Increased Vulnerability to Soman Exposure in Aged Compared to Adult F344 Rats
Technical Report,01 Oct 2012,01 Oct 2014
U.S.Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground United States
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To determine the susceptibility of aged individuals to chemical warfare nerve agents CWNAs, we evaluated the 24-hour median lethal dose LD50 of soman GD in adult 2 months of age and aged 18 months of age male F344 rats, Aged rats proved more sensitive to GD-induced lethality with an LD50 of 50.0 mugkg 95 CI 63.8-78.00. To determine the etiology of theses differences, we measured whole blood and brain acetylcholinesterase AChE as well as plasma carboxylesterase CaE activity in nave aged and adult rats. Whole blood AChE revealed no differences however, an 18 decrease in baseline plasma CaE activity was observed in aged rats compared to adult rats. Brain AChE was modestly reduced in aged compared to adult rats in the frontal cortex 820, hippocampus 89, striatum 92, thalamus 91, and pons 83. Furthermore, aged rats showed a significantly greater sensitivity to the toxic effects of GD, displaying seizures and higher mortality rates at lower doses compared to adult rats. This increased sensitivity of aged rats to the toxic and lethal effects of GD has implications for dosing and efficacy of medical countermeasures in aged populations.