In vitro percutaneous absorption and metabolism in man of 2-chloro-4-ethylamino-6-isopropylamine-s-triazine (Atrazine).

Autor: Ademola, John, Sedik, Lena, Wester, Ronald, Maibach, Howard
Zdroj: Archives of Toxicology; Feb1993, Vol. 67 Issue 2, p85-91, 7p
Abstrakt: Atrazine is an extensively used herbicide in the USA. Our objective was to determine the absorption and metabolism (detoxification) of atrazine in human skin. Percutaneous absorption of atrazine in human skin from four sources was examined utilizing a flow-through in-vitro diffusion system. About 16.4% of the applied dose was absorbed by the skin. Radioactivity in the receptor fluid at 20 h was less than 5% of the administered dose. The highest concentration of the applied dose was found in the skin supernates, where 12.0% of the dose (68 nmol) was recovered. Some metabolites of atrazine were identified by thin layer and high pressure liquid chromatography after extraction of receptor fluid and the skin supernates. Two metabolites of atrazine [2-chloro-4-ethylamino-6-amino-striazine (desisopropylatrazine) and 2-chloro-4,6-diamino-s-triazine] were found in the receptor fluid and the skin supernates. An additional metabolite (2-chloro-4-amino-6-isopropylamino-s-triazine) was found in the skin supernates. Since desisopropylatrazine represented about 50% of the total metabolites formed during percutaneous absorption, cleavage of the N-isopropyl to the amino product was a key step in the metabolism of atrazine. Further metabolism may proceed by cleavage of the N-deethyl group to give totally dealkylated atrazine. The biotransformation of atrazine was studied in skin microsomal fraction supplemented with an NADPH-generating system. In analogy to metabolism during percutaneous absorption, atrazine was metabolized to its deisopropyl and deethylpropyl derivatives. In addition, 2-hydroxy derivatives of atrazine were formed by the skin microsomal fractions. The biotransformation of atrazine by skin microsomal enzymes indicates the metabolic capacity of the tissue. Cutaneous metabolism of atrazine may be an additional route by which human skin detoxifies the pesticide following topical exposure. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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