Multifactor Potency Scheme for Comparing the Carcinogenic Activity of Chemicals

Abstract

A scheme for ranking the quantitative activity of chemical carcinogens is described. This 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 described 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 because they represented qualitative descriptions of the general specificity or nonspecificity of chemicals with regard to the activity in rodents and have some bearing on the potential activity of chemicals in humans. To construct a measure to express the inactivity of chemicals toward the induction of cancer, a measure analogous to the TD50 has been developed: highest average daily dose (HADD) in milligrams chemical/kilogram 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.(ABSTRACT TRUNCATED AT 250 WORDS)