Species-Specific Cutaneous Biotransformation of the Pesticide Propoxur during Percutaneous Absorption in Vitro

Abstract

Propoxur (2-isopropoxyphenyl N-methylcarbamate) is a pesticide with a wide spectrum of applications, including use in agriculture and greenhouses. Percutaneous absorption and concurrent cutaneous metabolism of propoxur were studied in a two-compartment organ culture model. Nontoxic concentrations of [ 14C]propoxur were applied topically to skin discs from human, rabbit, and porcine origin. Permeation rates were comparable in human and rabbit skin, while pig skin was found to be twice as permeable. Furthermore, it was demonstrated that skin tissue of all three species had the capacity to metabolize propoxur. Hydrolysis of propoxur yielded 2-isopropoxyphenol (IPP), followed by phase II conjugation reactions. Interestingly, the type of IPP conjugation appeared to be species specific. In porcine skin cultures, glucuronides and sulfates were detected in equal amounts, whereas in human skin only sulfate conjugation was observed. For rabbit skin, glucuronidation was the major route of conjugation, with minor amounts of the sulfate conjugate and an unidentified metabolite. The percentage of propoxur metabolism in rabbit skin was not influenced by the dose in the range of 25-200 μg/cm 2; in contrast, human skin metabolism was virtually saturated at 100 μg/cm 2.