For definition of Groups, see Preamble Evaluation.
VOL.: 71 (1999) (p. 589)
Chem. Abstr. Name: 1,4-Dioxane
5.1 Exposure data
Exposure to 1,4-dioxane may occur during its manufacture and its use as a solvent in a wide range of organic products. It has been detected in ambient air.
5.2 Human carcinogenicity data
Deaths from cancer were not elevated in a single, small prospective study of workers exposed to low concentrations of dioxane.
5.3 Animal carcinogenicity data
1,4-Dioxane was tested for carcinogenicity by oral administration in mice, rats and guinea-pigs. It produced an increased incidence of hepatocellular adenomas and carcinomas in mice, tumours of the nasal cavity, liver subcutaneous tissues, mammary gland and peritoneal mesotheliomas in rats and tumours of the liver and gall-bladder in guinea-pigs. No increase in tumours was seen in rats following inhalation exposure. In the mouse-lung adenoma assay, intraperitoneal injection of 1,4-dioxane increased the incidence of lung tumours in males; no such effect was seen following oral administration. In a two-stage liver foci assay in rats, 1,4-dioxane showed promoting activity.
5.4 Other relevant data
1,4-Dioxane is rapidly absorbed upon inhalation or after oral administration, but its penetration of skin is poor. The major metabolite is b-hydroxyethoxyacetic acid, which is rapidly excreted. In rats, the elimination of 1,4-dioxane and its metabolites is progressively delayed as doses are increased, indicating saturation of metabolism.
No clinical signs or changes in mortality were found in a cohort of exposed workers. In rats, 1,4-dioxane produces degenerative and necrotic changes in liver and renal tubules. High doses can significantly increase the total hepatic cytochrome P450 content.
No reproductive effects of 1,4-dioxane exposure of rats have been reported.
Most of the broad of tests for genotoxic activity have produced negative results, but positive results were obtained in a cell transformation assay and conflicting results were obtained in mouse bone-marrow cell tests for micronucleus induction.
There is inadequate evidence in humans for the carcinogenicity of 1,4-dioxane.
There is sufficient evidence in experimental animals for the carcinogenicity of 1,4-dioxane.
1,4-Dioxane is possibly carcinogenic to humans (Group 2B).For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol. 11 (1976); Suppl. 7 (1987)
Last updated: 12 April 1999
See Also: Toxicological Abbreviations