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 principles 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 includes 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 health effects (e.g., neurotoxicity, developmental 

toxicity) and, with appropriate modifications, should be used in all health risk 

assessments. This document has not been revised to specifically address ecological risk 

assessment, however, initial guidance for ecological risk characterization is included in 

EPA's Framework for Ecological Risk Assessments (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 site- or media-specific 

risk assessments. Additional program-specific 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 risk 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 with different regulatory strategies, and 

occasionally analysis of the economic and social implications of regulatory decisions 

functions that we assign to risk management (emphasis added). (l) 
In 1984, EPA endorsed these distinctions between 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 approach to and use of risk assessment and 

issued an extensive report on their findings (4). This distinction suggests that EPA 

participants in the process can be grouped into two main categories, 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 develops chemical-specific 

risk assessments by collecting, analyzing, and synthesizing scientific data to produce the 

hazard identification, doseresponse, and exposure assessment portion of the risk 

assessment and to characterize risk. This group relies in part on Agency risk assessment 

guidelines to address science policy issues and scientific uncertainties. Generally, this 

group includes scientists and statisticians in the Office of Research and Development; the 

Office of Prevention, Pesticides and Toxics and other program offices; the Carcinogen 

Risk Assessment Verification Endeavor (CRAVE); and the Reference Dose (RfD) and 

Reference Concentration (RfC) Workgroups. 

Another group generates site or mediaspecific risk assessments for use in regulation 

development or site-specific decision-making. These assessors rely on existing databases 

(e.g., IRIS, ORD Health Assessment Documents, CRAVE and RfD/RfC Workgroup 

documents, and program-specific toxicity information) and media- or site-specific 

exposure information in developing risk assessments. This group also relies in part on 

Agency risk assessment guidelines and program-specific guidance to address science 

policy issues and scientific uncertainties. Generally, 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 the scope of risk assessments. The risk assessment process 

involves regularinteraction between risk assessors and risk managers, with overlapping 

responsibilities at various stages in the overall process. Shared responsibilities include 

initial decisions regarding the planning and conduct of an assessment, discussions as the 

assessment develops, decisions regarding new data needed to complete an assessment and 

to address significant uncertainties. At critical junctures in the assessment, such 

consultations shape the nature of, and schedule 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 Principles
The 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 assessment process have many shared responsibilities. 

Where responsibilities differ, it is important that participants confine themselves to tasks 

in their areas of responsibility and not inadvertently obscure differences between risk 

assessment and risk management. 

For the generators of the assessment, distinguishing between risk assessment and risk 

management means that scientific information is selected, evaluated, and presented 

without considering issues such as cost, feasibility, or how the scientific analysis might 

influence the regulatory or site-specific decision. Assessors are charged with (1) 

generating a credible, objective, realistic, and scientifically balanced analysis; (2) 

presenting information on hazard, dose-response, exposure and risk; and (3) explaining 

confidence in each assessment by clearly delineating strengths, uncertainties and 

assumptions, along with the impacts of these factors (e.g., confidence limits, use of 

conservative/non-conservative assumptions) on the overall assessment. They do not make 

decisions on the acceptability of any risk level 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 decisions, the distinction between risk assessment and risk 

management means refraining from influencing the risk description through 

consideration of other factors e.g., the regulatory outcome and from attempting to shape 

the risk assessment to avoid statutory constraints, meet regulatory objectives, or serve 

political purposes. Such management considerations are often legitimate considerations 

for the overall regulatory decision (see next principle), but they have no role in estimating 

or describing risk. However, decisionmakers and risk assessors participate in an Agency 

process that establishes policy directions that determine the overall nature and tone of 

Agency risk assessments and, as appropriate, provide policy guidanceon difficult and 

controversial risk assessment issues. Matters such 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, the 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 foundation for regulatory decision-making, but it is 

only one of several important components in such decisions. As the last step in risk 

assessment, the risk characterization identifies 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 regulatory process. As 
authorized by different statutes, decisionmakers 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 managers 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 benefits 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 other 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., costs and benefits) that, 

along with the risk assessment, shape the regulatory 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 important here as they are for the scientific 

components of the regulatory decision. Decision-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 factors, 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 practices draw on many sources. Obvious sources 

include the environmental laws administered 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 developing, defending, and enforcing risk 

assessmentbased regulation is another. Together these various sources stress the 

importance of a clear explanation of Agency processes for evaluating hazard, 

doseresponse, exposure, and other data that provide the scientific foundation for 

characterizing risk. 

This section focuses on two requirements for full characterization of risk. First, the 

characterization should address qualitative and quantitative features of the assessment. 

Second, it should identify the important strengths 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 assessment draws attention to the importance of the 

qualitative, as well as the quantitative, dimensions of the assessment. The 1983 NRC 
report carefully distinguished qualitative risk assessment from quantitative assessments, 

preferring risk statements that are not strictly numerical. 

The term risk assessment is often given narrower and broader meanings than we have 

adopted here. For some observers, the term is synonymous with quantitative risk 

assessment and emphasizes reliance on numerical results. 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 characterizations from the hazard identification, doseresponse, and exposure assessments; 

• Provides an evaluation of the overall quality of the assessment and the degree of 

confidence the authors have in the estimates of risk and conclusions drawn; 

• Describes risks to individuals and populations 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 carries different kinds of uncertainty and 

knowledge of these differences is important when uncertainties are combined for 

characterizing risk. 

2. The risk assessment process, with management input, involves decisions 

regarding the collection of additional data (versus living with uncertainty); in the 

risk characterization, a discussion of the uncertainties will help to identify where 

additional information could contribute significantly 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 comment on such issues as the quality and quantity 

of available data, gaps in the data base for specific chemicals, quality of the measured 

data, use of default assumptions, incomplete understanding of general biological 

phenomena, and scientific judgments or science policy positions that were employed to 

bridge information gaps. 

In short, broad agreement exists on the importance of a full picture of risk, particularly 

including a statement of confidence in the assessment and the associated uncertainties. 

This section discusses information content and uncertainty aspects of risk 
characterization, while Section III discusses various descriptors used in risk 

characterization. 

B. Guiding Principles

1. The risk characterization integrates 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 questions that the assessor asks about the data and 

the implications of the data for human risk. Each question calls for analysis and 

interpretation of the available studies, selection 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, because the questions and analyses are complex, 

a complete characterization includes 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 qualitative description based on factors such as the kind and 

quality of data on humans or laboratory animals, the availability of ancillary information 

(e.g., structureactivity analysis, genetic toxicity, 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, and 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 and their relevance to human outcomes. 

These issues make clear that the task of hazard identification is characterized by 

describing the full range of available information and the implications of that information 

for human health. 

b.DoseResponse Assessment What is known about the biological mechanisms and 

doseresponse relationships underlying any effects 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 identify and define effects of concern. This 

information is later used along with "real world" exposure information (see below) to 

develop estimates of the likelihood of adverse effects in populations potentially at risk. It 
should be noted that, in practice, hazard identification for developmental toxicity and 

other non-cancer health effects is usually done in conjunction with an evaluation of doseresponse relationships, since the determination of whether there is a hazard is often 

dependent on whether a dose response relationship is present. (6) Also, the framework 

developed by EPA for ecological risk assessment does not distinguish between hazard 

identification and dose-response assessment, but rather calls for a "characterization of 

ecological effects." (7) 

Methods for establishing doseresponse relationships often depend on various assumptions 

used in lieu of a complete data base, and the method chosen can strongly influence the 

overall assessment. The Agency's risk assessment guidelines often identify so-called 

"default assumptions" for use in the absence 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 characterizing a doseresponse relationship considers 

several key issues: 

1) the relationship between extrapolation models 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 different 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 long-term, cumulative exposure concentrations, 

while acute studies would be used in assessing peak levels of exposure; and 

6) the potential for differing susceptibilities among population subgroups. 

The Agency's Integrated Risk Information System (IRIS) is a repository for such 

information for EPA. EPA program offices also maintain program-specific databases, 

such as the OSWER Health Effects Assessment Summary Tables (HEAST). IRIS 

includes data summaries representing Agency consensus on specific chemicals, based on 

a careful review of the scientific issues listed above. For specific risk assessments based 

on data from any source, risk assessors should carefully review the information 

presented, emphasizing confidence in the data and uncertainties (see subsection 2 below). 

Specifically, when IRIS data are used, the IRIS statement of confidence should be 

included as an explicit part of the risk characterization for hazard and doseresponse 

information. 
c.Exposure Assessment What is known about the principal paths, patterns, and 

magnitudes of human exposure and numbers of persons who may be exposed? 

The exposure assessment examines a wide range of exposure parameters 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 contaminants; 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 parameters 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 relevant to risk assessment, including the 

appropriateness of the analytical detection limits. If models are applied, the 

appropriateness of the models and information on their validation should be presented. 

When assumptions are made, the source and general logic used to develop the 

assumptions (e.g., program guidance, analogy, 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., concentration, body uptake, duration/frequency of 

exposure) thought to account for the greatest uncertainty in the exposure estimate, due 

either to sensitivity or lack of data. 

4) The link between the exposure information and the risk descriptors discussed in 

Section III of this Appendix. Specifically, the risk assessor needs to discuss the 

connection between the conservatism or non-conservatism of the data/assumptions used 

in the scenarios and the choice of descriptors. 

5) Other information that may be important for the particular risk assessment. For 

example, for many assessments, other sources and background levels in the environment 

may contribute significantly to population exposures and should be discussed. 

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

In the risk characterization, conclusions about hazard and dose response are integrated 

with those from the exposure assessment. In addition, confidence about these 

conclusions, including information about the uncertainties 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 risk 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 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. 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 lack of knowledge about factors such as 

adverse effects or contaminant levels which may be reduced with additional study. 

Generally, risk assessments carry several categories of uncertainty, and each merits 

consideration. Measurement uncertainty refers to the usual error 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 should address these uncertainties. There are 

likewise uncertainties associated with the use of scientific models, e.g., dose-response 

models, models of environmental fate and transport. Evaluation of model uncertainty 

would consider the scientific basis for the model and available empirical validation. 

A different kind of uncertainty stems from data 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 should 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 risk assessment should reference the Agency 

guidance that explains the default assumptions or values. 

Often risk assessors and managers simplify discussion of risk issues 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 q1* for cancer 

risk, and the RfD/RfC for health effects other than cancer, to the exclusion of other 

information bearing on the risk case. However, since every assessment carries 

uncertainties, a simplified numerical presentation of risk is always incomplete and often 

misleading. For this reason, the NRC (1) and EPA risk assessment guidelines (2) call for 

"characterizing" risk to include qualitative information, a related numerical risk estimate 

and a discussion of uncertainties, limitations, and assumptions--default and otherwise. 

Qualitative information on methodology, alternative interpretations, and working 

assumptions (including defaults) is an important component of risk characterization. For 

example, specifying that animal studies rather than human studies were used in an 

assessment tells others that the risk estimate is based on assumptions about human 
response to a particular chemical rather than human data. Information that human 

exposure estimates are based on the subjects' presence in the vicinity 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 assessment based on these studies. Such uncertainties do 

not reduce the validity of the assessment. Rather, 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 available data, models, or assumptions in 

estimating risks. Examining the impact of selected, plausible alternatives on the 

conclusions of the assessment is an important part of the uncertainty 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 assessment, using best 

professional judgment, should outline the strengths and weaknesses of the plausible 

alternative approaches.1

An adequate description of the 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 uncertainty are addressed depends largely on the 

scope of the assessment and the resources available. For example, the Agency does not 

expect an assessment to evaluate and assess every conceivable exposure scenario for 

every possible pollutant, toexamine all susceptible populations potentially at risk, or to 

characterize every possible environmental scenario to estimate the cause and effect 

relationships between exposure to pollutants and adverse health 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 present risk conclusions and information 

regarding the strengths and limitations of the assessment for other risk assessors, 

EPA decision makers, and the public.

The risk assessment process calls for identifying and highlighting significant risk 

conclusions and related uncertainties partly to assure full communication among risk 

assessors and partly to assure that decisionmakers are fully informed. Issues are identified 

by acknowledging noteworthy qualitative and quantitative factors that make a difference 
in the overall assessment of hazard and risk, and hence in the ultimate regulatory 

decision. The key word is "noteworthy." Information that significantly influences the 

analysis is explicitly noted in all future presentations 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. Documents and presentations supporting regulatory or 

site-specific decisions should include both the numerical estimate and descriptive 

information; in short reports, this information 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 communicated to the risk manager in the risk 

characterization portion of the assessment. This communication is often accomplished 

through risk descriptors which convey information and answer questions about risk, each 

descriptor providing different information and insights. Exposure assessment plays a key 

role in developing these risk descriptors since 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 hierarchy of importance. These descriptors 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 information the risk manager needs. Use of a range of 

descriptors instead of a single descriptor enables Agency programs to present a picture of 

risk that corresponds to the range of different exposure conditions encountered for most 

environmental chemicals. This analysis, in turn, allows risk managers to identify 

populations at greater and lesser risk and to shape regulatory 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) important subgroups of the population, such as 

highly exposed or highly susceptible groups. Assessors may also use additional 

descriptors of risk as needed when these add to the clarity of the presentation. With the 

exception of assessments where particular descriptors clearly do not apply, some form of 

these three types of descriptors should be routinely developed and presented for Agency 

risk assessments2

. 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 offices, to meet these assessment needs. While 

gaps continue to exist, risk assessors should make their best efforts 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 concerning these descriptors. 

It is essential that presenters not only communicate the results of the assessment by 

addressing each of the descriptors where appropriate, but that they also communicate 

their confidence that these results portray a reasonable picture of the actual or projected 

exposures. This task will usually be accomplished by frankly commenting on the key 

assumptions and parameters that have the greatest impact on the results, the basis or 

rationale for choosing these assumptions/parameters, and the consequences of choosing 

other assumptions. 

B. Relationship Between Exposure Descriptors and Risk Descriptors

In the risk assessment process, risk is estimated as a function of exposure, with the risk of 

adverse affects increasing as exposure increases. Information on the levels of exposure 

experienced by different members of the population is key to understanding the range of 

risks that may occur. Risk assessors and risk managers should keep in mind, however, 

that exposure is not synonymous with risk. Differences among individuals in absorption 

rates, susceptibility, or other factors mean that individuals with the same level of 

exposure may be at different levels of risk. In most cases, the state of the science is not 

yet adequate to define distributions of factors such as population susceptibility. The 

guidance principles below discuss a variety of risk descriptors that primarily reflect 

differences in estimated exposure. If a full description of the range of susceptibility in the 

population cannot be presented, an effort should be made to identify subgroups that, for 

various reasons, may be particularly 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, etc., that might be putting them at this 

higher risk? 

• What is the average risk for individuals 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 central tendency descriptors are 

used to convey the variability in risk levels experienced by different individuals in the 

population. 

a. High end descriptor
For the Agency's purposes, high end risk descriptors are plausible estimates of the 

individual risk for those persons at the upper end of the risk distribution. Given 

limitations in current understanding of variability in individuals' 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 descriptors 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 exposure 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. When large populations are assessed,a large 

number of individuals may be included within 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 that are 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 inherent stochastic nature of 

the factors which give rise to exposure. Where differences in sensitivity can be identified 

within the population, high end estimates addressing sensitive individuals 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 90th, 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 factors are available, the 

distribution may be estimated through the use 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 estimation methods requires 

careful review and documentation by the risk assessor. If the input distributions are based 

on limited data, the resulting distribution should be evaluated carefully to determine 

whether it is an improvement over more traditional estimation techniques. If a 

distribution is developed, it should be described with a series of percentiles or population 

frequency estimates, particularly in the high 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 estimates 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 evaluate uncertainty in estimates (see section 5, 

below). However, it is generally inappropriate to combine distributions reflecting both 

uncertainty and variability to get a single overall distribution. Such a result 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 subset of 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 the ultimate objective of being within the 

distribution of actual expected exposures 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 cases 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 method results in a large uncertainty and 

requires explanation. 

b. Central tendency descriptor

Central tendency descriptors generally reflect central estimates of exposure or dose. The 

descriptor addressing central 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 estimate, used to approximate the arithmetic 

mean, can often be derived by using average values for all the exposure factors.5

 It does 

not necessarily represent a particular individual 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 estimate, 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 construct 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 Section 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 course, requires a great deal more information 

than is normally, if ever, available. 

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

• How many cases of a particular health effect might be probabilistically estimated 

in this population for a specific time period? 
• For non-carcinogens, what portion of the population 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 106? 

These questions can lead to two different descriptors of population risk. 

a. Probabilistic number of cases

The first descriptor is the probabilistic number of health effect cases estimated in the 

population of interest over a specified time period. This descriptor can be obtained either 

by (a) summing theindividual risks over all the individuals in the population, e.g. using 

an estimated distribution of risk in the population, 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 individual 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 adequately address sensitive subgroups for which 

different doseresponse curve or exposure estimates might be needed. 

Obviously, the more information one has, the more certain the estimate of this risk 

descriptor, but inherent uncertainties 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 example, 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.