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EC number: 239-387-8
CAS number: 15356-60-2
This endpoint is not required for the REACh registration purpose of D-Menthol. Nevertheless, we decided to use the chronic datas available on a mix of menthol isomers and on L-Menthol to derive some DNELs for Human health hazard assessment.Data Summary:No existence of intrinsic repeated dose study on L and DL-menthol.No effect observed up to 7500ppm
There is no data on D-menthol concerning the
repeated dose toxicity endpoint and it is not a requirement anyway for
this registration. Nevertheless, to develop a safer assessement the
derivation of some DNELs was based on the L and DL-menthol chronic
studies available following a read-across approach for this endpoint.
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
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
Details on the repeated dose studies :
Data from literature show no significant change in the body
weight or in haematological or clinical chemistry parameters
when L-menthol was administrated to rats (i.e. 200, 400 and
800mg/kg/day) by oral gavage for 28 days. At necropsy, a
significant increase in absolute and relative liver weight at
all doses in males and mid and high dose in female were
Moreover two older tests performed on DL-menthol for 13-weeks
respectively in rat (up to 937/998 mg/kg bw/d for males/females)
and mice (up to 3913/4773 mg/kg bw/d for males/females).
No toxicity was noted at the maximum dose tested in rat (i.e
1.5%), while in mice a slight body weight effect was observed at
the higher dose without any gross and microscopic pathology
related to the treatment. The NOAELs derived from these studies
were 937 mg/kg bw/d for the male rat, 998 mg/kg bw/d for the
female rat and 1956 mg/kg bw/d for the male mouse and 2386 mg/kg
bw/d for the female mouse.
It does not exist an intrinsic long-term repeated dose study on
However, data from literature revealed no treatment related
histopathological changes or increased incidences of tumours in
a 103-weeks oral administration of 2% corn oil of dl-menthol in
diet to rats. The NOAEL resulted from this study was 7500ppm
(i.e. 375 mg/kg/day).
A 2 years feeding
study on DL-Menthol in rats and mice shows no signs of toxicity or
negative effects in a concentration relevant for classification. Also
this study didn’t reveal any indication of tumor incidences with animals
treated. Hence it can be concluded that the substance does not meet the
criteria for classification and labeling for carcinogenicity or repeated
dose toxicity (STOST), as set out in Regulation (EC) NO. 1272/2008. By
read across approach we can extend the non classification justification
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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