Multifactor Potency Scheme for Comparing the Carcinogenic Activity of Chemicals

摘要

A scheme for ranking the quantitative activity of chemical carcinogens isdescribed. The activity scheme uses as its base, dose potency measured as TD50, which after conversion into an inverse log scale, a decile scale, is adjusted by weighting factors that describe other parameters of carcinogenic activity. These factors include positive or negative weightings for: the induction of tumors at tissues or organs associated with high historical control tumor incidences; the induction of tumors at multiple sites; the induction of tumors in both sexes of the species; and the induction of tumors in more than one species. These factors were chosen as they represented qualitative descriptions of the general specificity or non-specificity of chemicals with regard to the activity in rodents and have some bearing on the potential activity of chemicals in humans. In order to construct a measure to express the inactivity of chemicals towards the induction of cancer, a measure analogous to the TD50 has been developed: the highest average daily dose (HADD) in mg chemical/kg body weight administered in a chronic cancer study and that did not induce a statistical increase in tumors. HADD values were similarly converted to log decile units and adjusted by weighting factors according to lack of activity in both sexes of a species, and the lack of activity in more than one species.