Subchronic and Chronic Toxicity Studies of 2,4-Dinitrotoluene. Part II. CD® Rats

Abstract

Subchronic and chronic toxicities of 2,4-dinitrotoluene were studied in CD® rats. Feeding of 2,4-dinitrotoluene for 13 weeks at a low dose of 34 mg/kg per day in males and 38 mg/kg per day in females caused depressed weight gain. The middle dose of 93 and 108 mg/kg per day, respectively, was toxic, caused reticulocytosis and splenic hemosiderosis, and decreased spermatogenesis. The high dose of 266 and 145 mg/kg per day, respectively, was more toxic and lethal. Some rats had widespread and stiff-legged gaits and demyelination in the cerebellum and brain stem. After feeding up to 2 years, the low dose (0.57 and 0.71 mg/kg per day, respectively) caused no apparent toxic effects. The middle dose (3.9 and 5.1 mg/kg per day, respectively) was toxic; the high dose (34 and 45 mg/kg per day) was more toxic and shortened the life span. Target organs included the blood (toxic anemia), the liver (hepatocellular carcinoma), the testis (atrophy and depression of spermatogenesis), the connective tissue in males (fibromas), the mammary tissue in females (fibroadenomas), and the neuromuscular system in some rats.

Toxicity Assessment of 4-Amino-2-Nitrotoluene

“…This may be due to rats' reduced food consumption of feed containing 4A2NT and toxic effect of test chemical (Tables 6 and 7). The other reductive metabolite, 2A4NT, in subchronic toxicity study also showed decreased body weight gain in diet up to 169 mg/kg/d for male and female rats and 128.7 for male and 136.6 mg/kg/d for female mice 5 The subchronic study hematological results showed decreases in HGB, HCT, and RBC levels in male and female rats, suggestive of anemia that were also reported with parent compounds 2,4-DNT in rats and mice of subchronic toxicity 19,20 and other nitroaromatic compounds such as 2,4,6-trinitrotoluene (TNT) 21,22 and 1,3,5-trinitrobenzene (TNB). 23,24 There were no biologically meaningful differences in the hematological parameters studied.…”

Simultaneous phosphorus, nitrogen and dinitrotoluene removals in batch anaerobic/anoxic/aerobic sequentials

“…The amino-nitrotoluenes were intermediates in anaerobic DNT transformation, but the final products were not clearly identified [8]. The toxicity tests performed using Mutatox and green algae bioassays have confirmed that the inter metabolite products of nitroaromatic organics released under anaerobic conditions are very toxic [8,11].…”

Wildlife Toxicity Assessment for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene

“…No effects on serum IgE were observed [19,30]. The mid-dose animals had a greater decrease in weight gain, reticulocytosis, hemosiderosis in the spleen, and decrease or cessation of spermatogenesis.…”

“…Occasional neurological symptoms, such as straddling gait, were observed in some high-dose rats but without accompanying histopathological lesions [30,34]. Toxicity occurred in the mid-dose animals and included anemia, decreased weight gain, indicators of liver toxicity, and incidences of mammary tumors.…”