1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 TABLE OF CONTENTS

1. INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-1 1.1 BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-1 1.2 PURPOSE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-4 1.3 INTENDED AUDIENCE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-5 1.4 SELECTION OF STUDIES FOR THE HANDBOOK . . . . . . . . . . . . . . . . . . . 1-5 1.5 APPROACH USED TO DEVELOP RECOMMENDATIONS FOR EXPOSURE FACTORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-8 1.6 CHARACTERIZING VARIABILITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-11 1.7 USING THE HANDBOOK IN AN EXPOSURE ASSESSMENT . . . . . . . . . 1-12 1.8 THE USE OF AGE GROUPINGS WHEN ASSESSING EXPOSURE . . . . . 1-14 1.9 CONSIDERING LIFESTAGE WHEN CALCULATING EXPOSURE AND RISK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-16 1.10 GENERAL EQUATIONS FOR CALCULATING DOSE . . . . . . . . . . . . . . . 1-17 1.11 CUMULATIVE RISK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-2 1 1.12 RESEARCH NEEDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-22 1.13 ORGANIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-23 1.14 REFERENCES FOR CHAPTER 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-251 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 LIST OF TABLES Table 1-1. Considerations Used to Rate Confidence in Recommended Values . . . . . . . . . . . 1-2 8 Table 1-2. Summary of Exposure Factor References and Confidence Ratings . . . . . . . . . . . 1

- 30 Table 1-3. Characterization of Variability in Exposure Factors . . . . . . . . . . . . . . . . . . . . . . . 1-3 1 Table 1-4. Integrating EPA’s Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants with EPA’s Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens For Those Contaminants Which Act Via a Mutagenic Mode of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-3 2

LIST OF FIGURES Figure 1-1. Schematic of Dose and Exposure: Oral Route . . . . . . . . . . . . . . . . . . . . . . . . . . 1

- 331 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 

### 1. INTRODUCTION

1.1 BACKGROUND In 1993, the National Academ y of Sciences (NAS) released Pesticides in the Diets of Infants and Children (NAS, 1993), which highlight ed that im portant differences can exist between children and adults with respect to ri sks posed by pesticides. Because of physiological and behavioral differences, exposures am ong childre n are expected to be significantly different than exposures am ong adults. Children m a y be m o re exposed to som e environm ental toxicants because they consum e m o re food and water per unit of body weight and have a higher ratio of surface area to volum e than adults. Equally im portant, rapid changes in behavior and physiology during childhood m a y lead to differences in exposure during childhood as a child grows up. In 1995, EPA established a policy “to consider the risks to infants and children consistently and explicitly as a part of risk assessm ents generated during its decision m a king process, including the setting of standards to protect public health and the environm ent”(U.S. EPA 1995) . Recognizing that exposures am ong infants, toddlers, adolescents, and teenagers can vary significantly, the U.S. Environm ental Protection Agency (EPA) recently published its “ Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants (U.S. EPA. 2005a).” This update and revision of the 2002 interim final Child-specific Exposure Factors Handbook (U.S. EPA, 2002) is designed specifically to

com p lem e nt EPA’s recom m e nded set of childhood age groups:

< Less than 12 m onths old: birth to <1 m onth, 1 to <3 m onths, 3 to <6 m onths, 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.
Many studies have shown that young children can be exposed to various contam inants, including pesticides, during norm a l oral explora tion of their environm ent (i.e., hand-to-m outh behavior) by touching floors, surfaces, and obj ects such as toys (Eskenazi et al., 1999, Gurunathan et al., 1998, Lewis et al., 1999, Nishi oka et al., 1999). Dust and tracked-in soil

accum u lates m o st effectively in carpets, where young children spend significant am ount of tim e (Lewis et al., 1999). Children living in agricultural areas m a y experience higher exposures to

1-11 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 pesticides than do other children. Pesticides m a y be tracked into their hom es by fam ily m e m b ers. In addition, children living in agricultural areas m a y also play in nearby fields or be exposed via

consum ption of contam inated breast m ilk from their farm worker m o ther (Eskenazi et al., 1999). In term s of risk, children m a y also dif f

e r f r om adults in their vulnerability to environm ental pollutants because of toxicodynam i c differences (for exam ple, when exposures occur during periods of enhanced periods of susceptibility) and/or toxicokinetic dif f

e rences (i.e., differences in absorption, excretion, and m e tabolism ) (U.S. EPA, 2000c). Toxic contam inants in the environm ent can cause neurodevelopm ental disabilities. The developing brain and nervous system can be particularly sensitive to environm ental contam inants. For exam ple, elevated blood lead levels and prenatal exposures to even relatively low levels of lead result in behavior disorders and reductions of intellectual function. Exposure to high levels of m e thylm e rcury can result in developm ental disabilities (Myers and Davidson, 2000). Other authors have described the im portance of exposure tim ing (i.e., preconceptional, prenatal, and postnatal) and how it affects the outcom e s observed (Selevan et al., 2000). W ith respect to contam inants which are carcinogenic via a m u tagenic m ode of action, EPA has found that childhood is a particularly sensitive period of developm ent in which cancer potencies per year of exposure can be an order of m a gnitude higher than during adulthood (U.S. EPA, 2005c). Executive Order 13045: Protection of Children from Environmental Health Risks and Safety Risks , signed in 1997, requires all federal agencies to address health and safety risks to children, to coordinate research priorities on children’s health, and to ensure that their standards take into account special risks to children (EO, 1997). To help im plem ent the Order, EPA established the Of f i ce of Children’s Health Prot ection (OCHP) [renam ed the Office of Children’s Health Protection and Environm ental Educati on (OCHPEE) in 2005], whose job it is to work with Program and Regional offices within EPA to prom ote a safe and healthy environm ent for children by ensuring that all regulations, standards, policies, and risk assessm ents take into account risks to children. Legislation, such as the Food Quality Protection Act and the Safe Drinking W a ter Act am endm ents, have m a de coverage of children’s health issues m o re explicit, and research on children’s health issues is continually expanding. As a result of the em phasis on children’s risk, ORD developed a Strategy for Research on Environm ental Risks to Children (EPA, 2000c). The goal of this research strategy was to im prove the quality of risk assessm ents

1-21 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 f o r children. This Child-specific Exposure Factors Handbook is further intended to support EPA’s efforts to im prove exposure and risk assessm ents for children (U.S. EPA 2002). In 1997, EPA/ORD/NCEA published the Exposure Factors Handbook (U.S. EPA, 1997a). The handbook includes exposure factors and related data on both adults and children. OCHP’s child-related risk assessm ent policy and m e thodology guidance docum ent survey (U.S. EPA, 1999a) highlighted the Exposure Factors Handbook as a source of inform ation on exposure factors for children. EPA’s Children’s Environmental Health Yearbook (U.S. EPA, 1998) also lists the Exposure Factors Handbook as a source of exposure inform ation for children. However, the EPA Program Offices identified the need to consolidate all children’s exposure data into a single docum ent. The goal of this Child-specific Exposure Factors Handbook is to f u lf ill this need. This Handbook provides non-chem ical-specific data on exposure factors that can be used to assess doses from dietary and non-dietary inges tion exposure, derm al exposure, and inhalation exposure am ong children. This handbook provides generic exposure factors data for the EPA recom m e nded set of childhood age groups in the following areas:

C breast m ilk ingestion;

C food ingestion, including hom egrown foods and other dietary-related data;

C drinking water ingestion;

C soil ingestion;

C hand-to-m outh and object-to-m outh activity;

C derm al exposure factors such as surface areas and soil adherence;

C inhalation rates;

C activity duration and frequency in different locations and various

m i croenvironm ents;

C duration and frequency of consum er product use;

C body weight data; and

C duration of lifetim e. It is a com p ilation of available data from a variety of sources. Most of these data have been described in detail in EPA’s Exposure Factors Handbook (1997a), but data published after the release of the Exposure Factors Handbook are also included here. This latest handbook updates the 2002 interim final Child-Specific Exposure Factors Handbook (U.S. EPA, 2002).

1-31 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 W ith very few exceptions, the data presented here derive from the analyses of the individual study authors. Because the studies included here vary in term s of their objectives, design, scope, presentation of results, etc., the level of detail, statistics, and term inology m a y vary from study to study and from factor to factor. For exam ple, som e authors used geom etric m eans to present their results, while others used arithm e tic m eans or distributions. EPA m a de every attem p t to clearly label the statistics presented. Authors have som e tim es used different age ranges to describe data for children; in m o st cases, the original data are unavailable and the study results cannot be reallocated into the age groups used in this handbook. Every effort has been m a de to reallocate source data into the age groups recom m e nded by the EPA in the report entitled Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants (U.S. EPA, 2005a), when sufficiently detailed data are available. W ithin the constraint of presenting the original m a terial as accurately as possible, EPA has m a de an effort to present discussions and results in a consistent m a nner. The strengths and lim itations of each study are discussed to provide the reader with a better understanding of the uncertainties associated with the values derived from the study. Because of the large num ber of tables in this handbook, tables are presented at the end of each chapter, before the appendices, if any. In conjunction with the Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants , this handbook is adopting the age group notation “X to < Y” (e.g., the age group 3 to < 6 years is

m eant to span a 3-year tim e interval f r om a child’s 3rd birthday up until the day bef o re his or her 6th birthday).



### 1.2 PURPOSE The purpose of this update and revision of the Child-specific Exposure Factors Handbook is to (1) m o st im portantly, com p lem e nt EPA' s new set of recom m e nded childhood age groups, as noted above, including a standardized wa y to define specific age groups (X to < Y); (2) to highlight changes in risk assessm ent practice first presented in the EPA’s Cancer Guidelines regarding the need to consider children as lifestages rather than as subpopulations (U.S. EPA, 2005b); (3) em phasize a m a jor recom m e ndation in EPA’s Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens (U.S. EPA, 2005c) to sum exposures and risks across lifestages rather than relying on the use of a lifetim e average adult

1-41 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 exposure to calculate risk; and lastly, (4) to incorporate any new exposure factors data/research that have becom e available since the early 2000' s. As with the earlier version of the handbook, this new version will sum m a rize key data on hum an behaviors and characteristics which affect children’s exposure to environm ental contam inants, and provide recom m e nded values to use for these factors. These

recom m e ndations are not legally binding on any EPA program and should be interpreted as suggestions that Program Offices or individual exposure assessors can consider and m odify as needed. The decision as to whether to use site-specific or national values for an assessm ent m a y depend on the quality of the com p eting data sets as well as on the purpose of the specif ic

assessm ent. The handbook has strived to include discussions of the issues which assessors should consider in assessing exposure am ong children of different ages, and m a y be used in conjunction with the EPA docum ent entitled Socio-demographic Data Used for Identifying Potentially Highly Exposed Populations (U.S. EPA, 1999b)

. This handbook is intended to be a continuously evolving docum ent. Updates will be posted in the NCEA hom e page as new data becom e available.



### 1.3 INTENDED AUDIENCE The Child-Specific Exposure Factors Handbook m a y be used by exposure and risk assessors, econom ists, and other interested parties as a source for data and/or EPA

recom m e ndations on num eric estim ates for behavioral and physiological characteristics needed to estim ate childhood exposure to toxic contam inants.



### 1.4 SELECTION OF STUDIES FOR THE HANDBOOK The data presented in this handbook have been com p iled from various sources, which include EPA’s Exposure Factors Handbook (U.S. EPA, 1997a), governm e nt reports, and inf o rm ation presented in the peer-reviewed scientif ic literature. Studies were chosen that were seen as useful and appropriate for estim ating exposure factors. The handbook contains

sum m a ries of selected studies published through June 2006.

1-51 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 General Considerations Many scientific studies were reviewed for possible inclusion in this handbook. Generally, studies identif ied in the Exposure Factors Handbook (U.S. EPA, 1997a) as key studies were also included, as are new studies that becam e available after publication of the 2002 Child-Specific Exposure Factors Handbook (U.S. EPA, 2002). Key studies from the Exposure Factors Handbook were generally defined as the m o st useful for deriving exposure factors. The

recom m e nded values for m o st exposure factors are based on the results of these studies. As in the Exposure Factors Handbook, the key studies were selected based on the following considerations:

C Level of peer review : Studies were selected predom inantly fromthe peerreviewed literature and final governm e nt reports. Internal or interim reports were therefore avoided.

C Accessibility : Studies were preferred that the user could access in their entirety if needed.

C Reproducibility : Studies were sought that contained sufficient inform ation so that

m e thods could be reproduced, or at least so the details of the author’s work could be accessed and evaluated.

C Focus on exposure factor of interest : Studies were chosen that directly address the exposure factor of interest or address related factors that have significance for the factor under consideration. As an exam ple of the latter case, one selected study contains useful ancillary inform ation concerning fat content in fish, although it does not directly address fish consum ption.

C Pertinence of data to the U.S. : Studies were selected that addressed the U.S. population. Data from populations outside the U.S. were som e tim es included if U.S. data were lim ited for a specific exposure factor. Studies sim ilar in

m e thodology are also used to support or enhance the U.S. data.

1-61 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 C Primary data : Studies were deem ed preferable if based on prim ary data, but studies based on secondary sources were also included when they offered an original analysis. For exam ple, the handbook cites studies of food consum ption based on original data collected by the U. S. Departm e nt of Agriculture (USDA) National Food Consum ption Survey.

C Currency of information : Studies were chosen only if they were sufficiently recent to represent current exposure conditions. This is an im portant consideration for those factors that change with tim e. In som e instances, recent data were very lim ited. Therefore, the data provided in these instances were the only available data. Lim itations as to the age of the data were noted.

C Adequacy of data collection period : Because m o st users of the handbook are prim arily addressing chronic exposures, studies were sought that utilized the m o st appropriate data collection techniques for the characterization of long-term behavior.

C Validity of approach : Studies that used experim e ntal procedures or approaches that m o re likely or closely capture the desired m easurem ent were selected. In general, direct exposure data collection techniques, such as direct observation, personal m onitoring devices, or other known m e thods were preferred where available. If studies utilizing direct m easurem ent were not available, studies were selected that rely on validated indirect m easurem ent m e thods such as surrogate

m easures (e.g., heart rate for inhalation rate) and questionnaires. If questionnaires or surveys were used, proper design and procedures include an adequate sam p le size for the population under consideration, a response rate large enough to avoid biases, and avoidance of bias in the design of the instrum e nt and interpretation of the results.

C Representativeness of the population : Studies seeking to characterize the national population, a particular region, or sub-population were selected if they were

1-71 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 appropriately representative of that population. Studies with lim itations in areas where little data exist were included and are noted as such.

C Variability in the population : Studies were sought that characterized any variability within populations (e.g., variability due to age, gender, ethnicity).

C Minimal (or defined) bias in study design : Studies were sought that were designed with m i nim a l bias, or if biases were suspected to be present, the direction of the bias (i.e., an overestim ate or underestim ate of the param e ter) is either stated or apparent from the study design.

C Minimal ( o r defined) uncertainty in the data : Studies were sought that have

m i nim a l uncertainty in the data, which was judged by evaluating all the considerations listed above. Studies that identify uncertainties, such as those due to inherent variability in environm ental and exposure-related param e ters or possible m easurem ent error, were pref erred. Studies that docum ent quality assurance/quality control m easures were also pref erred.



### 1.5 APPROACH USED TO DEVELOP RECOMMENDATIONS FOR EXPOSURE FACTORS As discussed above, EPA first reviewed all literature pertaining to a factor and determ ined key studies. These key studies were used to derive recom m e ndations for the values of each factor for each of the childhood age groups discussed earlier. The recom m e nded values were derived solely from EPA’s interpretation of the available data. Different values m a y be appropriate for the user in consideration of policy, precedent, strategy, or other factors such as site-specific inform ation. EPA’s procedure for developing recom m e ndations was as follows:

1. Key studies were evaluated in term s of both quality and relevance to specific populations (general U. S. population, age groups, gender, etc.). The criteria for assessing the quality of studies are described in Section 1.4.

1-81 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 2. If only one study was classified as key for a particular factor, the m e an value from that study was selected as the recom m e nded central tendency value for that population. If

m u ltiple key studies with reasonably equal quality, relevance, and study design inform ation were available, a weighted m ean (if appropriate, considering sam p le size and other statistical factors) of the studies was chosen as the recom m e nded m e an value. If the key studies were judged to be unequal in quality, relevance, or study design, the range of m eans is presented and the user of this handbook m u st em ploy judgm ent in selecting the m o st appropriate value for the lifestage or local population of interest.

3. The variability of the f actor across the lif estage was discussed. This docum ent attem p ts to characterize the variability of each of the factors. Variability refers to true heterogeneity or diversity in a population. Differences am ong individuals in a population are ref e rred to as inter-individual variability, dif f

e rences f o r one individual over tim e is ref e rred to as intra-individual variability. Since m o st of the studies used to derive exposure factors data are short term in nature, they present the variability in short term exposures across a population sam p le and often do not allow analysis of either intertem poral variability within individuals nor inter-individual variability of long term average exposures. Inter-individual variability in this handbook is characterized in one

or m o re of the f o llowing ways: (1) as a table with various percentiles or ranges of values; (2) as analytical distributions with specif i ed param e ters; and/or (3) as a qualitative discussion.

4. Uncertainties were discussed in term s of data lim itations, the range of circum stances over which the estim ates were (or were not) applicable, possible biases in the values them selves, a statem ent about param e ter uncertainties (m easurem ent error, sam p ling error) and m odel or scenario uncertainties if m odels or scenarios were used to derive the

recom m e nded value.

5. Finally, EPA assigned a confidence rating of low, m e dium or high to each recom m e nded value. This rating is not intended to represent an uncertainty analysis; rather, it represents EPA’s judgm ent on the quality of the underlying data used to derive the recom m e ndation.

1-91 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 This judgm ent was m a de using the guidelines shown in Table 1-1. Table 1-1 is an adaptation of the General Considerations discussed in Section 1.4. Clearly this is a continuum from low to high, and judgm ent was used to determ ine these ratings. Recom m e ndations given in this handbook are accom p anied by a discussion of the rationale f o r their qualitative rating.

Table 1-2 sum m a rizes the principal exposure factors addressed in this Handbook and identifies the key tables that the reader m a y refer to when searching for a specific exposure factor. It is im portant to note that the study elem ents listed in Table 1-1 do not have the sam e weight when arriving at the overall confidence rating for the various exposure factors. The relative weight of each of these elem ents depend on the exposure factor of interest. Also, the relative weights given to the elem ents for the various factors were subjective and based on the professional judgem e nt of the authors of this handbook. In general, m o st studies would rank high with regard to "level of peer review," "acce ssibility," "focus on the factor of interest," and "data pertinent to the U.S." These elem ents are im portant considerations for inclusion of a study in this handbook. However, a high score of these elem ents does not necessarily translate into a high overall score. Other elem ents in Table 1-1 were also exam ined to determ ine the overall score. For exam ple, the adequacy of the data collection period m a y be m o re im portant when determ ining usual intake of foods in a population; on the other hand, it is not as im portant for factors where long-term variability m a y be sm all, such as tapwater intake. In the case of tapwater intake, the currency of the data was a critical elem ent in determ ining the final rating. In addition, som e exposure factors

are m o re easily m easured than others. For exam ple, soil ingestion by children is estim ated by

m easuring, in the feces of children, the levels of certain elem ents found in soil. Body weight, however, can be m easured directly, and it is therefore a m o re reliable m easurem ent. The fact that soil ingestion is m o re difficult to m easure than body weight is reflected in the confidence rating given to both of these factors. In general, the better the m e thodology used to m easure the exposure factor, the higher the confidence in the value.

1-101 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 

### 1.6 CHARACTERIZ ING VARIABILITY AND UNCERTAINTY It is critical to note the distinction between uncertainty and variability. Uncertainty reflects our inability to be sure about the true valu e of a factor. Variability refers to the fact that children are not exactly alike - thus, for any given age, they m a y be different in term s of their weight, their behavior, what they like to eat and how m u ch they eat, etc. These differences are im portant for exposure and risk assessors, as well as risk m a nagers, to take into account if the range of exposures and risks faced by children are to be understood. For exam ple, if one were to consider acute risks to US children under the age of 18 (about 73 m illion in 2005 - U.S. Census Bureau, the upper 99 th percentile, while at the upper reaches of the range of variability, still accounts for 730,000 children on any given day - this m a y be im portant inform ation for an exposure assessor to share with a risk m a nager. This docum ent characterizes variability of each of

the f actors. Variability is characterized in one or m o re of the f o llowing ways: (1) as a table with various percentiles or ranges of values; (2) as analytical distributions with specif i ed param e ters; and/or (3) as a qualitative discussion. Analyses to fit standard or param e tric distributions (e.g., norm a l, lognorm a l) to the exposure data have not been perform e d by the authors of this handbook, but have been reproduced as they were found in the literature. Recom m e ndations on the use of these distributions are m a de where appropriate based on the adequacy of the supporting data. The list of exposure factors and the way in which variability has been characterized throughout this handbook (i.e., average, m e dian, upper percentiles,

m u ltiple percentiles, fitted distribution) are presented in Table 1-3. The term “upper percentile” is used throughout this handbook, and it is intended to represent values in the upper tail (i.e., between 90th and 99.9th percentile) of the distributi on of values for a particular exposure factor. A detailed presentation on variability and uncertainty for exposure factors and algorithm s used in estim ating exposure is presented in EPA’s Exposure Factors Handbook (U.S. EPA, 1997a). In the recom m e ndations, an attem p t was m a de to present percentile values that are consistent with the exposure estim ators defined in Guidelines for Exposure Assessment (U.S. EPA, 1992a) (i.e., m ean, 50th, 90th, 95th, 98th, and 99.9th percentile). However, this was not always possible, because the data available were lim ited for som e factors, or the authors of the study did not provide such inform ation It is im portant to note, however, that these percentiles were discussed in the guidelines within the context of risk descriptors and not individual exposure factors. For exam ple, the guidelines state that the assessor m a y derive a high-end

1-111 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 estim ate of exposure by using m a xim u m or near m a xim u m values for one or m o re sensitive exposure factors, leaving others at their m ean value. The use of probabilistic analysis such as Monte Carlo requires a selection of distributions or histogram s for the input param e ters. This handbook is not intended to provide com p lete guidance on the use of probabilistic analyses. There are ef f

o rts in the Agency and elsewhere aim e d at providing guidance on the use of these techniques.



### 1.7 USING THE HANDBOOK IN AN EXPOSURE ASSESSMENT Som e of the steps for perform i ng an exposure assessm ent are (1) determ ining the pathways of exposure; (2) identifying the environm ental m e dia which transports the contam inant; (3) determ ining the contam inant concentration; (4) determ ining the exposure tim e, frequency, and duration; and (5) identifying the exposed populations and lifestages. Many of the issues related to characterizing exposure from selected exposure pathways have been addressed in a num ber of existing EPA guidance docum ents. These include, but are not lim ited to the f

o llowing:

C Guidelines for Exposure Assessment (U.S. EPA, 1992a);

C Dermal Exposure Assessment: Principles and Applications (U.S. EPA, 1992b);

C Methodology for Assessing Health Risks Associated with Indirect Exposure to Combustor Emissions (U.S. EPA, 1990);

C Risk Assessment Guidance for Superfund, Part A (U.S. EPA, 1989);

C Risk Assessment Guidance for Superfund, Part E (U.S. EPA, 2004);

C Estimating Exposures to Dioxin-Like Compounds (U.S. EPA, 1994a);

C Selection Criteria for Mathematical Models Used in Exposure Assessments: Groundwater Models (U.S. EPA, 1988a);

C Selection Criteria for Mathematical Models Used in Exposure Assessments: Surface Water Models (U.S. EPA, 1987);

C Standard Scenarios for Estimating Exposure to Chemical Substances During Use of Consumer Products (U.S. EPA, 1986a);

C Pesticide Assessment Guidelines, Subdivisions K (U.S. EPA, 1984) and U , (U.S. EPA, 1986b);

1-121 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 C Methods for Assessing Exposure to Chemical Substances, Volumes 1-13 (U.S. EPA, 1983-1989);

• Guiding Principles for Monte Carlo Analysis (U.S. EPA, 1997b);

• Policy for Use of Probabilistic Analysis in Risk Assessment at the U.S. Environmental Protection Agency, May 15, 1997 ;

• Guiding Principles for Monte Carlo Assessments (EPA/600/R-97/001) ( http://www.epa.gov/ncea/monteabs.htm)

• Options for Developing Parametric Probability Distributions for Exposure Factors (EPA/600/R-00/058) July 2000 (U.S. EPA, 2000a)

• Sociodemographic Data for Identifying Potentially Highly Exposed Populations (U.S. EPA, 1999)

• Framework for Cumulative Risk Assessment (U.S. EPA, 2003a)

• Example Exposure Scenarios (U.S. EPA 2003b)

• Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants (U.S. EPA, 2005a)

• Cancer Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005b) and Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens (U.S. EPA, 2005c)

These docum ents m a y serve as valuable inform ation resources to assist in the assessm ent of exposure. The reader is encouraged to refer to them for m o re detailed discussion. Most of the data presented in this handbook are derived from studies that target (1) the general population (e.g., USDA food consum ption surveys) or (2) a sam p le population from a specific area or group (e.g., Calabrese’s et al. ( 1989) soil ingestion study using children from the Am herst, MA area). It is necessary for risk or exposure assessors characterizing a diverse population to identify and enum erate certain groups within the general population who are at risk for greater contam inant exposures or who exhibit a heightened sensitivity to particular contam inants. For further guidance on addressing susceptible populations, the reader is referred to Socio-demographic Data Used for Identifying Potentially Highly Exposed Subpopulations (U.S. EPA, 2001)

1-131 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1.8 THE USE OF AGE GROUPING S WHEN ASSESSING EXPOSURE W h en this handbook was first published in 2002, no specific guidance existed with regard to which age groupings should be used when assessing children’s exposure. Age groupings varied from case to case and am ong Program and Regional offices within the EPA. They depended on availability of data and were ofte n based on professional judgem e nt or historical

use. The developm ent of standardized age bins was the subject of discussion in a 2000 EPA workshop titled “Issues Associated with Considering Developm ental Changes in Behavior and Anatom y W h en Assessing Exposure to Children” (U.S. EPA, 2000b). The purpose of this workshop was to gain insight and input into factor s that need to be considered when developing standardized age bins and to identify future research necessary to accom p lish these goals. Panelists were divided into two groups. One group focused their discussions on defining and characterizing the im portant facets of behavior al developm ent during childhood while the other group focused on defining and characterizing the physiological developm ent during childhood. During the workshop, it was recognized that the ultim ate goal of exposure assessm ent is to develop a day-to-day m odel of hum an life that can predict the contam inant exposures an individual is likely to face at any point in life. However, this is not likely to be accom p lished in the near future and assessors often need to classify individuals into age bins in order to sim p lify the exposure m odel. The recom m e ndations listed below are those of the panel m e m b ers and were considered by EPA in the developm ent of age groupings:

• Panelists agreed that child development is a series of discrete events, but these events occur along a contiuum.

• Age grouping/bins are a useful guide to fulfill the Agency’s immediate need, but are only a crude approximation of an underlying distribution. Ultimately, sufficient data should be gathered to develop a continuous multivariate model that can replace bins.

• Adequacy of existing exposure data is highly variable.

• A considerable amount of additional information already exists, but it is dispersed in the literature. It was recommended that EPA consults with experts in

1-141 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 developmental biology, physiology, pharmacology, and toxicology and conducts an in-depth review of the literature.

• Long term research should include the development of integrated data sets that combines information about the exposure factors with biomarkers of exposure and effects.

• The definition of age groups/bins for childhood exposure assessment are inextricably linked to toxicokinetic and toxicodynamic issues.

• The two break out groups (i.e., behavioral and physiological) offered the following preliminary ideas for age groupings:
Age grouping based on behavioral characteristics 0-2 m onths 2 - 6 m onths 6-12 m onths 1-2 years 2-6 years 6-11 years 11-16 years 16-21 years Age grouping based on physiological characteristics 0-1 m onth 1-6 m onths 6-12 m onths 1- 3 years 3-9 years 9-21 years One can observe that there was fairly good agreem ent am ong the two groups with regard to the age groupings that are im portant for infants and toddlers. However, there was som e disagreem ent with regard to the older children. Appropriate consideration of age groupings depend not only on behavioral and physiological ch aracteristics, but also on the specific scenario being studied and contam inant of concern.

1-151 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Based upon consideration of the findings of the technical workshop, as well as analysis of available data, EPA developed guidance which established a set of recom m e nded age groups for developm ent of exposure factors for children entitled “ Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants ” (U.S. EPA, 2005a). This revision of the Handbook was developed specifically to present exposure factors data in a m a nner consistent with EPA’s recom m e nded set of childhood age groupings. The recom m e nced age groups are as follows: Birth to <1 m onth; 1 to < 3 m onths; 3 to < 6

m onths; 6 to < 12 m onths; 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 (U.S. EPA, 2005a).

1.9 CONSIDERING LIFESTAGE WHEN CALCULATING EXPOSURE AND RISK A key com ponent of EPA’s Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants (U.S. EPA 2005a) involves the need to sum age-specific differences in exposure across tim e when assessing long-term exposure, as well as integrating these age-specific exposures with age-specific differences in toxic potency in those cases where inform ation exists to describe such differences: an exam ple is carcinogens that act via a m u tagenic m ode of action ( Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens - U.S. EPA, 2005c). W h en assessing chronic risks, rather than assum i ng a constant level of exposure for 70 years (usually consistent with an adult level of exposure), the Agency is now recom m e nding that assessors should calculate chronic exposures by sum m i ng tim e-weighted exposures that occur at each lifestage; this handbook provides data arrayed by childhood age in order to support this new guidance. This approach is expected to increase the accuracy of risk asse ssm ents because it will take into account lifestage differences in exposure. Depending on whethe r body-weight-adjusted childhood exposures are either sm aller or larger as com p ared with those for adults, calculated risks could either decrease or increase as com p ared with the historical appr oach of assum i ng a lifetim e of a constant adult level of exposure. The Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens also recom m e nded that in those cases where age-related differences in toxicity were also found to occur, differences in both toxicity and exposure would need to be integrated across all relevant age intervals. This guidance describes such a case for carcinogens that act via a

1-161 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 m u tagenic m ode of action, where age dependent potency adjustm e nts factors (ADAFs) of 10x and 3x are recom m e nded for children ages birth < 2 years, and 2 < 16 years, respectively when there is exposure during those years. Table 1-4, along with Chapter 6 of the “ Supplemental Guidance ” have been developed to help the reader understand how to use the new sets of exposure and potency age groupings when calculating risk through the integration of lifestage specific changes in exposure and potency. Thus, Lifetim e Cancer Risk (for a population with average life expectancy of 70 years) = Σ (Exposure x Duration x Potency x ADAF) sum m e d across all the age groups presented in Table 1-4. This is a departure from the way cancer risks have historically been calculated based upon the prem ise that risk is proportional to the daily average of long term adult dose.

1.10 GENERAL EQUATIONS FOR CALCULATING DOSE The definition of exposure as used in the Exposure Guidelines (U.S. EPA, 1992a) is the “contact of a chem ical, physical, or biological ag ent with the outer boundary of an organism .” This m eans contact with the visible exterior of a person such as the skin, and openings such as the m outh, nostrils, and lesions. The process of a contam inant entering the body can be described in two steps: contact (exposure) followed by entry (crossing the boundary). The dose is the am ount of agent available at hum an exchange boundaries (skin, lungs, gut) where absorption takes place during som e specified tim e. An exam ple of exposure and dose for the oral route as presented in the EPA Exposure Guidelines is shown in Figure 1-1. Starting with a general integral equation for exposure (U.S. EPA, 1992a), several dose equations can be derived depending upon boundary assum p tions.
Average Daily Dose (ADD) has been used when assessing risks for m a ny noncancer effects

- this m e tric averages doses over the period of tim e over which exposure occurred. The ADD can be calculated by averaging the potential dose (D pot ) over body weight and an averaging tim e.

ADD pot = [C x IR x ED] / [BW x AT] (1-1)

W h ere: C = Contam inant Concentration

1-171 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 IR = Intake Rate ED = Exposure Duration BW = Body W e ight AT = Averaging Tim e
Note that the advent of childhood age groupings m eans that separate ADD’s should be calculated for each age group considered. Chronic exposures can then be calculated by sum m i ng across each lifestage specific ADD.Cancer risks have traditionally been calculated in those cases where a linear nonthreshold m odel is assum e d, in term s of lif etim e probabilities by utilizing dose values presented in term s of lifetim e ADDs (LADDs). The LADD takes the form of the Equation 1-1, with lifetim e replacing averaging tim e. W h ile the use of LADD m a y be appropriate when developing screening level estim ates of cancer risk, as discussed in Section 1.9 above, EPA is now

recom m e nding that risks should be calculated by integrating exposures or risks throughout all lif estages. Contam inant concentration is the concentration of the contam inant in the m e dium (air, food, soil, etc.) contacting the body and has units of m a ss/volum e or m a ss/m a ss. The intake rate refers to the rates of inhalation, ingestion, and derm al contact, depending on the route of exposure. For ingestion, the intake rate is sim p ly the am ount of food containing the contam inant of interest that an individual ingests during som e specific tim e period (units of

m a ss/tim e). Much of this handbook is devoted to rates of ingestion for som e broad classes of food. For inhalation, the intake rate is the rate at which contam inated air is inhaled. Factors that affect derm al exposure are the am ount of m a terial that com e s into contact with the skin and the rate at which the contam inant is absorbed. The exposure duration is the period of tim e over which exposure occurs. The length of tim e a person lives in an area, frequency of bathing, tim e spent indoors versus outdoors, etc., all affect the exposure duration. Chapter 9, Activity Factors, gives som e exam ples of population behavior/activity patterns that m a y be useful for estim ating exposure durations. W h en the above param e ter values intake rate (IR) and exposure duration (ED) rem a in constant over tim e, they are substituted directly into the exposure equation. W h en they change with tim e, a sum m a tion approach is needed to calculate exposure. In either case, the exposure

1-181 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 duration is the length of tim e exposure occurs at the concentration and the intake rate specified by the other param e ters in the equation. Dose can be expressed as a total am ount (with units of m a ss, e.g., m g ) or as a dose rate in term s of m a ss/tim e (e.g., m g /day), or as a rate norm a lized to body m a ss (e.g., with units of m g of contam inant per kg of body weight per day (m g/kg-day)). The dose is usually expressed in term s of m g /kg-day or other m a ss/m a ss-tim e units. In m o st cases (inhalation and ingestion exposure), the dose-response param e ters for carcinogen risks have been adjusted for the difference in absorption across body barriers between hum ans and the experim e ntal anim als used to derive such param e ters. Therefore, the exposure

assessm ent in these cases is based on the potential dose, with no explicit correction f o r the fraction absorbed. However, the exposure assessor needs to m a ke such an adjustm e nt when calculating derm al exposure and in other specific cases when current inform ation indicates that the hum an absorption factor used in the derivation of the dose-response factor is inappropriate. For carcinogens, the duration of a lifetim e has traditionally been assigned the nom inal value of 70 years as a reasonable approxim a tion. For exposure estim ates to be used for

assessm ents other than carcinogenic risk, various averaging periods have been used. For acute exposures, the doses are usually averaged over a day or a single event. For nonchronic noncancer effects, the tim e period used is the actual period of exposure (exposure duration). The objective in selecting the exposure averaging tim e is to express the exposure in a way which can be

com b ined with the dose-response relationship to calculate risk. The body weight to be used in the exposure Equation 1-1 depends on the units of the exposure data presented in this handbook. For the food ingestion and water intake data presented in chapters 3 and 4 respectively, the body weights of the surveyed populations were known in the USDA surveys and they were explicitly factored into the food intake data in order to calculate the intake as g/d/kg body weight. In this case, the body weight has already been included in the “intake rate” term in Equation 1-2 and the exposure assessor does not need to explicitly include body weight. Body weight data presented in chapter 11 m a y be used in other instances when the intake rate has not been norm a lized by body weight. The units of intake in this handbook for som e of the exposure factors (e.g., breast m ilk intake) are not norm a lized to body weight. In this case, the exposure assessor needs to use (in Equation 1-1) the average weight of the exposed population during the tim e when the

1-191 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 exposure actually occurs. If the body weight of the individuals in the population whose risk is being evaluated is non-standard in som e way (e.g., children m a y be sm aller than the national population) and if reasonable values are not available in the literature, then a m odel of intake as a function of body weight m u st be used. One such m odel is discussed in Appendix 1A of the Exposure Factors Handbook (U.S. EPA, 1997a). Som e of the param e ters (prim a rily concentrations) used in estim ating exposure are exclusively site specific, and therefore default

recom m e ndations could not be used. It should be noted that body weight is correlated with food

consum ption rates and inhalation rates. The link between the intake rate value and the exposure duration value is a com m o n source of confusion in defining exposure scenarios. It is im portant to define the duration estim ate so that it is consistent with the intake rate:

C

C The intake rate can be based on an individual event (e.g., serving size per event). The duration should be based on the num ber of events or, in this case, m e als. The intake rate also can be based on a long-term average, such as 10 g/day. In this case the duration should be based on the total tim e interval over which the exposure occurs. The objective is to def i ne the term s so that, when m u ltiplied, they give the appropriate estim ate of m a ss of contam inant contacted. This can be accom p lished by basing the intake rate on either a long-term average (chronic exposure) or an event (acute exposure) basis, as long as the duration value is selected appropriately. Inhalation dosim etry is em ployed to derive the hum an equivalent exposure concentrations (HEC) on which inhalation unit risks, and reference concentrations, are based (U.S. EPA, 1994b). EPA has traditionally approxim a ted child ren’s respiratory exposure by using adult values, although a recent review (Ginsberg, et al., 2005) concluded that there m a y be som e cases where young children' s greater ventilation rate per body weight or pulm onary surface area as

com p ared to adults can result in greater exposures than adults. The im plications of this difference for inhalation dosim etry and children' s risk assessm ent were recently discussed at a peer involvem e nt workshop hosted by EPA in 2006 (workshop results and references to be published in 2007). Consideration of lifestage-particular physiological characteristics in the dosim etry analysis m a y result in a refinem e nt to the hum an equivalent concentration (HEC) to insure

1-201 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 relevance in risk assessm ent across lif estages, or m i ght conceivably conclude with m u ltiple HECs, and corresponding inhalation unit risk values (e.g., separate for childhood and adulthood) (U.S. EPA, 2005b, c). The RfC m e thodology, which is described in Methods for Derivation of Inhalation Reference Concentrations and Applications of Inhalation Dosimetry (U.S. EPA, 1994b), allows the user to incorporate population/lifestage-specific assum p tions in to the m odels. There are no specific exposure factor assum p tions in the derivation of RfDs. The

assessm ent of the potential for adverse health effect s in infants and children is part of the overall hazard and dose-response assessm ent for a contam inant. Available data pertinent to children’s health risks are evaluated along with data on adults and the no-observed-adverse-effect-level (NOAEL) or benchm ark dose (BMD) f o r the m o st sensitive critical ef f

ect(s), based on consideration of all health ef f

ects. By doing this, protection of the health of children will be considered along with that of other sensitive populations. In som e cases, it is appropriate to evaluate the potential hazard to children separately from the assessm ent for the general population or other population subgroups. However, the Food Quality Protection Act (FQPA) of 1996 states that for threshold effects, “an additional tenfold margin of safety for the chemical residue and other sources of exposure shall be applied for infants and children to take into account potential pre- and post

natal toxicity and completeness of data with respect to exposure and toxicity to infants and children. Notwithstanding such requirement for an additional margin of safety, the Administrator may use a different margin of safety for the pesticide chemical residue only if, on the basis of reliable data, such margin of safety will be safe for infants and children. ”
In addition, FQPA lists several factors that m u st be considered when assessing risks to children, such as available inf o rm ation concerning the special susceptibility of children to pesticide chem ical residues, neurological differences between children and adults, and effects of in utero exposure.

1.11 CUMULATIVE RISK EPA recognizes that children m a y be exposed to m i xtures of contam inants both indoors and outdoors. Exposure m a y also occur through m o re than one pathway. New directions in risk

assessm ents in EPA put m o re em phasis on total exposures via m u ltiple pathways (U.S. EPA, 2003a). Over the last several years, EPA ha s developed a m e thodology for assessing risk from

1-211 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 m u ltiple contam inants. For m o re inform ation, the reader is referred to EPA’s Framework for Cumulative Risk Assessment (U.S. EPA, 2003a).



### 1.12 RESEARCH NEEDS The data for several exposure factors for children are lim ited. The following list is a

com p ilation of areas for future research related to childhood exposure factors:

C More recent inform ation is needed on breastm ilk consum ption and the incidence and duration of breastfeeding.

C Inform ation on children’s food handling practices that m i ght exacerbate exposure is needed to better characterize exposures am ong children.

C Further research on fish intake am ong children, particularly recreational and subsistence populations, is needed.

C Further research is needed on consum ption of ethnic foods by children.

C Research is needed to better estim ate soil intake rates, particularly on how to extrapolate short-term data to chronic exposures. Research is also needed to refine the m e thods to calculate soil intake rates (i.e., inconsistencies am ong tracers and input/output m i salignm ent errors indicate a fundam e ntal problem with the

m e thods). In addition, there are no data for children <1 year or >7 years of age. Additional inform ation on soil ingestion am ong children that provides better estim ates of upper percentile rates is needed, in particular. Research is also needed to better understand the relative contribution of soil vs. dust ingestion.

1-22 C Further research is needed on dermal and non-dietary ingestion exposure factors, including the microenvironments in which children spend time and the types of materials that they contact, as well as information on the rate at which they1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 contact contam inated surfaces, the fraction of the contam inants that are transferred to skin and object surfaces, and the am ount of the object/skin entering the m outh.

C Further research is needed to obtain better soil adherence rates for additional activities involving children.

C Further data is needed on the frequency and duration of use and kinds of consum er products used by children.

C Additional data on inhalation dosim etry and m odeling, including inhalation rates that are specif i c to children’s activities.

C Research is needed to derive a m e thodology to extrapolate from short-term data to long-term or chronic exposures.

1.13 ORGANIZ A TION The handbook is organized as follows: Chapter 1 P rovides the overall introduction to the handbook.
Chapter 2 P rovides factors for estim ating exposure through ingestion of breast m ilk.
Chapter 3 P rovides factors for estim ating hum an exposure through ingestion foods, including fish.
Chapter 4 P rovides factors for estim ating exposure through ingestion of drinking water.
Chapter 5 P rovides factors for estim ating exposure as a result of ingestion of soil.

1-231 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Chapter 6 P resents factors for estim ating exposure to environm ental contam inants from other non-dietary ingestion such as hand-to

m outh and object-to-m outh activity. -

Chapter 7 P rovides factors for estim ating exposure as a result of inhalation of vapors and particulates.
Chapter 8 P rovides factors for estim ating derm al exposure to environm ental contam inants that com e in contact with the skin.
Chapter 9 P resents data on activity factors (activity patterns, population

m obility, and occupational m obility).
Chapter 10 Presents data on consum er product use.
Chapter 11 Presents data on body weight.

1-241 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 

### 1.14 REFERENCES FOR CHAPTER 1
Calabrese, E.J.; Pastides, H.; Barnes , R.; Edwards, C.; Kostecki, P.T.; et al. (1989) How m u ch soil do young children ingest: an epidem iologic study. In: Petroleu m Contam inated Soils, Lewis Publishers, Chelsea, MI. pp. 363-397. EO (1997). Executive Order 13045. Protection of Children for Environm ental Health Risks and Safety Risks. Available on line at http://yosem ite.epa.gov/ochp/ochpweb.nsf/content/whatwe_executiv.htm

. Eskenazi, B.; Bradm a n, A.; Castriona, R. (1999) Expos ure of children to organophosphate pesticides and their potential adverse health effects. Envir onm ental Health Perspectives, 107(S3): 409-19. Gilbert, R.O. (1987) Statistical m e thods for envir onm ental pollution m onitoring. New York: Van Nostrand Reinhold. Ginsberg G.; Foos B.; Firestone M. (2005) Review and an alysis of inhalation dosim etry m e thods for application to children' s risk assessm ent. J Toxico l. Environ. Health A. 68(8):573-615. Gurunathan, S.; Robson, M.; Freem an N.; Buckley, B.; Roy, A.; Meyer, R.; Bukowsk i, J.; Lioy, P.J. (1998) Accum u lation of chloropyrifos on residential surfaces a nd toys accessible to children. Environm ental Health Perspectives, 106(1):9-16. Lewis, R. G.; Fortune C.; W illis, R. D. ; Cam a nn, D. E.; Antley, J. T. ( 1999) Distribution of pesticides and polycyclic arom atic hydrocarbons in house dust as a f unction of particle size. Environm ental Health Perspectives, 107(9). Myers, G.J.; Davidson, P.W

. (2000) Does m e thylm e rc ury have a role in causing developm ental disabilities in children? Environm ental Health Perspectives, 108(S3):413-420. Nishioka, M.G.; Burkholder, H.M.; and Brinkm an , M.C.; Lewis, R.G. (1999) Distribution of 2,4-dihlorophenoxyacetic acid in floor dust throughout hom es following hom eowner and com m e rcial lawn application: quantitative effects of children, pe ts, and shoes. Environ. Sci. Technol., 33:1359-1365. Selevan, S.G.; Kim m e l, C.A.; Mendola, P. (2000) Identifying critical windows of exposure for children' s healthm onograph based on papers developed from the W o rks hop: Identifying Critical W i ndows of Exposure for Children' s Health held Septem ber 14-15, 1999 in Rich m ond, VA. Environm ental Health Perspectives, 108(S3):451-5.
U.S. Census ((2006). State Population Estim ates - Character istics. Table 1: Estim ates of the population by selected age groups in the United States, States, and Puerto Rico. Available on line at: http://www.census.gov/popest/states/as rh/tables/SC-EST2005-01Res.xls.
U.S. EPA. (1983-1989) Methods for assessing exposure to chem ical substances. Volum e s 1 13. W a shington, DC: Office of Toxic Substances, Exposure Evaluation Division.
U.S. EPA. (1984) Pesticide assessm ent guidelines subdivisi on K, exposure: reentry protection. Office of Pesticide Program s, W a shington, DC. EPA/540/9-48/001. Av ailable from NTIS, Springfield, VA; PB-85-120962.
U.S. EPA. (1986a) Standard scenarios for estim ating e xposure to chem ical substances during use of consum er products. Volum e s I and II. W a shington, DC: Offi ce of Toxic Substance, Exposure Evaluation Division.
U.S. EPA. (1986b) Pesticide assessm ent guidelines subdi vision U, applicator exposure m onitoring. Office of Pesticide Program s, W a shington, DC. EPA/540/9-87/ 127. Available from NTIS, Springfield, VA; PB 85 133286.

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1-26 U.S. EPA. (1987) Selection criteria for m a them atical m odels used in exposure assessm ents: surface water m odels. Exposure Assessm ent Group, Office of Health and E nvironm ental Assessm ent, W a shington, DC. W P A/600/8 87/042. Available from NTIS, Springfield, VA; PB-88-139928/AS. U.S. EPA. (1988a) Selection criteria for m a them atical m odels used in exposure assessm ents: groundwater m odels. Exposure Assessm ent Group, Office of Health and E nvironm ental Assessm ent, W a shington, DC. EPA/600/8 88/075. Available from NTIS, Springfield, VA; PB-88-248752/AS. U.S. EPA. (1989) Risk assessm ent guidance for Superfund. Hum a n health evaluation m a nual: part A. Office of Solid W a ste and Em ergency Response, W a shington, DC. Available from NTIS, Springfield, VA; PB 90-155581. http://www.epa.gov/oswer/riskassessm ent/ragsa/index.htm U.S. EPA. (1990) Methodology for assessing health risks asso ciated with indirect exposure to com bustor em issions. EPA 600/6-90/003. Available from NT IS, Springfield, VA; PB-90-187055/AS. U.S. EPA. (1992a) Guidelines for exposure assessm ent. W a shington, DC: Office of Research and Developm ent, Office of Health and Environm ental Assessm ent. EPA/600/Z-92/001. U.S. EPA. (1992b) Derm al exposure assessm ent: principles a nd applications. W a shington, DC: Office of Health and Environm ental Assessm ents. EPA/600/8-9/011F.
U.S. EPA. (1994a) Estim ating exposures to dioxin-like com pounds. (Draft Report). Office of Research and Developm ent, W a shington, DC. EPA/600/6-88/005Cb.
U.S. EPA. (1994b) Methods for Derivation of Inhalation Re ference Concentrations and Applications of Inhalation Dosim e try. EPA/600/8-90/066F. October, 1994.
U.S. EPA. (1995). Policy on evaluating health risks to children. Science Policy Council. October 20, 1995. Available on line at http://www.epa.gov/OSA/spc/2poleval.htm

. U.S. EPA. (1997a) Exposure factors handbook. W a shingt on, DC: National Center for Environm ental Assessm ent, Office of Research and Developm ent. EPA/600/P-95/002Fa,b,c.
U.S. EPA. (1997b) Guiding principles for Monte Carl o analysis. W a shington, DC: Office of Research and Developm ent, Risk Assessm ent Forum

. EPA/600/R-97/001.
U.S. EPA. (1998) The EPA children' s environm ental h ealth yearbook. W a shington, DC: U.S. Environm ental Protection Agency.
U.S. EPA. (1999a) Child-related risk assessm ent polic y and m e thodology guidance docum ent survey, draft report. W a shington, DC: Office of Children' s Health Protection.
U.S. EPA. (1999b) Sociodem ographic Data Used for Identifying Potentially Highly Exposed Populations. U.S. Environm ental Protection Agency, W a shington, DC, EPA/600/R-99/060. Available on line at: ( http://cfpub.epa.gov/ncea/cfm / recordisplay.cfm ? d eid=22562.
U.S. EPA. (2000a) Options for developing param e tric pr obability distributions for exposure factors. W a shington, DC: National Center for Environm ental Assessm ent, Office of Research and Developm ent. EPA/600/R-00/058). (http://www.epa.gov/ncea/param p rob4ef.htm )

. U.S. EPA. (2000b) Sum m a ry Report of the Technical W o rkshop on Issues Associated with Considering Developm ental Changes in Behavior and Anatom y W h en Assessing Exposure to Children. Draft report. W a shington, DC: Office of Research and Developm ent, Risk Assessm ent Forum , Septem ber, 2000.
U.S. EPA. (2000c) Office of Research and Developm ent. Strategy for research on environm ental risks to children. W a shington, DC: Office of Research and Developm ent. EPA/600/R-00/068.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

1-27 U.S. EPA. (2001) Identifying Potentially Highly Exposed Children' s Populations. Draft Report. W a shington, DC: National Center for Environm ental Assessm en t, Office of Research and Developm ent. U.S. EPA. (2002) Child-Specific E xposure Factors Handbook (Interim Final). W a shington, D.C., National Center for Environm ental Assessm ent, Office of Re search and Developm ent. EPA-600-P-00-002B.
U. S. EPA. (2003a) Fram ework for Cum u lative Risk Asse ssm ent. W a shington, DC: U.S. Environm ental Protection Agency, Risk Assessm ent Forum

. EPA/630/P-02/001F. Available on line at: http://cfpub.epa.gov/ncea/raf/recordisplay.cfm ? d eid=54944.
U.S. EPA. (2003b) Exam ple Exposure S cenarios. National Center for Environm ental Assessm ent, W a shington, DC; EPA/600/R03/036. Available on line at: http://cfpub.epa.gov/ncea/cfm / recordisplay.cfm ? d eid=85843. U.S. EPA. (2004) Risk assessm ent guidance for Superfund. Hum a n health evaluation m a nual: part E. Supplem ental Guidance for Derm al Risk Assessm ent. Office of Solid W a ste and Em ergency Response, W a shington, DC. EPA/540/R/99/005. http://www.epa.gov/oswer/riskassessm ent/ragse/index.htm
U.S. EPA. (2005a) Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environm ental Contam inants (2005). U.S. Environm en tal Protection Agency, W a shington, D.C., EPA/630/P

03/003F. Available on line at: http://oaspub.epa.gov/eim s /xm l report.display? deid=146583&z_chk=33084

. U.S. EPA. (2005b) Guidelines for Carcinogen Risk Assessm ent. Risk Assessm ent Forum , W a shington, DC. EPA/630/P-03/001F.
U.S. EPA. (2005c) Supplem ental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens. Risk Assessm ent Forum , W a shington, DC . EPA/630/R-03/003F. Available on line at: http://cfpub.epa.gov/ncea/cfm / recordisplay.cfm ? d eid=116283.Table 1-1. Considerations Used to Rate Confidence in Recom m e nded Values CONSIDERATIONS HIGH CONFIDENCE LOW CONFIDENCE Study Elements Level of peer review The studies received high The studies received lim ited level of peer review (e.g., they peer review. appear in peer review journals). Accessibility The studies are widely The studies are difficult to available to the public. obtain (e.g., draft reports, unpublished data). Reproducibility The results can be reproduced The results cannot be or m e thodology can be reproduced, the m e thodology is followed and evaluated. hard to follow, and the author(s) cannot be located. Focus on factor of The studies focused on the The purpose of the studies was interest exposure factor of interest. to characterize a related factor. Data pertinent to U.S. The studies focused on the The studies focused on U.S. population. populations outside the U.S. Prim ary data The studies analyzed prim ary The studies are based on data. secondary sources. Currency T he data were published after The data were published before 1990. 1990. Adequacy of data The study design captures the The study design does not very collection period m easurem ent of interest (e.g., accurately capture the usual consum ption patterns of m easurem ent of interest. a population). Validity of approach The studies used the best There are serious lim itations m e thodology available to capture the m easurem ent of interest. with the approach used.

1-28Study sizes The sam p le size is greater than 100 sam p les. The sam p le size depends on how the target population is defined. As the size of a sam p le relative to the total size of the target population increases, estim ates are m a de with greater statistical assurance that the sam p le results reflect actual characteristics of the target population. The sam p le size is less than 20 sam p les.

Representativeness of the population The study population is the sam e as population of interest. The study population is very different from the population of interest. a Variability in the population The studies characterized variability in the population studied. The characterization of variability is lim ited. Lack of bias in study design(a high rating is desirable) Potential bias in the studies are stated or can be determ ined from the study design. The study design introduces biases in the results.

Response rates

In-person interviews Telephone interviews Mail surveys The response rate is greater than 80%. The response rate is greater than 80%. The response rate is greater than 70%. The response rate is less than 40%. The response rate is less than 40%. The response rate is less than 40%. Measurem ent error T he study design m i nim i zes m easurem ent errors. Uncertainties with the data exist due to m e asurem ent error. Other Elements Num b er of studies The num ber of studies is greater than 3. The num ber of studies is 1. Agreem ent between researchers The results of studies from different researchers are in agreem ent. The results of studies from different researchers are in disagreem ent.

a Differences include age, sex, race, incom e , or other dem ographic param e ters.

1-29Table 1-2. Sum m a ry of Exposure Factor References and Confidence Ratings EXPOSURE FACTOR REFERENCE CONFIDENCE RATING (mean/upper

percentile) Breast m ilk intake rate Table 2-11 Medium /Medium Drinking water intake rate Table 4-7 H igh/High Food Intake- General Population (fruit, vegetables, meats, dairy products, grains, fats, fish) Table 3-50 High/Low

Fish intake - Recreational T able 3-50 Low/Low Fish Intake - Native Am erican Subsistence Population Table 3-50 Low/Low

Hom e produced food intake Table 3-50 Low/Low Soil ingestion rate Table 5-21 Medium /Low Mouthing behavior Table 6-21 (m outhing tim e) Table 6-22 (m outhing frequency) Low/Low
Inhalation rate Table 7-21 Medium /Medium

Derm al Factors S urface Area W hole Body: Tables 8-6, 8-7, 8-8 Body Parts: Table 8-3 Solid Adherence Tables 8-9, 8-10, 8-16 Medium /Medium

Body W e ight Age 0 to <2 m onths: Table 11-1 Older Infants and Children: Tables 11 9, 11-10, 11-11 - High/High

Activities (Showering, Swim m i ng, Tim e Indoors/Outdoors, etc.) Tables 9-75 and 9-76 Medium /Medium

1-30Table 1-3. Characterization of Variability in Exposure Factors

Exposure Factors Average Median Upper percentile Multiple Percentiles Fitted Distributions Breast m ilk intake rate 

### T T

Total intake rate f o r m a jor food groups 

### T T T Qualitative discussion for

long-term 

### T

Individual food intake rate 

### T Drinking water intake rate 

### T T T T Fish intake rate for general population, recreational m a rine, recreational freshwater, and Native Am erican 

### T T T T

Serving size for foods 

### T T

Hom e produced food intake rates 

### T T T T

Soil intake rate 

### T T T Qualitative discussion for

long-term Mouthing Behavior 

### T Inhalation rate 

### T T T Surface area Soil adherence 

### T T T T Body weight 

### T T T T Tim e indoors Tim e outdoors Showering tim e 

### T T T T T T

1-31Table 1-4. Integrating EPA’s Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants with EPA’s Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens For Those Contam inants W h ich Act Via a Mutagenic Mode of Action

Exposure Age Group E xposure Duration (yr) ADAF (Age-Dependent Potency Adjustment Factor) birth to < 1 m onth 0.083 10x 1 < 3 m onths 0.167 10x 3 < 6 m onths 0.25 10x 6 < 12 m onths 0.5 10x 1 to < 2 years 1 10x 2 to < 3 years 1 3x 3 to < 6 years 3 3x 6 to < 11 years 5 3x 11 to < 16 years 5 3x 16 to < 21 years 5 1x > 21 years (21 to < 70 yr) 4 9 1 x Note: Age groups for cancer potency adjustm e nt (birth to < 2 years; 2 to < 16 years; and 16 years and above) are represented by the three colored bands of exposure age groups.

1-321-33 O rgan Chem ical Effect Exposure Internal Dose Biologically Effective Dose

M etabolism A pplied Dose Potential Dose

G .I. Tract

U ptake M outh

Intake Figure 1-1. Schematic of Dose and Exposure: Oral Route Source: U.S. EPA, 1992a