RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) is a synthetic, high-impact, relatively stable explosive that has been in use since WWII. Exposure to RDX can occur in occupational settings (e.g., during manufacture) or through the inadvertent ingestion of contaminated environmental media such as groundwater. The toxicology of RDX is dominated by acute clonic-tonic seizures at high doses, which remit when exposure is removed and internal RDX levels decrease. Subchronic studies have revealed few other measurable toxic effects. The objective of this study was to examine the acute effects of RDX on the mammalian brain and liver using global gene expression analysis based on a predetermined maximum internal dose. Male Sprague-Dawley rats were given a single, oral, nonseizure-inducing dose of either 3 or 18 mg/kg RDX in a gel capsule. Effects on gene expression in the cerebral cortex and liver were assessed using Affymetrix Rat Genome 230 2.0 whole genome arrays at 0, 3.5, 24, and 48 h postexposure. RDX blood and brain tissue concentrations rapidly increased between 0 and 3.5 h, followed by decreases at 24 h to below the detection limit at 48 h. Pairwise comparison of high and low doses at each time point showed dramatic differential changes in gene expression at 3.5 h, the time of peak RDX in brain and blood. Using Gene Ontology, biological processes that affected neurotransmission were shown to be primarily down-regulated in the brain, the target organ of toxicity, while those that affected metabolism were up-regulated in the liver, the site of metabolism. Overall, these results demonstrate that a single oral dose of RDX is quickly absorbed and transported into the brain where processes related to neurotransmission are negatively affected, consistent with a potential excitotoxic response, whereas in the liver there was a positive effect on biological processes potentially associated with RDX metabolism.

The procedures currently used by the U.S. Army Center for Health Promotion and Preventive Medicine (USACHPPM) for the analysis of energetics and related compounds in water and soils are presented. These procedures are based on the use of isoamyl acetate to extract the analytes of interest from their environmental matrices with subsequent analysis using gas chromatography with electron capture detection. The suite of compounds included are those that have been of environmental significance for years (such as 2,4,6-trinitrotoluene, hexahydro-1,3,5-trinitro-1,3,5-triazine, and dinitrotoluenes) and are the subject of several U.S. Environmental Protection Agency SW-846 methods. The procedures presented in this study are the product of years of development and refinement of methods used for the analysis of many real-world samples by the USACHPPM explosives analysis laboratory. The development, performance, advantages, and details of these procedures are described. The extension of these methods to the analysis of other media is also briefly discussed.

A method has been developed to determine the concentration of nitroaromatics and nitramines in drinking water at levels below those previously achieved by gas chromatography. The nitroaromatics and nitramines are extracted from water using toluene and isoamyl acetate, respectively. The extracts are analyzed via a gas chromatograph equipped with a DB-1301 widebore fused-silica capillary column and an electron capture detector. Method detection limits of 0.003 micrograms/L for 2,6-dinitrotoluene (2,6-DNT), 0.04 micrograms/L for 2,4-dinitrotoluene (2,4-DNT), 0.06 micrograms/L for 2,4,6-trinitrotoluene (TNT), 0.3 micrograms/L for cyclotrimethylenetrinitramine (RDX), and 6.0 micrograms/L for cyclotetramethylenetetranitramine (HMX) have been obtained using this method.

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