Subchronic and Chronic Toxicity Studies of 2,4-Dinitrotoluene. Part III. CD-1® Mice

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Abstract
Subchronic and chronic toxicities of 2,4-dinitrotoluene (2,4-DNT) were evaluated in CD-1® mice. 2,4-DNT was more toxic to males than to females. Male mice fed 47 mg/kg per day or 137 mg/kg per day for 13 weeks gained less weight. However, females fed 52 or 147 mg/kg per day had no adverse effects. Feeding of 413 mg/kg per day for males or 468 mg/kg per day for females lowered feed consumption, depressed body weight, and caused mild anemia and mild hepatocellular dysplasia in both sexes and mild testicular degeneration in males. Both males and females were fed an average of 14 (low dose), 95 (middle dose), or 898 mg/kg per day (high dose) for up to 24 months. In males, there was a high incidence of epithelial renal tumor and hepatocellular dysplasia in all dose groups, Incidence of testicular atrophy was increased in the middle-and high-dose males. In addition, the high dose caused toxic anemia and death. In females, the high dose was associated with toxic anemia, hepatocellular dysplasia, nonfunctional follicle with a lack of corpora lutea, an effect analogous to the testiclar atrophy in males, and death. A generalized pigmentation, probably of 2,4-DNT metabolite origin, was seen in many tissues of especially the high-dose males and females.