| SKIN PIGMENTATION | OPINION variable, but it also irritated the skin.
There were also reports that its use led to confetti-like areas of depigmentation (leukoderma-en-confetti) in the treated areas of the skin, as well as vitiligo-like areas of depigmentation at sites remote from the site of treatment, even after the discontinuation of therapy (vitiligo is a dermatological condition where there is a loss of pigment from areas of skin, resulting in irregular white patches). Of more concern is the possibility that
hydroquinone might cause cancer, although to date there has been no case of cancer that irrefutably links the disease to the use of hydroquinone-containing creams. Nevertheless, the risk is supported on both theoretical and circumstantial grounds. Hydroquinone is a metabolite of the solvent benzene, and the binding of hydroquinone and another benzene metabolite, p-benzoquinone, to DNA has been advanced as an explanation of benzeneÕs carcinogenicity. Furthermore, animal toxicology studies have shown that very high doses of hydroquinone can cause cancer, although the difficulty of extrapolating the results of animal experiments to humans is as true here as anywhere.
Regulatory actions In response to mounting evidence of the harmful effects of prolonged use of hydroquinone, the
European
Commission issued a Directive in February 2000 banning its use in skin- lightening creams (although its use in hair dyes was not prohibited). In the US its use remains permitted, although in 2006 the FDA issued a Proposed Rule that would have classified over-the-counter (OTC) skin bleaching drug products as not generally recognised as safe and effective (GRASE), misbranded, and new drugs within the meaning of the Federal Food, Drug, and Cosmetic Act (and thus requiring an abbreviated new drug application (ANDA)
for continued
marketing). The Proposed Rule was based on new evidence of carcinogenicity in rats and mice to OTC skin lightening products containing hydroquinone. The proposal met with a number of objections, including from the American Academy of Dermatology Association and, so far, no final rule has appeared. A number of other countries have outlawed skin-lightening products that
hasten the removal of pigmented cells, alpha hydroxyacids also have some skin-lightening effect of their own. The disadvantage of using alpha
hydroxyacids is that they increase the likelihood of skin irritation, particularly at higher hydroquinone concentrations, and for this reason some products also contain an anti-inflammatory agent such as cortisone. However, hydroquinone is not the only
compound used for skin lightening, although some compounds are used more to treat disorders of pigmentation than for cosmetic purposes. Topical retinoids have been used for the treatment of skin discolouration such as melasma. They seem to work by accelerating skin cell turnover, thus promoting exfoliation, rather than inhibiting melanin formation, but are generally regarded as less effective than hydroquinone. On the other hand, some individuals who do not respond to hydroquinone alone do show a response when a retinoid is added to their regimen.
Hydroquinone is not the only
compound used for skin lightening, although some compounds are used
more to treat disorders of pigmentation than for cosmetic purposes. Topical retinoids have been used for the
treatment of skin discolouration, such as melasma.
contain hydroquinone, including Japan, Australia and South Africa. However, it is not unknown for illegal products to reach the market, and enforcement agencies need to keep a constant vigil to prevent their distribution and sale. As
previously mentioned,
hydroquinone works by preventing the formation of melanin, so before any lightening of the skin is noticeable, the pre-existing melanin must be removed, which normally occurs by a process of exfoliation. In order to accelerate this process, some skin-lightening products combine hydroquinone with alpha hydroxy acids, such as lactic acid or glycolic acid, which accelerate the exfoliation process. In fact, because they
Natural products A number of other compounds are used in skin-lightening preparations, most of which are of natural origin. Arbutin, for example, is a glycosylated form of hydroquinone (hydroquinone-O- -D- glucopyranoside) found in the leaves of cranberry, bearberry, and blueberry plants, most types of pears, and a number of other plants. It acts effectively as a prodrug of hydroquinone, slowly releasing the active substance. For this reason, it is generally less irritating than hydroquinone itself, although there are no protocols establishing just what concentration is appropriate in a cosmetic formulation. Ultimately, as a prodrug of hydroquinone, it should probably be treated with the same degree of caution. Deoxyarbutin, a synthetic derivative of
arbutin, has also shown some activity in lightening the skin tone and, according to some reports, is less cytotoxic than hydroquinone. Another natural product that has been used as a skin lightening agent is azelaic acid, a straight-chain, saturated dicarboxylic acid originally isolated from the fungus that causes pityriasis versicolor, a condition in which there are patches of increased or decreased pigmentation on the skin. Azelaic acid appears to act selectively on
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