Thirteen-week inhalation toxicity of 1,4-dioxane in rats.

Abstract

Thirteen-week inhalation toxicity of 1,4-dioxane was examined by repeated inhalation exposure of male and female F344 rats to 0 (control), 100, 200, 400, 800, 1600, 3200, or 6400 ppm (v/v) 1,4-dioxane vapor for 6 h/day and 5 days/wk. All the 6400-ppm-exposed males and females died during the first week. Terminal body weight decreased, and relative weights of liver, kidney, and lung increased. AST increased in the 200 ppm-and 3200-ppm-exposed females, and ALT increased in the 3200-ppm-exposed males and females. Nuclear enlargement of nasal respiratory epithelial cells occurring in the 100-ppm-exposed males and females was the most sensitive, followed by the enlarged nuclei in the olfactory, tracheal, and bronchial epithelia. 1,4-Dioxane-induced liver lesions occurred at higher exposure concentrations than the nasal lesions did, and were characterized by single-cell necrosis and centrilobular swelling of hepatocytes in males and females. Glutathione S-transferase placental form (GST-P) positive liver foci were observed in the 1600-ppm-exposed females and 3200-ppm-exposed males and females, which are known as a preneoplastic lesion in rat hepatocarcinogenesis. Plasma levels of 1,4-dioxane increased linearly with an increase in the concentrations of exposure to 400 ppm and above. The enlarged nuclei in the nasal epithelia and the GST-P-positive liver foci were discussed in light of the possible development of nasal and hepatic tumors by long-term inhalation exposure to 1,4-dioxane. A lowest-observed-adverse-effect level (LOAEL) was determined at 100 ppm for the nasal endpoint in both male and female rats.

• Authors: Tatsuya Kasai, Misae Saito, Hideki Senoh, Yumi Umeda, Shigetoshi Aiso, Hisao Ohbayashi, Tomoshi Nishizawa, Kasuke Nagano, Shoji Fukushima
• Journal: Inhalation toxicology (Inhal Toxicol) Vol. 20 Issue 10 Pg. 961-71 (Aug 2008) ISSN: 1091-7691 [Electronic] England
• PMID: 18668411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dioxanes
• 1,4-dioxane

Topics

• Administration, Inhalation
• Animals
• Bronchi (drug effects)
• Dioxanes (administration & dosage, blood, toxicity)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Liver (drug effects)
• Male
• Nasal Cavity (drug effects)
• Rats
• Rats, Inbred F344
• Trachea (drug effects)