Abstract
The study reported herein examined the metabolism of 14C‐labeled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) resulting from a single oral gavage of 5 ml/kg to male and female Yucatan miniature pigs (43 mg/kg, 56 μCi/kg in 0.5% carboxymethylcellulose in water). Blood, urine, and feces were collected at selected times of 1, 6, 12, and 24 h postdose. At 24 h postdose, liver samples were collected. Blood, plasma, liver, and excreta were analyzed for total RDX-derived radioactivity and metabolites were identified. Urine was the major route of elimination of 14C-RDX-derived radioactivity in both males and females. Relatively low levels of radioactivity were found in gastrointestinal contents and in feces, suggesting nearly complete absorption of 14C-RDX following an oral dose. Analysis of urine by liquid chromatography–mass spectrometry (LC/MS) identified quantifiable levels of two ring-cleavage metabolites, 4-nitro-2,4-diazabutanal and 4‐nitro-2,4-diaza-butanamide, as well as parent RDX. The 4-nitro-2,4-diazabutanal, was seen in earlier studies of aerobic metabolism of RDX. The 4-nitro-2,4-diaza-butanamide, an amide, was not previously reported but was tentatively identified in this study. Analysis by a more sensitive method (LC/MS/MS) also showed trace amounts of the RDX metabolites 1-nitroso-3, 5-dinitro-1, 3, 5-triazacyclohexane (MNX) (in both male and female urine) and 1-nitro-3, 5-dinitroso-1,3,5-triazacyclohexane (DNX) (in male urine). Analysis of plasma by LC/MS/MS also revealed quantifiable levels of RDX and trace levels of MNX, DNX, and 1,3,5,-trinitroso-1,3,5-triazacyclohexane (TNX). None of the liver extracts showed quantifiable levels of RDX or any identifiable metabolites. Most of the radioactivity was in the form of water-soluble high-molecular-weight compounds. RDX when given orally to pigs was rapidly metabolized by loss of two nitro groups followed by ring cleavage.
The views, opinions, and/or findings presented in this publication should not be construed as official Department of Defense position, policy, or decision unless designated by other official documentation. This work was presented in part at the 45th Annual Meeting of Society of Toxicology, March 5–9, 2006, at San Diego, CA.
Notes
Levine, B. S., Furedi-Machacek, E. M., Rac, V. S., Gordon, D. E., and Lish, P.M. 1983. Determination of the chronic mammalian toxicological effects of RDX: Twenty-four month chronic toxicity/carcinogenicity study of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in Fischer 344 rat. Phase V, Vol. 1. Contract DAMD 17–79-C-9161. IIT Research Institue, Chicago. ADA 160774. U.S. Army Medical Research and Development Command, Fort Detrick, MD.
Lish, P. M., Levine, B. S., Furedi-Machacek, E. M., Sagartz, E. M., and Rac. Y. S. 1984 Determination of the chronic mammalian toxicological effects of RDX: Twenty-four month chronic toxicity/carcinogenicity study of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in the B6C3F1 hybrid mouse. Phase VI, Vol. I. Contract DAMD 17–79-C-9161. IIT Research Institue, Chicago. ADA 160774. U.S. Army Medical Research and Development Command, Fort Detrick, MD