Distribution of 1,4-dioxane by combined inhalation plus oral exposure routes in rats

Abstract

1,4-Dioxane is used in large amounts by industry. Human exposure to 1,4-dioxane is via both air and water. Recently we reported that the toxicity of chloroform is enhanced when exposure is by multiple exposure routes rather than a single exposure route. In this study, rats were exposed simultaneously to 1,4-dioxane by two routes, inhalation and oral, and the distribution of 1,4-dioxane in the blood, lung, liver, brain, kidney and abdominal fat of rats were determined. To assess the contribution of each route, unmodified 1,4-dioxane (DX) was administered by inhalation and deuterated 1,4-dioxane (DX-d 8 ) was administered orally, and DX and DX-d 8 were analyzed by mass spectrometer (MS). Exposure by both inhalation and oral administration resulted in DX and DX-d 8 concentrations in the blood and tissues which were higher than when exposure was by either inhalation or oral administration alone. The distribution of 1,4-dioxane in the combined inhalation plus oral administration conformed with its physicochemical properties and the tissue partition coefficients. Our results support the well accepted tenet that when investigating the toxicity of a chemical, the route of exposure is an important consideration, and in addition, our results suggest that when exposure is by multiple routes, exposure by one route may, to some extent, have an affect on exposure by the second route.

Distribution of 1,2-dichloropropane in blood and other tissues of rats after oral administration

“…Six rats were used for each collection. 0.2 mL blood samples were collected into 10-mL headspace sampler (HS)-vials, and 0.2 mL of distilled water was added to each sample (Take et al, 2009(Take et al, , 2010(Take et al, , 2012(Take et al, , 2014a(Take et al, , 2014b. The lung, liver, kidney, and abdominal fat were removed from each rat, and tissue samples (range from about 0.2 to 0.6 g) were placed into separate 10-mL HS-vials.…”

“…The lung, liver, kidney, and abdominal fat were removed from each rat, and tissue samples (range from about 0.2 to 0.6 g) were placed into separate 10-mL HS-vials. Then, 5 mL of distilled water was added to the vials, and the vials were immediately sealed with an aluminum crimp cup (Take et al, 2010(Take et al, , 2012(Take et al, , 2014b.…”