van de Sandt J J, Rutten A A, van Ommen B
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Toxicol Appl Pharmacol. 1993 Nov;123(1):144-50. doi: 10.1006/taap.1993.1231.
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 micrograms/cm2; in contrast, human skin metabolism was virtually saturated at 100 micrograms/cm2.
残杀威（2-异丙氧基苯基N-甲基氨基甲酸酯）是一种应用广泛的杀虫剂，包括用于农业和温室。在双室器官培养模型中研究了残杀威的经皮吸收和同时发生的皮肤代谢。将无毒浓度的[14C]残杀威局部应用于来自人、兔和猪的皮肤圆盘。人皮肤和兔皮肤的渗透速率相当，而猪皮肤的渗透性是前者的两倍。此外，还证明了所有这三个物种的皮肤组织都有代谢残杀威的能力。残杀威水解产生2-异丙氧基苯酚（IPP），随后发生II相结合反应。有趣的是，IPP结合的类型似乎具有物种特异性。在猪皮肤培养物中，检测到等量的葡萄糖醛酸苷和硫酸盐，而在人皮肤中仅观察到硫酸盐结合。对于兔皮肤，葡萄糖醛酸化是主要的结合途径，有少量的硫酸盐结合物和一种未鉴定的代谢物。兔皮肤中残杀威代谢的百分比在25-200微克/平方厘米范围内不受剂量影响；相比之下，人皮肤代谢在100微克/平方厘米时几乎达到饱和。
