Further development of a multifactor potency scheme for chemical carcinogens

This potency scheme expands a previously reported approach (Nesnow S. Mutat Res 1990; 239:83-115) and uses as its base dose potency measured as TD50. The TD50 is converted into an inverse log scale, a decile scale, and is adjusted by weighting factors that describe other parameters of carcinogenic potency. 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 malignant tumors; 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. To express the inactivity of chemicals towards the induction of cancer, the highest average daily dose (HADD) that did not induce a statistical increase in tumors was employed. 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. Three ranking schemes were developed and applied to a 225-chemical data set obtained from the National Toxicology Program Technical Reports: the carcinogen potency-F344 rat; the carcinogen potency-B6C3F1 mouse; and the carcinogen potency-combined, a potency scheme based on selecting data from either the F344 rat or B6C3F1.