. "Appendix D: Environmental Protection Agency Response to Recommendations from Selected NRC Reports: Policy, Activity, and Practice." Science and Decisions: Advancing Risk Assessment. Washington, DC: The National Academies Press, 2009.
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Science and Decisions: Advancing Risk Assessment
Appendix D
Environmental Protection Agency Response to Recommendations from Selected NRC Reports: Policy, Activity, and Practice
Table D-1 was developed as an information resource to illustrate the kinds of policies and activities that the Environmental Protection Agency (EPA) has undertaken in response to previous National Research Council recommendations (NRC 1983, 1994, 1996) for the list of bulleted topics presented below. This is not a comprehensive review. Rather, it presents representative recommendations from these key National Research Council reports, beginning with the so-called Red Book; related EPA policies as reflected in guidance documents and other materials; and related implementation activities, along with an assessment of some of these guidance documents and implementation activities as summarized in a 2006 report from the Government Accountability Office (GAO).
Many of the individual National Research Council reports and EPA documents address the risk-assessment issues below repeatedly and with some variations in a single report. As a result, passages quoted or summarized in the table are highly selected “snapshots” and are not the only examples for the indicated topic in a given report. In addition, the “response” to recommendations in the table is considered somewhat loosely, as it simply considers whether EPA addressed the issue at some point in time. For a full picture on any topic of interest, the committee advises readers to begin with pages cited in the table and to look beyond those citations for related information. Note also that several National Research Council recommendations and EPA policy statements cover multiple topics (such as both “risk characterization” and “uncertainty” or both “models” and “defaults”). Several issues are therefore discussed under several topic headings.1,2
1
Empty cells indicate only that the committee could not easily identify and isolate a representative quotation, not that related policies or implementation activities do not exist.
2
As explained in Chapter 2, the report cited as “NRC 1994” (Science and Judgment in Risk Assessment) gave special attention to issues arising under the Clean Air Act Amendments of 1990, and many of the recommendations in that report focused on air issues. A recommendation directed mainly to the air program is designated by “(Directed to Air Program).” Similarly, a recommendation directed mainly to the IRIS program is designated by “(Directed to IRIS Program).”
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Appendix D
Environmental Protection Agency Response to Recommendations from Selected NRC Reports: Policy, Activity, and Practice
Table D-1 was developed as an information resource to illustrate the kinds of policies and activities that the Environmental Protection Agency (EPA) has undertaken in response to previous National Research Council recommendations (NRC 1983, 1994, 1996) for the list of bulleted topics presented below. This is not a comprehensive review. Rather, it presents representative recommendations from these key National Research Council reports, beginning with the so-called Red Book; related EPA policies as reflected in guidance documents and other materials; and related implementation activities, along with an assessment of some of these guidance documents and implementation activities as summarized in a 2006 report from the Government Accountability Office (GAO).
Many of the individual National Research Council reports and EPA documents address the risk-assessment issues below repeatedly and with some variations in a single report. As a result, passages quoted or summarized in the table are highly selected “snapshots” and are not the only examples for the indicated topic in a given report. In addition, the “response” to recommendations in the table is considered somewhat loosely, as it simply considers whether EPA addressed the issue at some point in time. For a full picture on any topic of interest, the committee advises readers to begin with pages cited in the table and to look beyond those citations for related information. Note also that several National Research Council recommendations and EPA policy statements cover multiple topics (such as both “risk characterization” and “uncertainty” or both “models” and “defaults”). Several issues are therefore discussed under several topic headings.1,2
1
Empty cells indicate only that the committee could not easily identify and isolate a representative quotation, not that related policies or implementation activities do not exist.
2
As explained in Chapter 2, the report cited as “NRC 1994” (Science and Judgment in Risk Assessment) gave special attention to issues arising under the Clean Air Act Amendments of 1990, and many of the recommendations in that report focused on air issues. A recommendation directed mainly to the air program is designated by “(Directed to Air Program).” Similarly, a recommendation directed mainly to the IRIS program is designated by “(Directed to IRIS Program).”
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Aggregate and Cumulative Risk
Default Assumptions and Options
Distinguishing and Linking Risk Assessment and Risk Management
Distinguishing Science and Science Policy
Exposure Assessment (and Methods Validation)
Health-Risk and Toxicity Assessment for Cancer and Other End Points
Inference Guidelines
Interagency and Outside Collaboration
Iterative Approach to Risk Assessment
Models and Model Validation
Peer Review and Expert Panels
Priority-Setting and Data-Needs Management
Problem Formulation and Ecologic Risk Assessment
Public Review and Comment; Public Participation
Risk Characterization
Risk Communication in Relation to Risk Management
Uncertainty Analysis and Characterization
Variability and Differential Susceptibility
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TABLE D-1 Environmental Protection Agency Response to National Research Council Recommendations of 1983-2006: Policy, Activity, and Practice
Topic
NRC Report: Recommendationa
EPA Response: Stated Policyb
EPA Response: Implementation Activityc
Aggregate and Cumulative Risk
NRC 1994 at 240: “EPA should consider using appropriate statistical (e.g., Monte Carlo) procedures to aggregate cancer risks from exposure to multiple compounds.”
EPA 1997a Science Policy Council Memorandum: “This guidance directs each office to take into account cumulative risk issues in scoping and planning major risk assessments and to consider a broader scope that integrates multiple sources, effects, pathways, stressors and populations for cumulative risk analyses in all cases for which relevant data are available.”
EPA 2003a: Human Health Research Strategy at E-2: “ORD’s research program on aggregate and cumulative risk will address the fact that humans are exposed to mixtures of pollutants from multiple sources. Research will provide the scientific support for decisions concerning exposure to a pollutant by multiple routes of exposure or to multiple pollutants having a similar mode of action. ORD will also develop approaches to study how people and communities are affected following exposure to multiple pollutants that may interact with other environmental stressors.”
EPA1997b Cumulative Risk Assessment Guidance: “Agency managers need to place special emphasis on cumulative risk (that is, the potential risks presented by multiple stressors in aggregate). The specific elements of risk evaluated need to be determined as an explicit part of the Planning and Scoping (PS) stage of each risk assessment…. The Agency will support research to improve our understanding of cumulative risks and to develop methods to account for the multiple elements of risks that affect humans, animals, plants and their environment. In addition, the Science Policy Council will support workshops for risk assessors and managers to discuss implementation opportunities and problems, and solutions.”
Also: The research strategy identified the following research objectives related to cumulative risk: “(1) Determine the best and most cost effective ways to measure human exposures in all relevant media, including pathway-specific measures of multimedia human exposures to environmental contaminants across a variety of relevant microenvironments and exposure durations and conditions; (2) Develop exposure models and methods suitable for EPA and the public to assess aggregate and cumulative risk, including mathematical and statistical relationships among sources of environmental contaminants, their environmental fate, and pathway specific concentrations; models linking dose and exposure from biomarker data; and approaches to assess population-based cumulative risk, including those involving exposure to stressors other than
EPA 2000a Supplementary Guidance for Conducting Health Risk Assessment of Chemical Mixtures at xiv: This guidance updates the 1986 agencywide guidance on chemical mixtures and “describes more
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Topic
NRC Report: Recommendationa
EPA Response: Stated Policyb
EPA Response: Implementation Activityc
detailed procedures for chemical mixture assessment using data on the mixture of concern, data on a toxicologically similar mixture, and data on the mixture component chemicals. [It] is organized according to the type of data available to the risk assessor, ranging from data rich to data poor situations…. An evaluation of the data may lead the user to decide that only a qualitative analysis should be performed. This generally occurs in cases where data quality is poor, inadequate quantitative data are available, data on a similar mixture cannot be classified as “sufficiently similar” to the mixture of concern, exposures cannot be characterized with confidence, or method-specific assumptions about the toxicologic action of the mixture or of its components cannot be met. When this occurs, the risk assessor can still perform a qualitative assessment that characterizes the potential human health impacts from exposure to that mixture.”
pollutants; and (3) Provide the scientific basis to predict the interactive effects of pollutants in mixtures and the most appropriate approaches for combining effects and risks from pollutant mixtures.”
GAO 2006 at 50: “The extent to which program offices assess the effects of cumulative and aggregate exposures is related to the regulatory responsibilities of each office and by the availability of data. For example, the hazardous air pollutant office routinely analyzes a mix of chemicals from various emitting sources, such as petroleum refineries, to regulate hazardous air pollutants. Similarly, as mentioned above, the Office of Pesticide Programs is required to consider exposure to pesticides from various pathways, such as food, drinking water, and residential uses, and various routes, such as eating, breathing, and contact with skin.”
Note: The Toxic Substances Control Act does not require the Office of Pollution Prevention and Toxics to assess the risks of a new chemical that may occur through its interaction with other chemicals. The office also assesses the risks of existing chemicals but cannot conduct cumulative risk assessment for classes of chemical that share a common mode of action because no data exist.
EPA 2003b Framework for Cumulative Risk Assessment at xvii: “a simple, flexible structure for conducting and evaluating cumulative risk assessment within the EPA…. The framework describes three main phases to a cumulative risk assessment: (1) planning, scoping, and problem formulation, (2) analysis, and (3) risk characterization…Research and development needs are also discussed, including understanding the timing of exposure and its relationship to effects;
GAO 2006 at 49: “The branch of the Office of Air Quality Planning and Standards that regulates hazardous air pollutants employs the Multiple Pathways of Exposure model to
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understanding the composition and toxicity of mixtures; applying the risk factor approach; using biomarkers; considering hazards presented by nonchemical stressors; methods for combining different types of risk; and development of default values for cumulative risk assessments, among others.”
assess and predict the movement and behavior of chemicals in the environment. [It] includes procedures to estimate human exposures and health risks that result from the transfer of pollutants from the air to soil and surface water bodies and the subsequent uptake of the pollutant by plants, animals, and humans. The model specifically addresses exposures from breathing; consuming food, water, and soil; and contact with skin.”
EPA 2001 and 2002: General Principles for Performing Aggregate Exposure and Risk Assessments: This document “focus[es] on describing principles to guide the way in which aggregate exposure and risk assessment may be performed when more extensive distributional data and more sophisticated exposure assessment, methods and tools are available…. [The guidance] looks beyond the Interim Guidance to encompass the use of distributional data for all pathways of exposure when data are available. A distributional data analysis (as opposed to a point estimate approach) is preferred because this tool allows an aggregate exposure assessor to more fully evaluate exposure and resulting risk across the entire population, not just the exposure of a single, high-end individual.” (EPA 2001, p. 4) The 2002 guidance (EPA 2002a, p. ii) “provides guidance to OPP scientists for evaluating and estimating the potential human risks associated with such multichemical and multipathway exposures to pesticides.”
GAO 2006 at 49: EPA developed the Total Risk Integrated Methodology (TRIM) and created the TRIM Fate, Transport, and Ecological Exposure model that describes the movement of air pollutants emitted from any type of stationary source as well as their transformation over time in water, air and soil.
64 Fed. Reg. 38705[1999]: The Integrated Urban Air Toxics Strategy includes guidance on assessing cumulative risks on both the national and the urban-
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Topic
NRC Report: Recommendationa
EPA Response: Stated Policyb
EPA Response: Implementation Activityc
neighborhood scales. It provides “an overview of EPA’s national effort to reduce air toxics, including stationary and mobile source standards, cumulative risk initiatives, assessment approaches, and education and outreach.” The “national air toxics program includes activities under multiple Clean Air Act (Act) authorities to reduce air toxics emissions from all sources, including major industrial sources, smaller stationary sources, and mobile sources such as cars and trucks. By integrating activities under different parts of the Act, EPA can better address cumulative public health risks and adverse environmental impacts posed by exposures to multiple air toxics in areas where the emissions and risks are most significant.”
EPA 2004a: Air Toxics Risk Assessment Reference Library at 14-1: The guidance states that “multipathway risk assessment may be appropriate generally when air toxics that persist and which also may bioaccumulate and/or biomagnify are present in releases. These generally will focus on the persistent bioaccumulative hazardous air pollutant (PB-HAP) compounds (Exhibit 14-1), but specific risk assessments may need to consider additional chemicals that persist and which also may bioaccumulate and/or biomagnify. For these compounds, the risk assessment generally will need to consider exposure pathways other than inhalation-in particular, pathways that involve deposition of air toxics onto soil and plants and
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into water, subsequent uptake by biota, and potential human exposures via consumption of contaminated soils, surface waters, and foods. Substances that persist and bioaccumulate readily transfer between the air, water, and land. Some may travel great distances, and linger for long periods of time in the environment.” The guidance provides information on planning, scoping, problem formulation, data analysis, and risk characterization.
EPA 2002a Guidance on cumulative risk assessment of pesticide chemicals that have a common mechanism of toxicity: Provides “guidance to OPP scientists for evaluating and estimating the potential human risks associated with such multichemical and multipathway exposures to pesticides…” (p. ii). “Cumulative risk assessments may play a significant role in the evaluation of risks posed by pesticides, and will enable OPP to make regulatory decisions that more fully protect public health and sensitive subpopulations, including infants and children…. The purpose of this guidance is to set forth the basic assumptions, principles, and analytical framework that are recommended for use by OPP risk assessors in conducting cumulative risk assessments. It is also intended to inform decision makers and the public of the principles and procedures generally followed in the conduct of cumulative risk assessments on pesticide chemicals” (p. 7).
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Topic
NRC Report: Recommendationa
EPA Response: Stated Policyb
EPA Response: Implementation Activityc
Default Assumptions and Options (see also Risk Characterization, Models, Uncertainty Analysis)
NRC 1994 at 8: “EPA should continue to regard the use of default options as a reasonable way to deal with uncertainty about underlying mechanisms in selecting methods and models for use in risk assessment.”
EPA 2005a Carcinogen Risk Assessment Guidelines, Appendix A (71 FR 17809-12): The guideline “covers [five] major default options commonly employed when data are missing or sufficiently uncertain in a cancer risk assessment…. These options are predominantly inferences that can help use the data observed under empirical conditions in order to estimate events and outcomes under environmental conditions.”
GAO 2006 at 41: “To a large degree, the use of defaults is intertwined with EPA’s ability to get the data it needs. As was discussed previously, EPA has targeted research, both within EPA and through its grant programs, to understand variability and uncertainty in the data derived from studies of laboratory animals, and this research may further reduce EPA’s need to rely on default options.”
NRC 1994 at 8: “EPA should explicitly identify each use of a default option in risk assessments.”
EPA 2004b at 51: “EPA’s current practice is to examine all relevant and available data first when performing a risk assessment. When the chemical- and/or site-specific data are unavailable (i.e., when there are data gaps) or insufficient to estimate parameters or resolve paradigms, EPA uses a default assumption in order to continue with the risk assessment. Under this practice EPA invokes defaults only after the data are determined to be not usable at that point in the assessment—this is a different approach from choosing defaults first and then using data to depart from them. The default assumptions are not chemical- or site-specific, but are relevant to the data gap in the risk assessment. They are based on peer reviewed studies and extrapolation to address specific data gaps. These defaults are based on published studies, empirical observations, extrapolation from related observations, and/or scientific theory.”
GAO 2006 at 40: “The majority of IRIS assessments completed since 1997 describe the defaults used in the analysis and any departures from those defaults.
NRC 1994 at 8: “EPA should clearly state the scientific and policy basis for each default option.”
“Despite the increased focus on more transparency in the use of defaults, EPA acknowledges it could more consistently describe how the default was developed and explain why it is a reasonable assumption. In its staff paper, EPA acknowledges it needs to ensure that the defaults are supported by the best available data and should look for opportunities to increase certainty and confidence in the defaults and extrapolations used.”
EPA 2004a: The Office of Air Quality Planning and Standard’s Air Toxics Risk Assessment Reference Library (EPA 2004a) discusses defaults that should be used when preparing risk assessments. This is discussed, for example, when conducting screening analyses: “For complete or potential exposure pathways identified in the exposure pathway evaluation, the screening analysis may involve
EPA 1996 Proposed Carcinogen Risk Assessment Guidelines at 61 FR 18000:
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Risk characterization includes “risk estimates and their attendant uncertainties, including key uses of default assumptions when data are missing or uncertain.”
comparing media concentrations at points of exposure to ‘screening’ values (based on protective default exposure assumptions) and estimating exposure doses based on study area-specific exposure conditions. The assessor then compares estimated doses with health-based guidelines to identify substances requiring further evaluation.”
Also at 17966-17970ff: Explaining the scientific and policy bases of five “major” default options.
Also at 17964ff: “Pursuant to [the National Research Council recommendation related to criteria for departure from defaults] the following discussion presents…general policy guidance on using and departing from defaults in specific risk assessments.”
NRC 1994 at 8: “The agency should consider attempting to give greater formality to its criteria for a departure from default options, in order to give greater guidance to the public and to lessen the possibility of ad hoc, undocumented departures from default options that would undercut the scientific credibility of the agency’s risk assessments. At the same time, the agency should be aware of the undesirability of having its guidelines evolve into inflexible rules.”
EPA 2005a Carcinogen Risk Assessment Guidelines at 71 FR 17770ff: “Rather than viewing default options as starting points from which departures may be justified by new scientific information, these cancer guidelines view a critical analysis of all of the available information that is relevant to assessing the carcinogenic risk as the starting point from which a default option may be invoked if needed to address uncertainty or the absence of critical information[emphasis in original].”
Also Appendix A at 17809ff: Discusses default options and alternative approaches.
EPA 2000b Risk Characterization Handbook at 21: Directs risk assessors to “describe the uncertainties inherent in the risk assessment and the default positions used to address these uncertainties or gaps in the assessment.”
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Topic
NRC Report: Recommendationa
EPA Response: Stated Policyb
EPA Response: Implementation Activityc
Also at 41: “Risk assessors should carefully consider all available data before deciding to rely on default assumptions. If defaults are used, the risk assessment should reference the Agency guidance that explains the default assumptions or values.”
NRC 1994 at 186: “EPA sometimes attempts to ‘harmonize’ risk-assessment procedures between itself and other agencies, or among its own programs, by agreeing on a single common model assumption, even though the assumption chosen might have little more scientific plausibility than alternatives (e.g., replacing FDA’s body-weight assumption and EPA’s surface-area assumption with body weight to the 0.75 power)…. Rather than ‘harmonizing’ risk assessments by picking one assumption over others when several assumptions are plausible and none of the assumptions is clearly preferable, EPA should maintain its own default assumption for regulatory decisions but indicate that any of the methods might be accurate and present the results as an uncertainty in the risk estimate or present multiple estimates and state the uncertainty in each. However, ‘harmonization’ does serve an important purpose in the context of uncertainty analysis—it will help, rather than hinder, risk assessment if agencies cooperate to choose and validate a common set of uncertainty distributions.”
EPA 2005a Carcinogen Risk Assessment Guidelines at 70 FR 17808: “Important features [of the risk characterization] include the constraints of available data and the state of knowledge, significant scientific issues, an significant science and science policy choices that were made when alternative interpretation of data exist [citations omitted]. Choices made about using data or default options in the assessment are explicitly discussed in the course of the analysis, and if a choice is a significant issue, it is highlighted in the summary.”
Note: Although both the 1996 and 2005 guidelines refer to the scaling-factor issue (at 61 FR 17968 and 71 FR 17796, respectively), it is not clear whether EPA has addressed interagency harmonization to the extent recommended.
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NRC 1994 at 241: “EPA’s guidelines should clearly state a default option of nonthreshold low-dose linearity for genetic effects on which adequate data (e.g., data on chromosomal aberrations or dominant or X-linked mutations) might exist. This default option allows a reasonable quantitative estimate of, for example, first-generation genetic risk due to environmental chemical exposure.”
EPA 2005a Carcinogen Risk Assessment Guidelines at 70 FR 17811: “The linear approach is used when a view of the mode of action indicates a linear response, for example, when a conclusion is made that an agent directly causes alterations in DNA, a kind of interaction that not only theoretically requires one reaction but also is likely to be additive to ongoing, spontaneous gene mutation.”
Distinguishing Linking Risk Assessment and Risk Management (see also Problem Formulation)
NRC 1983 at 7: “Regulatory agencies should take steps to establish and maintain a clear conceptual distinction between assessment of risks and the consideration of risk management alternatives; that is, the scientific findings and policy judgments embodied in risk assessments should be explicitly distinguished from the political, economic, and technical considerations that influence the design and choice of regulatory strategies.”
EPA 1984 at 3: “Scientists assess a risk to find out what the problems are. The process of deciding what to do about the problems is ‘risk management.’ … The distinction between the two activities has become an attractive means for understanding and improving upon the two fundamental processes involved in environmental decision-making.”
Administrators William Ruckelshaus and Lee Thomas mandated and funded a series of training programs for (1) the entire SES corps and other senior management and (2) agency staff in all program and regional offices. The training materials were based in materials developed initially by Bernard Goldstein and Jack Moore. There was a heavy financial investment in the program, which ran for about 5 y (approximately 1987-1992), with remnants and updates continuing sporadically even today.
EPA 1984 at 30: “First, we want to obtain a better and more consistent information base for making decisions about the control of risk. Second, we want to use the various analytic methods associated with risk management whenever appropriate in developing environmental policy; we also want to place more emphasis on figuring out what we have achieved in terms of risk reduction through past efforts and on locating and efficiently managing the serious risks remaining. Third, we must communicate to the public what we are doing, why we are doing it in risk management terms, and how the risk management approach will improve the way that EPA carries out its mission.”
NRC 1983 at 49: “Two kinds of policy can potentially affect risk assessment: that which is inherent in the assessment process itself and that which governs the selection of regulatory options. The latter, risk management policy, should not be allowed to control the former, risk-assessment policy.”
EPA 1986 Guidelines for Carcinogen Risk Assessment at 51 FR 33993: “Regulatory
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Topic
NRC Report: Recommendationa
EPA Response: Stated Policyb
EPA Response: Implementation Activityc
in a risk assessment be reported in a written risk-assessment document.”
EPA 2000b Risk Characterization Handbook at A-3: “Key scientific concepts, data and methods (e.g., use of animal or human data for extrapolating from high to low doses, use of pharmacokinetics data, exposure pathways, sampling methods, availability of chemical-specific information, quality of data) should be discussed. To ensure transparency, risk characterizations should include a statement of confidence in the assessment that identifies all major uncertainties along with comment on their influence on the assessment, consistent with the Guidance on Risk Characterization.”
(See “Risk Characterization” section above for other relevant policy statements in EPA risk-assessment guidelines and other sources.)
NRC 1994 at 12: “EPA should conduct formal uncertainty analyses, which can show where additional research might resolve major uncertainties and where it might not.”
EPA 1997c Guiding Principles for Monte Carlo Analysis at 1: “Such probabilistic analysis techniques as Monte Carlo analysis, given adequate supporting data and credible assumptions, can be viable statistical tools for analyzing variability and uncertainty in risk assessments and presents an initial set of principles to guide the agency in using probabilistic analysis tools.”
NRC 1994 at 12: “EPA should consider in its risk assessments the limits of scientific knowledge, the remaining uncertainties, and the desire to identify errors of either overestimation or underestimation.”
NRC 1994 at 12: “Despite the advantages of developing consistent risk assessments between agencies by using common assumptions (e.g., replacing surface area
EPA 1996 Proposed Guidelines on Carcinogen Risk Assessment at 125: “The rationale for adopting the oral scaling factor of body weight to the 0.75 power
EPA did not adopt this recommendation in the 1996 guidelines.
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with body weight to the 0.75 power), EPA should indicate other methods, if any, that might be more accurate.”
has been discussed above in the explanation of major defaults. The empirical basis is further explored in Federal Register 57(109): 24152 [1992]. The more accurate approach is to use a toxicokinetic model when data become available or to modify the default when data are available as encouraged under these guidelines. As the EPA [57 Fed. Reg. 24152 [1992] discussion explores in depth, data on the differences among animals in response to toxic agents are basically consistent with using a power of 1.0, 0.75, or 0.66. The Federal agencies chose the power of 0.75 for the scientific reasons given in the previous discussion of major defaults; these were not addressed specifically in the NRC report. It was also considered appropriate, as a matter of policy, for the agencies to agree on one factor. Again, the default for inhalation exposure is a model that is constructed to become better as more agent-specific data become available.”
NRC 1994 at 12: “When ranking risks, EPA should consider the uncertainties in each estimate, rather than ranking solely on the basis of point estimate value. Risk managers should not be given only a single number or range of numbers. Rather, they should be given risk characterizations that are as robust (i.e., complete and accurate) as can be feasibly developed.”
EPA 2004b at 16: “Since uncertainty and variability are present in risk assessments, EPA usually incorporates a ‘high-end’ hazard and/or exposure level in order to ensure an adequate margin of safety for most of the potentially exposed, susceptible population, or ecosystem. EPA’s high-end levels are around 90% and above—a reasonable approach that is consistent with the NRC discussion (NRC 1994). This policy choice is consistent with EPA’s legislative mandates (e.g., adequate margin of safety). Even with a high-end value, there will be exposed people or environments at greater risk and at lower risk. In addition to the high-end values,
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Topic
NRC Report: Recommendationa
EPA Response: Stated Policyb
EPA Response: Implementation Activityc
EPA programs typically estimate central tendency values for risk managers to evaluate. This provides a reasonable sense of the range of risk that usually lies on the actual distribution.”
NRC 1994 at 242: “The distinction between uncertainty and individual variability ought to be maintained rigorously at the level of separate risk-assessment components (e.g., ambient concentration, uptake, and potency) as well as at the level of an integrated risk characterization.”
EPA 2000b Risk Characterization Handbook at 40: “The risk assessor should strive to distinguish between variability and uncertainty to the extent possible (see 3.2.8 for a discussion of uncertainty). Variability arises from true heterogeneity in characteristics such as dose-response differences within a population, or differences in contaminant levels in the environment. The values of some variables used in an assessment change with time and space, or across the population whose exposure is being estimated. Assessments should address the resulting variability in doses received by members of the target population. Individual exposure, dose, and risk can vary widely in a large population. Central tendency and high end individual risk descriptors capture the variability in exposure, lifestyles, and other factors that lead to a distribution of risk across a population (e.g., see Guidelines for Exposure Assessment).”
Variability and Differential Susceptibility
NRC 1994 at 11: “Federal agencies should sponsor molecular, epidemiological, and other types of research to examine the causes and extent of interindividual variability in susceptibility to cancer and the possible correlations between
EPA 1997d Exposure Factors Handbook: Risk assessors have used the Exposure Factors Handbook to account for variation in exposure. The purposes of the handbook are to “(1) summarize data on human behaviors and characteristics which affect exposure to environmental contaminants,
GAO 2006 at 47: “Another way EPA addresses variability is through research. One of ORD’s four strategic research directions in its Human Health Research Strategy is designed to improve the understanding of why some people and groups are more susceptible and highly exposed than others.
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susceptibility and such covariates as age, race, ethnicity, and sex.”
and (2) recommend values to use for these factors” (p. 1-1). The document includes over 150 data tables with information on exposure scenarios. It also discusses variability and attempts to characterize the variability of each of the exposure factors “(1) as tables with various percentiles or ranges of values; (2) as analytical distributions with specified parameters; and/or (3) as a qualitative discussion” (p. 1-5). The handbook discusses how risk assessors can identify the types of variability and ways that variability can be analyzed.
According to this strategy, ORD’s research on subpopulations will focus on three factors—life stage, genetic factors, and pre-existing diseases—that have been identified by a program office and the scientific community as having a high priority for risk assessment. In 2000, ORD released its Strategy for Research on Environmental Risks to Children to strengthen the scientific foundation of risk assessment and management decisions that affect children and guide EPA’s research needs and priorities over the following 5 to 10 years. Approximately 75 percent of the funding for this strategy will be dedicated to research grants under the STAR program, such as those designed to evaluate children’s exposure to pesticides.”
GAO 2006 at 46: “To further its understanding of variability in exposure, EPA has undertaken a number of research projects. For example, one of ORD’s laboratories conducted the National Human Activity Pattern Survey to provide detailed human exposure information for specific populations and allow EPA to better understand actual human exposure to pollutants in real-world situations. The survey results are stored in the Consolidated Human Activity Database to help risk assessors estimate the time that exposed people spend in various environments and their inhalation, ingestion, and dermal absorption rates while in those environments. This laboratory also conducts research to define, quantify, and reduce the uncertainty associated with the exposure and risk assessments, to develop improved methods to more accurately measure exposure and dose, and to develop technical information
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Topic
NRC Report: Recommendationa
EPA Response: Stated Policyb
EPA Response: Implementation Activityc
and quantitative tools to predict the nature and magnitude of human exposures to environmental contaminants. A recent EPA study was designed to identify chemicals commonly used in homes or day care centers, and whether children in these environments encountered the chemicals in the course of their daily activities. The research sought to identify the major routes (i.e., breathing and ingestion) and sources (i.e., dust, food, air, soil, and water) through which children come into contact with chemicals.
“Variability also exists with regard to susceptibility to adverse affects because of inherent differences among humans.”
NRC 1994 at 11: “EPA should adopt a default assumption for differences in susceptibility among humans in estimating individual risks.”
EPA 1996 Proposed Guidelines for Carcinogen Risk Assessment at 125: “The issue of a default assumption for human differences in susceptibility has been addressed under the major defaults discussion in section 1.3 with respect to margin of exposure analysis. The EPA has considered but decided not to adopt a quantitative default factor for human differences in susceptibility when a linear extrapolation is used. In general, the EPA believes that the linear extrapolation is sufficiently conservative to protect public health. Linear approaches (both LMS and straight line extrapolation) from animal data are consistent with linear extrapolation on the same agents from human data (Goodman and Wilson 1991; Hoel and Portier 1994). If actual data on human variability in sensitivity are
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available they will, of course, be used.”
EPA 2005a Guidelines for Cancer Risk Assessment at 17802: “The dose-response estimate strives to derive separate estimates for susceptible populations and lifestages so that these risks can be explicitly characterized. For a susceptible population, higher risks can be expected from exposures anytime during life, but this applies to only a portion of the general population…. In contrast, for a susceptible lifestage, higher risks can be expected from exposures during only a portion of the lifetime, but everyone in the population may pass through those lifestages.”
Also at 17811: “As a default for oral exposure, a human equivalent dose for adults is estimated from data on another species by an adjustment of animal applied oral dose by a scaling factor based on body weight to the ¾ power. The same factor is used for children because it is slightly more protective than using children’s body weight (see sec. 3.1.3).”
NRC 1994 at 11: “The distinction between uncertainty and individual variability should be maintained rigorously in each component of risk assessment.”
EPA 2000b Risk Characterization Handbook at 40: “The risk assessor should strive to distinguish between variability and uncertainty to the extent possible.”
GAO 2006 at 45: “All program offices address exposure variability in their risk assessments, although they do so in different ways. For example, risk assessors in the Office of Air Quality Planning and Standards who set certain air quality standards for six principal pollutants said they consider individual activity patterns for sensitive populations like children or asthmatics in exposure modeling by including a distribution of breathing rates to reflect variability
EPA 2000b Risk Characterization Handbook at 40: “The risk assessor should strive to distinguish between variability and uncertainty to the extent possible (see 3.2.8 for a discussion of uncertainty). Variability arises from true heterogeneity in
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Topic
NRC Report: Recommendationa
EPA Response: Stated Policyb
EPA Response: Implementation Activityc
characteristics such as dose-response differences within a population, or differences in contaminant levels in the environment. The values of some variables used in an assessment change with time and space, or across the population whose exposure is being estimated. Assessments should address the resulting variability in doses received by members of the target population. Individual exposure, dose, and risk can vary widely in a large population. Central tendency and high end individual risk descriptors capture the variability in exposure, lifestyles, and other factors that lead to a distribution of risk across a population (e.g., see Guidelines for Exposure Assessment).”
inherent in the population. Furthermore, by modeling to protect the most sensitive or at-risk groups, they are assured of protecting the rest of the population. Variability in exposure to the six principal pollutants is generally described qualitatively in scientific summaries for each pollutant. The Office of Water includes an analysis of risks to various subpopulations and a narrative discussion of the strengths and weaknesses of the studies it used to estimate exposure, but generally does not include a quantitative analysis. The Office of Pesticide Programs considers 24 different population subgroups in its exposure estimates, including differences in age, gender, ethnicity, and geographic dispersion. When data allow, the Office of Pesticide Programs develops a distribution of exposures and risks for its more refined risk assessments.”
EPA 2003b Framework for Cumulative Risk Assessment at 65: “NRC (1994) notes a clear difference between uncertainty and variability and recommends that the distinction between these two be maintained: A distinction between uncertainty (i.e., degree of potential error) and interindividual variability (i.e., population heterogeneity) is generally required if the resulting quantitative risk characterization is to be optimally useful for regulatory purposes, particularly insofar as risk characterizations are treated quantitatively. The distinction between uncertainty and individual variability ought to be maintained rigorously at the level of separate risk assessment components (e.g., ambient concentration, uptake, and potency) as well as at the level of an integrated risk characterization.”
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NRC 1994 at 220: “If there is reason to believe that risk of adverse biological effects per unit dose depends on age, EPA should present separate risk estimates for adults and children. When excess lifetime risk is the desired measure, EPA should compute an integrated lifetime risk, taking into account all relevant age-dependent variables.
EPA 2005b Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens at 1: “The National Research Council (NRC, 1994) recommended that ‘EPA should assess risks to infants and children whenever it appears that their risks might be greater than those of adults.’ This document focuses on cancer risks from early-life exposure compared with those from exposures occurring later in life. Evaluating childhood cancer and childhood exposures resulting in cancer later in life are related, but separable, issues.”
GAO 2006 at 46: “Legislation can also require EPA to consider potentially susceptible populations and life stages. For example, the Safe Drinking Water Act Amendments mandate that EPA consider risks to groups within the general population that are at greater risk of adverse health effects, including children, the elderly, and people with serious illnesses. In addition, the Food Quality Protection Act contains special provisions for the consideration of risks to children from pesticides. In 1995, EPA’s Science Policy Council called for EPA to consider the risks to infants and children consistently and explicitly as part of its risk assessments. In 1997, the White House issued an executive order that required EPA and other federal agencies to identify and assess environmental health and safety risks that may disproportionately affect children and to ensure that policies, programs, activities, and standards address such disproportionate risks.”
“EPA does not usually explore or consider interindividual variability in key biologic parameters when it uses or evaluates various physiologic or biologically based risk-assessment models (or else evaluates some data but does not report on this in its final public documents). In some other cases, EPA does gather or review data that bear on human variability, but tends to accept them at face value without ensuring that they are representative of the entire population. As a general rule, the larger the number of characteristics with an important effect on risk or the more variable those characteristics are, the larger the sample of the human population needed to establish confidently the mean and range of each of those characteristics.”
EPA 2004b at 42: “Consideration of the variability among humans is a critical aspect of risk assessment. It is the goal of EPA risk assessments to identify all potentially affected populations, including human populations (e.g., gender, nutritional status, genetic predisposition) and life-stages (e.g., childhood, pregnancy, old age) that may be more susceptible to toxic effects or are highly or disproportionately exposed.”
Also at 43: “When data are available to describe toxicological differences for a susceptible population or life-stage, then those data are summarized and analyzed, and the decisions based on this information are presented. It is preferable to have population- and chemical-specific data to describe a susceptibility to toxic effects.”
aExample of recommendation from NRC 1983, 1994, or 1996.
bExample of EPA policy bearing on issues raised in the recommendation in the form of written guidelines, reports, or policy memoranda.
cCommentary, practice, or activities related to issues raised in the National Research Council recommendation and related EPA guidance.
dThese guidelines were not specifically in response to the National Research Council report but reflect agency policy related to this topic.
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REFERENCES
EPA (U.S. Environmental Protection Agency). 1984. Risk Assessment and Management: Framework for Decision Making. EPA 600/9-85-002. Office of the Administrator, U.S. Environmental Protection Agency, Washington, DC.
EPA (U.S. Environmental Protection Agency). 1986. Guidelines for Carcinogen Risk Assessment. EPA/630/R-00/004. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54933 [accessed June 3, 2007].
EPA (U.S. Environmental Protection Agency). 1989a. Exposure Factors Handbook. EPA/600/8-89/043. NTIS PB90-106774/AS. Office of Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC.
EPA (U.S. Environmental Protection Agency). 1989b. Risk Assessment Guidance for Superfund: Volume I—Human Health Evaluation Manual (Part A). Interim Final. EPA-540/1-89/002. Office of Emergency and Remedial Response, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://www.epa.gov/oswer/riskassessment/ragsa/pdf/rags-vol1-pta_complete.pdf [accessed Oct. 16, 2007].
EPA (U.S. Environmental Protection Agency). 1992a. Guidelines for Exposure Assessment. EPA/600/Z-92/001. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC. May 1992 [online]. Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=15263 [accessed Oct. 10, 2007].
EPA (U.S. Environmental Protection Agency). 1992b. Guidance on Risk Characterization for Risk Managers and Risk Assessors. Memorandum to Assistant Administrators, and Regional Administrators, from F. Henry Habicht, Deputy Administrator, Office of the Administrator, Washington, DC. February 26, 1992 [online]. Available: http://www.epa.gov/oswer/riskassessment/pdf/habicht.pdf [accessed Oct. 10, 2007].
EPA (U.S. Environmental Protection Agency). 1994a. Model Validation for Predictive Exposure Assessments. U.S. Environmental Protection Agency, Washington, DC. July 4, 1994 [online]. Available: http://www.epa.gov/ord/crem/library/whitepaper_1994.pdf [accessed Oct.15, 2007].
EPA (U.S. Environmental Protection Agency). 1994b. Report on the Workshop on Cancer Risk Assessment Guidelines Issues. EPA/630/R-94/005a. Office of Research and Development, Risk Assessment Forum, Washington, DC.
EPA (U.S. Environmental Protection Agency). 1994c. Peer Review and Peer Involvement at the U.S. Environmental Protection Agency. Memorandum to Assistant Administrators, General Counsel, Inspector General, Associate Administrators, Regional Administrators, and Staff Office Directors, from Carol M. Browner, Administrator, U.S. Environmental Protection Agency. June 7, 1994 [online]. Available: http://www.epa.gov/osa/spc/pdfs/perevmem.pdf [accessed Oct. 16, 2007].
EPA (U.S. Environmental Protection Agency). 1995a. Policy for Risk Characterization at the U.S. Environmental Protection Agency. Memorandum from Carol M. Browner, Office of the Administrator, U.S. Environmental Protection Agency, Washington, DC. March 21, 1995 [online]. Available: http://64.2.134.196/committees/aqph/rcpolicy.pdf [accessed Oct. 10, 2007].
EPA (U.S. Environmental Protection Agency). 1995b. Guidance for Risk Characterization. Science Policy Council, U.S. Environmental Protection Agency. February 1995 [online]. Available: http://www.epa.gov/osa/spc/pdfs/rcguide.pdf [accessed Oct. 15, 2007].
EPA (U.S. Environmental Protection Agency). 1996. Proposed Guidelines for Carcinogen Risk Assessment. EPA/600/P-92/003C. Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC. April 1996 [online]. Available: http://www.epa.gov/ncea/raf/pdfs/propcra_1996.pdf [accessed Oct. 15, 2007].
EPA (U.S. Environmental Protection Agency). 1997a. Cumulative Risk Assessment Guidance—Phase I Planning and Scoping. Memorandum to Assistant Administrators, General Counsel, Inspector General, Associate Administrators, Regional Administrators, and Staff Office Directors, from Carol M. Browner, Administrator, and Fred Hansen, Deputy Administrator, Office of Administrator, U.S. Environmental Protection Agency, Washington, DC. July 3, 1997 [online]. Available: http://www.epa.gov/swerosps/bf/html-doc/cumulrsk.htm [accessed Oct. 15, 2007].
EPA (U.S. Environmental Protection Agency). 1997b. Guidance on Cumulative Risk Assessment. Part 1. Planning and Scoping. Science Policy Council, U.S. Environmental Protection Agency, Washington, DC. July 3, 1997 [online]. Available: http://www.epa.gov/osa/spc/pdfs/cumrisk2.pdf [accessed Oct. 10, 2007].
EPA (U.S. Environmental Protection Agency). 1997c. Guiding Principles for Monte Carlo Analysis. EPA/630/R-97/001. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://www.epa.gov/NCEA/pdfs/montcarl.pdf [accessed June 3, 2007].
OCR for page 365
Science and Decisions: Advancing Risk Assessment
EPA (U.S. Environmental Protection Agency). 1997d. Exposure Factors Handbook, Vol. 1. General Factors. EPA/600/P-95/002F. Office of Research and Development, National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://www.epa.gov/ncea/efh/ [accessed June 3, 2007].
EPA (U.S. Environmental Protection Agency). 1998. Guidelines for Ecological Risk Assessment. EPA/630/R-95/002F. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=12460 [accessed June 3, 2007].
EPA (U.S. Environmental Protection Agency). 2000a. Supplementary Guidance for Conducting Health Risk Assessment of Chemical Mixtures. EPA/630/R-00/002. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC. August 2000 [online]. Available: http://www.epa.gov/ncea/raf/pdfs/chem_mix/chem_mix_08_2001.pdf [accessed Oct. 15, 2007].
EPA (U.S. Environmental Protection Agency). 2000b. Risk Characterization: Science Policy Council Handbook. EPA 100-B-00-002. Office of Science Policy, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://www.epa.gov/OSA/spc/pdfs/rchandbk.pdf. [accessed June 3, 2007].
EPA (U.S. Environmental Protection Agency). 2000c. Benchmark Dose Technical Guidance Document. EPA/630/R-00/001. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://www.epa.gov/ncea/pdfs/bmds/BMD-External_10_13_2000.pdf [accessed June 3, 2007].
EPA (U.S. Environmental Protection Agency). 2000d. Per Review Handbook., 2nd Ed. EPA 100-B-00-001. Science Policy Council, Office of Science Policy, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC. December 2000 [online]. Available: http://www.epa.gov/osa/spc/pdfs/prhandbk.pdf [accessed Oct. 16, 2007].
EPA (U.S. Environmental Protection Agency). 2000e. EPA Quality Manual for Environmental Programs. 5360A1. Office of Environmental Information, U.S. Environmental Protection Agency, Washington, DC. May 5, 2000 [online]. Available: http://www.epa.gov/quality/qs-docs/5360.pdf [accessed Oct. 15, 2007].
EPA (U.S. Environmental Protection Agency). 2001. General Principles for Performing Aggregate Exposure and Risk Assessments. Office of Pesticide Programs, U.S. Environmental Protection Agency, Washington, DC. November 28, 2001 [online]. Available: http://www.epa.gov/pesticides/trac/science/aggregate.pdf [accessed Oct. 15, 2001].
EPA (U.S. Environmental Protection Agency). 2002a. Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity. Office of Pesticide Programs, U.S. Environmental Protection Agency, Washington, DC. January 14, 2002 [online]. Available: http://www.epa.gov/pesticides/trac/science/cumulative_guidance.pdf [accessed Oct. 16, 2007].
EPA (U.S. Environmental Protection Agency). 2002b. Lessons Learned on Planning and Scoping for Environmental Risk Assessments. Prepared by the Planning and Scoping Workgroup of the Science Policy Council Steering Committee, U.S. Environmental Protection Agency, Washington, DC. January 2002 [online]. Available: http://www.epa.gov/OSA/spc/pdfs/handbook.pdf [accessed Oct. 16, 2007].
EPA (U.S. Environmental Protection Agency). 2002c. Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility and Integrity of Information Disseminated by the Environmental Protection Agency. EPA/260R-02-008. Office of Environmental Information, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://www.epa.gov/QUALITY/informationguidelines/documents/EPA_InfoQualityGuidelines.pdf [accessed Oct. 10, 2007].
EPA (U.S. Environmental Protection Agency). 2003a. Human Health Research Strategy. EPA/600/R-02/050. Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://www.epa.gov/nheerl/humanhealth/HHRS_final_web.pdf [accessed June 3, 2007].
EPA (U.S. Environmental Protection Agency). 2003b. Framework for Cumulative Risk Assessment. EPA/630/P-02/001F. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54944 [accessed June 3, 2007].
EPA (U.S. Environmental Protection Agency). 2003c. A Summary of General Assessment Factors for Evaluating the Quality of Scientific and Technical Information. EPA 100/B-03/001. Science Policy Council, U.S. Environmental Protection Agency, Washington, DC. June 2003 [online]. Available: http://www.epa.gov/osa/spc/pdfs/assess2.pdf [accessed Oct. 12, 2007].
EPA (U.S. Environmental Protection Agency). 2004a. Air Toxics Risk Assessment Reference Library, Vol. 1-Technical Resource Manual, Part III: Human Health Risk Assessment: Multipathway. EPA-453-K-04-001. Office of Air Quality Planning and Standards, U.S. Environmental Protection Agency, Research Triangle Park, NC [online]. Available: http://www.epa.gov/ttn/fera/risk_atra_vol1.html#part_iii [accessed Oct. 12, 2007].
EPA (U.S. Environmental Protection Agency). 2004b. An Examination of EPA Risk Assessment Principles and Practices. EPA/100/B-04/001. Office of the Science Advisor, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://www.epa.gov/OSA/pdfs/ratf-final.pdf [accessed June 3, 2007].
OCR for page 366
Science and Decisions: Advancing Risk Assessment
EPA (U.S. Environmental Protection Agency). 2005a. Guidelines for Carcinogen Risk Assessment (Final). EPA/630/P-03/001F. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC. March 2005 [online]. Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=116283 [accessed Oct. 16, 2007].
EPA (U.S. Environmental Protection Agency). 2005b. Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens. EPA/630/R-03/003F. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC [online]. Available: http://www.epa.gov/iris/children032505.pdf [accessed Oct. 19, 2007].
GAO (U.S. Government Accountability Office). 2006. Human Health Risk Assessment. GAO-06-595. Washington, DC: U.S. Government Printing Office [online]. Available: http://www.gao.gov/new.items/d06595.pdf [accessed Oct. 11, 2007].
Gilman, P. 2003. Statement of Paul Gilman, Assistant Administrator for Research and Development and EPA Science Advisor, U.S. Environmental Protection Agency, before the Committee on Transportation and Infrastructure, Subcommittee on Water Resources and the Environment, U.S. House of Representatives, March 5, 2003 [online]. Available: http://www.epa.gov/ocir/hearings/testimony/108_2003_2004/2003_0305_pg.pdf [accessed Feb. 9, 2007].
Goodman, G., and R. Wilson. 1991. Predicting the carcinogenicity of chemicals in humans from rodent bioassay data. Environ. Health Perspect. 94:195-218.
Hoel, D.G., and C.J. Portier. 1994. Nonlinearity of dose-response functions for carcinogenicity. Environ. Health Perspect. 102(Suppl 1):109-113.
NRC (National Research Council). 1983. Risk Assessment in the Federal Government: Managing the Process. Washington, DC: National Academy Press.
NRC (National Research Council). 1994. Science and Judgment in Risk Assessment. Washington, DC: National Academy Press.
NRC (National Research Council). 1996. Understanding Risk: Informing Decisions in a Democratic Society. Washington, DC: National Academy Press.
