Pharmacodynamic effects carcinogenicity

The mid and low doses for a carcinogenicity study are to provide information for assessing the relevance of the study findings to humans. The low dose should be equal to, or a multiple of, the maximum dose proposed for human testing. The rationale for the selection of the low and mid dose needs to be provided on the basis of pharmacokinetic linearity and saturation of metabolic pathways, human exposure and therapeutic dose, pharmacodynamic response in the test species, alteration in the normal physiology of the test species, mechanistic information and the potential for threshold effects, and the unpredictability of toxicity progression observed in other toxicology studies. 

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