Category analysis of the substituted anilines studied in a 28-day repeat-dose toxicity test conducted on rats: Correlation between toxicity and chemical structure†

†Presented at the 13^th International Workshop on QSARs in the Environmental Sciences (QSAR 2008), 8–12 June 2008, Syracuse, USA.

Abstract

In order to establish methods for estimating the repeat-dose toxicity of chemicals on the basis of their chemical structure, an analysis of a category formed for 14 substituted anilines was conducted. This analysis was based on the results of a 28-day repeat-dose toxicity test conducted on rats in which these 14 chemicals were studied. The intensities of the toxicological effects of the 14 substituted anilines on each target organ at specific dosages were described using the values and histopathological findings of the test. The results clarified the characteristics of the chemical structure that induced specific toxicological effects on specific targets at a particular dosage. Hemolysis was the most frequently observed finding in the test reports in the case of the 14 substituted anilines. Strong linear correlations between the dosage and proportion of decrease in the erythrocyte count were found in the case of chemicals that induced strong hemolytic effects. In particular, for dimethylanilines, strong linear correlations were found between the calculated hemoglobin-binding index and the proportion of decrease in the erythrocyte count at a particular dosage. Thus, the results of our analysis demonstrate that it is possible to correlate the values obtained for substituted anilines from 28-day repeat-dose toxicity tests with their quantitatively determined molecular properties. The intensity of hemolysis and the effects on the liver tended to be low in the case of chemicals with a high water solubility, such as aminophenols and benzene sulfonic acids. However, a similar trend was not observed in the case of the effects of these chemicals on the kidney.

†Presented at the 13^th International Workshop on QSARs in the Environmental Sciences (QSAR 2008), 8–12 June 2008, Syracuse, USA.

Keywords:

• repeat-dose toxicity
• category analysis
• rat
• substituted anilines

Acknowledgments

This work was supported by a NEDO grant for the “Development of Hazard Assessment Techniques Using Structure-activity Relationship Methods.” The authors thank Professor Yamazoe of Tohoku University for his helpful comments and discussions.

Notes

†Presented at the 13^th International Workshop on QSARs in the Environmental Sciences (QSAR 2008), 8–12 June 2008, Syracuse, USA.