Oral Toxicity of 2,4-Dinitroanisole in Rats

Subacute and subchronic studies were conducted to assess the toxicity of 2,4-dinitroanisole (DNAN) and to provide information important for protecting the health of military and civilian personnel. In the subchronic study, male and female Sprague-Dawley rats were dosed with DNAN via oral gavage at 0, 1.25, 5, 20, and 80 mg/kg/d. Likely owing to its conversion to 2,4-dinitrophenol, an inhibitor of energy homeostasis, DNAN caused an apparent increase in metabolism, leading to reduced feed efficiency ratios and body mass gains in males. Anemia, splenic enlargement, hemosiderosis, and extramedullary hematopoiesis indicated blood as a target organ, with females more sensitive than males. The DNAN was a testicular toxicant, causing decreased mass of testes and epididymides, as well as degeneration and atrophy of testicular seminiferous tubules and epididymal aspermia. Stereotypical behavior in males, gait irregularities, and cerebellar lesions indicated that DNAN is neurotoxic. Splenic enlargement, anemia, testicular toxicity, and neurotoxicity occurred only at or near lethal doses in the subchronic study.