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Tytuł:
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Thirteen-week inhalation toxicity of 1,4-dioxane in rats.
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Autorzy:
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Kasai T; Japan Bioassay Research Center, Japan Industrial Safety and Health Association, Hadano, Kanagawa, Japan. />Saito M
Senoh H
Umeda Y
Aiso S
Ohbayashi H
Nishizawa T
Nagano K
Fukushima S
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Źródło:
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Inhalation toxicology [Inhal Toxicol] 2008 Aug; Vol. 20 (10), pp. 961-71.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: London : Informa Healthcare
Original Publication: New York, N.Y. : Hemisphere Pub. Corp., c1989-
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MeSH Terms:
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Dioxanes/*toxicity
Administration, Inhalation ; Animals ; Bronchi/drug effects ; Dioxanes/administration & dosage ; Dioxanes/blood ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Liver/drug effects ; Male ; Nasal Cavity/drug effects ; Rats ; Rats, Inbred F344 ; Trachea/drug effects
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Substance Nomenclature:
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0 (Dioxanes)
J8A3S10O7S (1,4-dioxane)
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Entry Date(s):
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Date Created: 20080801 Date Completed: 20081103 Latest Revision: 20191027
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Update Code:
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20240104
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DOI:
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10.1080/08958370802105397
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PMID:
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18668411
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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.
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