US EPA

62912 

Journal Article 

Dose-response and ultrastructural alterations in dioxane carcinogenesis. Influence of methylcholanthrene on acute toxicity 

Argus, MF; Sohal, RS; Bryant, GM; Hoch-Ligeti, C; Arcos, JC 

1973 

Yes 

European Journal of Cancer
ISSN: 0959-8049
EISSN: 1879-0852 

European Journal of Cancer (1965) 

9 

4 

237-243 

English 

4778367 

10.1016/0014-2964(73)90088-1 

WOS:A1973P526300001 

https://linkinghub.elsevier.com/retrieve/pii/0014296473900881
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A dose-response study with dioxane revealed the hepatocarcinogenicity of this compound in male rats to be a function of the total oral dose administered. The progressive development of these tumors was studied histopathologically, and detailed electronmicroscopy was carried out on precancerous liver tissue and on hepatocellular carcinoma produced by dioxane. The LD50 dose of dioxane in male rats (5•60 g/kg body weight) is significantly decreased (5•18 g/kg) in animals pretreated with 3-methylcholanthrene. This suggests that a metabolite is involved in the toxicity and possibly carcinogenicity of dioxane, and that both may be potentiated by enzyme inducers. Because certain hydroperoxides are known to be carcinogenic, it was shown by micro-iodimetric titrations that the dioxane used does not contain a dioxane hydroperoxide and that no peroxide is formed under the conditions of administration. 

Animals; Carcinogens; Dioxins administration dosage toxicity; Dose-Response Relationship Drug; Enzyme Induction; Lethal Dose 50; Liver Neoplasms chemically induced pathology; Male; Methylcholanthrene pharmacology; Microscopy Electron; Neoplasms Experimental chemically induced pathology; Precancerous Conditions pathology; Rats