Percutaneous Absorption and Metabolism of Coumarin in Human and Rat Skin

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 μCi per cell) absorption in skin was measured by using two vehicles: ethanol (15 μl 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. © 1997 John Wiley & Sons, Ltd.

Simple Synthesis of Some Novel Polyfunctionally Derivatives of 2H-Coumarin-2-One.

“…Compound (2) was considered good starting material for preparing many (pyrimidine, pyridine, piperidine, oxazepine)-2H-coumarin-2-one derivatives thus, the reaction of (2) with different amines via elimination of ethanol molecule afforded intermediates (3,5,7,9,11) which cyclized by nucleophilic addition of amine into the cyano group to afford derivatives (4,6,8,10,12), all these products were confirmed by analytical and spectral analysis (Table 1, 2).…”

“…Coumarins and their derivatives are used in the field of biology, medicine and polymer science. They are also, present or used in perfumes and cosmetics [4,8] cigarettes [5][6][7][8], alcoholic beverages [9] and laser dye [10]. In addition, coumarins have been found to be connected with a number of cases of homicide and suicide in Korea [11].…”

Dermatotoxicity of epicutaneously applied anticoagulant warfarin

“…Permissive role of the skin for warfarin effects might rely on a number of enzyme systems present in the skin, which might metabolize warfarin (Martin et al, 1987). However, in vitro percutaneous absorption/metabolic studies of coumarin in rat skin revealed no metabolic changes during absorption (Yourick and Bronaugh, 1997;Beckley-Kartey et al, 1997). In corroboration of these studies, our data, which demonstrated increased prothrombin (PT) and partial thromboplastin time (PTT) following epicutaneous warfarin application in rats (Kataranovski et al, 2003), suggest the access of unchanged warfarin to general circulation following percutaneous absorption.…”

Método espectroscópico para determinação de cumarina em xarope de Mikania glomerata Sprengel

“…Os xaropes de Mikania glomerata Sprengel, além de cumarina possuem outros constituintes que podem interferir na análise espectroscópica, e por este motivo optou-se trabalhar com um processo extrativo da cumarina utilizando solventes como clorofórmio e hexano, visto que o logaritmo do coefi ciente de partição octanol/água (log P) da cumarina é igual a 1,39 (Yourick & Bronaugh, 1997). O coefi ciente de partição determinado para cumarina em hexano e clorofórmio está apresentado na Tabela 1.…”