A RASH analysis of National Toxicology Program data: Predictions for 30 compounds to be tested in rodent carcinogenesis experiments

Abstract

Relative potencies for 30 compounds scheduled for carcinogenic testing in the 2-year rodent bioassays were estimated based on comparisons with a wide variety of bioassay data for benzo[a]pyrene, nicotine, cisplatin, aflatoxin B1, and cyclophosphamide. Potential for oncogenic transformation of each of the compounds was estimated from short-term bioassays. Promoting strength was assigned on the basis of comparisons of the product of relative potency and test dose with the distribution of similar products obtained for 67 common compounds in the database of Gold et al. A potency class for promotion was assigned on the basis of whether the potency-adjusted test dosage was > 2σ below the mean, > 1σ below the mean, within ±σ of the mean, > σ above the mean, or > 2σ above the mean, as determined from the 67 compounds. The underlying hypothesis is that a weak test dose may have a low probability of revealing a potential carcinogen, whereas a strong dose may have a high probability of producing false-positive results. Predictions are therefore directed at the central 68% of the log-normal frequency distribution according to the assumption that ±σ represents the ideal test dose.