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Research ArticleArticle

Absorption, Metabolism, and Disposition of 1,3-Diphenyl-1-Triazene in Rats and Mice after Oral, i.v., and Dermal Administration

James M. Mathews and Kristi S. De Costa
Drug Metabolism and Disposition December 1999, 27 (12) 1499-1504;
James M. Mathews
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Kristi S. De Costa
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Abstract

1,3-Diphenyl-1-triazene (DPT) is used in the synthesis of polymers and dyes, and has been found as an impurity in the color additives D&C Red 33 and FD&C Yellow 5. [14C]DPT, randomly labeled in the phenyl rings, was used to investigate its disposition in rodents. Dermal doses to rats and mice (2 and 20 mg/cm2) were poorly absorbed (≤7%) in 72 h of exposure. Oral doses of DPT (20 mg/kg) to male rats and mice were well absorbed and excreted mainly in the urine, with exhalation of volatile organics accounting for about 1% of the dose. The sole volatile component present in breath was benzene, and all of the metabolites present in urine were composed of those known for the differential metabolism of benzene and for aniline in the two species. Benzene and aniline were detected in the blood of rats administered oral doses of DPT, and relatively high circulating levels of their metabolites were measured as early as 15 min postdosing. Metabolites of these two carcinogens were also formed in human liver slices, indicating a carcinogenic potential for DPT in humans.

Footnotes

  • Send reprint requests to: James M. Mathews, Ph.D., Research Triangle Institute, P.O. Box 12194, 3040 Cornwallis Rd., Research Triangle Park, NC 27709. E-mail: mathews{at}rti.org

  • ↵1 Preliminary accounts of this work were presented at the 8th North American ISSX Meeting (Hilton Head, SC, 1997).

  • This work was performed under National Institute of Environmental Health Sciences Contract No. N01-ES-75407.

  • Abbreviations used are::
    DPT
    1,3-diphenyl-1-triazene
    CYP
    cytochrome P-450
    F-344
    Fischer 344
    ABT
    1-aminobenzotriazole
    • Received March 8, 1999.
    • Accepted September 13, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 27 (12)
Drug Metabolism and Disposition
Vol. 27, Issue 12
1 Dec 1999
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Research ArticleArticle

Absorption, Metabolism, and Disposition of 1,3-Diphenyl-1-Triazene in Rats and Mice after Oral, i.v., and Dermal Administration

James M. Mathews and Kristi S. De Costa
Drug Metabolism and Disposition December 1, 1999, 27 (12) 1499-1504;

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Research ArticleArticle

Absorption, Metabolism, and Disposition of 1,3-Diphenyl-1-Triazene in Rats and Mice after Oral, i.v., and Dermal Administration

James M. Mathews and Kristi S. De Costa
Drug Metabolism and Disposition December 1, 1999, 27 (12) 1499-1504;
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