## GUIDANCE FOR RISK CHARACTERIZATION

U.S. Environmental Protection Agency Science Policy Council February, 1995

CONTENTS

I. The Risk Assessment/Risk Management Interface

II. Risk Assessment and Risk Characterization

III. Exposure and Risk Descriptors

PREFACE

This guidance contains princi ples for developing and describing EPA risk assessments, with a particular emphasis on risk characterization. The current document is an update of the guidance issued with the Agency's 1992 policy (Guidance on Risk Characterization for Risk Managers and Risk Assessors, February 26, 1992). The guidance has not been substantially revised, but in cludes some clarifications and changes to give more prominence to certain issues, such as the need to explain the use of default assumptions.

As in the 1992 policy, some aspects of this guidance focus on cancer risk assessment, but the guidance applies generally to human hea lth effects (e.g., neurotoxicity, developmental toxicity) and, with appropriate modificati ons, should be used in all health risk assessments. This document has not been revi sed to specifically address ecological risk assessment, however, initial guidance for ecol ogical risk characterization is included in EPA's Framework for Ecological Risk Asse ssments (EPA/630/R-92/001). Neither does this guidance address in detail the use of risk assessment information (e.g., information from the Integrated Risk Information System (IRIS)) to generate s ite- or media-specific risk assessments. Additional program-specifi c guidance will be developed to enable implementation of EPA's Risk Characterization Policy. Development of such guidance will be overseen by the Science Policy Council and will involve risk assessors and risk managers from across the Agency.

I. THE RISK ASSESSMENT RISK MANAGEMENT INTERFACE

Recognizing that for many people the term risk assessment has wide meaning, the National Research Council's 1983 report on ri sk assessment in the federal government distinguished between risk assessment and risk management.

"Broader uses of the term [risk assessment] than ours also embrace analysis of perceived risks, comparisons of risks associated w ith different regulato ry strategies, and occasionally analysis of the economic and so cial implications of regulatory decisions functions that we assign to risk management(emphasis added). (l)In 1984, EPA endorsed these distinctions betwee n risk assessment and risk management for Agency use (2), and later relied on them in developing risk assessment guidelines (3). In 1994, the NRC reviewed the Agency's appro ach to and use of risk assessment and issued an extensive report on their findings (4). This di stinction suggests that EPA participants in the process can be grouped into two main cat egories, each with somewhat different responsibilities, based on their roles with respect to risk assessment and risk management.

A. Roles of Risk Assessors and Risk Managers

Within the Risk Assessment category there is a group that devel ops chemical-specific risk assessments by collecting, analyzing, and synthesizing scie ntific data to produce the hazard identification, doseresponse, and exposure assessment portion of the risk assessment and to characterize risk. This gr oup relies in part on Agency risk assessment guidelines to address science policy issues a nd scientific uncertain ties. Generally, this group includes scientists and st atisticians in the Office of Research and Development; the Office of Prevention, Pesticides and Toxics and other program of fices; the Carcinogen Risk Assessment Verification Endeavor ( CRAVE); and the Reference Dose (RfD) and Reference Concentration (RfC) Workgroups.

Another group generates site or mediaspeci fic risk assessments for use in regulation development or site-specific decision-maki ng. These assessors rely on existing databases (e.g., IRIS, ORD Health A ssessment Documents, CRAVE and RfD/RfC Workgroup documents, and program-specific toxicity in formation) and media- or site-specific exposure information in developing risk assessm ents. This group also relies in part on Agency risk assessment guidelines and program-specific guidance to address science policy issues and scientific uncertainties. Ge nerally, this group includes scientists and analysts in program offices, regional offices, and the Office of Research and Development.

Risk managers, as a separate category, integrate the risk characterization with other considerations specified in applicable statutes to make and justify regulatory decisions. Generally, this group includes Agency managers and decisionmakers. Risk managers also play a role in determining th e scope of risk assessments. The risk assessment process involves regularinteraction betw een risk assessors and risk managers, with overlapping responsibilities at various stag es in the overall process. Sh ared responsibilities include initial decisions regard ing the planning and conduct of an assessment, discussions as the assessment develops, decisions regarding new da ta needed to complete an assessment and to address significant uncertainties. At cri tical junctures in the assessment, such consultations shape the nature of, and schedul e for, the assessment. External experts and members of the public may also play a role in determining the scope of the assessment; for example, the public is often concerned about certain chemicals or exposure pathways in the development of site -specific risk assessments.

B. Guiding PrinciplesThe following guidance outlines principles for those who generate, review, use, and integrate risk assessments for decision-making.

1. Risk assessors and risk managers should be sensitive to distinctions between risk assessment and risk management.

The major participants in the risk assessmen t process have many shared responsibilities. Where responsibilities differ, it is important th at participants confine themselves to tasks in their areas of responsibility and not ina dvertently obscure differences between risk assessment and risk management.

For the generators of the assessment , distinguishing between risk assessment and risk management means that scientific informa tion is selected, evaluated, and presented without considering issues such as cost, feas ibility, or how the scientific analysis might influence the regulatory or site-specific decision. Assessors are charged with (1) generating a credible, objectiv e, realistic, and scientifically balanced analysis; (2) presenting information on hazard, dose-respons e, exposure and risk; and (3) explaining confidence in each assessment by clearly delineating strengths, uncertainties and assumptions, along with the impacts of th ese factors (e.g., conf idence limits, use of conservative/non-conservative assumptions) on the overall assessment. They do not make decisions on the acceptability of any risk le vel for protecting public health or selecting procedures for reducing risks.

For users of the assessment and for decisionmakers who integrate these assessments into regulatory or site-specific d ecisions, the distinction between risk assessment and risk management means refraining from infl uencing the risk description through consideration of other factor s e.g., the regulatory outcome a nd from attempting to shape the risk assessment to avoid statutory constr aints, meet regulator y objectives, or serve political purposes. Such management consider ations are often legi timate considerations for the overall regulatory decision (see next prin ciple), but they have no role in estimating or describing risk. However, decisionmakers and risk assessors participate in an Agency process that establishes policy directions thatdetermine the overall nature and tone of Agency risk assessments and, as appropria te, provide policy guidanceon difficult and controversial risk assessment issues. Matters su ch as risk assessment priorities, degree of conservatism, and acceptability of particular risk levels are reserved for decisionmakers who are charged with making decisions regarding protection of public health.

2. The risk assessment product, that is, th e risk characterization, is only one of several kinds of information used for regulatory decision-making.

Risk characterization, the last step in risk assessment, is the starting point for risk management considerations and the foundati on for regulatory decision-making, but it is only one of several important components in su ch decisions. As the last step in risk assessment, the risk characterization iden tifies and highlights the noteworthy risk conclusions and related uncertainties. Each of the environmental laws administered by EPA calls for consideration of other factors at various stages in the re gulatory process. Asauthorized by different statutes, decisionm akers evaluate technical feasibility (e.g., treatability, detection limits), economic, social, political, and legal factors as part of the analysis of whether or not to regulate and, if so, to what extent. Thus, regulatory decisions are usually based on a combination of the technical analysis used to develop the risk assessment and information from other fields.

For this reason, risk assessors and manage rs should understand that the regulatory decision is usually not determined solely by the outcome of the risk assessment. For example, a regulatory decision on the use of a particular pesticide considers not only the risk level to affected populations , but also the agricultural bene fits of its use that may be important for the nation's food supply. Similarly, assessment efforts may produce an RfD for a particular chemical, but ot her considerations may result in a regulatory level that is more or less protective than the RfD itself.

For decisionmakers, this means that societal considerations (e.g., co sts and benefits) that, along with the risk assessment, shape the regul atory decision should be described as fully as the scientific information set forth in the risk characterization. Information on data sources and analyses, their strengths and limitations, confidence in the assessment, uncertainties, and alternative analyses are as im portant here as they are for the scientific components of the regulatory decision. Decisi on-makers should be able to expect, for example, the same level of rigor from the economic analysis as they receive from the risk analysis. Risk management decisions involve numerous assumptions and uncertainties regarding technology, economics and social factor s, which need to be explicitly identified for the decisionmakers and the public.

II. RISK CHARACTERIZATION

A. Defining Risk Characterization in the Context of Risk Assessment

EPA risk assessment principles and practi ces draw on many sources. Obvious sources include the environmental laws administer ed by EPA, the National Research Council's 1983 report on risk assessment (l), the Agency 's Risk Assessment Guidelines (3), and various program specific guidance (e.g., the Risk Assessment Guidance for Superfund). Twenty years of EPA experience in de veloping, defending, and enforcing risk assessmentbased regulation is another. Together these various sources stress the importance of a clear explanation of Ag ency processes for evaluating hazard, doseresponse, exposure, and other data th at provide the scie ntific foundation for characterizing risk.

This section focuses on two requirements for full characterization of risk. First, the characterization should address qualitative and quantitative fe atures of the assessment. Second, it should identify the important streng ths and uncertainties in the assessment as part of a discussion of the confidence in the assessment. This emphasis on a full description of all elements of the assessmen t draws attention to the importance of the qualitative, as well as the quantitative, dimensions of the assessment. The 1983 NRCreport carefully distinguished qualitative risk assessment from quantitative assessments, preferring risk statements that are not strictly numerical.

The term risk assessmentis often given narrower and br oader meanings than we have adopted here. For some observers, the term is synonymous with quantitative risk
assessmentand emphasizes reliance on numerical re sults. Our broader definition includes quantification, but also includes qualitative expressions of risk. Quantitative estimates of risk are not always feasible, and they may be eschewed by agencies for policy reasons. (1)

EPA's Exposure Assessment Guidelines define risk characterization as the final step in the risk assessment process that:

• Integrates the individual characterizati ons from the hazard identification, doseresponse, and exposure assessments;

• Provides an evaluation of th e overall quality of the assessment and the degree of confidence the authors have in the estimat es of risk and conclusions drawn;

• Describes risks to individuals and populati ons in terms of extent and severity of probable harm; and

• Communicates results of the risk assessment to the risk manager. (5)

Particularly critical to full characterization of risk is a frank and open discussion of the uncertainty in the overall assessment and in each of its components. The uncertainty discussion is important for several reasons.

1. Information from different sources carri es different kinds of uncertainty and knowledge of these differences is importa nt when uncertaintie s are combined for characterizing risk.

2. The risk assessment process, with management input, involves decisions regarding the collecti on of additional data (versus liv ing with uncertainty); in the risk characterization, a discussion of the uncertainties will help to identify where additional information could contribute si gnificantly to reducing uncertainties in risk assessment.

3. A clear and explicit statement of the strengths and limitations of a risk assessment requires a clear and explicit statement of related uncertainties.

A discussion of uncertainty requires commenton such issues as the quality and quantity of available data, gaps in the data base fo r specific chemicals, quality of the measured data, use of default assumptions, incomp lete understanding of general biological phenomena, and scientific judgments or scie nce policy positions th at were employed to bridge information gaps.

In short, broad agreement exists on the importa nce of a full picture of risk, particularly including a statement of confidence in the a ssessment and the associated uncertainties. This section discusses information cont ent and uncertainty aspects of riskcharacterization, while Section III discu sses various descriptors used in risk characterization.

B. Guiding Principles

1. The risk characterization integrat es the information from the hazard identification, dose-response, and exposure assessments, using a combination of qualitative information, quantitative information, and information regarding uncertainties.

Risk assessment is based on a series of questi ons that the assessor asks about the data and the implications of the data for human ri sk. Each question calls for analysis and interpretation of the available studies, selecti on of the data that are most scientifically reliable and most relevant to the problem at hand, and scientific conclusions regarding the question presented. As suggested below, becau se the questions and analyses are complex, a complete characterization in cludes several different kinds of information, carefully selected for reliability and relevance.

a. Hazard Identification What is known about the capacity of an environmental agent for causing cancer (or other adverse effects) in humans and laboratory animals?

Hazard identification is a quali tative description based on fa ctors such as the kind and quality of data on humans or laboratory animal s, the availability of ancillary information (e.g., structureactivity analysis, genetic toxici ty, pharmacokinetics) from other studies, and the weightofthe-evidence from all of these data sources. For example, to develop this description, the issues addressed include:

1) the nature, reliability, a nd consistency of the particular studies in humans and in laboratory animals;

2) the available information on the mechanistic basis for activity; and

3) experimental animal responses an d their relevance to human outcomes.

These issues make clear that the task of hazard identification is characterized by describing the full range of available informati on and the implications of that information for human health.

b. DoseResponse Assessment What is known about the biological mechanisms and doseresponse relationships underlying any e ffects observed in the laboratory or epidemiology studies providing data for the assessment?

The dose response assessment examines quantitative relationships between exposure (or dose) and effects in the studies used to id entify and define effects of concern. This information is later used along with "real wo rld" exposure information (see below) to develop estimates of the likelihood of adverse e ffects in populations pote ntially at risk. Itshould be noted that, in practice, hazard id entification for devel opmental toxicity and other non-cancer health effects is usually done in conjunction with an evaluation of doseresponse relationships, since the determinati on of whether there is a hazard is often dependent on whether a dose response relati onship is present. (6 ) Also, the framework developed by EPA for ecological risk asse ssment does not distinguish between hazard identification and dose-response assessment, but rather calls for a "characterization of ecological effects." (7)

Methods for establishing doseresponse relati onships often depend on various assumptions used in lieu of a complete data base, and the method chosen can st rongly influence the overall assessment. The Agency's risk asse ssment guidelines often identify so-called "default assumptions" for use in the absen ce of otherinformation. The risk assessment should pay careful attention to the choice of a hightolow dose extrapolation procedure. As a result, an assessor who is characte rizing a doseresponse relationship considers several key issues:

1) the relationship between extrapolation m odels selected and available information on biological mechanisms;

2) how appropriate data sets were selected from those that show the range of possible potencies both in laboratory animals and humans;

3) the basis for selecting interspecies dose scaling factors to account for scaling doses from experimental animals to humans;

4) the correspondence between the expected route(s) of exposure and the exposure route(s) utilized in the studies forming the basis of the dose-response assessment, as well as the interrelationships of potential effects from di fferent exposure routes;

5) the correspondence between the expected duration of exposure and the exposure durations in the studies used in forming the basis of the dose-response assessment, e.g., chronic studies would be used to assess l ong-term, cumulative exposure concentrations, while acute studies would be used in a ssessing peak levels of exposure; and

6) the potential for differing susceptibilities among population subgroups.

The Agency's Integrated Risk Informati on System (IRIS) is a repository for such information for EPA. EPA program offices al so maintain program-specific databases, such as the OSWER Health Effects Asse ssment Summary Tables (HEAST). IRIS includes data summaries representing Agency consensus on specific chemicals, based on a careful review of the scientific issues lis ted above. For specific risk assessments based on data from any source, risk assessors should ca refully review the information presented, emphasizing confidence in the data and uncertainties (see subsection 2 below). Specifically, when IRIS data are used, th e IRIS statement of confidence should be included as an explicit partof the risk characteriza tion for hazard and doseresponse information.c. Exposure Assessment What is known about the pr incipal paths, patterns, and magnitudes of human exposure and number s of persons who may be exposed?

The exposure assessment examines a wide range of exposure paramete rs pertaining to the environmental scenarios of people who may be exposed to the agent under study. The information considered for the exposure assessment includes monitoring studies of chemical concentrations in environmental media, food, and other materials; modeling of environmental fate and transport of contam inants; and information on different activity patterns of different population subgroups . An assessor who characterizes exposure should address several issues:

1) The basis for the values and input parame ters used for each exposure scenario. If the values are based on data, there should be a discussion of the quality, purpose, and representativeness of the database. For monitoring data, there should be a discussion of the data quality objectives as they are re levant to risk assessment, including the appropriateness of the analytical detec tion limits. If models are applied, the appropriateness of the models and informati on on their validation s hould be presented. When assumptions are made, the source a nd general logic used to develop the assumptions (e.g., program guidance, anal ogy, professional judgment) should be described.

2) The confidence in the assumptions made about human behavior and the relative likelihood of the different exposure scenarios.

3) The major factor or factors (e.g., concen tration, body uptake, duration/frequency of exposure) thought to account fo r the greatest uncertainty in the exposure estimate, due either to sensitivity or lack of data.

4) The link between the exposure informati on and the risk descriptors discussed in Section III of this Appendix. Specifically, the risk assessor needs to discuss the connection between the conserva tism or non-conservatism of the data/assumptions used in the scenarios and the choice of descriptors.

5) Other information that may be importantfor the particular risk assessment. For example, for many assessments, other source s and background levels in the environment may contribute significantly to populati on exposures and should be discussed.

2) The risk characterization includes a discussion of uncertainty and variability.

In the risk characterization, conclusions a bout hazard and dose res ponse are integrated with those from the exposure assessment . In addition, confidence about these conclusions, including information about the unc ertainties associated with each aspect of the assessment in the final risk summary, is highlighted. In the previous assessment steps and in the risk characterization, the ri sk assessor must distinguish between variability and 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 bei ng 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. The central tendency and high end individual risk descriptors (discussed in Section III below) are intended to capture the variability in exposure, lifestyles, and other factors that lead to a distribution of risk across a population.

Uncertainty, on the other hand, represents l ack of knowledge about factors such as adverse effects or contaminant levels wh ich may be reduced with additional study. Generally, risk assessments carry several cat egories of uncertainty, and each merits consideration. Measurement uncertainty refe rs to the usual erro r that accompanies scientific measurements--standard statistical techniques can often be used to express measurement uncertainty. A substantial amount of uncertainty is often inherent in environmental sampling, and assessments shoul d address these uncertainties. There are likewise uncertainties associat ed with the use of scientif ic models, e.g., dose-response models, models of environmental fate and transport. Evaluation of model uncertainty would consider the scientific basis for th e model and available empirical validation.

A different kind of uncertainty stems from da ta gaps that is, estimates or assumptions used in the assessment. Often, the data gap is broad, such as the absence of information on the effects of exposure to a chemical on humans or on the biological mechanism of action of an agent. The risk assessor shoul d include a statement of confidence that reflects the degree to which the risk assessor believes that the estimates or assumptions adequately fill the data gap. For somecommon and important data gaps, Agency or program-specific risk assessment guidance provides default assumptions or values. Risk assessors should carefully consider all available data before deciding to rely on default assumptions. If defaults are used, the riskassessment should reference the Agency guidance that explains the de fault assumptions or values.

Often risk assessors and managers simplify di scussion of risk issu es by speaking only of the numerical components of an assessment. That is, they refer to the alpha-numeric weight-of-the-evidence classification, unit risk, the riskspecific dose or the q 1 * for cancer risk, and the RfD/RfC for health effects ot her than cancer, to th e exclusion of other information bearing on the risk case. Ho wever, since every assessment carries uncertainties, a simplified numerical presentationof risk is always incomplete and often misleading. For this reason, the NRC (1) and EP A risk assessment guidelines (2) call for "characterizing" risk to incl ude qualitative information, a related numerical risk estimate and a discussion of uncertainti es, limitations, and assumptions--default and otherwise.

Qualitative information on methodology, alte rnative interpretations, and working assumptions (including defaults) is an importa nt component of risk characterization. For example, specifying that animal studies rather than human studies were used in an assessment tells others that the risk es timate is based on assumptions about humanresponse to a particular chemical rather than human data. Information that human exposure estimates are based on the subjects' presence in the vicin ity of a chemical accident rather than tissue measurements defines known and unknown aspects of the exposure component of the study.

Qualitative descriptions of this kind provide crucial information that augments understanding of numerical risk estimates. Uncertainties such as these are expected in scientific studies and in any risk assessmentbased on these studies. Such uncertainties do not reduce the validity of the assessment. Rath er, they should be highlighted along with other important risk assessment conclusions to inform others fully on the results of the
assessment.

In many cases, assessors must choose among av ailable data, models, or assumptions in estimating risks. Examining the impact of selected, plausible alternatives on the conclusions of the assessment is an importantpart of the uncertain ty discussion. The key words are "selected" and "plausible;" listing all alternatives to a particular assumption, regardless of their merits would be superfluous . Generators of the a ssessment, using best professional judgment, should outline the st rengths and weaknesses of the plausible alternative approaches. 1

An adequate description of th e process of alternatives selection involves several aspects.

a. A rationale for the choice.

b. Discussion of the effects of alternatives selected on the assessment.

c. Comparison with other plausible alternatives, where appropriate.

The degree to which variability and uncerta inty are addressed depends largely on the scope of the assessment and the resources av ailable. For example, the Agency does not expect an assessment to evaluate and asse ss every conceivable exposure scenario for every possible pollutant, toexamine all suscepti ble populations potential ly at risk, or to characterize every possible environmental scen ario to estimate the cause and effect relationships between exposure to pollutants and adverse h ealth effects. Rather, the discussion of uncertainty and variability should reflect the type and complexity of the risk assessment, with the level of effort for analysis and discussion of uncertainty corresponding to the level of effort for the assessment.

3. Well balanced risk characterizations p resent risk conclusions and information regarding the strengths and limitations of the assessment for ot her risk assessors, EPA decision makers, and the public.

The risk assessment process calls for iden tifying and highlighti ng significant risk conclusions and related uncertainties part ly to assure full communication among risk assessors and partly to assure that decisionmakers are fully informed. Issues are identified by acknowledging noteworthy qualita tive and quantitative factor s that make a differencein the overall assessment of hazard and ri sk, and hence in the ultimate regulatory decision. The key word is "noteworthy." Info rmation that significantly influences the analysis is explicitly noted in all future pr esentations of the risk assessment and in the related decision. Uncertainties and assumptions that strongly influence confidence in the risk estimate also require special attention.

Numerical estimates should not be separated from the descriptive information that is integral to risk characterization. Document s and presentations s upporting regulatory or site-specific decisions should include both the numerical estimate and descriptive information; in short reports, this info rmation can be abbreviated. Fully visible information assures that important features of the assessment are immediately available at each level of review for evaluating whether risks are acceptable or unreasonable.

III. EXPOSURE ASSESSMENT AND RISK DESCRIPTORS

A. Presentation of Risk Descriptors

The results of a risk assessment are usually co mmunicated to the risk manager in the risk characterization portion of the assessment. This communication is often accomplished through risk descriptors which convey information and answ er questions about risk, each descriptor providing different information and insights. E xposure assessment plays a key role in developing these risk descriptors si nce each descriptor is based in part on the exposure distribution within the population of interest.

The following guidance outlines the different descriptors in a convenient order that should not be construed as a hi erarchy of importance. These de scriptors should be used to describe risk in a variety of ways for a given assessment, consistent with the assessment's purpose, the data available, and the informati on the risk manager needs. Use of a range of descriptors instead of a single descriptor enables Agency progr ams to present a picture of risk that corresponds to the range of differe nt exposure conditions encountered for most environmental chemicals. This analysis, in turn, allows risk managers to identify populations at greater and le sser risk and to shape regul atory solutions accordingly.

Agency risk assessments will be expected to address or provide descriptions of (1) individual risk that include the central tendency and high end portions of the risk distribution, (2) population risk, and (3) impor tant subgroups of the population, such as highly exposed or highly susceptible groups. Assessors may also use additional descriptors of risk as needed when these a dd to the clarity of the presentation. With the exception of assessments where particular desc riptors clearly do not apply, some form of these three types of descriptors should be r outinely developed and presented for Agency risk assessments 2 . In other cases, where a descriptor would be relevant, but the program lacks the data or methods to develop it, the program office should design and implement a plan, in coordination with other EPA offi ces, to meet these assessment needs. While gaps continue to exist, risk assessors should make their best effort s to address each risk descriptor, and at a minimum, should briefly discuss the lack of data or methods. Finally,presenters of risk assessment information should be prepared to routinely answer questions by risk managers c oncerning these descriptors.

It is essential that presenters not only communicate the results of the assessment by addressing each of the descriptors where ap propriate, but that th ey also communicate their confidence that these results portray a r easonable picture of th e actual or projected exposures. This task will usually be a ccomplished by frankly commenting on the key assumptions and parameters that have the gr eatest impact on the results, the basis or rationale for choosing these assumptions/param eters, and the consequences of choosing other assumptions.

B. Relationship Between Exposure Descriptors and Ri sk Descriptors

In the risk assessment process, risk is estimatedas a function of exposur e, with the risk of adverse affects increasing as exposure increases. Informati on on the levels of exposure experienced by different member s of the population is key to understanding the range of risks that may occur. Risk assessors and ri sk managers should keep in mind, however, that exposure is not synonymous with ris k. Differences among indi viduals in absorption rates, susceptibility, or othe r factors mean that individua ls with the same level of exposure may be at different leve ls of risk. In most cases, th e state of the science is not yet adequate to define distributions of f actors such as population susceptibility. The guidance principles below disc uss a variety of risk descri ptors that primarily reflect differences in estimated exposure. If a full desc ription of the range of susceptibil ity in the population cannot be presented, an effort shoul d be made to identify subgroups that, for various reasons, may be pa rticularly susceptible.

C. Guiding Principles

1. Information about the distribution of individual exposures is important to communicating the results of a risk assessment.

The risk manager is generally interested in answers to questions such as the following:

• Who are the people at the highest risk?

• What risk levels are they subjected to?

• What are they doing, where do they live, et c., that might be putting them at this higher risk?

• What is the average risk for individu als in the population of interest?

Individual exposure and risk descriptors are intended to provide answers to these questions so as to illuminate the risk management decisions that need to be made. In order to describe the range of risks, both high end and cen tral tendency descriptors are used to convey the variability in risk levels experienced by different individuals in the population.

a. High end descriptorFor the Agency's purposes, high end risk de scriptors are plausible estimates of the individual risk for those persons at th e upper end of the risk distribution. Given limitations in current understand ing of variability in individu als' sensitivity to toxins, high end descriptors will usually address high end exposure or dose (herein referred to as exposure for brevity). The intent of these desc riptors is to convey estimates of exposure in the upper range of the distribution, but to avoid estimates which are beyond the true distribution. Conceptually, high end exposur e means exposure above about the 90th percentile of the population distribution, but not higher than the individual in the population who has the highest exposure. Wh en large populations are assessed,a large number of individuals may be included with in the "high end" (e.g., above 90th or 95th percentile) and information on the range of exposures received by these individuals should be presented.

High end descriptors are intended to estimate the exposures thatare expected to occur in small, but definable, "high end" segments of the subject population. 3 The individuals with these exposures may be members of a special population segment or individuals in the general population who are highly exposed because of the inhe rent stochastic nature of the factors which give rise to exposur e. Where differences in sensitivity can be identified within the population, high end estimates ad dressing sensitive indi viduals or subgroups can be developed.

In those few cases in which the complete data on the population distributions of exposures and doses are available, high end exposure or dose estimates can be represented by reporting exposures or doses at a set of selected percentiles of the distributions, such as the 90t h, 95th, and 98th percentile. High end exposures or doses, as appropriate, can then be used to calculate high end risk estimates.

In the majority of cases where the complete distributions are not available, several methods help estimate a high end exposure or dose. If sufficient information about the variability in chemical concentrations, activity patterns, or other fact ors are available, the distribution may be estimated through the us e of appropriate modeling (e.g., Monte Carlo simulation or parametric statistical methods ). The determination of whether available information is sufficient to support the use of probabilistic esti mation methods requires careful review and documentation by the risk as sessor. If the input di stributions are based on limited data, the resulting distribution s hould be evaluated carefully to determine whether it is an improvement over more traditional estimation techniques. If a distribution is developed, it s hould be described with a series of percentiles or population frequency estimates, particularly in the hi gh end range. The assessor and risk manager should be aware, however, that unless a great deal is known about exposures and doses at the high end of the distribution, these estimat es will involve considerable uncertainty which the exposure assessor will need to describe. Note that in this context, the probabilistic analysis addresses variability of exposure in the population. Probabilistic techniques may also be applied to evalua te uncertainty in estimates (see section 5, below). However, it is generally inappropriate to combine distributions reflecting both uncertainty and variability to get a single overa ll distribution. Such a re sult is not readily interpretable for the concerns of environmental decision-making.If only limited information on the distribution of the exposure or dose factors is available, the assessor should approach estimating the high end by identifying the most sensitive variables and using high end values for a subsetof these variables, leaving others at their central values. 4 In doing this, the assessor needs to avoid combinations of parameter values that are inconsistent(e.g., low body weight used in combination with high dietary intake rates), and must keep in mind th e ultimate objective of being within the distribution of actual expected expo sures and doses, and not beyond it.

If very little data are available on the ranges for the various variables, it will be difficult to estimate exposures or doses and associated risks in the high end with much confidence. Onemethod that has been used in such cas es is to start with a bounding estimate and "back off" the limits used until the combination of parameter values is, in the judgment of the assessor, within the distribution of expected exposure, and still lies within the upper 10% of persons exposed. Obviously, this me thod results in a large uncertainty and requires explanation.

b. Central tendency descriptor

Central tendency descriptors ge nerally reflect central estima tes of exposure or dose. The descriptor addressing centra l tendency may be based on either the arithmetic mean exposure (average estimate) or the median exposure (median estimate), either of which should be clearly labeled. The average estima te, used to approximate the arithmetic mean, can often be derived by using aver age values for all the exposure factors. 5 It does not necessarily represent a particular indi vidual on the distribution. Because of the skewness of typical exposure profiles, the arithmetic mean may differ substantially from the median estimate (i.e., 50th percentile esti mate, which is equal to the geometric mean for a log normal distribution). The selection of which descriptor(s) to present in the risk characterization will depend on the available data and the goals of the assessment. When data are limited, it may not be possible to c onstruct true median or mean estimates, but it is still possible to construct estimates of central tendency. The discussion of the use of probabilistic techniques in S ection 1(a) above also applies to estimates of central tendency.

2. Information about population exposure leads to another important way to describe risk.

Population risk refers to an assessment of the extent of harm for the population as a whole. In theory, it can be calculated by summing the individual risks for all individuals within the subject population. This task, of c ourse, requires a great deal more information than is normally, if ever, available.

The kinds of questions addre ssed by descriptors of population risk include the following:

• How many cases of a particular health e ffect might be probabilistically estimated in this population for a specific time period?• For non-carcinogens, what portion of the populat ion is within a specified range of some reference level; e.g., exceedance of the RfD (a dose), the RfC (a concentration), or other health concern level?

• For carcinogens, what portion of the population is above a certain risk level, such as 10 6 ?

These questions can lead to two diffe rent descriptors of population risk.

a. Probabilistic number of cases

The first descriptor is the probabilistic numbe r of health effect cas es estimated in the population of interest over a specified time peri od. This descriptor can be obtained either by (a) summing theindividual risks over all th e individuals in the population, e.g. using an estimated distribution of risk in the populat ion, when such information is available, or (b) through the use of a risk model that assumes a linear nonthreshold response to exposure, such as many carcinogenic models. In these calculations, data will typically be available to address variability in individua l exposures. If risk varies linearly with exposure, multiplying the mean risk by the population size produces an estimate of the number of cases. 6 At the present time, most cancer potency values represent plausible upper bounds on risk. When such a value is used to estimate numbers of cancer cases, it is important to understand that the result is also an upper bound. As with other risk descriptors, this approach may not adequa tely address sensitive subgroups for which different doseresponse curve or expo sure estimates might be needed.

Obviously, the more information one has, th e more certain the estimate of this risk descriptor, but inherent uncer tainties in risk assessment methodology place limitations on the accuracy of the estimate. The discussion of uncertainty involved in estimating the number of cases should indicate that this descriptor is not to be confused with an actuarial prediction of cases in the population (which is a statistical prediction based on a great deal of empirical data).

In general, it should be recognized that when small populations are exposed, population risk estimates may be very small. For exampl e, if 100 people are exposed to an individual lifetime cancer risk of 10 -4 , the expected number of cases is 0.01. In such situations,individual risk estimates will usually be a more meaningful parameter for decisionmakers.