Add time:08/15/2019         Source:sciencedirect.com

Studies have demonstrated that several chemicals are absorbed and metabolized during skin permeation. We investigated the absorption and metabolism of the pesticide butachlor. Radiolabeled butachior was measured in human (n = 5) skin and the unchanged compound and metabolites were quantified by high-pressure liquid chromatography (HPLC) and thin-layer chromatography (TLC). Following a 24-hr exposure, an average butachlor quantity of ∼5.00% of the applied dose (1.01 μg) was absorbed by the skin. The mean peak penetration rate was 0.7% of the applied dose per hour. The skin retained 1.40 to 8.10% of the applied butachior. The retention of 1.4 to 8.1% of the pesticide by the skin suggests the importance of monitoring human skin following topical exposure. Of the dose recovered in the skin, 0.9% was metabolized to 4-hydroxybutachlor, while 1.8% of the dose in the receptor fluid was recovered as polar conjugates (cysteine, 0.29% dose; glutathione, 0.1% dose; unidentified metabolites, 1.4% dose); 2.8 and 6.8% of the dose absorbed by the skin (∼5.0%) were recovered as metabolites in the receptor fluids and skin homogenates, respectively. Similar to metabolism during percutaneous absorption, butachlor was metabolized to its conjugated and hydroxyl derivatives by skin fractions. The rate of butachlor glutathione and butachlor cysteine formation using skin cytosolic fractions were 12.0 ± 1.5 and 48.0 ± 3.6 pmol/min/mg protein ± SD, respectively. When human skin microsomes were incubated with butachlor, 4-hydroxybutachior was formed at the rate of 55.0 ± 15.0 pmol/min/ mg protein ±SD. 4-Hydroxybutachlor formation was totally dependent on the presence of NADPH. The biotransformation of butachlor using skin fractions indicates the metabolic capacity of the tissue. The biological significance of these metabolites in the disposition of butachlor requires further investigation.

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