Review of the Department of Labor's Site Exposure Matrix Database (2013)

Summary

Beginning with the development of the atomic bomb during World War II, the United States continued to build nuclear weapons throughout the Cold War. Thousands of people mined and milled uranium, conducted research on nuclear warfare, or worked in nuclear munitions factories around the country from the 1940s through the 1980s. Such work continues today, albeit to a smaller extent. The Department of Energy (DOE) is now responsible for overseeing those sites and facilities, many of which were, and continue to be, run by government contractors.

The materials used at those sites were varied and ranged from the benign to the toxic and highly radioactive. Workers at DOE facilities often did not know the identity of the materials with which they worked and often were unaware of health risks related to their use. In many instances, the work was considered top secret, and employees were cautioned not to reveal any work-related information to family or others. Workers could be exposed to both radioactive and nonradioactive toxic substances for weeks or even years. Consequently, some of the workers have developed health problems and continue to have concerns about potential health effects of their exposures to occupational hazards during their employment in the nuclear weapons industry.

In response to worker concerns, the U.S. Congress in 2000 authorized compensation for DOE workers in the Energy Employees Occupational Illness Compensation Program Act (EEOICPA) (Public Law 106-398, Title XXXVI). Initially, former workers filed compensation claims with their state worker compensation offices, but in 2005 the compensation process was transferred to the Department of Labor (DOL) to expedite the claims process. To receive compensation, workers

must attest that they suffer from a disease that is linked to an exposure at one or more of the sites that are listed by DOL.

DOL uses a database, the Site Exposure Matrix (SEM), as a tool to assist with compensation determinations for DOE contractors who have illnesses related to their work for DOE. SEM was developed to organize, display, and communicate information on the toxic substances and possible health effects associated with them for each DOE site, buildings at the sites, and job processes conducted in those buildings. Originally developed for DOL claims examiners, the database is available to the public, and individuals can submit site-related and toxic substance—related information to it. However, the database has been criticized by claimants and their advocates, particularly regarding the accuracy of its substance—disease links. SEM has also been the subject of a study by the Government Accountability Office, which has evaluated its use in DOL’s EEOICPA claims process.

COMMITTEE’S CHARGE AND APPROACH

In response to the concerns expressed by workers and their representatives, DOL asked the Institute of Medicine (IOM) to review the SEM database and its use of a particular database, Haz-Map, as the source of its toxic substance—occupational disease links. Accordingly, this IOM consensus report reflects careful consideration of its charge by the committee, and describes the strengths and shortcomings of both databases (see Box S-1 for the Statement of Task). To complete its task, IOM formed an ad hoc committee of experts in occupational medicine, toxicology, epidemiology, industrial hygiene, public health, and biostatistics to conduct an 18-month study to review the scientific rigor of the SEM database. The committee held two public meetings at which it heard from DOL Division of Energy Employee Occupational Illness Compensation (DEEOIC) representatives, the DOL contractor that developed the SEM database, the developer of the Haz-Map database, DOE worker advocacy groups, and several individual workers. The committee also submitted written questions to DOL to seek clarification of specific issues and received written responses from DEEOIC. The committee’s report considers both the strengths and weaknesses of the SEM and the Haz-Map databases, recognizing that the latter was developed first and for a different purpose. The committee then discusses its findings and recommends improvements that could be made in both databases with a focus on enhancing the usability of SEM for both DOL claims examiners and for former DOE workers and their representatives.

HAZ-MAP

Overview

The Haz-Map database contains health effects information on approximately 7,000 hazardous agents (as of December 2012) found in the workplace. The database was “designed for health and safety professionals and for consumers seeking information about the adverse effects of workplace exposures to chemical and biological agents” (http://hazmap.nlm.nih.gov/about-us; accessed December 19, 2012). It was not designed for compensation purposes. The two major types of information in Haz-Map are lists of hazardous agents (also referred to as toxic substances); hazardous jobs, industries, processes, and job tasks (the industrial hygiene perspective); and lists of occupational diseases and symptoms and physical findings (signs) (the epidemiologic perspective). Information from numerous textbooks, journal articles, and electronic databases is cataloged and summarized to create the database and to establish causal links between hazardous agents and occupational diseases. Although Haz-Map was initially developed and maintained privately, since 2002 the National Library of Medicine (NLM) has published Haz-Map on its website (http://hazmap.nlm.nih.gov), where it is periodically updated for content with revisions provided by the Haz-Map developer.

The committee appreciates the enormous amount of work that has gone into the development and maintenance of Haz-Map to assist health providers in identifying and possibly preventing occupational diseases, but it identified several limitations of the database and focused on its use for SEM in the context of the EEOICPA compensation system. The limitations include the lack of transparency in data sources used for determining each toxic substance—occupational disease link and in the criteria for establishing the links, particularly in connection with noncancer end points; the lack of a clear weight-of-evidence approach; the lack of peer review; the overreliance on textbooks such that information may be neither comprehensive nor up to date; and lack of clarity on what toxic substances and fields have been updated by the Haz-Map developer.

Findings

The DEEOIC’s interpretation of the statutorily imposed causative burden in the claims adjudication process is not part of the committee’s charge. However, the committee felt that it was important to discuss how the substance—disease links in SEM, by relying on Haz-Map’s criteria for establishing links, may affect the interpretation of causation.

The use of Haz-Map’s disease links for EEOICP workers’ compensation claims differs substantially from its original intent. The database uses strict criteria for identifying toxic substances that cause cancer; that is, they must be categorized as in Group 1 by the International Agency for Research on Cancer

(IARC). But it has ambiguous criteria for identifying toxic substances that cause diseases other than cancer. EEOICPA states that an illness or a disease may be compensable if “it is at least as likely as not that exposure to a toxic substance at a DOE facility was a significant factor in aggravating, contributing to, or causing the illness.” However, the “Diseases” field of Haz-Map, which contains the toxic substance—occupational diseases links used in SEM, does not capture information on exposures that aggravate or contribute to disease; rather, it contains only links between exposure and disease that are designated as causative by its developer.

SITE EXPOSURE MATRIX

Overview

SEM is a key resource for the EEOICPA Part E compensation program. It imports information from the Haz-Map “Diseases” field to provide toxic substance—occupational disease links for the SEM “Specific Health Effects” field. SEM was designed to function as a repository of information about toxic substances present at facilities covered under EEOICPA Part E that would “assist claimants and claims examiners by putting toxic substances present at DOE sites and scientifically established illness and disease links information in one convenient location.” The claims examiner manual states that “the SEM is not used to establish or deny causation by itself, but is used as a tool to assist in the evaluation of causation in light of the evidence as a whole.” DOL emphasizes that SEM is only one of the tools used by claims examiners to assist in determining eligibility for compensation under Part E.

As of December 2012, 13,697 toxic substances and 14 DOE facilities are listed in SEM. The database contains exposure information about a DOE facility, including uranium mining and milling sites and ore-buying stations, toxic substance information, and a record history. It should be emphasized that SEM is site-driven and that a user must first specify a DOE facility of interest to access information on toxic substances.

Findings

The committee noted several strengths of SEM, including its development with consultation from DOE experts and former workers and its attempt to be comprehensive in listing toxic substances found at DOE sites and their associated diseases. However, the committee also identified major weaknesses: difficulties in accessing information; lack of detailed exposure information; and poor handling of complex exposures, including exposures to mixtures, lack of clarity for why certain links are missing, incomplete or inconsistent exposure profiles for particular locations and jobs, disregard of epidemiologic studies of DOE workers, and the sole use of Haz-Map for toxic substance—occupational disease links.

The committee conducted an exercise to illustrate where toxic substance—disease links might be missing in SEM and to identify reasons for the omissions. Overall, the committee found that links may be missing in SEM for several reasons, including ambiguous criteria for establishing the links in Haz-Map (the source of the SEM links); lack of consistency between the Haz-Map “Diseases” field and the SEM “Specific Health Effects” field for some substances; an inability to deal with complex exposures, such as exposures to mixtures; and delays in updating links in Haz-Map and thus in SEM.

RECOMMENDATIONS

The committee found that focusing on information in only one SEM field, “Specific Health Effects,” as imported from the Haz-Map “Diseases” field, without consideration of the EEOICPA claims process was difficult because its review lacked context. Furthermore, the “Specific Health Effects” field did not permit consideration of many aspects of occupational health, including level of exposure (concentration, frequency, and duration), strength of association, and exposure to more than one chemical at a time. Nevertheless, the committee came to three overarching recommendations for improving the toxic substance—disease links in SEM:

1. Add supplemental information sources to the health effects information imported from Haz-Map.

2. Improve the structure and function of SEM, including the addition of available exposure information.

3. Use an external advisory panel to review the health effects information in SEM.

Although those three recommendations focus on improving SEM, recommendations 1 and 3 and portions of recommendation 2 are also applicable to Haz-Map. The committee believes that establishing a formal oversight and review process for the Haz-Map database and using a weight-of-evidence approach are critical for both maintaining and expanding the Haz-Map database and for its use in SEM. Expansion of the information used in Haz-Map and inclusion of citations for all the information in each of its fields would greatly enhance its utility not only for SEM but also for other users. Peer review of the database would also increase public confidence in its accuracy and comprehensiveness and help ensure that it contains the most current information available, irrespective of its use for SEM.

Each of these recommendations is discussed in greater detail in the following sections.

RECOMMENDATION 1: Use supplemental information sources for the Site Exposure Matrix database.

The committee found that supplemental data sources, in addition to the occupational—disease links imported from Haz-Map, are necessary to provide a more comprehensive picture of the adverse effects that may be associated with exposure to the toxic substances found at DOE sites. The committee suggests that two types of information might be used to supplement the data field imported from Haz-Map: bibliographic information, such as that in TOXLINE, and evaluative information, such as that in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) database and the National Toxicology Program (NTP) substance—specific reports.

Use of bibliographic databases, such as TOXLINE and PubMed, would require the use of trained and knowledgeable staff to interpret the information from the documents cited in the databases and draw conclusions regarding links between toxic substances and possible occupational diseases. The committee suggests that those databases be searched periodically, but recognizes that incorporating information from them will be time-consuming and will require expert review.

Many toxic substances have already been evaluated by authoritative organizations, and the committee encourages use of the evaluations for SEM. The committee acknowledges that some sources of evaluative information are already used to make the toxic substance—disease links in Haz-Map, as listed in the Haz-Map reference list, but their use does not appear to be systematic or comprehensive, and in some cases, including NTP toxicology reports, they are not used at all. The advantage of including evaluative databases and documents is that they typically use a weight-of-evidence approach to draw conclusions about the strength of an association between exposure to a toxic substance and a disease. They also typically have a defined method, describe the evidence base of their conclusions, and, for the most part, are periodically updated with new evidence and documentation of whatever changes have been made in the conclusions. Among the databases and documents that evaluate health effects of individual toxic substances or groups of related chemicals are the EPA’s IRIS database and background documents, the Agency for Toxic Substances and Disease Registry (ATSDR) toxicologic profiles, NTP toxicology studies, the background document for the preamble to the Occupational Safety and Health Administration’s permissible exposure limits, IARC monographs, the California Environmental Protection Agency Office of Environmental Health Hazard Assessment (Cal/EPA OEHHA) toxicity-criteria database and staff reports, documentation for the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit values (these are not publicly available but must be purchased), National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit documentation, and the NIOSH Pocket Guide to Chemical Hazards. For virtually all those information sources, conclusions on the toxicity of a substance

are drawn by a group of experts on the basis of established criteria and a weight-of-evidence approach.

RECOMMENDATION 2: Improve the structure and function of the Site Exposure Matrix database.

The committee has a number of specific suggestions for the SEM database that it believes will help users (both claims examiners and the public) to navigate the database and retrieve information more effectively. The committee has tried to be realistic about modifying the SEM and to limit the number of its suggested changes. However, it believes that such changes will greatly improve both the usability of the database for claims examiners and the public and the strength of associations between exposure to toxic substances and possible diseases.

First, the committee believes that the current links between toxic substances and occupational diseases must include appropriate bibliographic references in both SEM and Haz-Map. The committee spent considerable time in attempting to determine the evidence used to make the links in Haz-Map and thus in SEM and in many cases was unable to do so. The Haz-Map “Diseases” field does not reference the evidence base (or citations) used to determine a specific substance—disease link. Such information should be provided. If appropriate citations to the evidence were included in Haz-Map and in the SEM, the transparency of the database would be improved, and the strength of links could be assessed more easily.

Second, the committee recommends expanding SEM search capabilities. For example, better search capabilities would assist users in identifying toxic substances and subsequently the diseases associated with specific job descriptions (such as for a plumber) for more than one site. Currently, this must be done site by site.

Third, although the committee was asked to comment on the National Institutes of Health (NIH)—NLM review process for Haz-Map and on the Haz-Map developer’s review process, the committee notes that several levels of review should be used for both Haz-Map and SEM. The peer review process is discussed in connection with Recommendation 3 below, but a quality-control review of both databases is critical for ensuring their accuracy. The committee suggests that DOL or its contractor conduct a quality control review of all records to ensure that the data abstracted from each information source are correctly cited, have no typographic errors, and are complete (that is, that no important information has been omitted).

RECOMMENDATION 3: Establish an expert advisory panel for the Site Exposure Matrix database.

To accomplish the two major recommendations given above, the committee recommends that DOL establish an expert advisory panel. This is not the first

time that such a panel has been suggested and there is a precedent for such a panel as required in Part B of EEOICPA. Furthermore, the proposed EEOICPA Amendment Act of 2011(H.R. 1030) would have required the President to establish an Advisory Board on Toxic Substances and Worker Health to review and approve the SEM database.

An expert advisory panel could perform several important functions with regard to the SEM. This IOM committee recommends that the expert advisory panel be broad based, external to DOL and its current SEM contractor, and include a variety of expertise such as epidemiology, occupational medicine, toxicology, and industrial hygiene. The committee also recommends that the advisory panel include representation of the claimants and their advocacy organizations.

The expert advisory panel would have several immediate tasks:

•   Establish the criteria for the evidence base for causal links between exposure to a toxic substance and an occupational disease; criteria might be expanded to include a category of “evidence of no association” as is used by IOM and IARC.

•   Determine the information sources that might be reviewed to identify information on possible links.

•   Develop a worksheet or other documentation to capture the evidence taken from each information source, including Haz-Map.

•   Oversee revisions of SEM to add appropriate fields for capturing supplemental information (such as, chemical interactions, route of exposure, and IARC 2A designations), supplemental information sources (such as NTP, ATSDR toxicological profiles, and IRIS), and update information (such as the date of the last revision of the record and the fields revised).

The expert advisory panel would also have several ongoing responsibilities in support of EEOICPA, Part E:

•   Peer review of all new links in SEM that are based on both Haz-Map and the supplemental information described earlier. This might include determining whether the appropriate references are screened and the data are accurately cited.

•   Assessment of occupational diseases that might result from complex exposures.

•   Identification of potential new links and tracking them for possible future inclusion in SEM, including those suggested by external sources.

•   As time permits, review of existing causal links in SEM that are based solely on Haz-Map.

•   Periodic review of a sample of the toxic substance—disease links from both accepted and rejected claims to determine whether SEM links are actually assisting in the claims process and, if not, what improvements

   could be made in the toxic substance—disease links or what other information might be added to the SEM that would help claimants and claims examiners, such as available monitoring information, disease terminology, or results of cohort studies of DOE workers.

The committee recognizes that peer review is not a simple task, but it is critical if the SEM is to provide both DOL claims examiners and claimants with comprehensive, accurate, and understandable information. The committee also acknowledges that several approaches may be used to institute a peer review process for SEM, all of which have advantages and disadvantages. These approaches might include having the expert advisory panel review contractor assessments of the evidence available on toxic substance, having the expert advisory panel review the available evidence on a substance that was gathered by a contractor, or having the available evidence assessed by an internal expert advisory panel and then having the assessments reviewed by external experts. A major feature of each option is that all information and actions are documented so that the evidence base used to make decisions about the links between toxic substances and occupational diseases is transparent.

In summary, the committee recognizes the pressing need for SEM and the urgency with which it was developed and understands its inherent dynamic nature and the need to be able to adapt to updated and new information. However, as the EEOICPA claims process has evolved and new claims have continued to be submitted to DOL, the need for peer review of SEM (as well as Haz-Map) has increased. The committee believes that implementation of the recommendations in this report will make it possible for the DOL claims process to be improved for both claims examiners and claimants.

STATEMENT OF TASK QUESTIONS AND RESPONSES

In addition to offering recommendations to improve SEM, the committee provides here concise responses to the eight questions in its Statement of Task.

1. What, if any, occupational diseases that might have affected the DOE contractor workforce are missing from SEM?
The committee examined the list of diseases in SEM and found that some diseases such as those of the cardiovascular system and ovarian cancer are not listed in it. Occupational diseases are listed in SEM only if they are associated with exposure to a toxic substance, so diseases associated with a particular job or worker population may not be included. Such organizations as IARC also look at associations between specific occupations (including painters and welders) and diseases in those workers without reference to exposure to specific toxic substances. DOL should consider those types of associations to identify other occu-

  pational diseases that may affect the DOE contractor workforce. Furthermore, epidemiology studies conducted on DOE worker cohorts are not included in SEM. Given the opportunity to assess effects in the population of interest, results of those studies should be carefully considered by DOL and the recommended expert advisory panel.

2. What, if any, links between occupational diseases and toxic substances present at DOE sites are missing from SEM?
The committee notes that some links between toxic substances found at DOE sites and diseases associated with them are not in SEM, such as the link between asbestos and ovarian cancer. The committee notes, however, that given the lack of exposure information in SEM—including period of use and intensity and frequency of exposure—it is difficult to ascertain whether occupational exposures were acute or chronic and were sufficient to result in chronic occupational disease. The committee did not conduct a systematic review of all the substance—disease links in SEM, which includes more than 13,000 substances and more than 120 occupational diseases.

3. Is there additional literature (preferably human epidemiological in nature) that might be incorporated into SEM to strengthen or add to the existing links between toxic substances and occupational diseases? Are the existing links sufficiently robust?
Because SEM incorporates toxic substance—occupational disease links only from Haz-Map, any information missing from Haz-Map is necessarily missing from SEM. Because Haz-Map does not adequately reference the evidence used to establish each toxic substance—disease link (except for cancer), the committee was unable to determine what additional literature might make the Haz-Map links more robust. The committee strongly recommends that evidence used to establish the Haz-Map links be clearly referenced in the Haz-Map “Diseases” field. Furthermore, the committee has commented on the information sources used for Haz-Map (see Chapter 2) and on the use of additional epidemiologic information in SEM (see Chapter 3), particularly the use of DOE worker cohort studies. Better and more comprehensive use of the existing data sources, such as IARC and ATSDR, and new ones—such as Cal/EPA OEHHA background documents, NTP, and IRIS—would substantially improve the robustness of the links in both Haz-Map and SEM. The recommended expert advisory panel could provide advice on the best way to incorporate the epidemiologic studies conducted in DOE worker populations; the exposures of these workers are directly relevant to the claimant populations.

4. What, if any, other occupational disease databases might be used to supplement the Haz-Map information in SEM?
Haz-Map is used for SEM because it provides causal toxic substance—occupational disease links in an easily captured field. Haz-Map is a unique database, and the committee was unable to identify any other databases that explicitly link occupational exposures to toxic substances to occupational diseases. However, the committee does not believe that lack of such databases means that other sources of information might not be used to supplement either Haz-Map or SEM. The committee emphasizes that databases alone, whether occupational or other, are not sufficient resources to supplement Haz-Map information in SEM, and it recommends that such documents as ATSDR toxicological profiles, NTP reports, and EPA background documents be reviewed by the proposed expert advisory panel. Many of those documents contain information on health effects seen in worker populations that have been exposed to the substances of interest. Another database that might be used is EPA’s IRIS, which has clear documentation of the evidence on which EPA’s conclusions are based.

5. How scientifically rigorous are the disease links contained in SEM and Haz-Map?
The toxic substance—disease links in Haz-Map, and thus in the SEM, for cancer are scientifically rigorous inasmuch as they are based solely on IARC’s determination that there is sufficient evidence that a given substance is carcinogenic in humans (Group 1). However, for noncancer health effects in Haz-Map and SEM, it is difficult to determine the evidence base for some of the links. Therefore, the committee is unable to state with certainty how rigorous the links are and finds that the rigor of links varies. In some cases disease links are based on one case report and in others on a substantial body of evidence. Furthermore, the links for mixtures are not robust.

6. What are the strengths and weaknesses of the NIH/NLM peer review process with regard to Haz-Map? How might this process be improved?
There is no NIH or NLM peer review process for Haz-Map. The committee finds that that is a critical weakness for the database. NLM indicated that its staff copyedits the toxic substance profiles for Haz-Map and makes the links to other NLM databases, such as the Hazardous Substances Data Bank (HSDB), but NLM does not conduct any peer review of the substance—disease links determined by the Haz-Map developer. NLM also does not conduct peer review of any of the publications listed in PubMed; that is the responsibility of each journal. NLM does

  not conduct peer reviews of any external publications, even manuscripts. It is merely a platform for Haz-Map, and has little involvement in content. NLM does facilitate the peer review process for the HSDB, a database cited in Haz-Map, using an external group of experts. There are several options for a peer review process for both Haz-Map and SEM.

7. Can any known (epidemiologically significant) synergistic effects between chemicals/chemicals or chemicals/radiation be placed in SEM? If so, what are the sources of these links and are they occupational in nature?
Research on synergism underscores that this type of chemical—chemical interaction is a valid scientific phenomenon. Such interactions, some of which are occupational, could be flagged in SEM for evaluation case by case. ATSDR and EPA conduct health assessments of chemical interactions, and these could be included in SEM in a new field as supplemental information. The evidence base on chemical—radiation interactions is less robust, especially in humans. However, as more information becomes available, the proposed expert advisory panel could revisit this topic and determine whether such interactions should be flagged in SEM.

8. What consistent process or approach could be used to consider a disease or cancer established when studies are inconclusive, inconsistent, or conflicted in some way?
As discussed above, the committee strongly recommends that an expert advisory panel be established to review the evidence on any potential toxic substance—disease link. Such a panel, using a weight-of-evidence approach, could determine how to assess inconclusive, inconsistent, or conflicted studies for purposes of evaluating whether there is a causal link. The panel may wish to develop its own criteria for weighing evidence or use criteria established by other authoritative organizations, such as IARC, NTP, and IOM.

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