Journal Article

Single Administration Toxicokinetic Studies of Decalin (Decahydronaphthalene) in Rats and Mice

Jeffrey A. Dill, Alfred F. Fuciarelli, Kyeonghee M. Lee, Kathleen M. Mellinger, Po C. Chan, Leo T. Burka and Joseph H. Roycroft

in Toxicological Sciences

Volume 72, issue 2, pages 210-222
Published in print April 2003 | ISSN: 1096-6080
Published online April 2003 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfg027
Single Administration Toxicokinetic Studies of Decalin (Decahydronaphthalene) in Rats and Mice

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Decalin (decahydronaphthalene) is an industrial solvent known to cause α2u-globulin nephropathy in male rats. Studies were conducted using decalin (mixture of cis and trans isomers) to (1) characterize systemic elimination of decalin in rats and mice and (2) evaluate disposition of decalin, its metabolites, and kidney α2u-globulin in young and old rats of both sexes following a single 6-h whole-body inhalation exposure at up to 400 ppm decalin. Additionally, a separate group of young male F344/N rats were administered either cis- or trans-decalin iv at doses up to 20 mg/kg to assess disposition of each isomer, its metabolites, and kidney α2u-globulin. Decalin was eliminated from blood in a dose-dependent manner, regardless of sex, age, or species. C0 and AUC increased supra-proportionally with exposure concentration. Mice were more efficient in eliminating decalin than rats at lower exposure concentrations, but nonlinear elimination kinetics were more noticeable at 400 ppm. Sex differences in blood decalin elimination were observed in rats; females had a consistently higher AUC at all exposure concentrations. There was a dose-dependent increase in kidney decalin, decalone, and α2u-globulin in male rats exposed to decalin. Kidney α2u-globulin and decalone concentrations in old male rats were substantially lower than those in young males, but were similar to those observed in all (young and old) females. Compared to old males and all females, young male rats had significantly lower urinary decalol concentrations, but higher kidney decalin, decalone, and α2u-globulin concentrations. Administration of decalin to male rats as either the cis or trans isomer revealed that more cis -decalone is produced per unit dose as compared to trans-decalone, and that more trans-decalin accumulated in the kidney (as α2u-globulin-ligand complexes) compared to cis-decalin. These patterns of isomer-specific metabolism were also reflected in the cis/trans ratios of decalin in blood, as well as urinary decalol metabolites. The ratio of α2u-globulin to the total amount of decalin plus decalone measured in the male rat kidney was approximately 1.0. Therefore, α2u-globulin was a key factor in the accumulation of decalin and decalone in kidneys of young male rats, decalin and decalone were practically absent in all females and in old males.

Keywords: decalin (decahydronaphthalene); decalone; decalol; α2u-globulin; toxicokinetics

Journal Article.  8919 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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