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EC number: 218-690-9
CAS number: 2216-51-5
In a combined repeated dose/carcinogenicity study (NCI, 1979), in both dose groups (0.375% and 0.75% DL Menthol in diet of rats and 0.2 and 0.4% in the diet of mice), neither toxicity nor carcinogenicity in Fischer 344 rats or B6C3F1 mice was found after 103 weeks exposure. The mean body weights of the dosed rats and mice were slightly lower than those of corresponding controls. This could be explained by less palatability of the Menthol containing food combined with a smaller feed uptake.
L Menthol does not
meet the criteria for classification and labelling for carcinogenicity,
as set out in Regulation (EC) NO. 1272/2008 and Directive 67/548/EEC.
Justification for Read-across:
Based on the identical profiles of the different Menthols we can
use them for read across studies as laid out in detail in the Read-Across
Justification for Menthols (see file MentholsReadAcrossFinal.pdf in
section 13). 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.
In OECD SIDS, L Menthol (CAS 2216-51-5), D Menthol (CAS
15356-60-2) and DL Menthol (CAS 89-78-1) were recognized as a category
group. Investigations on toxicokinetics show that L-, DL- and the
unspecified Menthol are well absorbed via the oral route. For all of the
isomers, elimination is rapid and mainly occurs as glucuronic acid
conjugates via urine, minor amounts via faeces. Significant differences
in toxicokinetic properties of Menthol isomers were not reported.
The available toxicity data indicate very similar toxicity
profiles for D-, L-, DL Menthol and the unspecified Menthol isomer
mixture. In mammalian species the low toxicity was manifested in LD50
values generally greater than 2000 mg/kg bw in acute studies, limited
toxicity in repeated dose studies, and no effects in teratology
evaluations. Irritation to skin and eyes was slight to moderate. DL
Menthol is a racemic mixture of D- and L- isomers and contains both
isomers in equal proportion. Data gaps for L Menthol can therefore be
filled by the respective results with the racemic mixture and or results
of the D Menthol isomer respectively.
Due to above discussion, to this endpoint, carcinogenic properties
of L Menthol can be thought equivalent to the tested substance DL
In a combined repeated dose/carcinogenicity study (NCI, 1979), in
both dose groups (0.375% or 0.75% DL Menthol in diet of rats and 0.2 or
0.4% in the diet of mice), neither toxicity nor carcinogenicity in
Fischer 344 rats or B6C3F1 mice was found after 103 weeks exposure.
In male rats, no tumors occurred at incidences which were
considered to be associated with the administration of DL Menthol.
In female rats, no tumors occurred at higher incidences in dosed
groups than in control groups. Fibroadenomas of the mammary gland
occurred at lower incidences in the low-dose (10/49) and high-dose
(7/49) groups than in the control group (20/50), and
alveaolar/bronchiolar adenomas or carcinomas of the lung occurred only
in the controls (3/50).
In mice of either sex, no tumors occurred in dosed groups at
incidences that were significantly different from those for
corresponding control groups.
(highest tested dose levels in rats approx. 375 mg/kg bw/day, in
mice approx. 667 mg/kg bw/day). Since DL Menthol contains the two
isomers in a 50:50 ratio it can be assumed that neither L- nor D Menthol
had carcinogenic properties.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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