Teratologic Evaluation of Dinitrotoluene in the Fischer 344 Rat

Abstract

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.