A novel bottom-up approach to bounding low-dose human cancer risks from chemical exposures

We propose a novel bottom-up approach to the bounding of low-dose human cancer risks from chemical exposures that does not rely at all upon high-dose data for human or animal cancers. This approach can thus be used to provide an independent "reality check" on low-dose risk estimates derived with dose-response models that are fit to high-dose cancer data. The approach (1) is consistent with the "additivity to background" concept, (2) yields central and upper-bound risk estimates that are linear at all doses, and (3) requires only information regarding background risk, background (endogenous) exposure, and the additional exogenous exposure of interest in order to be implemented. After describing the details of this bottom-up approach, we illustrate its application using formaldehyde as an example. Results indicate that recent top-down risk extrapolations from occupational cohort mortality data for workers exposed to formaldehyde are overly conservative by substantial margins.