Metabolism and excretion of 2,4-dinitrotoluene in male and female Fischer 344 rats after different doses.
Metabolism and excretion of 2,4-dinitrotoluene in male and female Fischer 344 rats after different doses.
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不同剂量后2,4-二硝基甲苯在雄性和雌性Fischer 344大鼠中的代谢和排泄。
DOI：
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发表时间：
1981
影响因子：
3.9
通讯作者：
R. Long
中科院分区：
文献类型：
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作者：
D. Rickert;R. Long
雌性Fischer 344大鼠对2，4-二硝基甲苯（2，4-DNT）的肝癌效应的敏感性低于雄性大鼠。本研究比较了雄性和雌性大鼠经口给予10、35或100 mg/kg 14 C-2，4-DNT后2，4-DNT的代谢和排泄。所有给药后14 C的主要消除途径为尿液。在大鼠尿液中鉴别出4-（N-乙酰基）氨基-2-硝基苯甲酸（4Ac 2NBAcid）、2，4-二硝基苯甲酸（2，4-DNMBAcid）、2-氨基-4-硝基苯甲酸（2A 4 NBAcid）和2，4-二硝基苄醇葡糖苷酸（2，4-DNBAlcG）。这四种化合物占尿液中排泄的放射性的85%以上。与雄性大鼠相比，在10或35 mg/kg剂量下，雌性大鼠尿液中以2，4-DNBAlcG形式排泄的剂量百分比显著更高。两种性别动物的2，4-DNT代谢物尿排泄均显示出剂量依赖性变化。与10或35 mg/kg剂量组相比，100 mg/kg剂量组雄性以2，4-DNBAcid形式排泄的剂量百分比较小。与10或35 mg/kg剂量组相比，100 mg/kg剂量组雌性以2，4-DNBAcid和2，4-DNBAlcG形式排泄的剂量较少。2，4-DNT代谢或排泄的唯一性别差异足以解释对2，4-DNT致癌作用敏感性的性别差异，是雌性大鼠在10或35 mg/kg剂量下以2，4-DNBAlcG形式排泄的2，4-DNT百分比更高。
Female Fischer 344 rats are less susceptible to the hepatocarcinogenic effects of 2,4-dinitrotoluene (2,4-DNT) than males. This study is a comparison of the metabolism and excretion of 2,4-DNT in male and female rats after oral doses of 10, 35, or 100 mg of 14C-2,4-DNT per kg. The major route of elimination of 14C after all doses was the urine. 4-(N-Acetyl)amino-2-nitrobenzoic acid (4Ac2NBAcid), 2,4-dinitrobenzoic acid (2,4-DNMBAcid), 2-amino-4-nitrobenzoic acid (2A4NBAcid), and 2,4-dinitrobenzyl alcohol glucuronide (2,4-DNBAlcG) were identified in urine of rats. These four compounds accounted for greater than 85% of the radioactivity excreted in urine. Female rats excreted a significantly greater percentage of the dose in the urine as 2,4-DNBAlcG at doses of 10 or 35 mg/kg when compared to males. Both sexes showed dose-dependent changes in urinary excretion of 2,4-DNT metabolites. Males excreted a smaller percentage of the dose as 2,4-DNBAcid at 100 mg/kg than at 10 or 35 mg/kg. Females excreted less of the dose as 2,4-DNBAcid and 2,4-DNBAlcG at 100 mg/kg than at 10 or 35 mg/kg. The only sex difference in 2,4-DNT metabolism or excretion of sufficient magnitude to account for the sex difference in susceptibility to the hepatocarcinogenic effects of 2,4-DNT was the greater percentage of 2,4-DNT excreted as 2,4-DNBAlcG by female rats at 10 or 35 mg/kg.