Chapter 23
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U.S. Environmental Protection Agency Processes for Consensus Building for Hazard Identification R. S. Schoeny Office of Research and Development, Environmental Criteria and Assessment Office, U.S. Environmental Protection Agency, Cincinnati, OH 45268
Over the 19-year history of the U . S. Environmental Protection Agency (U.S. EPA), there have been substantial changes to the process whereby potentially hazardous materials are regulated. The objective of these regulations have always been protection of public health and of the environment. The basis for formulating regulations to this end has become increasingly reliant on the use of risk assessment, rather than by application of the best available technology for removal of all potentially hazardous agents (to limits of detection). The current philosophy of the Agency is that appropriate use of risk assessment can result in efficient application of limited resources to those situations wherein they are most needed. As reliance on risk assessment by the U.S. EPA has increased, so has the need for consistency and quality in the preparation and communication of these risk assessments; thus, the necessity of consensus or agreement has grown. The basis for consensus building is the use of commonly applied well-defined principles. The U.S. EPA applies the principles of risk assessment and risk management as described in the 1983 United States National Research Council's publication, "Risk Assessment in the Federal Government: Managing the Process". In this report, risk assessment is defined as: The use of the factual base to define the health effects of exposure of individuals or populations to hazardous materials and situations (1) while risk management is the process of weighing policy alternatives and selecting the most appropriate regulatory action, integrating the results of risk assessment with engineering data and with social, economic, and political concerns to reach a decision (i). NOTE: The views in this chapter are those of the author and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency. This chapter not subject to U.S. copyright Published 1991 American Chemical Society
Tweedy et al.; Pesticide Residues and Food Safety ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
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Risk assessment, the focus of this paper, is a process consisting of four components: hazard identification, dose-response assessment, exposure assessment, and risk characterization. Hazard identification is a qualitative index. It is concerned with the nature of the endpoints, the severity and structure-activity relationships, and ultimately, a judgement as to the likelihood that effects observed in one population (e.g. an experimental one) could also occur in another. The dose response assessment, by contrast, is a quantitative index. For toxic substances, the assessment can be described as the shape and slope of the dose—response curve. Exposure assessment evaluates the target of the hazard and the pathway taken. Risk characterization, the final step, combines information from the preceding three steps into judgements as to the incidence of adverse effects under the particular circumstances of exposure described in the exposure assessment. The use of these very general principles underlies the risk assessment methods and practices of the U.S. EPA. The public's appreciation of the quality of the overall evaluation of the threat, and the acceptance of its fairness by regulated industries depends on demonstrated scientific integrity of the risk assessment, consistency among the risk assessments and of the methodologies used for their preparation. Equally important is effective communication of the risk information as well as the uncertainties involved in its derivation. To ensure quality and consistency, the U.S. EPA has empanelled expert scientific groups to deal with scientific and policy issues, formulated guidelines for risk assessment, instituted review groups and developed other tools for use by its scientists. Scientific Groups Dealing with Risk Assessment at the U.S. EPA The Risk Assessment Forum was established to promote consensus regarding risk assessment issues and to ensure that this consensus is incorporated into appropriate risk assessment guidance. In order to accomplish this, the Forum brings together experts from across the Agency to study and report on selected issues. Every year U.S. EPA officials nominate scientists from offices and regions; members are selected by the Risk Assessment Council (see below) for three-year terms. There are currently 13 members selected from the various U.S. EPA offices based on their expertise in risk assessment and associated disciplines (such as toxicology, chemistry, epidemiology, statistics, etc.). Technical panels of members and other Agency scientists are convened by the Forum to deal with specific issues. In general, the Forum deals with generic issues fundamental to the risk assessment process, the analysis of data used in risk assessments and developing consensus on approaches to risk assessment. Examples of projects handled by the Forum are development of interim procedures for estimating risks associated with exposure to mixtures of chlorinated dibenzo-p-dioxins and dibenzofurans, use of proliferative hepatocellular lesions of the rat for risk assessment, and review of methods for deriving inhalation reference doses for non-cancer chronic toxicity.
Tweedy et al.; Pesticide Residues and Food Safety ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
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The Forum is also charged with development of new Risk Assessment Guidelines, revision of the current Guidelines and providing training in the use of the Guidelines. Actions taken or recommended by the Risk Assessment Forum are referred to the Risk Assessment Council for consideration of policy and procedural issues. The Risk Assessment Council was established to provide executive oversight of the development, review and implementation of EPA risk assessment policy. The Council is comprised of EPA senior officials who provide an Agency-wide perspective. Among the activities of the Council are the following: coordination of intra-Agency and inter-Agency risk assessment activities; development of initiatives to improve EPA's risk assessment processes; providing guidance on the interpretation of risk assessment information in the Agency's decision-making process; and referring specific issues to scientific or management groups as needed. The Risk Assessment Council interacts with the Risk Assessment Forum by providing direction as to priorities and by providing policy review of Forum products. The Council meets on a regular basis and, to the degree possible, reaches decisions by consensus. On occasion the Council will refer issues to the EPA Administrator. Also important in the process of achieving consensus on risk assessment are scientific review groups. The Carcinogen Risk Assessment Verification Endeavor (CRAVE) and Reference Dose (RfD) Work Groups are described in a subsequent section of this paper. Risk Assessment Information Exchange Guidelines. A fundamental component of the process of risk assessment at the EPA is the use of the Risk Assessment Guidelines of 1986. These were established partly in response to the NAS recommendation that federal regulatory agencies publish specific guidance for risk assessment. These Guidelines provide the public with a description of the processes utilized by the EPA and provide Agency scientists with a consistent framework for dealing with risk assessment problems. Each of the Guidelines provides not only technical information, but also descriptions of scientific policy decisions. Each stresses the importance of providing information on data gaps, assumptions, limitations and other areas of uncertainty for each risk assessment. Currently there are published Guidelines in five areas: carcinogenicity, developmental toxicity, mutagenicity, assessment of chemical mixtures and exposure assessment. The first three are similar in that each deals with both the hazard identification and dose response components of risk assessment. For potential carcinogens the EPA uses a weight-of-evidence evaluation procedure similar to that described by the International Agency or Research on Cancer. The U.S. EPA has enhanced the procedure by utilizing an expanded scheme which ranks available human and animal data as sufficient, limited, inadequate, no data or no evidence. This evaluation is used to give a preliminary categorization in one of the following groups: A, human carcinogen; B, probable human carcinogen, C, possible human car-
Tweedy et al.; Pesticide Residues and Food Safety ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
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cinogen; D, not classifiable as to human carcinogenicity; E, evidence of non-carcinogenicity for humans. Supporting data such as evidence of genotoxicity, structure-activity relationships, or metabolism data are used in determination of the final category. When appropriate data are available a quantitative or dose response assessment is done for these agents in groups A and B; quantitation is done for Group C agents on a case-by-case basis. The Guidelines provide direction as to the suitability of data, models for low-dose extrapolation, dose conversion assumptions and uncertainties to be presented. The Guidelines for the Health Risk Assessment of Developmental Toxicants define what U.S. EPA means by developmental toxicity; namely, any adverse effect to the developing organism. Some examples are prenatal or early postnatal death, structural abnormalities, altered growth, or functional deficits. The objectives of the Guidelines are to provide a rationale for approaches to evaluate the data, to detail the types of adverse effects, and to provide guidance for evaluating the relevance of animal study data for assessing the risk to humans. The qualitative risk assessment considers the relationship between maternal and developmental toxicity. Unlike the case of carcinogenicity, the Developmental Toxicity Guidelines do not use discrete classifications per se, but rather a narrative description of the weight-of-evidence. The dose—response assessment assumes a threshold for developmental toxicity. The available data are evaluated for the highest No-Observed-Effect-Level (NOEL) or No-Observed-Adverse-Effect-Level (NOAEL) and the Lowest-Observed-Adverse-Effect-Level (LOAEL), for maternal toxicity. A similar evaluation is made of data for endpoints indicating toxicity to the developing organism. Numerical uncertainty factors based on deficiencies in the quantitative data (the individual studies and the data base as a whole) and/or the validity of extrapolations, expressed as factors of 10, are used to derive a reference dose (RfD) from the above data. The Agency established Mutagenicity Guidelines out of concern that 10% of all human disease is related to specific genetic abnormalities. These Guidelines are concerned with heritable mutations occurring in germ cells rather than somatic cells. The mutagenicity Guidelines present a scheme based on an 8-category classification. Class 1 is assigned when there are positive data derived from human germ-cell mutagenicity studies, while class 8 is assigned when there is inadequate evidence bearing on either mutagenicity or chemical interaction with mammalian germ cells. In assessing the available data, weight is given to data derived from germ cells rather than somatic cells, assays performed in vivo rather than in vitro, with eukaryotic rather than prokarytic systems, and among eukaryotes, mammalian rather than submammalian organisms. In the dose-response assessment for mutagens, no threshold is assumed. At present, only data from whole animal tests, such as the mouse specific locus tests may be used for this quantitative phase. The choice of a mathematical model for the extrapolation to likely human exposure regimes from higher level animal data is on a case-by-case basis.
Tweedy et al.; Pesticide Residues and Food Safety ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
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The Guidelines for the Health Risk Assessment of Chemical Mixtures of necessity take somewhat different approaches to hazard identification and quantitative assessment. They provide aframeworkfor evaluating data as to its adequacy on interactions, health effects information, and exposure. There are descriptions of some default positions to be used in the absence of data on the mixture in question; e.g., use of data on a similar mixture or the use of information on the individual components of a mixture. In the latter case, the option is provided of employing in assumption of additivity of dose or response to calculate a hazard index. The Guidelines for Estimating Exposure provide a consistent approach to exposure assessments, and they enable a common organizational scheme entailing the determination or estimation of the magnitude,frequency,duration, and route of exposure for the substance in question. They present a formal approach or health and nonhuman assessments. In addition to the characterization of the chemical or mixture whose exposure is to be evaluated, an exposure assessment has five elements. They are the source (in plant, food additive, smokestack release), the pathways and environmental fate (emission rates, intermedia transfer, transport and transformation), measured or estimated concentrations, the exposed populations (workers, consumers, general human population, aquatic organisms), and an integrated exposure analysis using actual data, often supplemented by mathematical models. In addition to Guidelines the U.S. EPA currently has in use, there are others under development such as those for exposure-related measurement, and for the assessment of male and female reproductive risk. The Agency also plans to develop guidelines for the assessment of ecological risk and for the evaluation of pharmacokinetic data. Data Bases for Risk Assessment To assist its scientists in preparing risk assessments, the U.S. EPA has established several computerized data bases such as MIXTOX, Toxic Substances Release Inventory and the Chemical List and Information Pointer System. Among those available to the general public is the Integrated Risk Information System (IRIS). IRIS is the EPA's electronic information system containing summaries of chemical-specific data related to health risk assessment. It is the primary vehicle for communication of chronic health hazard assessments that represent Agency consensus following comprehensive review by intra-Agency work groups. IRIS contains chemical-specific information in summary format for approximately 400 chemicals and physical agents. These summaries provide the bases for the health hazard assessments as well as discussions of the uncertainties in the assessment. The chemical file consists of a summary of that assessment as well as other information, such as drinking water health advisories, regulatory actions, and physical-chemical properties. An IRIS chemical file is compiled when consensus is reached by a U.S. EPA review group on an assessment for carcinogenic or noncarcinogenic endpoints. IRIS was developed in response to repeated requests for defensible risk assessment information which can be used in situations such as Superfund
Tweedy et al.; Pesticide Residues and Food Safety ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
Downloaded by CALIFORNIA INST OF TECHNOLOGY on December 25, 2017 | http://pubs.acs.org Publication Date: December 31, 1991 | doi: 10.1021/bk-1991-0446.ch023
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site assessments, evaluation of unexpected spills, or for drinking water contamination. It was noted by U.S. EPA officials that risk assessments for specific environmental agents done independently by the various U.S. EPA offices were sometimes inconsistent; different data sets were used or diverse scientific judgements were rendered on the same data set. The end results were quantitative estimates of the potential health hazard of environmental contaminants varying by as much as two orders of magnitude. The use of such varying estimates in regulatory actions could result in legal and administrative complications. To ensure greater consistency across the Agency, a review process was developed to select the best scientific basis for each assessment and to ensure that guidelines were followed in the risk assessment process. This review process utilizes two intra-Agency work groups, the Reference Dose (RfD) Work Group (for noncarcinogenic endpoints) and the Carcinogen Risk Assessment Verification Endeavor (CRAVE) Work Group for carcinogenic risk assessments. These two work groups are comprised of scientists from the U.S. EPA program offices that are responsible for the development or regulatory application of health hazard assessments. The work groups evaluate existing chemical-specific assessments as to their scientific merit and ensure that risk assessment methodologies are applied in an appropriate and consistent manner and are congruent with published and proposed U.S. EPA Risk Assessment Guidelines. The work groups meet on a monthly basis to review U.S. EPA documents on which the risk assessment summaries are based, as well as the primary literature sources that are excerpted in the documents. The Work Groups deal with both hazard identification and dose-response assessment. For example, the CRAVE work group reviews the weight-of-evidence category for an agent to ascertain if the Guidelines have been followed or if there are new data which necessitated a change in category. Work Group members also discuss the choice of data sets for quantitative risk assessment, whether new data are available on the agent in question since publication of the U.S. EPA document, and if this new information would affect the proposed risk assessment. At the meeting, any conflicting risk estimates are discussed as to the sources of conflicts, as well as scientific justifications for alternate risk approaches, and underlying or general issues in risk assessment. An assessment is "verified" when the work group members come to a consensus that the assessment is scientifically sound, and is based on the best available data. Verified assessments are then communicated to the Agency and the public via IRIS. A recent decision by the Risk Assessment Council has indicated that the risk assessment information on IRIS should be considered as the official U.S. EPA advice for specific agents. The two review groups interact with both the Risk Assessment Council and the Risk Assessment Forum. Generic issues are often raised in the course of the discussions of the CRAVE and RfD Work Groups; these may be referred to the Forum for its input. The CRAVE has been the major arena wherein use of the Guidelines by the various offices has been tested; thus, this group has been a major source of suggestions for revision of the Guidelines for Carcinogen Risk Assessment. The Risk Assessment Council
Tweedy et al.; Pesticide Residues and Food Safety ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
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is kept informed as to the results of the CRAVE and RfD Work Group reviews. A subcommittee of the Council has recently been formed to serve as the IRIS oversight group. This group will provide advice as to policy and will help facilitate the flow of risk assessment information among scientists and managers. Education. In order for any of the above consensus-reaching processes to have the optimal effect on EPA risk assessments, it is necessary that the scientists in the program offices and in the field be kept informed as to chemical-specific and general risk assessment methods. IRIS and the other data bases provide assistance for the former as does the dissemination of chemical-specific risk assessment documents (for example, Health and Environmental Effects Documents, and Drinking Water Criteria Documents). The EPA also has a commitment to training of its personnel in the correct use and derivation of risk assessments. For example, there is a training course in the use of the Guidelines. This consists of a general briefing, a briefing specifically for managers, and day-long workshops for each of the five published Guidelines. Training is available on general risk assessment methods, on use of IRIS, and onriskcommunication. Conclusions Risk assessment is a very young, developing science. Many of the principles are evolving, some at a fairly rapid pace. It is particularly incumbent on a regulatory agency such as the U.S. EPA to keep pace with the science, but also to put forth risk assessments that are based on consistently applied principles. In order to stand the tests of the courts and public opinion, regulations must be founded on quality risk assessments that represent sound scientific judgements. It is to this end that the U.S. EPA is committed to providing tools for reaching consensus. Literature Cited 1. National Research Council, Committee on the Institutional Means for Assessment of Risks to Public Health (1983). "Risk Assessment in the Federal Government: Managing the Process." National Academy Press: Washington, DC. RECEIVED September 4, 1990
Tweedy et al.; Pesticide Residues and Food Safety ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
