Price C J, Tyl R W, Marks T A, Paschke L L, Ledoux T A, Reel J R
Fundam Appl Toxicol. 1985 Oct;5(5):948-61. doi: 10.1016/0272-0590(85)90176-9.
Technical grade dinitrotoluene (DNT) was administered by gavage (po) to timed-pregnant Fischer 344 rats on Gestational Days (gd) 7 through 20. Mortality rates for the DNT (14, 35, 37.5, 75, 100, or 150 mg/kg/day) groups were 4.5, 7.7, 0.0, 0.0, 4.3, and 46.2% of treated females, respectively. No deaths occurred in the positive control (hydroxyurea, 200 mg/kg/day) or vehicle control (corn oil) groups. At sacrifice on gd 20, the hematological profile for dams in the 100-mg/kg/day group exhibited characteristic signs of DNT toxicity. Treatment-related increases in maternal relative liver and spleen weight (% body weight), and a dose-related decrease in absolute maternal weight gain during gestation (i.e., minus gravid uterine weight) were observed across all DNT groups. A notable increase in prenatal mortality occurred at the high dose (16.8% resorptions or late fetal deaths per litter for controls vs 49.6% for DNT), but but did not reach statistical significance. No statistically significant effects on fetal growth or morphological development as a result of DNT treatment were observed. Hydroxyurea produced mild hematoxicity in dams and fetuses. Effects of hydroxyurea on fetal growth and morphological development included decreased fetal body weight and crown-rump length, and an increased percentage of malformed fetuses (30% per litter). In conclusion, DNT was not found to be teratogenic following oral administration to Fischer 344 rats; embryo/fetal toxicity was observed only at a dose which also produced 46.2% maternal mortality.
将工业级二硝基甲苯（DNT）经口灌胃给予妊娠第7至20天的Fischer 344定时妊娠大鼠。DNT各剂量组（14、35、37.5、75、100或150毫克/千克/天）的死亡率分别为接受治疗母鼠的4.5%、7.7%、0.0%、0.0%、4.3%和46.2%。阳性对照组（羟基脲，200毫克/千克/天）或溶剂对照组（玉米油）未出现死亡情况。在妊娠第20天处死时，100毫克/千克/天组母鼠的血液学指标呈现出DNT毒性的特征性迹象。在所有DNT组中均观察到与治疗相关的母鼠相对肝脏和脾脏重量增加（占体重百分比），以及妊娠期间母鼠绝对体重增加（即减去妊娠子宫重量）的剂量相关减少。高剂量组出现了显著的产前死亡率增加（对照组每窝吸收或晚期胎儿死亡为16.8%，DNT组为49.6%），但未达到统计学显著性。未观察到DNT处理对胎儿生长或形态发育有统计学显著影响。羟基脲在母鼠和胎儿中产生了轻度血液毒性。羟基脲对胎儿生长和形态发育的影响包括胎儿体重和顶臀长度减少，以及畸形胎儿百分比增加（每窝30%）。总之，对Fischer 344大鼠经口给药后未发现DNT具有致畸性；仅在产生46.2%母鼠死亡率的剂量下观察到胚胎/胎儿毒性。
