STATISTICAL MODELS AND METHODS ARTICLE Statistical Comparison of Carcinogenic Effects and Dose–Response Relationships in Rats and Mice for 2,4-Toluene Diamine to those Ascribed

The U.S. National Toxicology Program (NTP) conducted 2-year bioassays of commercial grade toluene diisocyanate (TDI) (80 % 2,4-TDI and 20 % 2,6-TDI) and 2,4-toluene diamine (TDA) and concluded that both were carcinogenic in rodents. In the TDI study, there was an unproven but likely formation of TDA either because of flawed test-substance handling and storage conditions and/or the atypical exposure conditions employed. Although the carcinogenic responses in both studies were qualitatively similar, several statistical analyses were performed to substantiate this possibility more rigorously. Seven different statistical approaches combine to yield a robust and consistent conclusion that, if only a small fraction (approximately 5%) of the dose of TDI were hydrolyzed to TDA in the TDI study, then that would be sufficient to explain the observed carcinogenic responses in the TDI study. Key Words: toluene diisocyanate (TDI), toluene diamine (TDA), tumorigenic re-sponses in rats and mice, hydrolyze TDI to TDA, flawed test-substanc