Vostal J J
Environ Health Perspect. 1983 Jan;47:269-81. doi: 10.1289/ehp.8347269.
The pharmacokinetic concepts of bioavailability and biotransformation are introduced into the assessment of public health risk from experimental data concerning the emissions of potentially mutagenic and carcinogenic substances from motor vehicles. The inappropriateness of an automatic application in the risk assessment process of analytical or experimental results, obtained with extracts and procedures incompatible with the biological environment, is illustrated on the discrepancy between short-term laboratory tests predictions that wider use of diesel engines on our roads will increase the risk of respiratory cancer and the widely negative epidemiological evidence. Mutagenic activity of diesel particulates was minimal or negative when tested in extracts obtained with biological fluids, was substantially dependent on the presence of nitroreductase in the microbial tester strain, and disappeared completely 48 hr after the diesel particles had been phagocytized by alveolar macrophages. Similarly, long-term animal inhalation exposures to high concentrations of diesel particles did not induce the activity of hydrocarbon metabolizing enzymes or specific adverse immune response unless organic solvent extracts of diesel particles were administered intratracheally or parenterally in doses that highly exceed the predicted levels of public exposure even by the year 2000. Furthermore, the suspected cancer producing effects of inhaled diesel particles have thus far not been verified by experimental animal models or available long-term epidemiological observations. It is concluded that unless the biological accessibility of the active component on the pollutant as well as its biotransformation and clearance by natural defense mechanisms are considered, lung cancer risk assessment based solely on laboratory microbial tests will remain an arbitrary and unrealistic process and will not provide meaningful information on the potential health hazard of a pollutant.
生物利用度和生物转化的药代动力学概念被引入到根据机动车排放潜在诱变和致癌物质的实验数据来评估公共卫生风险的过程中。通过与生物环境不兼容的提取物和程序获得的分析或实验结果在风险评估过程中自动应用的不恰当性，体现在短期实验室测试预测与广泛的负面流行病学证据之间的差异上，前者认为道路上柴油发动机的广泛使用会增加呼吸道癌症风险，而后者则持否定态度。当在生物流体提取物中进行测试时，柴油颗粒物的诱变活性极小或为阴性，其诱变活性很大程度上取决于微生物测试菌株中硝基还原酶的存在，并且在柴油颗粒被肺泡巨噬细胞吞噬48小时后完全消失。同样，长期动物吸入高浓度柴油颗粒并不会诱导烃代谢酶的活性或特定的不良免疫反应，除非以远远超过即使到2000年预测的公众暴露水平的剂量经气管内或肠胃外给予柴油颗粒的有机溶剂提取物。此外，吸入柴油颗粒的疑似致癌作用迄今尚未得到实验动物模型或现有的长期流行病学观察的证实。结论是，除非考虑污染物中活性成分的生物可及性及其通过自然防御机制的生物转化和清除，否则仅基于实验室微生物测试的肺癌风险评估将仍然是一个随意且不现实的过程，并且不会提供有关污染物潜在健康危害的有意义信息。
