Executive Summary

Many toxic substances in the environment, including man-made pollutants, can pose hazards to human health. Monitoring human exposures to these substances can be difficult. Many substances move readily from one environmental medium to another, and reliable monitoring data are sparse for most routes of human exposure. Furthermore, as discussed in the National Research Council’s 1991 report, Human Exposure Assessment for Airborne Pollutants, monitoring the environment by identifying and measuring concentrations of chemicals in environmental media (e.g., air, water, and soil) is not by itself an adequate basis for assessing human exposures.

Improved understanding of potential health risks has led to a search for indicators of biologic responses to exposure that reveal the progression of events within the body that lead to disease before disease occurs. Determining the concentrations of specific chemicals in human tissues—such as blood and adipose tissue—can serve in effect to integrate many kinds of human exposures across media and time. A well-designed national program to monitor toxic chemicals in human tissues is a necessary component of an anticipatory strategy aimed at early identification of and response to health and environmental problems concerning xenobiotic toxicants in the environment.

Used as one component of an effort to manage environmental quality and protect public health, tissue monitoring has valuable attributes:

  • Tissue samples can reflect exposures accumulated over time.

  • Tissue samples can reflect exposures by all environmental pathways and routes of entry into the body, including some that are difficult or impossible to assess by environmental measurement.

  • Pollutants in tissue samples have undergone the modifying effects of physiology, metabolism, and biologic availability, and thus can be used to help describe important exposure-response relationships.



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Monitoring Human Tissues for Toxic Substances Executive Summary Many toxic substances in the environment, including man-made pollutants, can pose hazards to human health. Monitoring human exposures to these substances can be difficult. Many substances move readily from one environmental medium to another, and reliable monitoring data are sparse for most routes of human exposure. Furthermore, as discussed in the National Research Council’s 1991 report, Human Exposure Assessment for Airborne Pollutants, monitoring the environment by identifying and measuring concentrations of chemicals in environmental media (e.g., air, water, and soil) is not by itself an adequate basis for assessing human exposures. Improved understanding of potential health risks has led to a search for indicators of biologic responses to exposure that reveal the progression of events within the body that lead to disease before disease occurs. Determining the concentrations of specific chemicals in human tissues—such as blood and adipose tissue—can serve in effect to integrate many kinds of human exposures across media and time. A well-designed national program to monitor toxic chemicals in human tissues is a necessary component of an anticipatory strategy aimed at early identification of and response to health and environmental problems concerning xenobiotic toxicants in the environment. Used as one component of an effort to manage environmental quality and protect public health, tissue monitoring has valuable attributes: Tissue samples can reflect exposures accumulated over time. Tissue samples can reflect exposures by all environmental pathways and routes of entry into the body, including some that are difficult or impossible to assess by environmental measurement. Pollutants in tissue samples have undergone the modifying effects of physiology, metabolism, and biologic availability, and thus can be used to help describe important exposure-response relationships.

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Monitoring Human Tissues for Toxic Substances Some agents are more concentrated and are, therefore, more readily detectable, in tissue samples than in the environment. Tissue samples can offer the opportunity to correlate the tissue concentration of toxicants with other tissue-based biologic markers or indicators of effect that might be predictive of injury or disease within a given person. Taken together, these characteristics make tissue monitoring a potentially important adjunct to conventional environmental monitoring and one that is uniquely valuable in indicating exposures and doses that may lead to harmful effects. THE NATIONAL HUMAN MONITORING PROGRAM The National Human Monitoring Program (NHMP) was established in 1967 within the U.S. Public Health Service to study changes in pesticide residues in the U.S. population. The primary activities of the NHMP are the National Human Adipose Tissue Survey (NHATS) and special studies that support other programs requiring data relevant to chemical exposures. The NHMP, including NHATS, was transferred to the Environmental Protection Agency (EPA) in 1970. Since 1981, the NHMP has been the responsibility of EPA’s Office of Toxic Substances (OTS). The NHATS was redesigned by OTS specifically to identify chemicals to which a representative sample of the U.S. population was being exposed, to establish baselines and trend data on chemicals for toxicologic testing, to identify populations at risk and to set priorities for risk reduction, and to help assess the effects of regulation. To accomplish these goals, the NHATS measures residues of chemicals in human adipose tissue. Since 1967, the NHATS has collected approximately 12,000 samples of adipose tissue—85–90% from autopsied cadavers and the remainder from surgical patients. Tissues are obtained through a national network of pathologists and medical examiners from 47 urban or metropolitan statistical areas (MSAs); no rural areas or small towns outside MSAs are included. In recent years, the number of specimens collected has dropped from an annual quota of 1,370 in the early 1970s to 500–800 samples in the 1980s. The NHATS has successfully documented widespread and significant prevalence of pesticide exposures in the general population. It also has shown that reduced use of polychlorinated biphenyls (PCBs), DDT, and dieldrin resulted in lower tissue concentrations of these compounds. A trend analysis for 1970– 1981 showed a dramatic decline in PCB concentrations after the regulation of PCBs in 1976.

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Monitoring Human Tissues for Toxic Substances The NHATS program has important and worthwhile goals. When it began some 20 years ago, the NHATS represented the state of the art in pesticide analysis in human tissues. However, while the objectives of the program have grown, program design and support have not kept pace. The NHATS is now out of date and only partially fulfills its objectives. Design and management problems have been compounded by insufficient financial support for the changing and expanding objectives, and the overall quality of the NHATS has deteriorated. In 1987, EPA proposed to introduce the National Blood Network (NBN) to monitor residues of industrial chemicals in the blood of volunteer donors from three U.S. blood-collection agencies. The NBN was intended to establish baselines and time trends for the nation and for various population groups. It was conceived as a way to complement the NHATS data by permitting less invasive collection of a tissue that reflected more recent exposures compared with the long-past exposures shown by adipose tissue collection. It also would have complemented the NHATS by focusing on volatile organic chemicals (e.g., benzene and trichloroethylene) and elements (e.g., lead, cadmium, and arsenic), as well as semivolatile organics. However, the NBN has not been implemented. The NHMP has carried out several special studies, alone and with the collaboration of other agencies. Such studies include an archive stability study; a study with the World Health Organization that measured lead and cadmium in blood; a clinical study of PCBs in transformer workers; development of a national body-burden database; and, with the Veterans’ Administration, a dioxin-furan study of Vietnam veterans exposed to Agent Orange. Because of budgetary limitations, the NHATS is the only operating component of the NHMP, and in late 1987, EPA announced its intention to eliminate the NHMP. Congress instructed EPA to retain the program, pending a review of its usefulness, and funds were made available through fiscal year 1990. CHARGE TO THE COMMITTEE In response to the congressional request, EPA asked the National Research Council (NRC) to review and evaluate the effectiveness and potential applications of the NHMP. The NRC’s Commission on Life Sciences formed the Committee on National Monitoring of Human Tissues within the Board on Environmental Studies and Toxicology. The committee’s tasks were as follows:

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Monitoring Human Tissues for Toxic Substances Organize a public workshop to identify relevant data and advise EPA on the scientific, technical, and database management issues relevant to the current conduct and future use and development of the monitoring program. Review the past applications and future uses of these databases, considering them in the context of the federal government’s overall strategy for monitoring the general population for exposures to various toxicants. Evaluate these programs in terms of their design, current and potential applicability, and relative priority, to assist the federal government in determining whether or how to continue such networks. Evaluate and provide recommendations for current and future resources for the NHMP and assess the validity of various potential uses for which such monitoring data have been proposed, whether from the NHMP or other sources. Assess the utility and cost effectiveness of the program and identify major scientific, technical, and ethical issues that should receive priority attention. Address the larger issue of developing consensus on biologic markers of environmental hazards in the context of overall federal efforts to monitor markers of human exposure to environmental toxicants. The first of those tasks was completed January 24–25, 1989, with a workshop held at the National Academy of Sciences in Washington, D.C. Committee members heard from NHATS users, potential users, and persons involved in the operation of specimen and tissue banks. The current report addresses the other five tasks. RELATIONSHIP OF TISSUE MONITORING TO EPA PROGRAM PRIORITIES The goals of the NHMP correspond broadly to EPA’s mission in recognition, evaluation, and control of environmental chemical hazards to human health. However, no detailed plan tying the NHMP to specific EPA regulatory programs or research objectives appears to have been developed. Some NHMP results have been used and cited by several EPA programs; e.g., the 1988 Environmental Progress and Challenges: EPA’s Update cites NHMP results in monitoring markers or indicators of exposures to PCBs, pesticides, and other agents of concern, such as dioxins, in human biologic samples. Recent EPA planning documents indicate that the NHMP or a successor program could be integrated readily into new research and program objectives. Measurement of exposures in a manner that leads to realistic projec-

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Monitoring Human Tissues for Toxic Substances tions of dose is explicitly recognized in the EPA planning document Protecting the Environment: A Research Strategy for the 1990s.” In this document, EPA described new initiatives aimed at broadening the research base for agency planning and developing new programs that transcend the previous “end-of-the-pipe” approach to environmental management. The emphasis on human health risk as a focus in regulatory programs specifically indicates the ongoing need and value of a national human monitoring program. Of the top five priorities for new research programs identified by EPA, the third is “development of a national data base on the extent of human exposure to pollution in the U.S.” Many of the individual subjects for research identified in the report are related directly to aspects of the present NHMP or to proposed enhancements. GOALS AND POTENTIAL USES OF A NATIONAL PROGRAM TO MONITOR HUMAN TISSUES The committee determined that an ideal national human monitoring program should do the following: Measure concentrations of known chemical contaminants in human tissues and help identify new or previously unrecognized hazards related to chemical substances found in the environment, especially those resulting from human activities. Establish trends in body burdens of toxicants that result from changes in manufacture, use, and disposal patterns, and thus monitor the results of programs intended to control specific chemical hazards. Provide biologic samples and data to aid in the evaluation of relationships between environmental exposure and toxic effects for purposes of risk assessment. Identify population groups (by age, geographic location, etc.) that might be at risk because of high body burdens. Provide data for comparison with results of complementary environmental monitoring programs. Provide human tissues essential for research on related matters, such as determination of body burdens; distribution of chemicals among body compartments; identification of biologic markers; and procurement, storage and analysis of human tissues. Allow assessment of past exposure to newly identified toxicants.

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Monitoring Human Tissues for Toxic Substances CONCLUSIONS AND RECOMMENDATIONS The committee strongly supports a U.S. population tissue monitoring program. Given the central role of chemicals in modern society, people will be exposed to chemicals. It is prudent that the general population be monitored to aid in assessing magnitudes of exposure and to determine the need for and effectiveness of regulations and other measures to limit risk. After a thorough review, the committee found that the current NHMP program is fundamentally flawed in concept and execution and should be replaced completely. The original goals of NHMP (and the NHATS as redesigned) are still valid. The committee further recommends that a new program of human tissue monitoring be developed with dispatch, that the NHMP be continued only until a successor program is established, and that the change be completed as soon as is consistent with an orderly transi tion. Certain aspects of the NHATS should be preserved and evaluated for continued support: the network for collection of adipose tissue specimens (though it will need modification), the tissue archive, and the record of past analyses. Toxicologic Issues Although tissue-monitoring data alone can signal the need to conduct studies on specific environmental chemicals, tissue monitoring to indicate past exposures to chemicals in the environment is best viewed as one component of a comprehensive environmental monitoring program. Information on chemical toxicity typically is inadequate; even if it were adequate, planned and unplanned releases of toxic substances and the resulting human exposures still would occur. The quantities of chemicals present in various media can be used to determine whether the media are potential routes of exposure; however, such measurements are not necessarily reflected in tissue concentrations. Tissue chemical measurements must be supplemented with knowledge of contaminant sources, environmental pathways, environmental concentrations, time patterns

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Monitoring Human Tissues for Toxic Substances and locations of exposure, routes of entry into the body, material toxicity, and latency. Relevance of Human Tissue Monitoring to Risk Assessment Risk assessment includes identification of a potential health risk due to exposure to a hazardous agent, determination of sources and magnitudes of exposure to the agent, estimation of the relationship between the potential risk or severity of disease and the dose of the agent, and the integration of this information into estimates of potential risk associated with various exposure conditions. Most risk assessment today is based on estimates of external exposure, which can be used to calculate dose. However, exposure data generally are imprecise and contribute considerably to uncertainty in the risk estimate. Bioavailability—the completeness of absorption of a substance from environmental media—differs according to many factors, including route of exposure and the chemical and physical properties of the substance. Interpretation of tissue concentrations must depend on inherent potency and a broad range of other factors, including exposure to other chemicals, can provide quantitative data on internal dose or biologically effective dose of a chemical or the resulting biologic effects and can theoretically provide greater precision in the risk-assessment process than can the use of crude exposure data. Choice of Tissues to Monitor It is not feasible to study a broad range of tissues in a general population sample. Instead, attempts must be made to identify tissues that most nearly account for the body burden of most of the chemicals of concern. When the NHATS was designed, pesticides were of greatest concern, especially halogenated hydrocarbons (particularly halogenated aromatic hydrocarbons), which tend to accumulate in adipose tissues. New trends of environmental exposures, advances in analytic chemistry, increased sensitivity of equipment, and the discontinuation of the use of most halogenated aromatic pesticides and many halogenated aromatic industrial chemicals make the study of other tissues important as well as feasible. The committee considered the collection of blood as well as other tissues and specimens, including lean tissue, hair, urine, and some other biologic fluids. The present evidence leads the committee to conclude that the basis

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Monitoring Human Tissues for Toxic Substances of a human tissue monitoring program should be broad, random collection of blood samples, supplemented by the continued collec tion of adipose tissue. This recommendation includes probability sampling; the needs cannot be satisfied by existing EPA plans regarding the proposed NBN. Blood collection should be supplemented by the continued collection of adipose tissue, in part to maintain historical continuity while new long-term series of blood measures are established and in part be cause some important residues are most concentrated in fat. Measurements of nonrandom samples of adipose tissue will continue to be important for several years, although they might be replaced later with studies of the lipid fraction of blood. While blood and adipose tissue are being collected, the program should undertake research on how the chemical measure of a xeno biotic toxicant in one tissue is correlated with that in another, so that the effects of nonrandomness in the adipose samples will be better understood, and the continued contribution of the adipose samples (including stored samples) can be evaluated properly. Regardless of the tissues collected, samples should be accompanied by standardized information on demographics, illness (especially terminal illness), and known occupational or other major exposures to chemicals. High priority should be given to the collection of matched adipose and blood specimens for future parallel analyses. Matched speci mens of fat from different anatomic regions also might be useful Sampling Methods One of the primary deficiencies in the NHATS is that donors of adipose tissues collected are not a representative sample of the U.S. population (see Chapter 4). Most population surveys compromise somewhat on ideal standards; however, departures from probability sampling in the NHATS exceed what most statisticians would consider acceptable. The main deficiencies are these:

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Monitoring Human Tissues for Toxic Substances Although the target population is the living U.S. population, the subjects on whom measurements are taken are an uncontrolled mix of recently deceased persons and surgical patients. The sample size has been driven by the budget, rather than by needs to satisfy important goals of the program. • Some important segments of the population are omitted from the sample. The exclusion of the rural population is the most serious omission. Although probability sampling was used in the selection of the metropolitan areas that are the first stage of sampling, problems of cooperation forced substitutions for 20% of the areas. Consequently, the extent to which the sample of areas now represents all metropolitan areas is uncertain. No sampling method has been designated for choosing the persons from whom specimens are taken. Each medical examiner or pathologist is given a quota by age, sex, and race, but the quotas are poorly adhered to; even if the quotas were met, the quota procedure would be inherently biased. There are no specific instructions for pathologists on the body part to be used for specimens. It is implicitly assumed that contaminant concentrations are the same in all adipose tissue in the body. Recent uses of composite measurements have made it impossible to provide prevalence estimates and seriously weakened the estimates of mean contamination concentrations for the sex, race, and age subdomains. Sampling errors have not been calculated, so users are not informed about the precision of the data. There is no plan for regular release of findings to the public. The basic structure of the NHATS is such that, even with major improvements, its ability to reflect the accumulations of toxic substances for the U.S. population would be seriously limited. If the NHATS were replaced, as the committee recommends, with a blood monitoring program as the primary method of measuring toxic substances in human tissue, the sampling plan should be patterned after the one used in National Health and Nutrition Examination Survey, which includes a close approximation to a probability sam ple of the U.S. population. Such a system also would permit interview with the sample persons to obtain data on covariates. Blood specimens should be collected in strict accord with the meth od of probability sampling at all stages. The methods used should

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Monitoring Human Tissues for Toxic Substances be efficient for giving virtually all persons in the United States a known probability of selection. During the time in which the NHATS is continued, selection methods should be revised to reduce subjective elements in the choices of counties, hospitals, and specimens. Collection, Short-Term Storage, and Archiving of Tissues Many authorities in environmental monitoring believe that a prospectively designed tissue bank should accompany environmental monitoring programs, although retrospective analysis is still an important function for an archive. Banked specimens and separately obtained specimens can reveal trends in environmental chemical exposure and identify agents responsible for pathophysiologic changes in humans, plants, and animals. The goals of a human-tissue bank operated in parallel with an environmental monitoring program should be clear and supported—with a long-term commitment—by the organization sponsoring the program. A specimen bank organized in conjunction with environmental monitoring will have many purposes and must support those purposes. The utility of a tissue bank depends on its correct operation; its resources; and the proper selection, collection, handling, and storage of specimens. Given the state of the NHATS current archive of tissue, the com mittee believes that the existing frozen samples of adipose tissue likely have little or no value to a successor program or to other par ties. However, the committee recommends that a successor program give the use of the current archive early consideration, specifically asking whether the archive should be saved indefinitely or discarded, and if it is to be saved, how it should be preserved and used. The committee advises the archiving of newly collected specimens according to state-of-the-art protocols. Samples should be collected and stored in a manner that preserves the possibility of basing measurements on individual samples, and a substantial part of the new program should be based on individual analyses. When it can be

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Monitoring Human Tissues for Toxic Substances shown explicitly that values based on individual samples are not needed, some degree of compositing might be appropriate. Chemical Assay of Specimens “Monitoring” implies routine measurement that is inherently closed-ended and based on established methods and practices. Requirements and approaches for monitoring programs vary, but usually proceed from a list of analytes (target chemicals) and assay methods that have been validated for the sample type and concentration range of interest. A successful monitoring program maintains results over time for comparison and must, therefore, be technically adequate at the outset (Chapter 6). Comparability is most easily achieved if assay methods are constant. The NHMP includes aspects that are not compatible with monitoring, such as recognition of new agents of concern and detection of chemicals not previously included in monitoring methods. These are appropriate to a population-based biologic surveillance program, but they require an approach to chemical analysis different from that for monitoring. The committee considered the following aspects of a monitoring program in its deliberations: Present knowledge does not permit designation of all substances that might be detectable in tissues or that would be important if detected. Present analytic technology is inadequate for surveillance of some chemicals, because of limitations in sensitivity, applicability, and cost. The importance of individual target chemicals will increase or decrease over time, but slowly. “Emergency” exposure assessments that might be required when a serious health hazard is discovered would be addressed best by focused special studies. Monitoring efforts will provide opportunities for exploration of tissue composition beyond a list of target chemicals. Those opportunities and other efforts parallel to the monitoring tasks should support continuing development of the monitoring program itself. Overall costs associated with a monitoring program can be reduced in several ways. Some reduce development costs and lead time, some reduce the number of assays needed for monitoring, and some reduce the cost per assay. Reductions in development costs can be achieved by targeting analytes with similar chemical properties to minimize the number or complexity of analytic protocols or by combining method development with actual sample analysis.

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Monitoring Human Tissues for Toxic Substances Both approaches have some merit, although they also have disadvantages. Once the relative importance of various possible uses of the data has been established, rationales for selecting target chemicals should be incorporated into a systemic weighting scheme and applied as com prehensively as feasible. Criteria for determining the relative importance of a candidate target chemical should be separated from issues of analytic feasibility until late in the planning effort. Identification of one or more analytes that might require a new assay protocol would be important in planning future method development. Design of an adaptable monitoring program with mechanisms for selection of new analytes, development and validation of collection, storage, and assay will permit a monitoring program to remain responsive to current needs and to take advantage of progress in analytic technology in an organized fashion. Many NHATS program decisions appear to have been arbitrary. The NHATS would benefit from regular strategic planning by EPA, frequent agency consultation with program contractors, scientific peer review, and solicitation of advice from interested federal agencies. These efforts would help maintain a clear decision-making process that is well documented and understood. Evaluation of data should be a continuing part of program reporting. One feature common to all NHATS project reports produced in the 1980s is the nearly complete limitation of analysis of final results to analytic validity. Interpretation of findings in relation to larger program goals (such as time trends, efficacy of interventions, relative importance of different environmental contaminants, and regional or demographic differences in exposures) is an important part of understanding and meeting additional data needs. The committee believes that only NHMP has broad responsibility for making certain that the program is productive in relation to the larger goals. Analytic methods research is conducted within EPA, at other government programs, and in academe. The NHATS must be able to articulate and, within EPA, influence research priorities for development of new analytic applications of emerging technology and to benefit from new developments.

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Monitoring Human Tissues for Toxic Substances The committee doubts that leadership in analysis can be delegated effectively to contracting organizations, and it believes that EPA must maintain substantially more activity and expertise in this regard. Since 1981, the analytic effort has been modified from year to year and developmental activities have supplanted monitoring to some degree. Including current efforts, data are available from only 2 collection years. Priority should be given to setting and maintaining a regular schedule for analysis of results of each assay type. Program Design and Management Issues Administrative and Agency Issues Organizational and administrative location of a human-tissue monitoring program in EPA is critical. The selection of an agency to lead national surveillance of chemical exposures is not simple; the multiagency history of the NHMP and the current ambivalence regarding the future of the NHMP are clear indications that the match between program goals, potential benefits, and EPA mandates is not perfect. Although a successful monitoring program must be relevant to regulatory needs, it could and should serve a wide range of client programs, without being dominated by any one. Unlike many other EPA programs, the NHMP has a purpose and rationale that transcends any individual EPA regulatory objective. The multiple aspects of a national human-tissue monitoring program has meant that, to some extent, the NHMP is not an integrated part of any specific EPA regulatory program and, therefore, is not at the top of any major agenda. The committee has specific concerns about the untoward effects of placing a monitoring program in any subunit with direct, major regulatory responsibilities. The committee firmly recommends that monitoring be kept strictly independent of regulation itself. The committee concludes that considerations of input to policy, impact, visibility, and independence argue for a location at the high est feasible organizational level. After considering the most likely government units to house a hu man-tissue monitoring program, and after hearing testimony at the

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Monitoring Human Tissues for Toxic Substances January 1989 workshop, the committee recommends that a national program to monitor human tissue remain within EPA. However, the location within EPA should be reconsidered, and the committee recommends that it be moved to an organization unit with EPA-wide responsibilities. A location that is geographically close to other programs and laboratories active in relevant technical disciplines would facilitate important exchanges about methods, as well as followup of findings. Funding The critical resources in a program of monitoring human tissues include funding and expertise in appropriate scientific fields. Sufficient funding, with assurance that it will remain adequate over the next few years, is essential. However, the final budget for a program should be determined after the program specifications have been formulated. The major factors involved in determining funding are the annual sample size, the set of chemical assays to be performed, the type of tissue to be collected, the size of the staff needed to monitor the program and analyze results, and requirements for research and development. Funding is flexible to a certain point. However, there is a minimum level of funding below which the program would not be worthwhile, and obviously, the greater the funding, the more detailed the analyses that can be conducted. EPA needs to make a commitment to request at least the minimal funding through the indefinite future. The committee firmly concludes that support should either be in creased enough to support a useful program, or the program should be eliminated. A clear decision to end the program would discourage present and potential users from expecting data that cannot be produced; would be a clear statement that EPA does not accord human-tissue monitoring a high priority; and would transfer institutional responsibility out of EPA, perhaps to another federal agency. Serious drawbacks to a decision to eliminate the monitoring program include the likelihood that no comprehensive, coordinated program would be developed elsewhere, loss of skilled staff and institutional memory, and perhaps destruction of specimens that have been banked and saved. The committee urges that EPA consider termination of human-tissue monitoring only

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Monitoring Human Tissues for Toxic Substances under the most compelling circumstances, and even then only after exploration of ways to ensure orderly transfer to another appropriate agency in less-straitened circumstances. The committee considered possible levels of funding. Funding of $3 million per year appears to be barely adequate to sustain the minimal activity needed to keep a program in long-term existence. The committee does not recommend support at this funding level. The next support level considered by the committee was $5 million per year, exclusive of staff salaries and overhead. Although the committee did not undertake detailed cost analyses, it believes that EPA’s history as well as the operation of other tissue-monitoring programs suggest that $5 million per year could support a substantial flow of high-quality, policy-relevant information. This level still is not munificent support, but it might be sufficient to serve EPA’s policy needs and bring some critical distinction to the program. Furthermore, it could be used to develop a solid base of competence, experience, and usefulness to support possible expansion in the future. Greater financial support—even up to the $25–50 million per year suggested by heads of other agencies—could be put to good use, given appropriate planning and the organizational setting and mission described in this report. However, such allocations do not appear feasible now, so their implications were not explored. The committee recommends that a full-time program manager and other staff be allocated funds adequate for the planning and full design of a new program concurrent with preparations for the absorp tion of the NHATS. At least $3 million per year will be needed to continue current activities and planning. This phase might take 12 months or more. The committee further recommends that, after the transition period, additional full-time staff be assigned and support be increased to at least $4 million per year for at least 2 years of consolidation. Science Review The committee recommends strong and continuing oversight of the new human-tissue monitoring program. Expert advice can be obtained in several ways, but the numerous

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Monitoring Human Tissues for Toxic Substances criteria required to establish and maintain a human-tissue monitor ing program point strongly to a standing outside scientific advisory body to advise program and EPA management. The body should be outside EPA; nearly all members should be knowledgeable about one or more scientific and technical disciplines important to the program. Advice provided by this group would include oversight of program content, program management, program planning, resource needs, technical operations, timeliness, and appropriate dissemination of results. The advisory body should have no other major responsibilities related to the program. The committee envisions quarterly meetings that would taper rapidly to annual meetings. Other Administrative Issues Details of program structure and organization depend heavily on a host of management decisions that the committee cannot foresee. Some of the issues that must be considered, however, include in-house scientific and managerial competence; professional staff members fully dedicated to human-tissue monitoring; and program design. Some professional staff members should be fully dedicated to the program, without competing duties. The committee specifically recommends that the program be de signed in a modular fashion as much as possible to permit critical core activities to be maintained even if other activities must be cur tailed, suspended, or ended at some future time. Analysis and Reporting of Data A structured approach to basic and more-exploratory data analysis is needed. The plan for each year’s monitoring effort should include a data-analysis plan, with analytic subprojects. Well-defined analyses should result in early reporting of findings; analyses that require method development or input that are not in the chemical analysis set might be reported less rapidly or less often. At a minimum, however, descriptive summary analyses of the data should appear with the same frequency as the chemical analyses.

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Monitoring Human Tissues for Toxic Substances Data from human-tissue monitoring cannot, in general, be fully interpreted without other information regarding tissue concentrations, patterns of exposures, and the metabolism and toxicology of individual chemicals. Reporting of those should be systematized, but this will require close collaboration of statistical analysts with persons providing other information. Comparison data, especially reports of tissue concentrations of chemical agents, should be sought continuously. Strong interagency and intra-agency collaborations in planning and exchange of data will be required to address measurement objections, facilitate the analysis of monitoring-program results, and result in a program that is most useful to cooperating agencies. The program must produce timely reports regularly. The committee recommends that at a minimum, an annual report of basic analyses should be produced within a year of completion of the sample collection. Reports almost certainly will undergo internal review. Extra-agency review of draft reports is desirable, especially peer review by persons on the scientific advisory panel and perhaps other persons with specific expertise. A human-tissue monitoring program should be designed as a multiple-user service activity. That creates substantial obligations for assisting users to understand what the program does and does not provide, for timely analysis and publication of results, for specific and helpful guidance in access to archived specimens, and for active marketing of products. A well-defined process for producing a range of outputs is an important part of the planning effort. A schedule should be widely and continually publicized and should be relaxed only under the most compelling circumstances. Scientific staff, who bear most of the responsibility for meeting a schedule, should recognize that timely, high-quality reports on important matters are a sine qua non. A specific person or persons must be responsible for outreach efforts, which are warranted by the multiuse nature of the program, the wide-ranging interest in the resulting data, and the clear indications that more passive approaches to publicizing program reports have failed to reach some critical target groups.

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Monitoring Human Tissues for Toxic Substances Cooperation and Information Transfer with Other Organizations A tissue-monitoring and archival program must cooperate and com municate with other branches of EPA, other government agencies, academic and private sectors, and foreign environmental programs. Not only are such cooperation and information exchange important in the operation of human-tissue monitoring but continuing informa tion exchange will be critical to the efficient operation of the new program. The committee thinks that special value might be found in the joint development of a small set of measurements to be made in similar ways across a broad range of programs or a means of establishing comparability among programs that could lead to a worldwide data base for environmental toxicants that persist over long times or migrate across long distances and across national boundaries.

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