Review of the Department of Defense Research Program on Low-Level Exposures to Chemical Warfare Agents (2005)

Historically, research related to chemical warfare agents (CWAs) has focused on the significant battlefield threat. This has meant exposures to certain CWAs, such as organophosphate nerve agents and sulfur mustard, at concentrations high enough to produce immediate health impacts. Therefore, there are limited data on effects associated with exposure to lower concentrations of CWAs. On the basis of experiences during and after Operation Desert Storm and with increased emphasis on force health protection, concerns related to the potential health effects resulting from exposure to CWAs at lower concentrations and for longer durations than those needed to produce frank effects at high concentrations became a higher priority for the U.S. Department of Defense (DOD). The threat of low-level CWA exposures includes the following:

• Downwind from or on the periphery of a CWA attack or CWA release.

• Entry into an area after a CWA.

• Exposure to CWA during decontamination operations or from partially decontaminated materiel, supplies, or surfaces.

• Exposure after deliberate (but ineffective) destruction of CWA munitions.

The DOD Low-Level Chemical Working Group was formed to develop research programs within the DOD Chemical and Biological Defense Program to understand the health effects of exposure to low-level CWAs, to defend against such exposure, to prevent unnecessary duplication of research efforts, and to focus and direct scientific investigations to address operational issues. The DOD Master Research Plan (Research Plan) developed for this research effort addresses research on operationally relevant performance decrements and delayed adverse health effects that potentially may be associated with low-level exposures to CWAs.

The objective of the Research Plan is to fully characterize the toxicity of CWAs to enable rational military decision making for issues related to doctrine, organization, training, materiel, leadership, personnel and facilities; that plan also addresses research on operationally relevant performance decrements. The Research Plan includes, but is not limited to, scientifically credible data necessary to answer questions about decision making in operational risk management; the range of sensitivities needed for detectors, sensors, and alarms; the efficiency needed for individual and collective protection systems; the effectiveness of decontamination measures and procedures; restoration of normal military operations; return of previously contaminated materiel to “normal” use; adverse long-term health sequelae; as yet unrecognized outcomes of exposure; and medical diagnostics, prophylaxes, pretreatments, and treatments (DOD 2003). The purpose of the DOD Research Plan is not to outline a research program to investigate Gulf War illnesses.

This Research Plan describes DOD’s planned research, from Fiscal Year 2002 (FY2002) to FY2007, to fill gaps in the toxicologic database for CWAs at low levels of exposure. Research to support the Research Plan objectives is planned within the existing framework of the DOD Chemical and Biological Defense Program. No separate basic research program, organization, or management structure is proposed. The fundamental goal of the DOD research program is to establish science-based exposure standards for military personnel. Every study proposed under that program is designed to answer one mandatory question: How do data from this work contribute materially toward a quantitative refinement of the human health risk assessment for low-level CWA exposures? Therefore, the Research Plan is based on the following three major thrusts:

• Characterize concentration-time relationships for low-level, longer-time CWA vapor exposures.

• Identify alternative, but physiologically significant, toxicologic end points.

• Conduct appropriate integration studies linking experimental data sets with predictive human health effects assessments (DOD 2003).

Approximately 700,000 U.S. troops were deployed in the Persian Gulf War. The veterans who served in the Gulf War potentially were exposed to a wide range of chemical agents, including CWAs (e.g., sarin), pesticides, paints, solvents, petroleum fuels and their combustion products, smoke from oil-well fires, and a host of other environmental agents in addition to psychological and physiological stress. Although most men and women who served in that war returned to normal activities, a large number of veterans have reported a range of unexplained symptoms, including fatigue, muscle and joint pain, loss of concentration, forgetfulness, headache, and rash. Many of these Gulf War veterans and some health scientists believe the symptoms are related to the veterans’ exposures to CWAs. In section 247 of the 1999 Defense Authorization Act (PL 105-261), Congress directed the Secretary of Defense to review and modify DOD policies and doctrines that relate to protecting personnel from low-level exposure to CWAs.

In response to that congressional mandate, the Secretary of Defense directed DOD’s Nuclear, Chemical, and Biological Defense Program to develop a research plan to obtain toxicologic and other data to assess health risk to military personnel. The data obtained from the proposed research would provide information to the Secretary of Defense to reassess policies and doctrines related to low-level exposure to CWAs. According to DOD (2003), the research is intended to accomplish two objectives. The first is to support operational commanders in the field with information for real-time decision making required to accomplish their missions while not unduly jeopardizing the health and performance capability of their forces. The second is to understand and prevent or reduce the potential health consequences of low-level exposure, which might not manifest immediately but could become evident months or years after the exposure.

There is considerable information on acute health effects of short-term, high-level exposures to CWAs, such as nerve agents and vesicants, and there are some data on acute effects of low-level exposure in hu-

mans. However, there is currently little information on delayed or chronic effects of low-level exposure to CWAs because before the Gulf War, CWA research focused on lethality and incapacitating effects. Because of interest in the unexplained symptoms among Gulf War veterans and uncertainty surrounding their links with exposures to multiple chemicals, including CWAs and other environmental agents, there has been an increase in research funding by DOD and the Department of Veterans Affairs on potential adverse health effects of low-level exposure to CWAs.

For the DOD Research Plan, CWAs of initial concern are nerve and vesicant agents. Nerve agents include tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX; the vesicant studied is sulfur mustard (HD). Other agents, such as tear gas and hydrogen cyanide, are also of interest to DOD, but they are assigned lower priority. Exposure duration and frequencies to be considered are those likely to be experienced by deployed military personnel. Concentrations of concern are those at and below which no observable adverse health effects (immediate or delayed) are expected for healthy military personnel, using accepted toxicologic tests and standard medical practices. Performance decrements significant to personnel carrying out their military duties are of greater concern than delayed health effects and therefore are assigned a higher priority.

The committee’s tasks are to review research proposed in the DOD Research Plan to generate toxicologic and other data to help protect military personnel from low-level exposure to CWAs, to provide recommendations regarding that research, and to develop recommendations for additional research as the committee deems appropriate. The committee also will provide guidance on appropriate risk assessment methods for assessing toxicologic risk to military personnel from low-level exposure to CWAs.

Chapter 2 of this report briefly discusses issues related to the toxicity of CWAs. Chapter 3 evaluates the DOD Research Plan on low-level

exposure to CWAs and provides conclusions and recommendations for the proposed research; that chapter also identifies gaps in the plan and makes recommendations for further research. Chapter 4 discusses the research issues related to health risk assessment of low-level exposure to CWAs.