The potential of organ specific toxicity for predicting rodent carcinogenicity

Relationships between organ specific toxicity (specifications of the presence or absence of 43 morphological effects in 32 organs) observed from 13-week subchronic studies and rodent carcinogenicity were investigated by manually measuring the concordance of each feature and also automatically using the RL (Rule Learner) induction program. Of the 32 organs, the presence or absence of any effect in liver or kidney was found very relevant to rodent carcinogenicity. While the concordance of Salmonella genotoxicity with rodent carcinogenicity was only 60%, the battery of liver and kidney was 74% accurate with 75% sensitivity and 71% specificity. Further, using the RL program, rule sets based on organ specific toxicity together with the default predictions based on Salmonella mutagenicity were on average 80% accurate with 83% sensitivity and 82% specificity.