Analysis of rodent photo cocarcinogenicity models for hazard evaluation and risk assessment: industry viewpoint

The general consensus in industry is that photo cocarcinogenicity models are experimental and may prove problematic for use as toxicological tools in routine compound development. Part of the reason for this is the fact that current designs yield similar study outcomes from multiple underlying activities (e.g. photoactivation vs tumor promotion) that can be considered of very different importance in IARC and OSTP human cancer risk assessment approaches. Importantly, photoactivation concerns are significant and, therefore, a decision scheme needs to be developed based on data to ensure that activities of this type do not go undetected. Assuming that this approach includes rodent photo cocarcinogenicity models at some level, then an increased level of understanding of the role of these rodent results in determination of any possible human health impact needs to be made. Learning about the mechanism of action from historical multistage carcinogenesis models will likely prove to be important in this process. Finally, given significant current uncertainty in extrapolation from mouse cocarcinogenicity models to humans, epidemiological data need to be used whenever possible to both test the utility of the model and ensure appropriate market decisions where possible.