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J Appl Toxicol 1997 May-Jun;17(3):153-8

Percutaneous absorption and metabolism of Coumarin in human and rat skin.

Yourick JJ, Bronaugh RL

Abstract

Coumarin is widely used as a fragrance in cosmetics, perfumes and soaps. The food and Drug Administration banned coumarin use in food because of reports that coumarin produced hepatotoxicity in rodents. Concerns about coumarin's safety have also been raised by toxicity testing conducted by the National Toxicology Program. Therefore, we initiated studies to measure the extent of coumarin absorption and metabolism in skin. [14C]Coumarin (ca. 0.5 microCi per cell) absorption in skin was measured by using two vehicles: ethanol (15 microliters cm-2) and an oil-in-water emulsion (3 mg cm-2). Absorption was determined for 24 h by using flow-through diffusion cells (0.64 cm2, exposed skin) with a receptor fluid consisting of HEPES-buffered Hank's balanced salt solution (pH 7.4). Coumarin metabolism was determined by high-performance liquid chromatography methodology. In rat skin (n = 3), the percentages of applied dose absorbed after 24 h were 54.9 +/- 0.63 (mean +/- SEM) and 86.8 +/- 5.4 for the ethanol and emulsion vehicles, respectively, with ca. 5% remaining in skin. In human skin (n = 2), the percentages of applied dose absorbed after 24 h were 64.4 +/- 0.29 and 98.0 +/- 5.3 for the ethanol and emulsion vehicles, respectively, with ca. 1% remaining in skin. The extent of skin absorption was greater from the emulsion vehicle than from the ethanol vehicle in both human and rat skin. Coumarin rapidly penetrated both rat and human skin with > 75% and > 95%, respectively, of the absorbed dose found in the receptor fluid within 6 h. No evidence of coumarin metabolism was found in either skin or receptor fluid fractions. These studies indicate that coumarin absorption is significant in skin. Systemic coumarin absorption must be expected after dermal contact with coumarin-containing products.


Category: Journal Article
PubMed ID: #9250536 DOI: 10.1002/(SICI)1099-1263(199705)17:3<153::AID-JAT426>3.0.CO;2-E
Includes FDA Authors from Scientific Area(s): Food
Entry Created: 2012-12-26
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