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

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.

Dinitrotoluene exposure in the copper mining industry and renal cancer: a case-cohort study

“…Our finding of elevated renal cancer risks among DNT-exposed workers is in accordance with previous evidence from animal experiments8 10 19 20 and a few epidemiological studies 4––6. The findings of Brüning et al 6 who demonstrate a dose-dependent increase in tubular damage by DNT exposure point to a biologically plausible pathological pathway from DNT exposure to cancerogenesis.…”

Biomarkers of Exposure, Effect, and Susceptibility in Workers Exposed to Nitrotoluenes

“…In summary, the positive test of protein and glucose in urine could be caused from tubular or glomerular damage by the nitrotoluenes. The nephrotoxicity of nitrotoluenes has been documented in an earlier study in miners exposed to DNT (3) and in rodents dosed 2NT (37) and 24DNT (38). The high levels of alkaline phosphatase and the low level of serum proteins could be a sign of hepatotoxic effects.…”

Cancer of the urinary bladder in highly exposed workers in the production of dinitrotoluenes: a case report

“…Technical dinitrotoluene (consisting of 2,4-and 2,6-dinitrotoluene isomers) has been clearly established as a carcinogen in rodents (Hong et al 1985;Leonard et al 1987). Hence, the question arises of human carcinogenic risks associated with low doses of environmental and occupational exposures which occur nowadays.…”

“…2,4-Dinitrotoluene is carcinogenic in experimental animals (Hong et al 1985;Leonard et al 1987). Both technical isomers, 2,4-and 2,6-dinitrotoluene, are mutagenic in Salmonella typhimurium TA98 strains with high nitroreductase and/or O-acetyltransferase activity (Sayama et al 1998), and the mechanisms of genotoxicity have been discussed.…”