APPENDIX E1 MODELING CONSUMER EXPOSURE TO PHTHALATE ESTERS

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Report to theU.S. Consumer Product Safety Commissionby theCHRONIC HAZARD ADVISORY PANEL ON PHTHALATESAND PHTHALATE ALTERNATIVESJuly 2014APPENDIX E1MODELING CONSUMER EXPOSURE TOPHTHALATE ESTERS

UNITED STATESCONSUMER PRODUCT SAFETY COMMISSION4330 EAST WEST HIGHWAYBETHESDA, MD 20814MemorandumDate:July 14, 2014TO:Mary Ann Danello, Ph.D., Associate Executive Director for Health SciencesFROM:Michael A. Babich, Ph.D., Chemist, Division of Health SciencesKent R. Carlson, Ph.D., ToxicologistSUBJECT :Modeling consumer exposure to phthalate esters (PEs) *†The attached report provides the U.S. Consumer Product Safety Commission’s (CPSC’s) HealthSciences’ staff assessment of consumer exposures to phthalate esters from all sources and routesof exposure, including diet, teethers and toys, child care articles, and personal care products. Thiswork was performed at the request of the Chronic Hazard Advisory Panel (CHAP) on phthalatesand phthalate substitutes.*These comments are those of the CPSC staff, have not been reviewed or approved by, and may not necessarilyreflect the views of, the Commission.†Leslie E. Patton, Ph.D., Toxicologist, who is no longer with CPSC, contributed to this report.CPSC Hotline: 1-800-638-CPSC (2772) CPSC's Web Site: http://www.cpsc.gov

TABLE OF CONTENTS1Introduction . 12Methodology . 2342.1Sources and Scenarios . 22.2Calculations . 42.3Input Data . 62.4Dietary Exposures . 12Results . 263.1Total Exposure . 263.2General Sources of Phthalate Ester Exposure . 263.3Individual Scenarios for Phthalate Ester Exposure . 353.4Comparison with Other Studies . 38Discussion . 414.1Uncertainty and Limitations . 414.1.1Scope . 414.1.2Modeling Assumptions . 424.1.3Specific Exposure Scenarios . 434.2Comparison with Other Studies . 464.3Regulatory Considerations . 474.4Data Gaps . 474.5Conclusions . 485Supplemental Data . 496References . 58Appendix E1 ‒ i

LIST OF TABLESTable E1-1 Phthalate esters in this report. . 2Table E1-2 Sources of exposure to phthalate esters included by exposure route. . 3Table E1-3 Phthalate ester concentrations in personal care products (µg/g). . 7Table E1-4 Phthalate ester concentrations in household products (µg/g).a . 9Table E1-5 Phthalate esters used in PVC products. . 10Table E1-6 Phthalate ester concentrations in environmental media . 11Table E1-7 Physiological parameters. . 13Table E1-8 Product use parameters for women. . 15Table E1-9 Product use parameters for infants. . 17Table E1-10 Product use parameters for toddlers. . 18Table E1-11 Product use parameters for children. . 19Table E1-12 Phthalate ester migration into artificial saliva. 21Table E1-13 Phthalate ester migration from adult toys. . 21Table E1-14 Estimated percutaneous absorption rates (h-1) for phthalate esters. . 22Table E1-15 Maximum diethyl phthalate (DEP) exposure (mg/d) from prescription drugs byage group. . 23Table E1-16 Mean and 95th percentile concentrations of selected phthalate esters in foodcommodities (µg/g). . 24Table E1-17 Average daily food consumption (g/d) by age group (EPA, 2007). . 25Table E1-18 Estimated mean and 95th percentile total phthalate ester exposure (µg/kg-d) bysubpopulation. . 27Table E1-19 Categories of exposure sources. . 28Table E1-20 Sources of phthalate ester exposure (percent of total exposure) for women. . 29Table E1-21 Sources of phthalate ester exposure (percent of total exposure) for infants. . 30Table E1-22 Sources of phthalate ester exposure (percent of total exposure) for toddlers. . 31Table E1-23 Sources of phthalate ester exposure (percent of total exposure) for children. . 32Table E1-24 Scenarios contributing 10% of the total exposure to individual phthalate esters. 36Table E1-25 Comparison of modeled estimates of total phthalate ester exposure (µg/kg-d). . 37Table E1-26 Comparison of modeled estimates of total phthalate ester exposure (µg/kg-d) withestimates from biomonitoring studies. . 39Appendix E1 ‒ ii

Table E1-S1 Estimated phthalate ester (PE) exposure (µg/kg-d) by individual exposure scenariofor women. . 49Table E1-S2 Estimated phthalate ester exposure (µg/kg-d) by individual exposure scenario forinfants. 52Table E1-S3 Estimated phthalate ester exposure (µg/kg-d) by individual exposure scenario fortoddlers. 54Table E1-S4 Estimated phthalate ester exposure (µg/kg-d) by individual exposure scenario forchildren. . 56Appendix E1 ‒ iii

LIST OF FIGURESFigure E1-1 Estimated phthalate ester exposure (µg/kg-d) for eight phthalates and foursubpopulations. . 33Figure E1-2 Sources of phthalate ester exposure. 34Figure E1-3 Comparison of modeled exposure estimates (this study) with exposures derivedfrom human biomonitoring studies. . 40Appendix E1 ‒ iv

ABBREVIATIONS PDHEPPDHEXPDHT*3β-hydroxysteroid dehydrogenaseantiandrogenicity; antiandrogenicattention deficit hyperactivity disorderacceptable daily intakeanogenital distanceanogenital indexAutistic Spectrum DisordersAgency for Toxic Substances and Disease Registryacetyl tributyl citrateBehavior Assessment System for Children-Parent Rating Scalesbutylbenzyl phthalateBritish Industrial Biological Research Associationbenchmark dosebenchmark dose (lower confidence limit)Brazelton Neonatal Behavioral AssessmentBehavior Rating Inventory of Executive Functionbehavioral symptoms indexChild Behavior Check ListCenters for Disease Control and Prevention, U.S.Center for the Evaluation of Risks to Human Reproductionconsumption factorChronic Hazard Advisory PanelChinese hamster ovarycentral nervous systemConsumer Product Safety Commission, U.S.Consumer Product Safety Improvement Act of 2008cumulative risk assessmentcranial suspensory ligamentmono(carboxy-isononyl) phthalate (also, CNP, MCNP)mono(carboxy-isooctyl) phthalate (also COP, MCOP)diallyl phthalatedibutyl phthalatedicyclohexyl phthalatedi-n-decyl phthalatedi(2-ethylhexyl) adipatedi(2-ethylhexyl) phthalatedi(2-ethylhexyl) terephthalatediethyl phthalatedi-n-heptyl phthalatedi-n-hexyl phthalatedihydrotestosteroneList applies to main report and all appendices.Appendix E1 ‒ v

DIDIBPDIDPDIHEPPDIHEXPDINPDINCH RCICHinsl3IPJRCLDLHLMWLOAELLODdaily intakediisobutyl phthalatediisodecyl phthalatediisoheptyl phthalatediisohexyl phthalatediisononyl phthalate1,2-cyclohexanedicarboxylic acid, diisononyl ester1,2-cyclohexanedicarboxylic acid, diisononyl esterdiisooctyl phthalatediisopropyl phthalatedimethyl phthalatedi-n-hexyl phthalatedi-n-octyl phthalatedi(2-ethylhexyl) terephthalatedi-n-pentyl phthalatedi(2-propylheptyl) phthalatedelayed preputial separationdecrease spermatocytes and spermatidsdelayed vaginal openingEuropean Chemicals Agencyextracorporeal membrane oxygenationmedian effective doseEnvironmental Protection Agency, U.S.epididymal weightFood and Drug Administration, U.S.urinary excretion factorgestational daygamma-glutamyl transferasegood laboratory practicesgranulinhuman biomonitoringhuman chorionic gonadotrophinhazard indexhigh molecular weighthigh production volumehazard quotientInternational Agency for Research on CancerInternational Conference on Harmonisationinsulin-like factor 3intraperitoneallyJoint Research Centrelactation dayluteinizing hormonelow molecular weightlowest observed adverse effect levellevel/limit of detectionAppendix E1 ‒ vi

EAAPNDPNWPODPODIPPARαPPSPSUlevel/limit of quantitationmonobutyl phthalatemonobenzyl phthalatemono(3-carboxypropyl) phthalatemental development indexmono(2-ethyl-5-carboxypentyl) phthalatemono(2-ethylhexyl) phthalatemono(2-ethyl-5-hydroxyhexyl) phthalatemono(2-ethyl-5-oxohexyl) phthalatemonoethyl phthalatemonoisobutyl phthalatemono(isononyl) phthalateMullerian inhibiting substancemonomethyl phthalatemultinucleated gonocytemono-n-octyl phthalatemargin of exposureMount Sinai School of Medicinemolecular weightnot availableno antiandrogenic effects observedNational Center for Environmental AssessmentNational Health and Nutritional Examination SurveyNICU Network Neurobehavioral Scaleno observed adverse effect levelno observed effect levelnipple retentionNational Research Council, U.S.National Toxicology Program, U.S.Organisation for Economic Cooperation and Developmentmono(hydroxy-isodecyl) phthalatemono(hydroxy-isononyl) phthalateodds ratiomono(oxo-isodecyl) phthalatemono(oxo-isononyl) phthalateperipheral benzodiazepine receptorpsychomotor developmental indexphthalate esterpotency estimates for antiandrogenicitypostnatal daypostnatal weekpoint of departurepoint of departure indexperoxisome proliferator-activated receptor alphaprobability proportional to a measure of sizeprimary sampling unitAppendix E1 ‒ vii

OTMTPIBT PRODTXIB UFpolyvinyl chloridereference dosereproductive tract malformationSprague-Dawleysexually dimorphic nucleus of the preoptic areaStudy for Future Familiesscavenger receptor class B1social responsiveness scalesteroidogenic acute regulatory proteinseminal vesicle weight2,3,7,8-tetrachlorodibenzo-p-dioxintolerable daily intaketesticular dysgenesis syndrometoxicity equivalency factorstris(2-ethylhexyl) trimellitate2,2,4-trimethyl-1,3 pentanediol diisobutyratetestosterone production2,2,4-trimethyl-1,3 pentanediol diisobutyrateuncertainty factorAppendix E1 ‒ viii

1IntroductionThe Consumer Product Safety Improvement Act (CPSIA) *of 2008 (CPSIA, 2008) was enactedon August 14, 2008. Section 108 of the CPSIA permanently prohibits the sale of any “children’stoy or child care article” individually containing concentrations of more than 0.1% of dibutylphthalate (DBP), butylbenzyl phthalate (BBP), or di(2-ethylhexyl) phthalate (DEHP). Section108 prohibits on an interim basis the sale of “any children’s toy that can be placed in a child’smouth” or “child care article” containing concentrations of more than 0.1% of di-n-octylphthalate (DNOP), diisononyl phthalate (DINP), or diisodecyl phthalate (DIDP). In addition,Section 108 of the CPSIA directs the Consumer Product Safety Commission (CPSC) to convenea Chronic Hazard Advisory Panel (CHAP) “to study the effects on children’s health of allphthalates and phthalate alternatives as used in children’s toys and child care articles.” TheCHAP will recommend to the Commission whether any phthalates or phthalate alternatives otherthan those permanently banned should be declared banned hazardous substances.This report describes scenario-based estimates of phthalate exposure, which were performed byCPSC staff under the direction of the CHAP. The CHAP selected eight phthalates for study(Table E1-1) because they are subject to the CPSIA, are found in human tissue, and/or exposuredata are available. Data sources included reviews of phthalate exposure data (Clark, 2009;Versar/SRC, 2010; Clark et al., 2011). In addition, the CHAP requested the CPSC staff to: Include new concentration data that were not available to Clark or Versar/SRC;Emphasize the most recent concentration data, rather than the entire historical database;Include mouthing exposure to phthalate alternatives; andPerform additional sensitivity analyses.We estimated exposures of four subpopulations (women of reproductive age, infants, toddlers,and children) to eight phthalate esters (PEs) selected by the CHAP. Exposure to phthalatealternatives is described in a separate report.*Public Law 110-314.Appendix E1 ‒ 1

Table E1-1 Phthalate esters in this report.Abbr.aCASMFMW 4DNOP117-84-0C24H38O4390.6Di(2-ethylhexyl) phthalateDEHP117-81-7C24H38O4390.6Diisononyl 0.6–446.7)Diisodecyl 8.6–474.7)NameDiethyl phthalateDi-n-butyl phthalatecDiisobutyl phthalatecButylbenzyl phthalatedDi-n-octyl phthalatecaAbbr., abbreviation; CAS, Chemical Abstracts Service number, MF, molecular formula; MW,molecular weight.bDINP includes isomers with C8 – C10 ester groups; DIDP includes isomers with C9 – C11 estergroups.cSubject to a permanent ban in child care articles and children’s toys.dSubject to an interim ban in child care articles and toys that can be placed in a child’s mouth.2MethodologyIn this report, we estimated human exposure to selected PEs by identifying and evaluatingrelevant exposure scenarios. This approach required knowledge of all relevant sources of PEexposure, data on concentrations of PEs in environmental media and products, physiologicalparameters, and consumer use information. The scenario-based (indirect) approach iscomplementary to the biomonitoring approach, which is also employed by the CHAP. Thebiomonitoring (direct) approach provides robust estimates of total human exposure to PEs butdoes not provide information regarding the sources of exposure. The scenario-based approach,employed for this report, estimates the relative contributions of various sources of PE exposure.2.1 Sources and ScenariosHumans are exposed to PEs from many sources and through multiple pathways and scenarios(Wormuth et al., 2006; Versar/SRC, 2010; Clark et al., 2011). PEs are ubiquitous environmentalcontaminants present in air, water, soil, food, personal care products (cosmetics), drugs andmedical devices, automobiles, and consumer products. * PEs were also commonly used in toys*In this report, “consumer product” refers to products under the jurisdiction of the CPSC. This includes productsused in and around the home, recreational settings, and schools that are not regulated by other federal agencies, forexample, food, drugs, personal care products (cosmetics), and medical devices. The terms“personal care products”and “cosmetics” are used interchangeably in this report. Most of the personal care products discussed in the reportfall under the Food and Drug Administration’s definition of “cosmetic.”Appendix E1 ‒ 2

and child care articles before their use was restricted by the European Commission and theUnited States. The sources and scenarios that may contribute significantly to human exposurewere identified by CPSC staff and are listed in Table E1-2.Table E1-2 Sources of exposure to phthalate esters included by exposure route.SourceTarget Population (age range)InfantsToddlers(0 to 2)(2 to 3)Women(15 to 44)aChildren(3 to 12)Children’s ProductsTeethers & toysDbO, DO, DDChanging pad--DD--Play pen--DD--Air freshener, aerosolI (direct)cI (indirect)dI (indirect)I (indirect)Air freshener, liquidI (indirect)I (indirect)I (indirect)I (indirect)Vinyl upholsteryD--DDGloves, vinylD------Adhesive, generalpurposeD------I, D--I (indirect)dI (indirect)dInternal------Soap/body washDDDDShampooDDDDSkin lotion/creamDDDDDeodorant, aerosolD, I (direct)I (indirect)I (indirect)D, I (direct)ePerfume, aerosolD, I (direct)I (indirect)I (indirect)D, I (direct)eHair spray, aerosolD, I (direct)I (indirect)I (indirect)D, I (direct)eD----DIIIIHousehold ProductsPaint, aerosolAdult toysPersonal Care ProductsNail polishEnvironmental MediaOutdoor airAppendix E1 ‒ 3

Women(15 to 44)aSourceTarget Population (age range)InfantsToddlers(0 to 2)(2 to 3)Children(3 to 12)Indoor airIIIIDustOOOOSoilOOOOFoodOOOOWaterOOOOBev

BSI behavioral symptoms index . CBCL Child Behavior Check List . CDC Centers for Disease Control and Prevention, U.S. . Appendix E1 ‒ 1 1 Introduction The Consumer Product Safety Improvement Act (CPSIA) * of 2008 (CPSIA, 2008) was enacted on August 14, 2008. Section 108 of the CPSIA permanently prohibits the sale of any “children’s

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