A single dose of 4000 mg/kg of a spray-dried infusion did not produce any macroscopic signs of toxicity in mice. Peppermint oil has been shown to be minimally toxic in acute oral studies. Short-term and subchronic oral studies reported brain lesions in rats that were given very large doses of peppermint oil containing pulegone, pulegone alone or large amounts (> 200 mg/kg/day) of menthone. Pulegone is also a recognised hepatotoxin and large doses of peppermint oil have been shown to be hepatotoxic in cultured human hepatoma cells. Peppermint oil was negative in an Ames test and a mouse lymphoma mutagenesis assay, but gave equivocal results in a Chinese hamster fibroblast cell chromosome aberration assay. There is a case report of acute lung injury following IV injection of peppermint oil.
Although sensitisation to peppermint oil and/or its constituents has been reported, a solution containing 8% peppermint oil was shown not to be a sensitiser. Contact dermatitis to peppermint and menthol has been reported and there is a case report of chemical burn after peppermint oil ingestion; however, as long as the pulegone content is kept to a minimum, peppermint oil and peppermint extract are considered to have a very good safety profile.