Roos Peter H, Tschirbs Sebastian, Pfeifer Frank, Welge Peter, Hack Alfons, Wilhelm Michael, Bolt Hermann M
Institute of Occupational Physiology, University of Dortmund, Ardeystr. 67, D-44139 Dortmund, Germany.
Toxicology. 2004 Dec 15;205(3):181-94. doi: 10.1016/j.tox.2004.06.050.
Contaminated soils represent a potential health risk for the human population. Risk assessment for humans requires specific methods, which must reflect the peculiarities of human behaviour, physiology and biochemistry with respect to contaminant uptake and processing. Biomarkers of effect or exposure have become an appropriate tool. Organic pollutants influence the expression profile of cytochromes P450 (CYP), and CYP1A1 has been shown to be a suitable biomarker for polycyclic aromatic hydrocarbons (PAH). The latter are widely distributed in soils and constitute an important soil contamination. Upon intake of PAH-contaminated soils, CYP1A1 is induced in various organs of rats and minipigs. Increased CYP1A1-levels in lung, kidney and spleen, after oral soil intake, indicate that contaminants escape the primary duodenal and hepatic metabolism and reach further organs. Dose-response relationships reveal that induction effects are to be expected in children based on known exposure conditions. Generally, CYP1A1-induction does not correlate with results of toxicity tests with lower organisms, performed with the same soils. The organic carbon content is largely responsible for this discrepancy. It severely affects the toxicity of soil bound PAH for microorganisms, but obviously affects the mobilization efficiency for PAH in the gastro-intestinal tract of mammals to a minor extent. Soil remediation by different methods may result in a significant reduction of the PAH content and of toxicity. Ingestion of remediated soils by rats shows, however, that the induction potential for CYP1A1 is only slightly decreased after remediation. This means that the major inducing components resist biological remediation or soil washing and remain in the soil. Because data obtained with experimental animals form the guiding principle for in vitro tests to be developed, the suitability of the animal model used for extrapolations to humans has to be proven. Upon soil ingestion, minipigs show a tissue-specific response pattern, which substantially differs from that of rats, which are widely used as animal models. It is not known which response pattern resembles that of man. In summary, cytochromes P450, in particular CYP1A1, are suitable biomarkers to assess the bioavailability of soil bound contaminants and their effects on mammalian species. There are, however, a number of questions to be answered in order to develop an in vitro test for human risk assessment. This concerns, for example, the identification of the suitable animal model, the identification of biomarkers for other contaminants and concepts to transpose the in vivo data to in vitro technologies or to mathematical modelling.
受污染土壤对人类健康构成潜在风险。对人类进行风险评估需要特定方法，这些方法必须反映人类在污染物吸收和处理方面的行为、生理和生化特性。效应或暴露生物标志物已成为一种合适的工具。有机污染物会影响细胞色素P450（CYP）的表达谱，并且已证明CYP1A1是多环芳烃（PAH）的合适生物标志物。PAH广泛分布于土壤中，是土壤污染的重要组成部分。摄入受PAH污染的土壤后，大鼠和小型猪的各种器官中CYP1A1会被诱导。经口摄入土壤后，肺、肾和脾脏中CYP1A1水平升高，表明污染物逃避了十二指肠和肝脏的初级代谢，进入了其他器官。剂量反应关系表明，根据已知的暴露情况，预计儿童会出现诱导效应。一般来说，CYP1A1诱导与用相同土壤对低等生物进行的毒性试验结果不相关。有机碳含量在很大程度上导致了这种差异。它严重影响土壤中结合态PAH对微生物的毒性，但对哺乳动物胃肠道中PAH的迁移效率影响较小。不同方法进行土壤修复可能会使PAH含量和毒性显著降低。然而，大鼠摄入修复后的土壤表明，修复后CYP1A1的诱导潜力仅略有下降。这意味着主要的诱导成分抵抗生物修复或土壤冲洗，仍留在土壤中。由于用实验动物获得的数据是开发体外试验的指导原则，因此必须证明所使用的动物模型用于外推至人类的适用性。摄入土壤后，小型猪表现出组织特异性反应模式，这与广泛用作动物模型的大鼠有很大不同。尚不清楚哪种反应模式与人类相似。总之，细胞色素P450，特别是CYP1A1，是评估土壤结合污染物的生物可利用性及其对哺乳动物物种影响的合适生物标志物。然而，为了开发用于人类风险评估的体外试验，还有许多问题需要回答。这涉及例如合适动物模型的识别、其他污染物生物标志物的识别以及将体内数据转化为体外技术或数学模型的概念。
