Hydroquinone and its analogues in dermatology - a risk-benefit viewpoint.

Hydroquinone (HQ) has been used since the 1950s in commercially available over-the-counter skin lightener products and since the 1960s as a commercially available medical product. It is also used in cosmetic products such as hair dyes and products for coating finger nails. Beginning in 2001, HQ is no longer authorized for use in cosmetic skin lightening formulations in European Union countries, although products containing arbutin, an analogue of HQ, and botanicals, including plants that naturally contain HQ and arbutin, continue to remain available in European countries. The potential toxicity of HQ is dependent on the route of exposure, and toxicity in rodents is highly sex-, species-, and strain-specific. Subchronic and chronic toxicity in experimental animals is primarily limited to nephrotoxicity in male F-344 rats. Dermal toxicity studies, even those conducted in the sensitive male F-344 rat, are essentially devoid of systemic toxicity. Developmental and reproductive toxicity studies with HQ in rats and rabbits have not demonstrated significant effects. Cancer bioassay data for HQ demonstrate limited effects and are not sufficient to classify HQ for human carcinogenicity. Epidemiology and occupational studies of workers with extensive exposure to HQ have not reported any evidence of adverse systemic health effects or carcinogenicity. A risk-benefit approach is recommended for assessing the available data for HQ, arbutin, and other materials in use as, or proposed for use as, skin lighteners to provide optimal therapeutic benefits to patients with pigmentary changes of the skin.