Jonker D, Freidig A P, Groten J P, de Hollander A E M, Stierum R H, Woutersen R A, Feron V J
TNO Nutrition and Food Research, Zeist, The Netherlands.
Rev Environ Health. 2004 Apr-Jun;19(2):83-139. doi: 10.1515/reveh.2004.19.2.83.
Recent developments in hazard identification and risk assessment of chemical mixtures are reviewed. Empirical, descriptive approaches to study and characterize the toxicity of mixtures have dominated during the past two decades, but an increasing number of mechanistic approaches have made their entry into mixture toxicology. A series of empirical studies with simple chemical mixtures in rats is described in some detail because of the important lessons from this work. The development of regulatory guidelines for the toxicological evaluation of chemical mixtures is discussed briefly. Current issues in mixture toxicology include the adverse health effects of ambient air pollution; the application of such modern, sophisticated methodologies as genomics, bioinformatics, and physiologically based pharmacokinetic modeling; and databases for mixture toxicity. Finally, the state of the art of our knowledge on the potential adverse health effects of combined exposures to chemicals and non-chemical stressors (noise, heat/cold, microorganisms, immobilization, restraint, or transportation), research initiatives in these fields, and the development of an indicator for the cumulative health impact of multiple environmental exposures are discussed.
本文综述了化学混合物危害识别与风险评估的最新进展。在过去二十年中，研究和表征混合物毒性的经验性、描述性方法占据主导地位，但越来越多的机制性方法已进入混合物毒理学领域。由于这项工作带来的重要经验教训，本文详细描述了一系列在大鼠身上进行的简单化学混合物的实证研究。简要讨论了化学混合物毒理学评估监管指南的制定。混合物毒理学当前的问题包括环境空气污染对健康的不良影响；基因组学、生物信息学和基于生理学的药代动力学建模等现代复杂方法的应用；以及混合物毒性数据库。最后，讨论了我们对化学物质与非化学应激源（噪音、热/冷、微生物、固定、约束或运输）联合暴露潜在健康不良影响的认识现状、这些领域的研究倡议，以及多种环境暴露累积健康影响指标的发展。
