Qiao G L, Brooks J D, Riviere J E
Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Toxicol Appl Pharmacol. 1997 Dec;147(2):234-46. doi: 10.1006/taap.1997.8288.
Residue of the environmentally relevant biocide pentachlorophenol (PCP) is found mainly in soil, making dermal contact one of the primary routes for PCP exposure. To quantify exposure effects on dermal absorption and systemic disposition, [14C-UL]PCP was dosed nonocclusively or occlusively at 40 micrograms/cm2 in a soil-based mixture in an in vivo swine model. Additionally, antibiotics were also codosed with occlusive PCP in soil to examine the impacts of skin microbial PCP biodegradation on total dermal absorption. Under nonocclusive, occlusive, and occlusive-antibiotic conditions, total radiolabel absorption by 408 hr was 29.08, 100.72, and 86.21% dose, respectively. Tissue accumulation of PCP and its labeled metabolite(s) was very significant in swine since one-half to two-thirds of the absorbed dose was still present in tissues by 17 days after PCP dermal exposure. High 14C concentrations were found in liver, kidney, lung, ovary, and uterus. Urine and fecal routes were equally important for label excretion from the body. Occlusion enhanced total dermal absorption and changed the shape of the absorption profiles in the blood and plasma. Skin microorganism inhibition retarded 14C dermal absorption, altered local and systemic tissue distribution, and increased plasma/blood concentration ratios, suggesting skin microbial PCP degradation might play an important role in the altered absorption and disposition by occlusion. This study demonstrated significant dermal absorption and extensive tissue persistence of PCP after soil exposure. Occlusion and skin microflora growth may greatly impact dermal absorption, cutaneous disposition, and systemic toxic input. Therefore, exposure-specific PCP absorption and disposition profiles must be taken into consideration in risk analysis.
环境相关生物杀灭剂五氯苯酚（PCP）的残留主要存在于土壤中，这使得皮肤接触成为PCP暴露的主要途径之一。为了量化暴露对皮肤吸收和全身处置的影响，在体内猪模型中，将[14C-UL]PCP以40微克/平方厘米的剂量非封闭或封闭地施用于基于土壤的混合物中。此外，还将抗生素与封闭状态下土壤中的PCP共同给药，以研究皮肤微生物对PCP的生物降解对皮肤总吸收的影响。在非封闭、封闭和封闭-抗生素条件下，到408小时时，放射性标记的总吸收量分别为剂量的29.08%、100.72%和86.21%。PCP及其标记代谢物在猪体内的组织蓄积非常显著，因为在PCP皮肤暴露后17天，吸收剂量的二分之一至三分之二仍存在于组织中。在肝脏、肾脏、肺、卵巢和子宫中发现了高浓度的14C。尿液和粪便途径对于体内标记物的排泄同样重要。封闭增强了皮肤总吸收，并改变了血液和血浆中吸收曲线的形状。皮肤微生物抑制作用减缓了14C的皮肤吸收，改变了局部和全身组织分布，并增加了血浆/血液浓度比，这表明皮肤微生物对PCP的降解可能在封闭引起的吸收和处置改变中起重要作用。本研究表明，土壤暴露后PCP有显著的皮肤吸收和广泛的组织持久性。封闭和皮肤微生物生长可能会极大地影响皮肤吸收、皮肤处置和全身毒性输入。因此，在风险分析中必须考虑特定暴露情况下的PCP吸收和处置情况。
