Schut H A, Loeb T R, Grimes L A, Stoner G D
J Toxicol Environ Health. 1983 Oct-Dec;12(4-6):659-70. doi: 10.1080/15287398309530458.
After intraperitoneal (ip) and oral (po) administration of 2,6-dinitrotoluene (2,6-DNT), the distribution, elimination, and lung tumor response were determined in strain A mice. In a 30-wk bioassay and at total ip doses of 600, 1500, or 3000 mg/kg, or total po doses of 1200, 3000, or 6000 mg/kg, 2,6-DNT did not produce an increase in lung adenomas when compared to vehicle-treated controls. The urine was the major route of elimination of both ip and po administered 3H-labeled 2,6-DNT, with 87.6, 55.2, and 49.1% of ip doses of 1, 10, and 100 mg/kg, respectively, excreted within 4 h. The corresponding amounts excreted after po administration were 33.6, 25.2, and 24.3%, which increased to 53.7, 53.5, and 48.6% after 8 h. The distribution of 2,6-DNT in various tissues (blood, liver, kidneys, lungs, small and large intestine) showed no evidence for preferential uptake or retention at any of the ip or po doses. Terminal half-lives of radioactive material in the liver were 1.11, 0.95, and 1.16 h after ip doses of 1, 10, and 100 mg/kg, respectively. At all ip doses (1, 10, and 100 mg/kg), rapid and extensive metabolism of 3H-labeled 2,6-DNT was observed, as judged by the low amounts (less than 2% of the total 3H/tissue) of unchanged 3H-labeled 2,6-DNT that could be reisolated from blood, liver, small intestine, or lungs at 2 h after administration. The extent of 3H-labeled 2,6-DNT metabolism by these tissues after po administration was similar, except for the relatively high amounts of unchanged 3H-labeled 2,6-DNT (approximately 50% of the total 3H/tissue between 1 and 8 h after 100 mg/kg) present in the small intestine. At these times, negligible (less than 2%) unchanged 3H-labeled 2,6-DNT was present in the large intestine. It is concluded that ip or po administered 2,6-DNT is not carcinogenic in the strain A mouse lung-tumor bioassay. Excretion in the urine is the major mode of elimination after either ip or po administration, but is slower after po than after ip dosing. It is likely that the liver and small intestine are major sites of 2,6-DNT metabolism, and it is possible that po administered 2,6-DNT is also metabolized by the microflora of the large intestine.
在对A品系小鼠腹腔内（ip）和口服（po）给予2,6 - 二硝基甲苯（2,6 - DNT）后，测定了其分布、消除情况以及肺肿瘤反应。在一项为期30周的生物测定中，腹腔内总剂量为600、1500或3000 mg/kg，或口服总剂量为1200、3000或6000 mg/kg时，与赋形剂处理的对照组相比，2,6 - DNT并未使肺腺瘤数量增加。尿液是腹腔内和口服给予的3H标记的2,6 - DNT的主要消除途径，腹腔内给予1、10和100 mg/kg剂量后，分别有87.6%、55.2%和49.1%在4小时内排出。口服给药后相应的排出量分别为33.6%、25.2%和24.3%，8小时后增加到53.7%、53.5%和48.6%。2,6 - DNT在各种组织（血液、肝脏、肾脏、肺、小肠和大肠）中的分布表明，在任何腹腔内或口服剂量下，均未发现有优先摄取或潴留的迹象。腹腔内给予1、10和100 mg/kg剂量后，肝脏中放射性物质的终末半衰期分别为1.11、0.95和1.16小时。在所有腹腔内剂量（1、10和100 mg/kg）下，均观察到3H标记的2,6 - DNT迅速且广泛地代谢，这可通过给药后2小时从血液、肝脏、小肠或肺中重新分离出的未变化的3H标记的2,6 - DNT含量较低（占总3H/组织的不到2%）来判断。口服给药后这些组织对3H标记的2,6 - DNT的代谢程度相似，但小肠中存在相对较高含量的未变化的3H标记的2,6 - DNT（100 mg/kg给药后1至8小时占总3H/组织的约50%）。在这些时间点，大肠中未变化的3H标记的2,6 - DNT含量可忽略不计（不到2%）。结论是，在A品系小鼠肺肿瘤生物测定中，腹腔内或口服给予的2,6 - DNT无致癌性。尿液排泄是腹腔内或口服给药后的主要消除方式，但口服给药后比腹腔内给药慢。肝脏和小肠可能是2,6 - DNT代谢的主要部位，口服给予的2,6 - DNT也有可能被大肠中的微生物群代谢。
