title: Risk assessment of skin lightening cosmetics containing hydroquinone.
abstract: 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 × 10-9to 3.1 × 10-7cm/s, with the highest value superior than the HQ aqueous solution (1.6 × 10-7cm/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.
authors: Division of Risk Assessment, National Institute of Health Sciences, Tokyo, Japan; Department of Epidemiology and Environmental Health, Juntendo University, Faculty of Medicine, Tokyo, Japan. Electronic address: mariko@nihs.go.jp.
authors: Mariko
authors: M
authors: Matsumoto
authors: Josai University, Faculty of Pharmaceutical Sciences, Saitama, Japan.
authors: Hiroaki
authors: H
authors: Todo
authors: Division of Environmental Chemistry, National Institute of Health Sciences, Tokyo, Japan.
authors: Takumi
authors: T
authors: Akiyama
authors: Division of Risk Assessment, National Institute of Health Sciences, Tokyo, Japan.
authors: Mutsuko
authors: M
authors: Hirata-Koizumi
authors: Josai University, Faculty of Pharmaceutical Sciences, Saitama, Japan.
authors: Kenji
authors: K
authors: Sugibayashi
authors: Division of Environmental Chemistry, National Institute of Health Sciences, Tokyo, Japan.
authors: Yoshiaki
authors: Y
authors: Ikarashi
authors: Division of Risk Assessment, National Institute of Health Sciences, Tokyo, Japan.
authors: Atsushi
authors: A
authors: Ono
authors: Division of Risk Assessment, National Institute of Health Sciences, Tokyo, Japan.
authors: Akihiko
authors: A
authors: Hirose
authors: Department of Epidemiology and Environmental Health, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors: Kazuhito
authors: K
authors: Yokoyama
mesh_terms: D000279:Administration, Cutaneous; D061605:Administration, Intravenous; D000818:Animals; D019985:Benchmarking; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006873:Hydroquinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D008962:Models, Theoretical; D019055:No-Observed-Adverse-Effect Level; D010539:Permeability; D054772:Rats, Hairless; D018570:Risk Assessment; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D062327:Skin Lightening Preparations / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D012880:Skin Pigmentation / Q000187:drug effects*; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
chemical_list: D006873:Hydroquinones; D062327:Skin Lightening Preparations; C031927:hydroquinone
keywords: Benchmark dose; Dermal absorption; Hydroquinone; Margin of exposure; Permeation coefficients; Risk assessment