Estimates of the Proportion of Chemicals That Were Carcinogenic or Anticarcinogenic in Bioassays Conducted by the National Toxicology Program

Abstract

Estimates were made of the proportion of chemicals that were carcinogenic, anticarcinogenic, or either in 397 long-term bioassays conducted by the National Toxicology Program (NTP). The estimates were obtained from the global pattern of p-values obtained from statistical tests applied to individual experiments. These tests accounted for multiple comparisons using a randomization procedure and were found to operate at the correct level of significance. Representative estimates of the proportion of carcinogens [with 90% confidence intervals (CI)] compared to the NTP estimates were as follows: male mice, 0.32 (CI, 0.19-0.44), NTP = 0.29; female mice, 0. 28 (CI, 0.15-0.41), NTP = 0.34; male rats, 0.35 (CI, 0.23-0.47), NTP = 0.36; female rats, 0.34 (CI, 0.21-0.46), NTP = 0.28; all sexes and species, 0.59 (CI, 0.49-0.69), NTP = 0.51. Representative estimates of the proportion of anticarcinogens were as follows: male mice, 0. 34; female mice, 0.27; male rats, 0.40; female rats, 0.44; all sexes and species, 0.66. Thus, there was as much or more evidence in this study for anticarcinogenesis as carcinogenesis. Even though the estimators used were negatively biased, it was estimated that 85% of the chemicals were either carcinogenic or anticarcinogenic at some site in some sex-species group. This suggests that most chemicals given at high enough doses will cause some sort of perturbation in tumor rates.