Risk assessment of skin lightening cosmetics containing hydroquinone

•Rat skin permeation rates of hydroquinone (HQ) and HQ cosmetics were determined.•One cosmetic showed a higher permeation rate than that of HQ aqueous solution.•Plasma HQ levels after application of this cosmetic in humans were predicted.•The margin of exposure (MOE) was estimated with a human dose level and a benchmark dose.•The MOE is judged to be in a range safe for the consumer if HQ cosmetics are used properly.

Following reports on potential risks of hydroquinone (HQ), HQ for skin lightening has been banned or restricted in Europe and the US. In contrast, HQ is not listed as a prohibited or limited ingredient for cosmetic use in Japan, and many HQ cosmetics are sold without restriction. To assess the risk of systemic effects of HQ, we examined the rat skin permeation rates of four HQ (0.3%, 1.0%, 2.6%, and 3.3%) cosmetics. The permeation coefficients ranged from 1.2 × 10−9 to 3.1 × 10−7 cm/s, with the highest value superior than the HQ aqueous solution (1.6 × 10−7 cm/s). After dermal application of the HQ cosmetics to rats, HQ in plasma was detected only in the treatment by highest coefficient cosmetic. Absorbed HQ levels treated with this highest coefficient cosmetic in humans were estimated by numerical methods, and we calculated the margin of exposure (MOE) for the estimated dose (0.017 mg/kg-bw/day in proper use) to a benchmark dose for rat renal tubule adenomas. The MOE of 559 is judged to be in a range safe for the consumer. However, further consideration may be required for regulation of cosmetic ingredients.