Review of the U.S. Naval Medical Research Institute's Toxicology Program (1994)

A formal, written comprehensive 10-year plan was not provided as part of the materials for the subcommittee's evaluation. Instead, NMRITD provided an informal preliminary strategic-planning document entitled “Research Planning Document for FY 1992 – FY 2001.” The document identified the general factors influencing the Navy 's needs for toxicology research and the constraints on that work and described the stages for developing a strategic plan. Goals were to identify capabilities to be developed or expanded; elements of the goals and intermediate objectives were also outlined. Finally, proposed research projects were listed that related to achieving each goal during the 10-year period. The document focused on current work, but context was provided to position each project within the strategic-planning framework and to indicate the direction of future efforts. The proposed projects were heavily weighted toward evaluating issues arising from inhalation exposures. Less emphasis was placed on basic research than on applied research; emphasis was placed on various degrees of applications issues or methods. In addition to providing the research-planning document, NMRITD personnel made presentations and provided an outline regarding future program direction.

The subcommittee addressed the following questions regarding NMRITD 's strategic-planning effort and draft plan:

1. Does NMRITD's preliminary Ten-Year Strategic Plan incorporate good scientific concepts?

2. Does it address Navy-specific needs?

3. What changes to the plan would improve the science?

4. What role should basic research play in the overall toxicology program to be executed at NMRITD, as compared with the current emphasis on applied research?

5. What should be the balance between toxicological research and toxicity characterization?

6. Is there a need for a formal means to periodically evaluate the plan and its progress?

7. If so, what means should be used and how frequently should it be done?

Subcommittee members believe the preliminary Ten-Year Strategic Plan reflects valid scientific concepts. However, the plan needs to articulate more clearly a framework that incorporates accepted standards of science and demonstrates an opportunity for growth and flexibility. Prevention of adverse human health effects should be a major goal of the program. The plan must be explicitly integrated with the overall strategic plan of the Navy to place NMRITD in a pro-active position so that it can respond more effectively to the Navy's questions on specific weapon-systems acquisition and operational matters. The dimension of the program will be determined by the availability of resources. Nevertheless, a core program with a defined focus will serve as a nucleus for all future research directions.

The plan emphasizes sound scientific experimentation to support NMRITD 's recommendations on health and environmental issues of importance to the Navy. That is appropriate, but the plan should reflect

NMRITD's mission to a greater extent. Effective implementation of the plan must be directed toward collaboration with the other branches of the military.

Navy organizations concerned with congruent health and environmental issues should be communicating. Inputs from the Navy Environmental Health Center, including the epidemiology, medical, industrial hygiene, hazardous materials, and environmental divisions, are particularly essential if NMRITD is to better define its research priorities. Mixed messages within the system should be avoided if the Navy is to be a credible partner in triservice toxicological research.

Although the plan should focus on inhalation toxicology as a major concern, other routes of exposure cannot be neglected. The long-term plan should also focus on data generation to establish limits for occupational and environmental exposure levels for chemicals that are under consideration for use in weapons and other systems. A flexible plan allows for prospective problem solving (as opposed to reactive after a problem has been identified). The plan describes areas of research necessary to perform the activities in support of the mission and its functions and task statements. However, the balance between basic and applied research is not clearly stated. It will be important to have specialists who understand cancer and noncancer end points and mathematical modeling to support state-of-the-art risk assessments. The specialists should interface with others in academia, government agencies, and industry where new methods are being developed. Basic research could be bolstered through external contracts. The productivity of Navy toxicologists could be enriched through linkage to external programs. The primary function of the toxicology program should be to resolve issues unique to the Navy.

The above discussion addresses this issue, and further improvement will be realized by increasing competency in toxicology to enable NMRITD to generate the data necessary to fulfill its mission. Several factors have been identified that will influence the development of toxicology information. Such factors include scientific advances, regulatory

concerns, public concerns, decreased funding, and forced downsizing. These factors need to be addressed and reviewed on a regular basis as the plan is changed to improve the scientific focus.

The subcommittee concludes that the major emphasis on applied research is appropriate. Additional expertise and programs should be added at NMRITD to enhance toxicology capability and its application to health-based risk assessments. The Navy's needs suggest that additional emphasis be placed on reproductive and developmental toxicology, neurotoxicology, immunotoxicology, and genetic toxicology. Other specialties might be necessary as the Navy's needs evolve. The focus for the applied research should be on matters directly applicable to solving the Navy's problems. There is also a need for mechanistic toxicological research programs; these programs should focus on advancing scientific understanding of those broad toxicological issues that are deemed to have the most impact on the Navy's needs. The basic research programs should address issues that might be confidential or specific to the Navy, such as exposure to chemicals under hyperbaric conditions. The Navy should not conduct basic research if it can be acquired more economically from external sources or if it can be conducted more efficiently with another organization.

The balance between toxicological research and toxicity characterization should roughly be based on the mission of NMRITD. However, there should be sufficient flexibility so that toxicological research can be used to answer questions raised by the toxicity characterization. The Navy's selection process for acceptance of proposals and for funding should also dictate the mixture of research and toxicity characterization as defined by immediate and long-range needs. If decisions regarding the balance between research and toxicity characterization are made sole-

ly by research personnel at the detachment, there might be a tendency to favor basic research. The mission of NMRITD, however, is to compile biomedical data for materials of interest to the Navy, to develop occupational and environmental health-hazard evaluations and risk assessments, and to develop exposure limits to address specifically Navy exposure scenarios. The mission implies that a greater emphasis should be placed on toxicity characterization than on basic research.

The emphasis on descriptive toxicology is based on the fact that much of the data currently required for health-hazard analysis and risk assessment are obtained through classical toxicological experimentation, even though such work is often considered basic research. A significant portion of that work uses established protocols to meet immediate Navy needs for chemical and material evaluation. Thus, although the distinction between basic research and descriptive toxicology is sometimes blurred, NMRITD's mission suggests a balance in favor of descriptive toxicology.

Regardless of the balance, the role of the Navy in a triservice arrangement will still require additional civilian scientists. As previously mentioned, civilian scientists will help maintain continuity, stability, and the necessary personnel for the Navy program.

It will be important to review and clarify the program's direction on a regular basis. Annual review of the research plan with the best projections of need on a multiyear basis is a good practice for maintaining efficiency and minimizing costs. Periodic review will also help to avoid unnecessary research or research that does not reflect the future operational needs of the Navy. Such reviews should include an assessment of progress made toward incorporating recommendations from previous reviews.

The annual review process of the research plan can proceed in a number of ways. It is essential that input be included from the Navy commands who have knowledge of future needs and direction. The current Navy review process has merit. However, the review should also focus on past progress as well as future needs and direction. The subcommit-

tee emphasizes that external peer review by experts in each subspecialty of toxicology is essential for a state-of-the-art effort.

Review of the initial research proposals before undertaking the research is necessary. In addition, review of work in progress and the completed research is essential. Was the research conducted according to protocol and does it meet quality assurance standards? Answering these questions allows the Navy to evaluate its own research, as well as the work of its contractors.

The Navy could utilize some outside group to provide scientific review or establish a toxicology science advisory board of external reviewers. Another option is to contract with specialists on an as-needed basis. Chapter 4 of the NRC (1991) report Review of the U.S. Army Environmental Hygiene Agency Toxicology Division gives guidance on the establishment of peer-review procedures.

The current basic research effort is limited. There is a need for actual basic research programs, but such investigations should address issues that are confidential or needs that are specific to the Navy. The subcommittee recommends that the major emphasis should be on applied toxicological research as it relates directly to the environmental and occupational health needs of the Navy. This recommendation requires appropriate testing and mechanistic approaches. The ability to recruit and maintain competent scientists will depend on the establishment of a stable and intellectually stimulating research environment.

The subcommittee's recommendations on NMRITD's 10-year plan are the following:

• The long-term plan should focus on generating data to establish limits for occupational and environmental exposures to chemicals that are under consideration for use in weapons and other systems.

• NMRITD currently does not have the expertise required to conduct state-of-the-art work in reproductive and developmental toxicology, neurotoxicology, immunotoxicology, and genetic toxicology. Therefore,

a section of the long-term plan should be dedicated to increasing NMRITD's competency in those areas of toxicology to enable it to fulfill its mission.

• Additional expertise and programs should be added to NMRITD to conduct health-based risk assessments. The Navy's needs suggest additional emphasis in reproductive and developmental toxicology, genetic toxicology, immunotoxicology, and neurotoxicology. Other specialties might be necessary as needs evolve. However, the primary focus should remain on research directly applicable to solving the Navy's toxicological problems.

• The Navy's process for acceptance of proposals and for funding should dictate the mix of applied and basic research studies as defined by immediate and long-range needs.

• Annual review of the research plan with the best projections of need on a multiyear basis is a good practice for maintaining efficiency, ensuring scientific focus, and keeping costs at a minimum.

• External peer review by experts in each subspecialty of toxicology is essential for a state-of the-art effort; external peer review might be achieved through a science advisory board.