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Author: Wester Ronald C. Melendres Joseph Hui Xiaoying Cox Rebecca Serranzana Steffany Zhai Hongbo Quan Danyi Maibach Howard I.
Publisher: Taylor & Francis Ltd
ISSN: 1087-2620
Source: Journal of Toxicology and Environmental Health, Vol.54, Iss.4, 1998-06, pp. : 301-317
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Abstract
Hydroquinone is a ubiquitous chemical readily available as monographed in cosmetic and nonprescription forms for skin lightening, and is an important industrial chemical. The in vivo bioavailability for 24-h application in humans was 45.3 +/- 11.2% of dose from a 2% cream formulation containing [14C]hydroquinone, with the majority of radioactivity excreted in the first 24 h. Timed skin wash and skin tape-stripping sequences showed a rapid and continuous movement of hydroquinone into the stratum corneum of human volunteers. Plasma levels taken both ipsilateral and contralateral to the topical dosing site contained radioactivity at the first 0.5-h sampling time. Peak plasma radioactivity was at 4 h in the 8-h blood sampling period. In vitro percutaneous absorption with fresh viable human skin gave a bioavailability of 43.3% of dose, and flux was calculated at 2.85 mug/cm 2/h. In vitro, some of the skin samples were pretreated with the metabolic inhibitor sodium azide, which had no effect on percutaneous absorption. Receptor fluid accumulations and 24-h skin samples were extracted and the extracts subjected to thin-layer chromatography (TLC) . Control [14C]hydroquinone extraction and TLC had one radioactivity peak, hydroquinone. Receptor fluid and skin extraction had a second peak with the same R as benzoquinone, which was decreased with azide f treatment. No other peaks were found. Ethyl acetate extraction of urine from the in vivo study showed all radioactivity to be only water-soluble, free hydroquinone released following glucuronidase treatment. Risk assessment should not only involve the bioavailability of intact topical hydroquinone, but also consider phase I and phase II metabolism in both humans and any animal for which toxicity potential was assessed.
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