Are key or associative events in the PPAR-α activation MOA quantitatively predictive of hepatocarcinogenicity?
Another question to consider is whether potency for PPAR-α activation or its attendant sequelae is quantitatively associated with carcinogenic activity or potency. If so, differences in sensitivity for carcinogenesis (such as may occur across species) could be predicted using quantitative information about the key events alone. However, there are limitations in the dose–response data available for analyses of quantitative relationships between potencies for precursor events in the proposed PPAR-α activation MOA and for liver tumor induction. Most tumor data, including for the best-characterized PPAR-α agonists, are for exposure concentrations inducing well above 50% carcinogenic potency (TD50; the daily dose inducing tumors in half of the mice that would otherwise have remained tumor-free) with less-than-lifetime administration. Precursor events have typically been studied at a single dose, often eliciting a near maximal response, thus precluding benchmark-based comparisons across stud
Related Questions
- Why when I have received my activation key and go into Licence Control the Activate button is greyed out on my Windows Vista or Windows 7 machine?
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