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, DCDISCL A IMER

This document has been reviewed in accord an ce with U.S. Environm ental Protection Agency policy and approved for publication. Men tion of trade nam e s or comm ercial products
does not con s titu te endo r s em ent or re commendation f o r use.

Preferred Citati on: U.S

. E nvi ro nm ent a l Pr ot ect i o n Age n cy (EP A ). ( 2 00 5) G u i d ance o n sel ect i ng a g e g r o u p s fo r m oni t o ri ng and assessing ch ildh ood ex po su res to env i ron m e n tal con t am in a n ts. Nation a l Cen t er for Environ m en tal Assessm en t, Was h i n gt o n , D C ; EPA/ 6 3 0 / P

- 03/ 00 3F

. A v ai l a bl e fr om : Na tio n a l Techn i cal Inform atio n Serv ice, Sp ringfield , VA, and online at http://epa.gov/ ncea.

iiCONTE N T S

LIST OF TABLES

................................................................................................................. ........ iv LIST OF FI GURES

................................................................................................................ ....... iv ACKNOWLEDGMENTS ...............................................................................................................v FOREWORD

....................................................................................................................... .......... vi PREFACE

........................................................................................................................ ............. vii AUTHORS AND CONTRIBUT O RS .............................................................................................x EXECUTIVE SUMMARY

........................................................................................................... xi

1. INTRODUCTION ...............................................................................................................1
2. AGE GROUPS TO CONSIDER WH EN ASSE SSING C H ILDHOOD E X POS U RES TO ENVIR ONMENT A L CONTAMINANTS

.................................................................... 6 3. APPLYING THE RE COMMENDE D SET OF CHILDHOOD AGE GROUP S TO EXPOSURE ASSESSMENT ............................................................................................16
3.1. CONDUCTING SCREENING-LEV EL EXPOSURE ASSESSMENTS .................16
...................17 3.2. INTEGRATING EXPOSURE ACROSS M U LTIPLE AGE GROUPS

..................................18 3.3. ADDIT I ONAL CONSIDERAT IONS WHE N USING HUMAN E X POSURE MODELS AND ALGORITHMS I N RISK AS SESSMENT S
REFERENCES ..............................................................................................................................2 2
OTHE R RE COMMENDED REFE RENCES ................................................................................23
GLOSSARY

....................................................................................................................... ...........25
APPENDIX: PRELIMINAR Y REE VALUATI ON OF EXPOSURE FACTORS DATA FOR CHILDREN

.................................................................................................... 27

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

iiiLIST OF TABLES

Table 1. Exam ples of Early-L i fe Ag e Groups Used in Past Agency Exposure Assessm ents .................................................................................................................5

Table 2. Exam ples of Factors Consid ered in Deriving Age Groups Reflecting Behavioral Developm ent .............................................................................................9

Table 3. Exam ples of Factors Consid ered in Deriving Age Groups Reflecting Anatom ical/Physiological Developm ent ...................................................................10

Table 4. Recommended Set of Ch ildhood Age Groups for Agency Exposure Assessm ents ...............................................................................................................13

Table 5. Integrating This Age Grouping Guidance with the S upplem e n tal Guidance for Assessin g Susceptib ility from Early-L i fe Exposure to Carcinogens Th at Act via a Mutagenic Mode of Action ........................................................................18

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

LIST OF F I GURES
Figure 1. Relationship Between Exposure, Dose, and Effects in Risk Assessm ent ...................8
Figure 2. Com p arison of Single-Day Exposure Estim at es with Various Tim e

Averaged E xposures ..................................................................................................21

ivACKNOWLEDGME N TS

We would like to acknowledge the assistance of the f o llowin g outside s c ientif ic exp e r t s who participated in a peer invol vem e nt workshop in 2000 that led to the developm ent of this docum ent:

Thom as W

. Ar m s trong ExxonMobil Biom edical Sciences Sophie J. Balk Montefiore Medical Center, New York Deborah H. Bennett Departm e nt of P ublic Health Se rvice s , University of California, Davis Jam e s V. Bruckner College of Pharm acy, University of Georgia Michael Dinovi FDA Center for Food Safety and Applied Nutrition Richard Fenske University of W a shington School of Public Health Gary L. Ginsberg Connecticut Departm e nt of Public Health Lynn Goldm a n Johns Hopkins School of Public Health Robert Johnson Agency for Toxic Substances and D i sease Registry Celestine Kiss U.S. Consum er Product Safety Comm ission John C. Kissel University of W a shington School of Public Health Bruce P. Lanphear Children ’ s Medical Center, Cincinnati, OH Jam e s O. Leckie Stanf o rd Univers ity Melan i e A. Marty Calif ornia E P A Mary Kay O’Rourke University of Arizona George C. Rodgers University of Kentucky, Louisville P. Barry Ryan Rollins Sch ool of Public Health, E m ory University Margo Schwab Johns Hopkins School of Public Health Katherin e M

. Shea Pediatrician, Chapel Hill, NC Ki m b erly Thom pson (Chair) H arvard School of Public Health W illiam B. W e il Pediatrics, Michig an State Unive r sity Robin M. Whyatt Colum b ia Ma ilm an School of Public Health

At the sam e tim e, it is im portant to also recogni ze those scientists who provided peer review comments on the initial version of this docum ent, including:

Tim o thy J. Buckley Johns Hopkins Bloom be rg School of Public Health Christine F. Chaisson CF Chai sson Scientific Advisors, Inc. Jef f r ey H. Driver Inf o Scientif ic Corp. Ruth A. Etzel George W a s h ington University School of Public Health Robert J. Fa res Risk Manag e m e nt Initia tive Elaine M. F a ustm an, (Chair) University of W a shington School of Public Health Natalie C. G. Freem an Environm ental a nd Occupational Health Sciences Institute Gary L. Ginsberg, Ph.D. Connectic ut Departm e nt of Public Health Larry L. Needham Centers fo r Disease Con t rol and Prevention P. Barry Ryan Rollins Sch ool of Public Health, E m ory University Robin M. Whyatt Colum b ia Ma ilm an School of Public Health Mary S. W o lff Mt. Sinai S c hool of Medicine, New York

vFOREWORD

Based on the peer review and public comm ents, the Risk Assessm ent Forum technical panel has m a de a num be r of changes to the earlie r draft of this docum ent, including clarifying
the re lations hip between this report and other exposure assessm e nt guidance/m odels/tools,
im proving illustrative diagram s , expanding the c itations, and adding lang uage to th e preface to discuss scientific, regulatory, and leg a l cons traints associated w ith the con s idera tion of this guidance. E P A expects to develop case exam ples to illustrate the use of this guidance; these case
studies would then be made available on the Risk Assessm e n t Forum ’ s Web site.

viPREF ACE

The roots of this guid a nce reach b ack to the la te 1 980s with th e advent of planning for an EPA program in the area of residential exposu re m e thods and data developm ent, which was followed by the Risk Assessm ent Forum ’ s revision of EPA’s Guidelines for Exposure
Assessment in 1992. Soon thereafter, the National Acad em y of Sciences released its sem i nal reports, Science and Judgment in Risk Assessment and Pesticides in the Diets of Infants and
Children . B o th of these reports contained reco mm endations on how EPA should im prove its approaches to assessing potential ris k s to children. Since that tim e, there has been co nsiderab le
effort across the Agency ’s program offices and re search activities d i rected at developing risk

assessm ent guidance ap plicab le to c h ildr e n’s pa r tic ular exposures. The purpose of this docum ent is to com p lem e nt existin g EPA guidance and exp e rien ce to as sist Agency risk as sesso rs in
im proving the accuracy and cons istency of children’s exposu r e assessm ents. The docum ent describes a set of age groupings that can be us ed, and when necessary adapted, for purposes of designing m onitoring studies and conducting risk assessm ents focused on children. This guidance was developed by a technica l panel under the auspices of the Risk
Assessm ent Forum

. The Risk Assessm e nt Fo rum was established to prom ote scientific

consensus o n risk assessm e nt issues and to fost er the im plementation of this consensu s into th e Agency’s ris k assessm ent practices. To accom p lish this, the F o rum assembles expe rts from throughout EPA in a form al process to study and report on issues from an Agency-wide perspective. The document reflects the Foru m ’ s long-standing comm it m e nt to advancing

exposure assessm ent and to supplem ent the Agency’s Guidelin es for Exposure Assessm ent . This activity was initiated by Agency risk assessors, who requested th at the Forum study and provide

recomm endations on a set of early-lifestage age groupings for initia l consideration. As an initial step, the Forum hosted a p eer involvem e nt wor k shop in 2000 to bring togethe r f o r the f i rs t tim e scien tif ic ex perts in the areas of child development and exposure

assessm ent to answer the question of how knowledge of behavioral, anatom ical, and physiological changes in children can guide the developm ent of a generic set of age groupings. This workshop resulted in a recommended set of early -lifestage age gr oupings. Following the workshop, the Forum ’ s technical panel comm issione d 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 E x

posure Factors Handbook were used for this reevaluation.

viiThe expert review provided a num be r of recomme ndations for short-termanalyses and longerterm research to im prove the current databa se for childhood exposure. The Exposure Factors Program and individual research grants adm i nistered by the National Exposure Research Laboratory have begun to im ple m ent the findi ngs of the 2000 workshop and the 2001 expert review to guide future data-gat hering and research activ ities. Finally, an earlier draft of this document was in ter n ally and ex terna lly pe er reviewed in 2003 and made available for public comment at that tim e. The generic children’s age group

recomm endations were selected on the basis of the aforem entioned 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 anatom y and physiology that can serve as a starting set for consideration by Agency risk asse ssors and researchers. In specific situat ions, it is recognized that exposure factors data m a y not be availa ble f o r m a ny of the recomm e nded age groupings or that a specific age group m a y not need to be the s ubject of a particular assessm ent, so flexibility and professional judgm ent are essent ial in applying these generic ag e groupings. In order to use the age groupings appropriately, one should, wi thin the problem for m ulation step of any

assessm ent, consider the available ex posure data and the objectives of the assessm ent. The process of matching age groups to existing exposure data and com b in ing these with toxicity data can vary according to the circum stances; therefor e, this docum ent should be used in combination with other exposure and risk as sessm ent tools and guidance. There are many efforts underway within the Ag ency to address developm ental issues and to characterize physical variations that occur in different lifes tages throughout the life span. There will always be a need to balan ce the add e d value of increased reso lu tion against the cost of generating the necessary exposure data. The reco mmended age grouping s can focus future
research and data collection efforts so that one can m ove toward a goal of conducting exposure

assessm ents that add r ess all s i gnificant variations in lifes tage. Ultim ately, as our understand ing
of the factors determ ining potential susceptibi lity as a function of age im proves, exposure

assesso rs will be ab le to m a ke more inf o rm ed choices about the level of re solution n e e d ed to

m a ke the best public health decisions. EPA exposure assessm e n ts m a y be conducted dif f

erently than envision ed in this guidance
for m a ny reasons, includ ing but not lim ited to, chem ical- or route-specific exposure, hazard o r exposure/dose-response inform ati on, new scientific inform ation or understanding, or differences

viiiin science policy judgment. The practice of assessing exposure to t oxicants continues to develop, and specific components of this guida nce m a y becom e outdated or m a y otherwise require m o dification in individual se ttings. It is EPA’s inten t to us e, to the exten t practicable an d
consistent w ith Agency s t atu t es and regulations, the best available science in its risk assessm ents and regulatory actions, and this gu idance is not intended to provide any substantive or procedural obstacle in achieving that goal. Therefore, th is guidance has no binding effect on EPA or on any regulated entity. W h en EPA does use this guidance in developing exposure and risk

assessm ents, it will be because it has decided in the contex t o f that asses s m ent that th e approaches from this guidance are su itab l e and ap propriate. T h is judgm ent will b e tes t ed through peer review, and the exposure/risk asse ss m e nt will be m odified to use differen t approaches, if appropriate. This guidance does not establish any subs tantive “rules” unde r the Administra tive
Procedure A c t or any other law and has no bindi ng effect on EPA or any regulated entity, but instead represents a nonbinding statem ent of pol icy.

ixAUTHORS AND CONTRIBUTORS

Authors
Michael Firestone, Office of Children’s Heal th Protection/O ffice of the Adm i nistra tor
Elaine Hubal, Jacqueline Moya, Valerie Zart arian, Office of Research and Developm ent

Risk Assessment Foru m Staff

W illiam P. Wood, Executive Director
Gary Bangs, Science Coordinator

Contributors
Karen Pollard, Office of Solid W a ste and Em erge ncy Response
Jianping Xue, Karen Hammerstrom , Of fice of Research and Developm ent

Tom Brennan, Jeff Daws on, St even Knott, Tim o thy Leighton, Davi d Miller, Office of Pesticides and Toxic S ubstances

xEXE CUTI V E SUMM ARY

Guidance on Selecting Age Groups for M onitoring and Assessing Childhood Exposures
to Environm ental Contaminants provides a set of early-lifestage age groups for U.S.
Environm ental Protection Agency (EPA, or the Ag ency) scien tists to con s ider when as sessing children’s exposure to environm ental contam inants and the re sultant potential dose. These

recomm ended age grou ps are bas e d on curren t u nderstanding of differences in behavior and physiology that m a y i m pact exposur es in children. A consistent set of early-life age groups, supported by an underlying scientific rationale, is expected to im prove Agency exposure and risk

assessm ents f o r childr e n by incre a sin g the cons is tency and comparability of risk assessm e nts across the Agency, im proving accu racy and tran spar ency in assessm ents for those cas es where current practice m i ght too broadly combine be haviorally and physiolo gically disparate age groups, and fostering a consistent approach to future exposure surv eys and m onitoring efforts to generate im proved exposure factors for children

. A current impedim e nt to the creation and use of a consistent set of age groupings is the lack of adequate data to char acterize a num ber of physiological, behavioral, and other relevant

param e ters 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 toxicologica l va riability that can also im pact risk; such considerations, as discussed later, should occur th rou gh an iterative dialogu e between ex posure assessors and toxicologists

. Prior to the r e leas e of its revised Guidelines for Carcinogen Risk Assessment in 2005, the Agency often described all types of subgroups of individuals as subpopula tions. The guidelines recognized that it is helpful to distinguish betw een subgroups that form a relatively fixed portion of the population (e.g., subgroups ba sed on ethnicity) and subgroups su ch as age groups that are potentially inclusiv e of the en tire population over tim e. Acco rdingly, following the revised cancer guidelines, this guidance views childhood as a sequence of lifes tag e s and, therefore, trea ts age subgroups of children as lifestages, not subpopulations This guidance is expected to assist th e Agency in im ple m enting such regulatory
initiatives as Presidential Executive Order 13045 (http://yos em ite.epa.gov/ochp/ochpweb.nsf/ content/whatwe_executiv.htm ) , whic h directs all Federal agencies to (a) m a ke it a high priority to identify and assess environm en tal health risks and safety ri sks that m a y disproportionately

xiaffect children, and (b) ensure tha t th eir po lic ies, program s, activities, and standards address disproportionate risks to children that result from environm ental health risks or safety risks. Historically, various program s within EPA have independently developed approaches (including the use of age groupings) to address ch ildren’s exposure. These approaches were, in part, influenced by a combination of circum stances, including the goals of the enabling legislation, the assessm ent question at hand, and th e availability of data. The Agency risk assessor community, in an effort to foster grea ter cross-Agency consistency in approaches to
children’s risk assessm ent, re quested that EPA’s Risk Asse ssm e nt Forum (RAF) study and

recomm end a set of early-lifestage groupings fo r initial consideration in children’s risk

assessm ents. Prim arily on the basis of scientif ic discussions held dur ing the EPA RAF July 2000 peer involvem ent works hop and subsequent t echnical analysis by an RAF work group, the
Forum is recomm ending that the following age groups be considered in Agency exposure

assessm ents for children and used as a guide fo r future exposure data collection and analysis
effort s:

• Less than 12 m onths old: bi rth to <1 month, 1 to <3 m onths, 3 to <6 m o nths, and 6 to <12 m onths.

• Greater than 12 m onths 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 yea r s is m eant to span a 3-ye ar tim e inter v al f r om a child’s 3 r d birthday up un til the day before his or her 6th birthday). These age groupings and the supporti ng rationale for their selection have been subjected to internal and external s c ien t if ic peer review and reflect the
comments of the review ers. Other scientific bod ies, such a s the Inte rnatio nal Lif e Scie nces Institute, have also recommende d evaluating children’s exposure as a series of lifestages.
Due to lim its in currently available data on age-specific exposure factors for young children, criteria used to select these age groupings were often qua litative in nature. Narrow age groups were identified where rapid developm enta l changes occur, and broader age groups were identified as the rate of developm ent decrea sed. The experts involve d in defining these age groupings have also reco mm ended that this guidance be a “l iving document” and be updated as new data and analyses becom e available. After the workshop, the RAF work group

comm issioned an expert review and reevaluation of the data available for the recommended

xiigroupings: the data gather ed to support the draft Child-Specific Exposure Factors Handbook
were used for this reevaluation. This resulted in an issue paper that provided a num be r of

recomm endations for short-term analyses and lo nger-term research to im prove the database for childhood exposure.
Because childhood is a tim e of rapid behavioral and physiolo gical changes, it is im portant that exposure assessors consid er these significant differences when conducting an exposure

assessm ent. There m a y be instances for a partic u l ar ch em ical and/or expo sure scen ario where

com b ining som e of the recomm ende d age groups (e.g., com b ining the first three <1 year age groups into one representing birth to <6 m onths) is indicated; i.e ., variation in exposure factors and resulting exposures is insignificant. In addition, there may be in stances where it is not necessary to address ev ery age group listed above because exp o sure is un likely or the focus of
the risk assessm ent m a y be a h ealth effect for which only one or two of the above groups represent a critical window. W h er e there is a lack of exposure da ta for a particular age group of potential importance, the risk assessor should still consider how exposure for this age group

m i ght differ and the possible im plications for not explicitly including th e 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 com p onent of this guidance involves aggregating ag e-s p ecific differences in exposure across tim e when assessing long-term exposure, as well as integrating these agespecific exp o sures with age-specific differen ces in toxic potency in those cases where
inform ation exists to describe such differen ces: an exam ple is carcinogens that act via a mutagenic mode of action. W h en assessing chronic risks, rather than assum i ng a constant level of exposure for 70 years (usually consiste nt with an adult level of exposure), the Agen cy has
been m oving to consider exposure at different lifestages ; this guidance is m eant to be an aid in this continuing process. An assessor should sum across tim e-weighted values for all age periods when exposure is likely to occur. Th is approach is expected to increase th e accuracy o f risk

assessm ents because it w ill take into account lifes tage differen ces in expos ure. Depen d ing on whether body-weight-adjusted childh ood exposures are either sm aller or larger as compared with those for adults, calculated risks could either decr ease or increase as com p ared with th e approach
of assum i ng a lifetim e of a constant level of exposu re. If age-related differences in toxicity were also found to occur, differences in both toxicity and exposure would need to be integrated across
all relev a nt age interva l s

.

xiiiThe scope of this guidance is lim ited to r ecomm e nding a generic set of age groupings. However, it should be emphasized that other factor s not discussed in this docum ent can also have a significant im pact on exposure and dose, such as special population considerations associated
with ethnic and cultural variab ility (e.g., consideration for higher fish consum ption rates am ong

som e Native Am erican populations), gender diffe rences, and socioeconom i c, geographic, and
seasonal effects. W h en assess ing ex posure, an a ssessor sh ou ld consid er th e potential im pact of
these other f actors in arriving at a final se t of age groupings. For exam ple, the Agency recognizes that m a ternal behavior patterns, includ ing dietary intake, can a ffect fetal exposure. However, at the tim e of t h is writing, Agen cy m e thodologies have not been developed to separately evaluate fetal exposure (S AB, 2004). The Agency will be following scien t ific advances in understanding the im plications of su ch exposures and is currently developing a risk

assessm ent fram ework for children (U.S. EPA, 2 003a) that will allow for the inco rporation of such advances. Future guidance is anticipated. It is expected that the ag e groups identified in this guidance will be us ed as the bas i s for future updates of EPA’s interim fina l Child-Specific Exposure Factors H andbook . Accordingly,
this docum ent highlights a num ber of areas f o r r e s earch that will add r ess f illing expo s u re f actor s data gaps. T h ese areas of further analysis and res earch are su mmarized in the appendix to the

m a in text, and it is expected that this guidance wi ll direct the design of future exposuremonitoring studies. Finally, any futu re revisions to the Agency’s 1992 Guidelines fo r Exposure
Assessment will r e f l ect the recomm endations of this RAF guidance.

xiv1. INTRO DUCTION

The recommendations contained in this docum ent are designed to provide guidance to
U.S. Environm ental Protection Agency (EPA, or th e Agency) scientists on a standard set of age groups to consider when assessing, modeling, or monitoring childhood e xposures and potential
doses to environm ental contam inants. This guidance is intended to com p lem e nt existing

exposure assessm ent guidance, principles, approach es, and tools. Since 1992, EPA ha s released other Agency-wide guidance and other tools to ai d scien tis ts in the asse ss m e nt of early-lif e exposure, including

• Food Quality Protection Act Im ple m entation (U.S. EPA, 1996).

• Exposure Factors Handbook (U.S. EPA, 1997a ). A summa ry of the available statistical data on various factors used in assessing hum a n exposure.

• Guiding Principles for Monte Carlo Analysis (U.S. EPA, 1997b). A set of principles for applying the various techniqu es for conduc tin g quantitativ e analys es o f variability and uncertainty associated with exp o sure ass e ss m e nt.

• 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 availab l e and up-to-d ate s t at istical data on various factors assessing child ren exp o sures.

• “Consolidated Hu m a n Activity Databas e” (CHAD) (http://www.epa.gov/chadnet1/). Contains data obtained from pre-existing hum an activ ity s t udies tha t were colle cted a t city, state, and national levels. CHAD is intended to be an input file for exposure/intake dose m o deling and/or statistic al analysis. It is a m a ster database providing access to other hum a n activity databases using a consistent form at.

• “Stochas tic Hum a n Exposure a nd D o se Sim u lation” (SHEDS) (http://www.epa.gov/heasd/em rb/em r b.htm )

. A modeling system being developed for analyzing multim edia multip athway exposur es of both the general and sensitiv e groups or populations, such as children and the elderly.

In 1993, the National Academ y of Sc iences (NAS) released P e sticides in the Diets o f Infants and Children (N AS, 1993), which highlighted im por tant differences between children and adults with respect to risks posed by pesticid es. Som e of the principles in the NAS report

1provided the foundation for the Food Quality Pro t ection Act of 1996 (FQPA) and Executive Order 13045, “Protection of Childre n from Environm ental Health Ri sks and Safety Risk.” One of the provisions of the FQPA requires that children’s aggregat e exposure be considered when establishing pesticide tolerances (legal lim its for residues in food). Ex ecutive Order 13045 also
broadened consideration of i m pacts on children by stating th at “each Fed e ral agency: shall
ensure th at its policie s, p r ogram s, activities, and standards add r ess disprop o rtion a te risks to
children that result from environm ental health ri sks or safety risks” (Clinton, 1997). In response
to thes e regu lato ry initia tives, EPA has been investigating ways to im prove Agency risk

assessm ents for children. An EPA workgroup, convened under the auspices of the Risk Assessm ent Forum (RAF),
concluded that a m a jor issue facing the Agency is how to consisten tly con s ider ag e- related changes in behavior and physiology when assess ing early-lifestage expos ure and potential dose.
This issue is critica l f o r s c ientists inv o lved in p r e p aring expo sure ass e ss m e nts applic able to children and for use in evaluating lifestage-inte grated lifetime exposures . Therefore, the RAF convened a technical peer involvem e nt workshop in July 2000 to consider developm ental changes when assessing exposures in children and comm issi oned 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 hum an developm ent is best treated as a continuum —physiologi cally, anatom ically, behaviorally, and for other param e ters. However, there are id entifiab l e periods of developm ent that occur in success i ve s t ages in each individu al

. Because of the inhere nt differences between each lifestag e, it is im portant to characterize expo sure as a fun c tion of lifes tage and to develop

m e thods to assess the factors contributing to these exposures. This document addresses the changes prior to adulthood; futu re docum ents m a y deal with char acteristics particular to other lifestag e s, s u ch as m a ternity and s e n e scence. Early-lifestage exposures to environm ental c ontam inants are often different from those in
late r stages of lif e for a num b er of reasons. For exam ple:

• Early-lifestage behaviors m a y contribute to higher expos ures. Physically, children are closer to the ground than are adults and theref ore live in a dustier, m o re contam inated environm ent. Young children spend tim e playing on the ground outside or on the floor indoors. Generally, child ren often spend m o r e tim e outdoors than do adults. Infants and toddlers engage in m outhing behaviors that can increase exposure to environmental contam inants. Young ch ildren are known to inadvertently and/or

2intentionally ingest significant am ounts of the soil that adheres to their hands. Children of all ages engage in risky be haviors that m a y increase exposure to environm ental agents.

• Physiologically, children’s m e tabolic rates a nd activity levels tend to be greater than those of adults. Accordingly, children consum e more water and food per unit of body weight than do adults. A ddition a lly, during th eir f i rst f e w yea r s, children consum e larger am ounts of a narrower range of specific foods than do adults. Also consistent with the i r higher m e tabolic rate s, children have higher respiratory rates on a perbody-weight basis. The greater m e tabolic rate s of children as com p ared with those of adults m a y lead to greater doses of th ose chem icals that are created by m e tabolic processes.

• The skin of infants (particularly new borns) is m o re perm eable to m a ny environm ental chem icals th an is th e skin of older ch ildren and adults. Children m a y have m o re cuts, scrapes, and rashes that would com p rom i se this barrier. Sim ilarly, the blood-brain barrier is less well developed in infants. Som e studies ind i cate that lead m a y be absorbed more efficiently from the gastro intestinal tract in very young children than in adults, although there are m a ny fa ctors aff ecting this (e.g., iron and calcium status).

• Additionally, infants and adults exhibit diffe rences in their m e tabolism and excretion of absorbed environm ental contam inants , leading to potential differences in biologically effective dose. Metabolic pathways are ge nerally less developed in infants as co mpared with those in adu lts. Depending on the specific substances involved, impaired m e tabolism m a y either in crease or decrease the toxicity of environm ental agents. T h e liver and kidneys of infants (younger than 1 year) also are less effectiv e at rem oving certain en vironm ental toxican ts f r o m the bloodstream than those of adults.

Prior to the release of its revised cancer gui delines (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 betw een subgroups that form a relatively fixed portion of the population (e.g., subgroups ba sed on ethnicity) and subgroups su ch as age groups that are potentially inclusiv e of the en tire population over tim e. Acco rdingly, following the revised cancer guidelines, this guidance views childhood as a sequence of lifes tag e s, and as such, tre a ts age subgroups of children as lifestages, not subpopulations. This guidance defines “lifestag e” as a distinguishable tim e fra m e in an individual’s life characterized by unique and relativel y stable behavioral and/or phys iological characteristics that are associated with developm ent and growth. Note that although the upper and lower bounds of lifestages may be both variable and uncertain, the age groups recomm en ded in this guidance were chosen to represent typical lifestages re levant to environm ental contam inant exposure.

3This em phasis on childhood as a sequence of lif estages has evolved from the earlier view of children as a subpopulation. For exam ple, whe n EPA released its Guid eline s for Ex posure Assessment (U.S. EPA, 1992), lifestages were considered to be c overed by the term “subgroup” and/or “subpopulation.” The 1992 guidance desc ribed the general concepts of exposure

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

assessm ent, and recommendations on presenting the results of the exposure assessm ent and characterizing uncertainty. The focus of the gui dance was on exposures in hum a ns. According to Section 5.3.5.2 of the guidelines.

It is often helpful for the ri sk assessor to describe risk by an identific ation, and if possible, ch aracterizatio n and quantification of the m a gnitude of the risk for specific highly exposed subgroups within the population. This descriptor is usef ul when there is (or is expected to be) a s ubgroup experiencing significantly di fferent exposures or doses from that of the larger populat ion. It is also helpf u l to de scribe risk by an identification, and if possib l e, characterizati on and quantification of the m a gnitude of risk for specific highly sensitive or h i ghly susceptible subgroups within the populat ion. This descriptor is useful when the sensitivity or susceptibility to the effe ct 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 th ese sub g roups, it will som e tim es 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 m a nner has been som e what elusive. Other scientific bodies, such as the
International Life Sciences In stitute, have also recommended ev aluating children’s exposure as a series of lifestages. Historically, Agency scient ists have applied expert judgm e nt 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 m outhing hands and objects duri ng early childhood). In som e cases, expert judgm ent has been applied to capture vulnerabl e periods of developm ent or critical windows when exposure to an environm ental contam inan t m a y be particularly dam a ging to a specific physiologic system (e.g., the effects of lead on he m oglobin due to age-related differences in iron deficiency). In m a ny cases, the selection of age groups has been heavily influenced by the quality and quantity of existing data to suppor t the developm ent of e xposure and potential dose
estim ates.

4The 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 indicat e use of the age groups defined here. In such cases, extrapolation of data, comb ining or splitting age groups, us e of other age groups, or other strategies may be appropriate wh en 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 us ed 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 exposu re. 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 ENVIRONMENT A L CONT AMINANT S

As noted in the introduction, in the early lifestages behavi or changes over tim e in ways
that can have an im portant im pact on exposure and potential dose. Rather than assum i ng an adult level of exposure for 70 years f o r chronic/ lifetim e risk assessm ents , incorporation of tim eweighted values for all age periods w h ere exposure is likely to occur is expected to increase the accuracy of risk assessm ents because it will tak e into accoun t lifestag e differences in exposure. Depending on whether body weight-adjusted childhood ex posures are either sm aller or larger as

com p ared with thos e for adults, p r edicted risks co uld either decreas e or in crease as compared
with assum i ng a lifetim e of adult-le vel exposure. If age-related diffe rences in toxicity were also found to occur (see U.S. EPA, 2005b), both differen ces in toxicity and exposure would need to be integ r ated for each relevant age in terval. For exam ple, crawling and mouthing of hands and objects during the 1- to <2-year period can potentially lead to de rm al and oral potential doses that are appreciably higher than those of adults in the sam e physical location, particularly indoors. Further, physiology changes over tim e 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 assessm e nt of risks from e xposure to environm ental contam inants. In July 2000, EPA held a workshop to exam ine developm ental factors and how they
influence the assessm ent of childhood exposure. Workshop participants included experts in the fields of pediatric m e dicine, t oxicology, risk assessm ent, and pub lic health. A summ a r y of the workshop discussions is provided in U.S. EPA (2000). The discus sions revealed that workshop participants preferred assessm en t approaches that could incor porate childhood developm ent as a continuous f unction. However, although rec ognizing the paucity of existing data, the participants concluded that age groupings (or bins) can be useful as guides for the developm ent of environmental exposure scenar ios. To that end, they offered som e prelim inary advice on possible age groups related to deve lopm ental change. Due to lim its in currently available data on age-specific exposure factors for ea rly lifestages, criteria used to select these age bins were often qualitative in nature. N a rrow age groups were identified where rapid developm ental changes occur, whereas m o re broad age groups were iden tif ied as th e rate of developm ent decreased. Prenatal developm ent was outside the scope of the workshop discussions, but participants
unanim ously stressed the im portance of including this lifestage in future exposure and risk

assessm ent guidance.

6Accurately sim u lating chem ical exposures of an individual conti nuously over a lifetim e would require detailed infor m ation regarding how a person’s behavior and physiology varies each day as one ages. One way exposure assesso rs can sim p lify exposure assessm ents 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 assessm e nt m odel with sufficient resolution (i.e., num ber of age bi ns) to address all signi ficant variations in lifestage exposure. This level of resolution m a y vary with the particular compound of i n terest and/or with the particular exposure scenario. The goal of this guidance is to recomm end a starting point based on our curren t understanding of differences in lifestage behavior and physiology that m a y i m pact expos ures. As our knowledge base and database develop, exposure

assesso rs will be ab le to m a ke more inf o rm ed choices abou t th e resolu ti on needed to m a ke the best public h ealth d ecisio n s. In addition, because there is a need to ba lance the added value of increased resolution against the cost of generating the necessar y exposure factor data, the age
bins recom m e nded here are designed to focus future research and data colle ction so that one can move toward a goal of conducting exposure assessm ents that address all signi ficant variations in
lif estag e

. To organize the workshop discussion, part icipants were divided into two subgroups
accord ing to their specific area s of expertise. One subgroup discussed beh a vioral developm ent and the other focused on physiology and anatom ical growth. Participants were asked to focus their discussion on those aspects of developm ent th at are particularly relevant to exposure and potential dose. These term s are defined in the E P A’s Guidelines for E x

p o sure Assessment (U.S. EPA, 1992) as

Exposure - Contact of a chem ical, physical , or biological agent with the outer boundary of an organism . Exposure is quan tified as the concentration of the agent in the m e dium [e.g., soil, water, air, f ood, etc.] in contact [with the organism], integ r ated o v er the tim e duration of that contact.

Potential Dose - The am ount of chem ical i ngested, inhaled, or in m a terial applied to the sk in.

Intern al Dos e - The am ount of chem i cal contained that has been absorbed and is available for interaction with bi olog ically significant recepto rs.

7Som e workshop participants found that the conc epts 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 assessm ent concepts of dose and effects is portrayed in Fi gure 1. Figure 1 also lists som e exam pl es of characteristics that im pact or otherwise provide an indication of expos ure, dose, and possible susceptibility to effects. These example char acteristics were discussed during the workshop.



### A

b

s o rb ed / In te r n

a

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s e 

### Ex p o s u r

e

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ect i v

e Do s e * T ime spent: Sleeping versus active; i n

door s v e rs u s ou t doors * B reathing zone * L evel of activity * M outhing behavior * B reast versus bottle feeding * F ood consumption

* H igh skin permeability

* S tomach pH
* P roportion of body fat
* L evel of extracellular fluid

* B ody weight

* H epatic enzyme function * R enal function * I mmune system function

* S keletal growth * R eproductive development * E ndocrine system changes C

h em

ical in air
, so il,

w a

t e r, food
, or o t h

e r
m

e dia in co n t act w i t h t h

e ou t e r bou n d a

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e or ga ni s m o v e r t i m e

Ab s o r p t i o n B a

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i s t r i bu t i on M

e t a

b o lis m E

x cr et io n

A

l t e re d S t ru c t u r e A

l te r e d F

u n c ti o n

Figure 1. Relationship Betw een Expo sure, Dose, and Effects in Risk Assessment.

The workshop subgroup addressing behavioral developm ent recomm ended dividing the first year of life into three groups : 0 to <3 m onths, 3 to <6 months, and 6 to <12 m onths. After the first year of life, it recommended the following groups: 12 to <24 m o nths, 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 f actors or “m ajor dom ains of behavioral developm ent” for
each rou t e o f exposure (U.S. EPA, 2000). For or al and dermal exposures, these facto r s included

gross m o tor developm ent, fine m o tor developm ent, cognitive developm ent, and social developm ent. For inhalation exposures, the rele vant factors included gross m o tor developm ent, activ ity level, and breath ing behavio r (e.g., the tr ansition from m outh to nasal breath in g). Table
2 contains som e exam pl es of the specific cons iderations supporting the age groups derived by the behavior subgroup.

Table 2. Examples of F a ctors Cons idered in Deriving Age Groups Reflecting Behavioral Development

Age Group Characteristics Relevant to Oral and Der m al Exposure Characteristics Relevant to Inhalation e x posure
Birth to <3 months Breast and bottle feeding. Hand-tom outh activities. Ti m e spent sl eeping/sedentary

.

3 to <6 m onths Solid fo od m a y be i n trod u ced. Contact with surfaces increase s. O bject/hand-tom outh activities increa se. Breathing zone close to th e floor.

6 to <12 m onths Food co nsumption ex pands . Children ’ s floor m obility increases ( s urface contact). Children are increasingly likely to m outh nonfo od items. Develop m ent of personal d u st clouds.

12 to <2 4 m onths Children cons ume full range of foods. They participate in increas ed pla y activities, are extre m ely curious, and exercise poor judgm ent. Breast and bottle feeding cease. Children walk upri ght, r u n , and cli m b. They occupy a wider variety of breathing z ones and eng a ge in

m o re vigorou s activities.

2 to <6 y ears Children begi n wearing adult-style clothing. Hand-to-m outh activities begin to m oderate. Occupancy of outdoor spaces increase s.

6 to <11 y ears There is decr eased oral co ntact with hands and objects a s well a s decrea sed der m al conta c t with surfac es. Children spend tim e in sch ool environm ents and begin pl ay in g sports.
11 to <1 6 y ears Sm oking m a y begin. The r e is an increased rat e of food cons um ption. Increas ed independence ( m ore time out of hom e). Workplace exposure can begin.
16 to <2 1 y ears High rate of food consum p tion begi ns. Independent driving begin s

. Expanded wo rk opp ortun iti es.

9The subgroup addressing anatom y/physio logical developm ent recomm ended the following groupings: birth to <1 m onth, 1 to <3 m onths, 3 to <6 m onths, 6 to <12 m o nths, 1 to <3 years, 3 to <8 (fem ale) or <9 (m ale) years, and 8 or 9 years to <16 (female) or <18 (m ale) years. The discussion that led to these age groups focused on anatom ical characteristics (e.g., weight and proportion of body fat) and specific organ and physiologi cal system s. These system s included skin, skeleton, liver, i mmune system , reproductive system , endocrine system , lung and respirato r y tract, g a strointestinal tract, circul atory system , renal system , cardiac sys t em , central nervous system , muscle, and sensor y organs. Table 3 contains som e exa m ples of the specific considerations supporting the age groups deri ved by the anatom y/physiology subgroup. The age groups listed in Table 3 were de rived largely from considering th e rate of change in the listed
characteristics.

Table 3. Examples of F a ctors Cons idered in Deriving Age Groups Reflecting Anatomical/Physiological Develop m ent

Age Gr oup An at om y/ Ph y s i o l o gy C h ar a c teri sti c s
B i rt h t o < 1 m ont h R a pi d gr o w t h and wei ght gai n

. Pr o p o r t i o n of b o d y fat i n c r eases. I n c r eas ed s k i n p e rm eab ility. Deficien cies in h e p a tic en zy me activ ity. Immatu re imm u n e syste m fun c tion s

. Hi gh o x y g e n requ irem en ts (lead in g to h i gh er inh a latio n rates). Sto m ach

m o re alkaline. Increases in e x tracellular fl u i d. R e nal f u nc t i on l e ss t h an p r edi c t e d by surface a r ea. 1 t o <3 m ont hs R a pi d gr o w t h and wei ght gai n

. Pr o p o r t i o n of b o d y fat i n c r eases. Defi ci enci es i n h e p a tic en zyme activ ity. Immatu re imm u n e syste m fun c tio n s

. High ox y g en requ irem en ts (l ead ing to h i gher inh a latio n ra tes). Stom ach m o re alkaline. Increases in ext r acellular flui d. Renal functio n less than pre d icted by surface a r ea. 3 t o <6 m ont hs R a pi d gr o w t h and wei ght gai n

. Pr o p o r t i o n of b o d y fat i n c r eases. Defi ci enci es i n h e p a tic en zyme activ ity. Immatu re imm u n e syste m fun c tio n s

. In creases in extracellular fl uid. Re nal function less t h a n pre d icted by s u rface a r ea.
6 t o <1 2 m ont hs R a pi d gr o w t h and wei ght gai n

. B o dy fat i n crease begi ns t o l e vel o ff. De fi ci enci es i n h e p a tic en zyme activ ity. Immatu re imm u n e syste m fun c tio n s . Rap i d d e crease in extracellular fl uid. Ca n begi n pred icting renal function by surface a r ea. 1 to <3 years So m e h e p a tic en zym e activ it ie s p e ak s, th en falls b ack to adu lt ran g e . M o st i m m u n e syste m fu n c tion s h a v e m a tu red

. Ex tracellu lar fl u i d b e co m e s m o re con s isten tly related to bod y size.
3 t o <8/ 9 y ears Peri o d of rel a t i v el y st abl e wei ght gai n an d sk el et al gro w t h ( a s o p pose d t o a pe ri o d

m a rked by gr o w t h s p urt s ).
8 / 9 t o <1 6 / 1 8 years Rap i d sk eletal g r o w t h . Ep iphyseal clo s ure (may tak e u n til ag e 2 0 ). Rap i d

r e pr odu ctiv e an d endo cr i n e syste m ch anges , i n cl usi v e of p ube rt y

. No te: Man y o f th e ch aracteristics listed in th i s tab l e are re pe ated across age groups (especi ally for a g es up to <12

m ont hs; e.g ., r a pi d g r o w t h an d wei g ht gai n )

. I n det e rm i n i ng t h e ra n g e of ages t o i n cl ude i n a pa rt i c ul ar age gr o u p , the rate of c h a nge in t h ese c h aracteristics was of ten a k e y facto r d i scussed at th e w o rk shop

.

10Early in the discussion of the anatomy/phys iology subgroup, the participants concluded that developm ental issues affecting exposure, pot ential dose, internal dose, and effects were too intertwined to allow an exclusive focus on potenti al dos e. Therefore, its p r elim inary advice on possible age groups reflects som e c onsideration of changes that im p act internal dose and effects.
For exam ple, this subgroup discussed the m a turity of hepatic enzym e activities (an indication of

m e tabolic function affecting internal dose) a nd the rate of reproductive developm ent (an
indication of a susceptible period for effects) in d e veloping its advice on age groups. Additional

exam ples are noted in T a ble 3. Although this subgroup’s recomm endati ons do reflect som e consideration of dose and effects issues, it should not be consid ered a co mprehensive treatm ent of this subject. The Agency is consideri ng childhood developm ent and its relationship to dose and effects through other efforts. The recommended age groups were proposed as a synthesis of the workshop

recomm endations from both the behavioral and an atom ical/physiological factors subgroups. As a result of continuing deliberati ons and reviews of available expos ure factors data, the RAF work group concluded that it m a y be necessary to further div i de th e 1 to <3 years age g r ou p. 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 disc ussions from workshop. In addition, it is supported by existing exposure fact ors inform ation (e.g., the data for m o uthing duration and frequency). The divi sion of 3 to <6 years was de em ed significant on the basis of behavioral changes occurring at or around 6 years that affect n ondietary (i.e., hand to mouth) intake and exposures due to changes in activity (e.g., initiation of school). The 6 to <11 years group captu res the relativ ely stable g r owth period after early childhood an d preced ing adolescence (the latter inducing significant behavioral, anatom i cal, and physiological changes). The work group further concluded that, in som e cases, an ad dition a l age group spann i ng 18 to <21 years could be considered. It is unclear whether this age gr oup should be considered part of the childhood lifestage or part of early adulthood. It is clear that it encompasses a period of continuing developm ent and m a y capture im portant events su ch as a chan ge in res i den ce and epiphyseal closure. Clearly factors other than age/developm enta l stage can have an im pact on exposure, including sex, geographical location, fam ily size, ethnic/cultu r al differences, seasonal variations,
and socioeconom i c status. Although these factor s could be evaluated by exposure assessors, this

11docum ent 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 R i sk A ssessment (U.S. EPA, 2003a), vulnerability to health effects resulting from exposures to envi ronm ental pollutants can vary on the basis of susceptibility, differential exposure, differential preparedness, and differential ability to recover. In conducting the hazard assessm ent portion of a risk assessm ent, the assessor should consider windows of vulnerability based on susceptibility to toxi c effects resulting from specific exposures (dose-response). In developing the exposure assessm e nt, the assessor should consider windows of vulnerability based on behaviors (crawling, m out hing) , activities (locations, product use, diet), physiological characteristics (oxyge n requirem e nts, caloric requirem e nts), and so on
that m a y lead to particularly high levels of expos ure. The analyses are combined to identify the lifestages that are at greatest risk on the ba sis of exposures and resulting effects. It is also important to note that exposure factors and resu lting developm ental stages m a y be a functio n of addition a l ind i vidual and populat ion characteristics. Thes e factors m a y be
charac ter i stics of the co mmunities in which children live an d are r a ised and includ e, as noted above, socioeconom ic status, ethnicity, cultural se tting, and geographical c onsiderations. Factors

m a y also be characteristics of the individual, including genetic susceptibility, nutritional status,
and health status. Vulnerabilities ass o ciated with individual and comm unity char acte r istics will

m a nifest as differences in susceptibility, diffe rential exposure, differential preparedness, and
dif f

e rentia l ability to rec over. The f o cus of th is guidance is specific to addressing vulnerability
associated w ith differential exposure due to life stage. Just as it is im possible to com p letely separate considerations of exposure and potential dose from c onsideration of internal dosim etry and response, so it is im possible to com p letely separate consideration of vulnerability due to
lif estag e f r om considera tion of vulne rability du e to the m a ny other s i gnif i cant ind i vid u al and community characteristics. The Agency is addressing the full range of i ssues associated with characterizing risks to children through a variety of init iatives, including development of a fram e w ork for children’s
risk assessm ent and developm ent of guidance for conducting cum u lative risk assessm e n t (U.S. EPA, 2003a ). As the Agency works to address cum u lative risk assessm ent, the full range of
vulnerab i lities will b e co nsidered m o re consisten t ly in both ex posure ass e s s m e nt and hazard

assessm ent, but thes e are not specifically add r ess e d in this guidance. In like m a nner, the Agency

12m a y be able to address fetal exposure and developm ental ef f

e cts at a f u ture date and inc l ude tha t lifestage in exposure assessm ent guidance. The focus of this guidance is to recommend ag e bins that address vulnerability resulting
from differential exposu r e. Because the focu s here is on exp o sure or po tential dose, pharm acokinetic considerations (i.e ., absorption, distribution, m e ta bolism
, and elim ination ) were not explicitly considered unle ss they had direct impacts on pote ntial dose (e.g., absorption at the portal of entry). However, it is im possible to completely separa te consideration of exposure and potential dose from cons idera tion of internal dosim etry and response. This difficulty was discussed during the workshop and is reflected in the resulting recomm ended age bins and in this
docum ent. 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. T h ese age groups should be considered initially when assessing childhood exposures to environm ental contam inants.

Table 4. Recommended Set of Childhood Age Groups for Agency Ex posure Assessments

Age Groups < 1 Year Age Groups $ 1 Year

Birth to <1 month 1 to <2 y ears 1 to <3 m onths 2 to <3 y ears 3 to <6 m onths 3 to <6 y ears 6 to <1 2 m onths 6 to <1 1 y ears 11 to <1 6 y ears 16 to <2 1 y ears

The age gro ups coverin g the firs t year of life are broken out because beh a vioral and physiological changes are occurring so rapidly during this period. During this tim e fram e , exposure m a y occur first through consum ption of hum a n (breast) m ilk or baby for m ula and, later, baby foods. Movem e nt is very lim ited at birth, but craw ling occurs during this period and first steps may also take place. Hand /object-to -mouth activities begin and then increas e rapid l y with inc r eas ing age. Ma jor deve lop m ental change s in m e tabolic pathways occur during the first
several m o nths surrounding birth. Prem ature delivery can have a m a jor physiological and

m e tabolic impact. Exposure to environm ental ch em icals during the first m onths is generally
lim ited.

13There m a y be instances f o r specific exposur e scenarios and com pounds where com b ining

som e of these age groups (e.g., com b ining the first three <1 year age groups into one

repres enting birth to <6 months ) is indicated; i. e., variation in exposure factors and resulting exposures is insignifican t. In add itio n, there m a y be instances where it is not necess a ry to address ev ery age group listed above because, for exam ple, the focus of the exposure an d risk

assessm ent m a y be on a health effect for which onl y one or two of the above groups represents a
critical window. W h ere there is a lack of exposure data for a particular age group of potential
im portance, the risk assessor should consider how this age group m i ght differ and the possible
im plications for not explicitly including the age group. It is r ecomm ende d that if age groups are split, com b ined, or exc l uded, the un derly i ng ra tionale shou ld be provided in the expo s u re

assessm ent, along with an analysis of the uncer tainty associated with these assum p tions. Given sufficient data, a scientifically based a pproach for selecting ag e groups other than
the ones recomm ended in this guidance would be to determ ine for which age groups there exist significant statistical differences in param e ter va lues. An example of one such analysis is presented in Tulve et al. (2002). In this analys is, the authors use a tree analysis to identify significant age differences in m outhing behavior . The m odel uses a recursive partitioning algorithm that successively splits the data in to homogeneous subgroups. Using this approach,
the authors identified two m a in age groups for the data that were evaluated: less than or equal to
24 m onths, and greater than 24 m ont hs. It is acknowledged here that a lack of data m a y be a cr itical impedim ent in conducting

assessm ents for each of these age b i n s and for m a king decisio n s regard ing com b ining or
elim inating age groups. In these cases, an analys is of the available data should be conducted first, and consideration given to the distribution of the data points am ong the recommended age groups. The age groups can be used unless the quan titative analysis of the data shows they do not fit within one age group. A lternatively, qualitative inform a tion m a y lead the assessor to
identif y pote n tia lly s i gnif i cant d i f f

e rences with in a recomm ended age bin. A possible approach
for estim ating exposure factors and potential dose when data are not available for a particular age bin includes the use of age-depende n t curve f i ttin g to help f i ll in the da ta gaps (see Ph illips, 1993). Any assum p tions used in assessing exposure for a particular age bin can be discussed in
the assessment. As noted above, it is recomm ended that if ag e groups are split, co m b ined, or excluded, the underlying scientific rationale be provided in the exposure asse ssm ent. It is im portant for

14exposure assessors to engage in an iterative dialogue with toxicolo gists and other health
scientists to determ ine the age groups (or portions of age groups) that will be the focus of any particular assessm ent. Furthe r, it is recomm ended that an ass e ssm ent includes splittin g,

com b ining, and/or elim inating age groups, th e exposure assessor consider the following:

• The basis (exposure and/or toxicological or risk) for determining which age groups should be sp lit, combined, and/or dr opped from the analys is and why. If the basis is exposure/dose considerati ons, what are the key fact ors driving the decision (behavioral and/or physiologica l)? If the basis is toxicol ogical, is there a key window of susceptib ility considered? If the b a sis is m i nim a l risk, des c ribe how th e exposure and toxicity considerations toge th er lead to th is c onclusion

.

• The criteria used to select par ticular age groups for assessment. These criteria m a y be quantitative or qualitative, depending on th e q u antity and quality of available data. As described m o re fully in the next s ection on implem entation, it is of param ount im portance to characterize the data, how be st to com b ine or extrapo l ate, and how such m a nipulation m a y c h ange the distribu tion (i.e., under- or overestim ate or m a sk outliers ) . An exam ple of a quantita tive cr iter ion is when data are statistica lly

com b ined across the individual ages with in the proposed age category, variability could be expressed as a coefficient of vari a tion th at is no g r ea ter than XX% f o r the key behavioral, physiological, or anatom ical param e ters that govern exposure or potential dose (see, e.g., Tulve et al., 2002) . An exam ple of a qualitative criterion is when the age range will not contain stages of developm ent that are clearly distinct from one another in term s of behavior, f ood consum ption patterns, or m a turation of physiological system s.

• The scientific uncertainties and potential biases introduced when combining or exclud ing a g e groups. There is no sim p le answer fo r the question “How different do two age ranges need to be before they ar e considered as independent age groups for exposure assessm ent? ” A difference m a y or m a y not be extrem ely i m portant, given the resulting risk estim ate. This aspect could be described in either qualitative (e.g., over- versus underestimate of e xposure) or quantita tive terms. Exam pl es of questions could include: Is an age gr oup described as less than 1 y ear more representative of 6 to <12 m onths of age than younger age groups ? How different are exposures for age groups that m i ght be combined? If data fo r one age group are used as a surrogate for another, is this likely to in crease/decrease estim a tes of e xposure? To what extent do distributions within one age group ov erlap with that of another?

• The types of data and information that, if available, would allow an analysis of whether it would be scientif ically jus tified to combine or sepa rate any o f

the recommended age groups in future exposure assessments. S u ch data could include biom onitoring data (e.g., National H ealth and Nutrition Exam ination Survey), environm ental m onitoring data, and/or expos ure factors data (suc h as those available in U.S. EPA, 2002). These discu ssions will help guide futu re data collection efforts to im prove future exposure and risk assessm ents.

153. APPLYING THE RECOMMENDED SET OF CHILDHOOD AGE GROUPS TO EXPOSURE ASS E SS MENT

This guidance provides a recomm ended set of early-life age groups fo r consideration in Agency exposure and risk assessm ents and when conducting exposure-m onitoring studies. The purpose in providing this guidance is to foster greater consiste ncy based on a sound scientific footing for program -specific assessments and resear ch initia tives f o r child re n. To further aid the

assesso r, so m e additional issu es ass o ciated with applying this guidance a r e discu ssed in this section (i.e., issues associated with application of age groupings to estim a te exposure and specify exposure scenarios). In addition, cas e studies ar e planned th a t w ill illustra te how the g u idance
docum ent can be applied in practice. These cas e studies will be posted on the Risk Assessm ent
Forum Web page (http://epa.gov/ncea/raf). When defining the assessm e nt plan or m odel, the exposure assessor, in consultation with the toxicologist, should consider how the pathways and route of e xposure, critical toxicological windows of susceptibility, and possi ble health outcom es fit into a risk assessm ent model. The scope of analysis will depend in part on whether all lif estag e s need to be e x am ined or whether exposure concerns are found to be lim ited to certain critical periods.

3.1. CONDUCTING SCREENING-LEV EL EXPO SURE ASSESSMENTS
According to EPA’s Guideline s for E x

posure Ass e ssment (U.S. EPA,1992), the purpose of a screening-level assessm e nt is typically to iden tif y pathwa ys of greatest concern and to provide a high-end and/or “bounding level” exposure estim ate to determ ine whether there are potential risks of concern that m i ght require a m o re refined analysis. To generate such estim ates, the guidelines suggest setting one or m o re sensitive variable s at the bounding level. F o r

exam ple, a screening assessm ent m i ght be base d on specific childhood lifestages where elevated exposures and/or greater sus ceptibility to the stressor of interest are anticipated. In practice, Agency program s often conduct sc reening-level assessm ents that use default

assum p tions that are selected to overestim ate risks. If the screening-level exposures to either a particular toxic agent or com b ina tion of agents are sufficiently be low reg u lato ry expo sure lev e ls for toxicity, a full risk as sessm en t is generally not warranted. Such screen ing asses s ments can allow m o re tim ely decisions and save resources fo r other actions. In m a ny such assessm ents, a single estimate that usually assum e s a com b ination of activity patterns and/or lifestages that are

16likely to produce am ong the highest exposure levels is used. As long as the exposure estim ates are des i gned to estim a te higher-than -expected ex posures and are well be low regulatory levels, no specific b i n for a lifestag e (inc luding children) need be consid ered in su ch an assessm ent.

3.2. INTEGRATING EXPOSURE AC ROSS MULTIPLE AGE GROUPS A key com p onent of this guidance is to prom ote the integ r atio n of age-spe c if ic differences in exposure (and where applicable, to xicity) when assessing long-term exposure. When assessing chronic risks, an assessor shoul d sum the exposures for all age periods when exposure is likely to occur. This approach is expected to increas e the accuracy of risk

assessm ents because it w ill take into account lifes ta ge differen ces in expos ure. Adjustm e nts for variations in toxicity (potency) m a y also need to be m a de for di fferent age groups, if such data
are available for the contam inant of c oncern. Other guidance, specific for pharm acodynam i c and pharm acokinetic differences in th e ages during which the exposure occurs, should be consulted. Depending on whether body weight-adjusted childhood ex posures are either sm aller or larger as

com p ared with thos e for adults, p r edicted risks co uld either decreas e or in c r ease as compared
with a r i sk a ssessm ent assum i ng a lif etim e of adult- leve l expo sure. If age-related differences in t oxicity were also found to occur, differences in both toxicity and exposure would need to be integrated for each relevant age interval. The com p le xity of this integ r ation will depend to a large degree on th e overlap of exposure- sp ecific and tox i city-specific age groups. For exam ple, assum e that potency (toxicity) was found to vary am ong 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-relev ant age groups. The exposure age groups are listed in the first
colum n, and the toxicity age groups are indicated by the three shaded ba nds. W h en assessing chronic risk, tim e-weighted risk (a function of exposure and t oxicity divided by the exposure duration) for each resulting age grou p would be calcu lated and then combined over the relevant
tim e fram e. Note that this exam ple represents a relatively s i mple cas e where the toxic i ty-based age groups overlap cleanly with the exposure-based age groups.

17Table 5. Integrating This Age Gro uping Guidance w i th the Supplemental Guidance for Assessin g Susceptib ility fro m Early-Life Exposure to Carcinogens That Act via a Mutag e nic Mode of Action

Exposure Age Groupings Exposure D u ration (yr) Potency Adjustment Birth to <1 month 0.08 3 10 ×

1 to <3 m onths 0.16 7 10 × 3 to <6 m onths 0.25 10 × 6 to <12 m o n t hs 0.5 10 ×

1 to <2 y ears 1 10 × 2 to <3 y ears 1 3 × 3 to <6 y ears 3 3 × 6 to <11 y ear s 5 3 × 11 to <1 6 y ears 5 3 × 16 to <2 1 y ears 5 1 × >21 y ears (21 <70) 49 1 ×

If exposure occurs only for a lim ited num b er of years (e.g., consider a fam ily that lives near a source of exposure for a 5-year period of tim e be fore moving aw ay), it is critical to

com b ine lifestage differences in exposure and dose-response for the relevant tim e interval.
Exam ple calculations are pr ovided in U.S. EPA (2005b).

3.3. ADDI TIONAL CONSIDERATIONS W H EN USING HUMAN EXPOSURE MODELS AND ALG O RITHMS IN RISK ASSESSME N TS A variety of modeling tools have been developed over the year s to facilitate exposure and
dose assessm ent as part of risk assessm ents. Som e assessors use route-specific equations to

com pute average daily dose (ADD) or lifetim e average daily dose (LADD), such as those in
EPA’s Exposure Factors Handbook (U.S. EPA, 1997a), with either determ inistic or probabilistic inputs. Others use probabilisti c time-series-based exposure mode ls, such as the aggregate and

cum u lative models developed in recent year s to address the FQPA (e.g., Calendex, CARES, Lifeline, SHEDS). These m odels simulate individuals on the basis of hum an activity
inform ation in databases such as those of the U.S. Census, the U.S. Departm e nt of Agr i culture’s Continuing Survey of Food Intake b y Individu als (CSFII), E P A’s Consolidated Human Activity Database (CHAD), or the National Hu m a n Activity Pattern Survey (NHAPS).

18There are a few probabilistic m odels fo r characterizing aggregate exposure and

cum u lative risk, and several are under development. As these m odels continue to evolve, they could be adapted to incorporate the new age grou pings into modules for sampling individuals for
a sim u lated population and for sam p l i ng values of exposure factors to be inserted into exposureroute-specific equations. Ev aluation of these age group-spec ific m odel estim a tes with
biom onitoring data would also be helpful. In the m eantim e, it is c r itica l that the expo sure

assesso r und erstand the assum p tions, structure, an d function of the specific m odel version being
used to cond uct an ass e ss m e nt. Such an understan d ing will allow the m o del outpu ts to be
inte rpre ted in light of th e recomm ended age gro ups descr i be d in this d o c u m e nt and will a llow f o r

a m o re complete characterization of uncertainties associated with the m odel param e ters used, as
well as with model struc t ure. W ith respect to applying the recommended age groupings to exposure factors used by
hum a n exposure m odels, it is im portant to understa nd how data are binned for each m o del input.
Model docum entation should clearly present how speci fic data are binned and what criteria were used to develop these bins. The goal of this guida nce is to provide an initial set of age groups for conducting exposure assessm ents and associated modeling based on our current understanding of differences in lifestage behavi or and physiology that m a y aff ect exposures. However, as
discussed ab ove, this gu idance recog n izes that th e leve l of model reso lu tion (i.e., num ber of age bins) needed m a y vary with th e particular com pound of interest and/or with the particular exposure scenario. Therefore, there m a y be instances where com b ining som e of these age

groups m a y be considered when estim a ting expos ure or po tential dose, especially if little variation in exposure m i ght be e xpected. Alternative bins m a y also be required for a specific model application or population of interes t . If s o, the sc ientif ic basis for the altern ative age bins
should be ex plicitly p r es ented. In su ch cases, it is expected th at binning m a y be diffe r ent from one exposure factor to th e next (i.e., criteria for b i nning th e diet ary d a ta w ill b e different from criteria for other, nondieta ry activity profiles). Data-specific bins used in the m odels shoul d follow the following principles: (1) bins should express representative and relevant m e trics for the range of individua ls grouped with each bin, and (2) the selected bins s hould not m a sk any truly unique pr ofile 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 sam p led from each database should be re p r esentative for each ag e group. The criteria

19chosen for such binning should be clearly articulated by the mode l developers, and the criteria rejected should be discussed also. S e lection of criteria should be tran sparent and relevant. In addition, data lim itations and the associated uncertainties need to be discussed. F o r

exam ple, were the d a ta adequate to s u fficiently investigate and identify significant differences across age groups? Available data sets m a y not allow the m odelers or the risk assessors to extract the data directly from the underlying s ources to conduct the desired age group-specific analys is. Potential app r o aches for ad dressing this issue include (1) reorga nizing the input dataset
to conform with the age groupi ngs needed, (2) using probabilistic sam p ling techniques to go beyond the categorical lim its of the underlying databa se to use all the data and then form at the probabilistic m odel output into the desired age groupings to represent exposure doses, or (3) developing a weighting schem e for the underlyi ng data set to m a ke it more aligned with the desired age groupings. For exam ple if 10% of th e observations for the 6- to 11-year-old group

com e from 6- and 7-year-olds a nd 90% com e from 10- to 11-yea r-olds, the data need to be statistically weighted so that eq ual w e ight is given to all ages within the group when estim ating the group m ean and variability statistics. It is expected that, as this guidance is applied to conduct exposure assessm e nts using the exposure modeling tools that ar e currently available or under developm ent, the recommended age groups will guid e analyses of existing expo sure facto r s data as well as the dev e lopm ent of new exposure factors research and data collection efforts.
Another im portant issue associated w ith using the age groups recomm ended in this guidance involves distinguishing between uncertainty and interi nd ividua l variab ility in an

exposure assessm ent. Uncertainty in the exposure estim a tes m a y be based on a lack of data for any of the significant exposure factors for a part icular age group or with assum p tions m a de in developm ent of the m o del structu r e. W ith early lif e stages, th e issue of in tersubje c t va riab ility
can be im portant due to rapid phys iological and behavioral change s, such that, even within a relatively narrow age gro up, variab il ity m a y be particularly large. This variability affects our understanding of the upper percentiles of exposure and risk and thus can be critical to earlylifestage risk assessm ent. Even given a high- quality, high-quantity set of data for each age group, there m a y still be significan t v a riab ility for a particular exposure factor , set of factors, o r exposure pathway. The better the data and our abili ty to characterize this variability, the better the basis for final selection of age groups for a specific assessm e nt. Data characterization should

20be im proved by EPA’s effort to update its Exposure Factors Handbooks (U.S. EPA, 1997a) to present available data for each of the recomm ended age grou pings.
For m o st exposure m o dels, exposure estim a tes can be presented in a variety of ways.
Prof iles of daily expo sur e as well as multiple -day average s , se asonal av era g es, and yea r ly

averages m a y be developed (see Figure 2). There are m odels and algorithm s that can be used to
calcu late av erage expo s u re across a season or th e highest exposure and the full distribution of

exposures w ithin a season for an age group. It is im portant to consider which exposure estim ate (m edian or higher percentile or a probabilistic an alysis) should be evaluated in an assessm ent, and the best choice m a y be age dependent. Any approach to tim e-averaging exposure should be
inform ed by a consideration of dose kinetics (e.g., absorption, distri bution, m e tabolism, and excretion) and effects (e .g., critical windows for effects, time to effect). Therefore, exposure assessors and toxicologists should w o rk closely to determ ine the m o st appropriate approach.

Figure 2. Comparison of Single-D ay Ex posure Estima tes w i th Various TimeAveraged Exposures.

21REFE RE NCES

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24GLOSSARY

Absorbed dose : the amount of a substan ce crossing a specific abso rption barrier, e.g., skin, through uptake processes.

Basal m e tabolic rate (BMR) : the m e tabolic rate under qui escent conditions, without the influence of activity, digestion, or othe r factors causing increased m e tabolism

. Breathing zone : the area around the nose and mouth fr om which air is inhaled, som e tim es described as a lim ited spherical zone extending around the nose and m outh.

Contam inant load ing : the quantity (m ass per unit surface area) of enviro nm ental con t am inant on a surface.

Derm al transfer coefficient: an em pirically defined param e ter developed to aggregate the m a s s transfer as soc i ated with a series of contacts with a conta m inated me dium . The transfer coefficient is a function of derm al exposure result ing from a particular activity and the loading of a contam inant on a surface.

Dose : the amount of a substance available for interaction with m e ta bolic processes or biologically significan t recepto rs. T h e result of an exposure to a stresso r in the env i ro nm ent, defined by the location, e.g., derm al, oral, and the transform a tion of the ag ent after crossing the outer boundary of the organism

. Endocrine system : the glands that secrete directly in to the bloodstream ; e.g., thyroid, adrenals, pituitary.
Epiphyseal closure : the tim e at which secondary bone for m ing centers, i.e., at the ends of the long bones, becom e a part of the en tire bone and cease ossification (at adu lthood).
Exposure : the interface between the or ganism and the enviro nm ent. Critical facto r s include th e source, pathway, and route (i.e ., derm al, oral, inhalation).
Exposure factors : the param e ters affecting the exposure, i.e., the interface be tween the organism and the env i ronm ent. There are phy sical, spatial, and tem poral factors, as well as the activ ity of the target organism

. Exposure scenarios : for any given pathway, a set of a ssociated exposure scenarios describes how an exposure tak e s place. This is needed to estim ate the p o tential d i stribution of ex posure by any given pathway. Exposure scenarios need to be identified to specify the values of exposure factors. An exposure scenario is def i ned by the com b ination of the following details: sources, exposed population (e.g., age or developm ental st age), tim e fr am e of exposure (e.g., acute, short term , chronic, interm ittent), lo cation of exposure (e.g., res i den ce, school, outdoors, in doors), and activity (e.g., m outhing, play ing soccer, m o wing lawns).

Internal dose : general term for the am ount absorbed without respect to specific absorption barriers or exchange boundaries.

25Lifestages : periods of developm ent that encom p ass a num be r of comm on traits or param e ters that are relatively constant. These have been broadly defined in colloquial term s, e.g., newborn, infant, toddler, preschooler, sc hool-aged, pre-adolescent, adoles cent. This docum ent defines lif estag e s on the bas i s of specif i c an atom ical and behavior al c o mm onalitie s.

Macroa ctiv ity : com p lex activities described as an entire event, e.g., showering, gardening, cooking.
Microactivity : the s i m p le activities that cons titu te m o re complex behav i ors, e.g., an infant’s mouthing behavior during indoor pl ay, in term s of num b er of hand-m outh events per unit of tim e. Mouthing behavior : hand-to-m outh and object-to-m outh contact. Varies by age and p e aks between 1 and 3 years of age. It m a y include s imple contact, licking, and insertion of fingers, hands, or objects in m o uth.

Potential do se : sim ilar to external dose, or loading; the total am ount of c ontam inant or agent contac ting the outer bou ndary or or if ice of the or ganism . The contac t ra te will af f

ect the to tal potential dose. Absorption is not cons idered, i.e., 100% absorption is assum e d.

Risk assessm e nt : a m e thod of estimating the probability of deleterious health or environm ental effects.
Variability : an expression of variation between elem ents of a data set, e.g., within a s a mple 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.

Ventila tory equivalent : the ratio of the m i nute volum e-to-oxygen uptake at body tem p erature,
am bient pressure, and w a ter vapor saturated air (unitless).

26APPE NDI X: PRELI MINARY REE VAL UATION OF EXPOSURE FACTORS DATA FOR CHILDRE N
The purpose of this appendix is to descri be the adequacy of data to support the

recomm ended age grou pings f o r children’ s expo sure and r e c o mm end areas of resear c h to f ill in the data gaps. In the “C harge to Experts” for the July 2000 workshop (see U.S. EPA, 2000a), several questions were posed to elicit discus sion on whether existing exposure inform ation is adequate to support a fine divi sion of childhood age groups. To explore this issue further, subsequent to the workshop, the Risk Assessm e n t Forum work group commissioned an expert review and reevaluation of da ta available in the d r aft Child-Specific Exposure Factors Handbook (CSEFH) (U.S. EPA, 2000b). This reevaluation of exposure factor s inform ation resulted in an issue paper titled “Age Group Recomm endati ons for Assessing Childhood Exposure and the Adequacy of Existing Exposure Factors Data for Ch ildren” (U.S. EPA, 2001a). This issue paper was prepared at the d i rection of the U.S. Environm ental Protection Agency (EPA), Risk Assessm ent Forum

. It was prepared by Versar , Inc., under E P A Contract No. 68-C99-238, Task Order 46. Mr. Steven Knott of the Risk Assess m e nt Forum served as T a sk Order Manager, providing overall direction, technical assistance, and guidance. This appendix summ a r izes and updates the results of the reevalua tion of exposure factors data discussed in the issue paper.

AUTHORS AND CONTRIBUTORS

The authors and contributors to the U

. S. EP A 2001 issue paper and this appendix (2005) are listed below.

IS S U E PA PE R
Dr. Paul Brubaker, P.E., DBAT, Vers ar, Inc./Brubaker Association, Inc.
Dr. Christine Chaisson, Chaisson Scientific Advisor, Inc.
Mr. Robert Fares, Risk Ma nagem e nt Initiative, LLC
Kathy Kelly , Technica l Editor
Dr. David Layton, Lawrence Li vermore National Laboratory
Susan Perry, W o rd Processing
Dr. Linda Phillips, Versar, Inc.
Dr. P. Barry Ryan, School of Public Health University Em or y
Dr. Edward Stanek, School of Public Health University of Massachusetts

Patricia W o od, W o rk Assignm ent Manager

27The prelim i n ary reevalu a tion of data avai lable in the draf t CS EFH was accom p lished 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 recomm endations for th e initial set of chil dhood age groups presented in Table 4 of the m a in text. In add itio n, the expe rts were asked to discus s q u ality assu ra nce issue s s u ch as those considered in selecting key studies for the CSEFH. The reques t ed quality assu rance discussion includes providing new “Confidence in Recommendations Ratings” (U.S. EPA, 2000a) for each exposure factor should it be pos sible to derive new recommendations from the existing data. The new ratings reflect a consider ation of attempting to use the existing data to address the initial set of childhood age groups. The issue paper explored whethe r ex isting ch ild -s pecific expo sure facto r s data can b e fit to the proposed EPA age groupings. The author s evaluated the followi ng exposure factors: breast m ilk intake, food intake, drinking water an d total fluid intake, soil ingestion and pica, nondietary ingestion factors, inh a lation factors, skin surface area and so il adherence to skin (derm a l), activity factors, and body weight. This issue paper provided a number of

recomm endations for short-term analyses and lo nger-term research to im prove the database for childhood exposure. A summary of the issue paper’s recom m e ndati ons for future research is presented in the sec tions that f o llow. The authors of the issue paper evaluated the da ta in the CSEFH as well as new data using the sam e characterization criteria used in the CS EFH. Although the authors of the issue paper provided new recomm e ndations on each factor f o r the recomm ended age groups, EPA is not ready to ado p t thes e reco mmendations until furt her analys es (s ee below) are conducted during the revisions to its draft CSEFH (U.S. EPA, 200 0a). However, the issue paper serves as a star ting po in t in id entif ying those ar e a s where re s earch is necessary to im prove the database to develop recomm endations for the proposed age groups. In addition to the research n eeds described in this appendix, th ere are other data gaps that cut across all pathways o f exposures. For exam pl e, accid e ntal ingestion as well as derm al and inhalation exposures from the use of consum er pr oducts m a y occur. Further data are needed on the frequency and duration of use of cons um er products by children. Methodologies to extrapolate from short-term studies to chronic ex posures are also lacking. It is im portant to note that there are e fforts underway in EPA and elsewhere that m a y produce data to address som e of these research needs. The Nati onal Children’s Study, sponsored by a consortium of Federal ag encie s , includ ing EPA, will exa m ine the ef fects of envir o nm ental influences on the health and developm ent of mor e than 100,000 ch ildren across the United States, follo w ing them from be fore birth un til age 21. In ad dition, EPA, in conjunction with National Ins titu te of Environm ental Health Scie nces (NIEHS), has funded a num ber of National Children’s Health Centers across the country to study environm enta l contributions to children’s health and disease. T a ble A-1 summarizes the av ailability of data for the proposed age bins. Recommendations for further analysis a nd research are provided below. These

recomm endations com e largely from the issu e paper but also include recommendations m a de by EPA Program Offices and Regions.

2829Table A-1. Availability of Data for the Proposed Age BinsAgeBinExposure Factor<1month1–2 months3–5 months6–11months1–2 years3–5 years6–10years11–15years16–21yearsBreast milkintake501mL/day(mean)SD andranges inTables 2-4and 2-9CSEFH716 mL/day(mean)SD andranges inTables 2-4and 2-9CSEFH797 mL/day(mean)SD andranges inTables 2-4and 2-9CSEFH680 mL/day(mean)SD andranges inTables 2-4and 2-9CSEFHNDNDNANANAFoodintakeChapter 3CSEFHChapter 3CSEFHChapter3CSEFHChapter3CSEFHChapter3CSEFHChapter3CSEFHChapter3CSEFHChapter3CSEFHChapter3CSEFHTapwaterintakeaaaTables4-3,4-5,4-7CSEFHTables4-3,4-5,4-7CSEFHTables4-3,4-5,4-7CSEFHTables4-3,4-5,4-7CSEFHTables4-3,4-5,4-7CSEFHTables4-3,4-5,4-7CSEFHSoilingestionNDNDNDNDaaaNDNDSoil ingestion(pica)NDNDNDNDNDbNDNDNDMouthingbehaviorNDNDa,ba,ba,ba,bNDNANABreathingratesaaaa6.8m3/day8.3 m3/day10m3/day13.5m3/day14.5m3/daySurfaceareaaaaaTables8-1,8-2,8-3CSEFHTables8-1,8-2,8-3CSEFHTables8-1,8-2,8-3CSEFHTables8-1,8-2,8-3CSEFHTables8-1,8-2,8-3CSEFHActivityfactorsNDNDNDNDaaaaaBodyweightTable 11-1CSEFHTable 11-1CSEFHTable 11-1CSEFHTable 11-1CSEFHTable 11-2CSEFHTable 11-2CSEFHTable 11-2CSEFHTable 11-2CSEFHTable 11-2CSEFHaData available, butreanalysis ofdata needed.bData very limited.CSEFH =Child-Specific Exposure FactorsHandbook(U.S. EPA,2002).NA =Not applicable.ND=Nodata.SD =Standarddeviation.A.1. DIETARY ROU TE OF EXPOSURE Oral ingestion exposures are typically asse ssed by considering tw o m a jor contributors: dietary exposures (from food, water, or breas t m ilk intake) and incidental or nondietary exposures (from mouthing hands an d objects or from the deliberate ingestion of nonfood item s ). The following summarizes the research needs for this route of exposure.

A.1.1. BREAST MILK INTAKE

• Collect d a ta that would a llow estim a tion of the va riab ility ( i .e., estim ation of distributions) across the populati on for m ilk intake as a function of age and/or infant weight. Studies should include consideration of the m a jor ethnic groups in the U.S. population, including Black, Asian, and Hispanic.

• Collect data that would allow estim a tion of the effect of a m o ther’s nutrient status on the f

a t/lip id con t ent of brea s t m ilk (both bef o re and d u ring lacta t ion). Data a r e needed on the types of lip ids that m a y change beca use of these variab les an d the m obility of such lip ids in the m ilk during lactation.

• The issue paper (U.S. EPA, 2001a) noted that the 6- through 11-m onth age group captures a period of rapidly decreasing breast m ilk intake. T h is observation is consistent with the July 2000 workshop discussion, whic h noted the expanding variety of foods

consum ed during this tim e period. Therefore, future breast m ilk in take data collection efforts should consider that it m a y be appr opriate to further divide the 6- through 11- month age group into two or three separate groups.

• Data are needed to determ ine the frequency of breast feeding in older infants and to provide statistical data on the likelih ood of breast feeding as the child ages.

• Data are needed to determ ine the preval ence of breast feedin g am ong wom e n and its variability as a function of age, socioeconom ic status, et hnicity. National Health and Nutrition Exam ination Survey (NHANES) data could be exam ined to study the feasibility of obtaining these data.

A.1.2. FOOD INTAK E Incorporate the analyses of the 1998 Continui ng Survey of Food Intake by Individuals (1998 CSFII) that was done by EPA’s Office of Pesticide Program s (OPP) in its Food Commodity Intake Database (FCID) to substa ntially im prove the estim ates of childhood food intake. The 1998 CSFII is a supplemental st udy that specifically targeted childhood food

consum ption patterns. Com b ining the 1998 data with the 1994–1996 data dram atically increases the num ber 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 m a y substantially im prove the estim ates of childhood w a ter intake. The 1998 CSFII is a supplem ental study that specifically targeted childhood consumption patterns. Use of the 1998 study should im prove overall conf idence in the water intake estim a tes for child ren.

30• Follow recommendation in the issue paper th at exposures from water intake be

norm a lized by body weight to the 3⁄4 power (BW 3/4 ). This recomm endation could apply equally to other exposure estim a tes (e.g., e xposure from food intake). However, a corresponding change in the approach to nor m a lizing the various m e asures of toxicity would also be needed. T h is issue needs to be explored further.

A.2. NONDIETARY INGESTIO N ROUTE OF EXPOSURE Incidental or nondietary ingestion exposure s result from the mouthing of contam inated hands and objects and from the deliberate i ngestion of nonfood item s (also know as pica behavior). Currently, two approaches to es tim ating these exposures are commonly em ployed. For ingestion of soil (whether delib erate or incidental) an estim a te of the am ount of s o il ingested is needed. F o r the ingestion of dustborne contaminants from contact with surfaces, a

m i croactivity approach, which takes into account the activities of the child, properties of the chem ical, and physical characteristics of child, is used. The following discussion addresses data on soil intake, expo sure frequency of

m i croactivities, and expo sure duratio n. Skin su rface area is addressed in the section discussing the derm al route of exposure (o b j ect surface area is cas e specific); transfer efficiencies are chem ical/m edia specific and are no t addressed in this docum ent. Contam inant loading on hands can be estimated from a m i croactivity approach to derm al exposure assessm e nt if sufficient data are available (see discussion in Section A.4).

A.2.1. SOIL INTAKE

• Collect soil ingestion data on a broader ra nge of childhood ages (e.g., 3 months to <13 years).

• Collect data that would allow estim a tion of va riability and distributi ons of intake across geographic areas, race, econom ic status, and o t h e r dem ographic variables, includ ing p i ca behavior.

• Collect d a ta that would allow the ch aracteri zation of seasonal varia tion in soil in take. These data would support the developm ent of distributional infor m ation for long-term exposures.

• Explore different ways of interpreting the ex istin g m a ss bala nce soil inta ke data ; thes e analyses could help im pr ove estim a tes in the n ear term . However, the sug g ested approach needs to be explored furt her and subjected to peer review.

• Conduct research to provide a better understa nding of the relative contribution of soil versus dust ingestion.

• Explore other m e thodologies for es tim a ting soil ingestion rates.

A.2.2. EXP O SURE F R EQUENCY AND EXP O SURE DURATION FOR DUSTBORNE AND SURF ACE CONTAMINANTS Children ’ s m i croactivity data a r e sp arse. The m a jor ity of inf o rm ation com e s f r om sm all studies, m a ny of which were designed to test m e thodologies for m onitoring m i croactivities. The lim ited data focus on the frequency and duration of m outhing hands and objects. As noted

31above, if m o uthing duration (m in/day) is used to estim ate exp o sure, then surface area needs to be presented per unit tim e (i.e., cm 2 / m in), not per event. Given the paucity of existing data, the issue paper concluded that no new m i croactivity recomm endations can be m a de at this tim e. The following recomm e ndations are m a de:

• A research program , including a comprehensiv e d a ta co llec tio n ef f

o rt, is needed to im prove estim a tes of m i croactivities fo r nondietary exposure assessm ent. Existing studies are sm all and include a variety of m e thodologies.

• System atic, probability -based stud ies should be undertak en that address a broad rang e of childhood age groups (at least to <6 years of age).

A.3. INHALATION ROUTE OF EXPOSURE The following discussion addresses i nhalation rates and the tim e spent in

m i croenviro nm ents. Note tha t the tim e spent in m i croenvironm ents is also used in som e derm al exposure models. Therefore, th e section on the derm al route of exposure refers back to the discussion provided in this section.

A.3.1. INHALATION RATE The issue paper (U.S. EPA, 2001a) indicat ed that existing data do not support

recomm endations for ch ildren les s th an 3 years o f age due to the lack of ventilatory equivalent data for these ages. Further, although the existing data m a y support a recomm endation for children aged 3 to <6 years, th e issu e paper no tes that the da ta are very lim ited. However, ventilatory rates m a y be derived using energy ex penditu res incorpora ting the la tes t USDA CSFII 1994–96 and 98 data. T h e paucity of data for young ch ildren is a particularly im portant source of uncertainty, given that the lim ited data (and the current unde rstanding of childhood physiology) suggest th at ventilato r y equivale n t s w ill b e higher for these age groups. The existing data do support recomm endat i ons for groupi ng children aged 6 to <11 years, 11 to <16 years, and 16 to <18 years. The issue paper autho r s who reevalu a ted th e inha lation ra te es tim ates reco mmended several areas of further analysis and research.

• First, the m o re recent CS FII data can be analyzed further to obtain food energy intake/energy expenditures for the entire initial se t of childhood age groups.

• For short-term, activity-specific inhalation ra te estim a tes, 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-spe c if ic inha la tion rate estim ates could also be developed using the Layton (1993) approach as m o dified by McCurdy (2000). Specifically, inhalation is calculated in the m a nner described above, but energy e xpenditure is estim a ted using a factorial approach in which an indivi dual’s activities are assigned en ergy expenditure values based

on a m u ltiplier of basal m e tabolic ra te ( t erm e d a MET). Daily estim ates of energy expenditures derived from this m e thod could be com p ared with estim ates derived from the CSFII to lend ins i ght into qua lity assuranc e is sues.

32• Finally, a critical area of resear ch ( e s p ecia lly f o r child ren le ss than 6 years of age) is the search or collection of ventilatory equivale nt (the ratio of the m i nute volume to oxygen uptake at body tem p erature, am bient pressure , and water vapor saturated air [unitless] ) data for children. These data m a y already be available from r e search in pharm acology. Any new data collection efforts should cons ider susceptible populations, such as asthm a tic ch ildr e n.

A.3.2. TIME SPENT I N MICROENVI RONM ENTS P URSUING MACROACTIVITI ES Children’s exposures in relation to activ ities are generally ca ptured as either macroactiv ities , e.g., playing a gam e of baseball, or microactivities , e.g., touching hand to m outh 10 tim es in 1 hour, the latter tak i ng place within a microenvironment , or specific space. Given the pauc ity of existing d a ta, th e issue paper authors concluded that new recomm endat i ons for children less than 1 year of age and 11 years of age and olde r cannot be m a de. Re fe rring to Hubal et al. (2000), the authors st ate that “the current database on children’s m a croactivities is sparse and data are insuf f icient to adequately assess exposures to environm ental contam inants. However, the results of the Hubal et al. (2000) evaluation of CHAD data for children less than 12 years of age are sufficient to prov ide reco mmendations for tim e in m i croenvironments and participa tion in cer tain m acroac tiv itie s f o r childr e n 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 res e arch.

• Develop m e thods for m o nitoring child ren’s activities and exposures.

• Collect population-based data on children’ s activities and exposures to allow characterization as a function of age, gender, environm ental setting (m icroenvironm ent), socioecono m i c status, race/ethnicity , geogra phic location, an d season. In particular, focus on young children (less than 4 years of ag e) and children aged 11 years and older.

A.4. DERMAL ROUTE OF EXPOSURE For derm al exposures to contam inants in soil, data on body surface area in contact with the contam i n ated soil, soil adherence data, and exposure frequency for each m i croactivity are needed. Overall, experts agree that th e assessm e nt of der m al exposures is an area that is ripe for research. T h e prelim inary reevaluation for dermal exposure factors focuse d on two factors in the equation for estim ating d e rm al exposure to con t am inants in soil: total skin surface an d soil adherence to skin. Surface area is d i scussed belo w in Section A.4.1. The issue paper expert providing the prelim inary reevalua tion concluded that soil adheren ce to skin is m o re closely related to activity than to age. Theref ore, no fu rther reevaluation was provided for this factor. Data on the frequency of m acr oactivities are sp arse. Resear c h in the f o llowing areas is

recomm ended.

• Data on the frequency of m acr oactivities are need ed. Most studies have f o cused on the duration of such activities (e.g., m i n/day) as opposed to the number of times the activities are performed each day. Exceptions include the frequency of sw imming and showering events.

33• More data are needed for the develop m ent of der m al transfer coefficients. EPA’s OPP has proposed an interim value of 5,200 cm 2 /hour for short-term exposure for children playing outdoors on law n s and indoors on car peted or hard flooring (U.S. EPA, 1997, 2001b).

• The m acroactiv ity app r o ach would benefit greatly from further research providing activ ity - and surface-specific derm al transfer coefficients for children. The prelim inary reevaluation did not include a review of this factor.

• As with the m acroactivity approach, few data exist to support the use of the m i croactivity approach to estim ating d e rm al exposures fr om contam inated surfaces. Mo st of the available studies focus on the frequency of m outhing events in childre n. For this sp ec if ic

m i croactivity and others (e.g., specific body pa rt contacts with surfaces) the data are extrem ely s p arse.

• Data on the area of surface th at is co ntacted during a m i croactiv ity even t are virtually nonexistent. As noted above in Secti on A.2.2, a system atic, com p rehensive data collection effort is needed to support these e xposure factors. The re m a ining factors in the

m i croactivity derm al exposure equati on are chem ical/m edia specific.

For the estim a tion of de rm al exposure from contact with contam inated water, skin surface area is addressed in the s ectio n that follow s . For estimating ab sorb ed dose, con s ult th e Superfund derm al guidance (U.S. EPA, 2004) for a com p lete discussion. One com p onent used in determ ining tim e spent bathing, showering, or swimming is discussed above in Section A.3.2. As noted above for estim a ting dermal exposure to soil, data on the freque ncy of m acroactivities were not in cluded in the prelim inary reevaluati on . Surface area exposed in these scen arios is highly dependent on the activity.

A.4.1. SKIN SURFACE AREA The expert p r oviding the prelim inary reevalua tion of skin surface area data reviewed the

sam e 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 recomm endations for estim ates of skin surface area for the in itial childhood ag e groups 2 years of age and older (EP A used the NHANES II data for children >2 years of age in th e draft CSEFH).

• For further analysis and research on s k in su rface area, th e expert recomm ended collecting new height and weight data for childr en less than 2 years of age.

• Further, although this expert concluded that dermal soil adherence is m o re activity specific than age specific and, therefore, deferred to the activity-specific

recomm endations of the draft CSEFH, the expert recomm ended that m o re detailed studies of derm al soil adherence be conducte d to determ ine variations among individuals and the effects of duration of activity, clothi ng use, and tim e of year on this factor.

34• In addition, im plicit in the expert’s review is the need to update skin su rface area estim ates for children 2 years of age and older using the newer NHANE S 99 plus data for height and weight.
The analyses should support the recomme nded initial set of childhood age groups provided in Table 4 of the m a in text.

A.5. HUMAN BODY WEIGHT Hum a n body weight is used to norm a lize daily exposure estim ates in the calculation of daily potential doses. For dietary exposures, the studies used to derive intake rates for food and water (nam e l y the CSFII 1994–96 and 1998 studies) include body weight infor m ation for each individual surveyed. Therefor e, the food and wa ter intake fo r a specific individual can be

norm a lized by the body weight for that individual to yield intake rates in un its of g/kg-day. For breast m ilk intake, nondietary ingestion exposures , inhalation exposures, and derm al exposures, such concurrent collection of body weight inform ation is absent from the relevant exposure factors data. Typically, these exposures will be norm alized by body weight inform ation from other sources, such as average body weight es tim a tes for the general U.S. population derived fro m data available in the NHANES studies. Th e following discussion conveys the results of the prelim inary reevaluation of hu m a n body weight data for the in itial set of childhood age groups. The expert providing the prelim inary reeval uation of body weight data for children highlighted several areas for furt her analysis of existing data.

• Further statistical analysis of the NHANES 99 pl us data will allow the derivation of multiple p e rcentiles and distributional info rm ation for the initial s e t of age groups.

• In addition to the relationship between ag e and weight, the existing data should be analyzed for other relationships (e.g., age and stature, body mass index) to develop a

more com p l e te understanding of body m e trics th at m a y have a bearing on exposures and risks.

• The NHANES 99 plus data should be analyzed further to develop body weight estim ates that are specific for selected ethnic groups.

35APPE NDI X REF E RE NCES

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