Category analysis of the substituted anilines studied in a 28-day repeat-dose toxicity test conducted on rats: correlation between toxicity and chemical structure.
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.
Sakuratani
Y
Y
Chemical Management Center, National Institute of Technology and Evaluation, Tokyo, Japan. sakuratani-yuki@nite.go.jp
Sato
S
S
Nishikawa
S
S
Yamada
J
J
Maekawa
A
A
Hayashi
M
M
D000814:Aniline Compounds / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006461:Hemolysis; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D021281:Quantitative Structure-Activity Relationship; D051381:Rats
D000814:Aniline Compounds