Carcinogenesis bioassay of chlorinated dibenzodioxins and related chemicals.

NIOSH skin notation profile: dioxane.

“…The carcinogenicity and tumor initiation and promotion abilities of dioxane have been evaluated in experimental animals following dermal application. King et al [1973] applied 0.2 milliliter (mL) of a solution of dioxane in acetone three times per week to skin of mice for 60 weeks. No increase in tumors was observed; however, when 50 μg of dimethylbenzanthracene (DMBA) was applied prior to the application of dioxane at an unspecified concentration, neoplastic lesions of the skin, lungs, and kidneys were reported [King et al 1973].…”

“…King et al [1973] applied 0.2 milliliter (mL) of a solution of dioxane in acetone three times per week to skin of mice for 60 weeks. No increase in tumors was observed; however, when 50 μg of dimethylbenzanthracene (DMBA) was applied prior to the application of dioxane at an unspecified concentration, neoplastic lesions of the skin, lungs, and kidneys were reported [King et al 1973]. Dioxane was not an initiator when Bull et al [1986] applied doses of 1,000 mg/kg dioxane to female mice prior to topical application of 1 μg of 12-O-tetradecanoylphorbol-13-acetate (TPA) three times per week for 20 weeks.…”

Adverse Outcome Pathways for Regulatory Applications: Examination of Four Case Studies With Different Degrees of Completeness and Scientific Confidence

“…The MOA is believed to involve either the KE cell proliferation in the absence of liver cytotoxicity leading to hyperplasia and tumor formation (USEPA, 2013) or the KE of liver cytotoxicity followed by regenerative hyperplasia and tumor formation (Dourson et al, 2014). The MOA hypothesis for liver tumors involving sustained proliferation of spontaneously transformed liver cells is supported by evidence that 1,4-dioxane is a tumor promoter in mouse skin and rat liver bioassays (King et al, 1973;Lundberg et al, 1987). Dose-response and temporal evidence also support the occurrence of cell proliferation prior to the development of liver tumors but suggest that cytotoxicity is not a required precursor event (JBRC, 1998;Kociba et al, 1974).…”

Studies on Metabolism of 1,4-Dioxane

“…This decrease was statistically significant at the p<0.001 level. 6King and coworkers (King et al 1973) found evidence that dioxane was a promotor of tumor activity in mice. Groups of 30 male and 30 female Swiss-Webster mice received a dermal application of dioxane in acetone.…”