Strategies to Protect the Health of Deployed U.S. Forces Assessing Health Risks to Deployed U.S. Forces: Workshop Proceedings (2000) / Chapter Skim
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7 Health Risks and Preventive Research Strategy for Deployed U.S. Forces from Toxicological Interactions Among Potentially Harmful Agents
7 Health Risks and Preventive Research Strategy for Deployed U.S. Forces from Toxicological Interactions Among Potentially Harmful Agents
Pages 150-182
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From page 150... ...
By doing so, it is implicit that potential health risks exist in deployments because of possible exposures to multiple chemicals, drugs, and biologics under stressful environmental and occupational conditions similar to those in the Persian Gulf War. This conclusion was reached based on the author's knowledge of toxicological interactions among chemicals and other agents and his assessment of the available literature information to date.
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Offers a preventive research strategy to DOD to avoid possible future Gulf War mnesses in deployed forces. The rationale, significance, and how-to 's for such a preventive research strategy are given in detail.
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Because this paper is to provide insight into health risks and a preventive research strategy for future deployed U.S. forces from toxicological interactions among potentially harmful agents, low dose is defined here as 0.2 LD50 or lower for any given chemical, drug, biological or physical agent.
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From page 153... ...
Therefore, multiple environmental and occupational stressors such as what deployed forces might face were not there. What would be the consequences if these hospital patients were also exposed to stressful environmental conditions?
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Third, because the real concern for environmental contamination is low-dose, long-term effects, acute and short-term toxicity studies cannot and should not be used to extrapolate to hazard identification for chronic toxicities. Finally, if environmental pollutants are active in any process that involves cascading amplification, such as hormonal effects or carcinogenic processes, they might cause toxicological interactions even at very low concentrations.
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In three NTP studies on the possible toxicological interactions between a 25-chemical mixture of groundwater contaminants and whole-body irradiation on hematopoiesis (Hong et al.
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Thus, receptor-mediated toxicity such as TCDD-Ah receptor interactions, as well as multistage carc~nogenes~s from environmental chemicals, should be considered as part of chem~cal-to-biological interactions. However, for assessing risks to deployed forces, the concern is about the probability of chemical in conjunction with biological agents such as vaccines or disease vectors causing synergistic adverse health consequences.
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1996a,b) had provided some insights to the possible mechanistic basis for the neurotoxic symptoms observed in the veterans afflicted with Gulf War Syndrome.
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suggested the symptoms of Gulf War Syndrome might be compatible with the interaction between multiple Thorium (Th) 2-inducing vaccinations and stressful circumstances.
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, and Jamal (1998~. BuCHE = butyrylcholinesterase; ~ DEET= N,N-diethyl-m-toluamide; MOPP = military op ¢, orations protective posture; NTE = neuropathy target In esterase; 0PIDP = organophosphate-induced delayed polyneuropathy; PB = pyridostigmine bromide; VX = ~ ~ nerve gas.
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From page 160... ...
Whether this summary of mechanistic basis for possible explanation of neurotoxicities in the Gulf War Syndrome is 100% in line with the latest advances in neurotoxicology is not the main issue. The significance is that a group of independent scientists came up with an explanation of the neurotoxicity observed in veterans with Gulf War Syndrome.
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From page 161... ...
However, in the context of the Gulf War Syndrome, multiple stressors might also include environmental hardship (extreme heat, poor resting conditions, poor food or waste intake, heavy and nonbreathable equipment and clothing, insect or other pests) , occupational hazard (dangerous tasks, injuries from work, exposure to fuels, burning oil field, possible nerve gases, radioactive residues)
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This point is taken into consideration later in the proposed preventive research strategy. Anthropogenic Stressors During Wars During the Persian Gulf War, oil wells were set on fire, which created pollution in disastrous proportion.
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This soldier's serum BuChE and recombinant atypical BuChE had far less binding affinity or sensitivity toward PB and other anti-ChEs. These authors concluded that genetic differences among BuChE variants might explain at least partially some of the long-term adverse consequences associated with the collection of symptoms of the Gulf War Syndrome.
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Systemic conditions characterized by chronic pain and fatigue include Chronic Fatigue Syndrome, fibromyalgia, somatoform disorders, and multiple chemical sensitivity (Clauw and Chrousos 1997~. Gulf War Syndrome and Sick Building Syndrome share considerable homology with these illnesses.
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from the Office of the Chairman, The Joint Chiefs of Staff, is any indication, DOD has only pushed forward in epidemiology study-related areas. Although epidemiological studies from past experiences provide useful information, they are generally after the fact, and they suffer from lack of sensitivity and the confounding problems of dealing with chemical mixtures or multiple stressors.
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Within each region, a list of the potential dangers military personnel might face regarding possible exposures to warfare agents, chemicals, environmental and physical stresses, diseases, pests, prophylactic drugs and biologics, and so on should be compiled and analyzed. Then, under the climatic conditions of each of these regions, animal studies should be carried out to detect at least the four major toxicity categories (i.e., immunotoxicity, developmental and reproductive toxicity, neurotoxicity, and carcinogenicity)
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Therefore, in neurotoxicity studies, a subset of experiments should be designed by neurobehavioral experimental toxicologists in conjunction with psychologists to assess psychological stress as a factor in the toxicological interactions among multiple stressors. As part of the short-term program, research efforts to learn maximally from the Persian Gulf War should also be encouraged.
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, among others, to detect and characterize interactions involving combinations of agents. The real strength of this approach is that relatively few data are required to implement it.
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The composition for this board should include, at a minimum, scientific expertise in the areas of neurotoxicology, immunotoxicology, reproductive and developmental toxicology, carcinogenesis, statistics, computer modeling, toxicological interactions, and multiple stressors. Other types of expertise could be added as such needs arise.
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1998~? New Tools: Computer Modeling and Molecular Biology Having actively engaged in the research area of the toxicology of chemical mixtures for the last 16 years or so, I have long since become resigned to the fact that the conventional animal toxicological testing methods would not work for chemical mixtures (Yang 1996,1997; Yang et al.1998~.
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Such a developmental strategy will enable us to handle extremely complex situations involving multiple stressors. Difficulties in Assessing and Predicting Agent Interactions Presently, there is some success in predicting toxicological interactions of simple chemical mixtures using the integrated approach of computer modeling and mechanistic toxicology (Andersen and
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From page 172... ...
To overcome these limitations, the next breakthrough must be based on the thorough understanding of the fundamental biology involved in the disruption of homeostasis and the development of a computer model able to handle very complex situations. Opportunities on the Horizon Thinking positively and considering that the complexity of issues related to chemical mixtures and multiple stressors are challenges for our intellectual capability, there are many opportunities to be explored and utilized.
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The first issue is related to the balance between long-term investment versus urgency for answers. The health problems related to the Gulf War Syndrome and the potential adverse health effects under possible conditions for future deployment of U.S.
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2. Because the Abou-Donia studies did not establish dose-response relationships, are they applicable to interpreting the Gulf War Syndrome in Gulf War veterans?
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DEET is used as an insect repellent against mosquitoes, biting flies, ticks, and other insects. Because there are no reliable estimates of DEET usage among service personnel during the Persian Gulf War, the Abou-Donia studies used a 1986 National Institute for Occupational Safety and Health study of the employees in the Everglades National Park to estimate a reasonably close dosage.
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Given our initial total ignorance of the Gulf War Syndrome and thinking about the tasks ahead of us, I would rather have the knowledge Abou-Donia et al.
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1997. Evaluation of neuromuscular symptoms in veterans of the Persian Gulf War.
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1998. Toxicological evaluation and risk assessment of chemical mixtures.
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1998. Gulf War Syndrome a model for the complexity of biological and environmental interaction with human health.
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1997. Illness in Gulf War Veterans.
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1997. Gulf War Syndrome: is it due to a systemic shift in cytokine balance towards a Th2 profile?
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1997. Toxicologic interactions of chemical mixtures.
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