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Distribution, elimination, and test for carcinogenicity of 2,4-dinitrotoluene in strain a mice

1982; Elsevier BV; Volume: 64; Issue: 2 Linguagem: Inglês

10.1016/0041-008x(82)90217-4

1096-0333

Herman A.J. Schut, Timothy R. Loeb, Gary D. Stoner,

Toxic Organic Pollutants Impact

2,4-Dinitrotoluene (2,4-DNT) was examined for its ability to produce lung tumors in strain A mice. Its tissue distribution and elimination in this mouse strain were also determined. At total doses of 600, 1500, or 3000 mg/kg, 2,4-DNT did not produce an increase in lung adenomas when compared to controls. The urine was found to be the major route of elimination, with 52.5, 60.1, and 70.0% of ip doses of 1, 10, and 100 mg/kg, respectively, excreted within 4 hr after administration. The distribution of 2,4-DNT in various tissues (blood, liver, kidneys, lungs, adipose tissue, small and large intestine) showed no evidence for preferential uptake or retention at any of the doses tested. At 0.25 to 4 hr after administration, the lungs contained 0.05 to 0.2% of the dose. Terminal half-lives of radioactive meterial in liver (1.1 to 1.7 hr) and kidney (0.9 to 1.4 hr) were not related to dose. At all doses (1, 10, and 100 mg/kg), rapid and extensive metabolism of 2,4-DNT by liver and small intestine was observed, as judged by the low amounts of 2,4-DNT (less than 13% of the total 3H/tissue) that could be re-isolated from these tissues. Blood and lungs contained much higher levels of unchanged 2,4-DNT and, in most cases, the extent of 2,4-DNT metabolism was similar in these two tissues, suggesting that the lung is not an active site of 2,4-DNT metabolism. It is concluded that 2,4-DNT is not carcinogenic in the strain A mouse lung tumor bioassay and that ip administered 2,4-DNT is rapidly eliminated in the urine. The liver and the small intestine are major sites of 2,4-DNT metabolism, while the lungs are relatively inactive in this respect.