title: Oral Toxicity of 2,4-Dinitroanisole in Rats.
abstract: 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.
authors.affiliation: Army Public Health Center, Toxicology Directorate, Aberdeen Proving Ground, MD, USA emily.m.lent.civ@mail.mil.
authors.forename: Emily May
authors.initials: EM
authors.lastname: Lent
authors.affiliation: Army Public Health Center, Toxicology Directorate, Aberdeen Proving Ground, MD, USA.
authors.forename: Lee C B
authors.initials: LC
authors.lastname: Crouse
authors.affiliation: Army Public Health Center, Toxicology Directorate, Aberdeen Proving Ground, MD, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallace
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000840:Anisoles / Q000633:toxicity*; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D053834:Explosive Agents / Q000633:toxicity*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006486:Hemosiderosis / Q000139:chemically induced; D008297:Male; D020258:Neurotoxicity Syndromes; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000473:pathology; D059551:Toxicity Tests, Subacute; D059550:Toxicity Tests, Subchronic
chemical_list: D000840:Anisoles; D053834:Explosive Agents; C539360:2,4-dinitroanisole
keywords: DNAN; anemia; dinitroanisole; insensitive munition; neurotoxicity