February 01, 2007

By: LESLIE S. BAUMANN

With a track record of safety and efficacy spanning more than 40 years, hydroquinone, a hydroxyphenolic derivative of benzene, is considered the most effective skin-lightening product for treatment of hyperpigmentary disorders (J. Eur. Acad. Dermatol. Venereol. 2006;20:781–7; Skin Therapy Lett. 2004;9:1–3). Globally, the most widely prescribed skin-lightening and depigmenting agents include magnesium l-ascorbyl-2-phosphate, hydroxyanisole, N-acetyl-4-S-cysteaminylphenol, arbutin (hydroquinone-b-d-glucopyranoside), and hydroquinone (Phytother. Res. 2006;20:921–34).

Used in over-the-counter products as well as prescription drugs, hydroquinone (HQ) is found in vegetables, fruits, and grains, as well as in plant-derived products such as coffee, tea, beer, and wine. It is known to reversibly inhibit cellular metabolism by affecting DNA and RNA synthesis.

For many years, HQ has been the first-line therapy for postinflammatory hyperpigmentation and melasma.

HQ exerts its depigmenting effect by efficiently inhibiting tyrosinase, decreasing its activity by 90%. It also is cytotoxic to melanocytes (Dermatol. Clin. 1988;6:185–92; J. Invest. Dermatol. 1984;82:308–10).

Besides HQ, other known inhibitors of tyrosinase include vitamin C, kojic acid, arbutin, mulberry extract, and licorice extract. Although HQ is useful as a sole therapeutic agent, it is often combined with other compounds such as tretinoin, glycolic acid, kojic acid, and azelaic acid.

 

 

The Search for Mutagenic Effects

Despite its long record of medical use, HQ raises concerns because it is derived from benzene and therefore has putative mutagenic properties. In addition, side effects have been associated with the long-term use of cosmetic products containing high HQ concentrations (J. Eur. Acad. Dermatol. Venereol. 2006;20:781–7). Indeed, HQ has been banned as a cosmetic skin-bleaching agent in Europe since January 2001 (Ned. Tijdschr. Geneeskd. 2004;148:768–71), and it is available there only in prescription form. The compound also is highly regulated in Asia.

Recently, investigators conducted a literature search focusing on the biochemistry and toxicology of HQ, benzene, and related molecules, with an eye toward the potential long-term side effects of HQ use in cosmetics. After surveying the large body of literature on the carcinogenicity of these compounds, particularly studies published since 1996, the investigators concluded that the long-term use of topical HQ does pose an increased risk of cancer, and they recommended that this benzene derivative no longer be used as a skin-lightening agent (J. Eur. Acad. Dermatol. Venereol. 2006;20:777–80).

Nevertheless, there are no reports in the medical literature of any human cutaneous or internal malignancies linked to HQ (J. Eur. Acad. Dermatol. Venereol. 2006;20:781–7). Animal experiments have linked HQ use to the induction of leukemia and renal adenomas.

In workers exposed to HQ, the most serious health effects have been pigmentation of the eye and, in a small number of cases, permanent corneal damage (Crit. Rev. Toxicol. 1999;29:283–330).

Because absorption of HQ is more rapid than its elimination through urine, daily use is now known to cause the agent to accumulate in the body (Ned. Tijdschr. Geneeskd. 2004;148:768–71).

Concerns about the effects of intermediate use of HQ, such as exogenous ochronosis and leukomelanoderma en confetti, contributed to the European ban on HQ in cosmetic products that was instituted in 2001 (J. Eur. Acad. Dermatol. Venereol. 2006;20:777–80; Ned. Tijdschr. Geneeskd. 2004;148:768–71).

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