Acute Inhalation Toxicity Study of 1, 4-Dioxane in Rats (Rattus norvegicus)

Abstract : 1,4-dioxane has been used as a stability additive in a number of industrial solvents and has found its way into the environment, especially in groundwater. At current and former military installations where solvents were used, there has been growing concern for assessing the health risk involving human exposure to dioxane. Consequently, we conducted an acute inhalation study, in which we exposed male and female Fischer 344 rats for 6 hours to 0, 100, 300, 800, 2200 or 6000 ppm dioxane and assessed them at 2 days post-exposure or 2 weeks following a recovery period. We also conducted a two-week inhalation study, in which we exposed male and female rats 6 hours/day, 5 days/week to 0, 100, 1600 or 3200 ppm dioxane and assessed them at 1 day post-exposure or following the 2-week recovery period. In the acute study, two rats in the highest exposure groups had vacuolar changes in their nasal cavities two days post-exposure but they fully recovered after two weeks. In the two-week study, animals responded with numerous degenerative changes (lesions in nasal cavity, liver and kidney; hepatic single-cell necrosis). Male rats in the mid- and high concentration groups did not recover fully from hepatic single cell necrosis two weeks after exposure. The lowest observed adverse effect level (LOAEL) for 1,4-dioxane in the 2-week study is 100 ppm.