The Subchronic Oral Toxicity of 2,4-Dinitroanisole (DNAN) in Rats
Abstract
To provide information important for protecting the health of military and civilian personnel, three studies were conducted to assess the toxicity of 2,4-dinitroanisole (DNAN). 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-day. Likely owing to its conversion to 2,4-DNP, an inhibitor of mitochondrial energy homeostasis, DNAN treatment caused an apparent increase in metabolism, leading to reduced feed conversion efficiency and reduced body mass gain in males. Anemia, splenic enlargement, hemosiderosis, and extramedullary hematopoeisis (EMH) indicated that the blood is a target organ for DNAN, with females being more sensitive than males. DNAN was a testicular toxicant, causing decreased mass of the testes and epididymides, as well as degeneration and atrophy of the testicular seminiferous tubules and epidymal aspermia. Stereotypical behavior in males, gait irregularities, and cerebellar glial lesions indicated that DNAN is neurotoxic. A BMDL10 of 2.3 mg/kg-day was derived based on EMH in females.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2012
- Accession Number
- ADA563070
Entities
People
- Emily M. Lent
- Lee C. Crouse
- Shannon M. Wallace
- Theresa Hanna
Organizations
- United States Army Public Health Command