PM10 Mechanisms of Toxic Action
Exhibit Hall
8:00 AM - Monday
(PM160) Evaluating oxidative stress as a potential mechanism of toxic action for RDX and RDX-related compounds.
Walski, K1, Inouye, L2, Ang, CY1, 1 ASI, Vicksburg, MS, USA2 USACE-ERDC, Vicksburg, MS, USA
ABSTRACT- The explosive compound, RDX, and its nitroso breakdown products have been detected in environmental media. Acute studies indicate that the LD50s of RDX and its mono-nitroso product (MNX) are similar and that RDX toxicity diminishes as more nitro groups are converted to nitroso groups. Literature data indicates that the kidney, liver, and brain have the highest RDX concentrations after intra-peritoneal dosing in rats; RDX concentrations in the brain and liver continue to increase over a 90-day period while that in the kidney remains unchanged after chronic exposure by gastric gavage. In this study, we examined the cell viability and antioxidant status of the HK-2 (kidney), H2.35 (liver) and CTX-TNA2 (brain) cells exposed to RDX and selected RDX breakdown products. Cell viability was not affected in the liver and kidney cells. However, low levels of cytotoxicity were observed in the brain cells, only at doses at or exceeding 30 mg/L; at 30 mg/L, cell viability was reduced ∼20% by RDX and ∼12% by MNX, but was not altered by the trinitroso derivative (TNX), indicating that toxicity to these cells decreases as RDX is degraded. Basal levels of glutathione and antioxidant enzymes were higher in the liver as compared to those of kidney and brain cells, possibly providing better protection against toxicity in the liver. Data on antioxidant status indicates that while the liver cells respond to the tested compounds by either maintenance of high levels or induction of antioxidants and antioxidant enzymes, the brain cells are less capable of inducing antioxidant production. While this data cannot definitively link oxidative stress to cell death upon exposure to RDX and its breakdown products, it does help elucidate potential mechanism behind differential tissue sensitivity.
Key words: glutathione, superoxide dismutase, catalase, cell lines