DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. ExpoKids READ ME Table of Contents I. ExpoKids Overview 2 II. ExpoKids Development 3 III. ExpoFIRST and ExpoKids 4 IV. Methods 6 V. Getting Started 8 VI. Tabs 9 A. Uploaded Table 9 B. Lifestage Tables 9 C. Lifestage Graphs 9 D. Media Graphs 9 E. Summary Graphs 9 VII. Explanation of Graphs 10 VIII. Assumptions and Limitations 12 I. References 13 1 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. I. ExpoKids Overview Aggregate exposure, the combined exposures from all pathways to a single chemical, is a critical children's health issue. ExpoKids Version 1.0 is an R-based tool that estimates relative sources of exposure within and across lifestages. The scope of the current version of this tool is limited to estimating average daily dose (ADD) from the oral exposure route for postnatal childhood lifestages (from birth to puberty) and includes adults as a comparator group. To capture potential differences in aggregate exposure at various childhood lifestages compared to those of adults, ExpoKids uses exposure estimates across lifestages generated by the publicly available US EPA's Exposure Factors Interactive Resource for Scenarios Tool (ExpoFIRST). ExpoKids illustrates aggregate oral exposures as average daily doses (ADD) and lifetime average daily doses (LADD) in 5 graphs organized across 7 postnatal and adult lifestages and 10 media. This visualization tool conveys ExpoFIRST findings, from available exposure data, in order to highlight the relative contributions of media and lifestages. 2 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. II. ExpoKids Development The goal of ExpoKids is to illustrates aggregate exposure estimates by lifestage based on exposure factor data in ExpoFIRST and user-defined concentration data. ExpoKids Version 1.0 characterizes exposure by estimating average daily dose (ADD) values for postnatal only and oral only exposure media with available data. 3 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. III. ExpoFIRST and ExpoKids ExpoFIRST estimates the ADDs from ten media (i.e., soil, dust, water, breastmilk, dairy, meat, fish, vegetables, fruit, and grains) [1], ADD was chosen as the ExpoKids metric because it captures typical exposures experienced by average Americans. ExpoFIRST itself does not evaluate aggregate exposure, but rather runs estimates for each medium separately. Subsequently, medium-specific ADD estimates are exported from ExpoFIRST to ExpoKids to develop aggregate exposure graphs (see Figure 1 for the ExpoKids workflow). ADD by Lifestage —-- I kji ¦ 1) ExpoFIRST 2) ExpoKids Figure 1. ExpoKids workflow _s£ J* s Lifestage Central tendency oral ADDs (mg/kg-day) for the EFH's ten children's age groups and the adult age group (ExpoKids can create five unique displays of ADD by lifestage, ADD by media, LADD by lifestage, LADD by media, and percent ADD by lifestage (summarized in Section V - Explanation of Graphs). Since the EFH follows the EPA's Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants as available data allows, ExpoKids also follows a similar renaming structure for reorganizing age groups into lifestages [3], The ingestion pathway, for instance, does not have data for all age groups under 1 year old and the EFH therefore commonly collapses these four age groups into one, named young infants in ExpoKids. The infant lifestage in ExpoKids treats the 1-3 years old EFH age groups similarly. In other words, eleven ExpoFIRST/EFH age groups were simplified to seven ExpoKids lifestages (Error! Not a valid bookmark self-reference.). Table 1) within the general population were estimated in ExpoFIRST for each medium using the following equation [1]: 4 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. C x IR x EF x ED Above, C = concentration (mg/mL or mg/g), IR = intake rate (mL/kg-day, g/kg-day, or mg/day depending on the medium), EF = exposure frequency (days/year), ED = exposure duration (years), AT = average time (days), and BW = body weight (kg) (US EPA, 2016). Age-specific central tendency estimates (either mean or median, depending on the exposure factor) from the EFH are used for IR, EF, ED, AT, and BW [2], Chemical concentration (C) is based on literature reported values in the media of interest. ExpoFIRST allows users to define an unlimited number of potential scenarios for various receptor populations and lifestages. In running ExpoFIRST for our illustrative case examples, we selected parameters to represent general population exposure. However, users can modify the parameters as appropriate to account for assessment- specific knowledge. 5 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. IV. Methods ExpoKids can create five unique displays of ADD by lifestage, ADD by media, LADD by lifestage, LADD by media, and percent ADD by lifestage (summarized in Section V - Explanation of Graphs). Since the EFH follows the EPA's Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants as available data allows, ExpoKids also follows a similar renaming structure for reorganizing age groups into lifestages [3], The ingestion pathway, for instance, does not have data for all age groups under 1 year old and the EFH therefore commonly collapses these four age groups into one, named young infants in ExpoKids. The infant lifestage in ExpoKids treats the 1-3 years old EFH age groups similarly. In other words, eleven ExpoFIRST/EFH age groups were simplified to seven ExpoKids lifestages (Error! Not a valid bookmark self-reference.). Table 1: Default EFH age bins and ExpoKids recategorized lifestages. EFH Age Bins ExpoKids Lifestage Total Years in Lifestage Birth to < 1 month 1 to < 3 months Young Infant12 1 3 to < 6 months 6 to < 12 months ~u o o _c 1 to < 2 years Infant1 2 T3 O 2 to < 3 years 3 to < 6 years Young Child 3 6 to < 11 years Child 5 11 to < 16 years Young Youth 5 16 to < 21 years Youth 5 21 to < 70 years Adult 49 Birth to < 70 years Lifetime 70 1 The young infant and infant lifestages were the only lifestages to combine multiple age bins. 2 The young infant lifestage is assumed to be 100% breastfed. Childhood ADD (defined as the time from birth to less than 21 years old) is also estimated in a new column for comparison against adulthood (21 years old to less than 70 years old) and lifetime (birth to less than 70 years old). After the data tables were 6 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. uploaded (R package: readxl), the melt function (R package: reshape2) rearranged the data into a readable format for the statistical program to create stacked bar plots using the ggplot function (R package: tidyverse). The resulting eleven graphs (one all media graph and ten medium specific graphs) display the estimated ADD values by lifestage. LADD values were then estimated by time-weighting each ADD value; in other words, each ADD was multiplied by a ratio of years spent within each lifestage divided by the total lifespan (70 years). For each medium, ADD per lifestage of interest (ADDj) was estimated from the age groups using the following equation: JXADDi x Yt) ADDj = 1Yt in which ADDi is the ADD value from the ExpoFIRST age group within the relabeled lifestage of interest, Yi is the length in years of that age group, £Yi js the total number of years in the new lifestage, and i represents the age group within the lifestage being estimated. LADD per lifestage (LADDj) of interest for the media was estimated from: ADDj x Yi LADDi = 1 1 1 Lifespan ADDs were also converted to percentages to understand the percent contribution of each medium within a lifestage using the following equation: ADDj % Lifestaqe Contribution,- = — x 100% ' a ' £ ADDj 7 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. V. Getting Started To run ExpoKids, users must first upload an Excel file with ADD values to the app for the following lifestages: • Birth to < 1 mo • 1 mo to < 3 mo • 3 mo to < 6 mo • 6 mo to < 1 yr • 1 yr to < 2 yr • 2 yr to < 3 yr • 3 yr to < 6 yr • 6 yr to < 11 yr • 11 yr to < 16 yr • 16 yr to < 21 yr • 21 yr to < 70 yr Specifically, ExpoKids was designed to run with EPA's ExpoFiRST. Users are encouraged to run their chemical of interest through ExpoFiRST first to calculate the ADD values (see website for details on ExpoFiRST). Once values are calculated, insert values into the "template.xlsx" file provided on the ExpoKids page and save with the chemical name, adding rows for media types as needed. Alternatively, users may test out ExpoKids with the "sample.xlsx" file. Once the file is ready, upload the file to ExpoKids to start viewing graphs. All graphs/tables will automatically update after the file is uploaded, apart from the media graphs. 8 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. VI. Tabs A. Uploaded Table View the uploaded ADD (mg/kg-day) table. B. Lifestage Tables View the uploaded table for ExpoKids' reorganized lifestages: • Young infant • Infant • Young child • Child • Young youth • Youth • Adult • Lifetime Two tables are displayed for ADD (mg/kg-day) and for LADD (mg/kg-day). C. Lifestage Graphs View graphs for: • ADD by Lifestage • LADD by Lifestage View pie graphs for: • ADD Cumulative Percent by Lifestage D. Media Graphs Use the checklist to select individual media groups to display graphs for ADD vs. lifestage and LADD vs. lifestage. E. Summary Graphs View the ADD by Lifestage graph and Cumulative Percent by Lifestage graph for childhood, adult, and lifetime. 9 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. VII. Explanation of Graphs Table 2: ExpoKids can display different graph types. Graph Type Graph Description ADD by lifestage Compares lifestages and media as relative contributors to an individual's lifetime exposure. LADD by lifestage Compares lifestage and media ADD contributions scaled by the number of years an individual spends in each lifestage; time duration within a lifestage is considered. ADD by lifestage per exposure pathway ADD by lifestage graph focused on a specific medium of interest (10 total). 10 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. LADD by lifestage per exposure pathway Lifestage LADD by lifestage graph focused on a specific medium of interest (10 total) Cumulative percent Converts relative ADD contributions within a lifestage to relative percentages within a lifestage. 11 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. VIII. Assumptions and Limitations Limited data constrains the utility of ExpoKids. Inhalation and dermal exposures may play a large role in consumer or residential exposure for some susceptible groups, but these are not specified by ExpoKids. Moreover, the ADD estimation assumed that the media concentrations remain constant over time for all lifestages. This fixed chemical concentration captures only a snapshot of a population's exposure at one point in time; to look at exposure as the population ages, concentration data would need to be collected over time. Similarly, the LADD was estimated separately for each lifestage and therefore, assumed that each lifestage was equivalent to the lifetime. This limitation is inherent to the LADD equation and results in LADDs that do not account for ingestion during other lifestages and, as a result, could underestimate total lifetime exposure. Furthermore, ExpoKids combines the smallest age groups from ExpoFIRST into the young infant and infant lifestages, resulting in a loss of detail for newborn ADD specificity. ExpoKids also shares limitations from ExpoFIRST. For instance, it calculates point estimates rather than probabilistic distributions. In addition, the effectiveness of ExpoKids relies on the chemical concentration data that users input into ExpoFIRST and its parameters chosen. ExpoFIRST also presently does not have an option to evaluate infant formula consumption; the illustrative case examples thereby assumed that young infants are exclusively breastfed even though supplementing breastmilk with infant formula is commonly practiced in the US and studies have indicated that, at 12 months, only 24% of young infants are breastfed [4], As a result, ExpoKids overestimates breastmilk consumption and does not represent formula fed infants who would have greater water consumption. No PBPK models are used in ExpoFIRST and accordingly do not allow for estimation of internal dose, if desired. Finally, ExpoFIRST also excludes the prenatal lifestage even though gestation may be a critical window of exposure. However, the gestational lifestage has a number of data gaps that currently makes exposure difficult to estimate [1], However, by combining the functionality of ExpoFIRST with the visual graphic capabilities of R, ExpoKids facilitates comparisons of aggregate exposure by media both within and across lifestages 12 ------- DRAFT: DO NOT CITE, QUOTE, OR DISTRIBUTE. IX. References 1. Office of Research and Development (ORD). Exposure Factors Interactive Resource for Scenarios Tool (ExpoFIRST), Version 2.0 [Internet], US Environmental Protection Agency; 2016. Available from: https://cfpub.epa.gov/ncea/risk/recordisplay.cfm?deid=322489 2. Exposure Factors Handbook: 2011 Edition [Internet], Washington (DC); 2011 Sep. Report No.: EPA/600/R-090/052F. Available from: https://www.epa.gov/sites/production/files/2015-09/documents/techoverview_efh- complete.pdf 3. Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants [Internet], Washington (DC): US Environmental Protection Agency; 2005. Report No.: EPA/630/P-03/003F. Available from: https://www.epa.gov/sites/production/files/2013-09/documents/agegroups.pdf 4. Grummer-Strawn LM, Scanlon KS, Fein SB. Infant feeding and feeding transitions during the first year of life. Pediatrics. 2008 Oct; 122 Suppl 2:S36-42. 13 ------- |