Registration Dossier
Registration Dossier
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EC number: 237-926-1 | CAS number: 14073-97-3
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
l-Menthone is reduced in the rabbit to d-neomenthol and excreted in urine as glucuronide.
l-Menthone in human liver microsomes metabolise to d-neomenthol and 7-hydroxymenthone.
Menthone has low skin permeability coefficient Ps=0.40±0.01x10^-3 cm/h
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
The investigation of menthone metabolism by Williams (1940) showed that this ketone undergoes a reduction to d-neomenthol. In addition, Miyazawa and Nakanishi (2006) showed that l-menthone in human liver microsomes could metabolise not only to d-neomenthol, but also to 7-hydroxymenthone. No other primary major metabolites of menthone were tested. Thereafter, this menthol conjugates to glucuronic acid and excreted as urinary glucuronide. A study in 4 male volunteers showed that urinary excretion of menthol conjugated with glucuronide in the 14 h time period has an average recovery of 40 % of the oral dose of 180 mg of peppermint oil. In another study, one subject dosed with 1 g of menthol excreted in 6 h urine pool 79 % of the dose of menthol as menthol glucuronide (Bhatia et al, 2008). In humans rats and rabbits, menthol is efficiently metabolized not only to menthol glucuronide but also to hydroxylated metabolites. Oxidation of the methyl and isopropyl groups of menthol has been reported to provide major metabolites in the rat after administration for up to 20 days. Therefore the major pathways of menthol metabolism are: 1) conjugation of the alcohol with glucuronic acid, 2) side-chain oxidation yielding polar metabolites, which may be conjugated and excreted (MacDougall et al, 2003; RIFM Expert Panel et al, 2008). An oral pharmacokinetic study in 12 volunteers showed that after 100 mg/menthol capsule administration, the plasma half-life of menthol glucuronide averaged 56.2 minutes (95 % confidence interval 51.0-61.5) (Bhatia et al 2008). It could be concluded, that oral exposure to menthol does not conduct to this accumulation in the body due to very short plasmatic half-life.
Gabbanini et al (2009) investigated the diffusion kinetic of menthone through SkinEthic(R) reconstructed human epidermis (RHE) and have found the low permeability coefficient Ps=0.40±0.01x10^-3 cm/h. A percutaneous absorption study in humans showed that after dermal patch containing 37.44 mg menthol application (2 to 8 patches), the mean terminal plasmatic half-live was 4.7±1.6 h. It could be concluded that daily or even twice-daily application of dermal patches is unlikely to result in substantial accumulation because the terminal half-live is relatively short (Bhatia et al, 2008).
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