1,4-Dioxane: prediction of in vivo clastogenicity.
1,4-Dioxane was analyzed with the CASE program to determine the structural basis of its potential genotoxicity and carcinogenicity. These investigations led to the prediction that while 1,4-dioxane was not genotoxic in vitro, it was an inducer of micronuclei in the bone marrow of rats and a carcinogen for both rats and mice. If it is assumed that the induction of micronuclei is the result of DNA damage, then this potential and the previous report of the in vivo induction of DNA strand breaks in rat liver raise the possibility of a genotoxic action for 1,4-dioxane. However it is also conceivable that we have identified a structural feature which contributes to the induction of micronuclei by a non-genotoxic mechanism.
Rosenkranz
H S
HS
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, PA 15261.
Klopman
G
G
D000818:Animals; D015197:Carcinogenicity Tests; D004247:DNA / Q000187:drug effects; D004146:Dioxanes / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship
D004146:Dioxanes; D009153:Mutagens; D004247:DNA; C025223:1,4-dioxane