Here we evaluate a multiplicative (relative) risk model for improved
cancer risk estimation of genotoxic compounds. According to this model,
cancer risk is proportional to the background
tumor incidence and to the internal dose of the genotoxic compound. Furthermore, the relative risk coefficient per internal dose is considered to be approximately the same across
tumor sites, sex, and species. In the present study, we demonstrate that the relative risk model is valid for
cancer risk estimation of
glycidol, a common food contaminant. Published
tumor data from
glycidol carcinogenicity studies in mice and rats were evaluated in combination with internal dose estimates from
hemoglobin adduct measurements in blood from mice and rats treated with
glycidol in short-term studies. A good agreement between predicted and observed
tumor incidence in responding sites was demonstrated in the animals, supporting a relative risk coefficient that is independent of
tumor site, sex, and species. There was no significant difference between the risk coefficients for mice (5.1% per mMh) and rats (5.4% per mMh) when considering internal doses of
glycidol. Altogether, this mechanism-based risk model gives a reliable risk coefficient, which then was extrapolated to humans considering internal dose, and background
cancer incidence.