Toxicity toxicologically relevant modes

Therefore, information on the toxicological mode(s) of action as well as mechanistic data are essential in establishing the relevance to humans of the toxicological effects observed in experimental animals. The evaluation of the relevance for humans of data from smdies in animals is aided by use of data on the toxicokinetics, including metabolism, of a substance in both humans and the animal species used in the toxicity tests, when they are available, even when they are relatively limited. 

In this chapter, we outline the issues and principles that are relevant to toxicity assessments of combined exposures. The scope of this overview is limited to combinations of chemicals, but excludes the topic of nonchemical stressors acting in concert with chemicals. Because the issues are of a generic nature, we draw on examples from human, environmental, and ecological toxicology. Section 3.2 briefly outlines approaches to mixture effects assessment (Chapter 4 elaborates these approaches in more detail), Section 3.3 discusses mixture effects in relation to modes and mechanisms of action, and Section 3.4 addresses the problems and possibilities of predicting mixture effects. In Sections 3.5 and 3.6, emphasis is on the predictability of synergism and on effects at low concentration or dose levels of chemicals in mixtures. Section 3.7 provides an overview of scarcely available data on mixture effects in real-world exposure scenarios. This chapter ends with an outlook to the future. 

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