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Abstract for TR-98

Bioassay of dl-Menthol for Possible Carcinogenicity

CASRN: 15356-70-4
Chemical Formula: C10H20O
Report Date: 1979

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Abstract

Menthol is a naturally occurring monocyclic terpene found in the oils of the mint tree Mentha arvensis. Menthol is well known for its cooling effects and its mint flavor and odor, which are the basis of the majority of its uses. The single largest use for menthol is probably in cigarettes. A survey of pharmaceutical products indicates that menthol is formulated in over-the-counter rubs and liniments (2-10% concentrations), antipruritic lotions, nasal sprays, expectorants, mouthwashes and sprays, cough drops, and foot powders.

A bioassay of dl-menthol for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice.

Groups of 50 rats of each sex and 50 mice of each sex were administered dl-menthol at one of the following doses, either 3,750 or 7,500 ppm for the rats and either 2,000 or 4,000 ppm for the mice, for 103 weeks, then observed for 1 or 2 additional weeks. Matched controls consisted of 50 untreated rats of each sex and 50 untreated mice of each sex. All surviving rats were killed at 105 weeks and all surviving mice at 104 weeks.

Mean body weights of dosed rats and mice were only slightly lower than those of corresponding controls. No other clinical signs related to administration of the dl-menthol were noted in the dosed groups of animals. A dose-related trend in mortality was observed only in the female mice. Survival at the end of the bioassay was at least 62% in all dosed and control groups of animals of each species, and sufficient numbers of animals were at risk for the development of late-appearing tumors.

In male rats, no tumors occurred at incidences which were considered to be related to the administration of dl-menthol.

In female rats, no tumors occurred at higher incidences in the dosed groups than in the 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 alveolar/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.

It is concluded that under the conditions of this bioassay, dl-menthol was not carcinogenic for either Fischer 344 rats or B6C3F1 mice.

 

Levels of Evidence of Carcinogenicity:
Sex Species Results
Male Rats: Negative
Female Rats: Negative
Male Mice: Negative
Female Mice: Negative