Biomarkers of oral exposure to 3-nitro-1,2,4-triazol-5-one (NTO) and 2,4-dinitroanisole (DNAN) in blood and urine of rhesus macaques (Macaca mulatta)

Abstract

The U.S. Department of Defense is using the chemicals 2,4-dinitroanisole (DNAN) and 3-nitro-1, 2,4-triazol-5-one (NTO) in new munitions development. In a screen for biomarkers of exposure, these compounds were measured in urine and blood of male rhesus monkeys after oral doses. NTO peaked at 4 h, with urinary concentrations at least 100-fold higher than that of blood or serum while 4-dinitrophenol (DNP), a metabolite of DNAN, appeared in blood at concentrations 10- to 20-fold higher than the parent compound. For human exposure monitoring, urine is optimal for NTO while the metabolite DNP in blood is best for DNAN.

• 2,4-dinitroanisole
• 2,4-dinitrophenol
• 3-nitro-1,2,4-triazol-5-one
• insensitive munitions
• rhesus

Acknowledgements

Special thanks to LTC William Smith, Mr Joseph Gruver and all the technicians of the WRAIR Large Animal Medicine Branch and Veterinary Surgery Branch for their generous and outstanding support. Grateful thanks to Katrina Keller and Steve Tebin at PHC for chemical analysis. Our colleague and friend Mike Hable passed away on April 2, 2013 during the writing of the manuscript.