Gulf War and Health Volume 8: Update of Health Effects of Serving in the Gulf War (2010) / Chapter Skim
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APPENDIX A: CHOLINESTERASE INHIBITORS AND MULITSYMPTOM ILLNESSES
APPENDIX A: CHOLINESTERASE INHIBITORS AND MULITSYMPTOM ILLNESSES
Pages 265-284
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From page 265... ...
This appendix reviews some of the known health effects that can result from these potential exposures and addresses the evidence potentially linking those exposures to multisymptom illness, including what is often called Gulf War illness. This appendix discusses how Gulf War veterans might have been exposed to cholinesterase inhibitors, the physiologic and toxicologic actions of these chemicals, and reviews some of the studies that have attempted to link various chemical agents to symptoms indicative of cholinesterase inhibition of veterans.
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. EXPOSURES TO CHOLINESTERASE INHIBITORS AND OTHER PESTICIDES DURING THE GULF WAR Pesticides Pesticides are defined by the federal Fungicide Insecticide Fumigant Rodenticide Act as any substance that kills, repels, or mitigates a pest.
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PB was used as a prophylactic antidote for exposure to nerve gas, which was known to have been previously used by Iraqi forces. The most complete documentation of the use of pesticides, cholinesterase inhibitors, and PB pills by Gulf War veterans was conducted by the RAND Corporation for the Department of Defense (DoD)
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. PB tablets were provided by the DoD to military personnel in the Gulf War theater as a prophylactic against cholinesterase-inhibiting nerve gas.
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The time during which nerve gas may have been released from Khamisiyah is uncertain because there were aerial attacks as well as ground detonations of explosives at this site. No reports of acute symptoms among potentially exposed military personnel have been linked to the nerve gas relesases from the Khamisiyah demolition.
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. Neurological and neuropsychological tests of South African workers exposed to organophosphate pesticides also found no association between history of chronic organophosphate exposure and test performance; however, previous organophosphate poisoning was predictive of lowered test performance (London et al., 1998)
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who could have been but were not deployed to the Gulf were included for comparison. There was no adjustment for potential confounders in the analysis, and Gulf War veterans were significantly older, taller, heavier, more likely male, and had higher diastolic blood pressure than the nondeployed counterparts.
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Job demand factors such as "occasional or frequent demand of high degrees of concentration, dissatisfaction with the physical work environmental, and unwillingness from immediate superiors to listen to one's problems were significant predictors of neuropsychological symptoms in a multivariable model." Among selfreported physical factors that remained significantly associated with neuropsychological factors after adjusting for confounders in a logistic model were "bathing in or drinking contaminated water, exposure to depleted uranium, contact with dead animals, and burning of waste or manure." An analysis of the prevalence of clusters of neuropsychological symptoms showed that physicochemical factors interacted with psychological factors in predicting symptoms; however, the physicochemical factor alone was not predictive of symptoms. Insecticides and use of lotions or sprays, which were significant in bivariate analysis, were no longer significant in the multivariate modeling.
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Depending on the multivariate analytic approach, there were weak associations between Gulf War illness and the following: • being exposed to fumes from munitions, • pesticide exposure, • drinking contaminated water, • being exposed to sandstorms, • seeing someone killed,
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The survey was mailed before some of the Gulf War veterans received notification of possible nerve gas exposure from the Khamisiyah detonation. Some 11,441 veterans responded to the questionnaire.
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; in each region, there was evidence of neuronal death and astrogliosis. The model developed in the Friedman report has obvious relevance to understanding how brief exposures to low doses of intoxicants might have unexpected adverse effects on the CNS in Gulf War veterans.
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To the extent that multisymptom illness in Gulf War veterans might be a consequence of exposure to toxins such as cholinesterase inhibitors, a potential explanation for this nonuniformity is the high degree of polymorphism in the proteins that detoxify a wide range of intoxicants. Foremost among these are the paroxonases, three esterases that metabolize oxidized lipids (PON1, 2, and 3)
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reviewed studies found through a search of the National Library of Medicine's PubMed database, using the key words "Gulf War," "epidemiology," and "acetylcholinesterase inhibitors." She concluded that these studies -- combined with veterans' self-reports of exposures in the Gulf War theatre (including those cited earlier in this report) , and studies of people occupationally exposed to cholinesterase inhibitors -- supported, through "triangular evidence," a causative association between exposure to cholinesterase inhibitors during deployment in the Gulf War and Gulf War illness.
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From page 278... ...
THE ROLE OF CHOLINESTERASE INHIBITORS AND PESTICIDES IN MULTISYMPTOM ILLNESS While pesticide and PB use appear to have been widespread during the Gulf War, there is no evidence that Gulf War veterans suffered acute toxicity from either nerve gas or pesticides on a wide scale during and after the conflict. Except for an association with Parkinsonism, there remains substantial doubt as to whether long-term illness results from low-level chronic exposure to pesticides, including cholinesterase inhibitors.
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From page 279... ...
Given the scarcity of evidence supporting the association of chronic multisymptom illness with low-level pesticide exposure in chronically exposed populations such as the Agricultural Health Study population; the lack of clear, persistent CNS effect in animal studies of cholinesterase inhibitors and pesticides; the potential for bias in studies that base conclusions on self-reports of illness and exposure; and the lack of sufficient weight of evidence from studies of Gulf War veterans; the Update committee finds insufficient support for the conclusion that pesticides, PB, insect repellents, or combinations thereof are responsible for multisymptom illness seen in Gulf War veterans. REFERENCES Abdel-Rahman, A., A
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2008. Acetylcholinesterase inhibitors and Gulf War illnesses.
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arylesterase activity with neurologic symptom complexes in Gulf War veterans. Toxicology and Applied Pharmacology 157(3)
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2000. Deployment stressors and a chronic multisymptom illness among gulf war veterans.
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2002. Risk factors for multisymptom illness in US Army veterans of the Gulf War.
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