# Spreading of Dangerous Skin-Lightening Products as a Result of Colourism: A Review
## 4 Hydroquinone
Studies on dermal absorption, carried out both in in vitro models and in in vivo experiments on humans, have shown that hydroquinone easily and rapidly penetrates human skin, although percutaneous absorption may be affected by the vehicle [44,45]; following absorption, it is found in the bloodstream and occurs partly as free hydroquinone, partly reversibly bound to proteins, and finally irreversibly bound to proteins [40]. It is excreted via the urine, but in a slower manner than in the absorption phase. Hydroquinone is metabolised in the liver as glucuronide and sulphate and oxidised to p-benzoquinone, especially in the bone marrow. It is known that p-benzoquinone causes specific mutations and is an initiator of carcinogenesis [46]. The use of skin-lightening products containing hydroquinone can cause short- and medium-term effects, both acute and chronic. The most common acute complication is irritant contact dermatitis [34]. Chronic side effects due to hydroquinone exposure are of more concern and include achronosis, nail discoloration, conjunctival melanosis and corneal degeneration [47]; however, ocular complications only occur in individuals exposed to atmospheric hydroquinone and have never been reported after topical application of the compound. The most common complication induced by prolonged exposure to hydroquinone is exogenous ochronosis, a localised hyperpigmentation of the skin with asymptomatic blue-black and grey-brown macules with no systemic manifestations, histologically characterised by banana-shaped ochre deposits and irregularly shaped collagen bundles in the dermis [48,49]. Although the aetiology of this hyperpigmentation is unknown, it has been suggested that hydroquinone may inhibit homogenistic acid oxidase in the dermis, resulting in local accumulation of homogenistic acid which then polymerises to form ochronotic pigment [47]. A unique complication of chronic hydroquinone use is trimethylaminuria or 'fishy smell syndrome', characterised by an unpleasant rotten fishy odour due to the excretion of trimethylamine in sweat, urine, saliva, vaginal secretions, and breath [34]. Hydroquinone probably induces this effect by reducing the enzymatic oxidation of trimethylamine to trimethylamine N-oxide [50]. The carcinogenicity and genotoxicity of hydroquinone are so well established in rodents that an association between long-term use of this compound as a skin brightener and squamous cell carcinoma in humans has been suggested [51, 52, 53]. However, regulatory authorities have concluded that there is insufficient data to classify hydroquinone as a carcinogen. For example, the American Conference of Governmental Industrial Hygienists classified hydroquinone as 'A3', which means that it is recognised as carcinogenic in animals but the relevance for humans is unknown [47]. Similarly, the International Agency for Research on Cancer (IARC) has classified hydroquinone in Group 3 (not classifiable as a human carcinogen); hydroquinone is not classifiable as a human carcinogen, based on limited evidence in experimental animals and inadequate evidence in humans. In the EU, hydroquinone is classified as Carc. Cat 2 H351 (suspected of causing cancer) and Muta. Cat 2 (suspected of causing genetic defects) according to Regulation (EC) No 1272/2008 (CLP Regulation), Annex VI1 [54]. Concerning the safety of arbutin, it is interesting to note that the Scientific Committee on Consumer Safety (SCCS), in its opinion on \(\alpha\)-arbutin [55], stated \"... the use of arbutin in skin whitening products is a complex situation for which the level of application and local availability of hydroquinone cannot be generalised. The factors causing the release of hydroquinone on the skin surface depend on the activity of bacteria and skin enzymes (glycosidases) in each individual and there is insufficient information on their quantitative variation. In addition, the dermal penetration of the active substance and its stability in formulations may vary. Therefore, a case-by-case evaluation is required' [55].