogues, it is possible to draw a conclusion based on a weight of evidence that 3-methoxybutan-1-ol does not have any significant genotoxic activity. This is based on data from in vitro gene mutation and cytogenetic assays (including chromosomal damage) and also data from in vivo cytogenetic assays in both somatic and germ cells. An evaluation of the chemical structure of 3-methoxybutan-1-ol using established SAR considerations supports this conclusion.
In view of the lack of an alert for likely genotoxicity for 3-methoxybutan-1-ol, together with the consistency of negative findings across a range of endpoints for 3 -methoxybutan-1-ol and structural analogues, it is considered unnecessary to conduct further genotoxicity testing on 3-methoxybutan-1-ol itself. The available data are sufficient to draw a conclusion, based on a weight of evidence, that 3-methoxybutan-1-ol has no significant genotoxic activity.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to criteria in Regulation (EC) No.1272/2008, the substance is not classified for genotoxicity. The weight of evidence indicates that 3-methoxybutan-1-ol has no significant genotoxic activity and does not warrant classification for genotoxicity.