Hydroquinone and its analogues in dermatology – a risk‐benefit viewpoint

Abstract

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.

Skin Whitening Cosmetics: Feedback and Challenges in the Development of Natural Skin Lighteners

“…Those substances may also still be used under strict dermatological supervision. Thus, the presence of hydroquinone, kojic acid, or azelaic acid is totally prohibited in cosmetic formulations by Swiss legislation, whereas hydroquinone is still authorized in the USA, where it is sold as an over-the-counter drug (concentration of hydroquinone not exceeding 2%), and products containing β-arbutin or plants that naturally contain hydroquinone and β-arbutin continue to remain available in European countries [132,150,151]. Moreover, numerous Asian and African countries have yet to legislate about the safety status of such substances [23].…”

[6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation of the ERK pathway

“…However, the recent discovery of their adverse side effects suggests that the applicability of these chemicals might be limited. It has been reported that kojic acid can cause allergic contact dermatitis [21] and that arbutin might carry carcinogenic risks [22] . Moreover, low stabili-www.nature.com/aps Yao C et al Acta Pharmacologica Sinica npg ties or high costs of available agents may also be issues of concern.…”

The rediscovery of the Redwood orpiment and a cocktail of plants macerates containing arbutin to defeat the Arribas-Silvestre’s syndrome in a bien agée upper class lady

“…Here follows the Felix von Luschan's chromatic scale [8,9] (Fig. 1) and in the successive Table I refer, it is possible to notice how the values decreases day after day.…”

“…The bleaching agents are not but herbs that contain high percentages of arbutin [7,8], that when in contact with the sweat of the skin, drives to hydroquinone.…”