Tamio Mizutani, Ichiko Ishida, Kenji Yamamoto
Feb 1, 1982
Citations
0
Influential Citations
41
Citations
Quality indicators
Journal
Toxicology and applied pharmacology
Abstract
Abstract In mice, a single ip dose of butylated hydroxytoluene (2,6-di- tert .-butyl-4-methylphenol, BHT) produces a proliferation of alveolar cells and an accompanying increase in lung weight. Twenty-three commercial and synthetic alkylphenols analogous to BHT were examined for the ability to cause increased wet and dry lung weights in mice. 2- tert .-Butyl-4-methylphenol, 2- tert .-butyl-4,6-dimethylphenol, and 2- tert .-amyl-4-methylphenol were highly effective agents. Comparison of the tested compounds showed that the structural feature essential for toxic activity was a phenolic ring having (i) a methyl group at the 4-position and (ii) ortho -alkyl group(s) which can result in a moderate hindering effect on the hydroxyl group. These structural requirements support the hypothesis that quinone methides or closely related metabolites which are formed by microsomal oxidation of the toxic phenols play a role in producing lung damage.