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EC number: 204-500-1 | CAS number: 121-82-4
In the rat, the distribution of RDX was essentially unaffected by route of administration or by dosage. The volume of distribution, 2.2 L/kg and the tissue/plasma ratios during the first 24 hr indicate that RDX does accumulate to some extent in all tissues examined.
However, RDX was not preferentially found in lipid-rich tissues of the central nervous system. In fact, the kidney consistently contained the highest concentration of RDX, but this concentration was at most only two to three-times the RDX content of the heart or brain.
While the RDX concentration in most tissues was fairly stable between 2 and 24 hr following oral administration, liver concentration varied widely, and the liver contained greater amounts of radioactivity than expected based on its RDX content, indicating the presence of RDX metabolites in this organ.
In these experiments, RDX was either given as a saline slurry or dissolved in DMSO. Rats dosed by gavage with 100 mg RDX/kg using a coarse, granular preparation of RDX did not convulse, but 10 rats dosed with 50 mg/kg using a finely powdered preparation all convulsed and two died. Approximately 20% of the rats in the metabolism studies died after being dosed by gavage with 50 mg of [14C]RDX/kg in DMSO solution. The acute LD50 of RDX was dependent on the physical form of the RDDX and on the method used to suspend or dissolved it.
Regarding these present experiments, the oral toxicity of the more finely powdered RDX, whose saline slurry was more stable, was equivalent to the oral toxicity of DMSO solutions of RDX. Both had LD50 values of about 100 mg/kg. The LD50 of the coarse, granular RDX was approximately 300 mg/kg. Differences in toxicity of these preparations were mirrored by the plasma RDX concentrations reached in rats dosed with different particle size RDX. Plasma RDX at 24 hr after a dose of 100 mg of coarse, granular RDX/kg was 3.04 µg/mL, while it reached 4.7 µg/mL after dose of only 50 mg of finely powdered RDX /kg.
Conclusions as to the distribution of RDX and its uptake and elimination kinetics are, however, equivalent regardless of how the RDX was prepared for dosing. Plasma RDX concentrations reached a dose-dependant plateau within several hours, maintained it for 24 hr and then declined over the next 2 days. Although qualitative comparisons between experiments with different RDX preparations should not be affected, quantitative comparisons between such experiments should be avoided if possible.
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