Dr. Johnson remarked that the wording is EPA wording and ATSDR certainly supports it. One of the things we have learned over the past several years is the absolutely essential involvement of communities in decisions that affect them, decisions on remediation of individual sites, decisions that relate to land use, decisions that relate to water quality standards for their site. One of the things we have not heard as a matter of disagreement between the Administration and the Congress and nongovernmental organizations is the essential role of communities. Title I is likely to be preserved in some form as to what eventually gets passed as statute.
The implications for ATSDR are yet to be worked through. Dr. Johnson thought that these community working groups that would be established ought to have a role in the health part as well. The current language gets more at land use remediation decisions, other kinds of restoration issues. He noted that these same groups ought to have as part of their agenda the health issues as well, and ATSDR would not be supportive of having an independent community group set up simply to deal with health. Our hope would be that these groups would handle health as well as the other issues.
Dr. Teta mentioned that ATSDR already has community groups. Dr. Johnson agreed, but they are discretionary. Under the revised statute, the groups would become nondiscretionary. They would be authorized and would be established at each site. Dr. Johnson did not anticipate any difficulty in working through this with EPA and with individual communities. There are some communities where the health issues may not be appropriate for placement on the agenda of a "community working group." It may be that the issues there are non-health issues. In which case, you would not make that part of their agenda. But for many sites, that should be part of their agenda.
Dr. Walker asked if the revised statute would result in a diminishing of ATSDR's role in the whole Superfund process. Dr. Johnson said no. He saw it as an enhancement. It is a modest enhancement which he thought was appropriate. It is not a usurpation of responsibilities that rightfully lie with EPA and with the states. It does, in a modest sense, enhance our involvement with communities and with EPA at sites. It continues much of the authorities added in 1986. The notion of applied research continues. The registry program continues. The surveillance, the epidemiology efforts continue. The health education would be broadened in a modest sense to include community education authority as well as authority for educational outreaches to nurses and nursing institutions. So, there is a modest increase in responsibility.
Dr. Walker noted that the revision would result in fewer toxicology profiles. Dr. Johnson noted that ATSDR has distributed over 1.3 million of these documents. What this language would do would be to give ATSDR more authority to determine when to update them and to republish them and would give ATSDR more authority to be more selective. There are substances outside this list of prioritized substances where we think a profile should be developed. In fact, we would like to have the clear authority to do that. Dr. Johnson agreed that there would be fewer new profiles. He stated that there would be more updates and revisions of extant profiles. The challenge to ATSDR is to keep the profiles up-to-date and to make them available to the public.
Dr. Shoemaker asked Dr. Johnson to amplify on the purpose in the revised statute that there would be a stronger link between remedial action and public health. Dr. Johnson noted that the Agency, by statute, by the 1986 Amendments to Superfund, must do a public health assessment of every site that is placed or proposed for placement on the National Priorities List (NPL). There are now some 1,350 sites. In addition, ATSDR has to do a public health assessment of sites that are petitioned of us by the public. We are running approximately 85 to 90 petitions per year. That is a considerable number of sites that we are supposed to be looking at by law each year.
Dr. Johnson noted further that as we do a public health assessment, we come to certain conclusions as to the level of hazards that site may be presenting to the public's health, and the conclusions that the Agency comes to are framed around a series of public health actions that we expect to be adopted, to be implemented by ourselves, by EPA, by states, and others. On occasion, we have found that, in part because of our failure to get the public health assessment done on a timely basis, some remedial actions have preceded in advance of finishing the public health assessment. We can understand that. Often, it comes down to a matter of resources. We would like to have our recommendations that are public health based factored into EPA's decisions and to the state's decisions on what remedial actions to take. In particular, there are instances when incineration is agreed to as a course of remediation; ATSDR is always called in after the fact by states or by local communities. We would like to have an opportunity to have our recommendations brought forward earlier so that some of these disconnects between government and the public might be reduced in number.
Dr. Walker raised the issue in the revised statute on establishing a national registry for persons exposed to toxic substances. He thought this was rather open-ended. Dr. Johnson noted that what this language does is expunge the language that directed ATSDR to establish two kinds of registries. The current language says, ATSDR, in cooperation with the states, shall establish a registry of all persons exposed to toxic substancesþand then the language continuesþand a registry of diseases. ATSDR has sought counsel from various sources, including the public, as to what a disease registry might be. The language was unartful from Congress as to what a disease registry should be. Rather than adding this as part of our statutory mandate, the revised language eliminates the disease registry mandate.
Dr. Johnson mentioned that there are major points of difference that the Congress, the Administration, and the public are still attempting to come to grips with on Superfund reauthorizationþmatters of liability and matters of how you go about a national program of establishing cleanup standards for Superfund sites. There are big issues on the matter of municipal liability. Whereas all of that has attempted to be dealt with in the Administration's bill, there is no indication of closure on some of those points of debate.
Overview of Risk Assessment in Public Health Practice
Dr. DeRosa gave a brief presentation on the risk assessment paradigm as it has been defined by the National Research Council in 1983 and discussed two recent reviews, one by the Office of Technology Assessment and another by the National Academy, about the merits of risk assessment. He then briefly presented the concept of risk analysis as it was defined by the Council on Environmental Quality in 1989 as a conceptual or decision-making framework in environmental health. Dr. DeRosa then outlined current risk assessment practice(s) at ATSDR.
Concurrent with the National Academy study, Congress authorized the Office of Technology Assessment to develop a report addressing research on health risk assessment, basically how can we move forward in this effort on a scientific basis? The report reaches two overarching conclusions that were recently summarized in Environmental Health Perspectives. One was that there was a need for a tighter integration across federal agencies in conducting and interpreting the results of research and applying those results in risk assessment. A second conclusion was that there needed to be a tighter linkage between the relevant components, not only of risk assessment, but of research and risk management as well.
Dr. Shoemaker noted that she had some trouble bringing what Dr. DeRosa presented down to the specifics of what would actually happen at a site. From the point of view of an engineer, the EPA tells the people involved at a certain site that you have to meet a certain standard, and then the engineers go out and try to design a system so that they can clean up this site and bring it down to that standard. The cost of this remediation is very sensitive to the standard. A two-fold difference in the standard can make a ten-fold difference in the cost, so it is very important what those numbers are.
Dr. Shoemaker noted further that the risk assessment comes up with that standard and then the risk management is at the point where you go to the engineers and you say, "you must meet this standard." Now, what you are talking about is bringing risk management and risk assessment in a more integrative fashion. How does this model change if you do that? Dr. DeRosa mentioned that the distinction between the end point conveyed by the risk assessor and what is a standard as defined by risk management practice needed clarification. Typically, the conclusion of the risk assessment is referred to as a criterion, or a series of criteria that are then folded in with the political, social, economic, other types of concerns that go into standard setting, so that the standard represents the end point of the risk management continuum. Dr. Shoemaker then remarked that at the end of risk management, engineers design the facility and incorporate in it some idea of how changes in the standard will affect the economics of cleanup.
Dr. DeRosa highlighted the first question that was shared with the Board, "Where should ATSDR head in its risk assessment program in terms of the appropriate balance of qualitative and quantitative approaches to risk assessment?" He noted that ATSDR was not asking the Board to respond to this at this point, but as an outgrowth of the presentations that would be presented by the ATSDR staff. Dr. DeRosa outlined specific issues that ATSDR would like to get some feedback on from the Board. He noted that they were reminiscent of some of the earlier issues identified and presented to the Board. These included (1) What is the appropriate role of animal and human data? (2) What are the best methods available for extrapolation in terms of animal-to-human data, sensitive population, high-to-low dose types of extrapolation? (3) Have we adequately predicated our approaches on science to provide a reasonable basis for this extrapolation and inference that we engage in? And, (4) while it is not a specific question, what would be some areas that might be opportunities to enhance that scientific basis for risk assessment? He alluded specifically to structure activity relationships and kinetic modeling, mechanism of toxic action, and approaches to low dose modeling.
Finally, Dr. DeRosa asked the Board if the significant-health- effects levels (SHELs) framework that would be presented in the afternoon represents an appropriate construct to integrate a range of different information, chemical-specific data as well as site-specific data in the face of multi-route, multi-chemical types of exposure scenarios?
Dr. Walker asked if ATSDR is moving more and more toward risk assessment than it has in the past to guide its activity and set priorities? Dr. DeRosa remarked that the move by ATSDR in that direction was one of more clearly articulating how ATSDR utilizes that information, how we might take better advantage of it. Dr. Teta thought that ATSDR may be moving more toward a quantitative risk assessment.
Dr. Jackson noted that we are confronted by two powerful traditions. On the one hand, you have the engineering tradition where you know the strength of steel and concrete, and you can apply safety factors and design a bridge. It is very quantitative, and that is what we bring forward from that tradition. The other very powerful and important tradition that we really need to make sure does not get lost is the public health tradition. The tradition in public health has really been to protect and identify the weakest, most sensitive members of the population. It has been profoundly successful. It is almost a type of failure analysis. He mentioned that some science panelists stated that they would not accept uncontrolled data. For example, they were rejecting results of cluster investigations of human illness because they were not controlled. He noted further, that you cannot get match controls for these episodes. That tradition of public health and epidemiology is where we are really learning about where the failures have occurred.
Dr. Ho raised a question on the use of non-cancer end points. Dr. DeRosa replied that in the derivation of minimal risk levels (MRLs), ATSDR selects the most sensitive end point based on a review of the literature for the basis of the MRL, assuming that if you have the most sensitive end point identified you will have protected against the other non-cancer health effects as well. The challenge is that as our ability to detect biologic change in systems increases, our ability to interpret the significance of those changes, particularly in the area of immunotoxicity, may not be adequate. Dr. DeRosa thought that this underscores the importance of having a strong deliberative process incorporating to the maximum extent biomedical judgment.
Science Base for ATSDR MRLs
Dr. Williams-Johnson provided the Board some background and historical perspective on the evolution of the MRLs. Dr. Selene Chou presented the current guidance for quantitative assessment and biomedical judgment employed in deriving the minimal risk levels. Dr. Chou spoke to some of the science issues that were addressed during the deliberations of the MRL work groups as they make their determinations for these estimates and how the biomedical judgment is exercised in various aspects of that deliberation process. Dr. Malcolm Williams provided an overview of the guidance that has been developed within the Division of Toxicology for identifying and clarifying adverse health effects, that are used as the basis for MRLs, and as are characterized in the toxicological profile. He presented some specific examples that have been developed for the chemical profile managers. These are guiding principles for determining when an effect is considered adverse and biologically significant as it relates to the extrapolation from animal data to humans.
The MRL was developed as a tool to be used by ATSDR health assessors for looking at the toxicity assessment associated with a compound that might be in the environment and to which humans might be potentially exposed. As such, ATSDR defines or looks at the MRL as being a guidance tool or a guidance value for the toxicity assessment as it applies to the greater view of risk assessment practice.
As defined in the ATSDR toxicological profiles, the minimal risk level is defined as an estimate of the daily human exposure to a substance that is likely to be without appreciable risk of non- cancer adverse health effects over a specified duration of exposure. The specified duration of exposure is identified by ATSDR as acute exposure (14 days or less); intermediate exposure (that period of time less than 1 year of exposure); and chronic exposure (as 1 year or more), a period which is somewhat different from other federal agencies in defining chronic exposure which is in some cases considered a lifetime exposure.
MRLs are used primarily within the Agency in developing the environmental media evaluation guides (EMEGs), and these toxicity assessments are used in conjunction with exposure assessments. MRLs also provide a basis for providing information to physicians and/or health officials at the state and local levels as it pertains to their information needs for assessing potential toxicity of contaminants in the environment. Taking into consideration that the MRLs are used in conjunction with other considerations for a potential exposure scenario, the MRL is not intended to be a value that is used in regulatory action but just as a guide for a toxicity assessment. Hence, the MRL should not be considered or construed to be an action level or a clean-up level.
Briefly, an MRL is derived for either the inhalation or the oral route of exposure, as the database permits, and specifically for these routes of exposure at the acute, intermediate, and chronic durations of exposure. Data based on evidence in humans for adverse health effects to a specific substance or the availability of animal data in the absence of human data are used to derive the MRL. These data points are determined to be the no-observed-adverse-effect level (NOAEL), or the subthreshold level, for the most sensitive end point, looking at the entire toxicological and epidemiological database for a specific substance. In the absence of an identified subthreshold level, the lowest-observed-adverse-effect level (LOAEL), or the threshold level, is used in deriving MRLs.
The uncertainty factor approach as defined by the National Academy of Science (NAS) is used as a model in developing the ATSDR MRLs. As defined by NAS, an uncertainty factors of 10 should be used when estimating acceptable daily intake for substances for which there is no valid human epidemiological data available. An additional uncertainty factor of 10 or a total uncertainty of 100 should be applied when human data are considered inconclusive or not available at all but long-term animal data are available.
An uncertainty factor of 1,000-fold should be used when long- term, acute human data are unavailable, i.e., human data is not available and experimental animal data are considered scanty. This uncertainty factor approach was further modified by ATSDR. For interhuman variability, a 10-fold factor is used for estimating the effects in a diverse population and the attempt to protect those that are most sensitive in the population.
Dr. Jackson noted that the National Academy of Sciences Committee on Pesticides in the Diet of Children reported that many drugs do not have an adequate database for developing organisms. There was concern with both the data paucity for the very young and the potential for heightened sensitivity. He mentioned the need for an additional safety factor.
Dr. Bergeisen noted that there was some confusion on how the MRLs are used. The MRLs are used as a guidance tool advisory for physicians and public health officials. It is not intended to support a regulatory action. But, when you look at the definition of the MRL, the NOAEL or LOAEL divided by the uncertainty factor, it is identical to the definition of the EPA reference dose which is used for regulatory action. He asked how the two are coordinated for the public?
Dr. DeRosa mentioned that ATSDR has begun discussions with a range of different groups within EPAþthe Office of Research and Development, members of the reference dose (RfD) work group as well as some former employees of EPA, about organizing a symposium to be held in the next specialty section of the Society of Toxicology this coming year. The focus will be on the entire range of issues that go into any differences or any common themes that may emerge about RfDs and MRLs. Dr. Longley agreed that this type of discussion is needed. He cited the need for a dialogue between both the regulators and the public health folks. Without that, the public ends up being completely confused.
Dr. Walker asked what ATSDR's experience with MRLs has been. Mr. Williams mentioned that this would be covered later by Dr. Mellard and Dr. Abouelnasr, but in general, ATSDR has found them to be a very viable source and a very important source of information in development of the public health assessment.
Dr. Chou then shared with the Board the current ATSDR operational and working framework in deriving minimum risk level. Dr. Williams also discussed with the Board the guidance that ATSDR uses in terms of assessing health effect end points that are used in the MRL process. He noted that the major objective of risk assessment is to determine the potential injury to the organism that results from exposure to hazardous substances. Therefore, it is crucial to the process that one has the ability to determine, detect, evaluate, and assess the significance of these health effect end points. The process of selecting the appropriate health effect end point is largely qualitative. The qualitative assessment of health effects can be viewed basically as a two-tiered process. The tiers involved are (1) the determination of an adverse effect and (2) the determination of severity.
Dr. Williams defined an adverse effect. He noted that adverse health effects can be viewed basically as those effects which will bring about functional impairment, and/or a pathological lesion which results in a diminished capacity of that organism to perform, and/or it may negatively impact upon the ability of the organism to withstand additional challenge. Dr. Williams then addressed the issue of severity or biological significance of the effect.
Dr. Williams presented specific issues that the MRL group faced, including the relevance of extrapolation of animal data to humans, species-related effects, selection of appropriate end points, biological effects of unknown significance, and the hepatic adaptive response. Other issues presented by Dr. Williams included renal pathology in the male rat, cholinesterase activity inhibition, organ weight changes, and body weight changes. All of these are specific issues which have been addressed by the ATSDR MRL group and are issues for which ATSDR has developed specific criteria.
Dr. Jackson questioned the statement made by Dr. Williams that a 20 to 50 percent cholinesterase inhibition is a non-serious LOAEL. He pointed out that at 20 percent, farm workers are pulled out of the field. The Defense Department yanks people out of production plants, and they are out for a month at a time. Dr. Jackson considers that "serious." In addition, the folks in so-called clean-air Nebraska are awash in cholinesterase inhibitors, and if you already have them 20 percent inhibited and then you are sending them out to the field with the crop dusters, you are reducing their compensatory ability, their ability to really respond to additional challenges.
Dr. Rifkind mentioned that it would be really a useful area for ATSDR to put some attention to getting some hard facts about what, in fact, are the extent of acceleration of human mixed function oxidase enzymes in exposure to toxic chemicals. She also noted that there is difficulty dealing with so many different chemicals and with such a variant amount of scientific data, some of which is very scanty. Dr. Rifkind also asked how the ATSDR MRL's differ from the EPA numbers. Dr. Chou, who is the ATSDR liaison to the EPA RfD work group meetings, noted that one difference between EPA's RfD and ATSDR's MRLs is, first of all, the duration of exposure. Right now, EPA only addresses chronic exposure and ATSDR addresses acute, intermediate, and chronic.
The Board questioned ATSDR on the rationale for the development of MRLs. Dr. DeRosa noted that the statutory directive given by Congress addressed the need to develop significant human exposure levels (SHELs). It was very difficult in looking at the language and in balancing that against the available science to interpret exactly what that meant and how it was to be done. After some discussion among representatives of both EPA and ATSDR, there was a sense that perhaps a qualitative approach to developing such guidance was the way to go, the issue of risk characterization perhaps being qualitative and/or quantitative. It was intentionally decided that the derivation would be very much analogous to what EPA had previously done by way of the reference dose.
Dr. DeRosa was involved in some of the early discussions revolving around the first 25 toxicological profiles, and it was very much an issue of defining the necessary resources to move forward and implement the statutory directives of Congress. So, MRLs were conceived as a stand-in or an interpretation in a preliminary sense of what would be used in lieu of the significant human exposure levels.
Another point that deserves mention is the issue of independent assessment. Again, the sense of Congress was, perhaps, reminiscent of the experience with the National Institute for Occupational Safety and Health and the Occupational Safety and Health Administration that an independent agency dealing with such issues would be useful. That such an independent assessment would be linked very closely to extensive peer and public review, again making the process as translucent to the public as possible, thereby engendering the maximum degree of trust in the types of guidance that would be developed.
Dr. DeRosa touched briefly on the issue that Dr. Teta raised, the hierarchy that ATSDR uses. ATSDR does have guidance that lays out this hierarchy. ATSDR does look at the database in aggregate with the idea of learning from any source of information, whether it is the animal database or the human epidemiologic data, what is the most sensitive end point that we might link to a particular chemical.
Dr. DeRosa noted that ATSDR prefers to use human data over animal data for a given route and duration of concern. That is one overriding principle in terms of hierarchy. ATSDR uses no- observed-adverse-effect levels in preference to low-observed- adverse-effect levels. Again, with the idea in mind that the NOAEL would be a more sensitive end point on which to base the MRL and ultimately more protective of human health.
Dr. Walker commented that it is very difficult to get a clear and concise answer from epidemiological data and most of the studies will say there is a need for further study. This puts ATSDR in a very difficult position as to animal data versus human data in deciding how to proceed. Dr. DeRosa noted that this is one of the reasons that ATSDR feels very strongly about pursuing some applied research in the area of mechanistic toxicology. The degree to which ATSDR can illustrate a concordance between the two groups, animal versus human, ATSDR would be in a stronger position in relying on the animal database.
Dr. Bergeisen asked for some clarification on the ATSDR categorization of durationþthe acute, the intermediate, and the chronic. Dr. DeRosa commented that they were different, but that the difference was an attempt to reflect exposure durations that would be relevant to health assessments at sites. These were the intervals that were considered to be most relevant to ATSDR's mandate in dealing with public health issues at sites.
Dr. Teta raised a point on the importance of expert judgment. That is, we apply safety factors for good reason because there is uncertainty. There tends to be greater uncertainty where there is less scientific data. There is typically less scientific data where there is less concern. Often the case is that a chemical was not a great concern, it was not well studied. An issue arises, and now it is of interest to set a level. You have a type of bias going on where you tend to set, in some cases, lower and lower levels for things that may not be of much concern. The things that are of concern are well studied. Often, we have more data, fewer uncertainty factors, and your level may end up higher than those things that are less hazardous.
Dr. DeRosa agreed with Dr. Teta and indicated that the linkage of this effort to the identification of research needs and the referral of those research needs to those who are able to implement that type of work is a key point that would allow us to move further on those poorly characterized chemicals. In the absence of data, the relatively higher magnitude of the uncertainty factor would be a compelling motivation for industry to provide some efforts to better define our concerns from a toxicological perspective.
Dr. Teta raised the issue of criteria for setting or changing safety factors. Dr. DeRosa noted that ATSDR has drafted some preliminary guidance for that purpose and are convening, at some point, a group of peer reviewers to look at that issue specifically.
Science Base for ATSDR EMEGs and Other Comparison Values
Dr. Abouelnasr gave the Board an overview of the science base for ATSDR's environmental media evaluation guides along with other comparison values. She noted that the question to the Board is, "Are the EMEGs and other comparison values appropriate for their intended use, that is, to select contaminants for further evaluation and public health assessments?" She focused specifically on the background of what the comparison values are (EMEGs, RMEGs, and cancer risk evaluation guides [CREGs]), why we need them, how we use them, and how we derive them. She also identified several other values that are used by ATSDR Health Advisors.
Dr. Walker asked what the major problems have been in terms of applying this process. Dr. Abouelnasr noted that one of the problems is the fact that the numbers can change frequently as more information is made available or other information is deleted. It has been very difficult to ensure that health assessors have the most up-to-date information, which is why ATSDR has placed it on a database. Other problems are in ensuring that the people who read and use the health assessment understand what the comparison values are used for and what they are not used for. There has been criticism that the comparison values are very conservative, and people feel that we were trying to indicate that there was or was not a problem by using comparison values, when indeed that is not the case. That is not how ATSDR uses them.
Dr. Walker asked how ATSDR and EPA could reach some agreement on the values that are used. Dr. DeRosa mentioned that there has to be a compelling reason for going forward with the different value, one that is technically based. An example might be an RfD that was placed on the EPA files in 1985-1986 based on a subchronic study. In a subsequent iteration of our evaluation of that chemical, we see a chronic study that has, we think, a greater degree of reliability and is pointing to some different qualitative and/or quantitative conclusions. In that case, we feel compelled to reflect that in our MRL. That would result in a divergence there. There is a point of different assessments being done at different points in time based on a database that may vary because of that passage of time.
Dr. Bergeisen pointed out that EPA has a problem in the field where risk assessors are usually not aware of the ATSDR values and they have to deal with the public. When there is a discrepancy in both values, the public gets very confused. One of EPA's goals is to coordinate its responses to the public and is working closely with ATSDR staff to achieve this. Dr. DeRosa agreed that this is an issue that needs to be resolved. The challenges are community involvement, effective communication strategies, and tightening the linkages between risk assessment and risk communication efforts.
Science Base for ATSDR Significant Health Exposure Levels
Dr. Cibulas gave the Board an overview of the framework ATSDR has considered for developing significant health exposure levels (SHELs). He wanted the Board's reaction to the SHEL framework and in particular in the construct to integrate chemical-specific data into site-specific data when multi-route or multi-media, multi-chemical data are available. He also discussed information needs in the development of this construct.
Dr. Cibulas mentioned several steps in the development of SHELs including (1) determining the tolerable level for a particular substance for each route of concern for that substance, (2) partitioning this tolerable level across all relevant exposure media to determine media-specific guidance values, (3) conducting the total integrated multi-media exposure assessment, and (4) comparing this total integrated multi-media exposure with the total tolerable level. To the extent that we are being exposed to more of the substance than the tolerable level, we would say that a significant human exposure level for that substance had been reached at that particular site.
Dr. Teta noted that she was supportive of developing the science base using physiologically based pharmacokinetics (PBPK) modeling, structure activity analysis, developing assays for estrogen receptors, and so forth. That is, in fact, new data advancing science. However, she did not know exactly where to start on the SHEL concept. She was concerned that more uncertainty was being added, especially through the partition operation. She did not think that overlay of judgment will occur out in the field.
Dr. Walker mentioned that this is actually an area that needs much further study and refinement, and he thought the Board ought to agree to work with the Agency on this. He shared the concern of Dr. Teta and thought that a working group should work with the Agency and see if the concept can be further refined and developed. Dr. Teta also thought that it should be peer reviewed externally. Dr. Shoemaker pointed out that there is no demographic division of the population. This would be a useful factor in the construct.
Dr. Bergeisen liked the concept of SHELs because one of the things EPA is looking for is public health input into the decision-making process when it comes to dealing with sites. It also fits in with the President's Executive Order on Environmental Justice which states that we have to look at cumulative risk. He was concerned however that the tolerable level is based on an MRL which is a nonregulatory tool. EPA could hope to use this concept for a regulatory decision, but if it is based on a nonregulatory tool, EPA would not be able to use it.
Dr. Rifkind noted that the tolerable level in the SHEL construct included the idea of a level of exposure which does not entail any appreciable risk. She did not hear any discussion on this and asked for some clarification. Further, she questioned the application of models and noted that validation is essential if the data is to used in real-life situations.
Dr. Wheeler discussed a slope model for determining blood lead in children. First, he characterized the multiple sources of lead exposure. He then took the CDC lead guidance value for blood lead of 10 micrograms per deciliter and considered every component that adds to the total blood lead. The problem comes in linking those environmental levels with the blood lead level. If one goes to the database, which is adequately described in the ATSDR toxicological profile, one can find slope factors that were done from studies on populations around where there was lead contamination and determine what the particular links are. In summary, Dr. Wheeler noted that this SHEL-type model(s) can provide a valuable tool for site-specific analysis. By introducing multi-route and multi-media, it gives you a more realistic view of all the different types of scenarios that can occur at a site.
ATSDR Public Health Assessments
Dr. Susten gave the Board an overview of the ATSDR Public Health Assessment. He pointed out that one of the major tasks for the health assessor is to decide whether or not an exposure to chemicals will cause harmful effects in the people exposed. To do this, the health assessor has gathered extensive information on the site, has used comparison values to select contaminants for further evaluation, and has determined whether or not people are exposed. At this point the health assessor uses toxicologic information along with site-specific information about exposure to draw conclusions about possible health effects in exposed people. This evaluation involves risk analysis, or more specifically, quantitative and qualitative health risk assessment.
Dr. Susten noted further that ATSDR is interested in the Board's evaluation on whether or not ATSDR's combination of quantitative and qualitative health risk assessment in public health assessments is appropriate for making public health decisions about exposure to chemicals. He mentioned that Dr. Mellard will give the Board three examples that show ATSDR's approach to health risk assessment.
The first example, which relies heavily on quantitative health risk assessment, explained (1) how health assessors estimate the exposure dose from drinking water contaminated with acrylonitrile, (2) how health assessors compare the estimated dose to minimal risk levels and toxicologic information, and (3) how health assessors decide which health effects are likely to occur in the exposed population.
The second example Dr. Mellard presented involved lead in residential yards. This example showed how the health assessor used not only quantitative health risk assessment but also qualitative factors, such as CDC's historical 500-1000 ppm lead in soil, frequency and distribution of lead in the yard, and epidemiological studies in arriving at a decision.
The last example showed how the health assessors evaluate carcinogens, first by determining the weight of evidence for carcinogenicity, and second by estimating cancer risk. Estimating cancer risk allows the health assessor to put the degree of exposure in perspective, while considering other factors, such as frequency and distribution of the carcinogen, background concentrations, and weight of evidence, that affect the decision-making process. Dr. Mellard gave examples that showed both the quantitative method for estimating cancer risk and the qualitative factors that affect the health assessor's conclusions about cancer risk.
Summary of Board's Response:
Has ATSDR appropriately balanced quantitative and qualitative risk assessment in its public health practice?Dr. Walker opened the discussion by repeating that risk assessment is simply one piece of an array of tools and techniques and data sets that ATSDR uses in making public health assessment or making decisions about actions that should be taken. It is not the sole driving force, but it is simply one of a number of tools and techniques that the Agency uses.
He noted that the Board had recommended that a working group be designated to refine the area of significant human exposure levels (SHELs). This group will be chaired by Dr. Ho. Other members would include Dr. Mattison, Dr. Longley, and Dr. Shoemaker. The group will work with the staff for further refinement of the SHEL issue, keeping in mind some of the questions that were raised by the Board members.
Dr. Rifkind mentioned that in the last day or so, she heard more about quantitative than about qualitative aspects of risk assessment. She did not understand how the qualitative dimension is being put into the risk assessment. She said that some numbers reported by ATSDR are overly conservative and may really be over protective. ATSDR's responsibility in public health is to be as protective as possible regarding hazards. But, protection against hazards also means that the public should not suspect it is being exposed to hazardous levels if it is not. Very conservative estimates have tremendous implications in terms of public concern, worry, and fears. She thought those are public health threats just as much as disease, in addition to economic implications. Dr. Rifkind applauded the effort of ATSDR to focus on the science base in conducting risk assessments. She supported efforts of ATSDR in determining exposure levels and encouraged research efforts on the methodology of measuring exposures.
Dr. Longley was uncomfortable with some of the numbers presented by ATSDR. He shared Dr. Rifkind's concern that interpretations are being made, oftentimes from very conservative estimates, and the concern that this can create in the community and in those who might be affected. Also, he mentioned that some end results were computed from what he would consider to be very imprecise data. He referred to the soil data in particular, which was then used to arrive at a very narrowly interpreted result. The order of magnitude essentially between no action and a very serious result. That, he found somewhat disturbing. Dr. Longley also mentioned that there has to be a significant improvement in quality assurance, quality control. He made specific reference to the sampling methodology and the soil depth where samples are taken. He suggested that EPA and ATSDR should develop a common database.
Dr. Shoemaker was concerned about the quantitative assessment. She mentioned that there does not seem to be adequate adjusting for variability in the population, including changes in weights and intake rates, and probability distributions within the population. She was looking more at a demographic basis. Dr. Shoemaker also was concerned with the uncertainty factors, which are enormous and vary from 10 to 10,000. The overall impact of this is that the concentrations that are being put forth for remediation are unnecessarily low, which can cost billions of extra dollars in terms of cleanup costs. The implication of even a factor of two in the standard can be enormous in terms of cleanup costs. She emphasized that we need to try to make these numbers more accurate. Dr. Shoemaker commented that in view of limited resources, the principal responsible parties could be asked to assume a greater share of the costs.
Dr. DeRosa noted that ATSDR has worked out a process by which private sector companies can come forward and volunteer to do research in lieu of rule making through toxicant authorities of EPA. ATSDR has initiated a memorandum of understanding-like arrangement that can be entered into. Currently, we have letters of intent from two private sector organizations and are in the process now of finalizing memorandums of understanding with those organizations. At this time, we anticipate approximately 10 of the priority data needs of the 120 or so that we have published in the Federal Register being addressed through this mechanism.
Dr. Shoemaker noted that she was not referring to research but to site characterization. She thought ATSDR could develop a very rigid protocol as to what kind of information it wants and then request this information. ATSDR would review the information and then decide what kind of standard should be set. She called this applied consulting. Mr. Williams pointed out the difficulty, in terms of public perception, when contractors are used in the field. There is also a question of statutory authority.
Dr. Mattison asked for information on the health assessments that have been completed. He wanted to know what the balance was on decision-making based on quantitative versus qualitative considerations? How has this impacted on the decision that was made? He noted that in the material the Board was provided, an overall summary, an overall evaluation of the total work product of the Agency, in this context, was not included.
Dr. Mattison said he had the impression he was being asked to respond to a question when the Agency itself had not actually tried to develop data that would allow a response to be made. He did not have the sense that there had been an evaluation of Agency performance in this context.
Dr. Walker asked if it was ATSDR's intention to give quantitative risk assessment a more prominent role in the decision-making process. Dr. DeRosa commented that what ATSDR would like to see is the development of tools that would allow us to be more realistic in our assessment of risk. The discussion on significant human exposure levels, or SHELs, was an intent to identify the types of tools, kinetic modeling, structure activity relationships, that would allow us to step back from the default uncertainty factors of ten, which are very crude models, and apply some more rigorous models in incorporating both site and chemical-specific information.
Dr. Lybarger mentioned that on the issue of quantitative versus qualitative, what we have is a number of pieces of information. Historically, those have all been qualitativethat was put into some kind of qualitative judgment of hazard. We are now generating a quantitative piece of information, quantitatively derived in the manner that was provided to the Board for the last 2 days. That is a new piece of information that is then entered into the qualitative judgment along with these other things that have historically been named. So, the final judgment made by the Agency still is a qualitative process, but it now includes a new piece of information that we did not have historically, some quantitative judgment of risk.
Dr. Lybarger mentioned that Dr. Mattison's point that should be taken back to ATSDR is, "How is having this new piece of information impacting the types of judgments we have been making. How did it make a difference? How did it either change what we said, change our recommendations, change the impact on the judgment we made on the site." He cautioned the Board not to go away with the misconception that we have two completely independent processes that come up with an answer and then we choose between the two. Both of those are integrated in a qualitative sense in a final judgment of hazard and recommendation for the site.
Dr. Ho commented that we need to focus more on what kind of end point we really want to assess or use as our standard and also to consider more carefully what kind of uncertainty factors we want to apply into the assessment of MRLs or SHELs.
Dr. Jackson stressed the need for dialogue with the National Institute of Environmental Health Sciences, with EPA, with CDC, and with the states on how one goes about the health risk assessment. He thought that this may have been done too independently. Dr. Jackson also cautioned, as did Dr. Rifkind, on the dangers of physiological based pharmacokinetics. Dr. Jackson advocated more on-site visits to see what is going on.
Dr. Harris commented that there were several work groups involving EPA and ATSDR, and one of these groups was tasked with developing a paper to look at the similarities and differences between EPA's baseline risk assessment and ATSDR's public health assessment.
Dr. Walker asked Dr. Mattison to clarify his request to ATSDR. Dr. Mattison said he would like to see a listing or a compilation of the health assessments that the Agency has done. If it is decided that a more efficient way of dealing with the request is to do some kind of a stratified sampling as opposed to a total sampling, this would be acceptable. He was looking for some characterization of what has been done, the way it has been used, and to the extent that it is possible, some evaluation of the process. The annual peer reviews that Dr. Andrews mentioned could be the first place to start.
Dr. Walker asked if this could be completed for the November meeting. Mr. Williams said, "no" and suggested that he meet with Dr. Mattison and discuss this issue further.
Dr. Andrews suggested that Dr. Mattison get together with the staff and work out an evaluative process that is achievable and mutually agreeable and look at how soon it could be brought back to the Board. Dr. Walker asked Dr. Mattison if he was agreeable to this. Dr. Mattison said, "Yes."
Role and Expectations of Board of Scientific Counselors - Response to ATSDR Communication
Dr. Walker noted that this issue is essentially a question of how can the Board more effectively help the Agency respond to the Agency's concerns that may be more specific than some of the questions that they were addressing. How best to utilize the Board's time.
Dr. Longley asked what were the expectations of the Agency. Dr. Walker noted that the expectation of the Agency is that the Board will provide some assistance and guidance in the Agency's activities. In the past, members of the staff have presented specific questions that they were looking for answers to. As an example, in the presentation of the public health assessment, the Board was asked, "Is ATSDR's combination of quantitative and qualitative health risk assessment in public health assessment appropriate for making decisions?" That is a question before the Board for which the staff is looking for answers. In a general way, the expectation is that the Board will provide advice and counsel to the Agency.
Dr. Jackson mentioned that one thing he found worked well with program reviews and advisory committees was having the advisory group break up into smaller groups composed of members with experience in a specific area. He suggested the engineers could meet with ATSDR staff involved with geological modeling before the meeting and the medical members could meet with the ATSDR staff doing health studies. He also suggested more dialogue in these groups and less of a presentational session. As an example, Dr. Jackson wanted to focus on how do you manage a work load of eighty sites a year. He thought this was an issue that ATSDR would want to discuss with the Board.
Dr. Walker mentioned that the participation of EPA in the discussion, at least the representative of EPA, was productive. He wondered if, in the future, we could not have at the table other agencies to participate in the discussion(s). If one is truly serious about interagency cooperation and collaboration, that would be a desirable approach. He asked for the Board's reaction.
Dr. Mattison thought the comments made by Dr. Jackson about subgroups working more closely with staff, trying to identify, maybe in a proactive way, issues that will have to be grappled with by the staff, and process or decisions over the coming year or several years were good. He also noted that the idea of making sure that there are linkages with all of the other federal agencies that have to respond to or utilize the information that is provided by ATSDR was appropriate.
Dr. Walker asked if ATSDR would clarify for the Board on specific projects, the kind of input they need. With reference to Dr. Jackson's comments that there may be specific projects or specific activities that require engineering expertise or another project that will require toxicological expertise or the expertise of pediatricians, Dr. Walker suggested that the Board could designate members to work closely with specific staff.
Dr. Andrews thought this would be helpful. ATSDR could easily work this through the Chair directly or through the Board member and get involvement throughout the year. Dr. Andrews asked if the time spent on a specific project or activity should be part of the two annual meetings or would there be an advantage to put that at a different time.
Dr. Jackson thought the Chairman could convene the Board as a group, give out assignments, and the meeting could take place at perhaps the ATSDR facility itself. There would be intense discussion within the group. The findings and recommendations would then be presented to the full Board.
Dr. Longley mentioned that it would be worth trying at least once. He would like to have discussions with the staff ahead of time, so that he could look at and discuss the kinds of materials and issues that were going to be discussed. This preparation would be useful, and the meeting would be more productive. It would have to start, not the day the Board members arrived, but maybe a few weeks before.
Dr. Ho asked for further information on the logistics of the working group that Dr. Walker appointed. How are they going to approach the problem? How will the members interact? He asked for help on how this group was going to function. Dr. Walker noted that Dr. Ho, as the Chair of the working group, could lay out a road map as to how the group would function, what he felt most comfortable with. The approaches may be project-specific. So, he thought the group who will work with the Agency on the SHEL question may want to use one approach, but with public health assessments, another approach may be used.
Dr. Rifkind stated that the Board might improve its efficacy if there were two things that were done. First, new members of the Board and even some who have been on the Board for a longer time could benefit from a review of what this Agency is doing altogether. How its resources are deployed and what are its many activities. This time the Board spent more time on a single issue, and Dr. Rifkind thought that was very useful. She suggested the Board continue to devote meetings to single issues where the members meet together as a group.
Another issue raised by Dr. Rifkind is the need to have more evidence presented about what the results of the activities of the Agency are. That is related directly to Dr. Mattison's point, but not only health assessments. Dr. Teta had raised this issue at a previous meeting. There has been a substantial amount of time and money put into health research efforts which are supposed to have an outcome in terms of public health. What is the outcome of those research efforts?
Dr. Andrews offered to convene a discussion of the Agency just prior to the next Board meeting, probably the evening before. Dr. Walker cautioned that as a Board, they did not want to get into micromanaging the Agency. That is not the Board's responsibility.
Dr. Longley requested an outline of the presentations that were to be made at the Board meeting and any backup materials ahead of time, organized somewhat in the manner that they are going to be presented. This would allow one to think over more leisurely the kinds of questions to ask, the kinds of areas that one would want to delve into a bit further. Dr. Walker mentioned it would be helpful if the Board could have hard copies of the slides or the overheads, the transparencies. He noted that he also had made this request at a previous meeting.
Dr. Bergeisen thanked the Board for the opportunity to participate in the discussions. He mentioned the Board's discussion on inviting Elliott Laws and Dr. Goldman from EPA to a future meeting. He suggested that they be invited to talk on a specific topic. Dr. Lynn Goldman has expressed her interest in coming and attending the Board meeting and so has Elliott Laws, as has Henry Longist, the Director of the Office of Emergency Response and Remediation.
BSC Working Group Resolution
At the request of the Chairman, a working group was formed to identify actions that would support and improve the Agency's response to protect and advocate for public health related to hazardous waste issues. Dr. Richard Jackson was asked to serve as the Chair of this working group. He prepared the following resolution for consideration by the members of the Board.
"The Board of Scientific Counselors, ATSDR, asserts that for ATSDR to effectively protect and advocate for public health related to hazardous waste issues, the following actions must be taken:
1. Funding of ATSDR must be independent from that of the Environmental Protection Agency (EPA), but drawn from the Hazardous Waste Trust Fund.
2. ATSDR should provide early and high-quality health input into EPA clean-up and site-closure decisions.
3. The level of ATSDR's review and allocation of resources should be correlated to the degree of response for each site since each site does not present equal public health hazards.
4. When gaps in the toxicologic data base are identified, ATSDR should be given authority to fill these gaps using funds recovered under EPA's cost recovery actions.
5. ATSDR should be given granting authority to support private organizations and, at times, consultants or local health experts.
6. ATSDR should become one of the Centers of the Centers for Disease Control and Prevention.
7. ATSDR should be provided staffing and resources to meet its obligation to assess the Federal Facility NPL sites or be relieved of these mandates."
Dr. Longley suggested that some wording be changed to ensure greater impact on legislators. As a result, Dr. Jackson changed the statement from "when gaps in the toxicologic database are identified" to "when data gaps of public health and public policy importance are identified." Dr. Longley agreed to this change.
Dr. Walker asked for the Board's comments on how the resolution was to be communicated and to whom. Dr. Jackson suggested that it would be appropriate to form this into a letter from the Chairman, that would go to Dr. Shalala as the Secretary of Health and Human Services, with copies to appropriate interested individuals. Since it is an issue of public record, Dr. Jackson did not see why one would refrain from sending informational copies to relevant people in Congress. Dr. Walker noted that this issue would be taken up with the ATSDR staff. Dr. Longley asked Dr. Jackson to comment further on the item in the resolution dealing with ATSDR becoming a part of CDC. Dr. Jackson, in turn, asked Dr. Johnson to comment of this issue. Dr. Johnson noted that there has been discussion within the Public Health Service for about 3 years as to where ATSDR, as an independent agency of the Public Health Service, should organizationally be placed. The Congress, when they created the Agency in 1980, had specific reasons for creating a new, separate, focused public health agency, one that was focused on environmental toxicants and working principally with EPA and with states.
In 1986, the Agency was finally elevated to a separate organizational structure within the Public Health Service structure. It is one of eight agencies that constitute the United States Public Health Service. It is the smallest. ATSDR is the most focused and often the most precariously positioned agency within the framework of the United States Public Health Service, precarious both in terms of political as well as budgetary and resource influences.
The Agency does a number of things that are quite closely coordinated with the Centers for Disease Control, particularly with their laboratories and the National Center for Environmental Health, and some work in the areas of surveillance and environmental epidemiology. The proposal that has been on the table for about 3 years is to have ATSDR become a new, stand- alone Center within the Centers for Disease Control. The Centers for Disease Control and Prevention is organized around something like nine different centers, ranging from infectious disease to a center for environmental health. The National Institute for Occupational Safety and Health is also a part of CDC. So, there are a number of organizational reasons why ATSDR could benefit from becoming a new center within the CDC, and there are also some political benefits from that. There are also numerous benefits to CDC. ATSDR, as small as it is, has been outstanding in working with state health departments, in creating a capacity in about half of the state health departments to address toxins in community environments where that capacity either was minimal or did not exist before. ATSDR has an expertise in toxicology that exceeds that at CDC. CDC has laboratory resources that we do not have, nor should we have, so there are a number of things that would be beneficial to CDC should we become part of them. There are clearly things that would be beneficial to ATSDR. It would make good sense and good government to have ATSDR moved into the CDC structure, and that is what is on the table.
Dr. Walker asked for a motion on the resolution. Dr. Jackson so moved. Dr. Longley seconded the motion. A vote was taken and the motion was passed. Again, Dr. Walker indicated that the details for communicating the resolution would be worked out with the staff.
Comments from the Public
Dr. John Keller, Senior Toxicologist for APEX Environmental, Inc., requested time to address the Board. He described briefly his early work with ATSDR on Tox Profiles. He commended ATSDR for the efforts made in matters relative to risk assessment. Also, he suggested that the Board members read the ATSDR cancer policy framework which he found to be a forward looking document. He said that the SHELs program should be expanded. He also pointed out some inconsistencies in what was said at the meeting with what one reads. For example, the idea that comparison values are not to be used as indices of health.Dr. Keller mentioned several groups that could help ATSDR. They included the Inter-national Society of Regulatory Toxicology and Pharmacology, of which he is an officer, and the Society of Toxicology of which he is currently the issues chair of the risk assessment specialty section. Dr. Keller also mentioned that the American Industrial Hygiene Association has a task group on risk assessment. He offered ATSDR help from these three groups.
Charge from Chairman to the Board
Dr. Walker suggested that for the next meeting, the Board would appreciate some discussion on health studies. Also, as a part of that discussion, other agencies should participate that are doing research that may be related to Superfund. The Board would like to hear their research agenda(s).A number of recommendations were made by the Board specifically dealing with the whole issue of balancing the qualitative and quantitative risk. Dr. Mattison's recommendation that we look at what progress has been made in the past and have an analysis of that before we arrive at some conclusion is a recommendation that the Board wants to make sure is followed.
The SHEL working group was appointed. Dr. Walker requested that Dr. Ho's group, along with staff, report back at the next meeting in November on their refinement of the whole SHEL process and procedures.
The Board recommended November 9-10, 1994, for the next meeting.
Closing Remarks
Dr. Johnson mentioned that there were two other working groups that have been extremely helpful to ATSDR over the years and the chairpersons of those two work groups have stepped down from the Board. He wondered what the thoughts were with the current Board in terms of (1) continuation of those two working groups, and (2) if the Board wished to continue them, the Agency would ask that the Chair designate lead persons.
One work group has been specific to minority health and that has been a work group that has been for the past 7 years extremely helpful to ATSDR in terms of guiding ATSDR program development in minority health, and now, more recently, trying to factor in what environmental justice means in the context of the minority health program that has been in place for some time. ATSDR needs the Board's reaction to (1) the continuation of that work group, and (2) a lead person, or any other aspects of that work that the Board wishes to react to.
The second group has been a work group that has been specific to the applied research program in the Great Lakes. It is a program that is done with EPA. It comes from a separate legislative initiative outside of Superfund. It is a program that the Congress indicates that they have an interest in, not only continuing into the near term, but also to increasing funding. To the new members, Dr. Johnson noted that this is a program of human health investigations in the Great Lakes states. It is entirely a research grant program. There are some thirteen grants. The current program had $3 million per year. The Congress has indicated a strong interest in increasing that to $5 million per year. The program of work is being done at universities and, in three instances, state health departments. Dr. Roger Minear, former Board member, chaired that work group and ATSDR needs the Board's advice on that work group, as well.
Dr. Walker recommended that Dr. Linda Murray be designated as the lead person on the minority working group. Dr. Walker noted that he would call Dr. Murray and advise her on this appointment.
Dr. Walker asked Dr. Mattison if he would assume the Chair of the Great Lakes group. Dr. Mattison accepted.
Dr. Johnson mentioned again his concern that ATSDR was not making the best use of the Board of Scientific Counselors. He committed to a number of actions on behalf of the Agency to improve how the Board and ATSDR work together. However, he thought that over the past 2 days there was an improvement. Also, from the Agency perspective, ATSDR needs to work with the Board more closely. He did not believe that some of the pressing scientific issues had been presented for the Board's reaction.
Dr. Johnson also mentioned that ATSDR seeks the Board's advice and guidance. However, ATSDR does not look to the Board to micromanage the programs. At the same time, he recognized that the questions of science are not easily separated or separable from matters of program development and execution.
Dr. Johnson noted that ATSDR is trying to make a serious impact on how we measure and assess human exposure in communities, and we need some of the Board's thinking and leadership in this area. He said that several persons had commented on the matter of physiologically based pharmacokinetics models and structure activity relationships. To what extent should those things be more prominent in how ATSDR develops some of its health-based recommendations? This is an area where ATSDR needs the Board's guidance.
The matter of multiple chemical sensitivity, which this Board at the last meeting said was important to ATSDR, needs the Board's active assistance and guidance. ATSDR would like to continue working through the Chair to have persons on the Board interact with ATSDR staff between the Board meetings, to the extent that resources and interest permit.
Dr. Shoemaker requested that as part of the initiation session on the operation of the Board and ATSDR that Dr. Andrews suggested could be given prior to the next meeting, she would appreciate it if it was explained how it all fits in with EPA and the eventual setting of standards for remediation? She was still unclear on that connection.
Dr. Walker mentioned that in a future meeting, the Board would also like to hear about ATSDR's educational effort.
Dr. Walker thanked the support staff for carrying out their responsibilities effectively and efficiently. He also thanked the ATSDR staff that came before the Board and made presentations.
There being no further business before the Board, Dr. Walker adjourned the meeting at 12:52 p.m.
I hereby certify that, to the best of my knowledge, the foregoing summary of minutes is accurate and complete.
Original Signed by Bailus Walker, Jr., Ph.D., Chair of the BSC
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