Sensitivity reactions associated with the use of mentholated products (including cigarettes) have been reported. Treatment of infants with mentholated nasal drops has evidently caused isolated cases of spasm of the larynx, and a few cases of nervous or digestive system disturbance have been associated with excessive inhalation or oral exposure to mentholated products. Menthol was reported to be a mild skin irritant in man, but caused more severe damage to the mucous membranes.
In rabbits, menthol was a mild skin irritant but severely irritated the eyes. It was of low acute toxicity in experimental animals treated by the oral and dermal routes, causing central nervous system effects. Liver and kidney changes have been seen in a number of studies in laboratory animals, involving oral and inhalation administration. Inhalation of menthol produced respiratory tract injury in rats and rabbits. In oral studies, there was no convincing evidence of carcinogenicity in rats and mice or of reproductive effects in mice, rats, rabbits and hamsters. No chromosome damage occurred in rats treated orally, although there were some indications of weak activity in mammalian cells in culture. Ames bacterial tests have, in general, given no evidence of mutagenicity but other assays in microorganisms have provided some suggestion of genotoxicity. Recessive lethal mutations were not induced in fruit flies.
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