Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

There is neither mutagenic nor cytogenic data for D-menthol (CAS 15356-60-2) but several datas on a menthol isomer called also "D-Menthol" (CAS 15356 -70 -4). To sustain our argumentation we built a weight of evidence based on all menthols isomers.

The number of the tests performed, the nature of the test items, the protocols used and the results obtained are scientifically acceptable to evaluate this endpoint sufficiently.

Justification for Read-across:

Based on the comparable profiles on OECD-Toolbox of the different menthols we can use them for read across studies. These isomers are L-menthol (CAS 2216-51-5), D-menthol (CAS 15356-60-2) and DL-menthol (CAS 89-78-1)

Moreover, a comparative physico-chemical profile of these isomers reinforces this similarity. As structural isomers, the members of the menthol category share the same molecular weight. Of particular importance to environmental  effects and human effects are the values for partition coefficient (log Kow around 3), vapour pressure (from 17 Pa at 25°C for the DL-menthol to 21 Pa 25°C for the natural L-menthol ) and water solubility ( moderately soluble from 410 mg/l at 25°C for the natural L-menthol to 470 mg/l at 25°C for the DL-menthol). The read across is consistent based on these physico-chemical parameters.

Details on endpoint datas:

L-menthol was neither mutagenic in in vitro gene mutation study in bacteria (Ames test), nor genotoxic on mammalian cells.

Moreover with menthol racemic, no mutagenicity was observed in several published bacterial studies. Recently, no mutagenicity of the substance menthol racemic was confirmed in a study (GLP) with five mutant strains of Salmonella typhimurium according OECD 471 guideline. Several publications support the non genotoxicity of menthol racemic. However, two in vivo studies revealed positive results in replicative DNA synthesis in mice and in rat.

Structure/activity relations and computer systems compiled under OECD-Toolbox don’t flag up any structural alerts, any DNA and protein binding potential on D-menthol and its isomers.

Moreover, a series of in vitro tests on the "D-menthol" (CAS 15356 -70-4) and the isomeric mixture do not suspect any mutagenic or genotoxic potential.

These evidences are strengthened by an in vivo test performed recently on the mixture of isomeric form (OECD / GLP).

Overall, we can conclude that D-menthol and its isomers have not genotoxic or carcinogenic hazard. Subsequently, additional carcinogenicity test can be waived based on the weight of evidence approach.


Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Due to the weight of evidence approach we can assume that D-menthol does not need to be classified for this endpoint.