EPA/630/P-03/003F 

 November 2005

Guidance on Selecting Age Groups for Monitoring and 

Assessing Childhood Exposures to Environmental 

Contaminants 

 

Risk Assessment Forum 

U.S. Environmental Protection Agency 

Washington, DC 
DISCLAIMER 

This document has been reviewed in accordance with U.S. Environmental Protection 

Agency policy and approved for publication. Mention of trade names or commercial products 

does not constitute endorsement or recommendation for use. 

 

Preferred Citation: 

U.S. Environmental Protection Agency (EPA). (2005) Guidance on selecting age groups for monitoring and

assessing childhood exposures to environmental contaminants. National Center for Environmental Assessment, 

Washington, DC; EPA/630/P-03/003F. Available from: National Technical Information Service, Springfield, VA, 

and online at http://epa.gov/ncea.

ii
CONTENTS

LIST OF TABLES......................................................................................................................... iv 

LIST OF FIGURES ....................................................................................................................... iv 

ACKNOWLEDGMENTS ...............................................................................................................v

FOREWORD................................................................................................................................. vi 

PREFACE..................................................................................................................................... vii 

AUTHORS AND CONTRIBUTORS .............................................................................................x 

EXECUTIVE SUMMARY ........................................................................................................... xi 

1. INTRODUCTION ...............................................................................................................1 

2. AGE GROUPS TO CONSIDER WHEN ASSESSING CHILDHOOD EXPOSURES

TO ENVIRONMENTAL CONTAMINANTS....................................................................6

3. APPLYING THE RECOMMENDED SET OF CHILDHOOD AGE GROUPS TO 

EXPOSURE ASSESSMENT ............................................................................................16 

3.1. CONDUCTING SCREENING-LEVEL EXPOSURE ASSESSMENTS .................16

3.2. INTEGRATING EXPOSURE ACROSS MULTIPLE AGE GROUPS ...................17

..................................18

3.3. ADDITIONAL CONSIDERATIONS WHEN USING HUMAN EXPOSURE 

 MODELS AND ALGORITHMS IN RISK ASSESSMENTS

REFERENCES ..............................................................................................................................22 

OTHER RECOMMENDED REFERENCES................................................................................23 

GLOSSARY ..................................................................................................................................25

APPENDIX: PRELIMINARY REEVALUATION OF EXPOSURE FACTORS DATA 

 FOR CHILDREN....................................................................................................27

APPENDIX REFERENCES..........................................................................................................36

iii
LIST OF TABLES 

Table 1. Examples of Early-Life Age Groups Used in Past Agency Exposure 

Assessments.................................................................................................................5 

Table 2. Examples of Factors Considered in Deriving Age Groups Reflecting 

Behavioral Development.............................................................................................9 

Table 3. Examples of Factors Considered in Deriving Age Groups Reflecting 

Anatomical/Physiological Development...................................................................10 

Table 4. Recommended Set of Childhood Age Groups for Agency Exposure 

Assessments...............................................................................................................13 

Table 5. Integrating This Age Grouping Guidance with the Supplemental Guidance 

for Assessing Susceptibility from Early-Life Exposure to Carcinogens That 

Act via a Mutagenic Mode of Action ........................................................................18 

Table A-1. Availability of Data for the Proposed Age Bins.......................................................29 

LIST OF FIGURES 

Figure 1. Relationship Between Exposure, Dose, and Effects in Risk Assessment ...................8 

Figure 2. Comparison of Single-Day Exposure Estimates with Various TimeAveraged Exposures..................................................................................................21 

 

iv
ACKNOWLEDGMENTS 

We would like to acknowledge the assistance of the following outside scientific experts 

who participated in a peer involvement workshop in 2000 that led to the development of this 

document: 

Thomas W. Armstrong ExxonMobil Biomedical Sciences 

Sophie J. Balk Montefiore Medical Center, New York 

Deborah H. Bennett Department of Public Health Services, University of

California, Davis 

James V. Bruckner College of Pharmacy, University of Georgia 

Michael Dinovi FDA Center for Food Safety and Applied Nutrition 

Richard Fenske University of Washington School of Public Health 

Gary L. Ginsberg Connecticut Department of Public Health 

Lynn Goldman Johns Hopkins School of Public Health 

Robert Johnson Agency for Toxic Substances and Disease Registry 

Celestine Kiss U.S. Consumer Product Safety Commission 

John C. Kissel University of Washington School of Public Health 

Bruce P. Lanphear Children’s Medical Center, Cincinnati, OH 

James O. Leckie Stanford University 

Melanie A. Marty California EPA 

Mary Kay O’Rourke University of Arizona 

George C. Rodgers University of Kentucky, Louisville 

P. Barry Ryan Rollins School of Public Health, Emory University 

Margo Schwab Johns Hopkins School of Public Health 

Katherine M. Shea Pediatrician, Chapel Hill, NC 

Kimberly Thompson (Chair) Harvard School of Public Health 

William B. Weil Pediatrics, Michigan State University 

Robin M. Whyatt Columbia Mailman School of Public Health 

At the same time, it is important to also recognize those scientists who provided peer review 

comments on the initial version of this document, including: 

Timothy J. Buckley Johns Hopkins Bloomberg School of Public Health 

Christine F. Chaisson CF Chaisson Scientific Advisors, Inc. 

Jeffrey H. Driver InfoScientific Corp. 

Ruth A. Etzel George Washington University School of Public Health 

Robert J. Fares Risk Management Initiative 

Elaine M. Faustman, (Chair) University of Washington School of Public Health 

Natalie C. G. Freeman Environmental and Occupational Health Sciences Institute 

Gary L. Ginsberg, Ph.D. Connecticut Department of Public Health 

Larry L. Needham Centers for Disease Control and Prevention 

P. Barry Ryan Rollins School of Public Health, Emory University 

Robin M. Whyatt Columbia Mailman School of Public Health 

Mary S. Wolff Mt. Sinai School of Medicine, New York 

v
FOREWORD 

Based on the peer review and public comments, the Risk Assessment Forum technical 

panel has made a number of changes to the earlier draft of this document, including clarifying 

the relationship between this report and other exposure assessment guidance/models/tools, 

improving illustrative diagrams, expanding the citations, and adding language to the preface to 

discuss scientific, regulatory, and legal constraints associated with the consideration of this 

guidance. EPA expects to develop case examples to illustrate the use of this guidance; these case 

studies would then be made available on the Risk Assessment Forum’s Web site. 

vi
PREFACE

The roots of this guidance reach back to the late 1980s with the advent of planning for an 

EPA program in the area of residential exposure methods and data development, which was 

followed by the Risk Assessment Forum’s revision of EPA’s Guidelines for Exposure 

Assessment in 1992. Soon thereafter, the National Academy of Sciences released its seminal 

reports, Science and Judgment in Risk Assessment and Pesticides in the Diets of Infants and 

Children. Both of these reports contained recommendations on how EPA should improve its 

approaches to assessing potential risks to children. Since that time, there has been considerable 

effort across the Agency’s program offices and research activities directed at developing risk 

assessment guidance applicable to children’s particular exposures. The purpose of this document 

is to complement existing EPA guidance and experience to assist Agency risk assessors in 

improving the accuracy and consistency of children’s exposure assessments. The document 

describes a set of age groupings that can be used, and when necessary adapted, for purposes of 

designing monitoring studies and conducting risk assessments focused on children. 

This guidance was developed by a technical panel under the auspices of the Risk 

Assessment Forum. The Risk Assessment Forum was established to promote scientific 

consensus on risk assessment issues and to foster the implementation of this consensus into the 

Agency’s risk assessment practices. To accomplish this, the Forum assembles experts from

throughout EPA in a formal process to study and report on issues from an Agency-wide 

perspective. The document reflects the Forum’s long-standing commitment to advancing 

exposure assessment and to supplement the Agency’s Guidelines for Exposure Assessment. This 

activity was initiated by Agency risk assessors, who requested that the Forum study and provide 

recommendations on a set of early-lifestage age groupings for initial consideration. 

As an initial step, the Forum hosted a peer involvement workshop in 2000 to bring 

together for the first time scientific experts in the areas of child development and exposure 

assessment to answer the question of how knowledge of behavioral, anatomical, and 

physiological changes in children can guide the development of a generic set of age groupings. 

This workshop resulted in a recommended set of early-lifestage age groupings. Following the 

workshop, the Forum’s technical panel commissioned an expert review and reevaluation of the 

data available for the groupings recommended by the workshop. The data sources gathered in 

developing the draft Child-Specific Exposure Factors Handbook were used for this reevaluation. 

vii
The expert review provided a number of recommendations for short-term analyses and longerterm research to improve the current database for childhood exposure. The Exposure Factors 

Program and individual research grants administered by the National Exposure Research 

Laboratory have begun to implement the findings of the 2000 workshop and the 2001 expert 

review to guide future data-gathering and research activities. 

Finally, an earlier draft of this document was internally and externally peer reviewed in

2003 and made available for public comment at that time. The generic children’s age group 

recommendations were selected on the basis of the aforementioned reviews and subsequent 

discussions with Agency risk assessors. 

This document recommends a set of age groupings based on current understanding of 

differences in lifestage behavior and anatomy and physiology that can serve as a starting set for 

consideration by Agency risk assessors and researchers. In specific situations, it is recognized 

that exposure factors data may not be available for many of the recommended age groupings or 

that a specific age group may not need to be the subject of a particular assessment, so flexibility 

and professional judgment are essential in applying these generic age groupings. In order to use 

the age groupings appropriately, one should, within the problem formulation step of any 

assessment, consider the available exposure data and the objectives of the assessment. The 

process of matching age groups to existing exposure data and combining these with toxicity data 

can vary according to the circumstances; therefore, this document should be used in combination 

with other exposure and risk assessment tools and guidance. 

There are many efforts underway within the Agency to address developmental issues and 

to characterize physical variations that occur in different lifestages throughout the life span. 

There will always be a need to balance the added value of increased resolution against the cost of 

generating the necessary exposure data. The recommended age groupings can focus future 

research and data collection efforts so that one can move toward a goal of conducting exposure 

assessments that address all significant variations in lifestage. Ultimately, as our understanding 

of the factors determining potential susceptibility as a function of age improves, exposure 

assessors will be able to make more informed choices about the level of resolution needed to 

make the best public health decisions. 

EPA exposure assessments may be conducted differently than envisioned in this guidance 

for many reasons, including but not limited to, chemical- or route-specific exposure, hazard or

exposure/dose-response information, new scientific information or understanding, or differences 

viii
in science policy judgment. The practice of assessing exposure to toxicants continues to 

develop, and specific components of this guidance may become outdated or may otherwise 

require modification in individual settings. It is EPA’s intent to use, to the extent practicable and 

consistent with Agency statutes and regulations, the best available science in its risk assessments 

and regulatory actions, and this guidance is not intended to provide any substantive or procedural 

obstacle in achieving that goal. Therefore, this guidance has no binding effect on EPA or on any 

regulated entity. When EPA does use this guidance in developing exposure and risk 

assessments, it will be because it has decided in the context of that assessment that the 

approaches from this guidance are suitable and appropriate. This judgment will be tested 

through peer review, and the exposure/risk assessment will be modified to use different

approaches, if appropriate. 

This guidance does not establish any substantive “rules” under the Administrative 

Procedure Act or any other law and has no binding effect on EPA or any regulated entity, but 

instead represents a nonbinding statement of policy. 

 

ix
 AUTHORS AND CONTRIBUTORS 

Authors

 

Michael Firestone, Office of Children’s Health Protection/Office of the Administrator 

Elaine Hubal, Jacqueline Moya, Valerie Zartarian, Office of Research and Development 

Risk Assessment Forum Staff 

William P. Wood, Executive Director 

Gary Bangs, Science Coordinator 

Contributors 

Karen Pollard, Office of Solid Waste and Emergency Response 

Jianping Xue, Karen Hammerstrom, Office of Research and Development 

Tom Brennan, Jeff Dawson, Steven Knott, Timothy Leighton, David Miller, Office of Pesticides 

and Toxic Substances 

x
EXECUTIVE SUMMARY 

Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures 

to Environmental Contaminants provides a set of early-lifestage age groups for U.S. 

Environmental Protection Agency (EPA, or the Agency) scientists to consider when assessing 

children’s exposure to environmental contaminants and the resultant potential dose. These 

recommended age groups are based on current understanding of differences in behavior and 

physiology that may impact exposures in children. A consistent set of early-life age groups, 

supported by an underlying scientific rationale, is expected to improve Agency exposure and risk 

assessments for children by increasing the consistency and comparability of risk assessments 

across the Agency, improving accuracy and transparency in assessments for those cases where 

current practice might too broadly combine behaviorally and physiologically disparate age 

groups, and fostering a consistent approach to future exposure surveys and monitoring efforts to 

generate improved exposure factors for children. 

A current impediment to the creation and use of a consistent set of age groupings is the 

lack of adequate data to characterize a number of physiological, behavioral, and other relevant 

parameters across age groups. It is important to note that the recommended age groups are 

based on exposure considerations and, as such, are not intended to take into account chemicalspecific toxicological variability that can also impact risk; such considerations, as discussed 

later, should occur through an iterative dialogue between exposure assessors and toxicologists. 

Prior to the release of its revised Guidelines for Carcinogen Risk Assessment in 2005, the 

Agency often described all types of subgroups of individuals as subpopulations. The guidelines 

recognized that it is helpful to distinguish between subgroups that form a relatively fixed portion 

of the population (e.g., subgroups based on ethnicity) and subgroups such as age groups that are 

potentially inclusive of the entire population over time. Accordingly, following the revised 

cancer guidelines, this guidance views childhood as a sequence of lifestages and, therefore, treats 

age subgroups of children as lifestages, not subpopulations 

This guidance is expected to assist the Agency in implementing such regulatory 

initiatives as Presidential Executive Order 13045 (http://yosemite.epa.gov/ochp/ochpweb.nsf/ 

content/whatwe_executiv.htm), which directs all Federal agencies to (a) make it a high priority 

to identify and assess environmental health risks and safety risks that may disproportionately 

xi
affect children, and (b) ensure that their policies, programs, activities, and standards address 

disproportionate risks to children that result from environmental health risks or safety risks. 

Historically, various programs within EPA have independently developed approaches 

(including the use of age groupings) to address children’s exposure. These approaches were, in 

part, influenced by a combination of circumstances, including the goals of the enabling 

legislation, the assessment question at hand, and the availability of data. The Agency risk 

assessor community, in an effort to foster greater cross-Agency consistency in approaches to 

children’s risk assessment, requested that EPA’s Risk Assessment Forum (RAF) study and 

recommend a set of early-lifestage groupings for initial consideration in children’s risk 

assessments. Primarily on the basis of scientific discussions held during the EPA RAF July 2000 

peer involvement workshop and subsequent technical analysis by an RAF work group, the 

Forum is recommending that the following age groups be considered in Agency exposure 

assessments for children and used as a guide for future exposure data collection and analysis 

efforts:

• Less than 12 months old: birth to <1 month, 1 to <3 months, 3 to <6 months, and 6 to 

<12 months. 

• Greater than 12 months old: 1 to <2 years, 2 to <3 years, 3 to <6 years, 6 to <11 

years, 11 to <16 years, and 16 to <21 years. 

Note that this guidance has adopted the age group notation “X to <Y” (e.g., the age group 

3 to <6 years is meant to span a 3-year time interval from a child’s 3rd birthday up until the day 

before his or her 6th birthday). These age groupings and the supporting rationale for their 

selection have been subjected to internal and external scientific peer review and reflect the 

comments of the reviewers. Other scientific bodies, such as the International Life Sciences 

Institute, have also recommended evaluating children’s exposure as a series of lifestages. 

Due to limits in currently available data on age-specific exposure factors for young 

children, criteria used to select these age groupings were often qualitative in nature. Narrow age 

groups were identified where rapid developmental changes occur, and broader age groups were 

identified as the rate of development decreased. The experts involved in defining these age 

groupings have also recommended that this guidance be a “living document” and be updated as 

new data and analyses become available. After the workshop, the RAF work group 

commissioned an expert review and reevaluation of the data available for the recommended 

xii
groupings: the data gathered to support the draft Child-Specific Exposure Factors Handbook 

were used for this reevaluation. This resulted in an issue paper that provided a number of 

recommendations for short-term analyses and longer-term research to improve the database for 

childhood exposure. 

Because childhood is a time of rapid behavioral and physiological changes, it is important 

that exposure assessors consider these significant differences when conducting an exposure 

assessment. There may be instances for a particular chemical and/or exposure scenario where 

combining some of the recommended age groups (e.g., combining the first three <1 year age 

groups into one representing birth to <6 months) is indicated; i.e., variation in exposure factors 

and resulting exposures is insignificant. In addition, there may be instances where it is not 

necessary to address every age group listed above because exposure is unlikely or the focus of 

the risk assessment may be a health effect for which only one or two of the above groups 

represent a critical window. Where there is a lack of exposure data for a particular age group of 

potential importance, the risk assessor should still consider how exposure for this age group 

might differ and the possible implications for not explicitly including the age group. In such 

cases, the uncertainty associated with these assumptions should be discussed with the underlying 

rationale for splitting, combining, or excluding particular age groups. 

A key component of this guidance involves aggregating age-specific differences in 

exposure across time when assessing long-term exposure, as well as integrating these agespecific exposures with age-specific differences in toxic potency in those cases where 

information exists to describe such differences: an example is carcinogens that act via a 

mutagenic mode of action. When assessing chronic risks, rather than assuming a constant level 

of exposure for 70 years (usually consistent with an adult level of exposure), the Agency has 

been moving to consider exposure at different lifestages; this guidance is meant to be an aid in 

this continuing process. An assessor should sum across time-weighted values for all age periods 

when exposure is likely to occur. This approach is expected to increase the accuracy of risk 

assessments because it will take into account lifestage differences in exposure. Depending on 

whether body-weight-adjusted childhood exposures are either smaller or larger as compared with 

those for adults, calculated risks could either decrease or increase as compared with the approach 

of assuming a lifetime of a constant level of exposure. If age-related differences in toxicity were 

also found to occur, differences in both toxicity and exposure would need to be integrated across 

all relevant age intervals.

xiii
The scope of this guidance is limited to recommending a generic set of age groupings. 

However, it should be emphasized that other factors not discussed in this document can also have 

a significant impact on exposure and dose, such as special population considerations associated 

with ethnic and cultural variability (e.g., consideration for higher fish consumption rates among 

some Native American populations), gender differences, and socioeconomic, geographic, and 

seasonal effects. When assessing exposure, an assessor should consider the potential impact of 

these other factors in arriving at a final set of age groupings. For example, the Agency 

recognizes that maternal behavior patterns, including dietary intake, can affect fetal exposure. 

However, at the time of this writing, Agency methodologies have not been developed to 

separately evaluate fetal exposure (SAB, 2004). The Agency will be following scientific 

advances in understanding the implications of such exposures and is currently developing a risk 

assessment framework for children (U.S. EPA, 2003a) that will allow for the incorporation of 

such advances. Future guidance is anticipated. 

It is expected that the age groups identified in this guidance will be used as the basis for 

future updates of EPA’s interim final Child-Specific Exposure Factors Handbook. Accordingly, 

this document highlights a number of areas for research that will address filling exposure factors 

data gaps. These areas of further analysis and research are summarized in the appendix to the 

main text, and it is expected that this guidance will direct the design of future exposuremonitoring studies. Finally, any future revisions to the Agency’s 1992 Guidelines for Exposure 

Assessment will reflect the recommendations of this RAF guidance. 

xiv
1. INTRODUCTION 

The recommendations contained in this document are designed to provide guidance to 

U.S. Environmental Protection Agency (EPA, or the Agency) scientists on a standard set of age 

groups to consider when assessing, modeling, or monitoring childhood exposures and potential 

doses to environmental contaminants. This guidance is intended to complement existing 

exposure assessment guidance, principles, approaches, and tools. Since 1992, EPA has released 

other Agency-wide guidance and other tools to aid scientists in the assessment of early-life 

exposure, including 

• Food Quality Protection Act Implementation (U.S. EPA, 1996). 

• Exposure Factors Handbook (U.S. EPA, 1997a). A summary of the available 

statistical data on various factors used in assessing human exposure. 

• Guiding Principles for Monte Carlo Analysis (U.S. EPA, 1997b). A set of principles 

for applying the various techniques for conducting quantitative analyses of variability 

and uncertainty associated with exposure assessment. 

• Standard Operating Procedures (SOPs) for Residential Exposure Assessments (U.S. 

EPA, 1997c). Procedures designed for those who assess exposure to pesticides in a 

residential setting. 

• Child-Specific Exposure Factors Handbook (Interim Report) (U.S. EPA, 2002). A 

summary of the available and up-to-date statistical data on various factors assessing 

children exposures. 

• “Consolidated Human Activity Database” (CHAD) (http://www.epa.gov/chadnet1/). 

Contains data obtained from pre-existing human activity studies that were collected at

city, state, and national levels. CHAD is intended to be an input file for 

exposure/intake dose modeling and/or statistical analysis. It is a master database 

providing access to other human activity databases using a consistent format. 

• “Stochastic Human Exposure and Dose Simulation” (SHEDS) 

(http://www.epa.gov/heasd/emrb/emrb.htm). A modeling system being developed for 

analyzing multimedia multipathway exposures of both the general and sensitive 

groups or populations, such as children and the elderly. 

In 1993, the National Academy of Sciences (NAS) released Pesticides in the Diets of

Infants and Children (NAS, 1993), which highlighted important differences between children 

and adults with respect to risks posed by pesticides. Some of the principles in the NAS report 

1
provided the foundation for the Food Quality Protection Act of 1996 (FQPA) and Executive 

Order 13045, “Protection of Children from Environmental Health Risks and Safety Risk.” One 

of the provisions of the FQPA requires that children’s aggregate exposure be considered when 

establishing pesticide tolerances (legal limits for residues in food). Executive Order 13045 also 

broadened consideration of impacts on children by stating that “each Federal agency: shall 

ensure that its policies, programs, activities, and standards address disproportionate risks to 

children that result from environmental health risks or safety risks” (Clinton, 1997). In response 

to these regulatory initiatives, EPA has been investigating ways to improve Agency risk 

assessments for children.

An EPA workgroup, convened under the auspices of the Risk Assessment Forum (RAF), 

concluded that a major issue facing the Agency is how to consistently consider age-related 

changes in behavior and physiology when assessing early-lifestage exposure and potential dose. 

This issue is critical for scientists involved in preparing exposure assessments applicable to 

children and for use in evaluating lifestage-integrated lifetime exposures. Therefore, the RAF 

convened a technical peer involvement workshop in July 2000 to consider developmental 

changes when assessing exposures in children and commissioned a subsequent expert analysis of 

existing exposure factors data (U.S. EPA, 2000). 

The RAF work group that developed the recommended age groupings also recognized 

that human development is best treated as a continuum—physiologically, anatomically, 

behaviorally, and for other parameters. However, there are identifiable periods of development 

that occur in successive stages in each individual. Because of the inherent differences between 

each lifestage, it is important to characterize exposure as a function of lifestage and to develop 

methods to assess the factors contributing to these exposures. This document addresses the 

changes prior to adulthood; future documents may deal with characteristics particular to other 

lifestages, such as maternity and senescence. 

Early-lifestage exposures to environmental contaminants are often different from those in 

later stages of life for a number of reasons. For example: 

• Early-lifestage behaviors may contribute to higher exposures. Physically, children 

are closer to the ground than are adults and therefore live in a dustier, more 

contaminated environment. Young children spend time playing on the ground outside 

or on the floor indoors. Generally, children often spend more time outdoors than do 

adults. Infants and toddlers engage in mouthing behaviors that can increase exposure 

to environmental contaminants. Young children are known to inadvertently and/or 

2
intentionally ingest significant amounts of the soil that adheres to their hands. 

Children of all ages engage in risky behaviors that may increase exposure to 

environmental agents. 

• Physiologically, children’s metabolic rates and activity levels tend to be greater than 

those of adults. Accordingly, children consume more water and food per unit of body 

weight than do adults. Additionally, during their first few years, children consume 

larger amounts of a narrower range of specific foods than do adults. Also consistent 

with their higher metabolic rates, children have higher respiratory rates on a perbody-weight basis. The greater metabolic rates of children as compared with those of 

adults may lead to greater doses of those chemicals that are created by metabolic 

processes. 

• The skin of infants (particularly newborns) is more permeable to many environmental 

chemicals than is the skin of older children and adults. Children may have more cuts, 

scrapes, and rashes that would compromise this barrier. Similarly, the blood-brain 

barrier is less well developed in infants. Some studies indicate that lead may be 

absorbed more efficiently from the gastrointestinal tract in very young children than 

in adults, although there are many factors affecting this (e.g., iron and calcium status). 

• Additionally, infants and adults exhibit differences in their metabolism and excretion 

of absorbed environmental contaminants, leading to potential differences in 

biologically effective dose. Metabolic pathways are generally less developed in 

infants as compared with those in adults. Depending on the specific substances 

involved, impaired metabolism may either increase or decrease the toxicity of 

environmental agents. The liver and kidneys of infants (younger than 1 year) also are 

less effective at removing certain environmental toxicants from the bloodstream than 

those of adults. 

Prior to the release of its revised cancer guidelines (U.S. EPA, 2005a), the Agency often 

described all types of subgroups of individuals as “subpopulations.” The revised guidelines 

recognized that it is helpful to distinguish between subgroups that form a relatively fixed portion 

of the population (e.g., subgroups based on ethnicity) and subgroups such as age groups that are 

potentially inclusive of the entire population over time. Accordingly, following the revised 

cancer guidelines, this guidance views childhood as a sequence of lifestages, and as such, treats 

age subgroups of children as lifestages, not subpopulations. 

This guidance defines “lifestage” as a distinguishable time frame in an individual’s life 

characterized by unique and relatively stable behavioral and/or physiological characteristics that 

are associated with development and growth. Note that although the upper and lower bounds of 

lifestages may be both variable and uncertain, the age groups recommended in this guidance 

were chosen to represent typical lifestages relevant to environmental contaminant exposure. 

3
This emphasis on childhood as a sequence of lifestages has evolved from the earlier view 

of children as a subpopulation. For example, when EPA released its Guidelines for Exposure 

Assessment (U.S. EPA, 1992), lifestages were considered to be covered by the term “subgroup” 

and/or “subpopulation.” The 1992 guidance described the general concepts of exposure 

assessment, including definitions and associated units, the planning and conduct of an exposure 

assessment, and recommendations on presenting the results of the exposure assessment and 

characterizing uncertainty. The focus of the guidance was on exposures in humans. According 

to Section 5.3.5.2 of the guidelines. 

It is often helpful for the risk assessor to describe risk by an identification, and if 

possible, characterization and quantification of the magnitude of the risk for specific 

highly exposed subgroups within the population. This descriptor is useful when there is 

(or is expected to be) a subgroup experiencing significantly different exposures or doses 

from that of the larger population. It is also helpful to describe risk by an identification, 

and if possible, characterization and quantification of the magnitude of risk for specific 

highly sensitive or highly susceptible subgroups within the population. This descriptor 

is useful when the sensitivity or susceptibility to the effect for specific subgroups within 

the population is (or is expected to be) significantly different from that of the larger 

population. In order to calculate risk for these subgroups, it will sometimes be necessary 

to use a different dose-response relationship.... A special case of a subpopulation is that 

of children. 

Typically, Agency assessors have classified individuals under the age of 21 years as 

youth or children. However, a system for subdividing this group in a consistent and 

scientifically supported manner has been somewhat elusive. Other scientific bodies, such as the 

International Life Sciences Institute, have also recommended evaluating children’s exposure as a 

series of lifestages. Historically, Agency scientists have applied expert judgment to create age 

groups used for exposure scenario building and/or model “binning” of exposure factors that 

capture periods of potentially high exposure or unusual exposure patterns (e.g., the frequency 

and duration of mouthing hands and objects during early childhood). In some cases, expert 

judgment has been applied to capture vulnerable periods of development or critical windows 

when exposure to an environmental contaminant may be particularly damaging to a specific 

physiologic system (e.g., the effects of lead on hemoglobin due to age-related differences in iron 

deficiency). In many cases, the selection of age groups has been heavily influenced by the 

quality and quantity of existing data to support the development of exposure and potential dose 

estimates. 

4
The case-by-case consideration of vulnerable periods and/or the availability of exposure 

data has led to variations in the specific age groups considered by different Program Offices for 

assessing childhood exposure. By defining a set of recommended age groups for consideration in 

assessing exposure, the Agency will be better able in the future to develop exposure factors data 

organized around these defined age groups. It is recognized, however, that there may still be 

cases where exposure and/or toxicity data are not available for the age groups recommended in 

this guidance or where such data do not indicate use of the age groups defined here. In such 

cases, extrapolation of data, combining or splitting age groups, use of other age groups, or other 

strategies may be appropriate when assessing exposure and risk. In such cases, the uncertainties 

associated with the method employed should be documented in the assessment. A few examples 

of various ways in which Agency programs have used available data sets in the past to address 

children’s exposure are shown in Table 1. 

Table 1. Examples of Early-Life Age Groups Used in Past Agency Exposure 

Assessments 

EPA Programs Reference Child Age Groups 

Draft Standard Operating 

Procedure (SOPs) for Residential 

Exposure Assessment 

Dermal and Non-dietary Oral: 

Toddlers: 3 to 5 years 

Inhalation: (NAFTA*) 1 to 6 

years

Office of Prevention, Pesticides, 

and Toxic Substances, Office of 

Pesticide Programs

Dietary exposure assessment 

models 

Oral: Infants: 0 to 1 years 

Children: 1 to 2, 3 to 5; 

6 to 12; 13 to 19 years 

Females: 13 to 50 years 

Office of Solid Waste and 

Emergency Response 

Risk Assessment Guidance for 

Superfund (RAGS) Parts E, A

Dermal 

and Soil Ingestion: 0 to 6 years

Drinking Water Program: 

-Water Intake 0 < 1 year 

Office of Water

Water Quality Criteria Program: 

-Water Intake 

-Fish Consumption 

0 < 10 year 

15 to 44 years (women) 

0 to 14 years 

15 to 44 years (women) 

NATA* National Scale 

Assessment (1996 emissions 

year). 

0-4, 5-11, 12-17, 18-64 years Office of Air & Radiation, 

Office of Air Quality Planning 

and Standards NAAQS* 1996 Ozone Risk 

Assessment for Children 6-13, 14-18 years

Note: The examples of program-specific age groupings for risk assessment are selected for illustrative purposes and 

may vary with specific cases and media and route of exposure. Available data for specific exposure influence age 

group selection. 

*NAFTA = North American Free Trade Agreement. 

*NATA = National Air Toxics Assessment 

*NAAQS = National Ambient Air Quality Standards.
2. AGE GROUPS TO CONSIDER WHEN ASSESSING CHILDHOOD EXPOSURES 

TO ENVIRONMENTAL CONTAMINANTS

As noted in the introduction, in the early lifestages behavior changes over time in ways 

that can have an important impact on exposure and potential dose. Rather than assuming an 

adult level of exposure for 70 years for chronic/lifetime risk assessments, incorporation of timeweighted values for all age periods where exposure is likely to occur is expected to increase the 

accuracy of risk assessments because it will take into account lifestage differences in exposure. 

Depending on whether body weight-adjusted childhood exposures are either smaller or larger as 

compared with those for adults, predicted risks could either decrease or increase as compared 

with assuming a lifetime of adult-level exposure. If age-related differences in toxicity were also 

found to occur (see U.S. EPA, 2005b), both differences in toxicity and exposure would need to 

be integrated for each relevant age interval. For example, crawling and mouthing of hands and 

objects during the 1- to <2-year period can potentially lead to dermal and oral potential doses 

that are appreciably higher than those of adults in the same physical location, particularly 

indoors. Further, physiology changes over time in ways that can affect potential dose, internal 

dose, and susceptibility to certain health effects. The key issue is how to capture these changes 

in an assessment of risks from exposure to environmental contaminants. 

In July 2000, EPA held a workshop to examine developmental factors and how they 

influence the assessment of childhood exposure. Workshop participants included experts in the 

fields of pediatric medicine, toxicology, risk assessment, and public health. A summary of the 

workshop discussions is provided in U.S. EPA (2000). The discussions revealed that workshop 

participants preferred assessment approaches that could incorporate childhood development as a 

continuous function. However, although recognizing the paucity of existing data, the 

participants concluded that age groupings (or bins) can be useful as guides for the development 

of environmental exposure scenarios. To that end, they offered some preliminary advice on 

possible age groups related to developmental change. Due to limits in currently available data on 

age-specific exposure factors for early lifestages, criteria used to select these age bins were often 

qualitative in nature. Narrow age groups were identified where rapid developmental changes 

occur, whereas more broad age groups were identified as the rate of development decreased. 

Prenatal development was outside the scope of the workshop discussions, but participants 

unanimously stressed the importance of including this lifestage in future exposure and risk 

assessment guidance. 

6
 Accurately simulating chemical exposures of an individual continuously over a lifetime

would require detailed information regarding how a person’s behavior and physiology varies 

each day as one ages. One way exposure assessors can simplify exposure assessments is to 

classify individuals into age bins within which behavioral and/or physiological characteristics are 

likely to remain relatively stable. This allows for the execution of an exposure assessment model 

with sufficient resolution (i.e., number of age bins) to address all significant variations in 

lifestage exposure. This level of resolution may vary with the particular compound of interest 

and/or with the particular exposure scenario. The goal of this guidance is to recommend a 

starting point based on our current understanding of differences in lifestage behavior and 

physiology that may impact exposures. As our knowledge base and database develop, exposure 

assessors will be able to make more informed choices about the resolution needed to make the 

best public health decisions. In addition, because there is a need to balance the added value of 

increased resolution against the cost of generating the necessary exposure factor data, the age 

bins recommended here are designed to focus future research and data collection so that one can 

move toward a goal of conducting exposure assessments that address all significant variations in 

lifestage. 

To organize the workshop discussion, participants were divided into two subgroups 

according to their specific areas of expertise. One subgroup discussed behavioral development 

and the other focused on physiology and anatomical growth. Participants were asked to focus 

their discussion on those aspects of development that are particularly relevant to exposure and 

potential dose. These terms are defined in the EPA’s Guidelines for Exposure Assessment (U.S. 

EPA, 1992) as 

Exposure - Contact of a chemical, physical, or biological agent with the outer 

boundary of an organism. Exposure is quantified as the concentration of the agent 

in the medium [e.g., soil, water, air, food, etc.] in contact [with the organism], 

integrated over the time duration of that contact. 

Potential Dose - The amount of chemical ingested, inhaled, or in material applied 

to the skin. 

Internal Dose - The amount of chemical contained that has been absorbed and is 

available for interaction with biologically significant receptors. 

7
Some workshop participants found that the concepts of potential dose, internal dose, and 

effects are too interrelated to narrow the focus of the discussion to potential dose alone. The 

relationship between the 1992 guidelines’ definition of exposure and the related risk assessment 

concepts of dose and effects is portrayed in Figure 1. Figure 1 also lists some examples of 

characteristics that impact or otherwise provide an indication of exposure, dose, and possible 

susceptibility to effects. These example characteristics were discussed during the workshop. 

Absorbed /

Internal

Dose

Biological

Effect /

Disease

Exposure

Biologically

Effective

Dose

* Time spent: Sleeping versus active; 

indoors versus outdoors

* Breathing zone 

* Level of activity 

* Mouthing behavior 

* Breast versus bottle feeding 

* Food consumption 

* High skin permeability 

* Stomach pH 

* Proportion of body fat 

* Level of extracellular fluid 

* Body weight 

* Hepatic enzyme function 

* Renal function 

* Immune system function 

* Skeletal growth 

* Reproductive development 

* Endocrine system changes 

Chemical in air, soil,

water, food, or other 

media in contact with

the outer boundary of

the organism over time

Absorption

Barrier

Distribution

Metabolism

Excretion

Altered Structure

Altered Function

Figure 1. Relationship Between Exposure, Dose, and Effects in Risk 

Assessment. 

The workshop subgroup addressing behavioral development recommended dividing the 

first year of life into three groups: 0 to <3 months, 3 to <6 months, and 6 to <12 months. After 

the first year of life, it recommended the following groups: 12 to <24 months, 2 to <6 years, 6 to 

8
<11 years, 11 to <16 years, and 16 to <21 years. The participants in this subgroup arrived at 

these groupings by considering key factors or “major domains of behavioral development” for 

each route of exposure (U.S. EPA, 2000). For oral and dermal exposures, these factors included 

gross motor development, fine motor development, cognitive development, and social 

development. For inhalation exposures, the relevant factors included gross motor development, 

activity level, and breathing behavior (e.g., the transition from mouth to nasal breathing). Table 

2 contains some examples of the specific considerations supporting the age groups derived by the 

behavior subgroup. 

Table 2. Examples of Factors Considered in Deriving Age Groups Reflecting 

Behavioral Development 

Age Group

Characteristics Relevant to Oral and 

Dermal Exposure

Characteristics Relevant to 

Inhalation exposure

Birth to <3 months Breast and bottle feeding. Hand-tomouth activities. Time spent sleeping/sedentary. 

3 to <6 months Solid food may be introduced. Contact 

with surfaces increases. Object/hand-tomouth activities increase. 

Breathing zone close to the floor. 

6 to <12 months Food consumption expands. Children’s 

floor mobility increases (surface contact). 

Children are increasingly likely to mouth 

nonfood items. 

Development of personal dust 

clouds. 

12 to <24 months Children consume full range of foods. 

They participate in increased play

activities, are extremely curious, and 

exercise poor judgment. Breast and 

bottle feeding cease. 

Children walk upright, run, and 

climb. They occupy a wider variety

of breathing zones and engage in 

more vigorous activities. 

2 to <6 years Children begin wearing adult-style 

clothing. Hand-to-mouth activities begin 

to moderate. 

Occupancy of outdoor spaces 

increases. 

6 to <11 years There is decreased oral contact with 

hands and objects as well as decreased 

dermal contact with surfaces. 

Children spend time in school 

environments and begin playing 

sports. 

11 to <16 years Smoking may begin. There is an 

increased rate of food consumption. 

Increased independence (more time 

out of home). Workplace exposure 

can begin. 

16 to <21 years High rate of food consumption begins. Independent driving begins. 

Expanded work opportunities. 

9
The subgroup addressing anatomy/physiological development recommended the 

following groupings: birth to <1 month, 1 to <3 months, 3 to <6 months, 6 to <12 months, 1 to 

<3 years, 3 to <8 (female) or <9 (male) years, and 8 or 9 years to <16 (female) or <18 (male) 

years. The discussion that led to these age groups focused on anatomical characteristics (e.g., 

weight and proportion of body fat) and specific organ and physiological systems. These systems 

included skin, skeleton, liver, immune system, reproductive system, endocrine system, lung and 

respiratory tract, gastrointestinal tract, circulatory system, renal system, cardiac system, central 

nervous system, muscle, and sensory organs. Table 3 contains some examples of the specific 

considerations supporting the age groups derived by the anatomy/physiology subgroup. The age 

groups listed in Table 3 were derived largely from considering the rate of change in the listed 

characteristics. 

Table 3. Examples of Factors Considered in Deriving Age Groups Reflecting 

Anatomical/Physiological Development 

Age Group Anatomy/Physiology Characteristics

Birth to <1 month Rapid growth and weight gain. Proportion of body fat increases. Increased skin

permeability. Deficiencies in hepatic enzyme activity. Immature immune system

functions. High oxygen requirements (leading to higher inhalation rates). Stomach

more alkaline. Increases in extracellular fluid. Renal function less than predicted by

surface area. 

1 to <3 months Rapid growth and weight gain. Proportion of body fat increases. Deficiencies in

hepatic enzyme activity. Immature immune system functions. High oxygen 

requirements (leading to higher inhalation rates). Stomach more alkaline. Increases

in extracellular fluid. Renal function less than predicted by surface area. 

3 to <6 months Rapid growth and weight gain. Proportion of body fat increases. Deficiencies in

hepatic enzyme activity. Immature immune system functions. Increases in

extracellular fluid. Renal function less than predicted by surface area. 

6 to <12 months Rapid growth and weight gain. Body fat increase begins to level off. Deficiencies in

hepatic enzyme activity. Immature immune system functions. Rapid decrease in 

extracellular fluid. Can begin predicting renal function by surface area. 

1 to <3 years Some hepatic enzyme activities peaks, then falls back to adult range. Most immune

system functions have matured. Extracellular fluid becomes more consistently related

to body size. 

3 to <8/9 years Period of relatively stable weight gain and skeletal growth (as opposed to a period

marked by growth spurts). 

8/9 to <16/18 years Rapid skeletal growth. Epiphyseal closure (may take until age 20). Rapid 

reproductive and endocrine system changes, inclusive of puberty. 

Note: Many of the characteristics listed in this table are repeated across age groups (especially for ages up to <12 

months; e.g., rapid growth and weight gain). In determining the range of ages to include in a particular age group,

the rate of change in these characteristics was often a key factor discussed at the workshop.

 

10
Early in the discussion of the anatomy/physiology subgroup, the participants concluded 

that developmental issues affecting exposure, potential dose, internal dose, and effects were too 

intertwined to allow an exclusive focus on potential dose. Therefore, its preliminary advice on 

possible age groups reflects some consideration of changes that impact internal dose and effects. 

For example, this subgroup discussed the maturity of hepatic enzyme activities (an indication of 

metabolic function affecting internal dose) and the rate of reproductive development (an 

indication of a susceptible period for effects) in developing its advice on age groups. Additional 

examples are noted in Table 3. Although this subgroup’s recommendations do reflect some

consideration of dose and effects issues, it should not be considered a comprehensive treatment 

of this subject. The Agency is considering childhood development and its relationship to dose 

and effects through other efforts. 

The recommended age groups were proposed as a synthesis of the workshop 

recommendations from both the behavioral and anatomical/physiological factors subgroups. As 

a result of continuing deliberations and reviews of available exposure factors data, the RAF work 

group concluded that it may be necessary to further divide the 1 to <3 years age group. The data 

available suggested a division of 1 to <2 years and 2 to <3 years as separate groups. This 

grouping is supported (in part) by the behavioral subgroup discussions from workshop. In 

addition, it is supported by existing exposure factors information (e.g., the data for mouthing 

duration and frequency). The division of 3 to <6 years was deemed significant on the basis of 

behavioral changes occurring at or around 6 years that affect nondietary (i.e., hand to mouth) 

intake and exposures due to changes in activity (e.g., initiation of school). The 6 to <11 years 

group captures the relatively stable growth period after early childhood and preceding 

adolescence (the latter inducing significant behavioral, anatomical, and physiological changes). 

The work group further concluded that, in some cases, an additional age group spanning 18 to 

<21 years could be considered. It is unclear whether this age group should be considered part of 

the childhood lifestage or part of early adulthood. It is clear that it encompasses a period of 

continuing development and may capture important events such as a change in residence and 

epiphyseal closure. 

Clearly factors other than age/developmental stage can have an impact on exposure, 

including sex, geographical location, family size, ethnic/cultural differences, seasonal variations, 

and socioeconomic status. Although these factors could be evaluated by exposure assessors, this 

11
document defers to existing Agency guidance (e.g., U.S. EPA, 1992) and tools (e.g., U.S. EPA, 

2002) for their consideration. 

As discussed in EPA’s A Framework for Cumulative Risk Assessment (U.S. EPA, 2003a), 

vulnerability to health effects resulting from exposures to environmental pollutants can vary on 

the basis of susceptibility, differential exposure, differential preparedness, and differential ability 

to recover. In conducting the hazard assessment portion of a risk assessment, the assessor should 

consider windows of vulnerability based on susceptibility to toxic effects resulting from specific 

exposures (dose-response). In developing the exposure assessment, the assessor should consider 

windows of vulnerability based on behaviors (crawling, mouthing), activities (locations, product 

use, diet), physiological characteristics (oxygen requirements, caloric requirements), and so on 

that may lead to particularly high levels of exposure. The analyses are combined to identify the 

lifestages that are at greatest risk on the basis of exposures and resulting effects. 

It is also important to note that exposure factors and resulting developmental stages may 

be a function of additional individual and population characteristics. These factors may be 

characteristics of the communities in which children live and are raised and include, as noted 

above, socioeconomic status, ethnicity, cultural setting, and geographical considerations. Factors 

may also be characteristics of the individual, including genetic susceptibility, nutritional status, 

and health status. Vulnerabilities associated with individual and community characteristics will 

manifest as differences in susceptibility, differential exposure, differential preparedness, and 

differential ability to recover. The focus of this guidance is specific to addressing vulnerability 

associated with differential exposure due to life stage. Just as it is impossible to completely 

separate considerations of exposure and potential dose from consideration of internal dosimetry 

and response, so it is impossible to completely separate consideration of vulnerability due to 

lifestage from consideration of vulnerability due to the many other significant individual and 

community characteristics. 

The Agency is addressing the full range of issues associated with characterizing risks to 

children through a variety of initiatives, including development of a framework for children’s 

risk assessment and development of guidance for conducting cumulative risk assessment (U.S. 

EPA, 2003a). As the Agency works to address cumulative risk assessment, the full range of 

vulnerabilities will be considered more consistently in both exposure assessment and hazard 

assessment, but these are not specifically addressed in this guidance. In like manner, the Agency 

12
may be able to address fetal exposure and developmental effects at a future date and include that

lifestage in exposure assessment guidance. 

The focus of this guidance is to recommend age bins that address vulnerability resulting 

from differential exposure. Because the focus here is on exposure or potential dose, 

pharmacokinetic considerations (i.e., absorption, distribution, metabolism, and elimination) were 

not explicitly considered unless they had direct impacts on potential dose (e.g., absorption at the 

portal of entry). However, it is impossible to completely separate consideration of exposure and 

potential dose from consideration of internal dosimetry and response. This difficulty was 

discussed during the workshop and is reflected in the resulting recommended age bins and in this 

document. 

On the basis of the 2000 workshop discussions as well as subsequent deliberations and 

reviews of available exposure factors data, the RAF work group developed the recommendations 

contained in Table 4. These age groups should be considered initially when assessing childhood 

exposures to environmental contaminants. 

Table 4. Recommended Set of Childhood Age Groups for Agency Exposure 

Assessments 

Age Groups <1 Year Age Groups $1 Year

Birth to <1 month 1 to <2 years 

 1 to <3 months 2 to <3 years 

 3 to <6 months 3 to <6 years 

 6 to <12 months 6 to <11 years 

11 to <16 years 

16 to <21 years 

 

The age groups covering the first year of life are broken out because behavioral and 

physiological changes are occurring so rapidly during this period. During this time frame, 

exposure may occur first through consumption of human (breast) milk or baby formula and, 

later, baby foods. Movement is very limited at birth, but crawling occurs during this period and 

first steps may also take place. Hand/object-to-mouth activities begin and then increase rapidly 

with increasing age. Major developmental changes in metabolic pathways occur during the first 

several months surrounding birth. Premature delivery can have a major physiological and 

metabolic impact. Exposure to environmental chemicals during the first months is generally 

limited. 

13
There may be instances for specific exposure scenarios and compounds where combining 

some of these age groups (e.g., combining the first three <1 year age groups into one 

representing birth to <6 months) is indicated; i.e., variation in exposure factors and resulting 

exposures is insignificant. In addition, there may be instances where it is not necessary to 

address every age group listed above because, for example, the focus of the exposure and risk 

assessment may be on a health effect for which only one or two of the above groups represents a 

critical window. Where there is a lack of exposure data for a particular age group of potential 

importance, the risk assessor should consider how this age group might differ and the possible 

implications for not explicitly including the age group. It is recommended that if age groups are 

split, combined, or excluded, the underlying rationale should be provided in the exposure 

assessment, along with an analysis of the uncertainty associated with these assumptions. 

Given sufficient data, a scientifically based approach for selecting age groups other than 

the ones recommended in this guidance would be to determine for which age groups there exist 

significant statistical differences in parameter values. An example of one such analysis is 

presented in Tulve et al. (2002). In this analysis, the authors use a tree analysis to identify 

significant age differences in mouthing behavior. The model uses a recursive partitioning 

algorithm that successively splits the data into homogeneous subgroups. Using this approach, 

the authors identified two main age groups for the data that were evaluated: less than or equal to 

24 months, and greater than 24 months. 

It is acknowledged here that a lack of data may be a critical impediment in conducting 

assessments for each of these age bins and for making decisions regarding combining or 

eliminating age groups. In these cases, an analysis of the available data should be conducted 

first, and consideration given to the distribution of the data points among the recommended age 

groups. The age groups can be used unless the quantitative analysis of the data shows they do 

not fit within one age group. Alternatively, qualitative information may lead the assessor to 

identify potentially significant differences within a recommended age bin. A possible approach 

for estimating exposure factors and potential dose when data are not available for a particular age 

bin includes the use of age-dependent curve fitting to help fill in the data gaps (see Phillips, 

1993). Any assumptions used in assessing exposure for a particular age bin can be discussed in 

the assessment. 

As noted above, it is recommended that if age groups are split, combined, or excluded, 

the underlying scientific rationale be provided in the exposure assessment. It is important for 

14
exposure assessors to engage in an iterative dialogue with toxicologists and other health 

scientists to determine the age groups (or portions of age groups) that will be the focus of any 

particular assessment. Further, it is recommended that an assessment includes splitting, 

combining, and/or eliminating age groups, the exposure assessor consider the following: 

• The basis (exposure and/or toxicological or risk) for determining which age groups 

should be split, combined, and/or dropped from the analysis and why. If the basis is 

exposure/dose considerations, what are the key factors driving the decision 

(behavioral and/or physiological)? If the basis is toxicological, is there a key window 

of susceptibility considered? If the basis is minimal risk, describe how the exposure 

and toxicity considerations together lead to this conclusion. 

• The criteria used to select particular age groups for assessment. These criteria may 

be quantitative or qualitative, depending on the quantity and quality of available data. 

As described more fully in the next section on implementation, it is of paramount 

importance to characterize the data, how best to combine or extrapolate, and how 

such manipulation may change the distribution (i.e., under- or overestimate or mask 

outliers). An example of a quantitative criterion is when data are statistically 

combined across the individual ages within the proposed age category, variability 

could be expressed as a coefficient of variation that is no greater than XX% for the 

key behavioral, physiological, or anatomical parameters that govern exposure or 

potential dose (see, e.g., Tulve et al., 2002). An example of a qualitative criterion is 

when the age range will not contain stages of development that are clearly distinct 

from one another in terms of behavior, food consumption patterns, or maturation of 

physiological systems. 

• The scientific uncertainties and potential biases introduced when combining or 

excluding age groups. There is no simple answer for the question “How different do 

two age ranges need to be before they are considered as independent age groups for 

exposure assessment?” A difference may or may not be extremely important, given 

the resulting risk estimate. This aspect could be described in either qualitative (e.g., 

over- versus underestimate of exposure) or quantitative terms. Examples of questions 

could include: Is an age group described as less than 1 year more representative of 6 

to <12 months of age than younger age groups? How different are exposures for age 

groups that might be combined? If data for one age group are used as a surrogate for 

another, is this likely to increase/decrease estimates of exposure? To what extent do 

distributions within one age group overlap with that of another? 

• The types of data and information that, if available, would allow an analysis of 

whether it would be scientifically justified to combine or separate any of the 

recommended age groups in future exposure assessments. Such data could include 

biomonitoring data (e.g., National Health and Nutrition Examination Survey), 

environmental monitoring data, and/or exposure factors data (such as those available 

in U.S. EPA, 2002). These discussions will help guide future data collection efforts 

to improve future exposure and risk assessments. 

15
3. APPLYING THE RECOMMENDED SET OF CHILDHOOD AGE GROUPS TO 

EXPOSURE ASSESSMENT 

This guidance provides a recommended set of early-life age groups for consideration in 

Agency exposure and risk assessments and when conducting exposure-monitoring studies. The 

purpose in providing this guidance is to foster greater consistency based on a sound scientific 

footing for program-specific assessments and research initiatives for children. To further aid the 

assessor, some additional issues associated with applying this guidance are discussed in this 

section (i.e., issues associated with application of age groupings to estimate exposure and specify 

exposure scenarios). In addition, case studies are planned that will illustrate how the guidance 

document can be applied in practice. These case studies will be posted on the Risk Assessment 

Forum Web page (http://epa.gov/ncea/raf). 

When defining the assessment plan or model, the exposure assessor, in consultation with the 

toxicologist, should consider how the pathways and route of exposure, critical toxicological 

windows of susceptibility, and possible health outcomes fit into a risk assessment model. The 

scope of analysis will depend in part on whether all lifestages need to be examined or whether 

exposure concerns are found to be limited to certain critical periods. 

3.1. CONDUCTING SCREENING-LEVEL EXPOSURE ASSESSMENTS 

According to EPA’s Guidelines for Exposure Assessment (U.S. EPA,1992), the purpose 

of a screening-level assessment is typically to identify pathways of greatest concern and to 

provide a high-end and/or “bounding level” exposure estimate to determine whether there are 

potential risks of concern that might require a more refined analysis. To generate such estimates, 

the guidelines suggest setting one or more sensitive variables at the bounding level. For 

example, a screening assessment might be based on specific childhood lifestages where elevated 

exposures and/or greater susceptibility to the stressor of interest are anticipated. 

In practice, Agency programs often conduct screening-level assessments that use default 

assumptions that are selected to overestimate risks. If the screening-level exposures to either a 

particular toxic agent or combination of agents are sufficiently below regulatory exposure levels 

for toxicity, a full risk assessment is generally not warranted. Such screening assessments can 

allow more timely decisions and save resources for other actions. In many such assessments, a 

single estimate that usually assumes a combination of activity patterns and/or lifestages that are 

16
likely to produce among the highest exposure levels is used. As long as the exposure estimates 

are designed to estimate higher-than-expected exposures and are well below regulatory levels, no 

specific bin for a lifestage (including children) need be considered in such an assessment. 

3.2. INTEGRATING EXPOSURE ACROSS MULTIPLE AGE GROUPS 

A key component of this guidance is to promote the integration of age-specific 

differences in exposure (and where applicable, toxicity) when assessing long-term exposure. 

When assessing chronic risks, an assessor should sum the exposures for all age periods when 

exposure is likely to occur. This approach is expected to increase the accuracy of risk 

assessments because it will take into account lifestage differences in exposure. Adjustments for 

variations in toxicity (potency) may also need to be made for different age groups, if such data 

are available for the contaminant of concern. Other guidance, specific for pharmacodynamic and 

pharmacokinetic differences in the ages during which the exposure occurs, should be consulted. 

Depending on whether body weight-adjusted childhood exposures are either smaller or larger as 

compared with those for adults, predicted risks could either decrease or increase as compared 

with a risk assessment assuming a lifetime of adult-level exposure. 

If age-related differences in toxicity were also found to occur, differences in both toxicity 

and exposure would need to be integrated for each relevant age interval. The complexity of this 

integration will depend to a large degree on the overlap of exposure-specific and toxicity-specific 

age groups. For example, assume that potency (toxicity) was found to vary among the following 

age groups: 0 <2 years, 2 <16 years, and 16 years and older. Table 5 illustrates how to consider 

both exposure- and toxicity-relevant age groups. The exposure age groups are listed in the first 

column, and the toxicity age groups are indicated by the three shaded bands. When assessing 

chronic risk, time-weighted risk (a function of exposure and toxicity divided by the exposure 

duration) for each resulting age group would be calculated and then combined over the relevant 

time frame. Note that this example represents a relatively simple case where the toxicity-based 

age groups overlap cleanly with the exposure-based age groups. 

17
Table 5. Integrating This Age Grouping Guidance with the Supplemental 

Guidance for Assessing Susceptibility from Early-Life Exposure to 

Carcinogens That Act via a Mutagenic Mode of Action 

Exposure Age Groupings Exposure Duration (yr) Potency Adjustment

Birth to <1 month 0.083 10×

1 to <3 months 0.167 10×

3 to <6 months 0.25 10×

6 to <12 months 0.5 10×

1 to <2 years 1 10×

2 to <3 years 1 3×

3 to <6 years 3 3×

6 to <11 years 5 3×

11 to <16 years 5 3×

16 to <21 years 5 1×

>21 years (21 <70) 49 1×

If exposure occurs only for a limited number of years (e.g., consider a family that lives 

near a source of exposure for a 5-year period of time before moving away), it is critical to 

combine lifestage differences in exposure and dose-response for the relevant time interval. 

Example calculations are provided in U.S. EPA (2005b). 

3.3. ADDITIONAL CONSIDERATIONS WHEN USING HUMAN EXPOSURE 

MODELS AND ALGORITHMS IN RISK ASSESSMENTS 

A variety of modeling tools have been developed over the years to facilitate exposure and 

dose assessment as part of risk assessments. Some assessors use route-specific equations to 

compute average daily dose (ADD) or lifetime average daily dose (LADD), such as those in 

EPA’s Exposure Factors Handbook (U.S. EPA, 1997a), with either deterministic or probabilistic 

inputs. Others use probabilistic time-series-based exposure models, such as the aggregate and 

cumulative models developed in recent years to address the FQPA (e.g., Calendex, CARES, 

Lifeline, SHEDS). These models simulate individuals on the basis of human activity 

information in databases such as those of the U.S. Census, the U.S. Department of Agriculture’s 

Continuing Survey of Food Intake by Individuals (CSFII), EPA’s Consolidated Human Activity 

Database (CHAD), or the National Human Activity Pattern Survey (NHAPS). 

18
There are a few probabilistic models for characterizing aggregate exposure and 

cumulative risk, and several are under development. As these models continue to evolve, they 

could be adapted to incorporate the new age groupings into modules for sampling individuals for 

a simulated population and for sampling values of exposure factors to be inserted into exposureroute-specific equations. Evaluation of these age group-specific model estimates with 

biomonitoring data would also be helpful. In the meantime, it is critical that the exposure 

assessor understand the assumptions, structure, and function of the specific model version being 

used to conduct an assessment. Such an understanding will allow the model outputs to be 

interpreted in light of the recommended age groups described in this document and will allow for 

a more complete characterization of uncertainties associated with the model parameters used, as 

well as with model structure. 

With respect to applying the recommended age groupings to exposure factors used by 

human exposure models, it is important to understand how data are binned for each model input. 

Model documentation should clearly present how specific data are binned and what criteria were 

used to develop these bins. The goal of this guidance is to provide an initial set of age groups for 

conducting exposure assessments and associated modeling based on our current understanding of 

differences in lifestage behavior and physiology that may affect exposures. However, as 

discussed above, this guidance recognizes that the level of model resolution (i.e., number of age 

bins) needed may vary with the particular compound of interest and/or with the particular 

exposure scenario. Therefore, there may be instances where combining some of these age 

groups may be considered when estimating exposure or potential dose, especially if little 

variation in exposure might be expected. Alternative bins may also be required for a specific 

model application or population of interest. If so, the scientific basis for the alternative age bins 

should be explicitly presented. In such cases, it is expected that binning may be different from

one exposure factor to the next (i.e., criteria for binning the dietary data will be different from

criteria for other, nondietary activity profiles). 

Data-specific bins used in the models should follow the following principles: (1) bins 

should express representative and relevant metrics for the range of individuals grouped with each 

bin, and (2) the selected bins should not mask any truly unique profile within the bin (i.e., do not 

hide a significant peak). If this data-binning process is done well for each database, then the 

values sampled from each database should be representative for each age group. The criteria 

19
chosen for such binning should be clearly articulated by the model developers, and the criteria 

rejected should be discussed also. Selection of criteria should be transparent and relevant. 

In addition, data limitations and the associated uncertainties need to be discussed. For 

example, were the data adequate to sufficiently investigate and identify significant differences 

across age groups? Available data sets may not allow the modelers or the risk assessors to 

extract the data directly from the underlying sources to conduct the desired age group-specific 

analysis. Potential approaches for addressing this issue include (1) reorganizing the input dataset 

to conform with the age groupings needed, (2) using probabilistic sampling techniques to go 

beyond the categorical limits of the underlying database to use all the data and then format the 

probabilistic model output into the desired age groupings to represent exposure doses, or 

(3) developing a weighting scheme for the underlying data set to make it more aligned with the 

desired age groupings. For example if 10% of the observations for the 6- to 11-year-old group 

come from 6- and 7-year-olds and 90% come from 10- to 11-year-olds, the data need to be 

statistically weighted so that equal weight is given to all ages within the group when estimating 

the group mean and variability statistics. 

It is expected that, as this guidance is applied to conduct exposure assessments using the 

exposure modeling tools that are currently available or under development, the recommended 

age groups will guide analyses of existing exposure factors data as well as the development of 

new exposure factors research and data collection efforts. 

Another important issue associated with using the age groups recommended in this 

guidance involves distinguishing between uncertainty and interindividual variability in an 

exposure assessment. Uncertainty in the exposure estimates may be based on a lack of data for 

any of the significant exposure factors for a particular age group or with assumptions made in 

development of the model structure. With early lifestages, the issue of intersubject variability 

can be important due to rapid physiological and behavioral changes, such that, even within a 

relatively narrow age group, variability may be particularly large. This variability affects our 

understanding of the upper percentiles of exposure and risk and thus can be critical to earlylifestage risk assessment. Even given a high-quality, high-quantity set of data for each age 

group, there may still be significant variability for a particular exposure factor, set of factors, or

exposure pathway. The better the data and our ability to characterize this variability, the better 

the basis for final selection of age groups for a specific assessment. Data characterization should 

20
be improved by EPA’s effort to update its Exposure Factors Handbooks (U.S. EPA, 1997a) to 

present available data for each of the recommended age groupings. 

For most exposure models, exposure estimates can be presented in a variety of ways. 

Profiles of daily exposure as well as multiple-day averages, seasonal averages, and yearly 

averages may be developed (see Figure 2). There are models and algorithms that can be used to 

calculate average exposure across a season or the highest exposure and the full distribution of 

exposures within a season for an age group. It is important to consider which exposure estimate 

(median or higher percentile or a probabilistic analysis) should be evaluated in an assessment, 

and the best choice may be age dependent. Any approach to time-averaging exposure should be 

informed by a consideration of dose kinetics (e.g., absorption, distribution, metabolism, and 

excretion) and effects (e.g., critical windows for effects, time to effect). Therefore, exposure 

assessors and toxicologists should work closely to determine the most appropriate approach. 

Figure 2. Comparison of Single-Day Exposure Estimates with Various TimeAveraged Exposures. 

21
REFERENCES 

ILSI (International Life Sciences Institute). (2003) Exposure factors database and associated user guide. Health and 

Environmental Sciences Institute. Available from: http://hesi.ilsi.org/Committees/TechnicalCommittee/RAM/; 

http://oaspub.epa.gov/eims/xmlreport.display?deid=63081&z_chk=65102. 

NAS (National Academy of Sciences). (1993) Pesticides in the diets of infants and children. Washington, DC:

National Academy Press. 

Phillips, LJ; Fares, RJ; Schweer, LG. (1993) Distributions of total skin surface area to body weight ratios for use in 

dermal exposure assessments. J Expo Anal Environ Epidemiol 3:331–338. 

Tulve, NS; Suggs, J; McCurdy, T; et al. (2002). Frequency of mouthing behavior in young children. J Expo Anal

Environ Epidemiol 12:259–264. 

USDA (Department of Agriculture). (2003) Pesticide Data Program. Washington, DC. Available from:

http://www.ams.usda.gov/science/pdp/. 

U.S. EPA (Environmental Protection Agency). (1992) Guidelines for exposure assessment. National Center for

Environmental Assessment, Washington, DC. 

U.S. EPA (Environmental Protection Agency). (1997a) Exposure factors handbook. National Center for 

Environmental Assessment, Washington, DC. EPA/600/P-95/002Fa. 

U.S. EPA (Environmental Protection Agency). (1997b) Guiding principles for Monte Carlo analysis. Risk 

Assessment Forum, Washington, DC. Available from: 

http://cfint.rtpnc.epa.gov/ncea/raf/recordisplay.cfm?deid=29596. 

U.S. EPA (Environmental Protection Agency). (1997c) Standard operating procedures (SOPs) for residential

exposure assessments [draft]. Prepared by the Office of Pesticide Programs, Washington, DC, and Versar, Inc., 

Springfield, VA, for the Office of Prevention, Pesticides and Toxic Substances under contract no. 68-W6-0030. 

U.S. EPA (Environmental Protection Agency). (1997d) Policy for use of probabilistic analysis in risk assessment at 

the U.S. Environmental Protection Agency. Washington, DC; EPA/630R-97/001. Available from:

http://epa.gov/osa/spc/htm/probpol.htm.

U.S. EPA. (Environmental Protection Agency). (2000) Summary report of the technical workshop on issues 

associated with considering developmental changes in behavior and anatomy when assessing exposure to children. 

Washington, DC. Available from: http://cfpub.epa.gov/ncea/raf/recordisplay.cfm?deid=20680. 

U.S. EPA (Environmental Protection Agency). (2002) Child-specific exposure factors handbook (interim report). 

Washington, DC; EPA-600-P-00-002B, 2002. Available from: 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=237196. 

U.S. EPA (Environmental Protection Agency). (2003a) Framework for children’s risk assessment. Washington, DC.

Available from: http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=22521.

U.S. EPA (Environmental Protection Agency). (2003b) A framework for cumulative risk assessment. Washington, 

DC. Available from: http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=54944. 

U.S. EPA (Environmental Protection Agency). (2005a) Guidelines for carcinogen risk assessment. Washington, DC; 

EPA/630/P-03/001b NCEA-F-0644b. Available from: http://www.epa.gov/cancerguidelines. 

U.S. EPA (Environmental Protection Agency). (2005b) Supplemental guidance for assessing susceptibility from

early-life exposure to carcinogens. Washington, DC. Available from: 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=116283. 

22
OTHER RECOMMENDED REFERENCES

Altshuler, K; Berg, M; Frazier, L; et al. (2003) Children’s environmental exposure. Available from: 

http://aquaticpath.umd.edu/appliedtox/paper3.pdf. 

Anderson, LM; Jones, AB; Miller, MS; et al. (1989) Metabolism of transplacental carcinogens. In: Napalkov, NP; 

Rice, JM; Tomatis, L; et al.; eds. Perinatal and multigeneration carcinogenesis. Lyon, France: International Agency 

for Research on Cancer. 

Anderson, LM; Diwan, BA; Fear, NT; et al. (2000) Critical windows of exposure for children’s health: cancer in 

human epidemiological studies and neoplasms in experimental animal models. Environ Health Perspect 108(Suppl

3):573–594. 

Benowitz, NL. (1996) Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 

18(2):188–204. 

CDC (Centers for Disease Control and Prevention). Available online at http://www.cdc.gov/nchs/nhanes.htm.

Clayton, CA; Pellizzari, ED; Whitmore, RW; et al. (2003) Distributions, associations, and partial aggregate 

exposure of pesticides and polynuclear aromatic hydrocarbons in the Minnesota Children's Pesticide Exposure Study

(MNCPES). J Expo Anal Environ Epidemiol 13(2):100–111. 

Cook, WO; Carson TL. (1985) Fonofos toxicosis and milk residues in dairy cattle. Vet Hum Toxicol 28(4):281–

282. 

Cresteil, T. (1998) Onset of xenobiotic metabolism in children: toxicological implications. Food Addit Contam 15

(Supplement):45–51. 

Daston, G; Faustman, E; Ginsberg, G; et al. (2004) A framework for assessing risks to children from exposure to 

environmental agents. Available from: http://ehp.niehs.nih.gov/members/2003/6182/6182.html. 

Day, NE; Brown, CC. (1980) Multistage models and primary prevention of cancer. J Natl Cancer Inst 64:977–989. 

Jaakkola, MS; Jaakkola, JJ. (1997) Assessment of exposure to environmental tobacco smoke. Eur Respir J 

10(10):2384–2397. 

Jauniaux, E; Gulbis, B; Acharya, G; et al. (1999) Maternal tobacco exposure and cotinine levels in fetal fluids in the 

first half of pregnancy. Obstet Gynecol 93(1):25–29. 

Kavlock, R; Boekelhelde, K; Chapin, R; et al. (2002) Issue on risks of phthalates to human reproduction. Reprod

Toxicol 16(5):451–734. 

Lambers, DS; Clark, KE. (1996) The maternal and fetal physiologic effects of nicotine. Semin Perinatol 20(2):115–

126. 

Lederman, SA. (1996) Environmental contaminants in breast milk from the central Asian republics. Reprod Toxicol

10(2):93–104. 

NRC (National Research Council). (1994) Science and judgment in risk assessment. Washington, DC: National 

Academy Press. 

Olin, SS; Sonawane, BR. (2003) Final report: workshop to develop a framework for assessing risks to children from

exposure to environmental agents. International Life Sciences Institute, Risk Science Institute. Washington, DC. 

Available from: http://ehp.niehs.nih.gov/members/2003/6183.html. 

23
Saillenfait, AM; Payan, JP; Fabry, JJP; et al. (1998) Assessment of the developmental toxicity, metabolism and

placental transfer of di-n-butyl phthalate administered to pregnant rats. Toxicol Sci 45:212–24. 

Spradbery, JP; Tozer RS. (1996) The efficacy of diazinon impregnated ear tags against buffalo fly and resulting 

weight gains and diazinon residues in meat and milk. Aust Vet J 73:6–10.

U.S. EPA (Environmental Protection Agency). (1991) Protection of human subjects. 40 Code of Federal

Regulations, Chapter I, Part 26. Available from: http://www.access.gpo.gov/nara/cfr/waisidx_00/40cfr26_00.html. 

U.S. EPA (Environmental Protection Agency). (2001) Age group recommendations for assessing childhood

exposure and the adequacy of existing exposure factors data for children. Washington, DC. Available from: 

http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_id=237196. 

U.S. EPA (Environmental Protection Agency). (2002) EPA’s guidelines for ensuring and maximizing the quality, 

objectivity, utility, and integrity of information disseminated by the Environmental Protection Agency. Washington, 

DC; EPA/260R-02-008. Available from: http://www.epa.gov/oei/qualityguidelines. 

U.S. EPA. (Environmental Protection Agency). (2003) EPA handbook for use of data from the National Health and 

Nutrition Examination Surveys (NHANES): a gold mine of data for environmental health analyses. Washington, 

DC. Available from: http://cfpub.epa.gov/si/osp_sciencedisplay.cfm?dirEntryID=56237. 

U.S. EPA (Environmental Protection Agency). (2004) Review of EPA’s draft supplemental guidance for assessing

cancer susceptibility from early-life exposure to carcinogens: a report by the Supplemental Guidance for Assessing

Cancer Susceptibility Review Panel, EPA Science Advisory Board. Washington, DC; EPA-SAB-04-003. Available 

from: http://www.epa.gov/sab. 

Whyatt, RM; Nicholson, WJ. (1991) Conducting risk assessments for preschoolers’ dietary exposure to pesticides. 

In: Tweedy, BG; Dishburger, HJ; Ballantine, LG; et al.; eds. Pesticide residues and food safety. Washington, DC: 

American Chemical Society; pp. 235–246. 

Whyatt, RM; Jedrychowski, W; Hemminki, K; et al. (2001) Biomarkers of polycyclic aromatic hydrocarbon-DNA

damage and cigarette smoke exposures in paired maternal and newborn blood samples as a measure of differential

susceptibility. Cancer Epidemiol Biomarker Prev 10(6):581–588. 

Whyatt, RM; Barr, DB; Camann, DE; et al. (2003) Contemporary-use pesticides in personal air samples during

pregnancy and blood samples at delivery among urban minority mothers and newborns. Environ Health Perspect

111(5):749–56. 

24
GLOSSARY 

Absorbed dose: the amount of a substance crossing a specific absorption barrier, e.g., skin, 

through uptake processes. 

Basal metabolic rate (BMR): the metabolic rate under quiescent conditions, without the 

influence of activity, digestion, or other factors causing increased metabolism.

Breathing zone: the area around the nose and mouth from which air is inhaled, sometimes 

described as a limited spherical zone extending around the nose and mouth. 

Contaminant loading: the quantity (mass per unit surface area) of environmental contaminant on 

a surface. 

Dermal transfer coefficient: an empirically defined parameter developed to aggregate the mass

transfer associated with a series of contacts with a contaminated medium. The transfer coefficient is a 

function of dermal exposure resulting from a particular activity and the loading of a contaminant 

on a surface. 

Dose: the amount of a substance available for interaction with metabolic processes or 

biologically significant receptors. The result of an exposure to a stressor in the environment, 

defined by the location, e.g., dermal, oral, and the transformation of the agent after crossing the 

outer boundary of the organism. 

Endocrine system: the glands that secrete directly into the bloodstream; e.g., thyroid, adrenals, 

pituitary. 

Epiphyseal closure: the time at which secondary bone forming centers, i.e., at the ends of the 

long bones, become a part of the entire bone and cease ossification (at adulthood). 

Exposure: the interface between the organism and the environment. Critical factors include the 

source, pathway, and route (i.e., dermal, oral, inhalation). 

Exposure factors: the parameters affecting the exposure, i.e., the interface between the organism

and the environment. There are physical, spatial, and temporal factors, as well as the activity of

the target organism. 

Exposure scenarios: for any given pathway, a set of associated exposure scenarios describes 

how an exposure takes place. This is needed to estimate the potential distribution of exposure by 

any given pathway. Exposure scenarios need to be identified to specify the values of exposure 

factors. An exposure scenario is defined by the combination of the following details: sources, 

exposed population (e.g., age or developmental stage), time frame of exposure (e.g., acute, short 

term, chronic, intermittent), location of exposure (e.g., residence, school, outdoors, indoors), and 

activity (e.g., mouthing, playing soccer, mowing lawns). 

Internal dose: general term for the amount absorbed without respect to specific absorption 

barriers or exchange boundaries. 

25
Lifestages: periods of development that encompass a number of common traits or parameters 

that are relatively constant. These have been broadly defined in colloquial terms, e.g., newborn, 

infant, toddler, preschooler, school-aged, pre-adolescent, adolescent. This document defines 

lifestages on the basis of specific anatomical and behavioral commonalities. 

Macroactivity: complex activities described as an entire event, e.g., showering, gardening, 

cooking. 

Microactivity: the simple activities that constitute more complex behaviors, e.g., an infant’s 

mouthing behavior during indoor play, in terms of number of hand-mouth events per unit of 

time. 

Mouthing behavior: hand-to-mouth and object-to-mouth contact. Varies by age and peaks 

between 1 and 3 years of age. It may include simple contact, licking, and insertion of fingers, 

hands, or objects in mouth. 

Potential dose: similar to external dose, or loading; the total amount of contaminant or agent 

contacting the outer boundary or orifice of the organism. The contact rate will affect the total 

potential dose. Absorption is not considered, i.e., 100% absorption is assumed. 

Risk assessment: a method of estimating the probability of deleterious health or environmental 

effects. 

Variability: an expression of variation between elements of a data set, e.g., within a sample or a 

population, within the set of daily behaviors of an individual or a group, or in the effects seen 

from exposure to a stressor. 

Ventilatory equivalent: the ratio of the minute volume-to-oxygen uptake at body temperature, 

ambient pressure, and water vapor saturated air (unitless). 

26
APPENDIX: PRELIMINARY REEVALUATION OF EXPOSURE FACTORS DATA 

FOR CHILDREN 

The purpose of this appendix is to describe the adequacy of data to support the 

recommended age groupings for children’s exposure and recommend areas of research to fill in 

the data gaps. In the “Charge to Experts” for the July 2000 workshop (see U.S. EPA, 2000a), 

several questions were posed to elicit discussion on whether existing exposure information is 

adequate to support a fine division of childhood age groups. To explore this issue further, 

subsequent to the workshop, the Risk Assessment Forum work group commissioned an expert 

review and reevaluation of data available in the draft Child-Specific Exposure Factors Handbook

(CSEFH) (U.S. EPA, 2000b). This reevaluation of exposure factors information resulted in an 

issue paper titled “Age Group Recommendations for Assessing Childhood Exposure and the 

Adequacy of Existing Exposure Factors Data for Children” (U.S. EPA, 2001a). This issue paper 

was prepared at the direction of the U.S. Environmental Protection Agency (EPA), Risk 

Assessment Forum. It was prepared by Versar, Inc., under EPA Contract No. 68-C99-238, Task 

Order 46. Mr. Steven Knott of the Risk Assessment Forum served as Task Order Manager, 

providing overall direction, technical assistance, and guidance. This appendix summarizes and 

updates the results of the reevaluation of exposure factors data discussed in the issue paper. 

AUTHORS AND CONTRIBUTORS 

The authors and contributors to the U.S. EPA 2001 issue paper and this appendix (2005) 

are listed below. 

ISSUE PAPER

Dr. Paul Brubaker, P.E., DBAT, Versar, Inc./Brubaker Association, Inc. 

Dr. Christine Chaisson, Chaisson Scientific Advisor, Inc. 

 

Mr. Robert Fares, Risk Management Initiative, LLC 

 

Kathy Kelly, Technical Editor 

 

Dr. David Layton, Lawrence Livermore National Laboratory 

 

Susan Perry, Word Processing 

 

Dr. Linda Phillips, Versar, Inc. 

 

Dr. P. Barry Ryan, School of Public Health University Emory 

Dr. Edward Stanek, School of Public Health University of Massachusetts 

Patricia Wood, Work Assignment Manager 

 

27
The preliminary reevaluation of data available in the draft CSEFH was accomplished 

through a panel of experts working under contract to Versar, Inc. (Springfield, VA). The experts 

were asked to judge whether a reevaluation of the underlying exposure factors data would 

support new recommendations for the initial set of childhood age groups presented in Table 4 of 

the main text. In addition, the experts were asked to discuss quality assurance issues such as 

those considered in selecting key studies for the CSEFH. The requested quality assurance 

discussion includes providing new “Confidence in Recommendations Ratings” (U.S. EPA, 

2000a) for each exposure factor should it be possible to derive new recommendations from the 

existing data. The new ratings reflect a consideration of attempting to use the existing data to 

address the initial set of childhood age groups. 

The issue paper explored whether existing child-specific exposure factors data can be fit 

to the proposed EPA age groupings. The authors evaluated the following exposure factors: 

breast milk intake, food intake, drinking water and total fluid intake, soil ingestion and pica, 

nondietary ingestion factors, inhalation factors, skin surface area and soil adherence to skin 

(dermal), activity factors, and body weight. This issue paper provided a number of 

recommendations for short-term analyses and longer-term research to improve the database for 

childhood exposure. A summary of the issue paper’s recommendations for future research is 

presented in the sections that follow. 

The authors of the issue paper evaluated the data in the CSEFH as well as new data using 

the same characterization criteria used in the CSEFH. Although the authors of the issue paper 

provided new recommendations on each factor for the recommended age groups, EPA is not 

ready to adopt these recommendations until further analyses (see below) are conducted during 

the revisions to its draft CSEFH (U.S. EPA, 2000a). However, the issue paper serves as a 

starting point in identifying those areas where research is necessary to improve the database to 

develop recommendations for the proposed age groups. 

In addition to the research needs described in this appendix, there are other data gaps that 

cut across all pathways of exposures. For example, accidental ingestion as well as dermal and 

inhalation exposures from the use of consumer products may occur. Further data are needed on 

the frequency and duration of use of consumer products by children. Methodologies to 

extrapolate from short-term studies to chronic exposures are also lacking.

It is important to note that there are efforts underway in EPA and elsewhere that may 

produce data to address some of these research needs. The National Children’s Study, sponsored 

by a consortium of Federal agencies, including EPA, will examine the effects of environmental 

influences on the health and development of more than 100,000 children across the United 

States, following them from before birth until age 21. In addition, EPA, in conjunction with 

National Institute of Environmental Health Sciences (NIEHS), has funded a number of National 

Children’s Health Centers across the country to study environmental contributions to children’s 

health and disease. Table A-1 summarizes the availability of data for the proposed age bins. 

Recommendations for further analysis and research are provided below. These 

recommendations come largely from the issue paper but also include recommendations made by 

EPA Program Offices and Regions. 

28
 29 Table A-1. Availability of Data for the Proposed Age Bins Age Bin Exposure Factor <1 

m

o

nth 1–2 months 3–5 months 6–11 m

o

nths 1–2 years 3–5 years 6–10 years 1

Breast milk intake 501 m

L/day 

(mean) SD a

nd 

ranges i

n

Tables 2-4 and 2-9CSEFH 

716 m

L/day

(mean) SD a

nd 

ranges i

n

Tables 2-4 and 2-9CSEFH 

797 m

L/day

(mean) SD a

nd 

ranges i

n

Tables 2-4 and 2-9CSEFH 

680 m

L/day

(mean) SD a

nd 

ranges i

n

Tables 2-4 and 2-9CSEFH 

N

D

N

D

N

A

N

Foo

d intake Chapter 3 

CSEFH 

Chapter 3 CSEFH 

 Chapter 3CSEFH 

 Chapter 3CSEFH 

 Chapter 3CSEFH 

 Chapter 3CSEFH 

 Chapter 3CSEFH 

 CC

Tap water intake a a a Tables 4-3,

4-5, 4-7CSEFH 

 Tables 4-3, 4-5, 4-7CSEFH 

 Tables 4-3, 4-5, 4-7CSEFH 

 Tables 4-3, 4-5, 4-7CSEFH 

 T4C

Soil ingestio

n

N

D

N

D

N

D

N

D a a a N

Soil ingestion(pica) 

N

D

N

D

N

D

N

D

N

D

b

N

D

N

Mouthi

ng behavior N

D

N

D a,b a,b a,b a,b

N

D

N

Breathing rates a a a a 6.8 m3

/day 8.3 m3/day 10

m3

/day 1

Surface area a a a a Tables 8-1,

8-2, 8-3CSEFH 

 Tables 8-1, 8-2, 8-3CSEFH 

 Tables 8-1, 8-2, 8-3CSEFH 

 T8C

Activity factors N

D

N

D

N

D

N

D a a a a 

Body weight Table 11-1

CSEFH 

Table 11-1CSEFH 

Table 11-1CSEFH 

Table 11-1CSEFH 

Table 11-2CSEFH 

Table 11-2CSEFH 

Table 11-2CSEFH 

TC

aData available, but reanalysis of 

data needed. bData very limited. 

CSEFH = Chil

d-Specific Exposure Factors Handbook (U.S. EPA, 2002). 

NA = Not applicable. ND = No data.SD = Standard deviation.
A.1. DIETARY ROUTE OF EXPOSURE 

Oral ingestion exposures are typically assessed by considering two major contributors: 

dietary exposures (from food, water, or breast milk intake) and incidental or nondietary 

exposures (from mouthing hands and objects or from the deliberate ingestion of nonfood items). 

The following summarizes the research needs for this route of exposure. 

A.1.1. BREAST MILK INTAKE 

• Collect data that would allow estimation of the variability (i.e., estimation of 

distributions) across the population for milk intake as a function of age and/or infant 

weight. Studies should include consideration of the major ethnic groups in the U.S. 

population, including Black, Asian, and Hispanic. 

• Collect data that would allow estimation of the effect of a mother’s nutrient status on the 

fat/lipid content of breast milk (both before and during lactation). Data are needed on the 

types of lipids that may change because of these variables and the mobility of such lipids 

in the milk during lactation. 

• The issue paper (U.S. EPA, 2001a) noted that the 6- through 11-month age group 

captures a period of rapidly decreasing breast milk intake. This observation is consistent 

with the July 2000 workshop discussion, which noted the expanding variety of foods 

consumed during this time period. Therefore, future breast milk intake data collection 

efforts should consider that it may be appropriate to further divide the 6- through 11-

month age group into two or three separate groups. 

• Data are needed to determine the frequency of breast feeding in older infants and to 

provide statistical data on the likelihood of breast feeding as the child ages. 

• Data are needed to determine the prevalence of breast feeding among women and its 

variability as a function of age, socioeconomic status, ethnicity. National Health and 

Nutrition Examination Survey (NHANES) data could be examined to study the feasibility 

of obtaining these data. 

A.1.2. FOOD INTAKE

Incorporate the analyses of the 1998 Continuing Survey of Food Intake by Individuals 

(1998 CSFII) that was done by EPA’s Office of Pesticide Programs (OPP) in its Food 

Commodity Intake Database (FCID) to substantially improve the estimates of childhood food 

intake. The 1998 CSFII is a supplemental study that specifically targeted childhood food 

consumption patterns. Combining the 1998 data with the 1994–1996 data dramatically increases 

the number of observations for some age groups. 

A.1.3. WATER INTAKE 

• Incorporate analysis of the 1998 CSFII data conducted by the Office of Water. The 1998 

CSFII may substantially improve the estimates of childhood water intake. The 1998 

CSFII is a supplemental study that specifically targeted childhood consumption patterns. 

Use of the 1998 study should improve overall confidence in the water intake estimates for 

children. 

30
• Follow recommendation in the issue paper that exposures from water intake be 

normalized by body weight to the 3⁄4 power (BW3/4). This recommendation could apply 

equally to other exposure estimates (e.g., exposure from food intake). However, a 

corresponding change in the approach to normalizing the various measures of toxicity 

would also be needed. This issue needs to be explored further. 

A.2. NONDIETARY INGESTION ROUTE OF EXPOSURE 

Incidental or nondietary ingestion exposures result from the mouthing of contaminated 

hands and objects and from the deliberate ingestion of nonfood items (also know as pica 

behavior). Currently, two approaches to estimating these exposures are commonly employed. 

For ingestion of soil (whether deliberate or incidental) an estimate of the amount of soil ingested 

is needed. For the ingestion of dustborne contaminants from contact with surfaces, a 

microactivity approach, which takes into account the activities of the child, properties of the 

chemical, and physical characteristics of child, is used. 

The following discussion addresses data on soil intake, exposure frequency of 

microactivities, and exposure duration. Skin surface area is addressed in the section discussing 

the dermal route of exposure (object surface area is case specific); transfer efficiencies are 

chemical/media specific and are not addressed in this document. Contaminant loading on hands 

can be estimated from a microactivity approach to dermal exposure assessment if sufficient data 

are available (see discussion in Section A.4). 

A.2.1. SOIL INTAKE 

• Collect soil ingestion data on a broader range of childhood ages (e.g., 3 months to <13 

years). 

• Collect data that would allow estimation of variability and distributions of intake across 

geographic areas, race, economic status, and other demographic variables, including pica 

behavior. 

• Collect data that would allow the characterization of seasonal variation in soil intake. 

These data would support the development of distributional information for long-term

exposures. 

• Explore different ways of interpreting the existing mass balance soil intake data; these 

analyses could help improve estimates in the near term. However, the suggested 

approach needs to be explored further and subjected to peer review. 

• Conduct research to provide a better understanding of the relative contribution of soil 

versus dust ingestion. 

• Explore other methodologies for estimating soil ingestion rates. 

A.2.2. EXPOSURE FREQUENCY AND EXPOSURE DURATION FOR DUSTBORNE 

AND SURFACE CONTAMINANTS 

Children’s microactivity data are sparse. The majority of information comes from small 

studies, many of which were designed to test methodologies for monitoring microactivities. The 

limited data focus on the frequency and duration of mouthing hands and objects. As noted 

31
above, if mouthing duration (min/day) is used to estimate exposure, then surface area needs to be 

presented per unit time (i.e., cm2/min), not per event. Given the paucity of existing data, the 

issue paper concluded that no new microactivity recommendations can be made at this time. 

The following recommendations are made: 

• A research program, including a comprehensive data collection effort, is needed to 

improve estimates of microactivities for nondietary exposure assessment. Existing 

studies are small and include a variety of methodologies. 

 

• Systematic, probability-based studies should be undertaken that address a broad range of 

childhood age groups (at least to <6 years of age). 

A.3. INHALATION ROUTE OF EXPOSURE 

The following discussion addresses inhalation rates and the time spent in 

microenvironments. Note that the time spent in microenvironments is also used in some dermal 

exposure models. Therefore, the section on the dermal route of exposure refers back to the 

discussion provided in this section. 

A.3.1. INHALATION RATE 

The issue paper (U.S. EPA, 2001a) indicated that existing data do not support 

recommendations for children less than 3 years of age due to the lack of ventilatory equivalent 

data for these ages. Further, although the existing data may support a recommendation for 

children aged 3 to <6 years, the issue paper notes that the data are very limited. However, 

ventilatory rates may be derived using energy expenditures incorporating the latest USDA CSFII 

1994–96 and 98 data. The paucity of data for young children is a particularly important source 

of uncertainty, given that the limited data (and the current understanding of childhood 

physiology) suggest that ventilatory equivalents will be higher for these age groups. The 

existing data do support recommendations for grouping children aged 6 to <11 years, 11 to <16 

years, and 16 to <18 years. 

The issue paper authors who reevaluated the inhalation rate estimates recommended 

several areas of further analysis and research. 

• First, the more recent CSFII data can be analyzed further to obtain food energy 

intake/energy expenditures for the entire initial set of childhood age groups. 

 

• For short-term, activity-specific inhalation rate estimates, the approach of Allan and 

Richardson (1998) could be explored further but would need to be supported with the 

collection of additional activity data for children. 

• Activity-specific inhalation rate estimates could also be developed using the Layton 

(1993) approach as modified by McCurdy (2000). Specifically, inhalation is calculated 

in the manner described above, but energy expenditure is estimated using a factorial 

approach in which an individual’s activities are assigned energy expenditure values based 

on a multiplier of basal metabolic rate (termed a MET). Daily estimates of energy 

expenditures derived from this method could be compared with estimates derived from 

the CSFII to lend insight into quality assurance issues. 

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• Finally, a critical area of research (especially for children less than 6 years of age) is the 

search or collection of ventilatory equivalent (the ratio of the minute volume to oxygen 

uptake at body temperature, ambient pressure, and water vapor saturated air [unitless]) 

data for children. These data may already be available from research in pharmacology. 

Any new data collection efforts should consider susceptible populations, such as 

asthmatic children. 

A.3.2. TIME SPENT IN MICROENVIRONMENTS PURSUING MACROACTIVITIES 

Children’s exposures in relation to activities are generally captured as either 

macroactivities, e.g., playing a game of baseball, or microactivities, e.g., touching hand to mouth 

10 times in 1 hour, the latter taking place within a microenvironment, or specific space. Given 

the paucity of existing data, the issue paper authors concluded that new recommendations for 

children less than 1 year of age and 11 years of age and older cannot be made. Referring to 

Hubal et al. (2000), the authors state that “the current database on children’s macroactivities is 

sparse and data are insufficient to adequately assess exposures to environmental contaminants. 

However, the results of the Hubal et al. (2000) evaluation of CHAD data for children less than 

12 years of age are sufficient to provide recommendations for time in microenvironments and 

participation in certain macroactivities for children in age groups of [1 to <3 years], [3 to <6 

years], and [6 to <11 years].” 

The expert authors recommended two specific areas of research. 

• Develop methods for monitoring children’s activities and exposures. 

• Collect population-based data on children’s activities and exposures to allow 

characterization as a function of age, gender, environmental setting (microenvironment), 

socioeconomic status, race/ethnicity, geographic location, and season. In particular, 

focus on young children (less than 4 years of age) and children aged 11 years and older. 

A.4. DERMAL ROUTE OF EXPOSURE

For dermal exposures to contaminants in soil, data on body surface area in contact with 

the contaminated soil, soil adherence data, and exposure frequency for each microactivity are 

needed. 

Overall, experts agree that the assessment of dermal exposures is an area that is ripe for 

research. The preliminary reevaluation for dermal exposure factors focused on two factors in the 

equation for estimating dermal exposure to contaminants in soil: total skin surface and soil 

adherence to skin. Surface area is discussed below in Section A.4.1. The issue paper expert 

providing the preliminary reevaluation concluded that soil adherence to skin is more closely 

related to activity than to age. Therefore, no further reevaluation was provided for this factor. 

Data on the frequency of macroactivities are sparse. Research in the following areas is 

recommended. 

• Data on the frequency of macroactivities are needed. Most studies have focused on the 

duration of such activities (e.g., min/day) as opposed to the number of times the activities 

are performed each day. Exceptions include the frequency of swimming and showering 

events. 

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• More data are needed for the development of dermal transfer coefficients. EPA’s OPP 

has proposed an interim value of 5,200 cm2

/hour for short-term exposure for children 

playing outdoors on lawns and indoors on carpeted or hard flooring (U.S. EPA, 1997, 

2001b). 

• The macroactivity approach would benefit greatly from further research providing 

activity- and surface-specific dermal transfer coefficients for children. The preliminary 

reevaluation did not include a review of this factor. 

• As with the macroactivity approach, few data exist to support the use of the microactivity 

approach to estimating dermal exposures from contaminated surfaces. Most of the 

available studies focus on the frequency of mouthing events in children. For this specific 

microactivity and others (e.g., specific body part contacts with surfaces) the data are 

extremely sparse. 

• Data on the area of surface that is contacted during a microactivity event are virtually

nonexistent. As noted above in Section A.2.2, a systematic, comprehensive data 

collection effort is needed to support these exposure factors. The remaining factors in the 

microactivity dermal exposure equation are chemical/media specific. 

For the estimation of dermal exposure from contact with contaminated water, skin 

surface area is addressed in the section that follows. For estimating absorbed dose, consult the 

Superfund dermal guidance (U.S. EPA, 2004) for a complete discussion. One component used 

in determining time spent bathing, showering, or swimming is discussed above in Section A.3.2. 

As noted above for estimating dermal exposure to soil, data on the frequency of macroactivities 

were not included in the preliminary reevaluation. Surface area exposed in these scenarios is 

highly dependent on the activity. 

A.4.1. SKIN SURFACE AREA 

The expert providing the preliminary reevaluation of skin surface area data reviewed the 

same studies and approach as used by EPA in the draft CSEFH. The experts recommended 

research in the following areas: 

• An analysis of the NHANES 99 plus or later data sets should be conducted to provide 

new recommendations for estimates of skin surface area for the initial childhood age 

groups 2 years of age and older (EPA used the NHANES II data for children >2 years of 

age in the draft CSEFH). 

• For further analysis and research on skin surface area, the expert recommended collecting 

new height and weight data for children less than 2 years of age. 

• Further, although this expert concluded that dermal soil adherence is more activity 

specific than age specific and, therefore, deferred to the activity-specific 

recommendations of the draft CSEFH, the expert recommended that more detailed 

studies of dermal soil adherence be conducted to determine variations among individuals 

and the effects of duration of activity, clothing use, and time of year on this factor. 

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• In addition, implicit in the expert’s review is the need to update skin surface area 

estimates for children 2 years of age and older using the newer NHANES 99 plus data for 

height and weight. 

The analyses should support the recommended initial set of childhood age groups 

provided in Table 4 of the main text. 

A.5. HUMAN BODY WEIGHT 

Human body weight is used to normalize daily exposure estimates in the calculation of 

daily potential doses. For dietary exposures, the studies used to derive intake rates for food and 

water (namely the CSFII 1994–96 and 1998 studies) include body weight information for each 

individual surveyed. Therefore, the food and water intake for a specific individual can be 

normalized by the body weight for that individual to yield intake rates in units of g/kg-day. For 

breast milk intake, nondietary ingestion exposures, inhalation exposures, and dermal exposures, 

such concurrent collection of body weight information is absent from the relevant exposure 

factors data. Typically, these exposures will be normalized by body weight information from

other sources, such as average body weight estimates for the general U.S. population derived 

from data available in the NHANES studies. The following discussion conveys the results of the 

preliminary reevaluation of human body weight data for the initial set of childhood age groups. 

The expert providing the preliminary reevaluation of body weight data for children 

highlighted several areas for further analysis of existing data. 

• Further statistical analysis of the NHANES 99 plus data will allow the derivation of 

multiple percentiles and distributional information for the initial set of age groups. 

• In addition to the relationship between age and weight, the existing data should be 

analyzed for other relationships (e.g., age and stature, body mass index) to develop a 

more complete understanding of body metrics that may have a bearing on exposures and 

risks. 

• The NHANES 99 plus data should be analyzed further to develop body weight estimates 

that are specific for selected ethnic groups. 

 

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APPENDIX REFERENCES 

Allan, M; Richardson, GM. (1998) Probability density functions describing 24-hour inhalation rates for use in

human health risk assessments. Hum Ecolo Risk Assess 4:379–408. 

Hubal, E; Sheldon, L; Burke, J; et al. (2000) Children’s exposure assessment: a review of factors influencing 

children’s exposure, and the data available to characterize that exposure. Environ Health Perspect 8(6):475. 

Layton, DW. (1993) Metabolically consistent breathing rates for use in dose assessments. Health Phys 64:23–36.

McCurdy, T. (2000) Conceptual basis for multi-route intake dose modeling using an energy expenditure approach. J 

Expo Anal Environ Epidemiol 10:86–97. 

U.S. EPA (Environmental Protection Agency). (2000a) Summary report of the technical workshop on issues 

associated with considering developmental changes in behavior and anatomy when assessing exposure to children. 

Risk Assessment Forum, Washington, DC; EPA/630/R-00/005. Available from: 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=20680. 

U.S. EPA (Environmental Protection Agency). (2000b) Child-specific exposure factors handbook [draft]. Office of

Research and Development, National Center for Environmental Assessment, Washington, DC; EPA/600/P-00/002A.

U.S. EPA (Environmental Protection Agency). (2001a) Age group recommendations for assessing childhood

exposures and the adequacy of existing exposure factors data for children. Risk Assessment Forum, Office of

Research and Development, Washington, DC; EPA/630/R-03/005. Available from:

http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_id=237196. 

U.S. EPA (Environmental Protection Agency). (2001b) Recommended revisions to the standard operating

procedures (SOPs) for residential exposure assessments. Policy No. 12. Science Advisory Council for Exposure, 

Office of Pesticide Programs, Washington, DC. 

U.S. EPA (Environmental Protection Agency). (2002) Child-specific exposure factors handbook [interim final]. 

Office of Research and Development, National Center for Environmental Assessment, Washington, DC; 

EPA/600/P-00/002B. Available from: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=55145. 

U.S. EPA (Environmental Protection Agency). (2004) Risk assessment guidance for Superfund. Volume I: Human 

health evaluation manual, part E: supplemental guidance for dermal risk assessment. Office of Superfund

Remediation and Technology Innovation, Washington, DC; EPA/540/R-99/005. 

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