2025 Volume 15 Issue 1 Pages 53-61
This article introduces issues of quantitative assessment of carcinogenicity without threshold and provides an overview of research on carcinogenic potency for known nitrosamines. In most cases of quantitative assessment of non-threshold carcinogenicity, low-dose extrapolation is performed based on animal study data and the ICH M7 guideline recommends using TD50 or BMDL10. These indices for carcinogenic potency require a detailed examination of the validity of carcinogenicity studies, bases of the index derivation, and a decision on the policy to use benchmark dose methods. Recently, we examined the biological validity of the CPCA proposed by EMA. As a result, for some known nitrosamines, there was a gap between the estimated AI by the CPCA and the 10−5 carcinogenic risk level derived from originally calculated BMDL10. Investigating the cause of this result would provide basic data to improve the CPCA or the establishment of a new method for estimating carcinogenic potency in future research.
