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 sc ale, and is adjusted by weighting factors that describe other paramete rs of carcinogenic potency, These factors include positive or negative weightings for: the induction of tumors at tissues or organs associat ed with high historical control tumor incidences; the induction of mal ignant tumors; the induction of tumors at multiple sites; the inductio n of tumors in both sexes of the species; and the induction of tumors in more than one species, To express the inactivity of chemicals towar ds the induction of cancer, the highest average daily dose (HADD) that did not induce a statistical increase in tumors was employed. HADD va lues were similarly converted to log decile units and adjusted by weig hting factors according to lack of activity in both sexes of a species and the lack of activity in more than one species. Three ranking sche mes were developed and applied to a 225-chemical data set obtained fro m the National Toxicology Program Technical Reports: the carcinogen po tency-F344 rat; the carcinogen potency-B6C3F1 mouse; and the carcinoge n potency-combined, a potency scheme based on selecting data from eith er the F344 rat or B6C3F1.