1,4-Dioxane, a dimer of ethylene oxide, is used extensively as an industrial solvent for lacquers, varnishes, paints, plastics, dyes, oils, waxes, resins, and cellulose acetate and as an inhibitor in chlorinated solvents. In biological and chemical laboratories, dioxane is employed as a solvent for tissue processing, liquid scintillation counting, and photochemical reactions.
A bioassay of 1,4-dioxane for possible carcinogenicity was conducted by administering the test chemical in the drinking water to Osborne-Mendel rats and B6C3F1 mice.
Groups of 35 rats and 50 mice of each sex were administered 1,4-dioxane at concentrations of either 0.5% to 1.0% (v/v) in the drinking water. Because of variations in the intake of water, the doses of test chemical received by the high-dose groups were not precisely twice those received by the low-dose groups; in the male mice, the high dose was only slightly greater than the low dose. The rats were dosed for 110 weeks and the mice for 90 weeks. Matched controls consisted of 35 untreated rats and 50 untreated mice of each sex. All surviving rats were killed at 110-117 weeks and all surviving mice at 90-93-weeks.
The mean body weights of the rats and mice were not consistently affected by the administration of dioxane. Survival rates of the dosed groups of rats and female mice were lower than those of corresponding control groups, but sufficient numbers of animals were at risk for development of late-appearing tumors.
In rats, the incidence of squamous-cell carcinomas of the nasal turbinates was statistically significant in tests for dose-related trend in females (P=0.008) and for direct comparison of high-dose with matched-control males(P<0.001) and direct comparison of dosed with control females (P; 0.003) (males: controls 0/33, low-dose 12/33, high-dose 16/34; females: controls 0/34, low-dose 10/35, high-dose 8/35). In the females, but not in the males, the incidence of hepatocellular adenomas was significant (P; 0.001) in tests for dose-related trend and for direct comparison of both low- and high-dose groups with controls (controls 0/31, low-dose 10/33, high-dose 11/32).
In both male and female mice, the incidence of hepatocellular carcinomas was statistically significant (P; 0.001), both in tests for dose-related trend and direct comparison of both dosed groups with controls (males: controls 2/49, low-dose 18/50, high-dose 24/47; females: controls 0/50, low-dose 12/48, high-dose 29/37). The incidences remained significant when hepatocellular adenomas were combined with hepatocellular carcinomas.
It is concluded that under the conditions of this bioassay, 1,4-dioxane induced hepatocellular adenomas in female Osborne-Mendel rats. 1,4-Dioxane was carcinogenic in both sexes of rats, producing squamous-cell carcinomas of the nasal turbinates, and in both sexes of B6C3F1 mice, producing hepatocellular carcinomas.