| Toxicity of the Organophosphate Chemical Warfare Agents GA, GB, and VX: Implications for Public Protection Nancy B. Munro, Kathleen R. Ambrose, and Annetta P. Watson Health Sciences Research Division, Oak Ridge National Laboratory, Oak
Ridge, TN 37831-6383 USA Abstract
The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxcity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent releaase, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. Key words: anticholinesterase, Chemical Stockpile Disposal Program, chemical warfare agent, GA, GB, nerve agent, organophosphate, organophosphorus-induced delayed neuropathy, sarin, tabun, VX. Environ Health Perspect 102:18-38 (1994) Address correspondence to N.B. Munro, Health Sciences Research Division, Oak Ridge National Laboratory, PO Box 2008, Oak Ridge, TN 37831-6383 USA. We acknowledge the contributions of Frederick Sidell, who provided expert consultation and reviewed the sections on acute nerve agent toxicity. Mohamed Abou-Donia, Thomas Bucci, Nada Grujic Chang, Jack Dacre, Marvin Goldman, Sanford Leffingwell, Dennis Opresko, and Barry Wilson also provided valuable information and/or review and comments. We acknowledge with much appreciation the special contributions of Jeffrey Ryman (Figure 1) and Emily Copenhaver (Figures 2 and 3) in producing electronic versions of these figures. This research was sponsored in part by the Office of the Program Executive Officer, Program Manager for Chemical Demilitarization, Department of the Army, under Interagency Agreement 40-1354-83, and by the Office of the Assistant Secretary of the Army under Interagency Agreement 1769-1354-A1 with Oak Ridge National Laboratory under Martin Marietta Energy Systems, Inc. contract DE-AC05-84OR21400 with the U.S. Department of Energy. Received 3 November 1992 ; accepted 15 November 1993.
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