Addendum to the Final Report on the Safety Assessment of Hydroquinone

Abstract

An assessment of the safety of Hydroquinone was first published in 1986 (J Am Coll Toxicol 5:123-65). The ingredient was found to be safe for use at limited concentrations for certain formulations. This addendum reviews new data and presents a revised conclusion regarding safety. Hydroquinone is an aromatic compound used principally in hair dyes and colors, but it is also in lipsticks, skin fresheners, and other skin care preparations. Hydroquinone in an aqueous solution was shown to be absorbed through human skin at a rate of 0.55 ± 0.13 μg/cm²/h. Hydroquinone is rapidly absorbed and excreted in urine in rats following oral administration. Absorption from an alcohol vehicle is greater than from an aqueous solution. Hydroquinone was found to be cytotoxic to rat hepatoma cells in culture, and nephrotoxic in male rats dosed orally by gavage. Oral administration of Hydroquinone to rats resulted in dose-dependent mortality, lethargy, tremors, and increased liver and kidney weights. Oral administration did not produce embryotoxic, fetotoxic, or teratogenic effects in rats. In rats, dermal application produced slight to severe irritation. In a guinea pig maximization test, induction with 2% Hydroquinone injected intradermal, followed by challenge with 0.5% Hydroquinone, showed extreme sensitization. In 80 patients known to be sensitive to aromatic compounds, 0.5% Hydroquinone elicited no reactions. Hydroquinone can cause depigmentation of skin. Various genotoxicity assays show that Hydroquinone can induce sister chromatid exchanges, chromosomal aberrations and loss, and increased frequency of mitotic crossovers. It also induced DNA strand breaks and inhibited DNA and RNA synthesis in rabbit bone marrow mitochondria. Forward mutation assays with or without metabolic activation were positive, but the results with the Ames test, a mouse test for somatic mutations, and other tests were negative. Hydroquinone, given to rats orally by gavage five times per week for up to 103 weeks at doses of 25 or 50 mg/kg, resulted in a significant increase of renal adenomas in males given 50 mg/kg and of mononuclear cell leukemia in females with both doses. At doses of 50 or 100 mg/kg on the same schedule, there was a significant increase in hepatocellular adenomas in both male and female mice. Other studies of Hydroquinone showed no significant difference in tumors between control and exposed groups, and marginal to no activity as a tumor promoter. It is concluded that Hydroquinone is safe at concentrations of ≤1% for aqueous cosmetic formulations designed for discontinuous, brief use followed by rinsing from the skin and hair. Hydroquinone should not be used in leave-on, nondrug cosmetic products.