@article {Halladay1456, author = {Jason S. Halladay and John-Michael Sauer and I. Glenn Sipes}, title = {Metabolism and Disposition of [14C]1-Nitronaphthalene in Male Sprague-Dawley Rats}, volume = {27}, number = {12}, pages = {1456--1465}, year = {1999}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {In rats and mice, 1-nitronaphthalene (1-NN) produces both lung and liver toxicity. Even though these toxicities have been reported, the metabolism and disposition of 1-NN have not been elucidated. Therefore, studies were performed to characterize its fate after i.p. and i.v. administration to male Sprague-Dawley rats. After i.p. administration of [14C]1-NN (100 mg/kg; 60 μCi/kg), 84\% of the dose was eliminated in the urine and feces by 48 h. At 96 h, 60\% of the dose was recovered in the urine, 32\% in the feces, and 1\% collectively in the tissues, blood, and gastrointestinal contents. The terminal phase rate constant (kterm) of 1-NN was 0.21 h-1, the terminal phase half-life (T1/2,term) was 3.40 h, and the systemic bioavailability was 0.67. When administered i.v. (10 mg/kg; 120 μCi/kg), 85\% of the dose was eliminated in the urine and feces by 24 h. At the end of the study (96 h), 56\% of the dose was recovered in the urine, 36\% in the feces, and 1\% collectively in the tissues, blood, and gastrointestinal contents. Interestingly, 88\% of the dose was secreted into bile by 8 h. Thekterm was 0.94 h-1 and theT1/2,term was 0.77 h. The major urinary metabolite after both routes of administration wasN-acetyl-S-(hydroxy-1-nitro-dihydronaphthalene)-l-cysteine. Other urinary metabolites identified include hydroxylated, dihydroxylated, glucuronidated, sulfated, and reduced metabolites, as well as dihydrodiol. The major biliary metabolite was hydroxy-glutathionyl-1-nitro-dihydronaphthalene. These data show that 1-NN undergoes extensive metabolism and enterohepatic recirculation, and the majority of the dose is eliminated in the urine. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/27/12/1456}, eprint = {https://dmd.aspetjournals.org/content/27/12/1456.full.pdf}, journal = {Drug Metabolism and Disposition} }