TSCA Work Plan Chemical 

Problem Formulation and Initial Assessment 

Cyclic Aliphatic Bromides Cluster 

Flame Retardants 

 

CASRN NAME 

25637-99-4 Hexabromocyclododecane 

3194-55-6 1,2,5,6,9,10-Hexabromocyclododecane 

3194-57-8 1,2,5,6-Tetrabromocyclooctane 

August 2015 

United States 

Environmental Protection Agency

EPA Document# 743-D1-5001 

August 2015 

Office of Chemical Safety and 

Pollution Prevention
Page 2 of 97 

TABLE OF CONTENTS 

TABLE OF CONTENTS ............................................................................................................. 2

AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS ............................................................ 5

ABBREVIATIONS .................................................................................................................... 6

EXECUTIVE SUMMARY ........................................................................................................... 8

1 INTRODUCTION ............................................................................................................ 11

1.1 SCOPE OF THE ASSESSMENT .............................................................................................................................. 12

1.2 REGULATORY AND ASSESSMENT HISTORY ............................................................................................................ 14

2 PROBLEM FORMULATION ............................................................................................. 16

2.1 PHYSICAL AND CHEMICAL PROPERTIES ................................................................................................................. 16

2.2 PRODUCTION VOLUME AND USES ...................................................................................................................... 17

2.2.1 Production Volume ................................................................................................................................. 17

2.2.2 Uses ........................................................................................................................................................ 18

2.2.2.1 Use in Expanded Polystyrene Foam (EPS) and Extruded Polystyrene Foam (XPS) ........................................... 18

2.2.2.2 Use in Textiles ................................................................................................................................................... 19

2.2.2.2.1 Use in Automotive Textiles ..................................................................................................................... 19

2.2.2.2.2 Historic Use in Textiles ............................................................................................................................ 20

2.2.2.3 Use in High Impact Polystyrene (HIPS) ............................................................................................................. 20

2.2.2.4 Other Identified Uses ....................................................................................................................................... 20

2.2.2.5 Summary of All Uses ......................................................................................................................................... 21

2.2.2.5.1 Summary of CDR Information ................................................................................................................. 21

2.2.2.5.2 Summary of EU Data ............................................................................................................................... 21

2.2.3 Future Market Trends ............................................................................................................................. 21

2.3 FATE AND TRANSPORT ..................................................................................................................................... 21

2.4 EXPOSURES .................................................................................................................................................... 22

2.4.1 Releases to the Environment .................................................................................................................. 22

2.4.2 Presence in the Environment .................................................................................................................. 23

2.4.2.1 Surface Water ................................................................................................................................................... 23

2.4.2.2 Wastewater ...................................................................................................................................................... 23

2.4.2.3 Sludge ............................................................................................................................................................... 23

2.4.2.4 Soil .................................................................................................................................................................... 23

2.4.2.5 Sediment .......................................................................................................................................................... 24

2.4.2.6 Biota ................................................................................................................................................................. 24

2.4.3 Occupational Exposure ........................................................................................................................... 24

2.4.4 General Population Exposure ................................................................................................................. 25

2.4.4.1 Ambient Air ...................................................................................................................................................... 25

2.4.4.2 Drinking Water ................................................................................................................................................. 25

2.4.4.3 Fish Consumption ............................................................................................................................................. 25

2.4.4.4 Biomonitoring ................................................................................................................................................... 25

2.4.5 Consumer Exposures ............................................................................................................................... 26

2.5 HAZARD ENDPOINTS ........................................................................................................................................ 26

2.5.1 Ecological Hazard ................................................................................................................................... 26

2.5.2 Human Health Hazard ............................................................................................................................ 27

2.6 RESULTS OF PROBLEM FORMULATION ................................................................................................................. 27

2.6.1 Conceptual Model .................................................................................................................................. 27

2.6.2 Analysis Plan ........................................................................................................................................... 31

2.6.2.1 Workers ............................................................................................................................................................ 31

2.6.2.2 Risks to General Population and Environmental Biota (aquatic, terrestrial and avian) .................................... 32

2.6.2.3 Consumers ........................................................................................................................................................ 33
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2.6.3 Sources and Pathways Excluded From Further Assessment ................................................................... 34

2.6.4 Uncertainties and Data Gaps ................................................................................................................. 34

2.6.4.1 Exposure Assessment ....................................................................................................................................... 34

2.6.4.1.1 Releases to the Environment .................................................................................................................. 34

2.6.4.1.2 Occupational Exposure ........................................................................................................................... 35

2.6.4.1.3 General Population and Consumer Exposure ......................................................................................... 35

2.6.4.2 Ecological Endpoints ......................................................................................................................................... 36

2.6.4.3 Human Health Endpoints ................................................................................................................................. 36

REFERENCES ........................................................................................................................ 37

APPENDICES ........................................................................................................................ 61

Appendix A Regulatory and Assessment History ................................................................ 61

Appendix B Uses Supplement Tables ................................................................................. 64

Appendix C Exposure Supplement Tables .......................................................................... 69

Appendix D Environmental Hazard Study Summaries ........................................................ 74

D-1 PERSISTENCE IN ENVIRONMENTAL MEDIA .......................................................................................................... 74

D-1-1 Air and Water ........................................................................................................................................ 74

D-1-2 Soil, Sediment and Sludge ...................................................................................................................... 74

D-1-3 Water and Wastewater ......................................................................................................................... 76

D-1-4 Bioaccumulation .................................................................................................................................... 76

D-2 TOXICITY TO AQUATIC ORGANISMS ................................................................................................................... 77

D-2-1 Aquatic Plant Toxicity ............................................................................................................................ 77

D-2-2 Aquatic Invertebrate Toxicity................................................................................................................. 78

D-2-3 Fish Toxicity ........................................................................................................................................... 80

D-3 TOXICITY TO TERRESTRIAL ORGANISMS .............................................................................................................. 83

D-3-1 Terrestrial Plant Toxicity ........................................................................................................................ 83

D-3-2 Soil Invertebrate Toxicity ....................................................................................................................... 83

D-3-3 Avian Toxicity ......................................................................................................................................... 84

Appendix E Human Health Hazard Study Summaries ......................................................... 85

E-1 TOXICOKINETICS ............................................................................................................................................ 85

E-2 ACUTE TOXICITY STUDIES ................................................................................................................................ 85

E-3 REPEATED-DOSE TOXICITY STUDIES ................................................................................................................... 86

E-4 REPRODUCTIVE AND DEVELOPMENTAL TOXICITY STUDIES ...................................................................................... 88

E-5 SKIN IRRITATION AND SENSITIZATION STUDIES ..................................................................................................... 94

E-6 GENOTOXICITY AND CANCER STUDIES ................................................................................................................ 94

LIST OF TABLES 

Table 2-1: Select Physical-Chemical Properties * ......................................................................... 17

Table 2-2: Summary of Use/Exposure Scenarios Considered for Assessment ............................. 28
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LIST OF APPENDIX TABLES

Table_Apx A-1: Regulatory and Assessment History of HBCD ..................................................... 61

Table_Apx B-1: 2012 CDR Production Data (Data Reported for 2011) ........................................ 64

Table_Apx B-2: Historic IUR and CDR Production Volumes.......................................................... 65

Table_Apx B-3: Summary of 2011 CDR Production Volume and Use Information ...................... 65

Table_Apx B-4: Uses of HBCD as Listed in the 2008 EU Risk Assessment .................................... 67

Table_Apx C-1: 2012 CDR Data (Data Reported for 2011) for Release Assessment .................... 69

Table_Apx C-2: Compilation of Release Factors and Other Release-Related Information in 

Various Risk Assessments ............................................................................................................. 70

Table_Apx C-3: Preliminary Values of Input Variables for Calculation of the Range of Release 

Rates from Manufacturing Sites or the Processing Sites of Each Processing Step ...................... 72

Table_Apx D-1: Percent Decrease in Total Initial Radioactivity in Viable Systems and Abiotic 

Controls During Sludge, Sediment, and Soil Simulation Tests Using 14C-labeled HBCD ............... 75

Table_Apx D-2: Toxicity of HBCD to Aquatic Plants ...................................................................... 78

Table_Apx D-3: Toxicity of HBCD to Aquatic Invertebrates.......................................................... 79

Table_Apx D-4: Toxicity of HBCD to Sediment Organisms ........................................................... 80

Table_Apx D-5: Toxicity of HBCD to Fish ...................................................................................... 82

Table_Apx D-6: Toxicity of HBCD to Terrestrial Plants ................................................................. 83

Table_Apx D-7: Toxicity of HBCD to Terrestrial Invertebrates ..................................................... 83

Table_Apx D-8: Toxicity of HBCD to Avian Species ....................................................................... 84

Table_Apx E-1: Acute Oral Toxicity of HBCD ................................................................................ 85

Table_Apx E-2: Acute Inhalation Toxicity of HBCD ....................................................................... 86

Table_Apx E-3: Repeated-Dose Toxicity of HBCD ......................................................................... 87

Table_Apx E-4: Reproductive and Developmental Toxicity of HBCD* ......................................... 89

Table_Apx E-5: Summary of Effects in Parental and F1 Rats After Dietary, Gestational, 

Lactational and Postnatal Exposure to HBCD ............................................................................... 93

Table_Apx E-6: Genotoxicity of HBCD .......................................................................................... 96

LIST OF FIGURES 

Figure 1-1: Generic Structure of Cyclic Aliphatic Bromides .......................................................... 12

Figure 2-1: Conceptual Model for HBCD ....................................................................................... 28

LIST OF APPENDIX FIGURES 

Figure_Apx 2.6.4-1: Stepwise Reductive Dehalogenation of HBCD ............................................. 76

Figure_Apx 2.6.4-2: Exposure-Response Array for Developmental and Reproductive Toxicity 

Studies of HBCD ............................................................................................................................ 92

Figure_Apx 2.6.4-3: Exposure-Response Array for Neurological Effects of HBCD ....................... 94

 
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AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS 

This report was developed by the United States Environmental Protection Agency (US EPA), 

Office of Chemical Safety and Pollution Prevention (OCSPP), Office of Pollution Prevention and 

Toxics (OPPT). The Work Plan Chemical Problem Formulation for the cyclic aliphatic bromides 

cluster was prepared based on currently available data. Mention of trade names does not 

constitute endorsement by EPA. 

EPA Assessment Team 

Leads: 

Susan A. Laessig, OPPT/Risk Assessment Division (RAD) 

Maria Szilagyi, OPPT/RAD 

Team Members: 

Katherine Anitole, OPPT/RAD 

Charles Bevington, OPPT/RAD 

Christina Cinalli, OPPT/RAD 

Ana Corado, OPPT/Environmental Assistance Division (EAD) 

Majd El-Zoobi, OPPT/RAD 

Conrad Flessner, OPPT/RAD 

Greg Fritz, OPPT/ Chemistry, Economics & Sustainable Strategies Division (CESSD) 

Amuel Kennedy, OPPT/RAD 

Emma Lavoie, OPPT/CESSD 

Timothy Lehman, OPPT/CESSD 

Laurence Libelo, OPPT/RAD 

Sue Slotnick, OPPT/National Program Chemicals Division (NPCD) 

Teresa Washington, OPPT/RAD 

Eva Wong, OPPT/RAD 

Management Leads: 

Mark Townsend, OPPT/RAD 

Nhan Nguyen, OPPT/RAD 

Acknowledgements 

Andrea Pavlick, visiting AAAS Science & Technology Policy Fellow, contributed to discussions 

during problem formulation. 

Portions of this document were prepared for EPA/OPPT by Abt Associates, the Eastern Research 

Group (ERG), Inc., the Syracuse Research Corporation (SRC) and Versar. 

Docket 

Please visit the public docket (Docket: EPA-HQ-OPPT-2015-0081) to view supporting 

information. 
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ABBREVIATIONS 

BFR Brominated Flame Retardant 

CASRN Chemical Abstract Service Registry Number 

CBI Confidential Business Information 

CDR Chemical Data Reporting 

CEC Commission for Environmental Cooperation 

CPSC Consumer Product Safety Commission 

EC European Commission 

ECHA European Chemicals Agency 

EFAST Exposure and Fate Assessment Screening Tool 

EPA Environmental Protection Agency 

EPS Expanded Polystyrene 

EU European Union 

FR Flame Retardant 

GD Gestation Day 

GLP Good Laboratory Practices 

HBCD Hexabromocyclododecane 

HIPS High Impact Polystyrene 

HPV High Production Volume 

HQ Hazard Quotient 

IRIS Integrated Risk Information System 

IUR Inventory Update Reporting Rule 

kg Kilogram(s) 

K

OW Octanol:Water partition coefficient 

lb Pound 

LOEL Lowest Observed Effect Level 

Log KOW Logarithmic Octanol:Water partition coefficient 

mg Milligram(s) 

MOE Margin of Exposure 

ng nanogram 

NHANES National Health and Nutrition Examination Survey 

NICNAS National Industrial Chemicals Notification and Assessment Scheme 

NKRA Not Known or Reasonably Ascertainable 

NOAEL No-observed-adverse-effect level 

OCSPP Office of Chemical Safety and Pollution Prevention 

OECD Organisation for Economic Co-operation and Development 

OPPT Office of Pollution Prevention and Toxics 

OSHA Occupational Safety and Health Administration

PBT Persistent, Bioaccumulative and Toxic 

pg picogram 

PMN Premanufacturing Notice 

PS Polystyrene 
Page 7 of 97 

PV Production Volume 

PVC Polyvinylchloride 

RA Risk Assessment 

RAR Risk Assessment Report 

REACH Registration, Evaluation, Authorisation and Restriction of Chemicals 

SNUR Significant New Use Rule 

SVOCs Semi-volatile organic chemicals 

TSCA Toxic Substances Control Act 

TG Test Guideline 

US United States 

WHO World Health Organisation 

WWTP Wastewater Treatment Plant 

XPS Extruded polystyrene 

yr Year 
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EXECUTIVE SUMMARY 

As part of EPA’s comprehensive approach to enhance the Agency’s management of existing 

chemicals, EPA/OPPT identified a work plan of chemicals for further assessment under the Toxic 

Substances Control Act (TSCA) in March 2012. Chemical risk assessments will be conducted if, 

as a result of scoping and problem formulation, there are exposures of concern, identified 

hazards and sufficient data for quantitative analysis. If an assessment identifies unreasonable 

risks to humans or the environment, EPA will pursue risk reduction. This document presents the 

problem formulation and initial assessment for the cyclic aliphatic bromides cluster as part of 

the TSCA Work Plan. 

EPA/OPPT has identified a cluster of cyclic aliphatic bromide flame retardant chemicals, 

including, hexabromocyclododecane (HBCD; CASRN 25637-99-4), 1,2,5,6,9,10-

hexabromocyclododecane (1,2,5,6,9,10-HBCD; CASRN 3194-55-6) and 1,2,5,6-

tetrabromocyclooctane (CASRN 3195-57-8), for risk assessment. These three chemicals have 

similar physical and chemical properties, and environmental fate characteristics. Uses for 

1,2,5,6-tetrabromocyclooctane have not been identified; the remaining two members of the 

cluster are used as flame retardants in polystyrene foams. HBCD and 1,2,5,6,9,10-HBCD have 

similar toxicological properties: known effects on the liver and reproductive system. 

For the purposes of this assessment, the use of “HBCD” refers to either CASRN (25637-99-4 or 

3194-55-6), or both. In addition, the conclusions drawn for this assessment will be applicable to 

both CASRNs. 

The conclusions from this problem formulation and initial assessment are that EPA/OPPT will 

evaluate current risk assessments, and if needed, conduct additional analyses as follows: 

• Workers: Evaluate the applicability of data from published risk assessments to US 

occupational exposure scenarios to determine if further assessment is needed. If the 

available data are not applicable, develop estimates of occupational exposures based on 

modeling and assumptions (e.g. approaches used in the new chemicals program). 

• General population and biota (aquatic, terrestrial and avian): Estimate releases to the 

environment in the US to evaluate potential exposure of general population and biota 

(aquatic, terrestrial and avian) to HBCD. The estimation approach may be based on 

information in available assessments, coupled with US specific information and/or 

estimation methods and assumptions. 

• Consumers: Use available or modeled data relevant to US exposure scenarios to 

estimate consumer exposure using available or modeled data relevant to US exposure 

scenarios with particular emphasis on sensitive populations. 

Several scenarios were identified where exposure to HBCD is expected to be low or unknown 

and further analysis is not recommended by EPA/OPPT under TSCA: 
Page 9 of 97 

• General population and environmental exposure from HBCD in landfills is not being 

assessed due to uncertainties in release from these sites. 

• General population exposure from HBCD in drinking water is not being assessed because 

drinking water monitoring data for the US are not available and conclusions from 

available risk assessments indicate a low concern from this exposure pathway (EC, 2008; 

Environment CA and Health CA, 2011; NICNAS, 2012). 

• Consumer exposure to HBCD in High Impact Polystyrene (HIPS) is not being assessed 

because the level of HBCD in HIPS in the US is unknown, it is not used in typical 

consumer products (e.g. computer or TV chassis), its use in other consumer products 

(e.g. electrical appliances) is enclosed limiting potential exposure and a low risk to 

consumers was indicated in available risk assessments. 

• Consumer exposure to HBCD in textile finishings is not being assessed because it was 

considered low risk by the CPSC in upholstered furnishings (CPSC, 2001), it was not 

reported to be used in consumer fabrics or textiles in the 2012 CDR (EPA, 2012a) and 

the extent of institutional (e.g. prisons), military or aviation use is unknown. 

• There are no adequate toxicological data based on inhalation or dermal exposures, nor 

is there a PBPK model readily available for route-to-route extrapolation. Therefore 

EPA/OPPT will not assess inhalation or dermal contact in this assessment. However, EPA 

is considering the quantification of incidental ingestion of particulates that would result 

from exposure to HBCD dust in occupational settings. A similar approach will be used to 

address consumer exposure to HBCD in dust. 

• There are no adequate lifetime exposure or carcinogenicity studies for HBCD. 

• Inhalation, dermal and lifetime exposure assessments are data gaps that add 

uncertainty to EPA’s risk assessment of HBCD. 

Hexabromocyclododecane (HBCD) has been used as a flame retardant in plastics (additive) and 

textiles (backcoating) since the 1980s. Evidence suggests that HBCD is bioaccumulative, 

environmentally persistent and toxic. Consequently, risk to human health and the environment 

have been assessed by several countries and global organizations. In 2010, OPPT prepared an 

action plan for HBCD. Subsequently, HBCD has been nominated for listing on the Toxic Releases 

Inventory (TRI; in review 2014) and EPA proposed a significant new use rule (SNUR) for use in 

consumer textiles (EPA, 2012e). 

During problem formulation, EPA/OPPT identified available fate, exposure and hazard data, and 

characterized potential exposures, receptors and effects. Data adequacy was determined by 
Page 10 of 97 

following published EPA/OPPT criteria1. EPA/OPPT reviewed the public literature (nominally to 

September 2014) and Agency information sources (public and confidential) to explore the 

sources, pathways, receptors and effects for consideration in the assessment. EPA also 

identified areas of data uncertainty and assumptions. 

Likely sources and pathways considered for analysis include: use of HBCD as a flame retardant 

in expanded polystyrene foam (EPS) and extruded polystyrene foam (XPS) in the building and 

construction industry accounting for 95% of HBCD use mainly in the form of insulation boards. 

The remaining uses are for high impact polystyrene (HIPS), mainly used for electronics, 

appliances and possible HBCD-containing textiles for institutional (e.g. prisons), military and 

aviation uses only (EPA, 2012e). HBCD is not used in consumer textiles that are manufactured in 

or imported into the US except for limited uses in certain automotive textiles. 

As outlined in the Conceptual Model for HBCD (Figure 2-1) EPA/OPPT identified the relevant 

TSCA use of HBCD for this assessment as its use as flame retardants in EPS and XPS products 

found in commercial and residential environments. EPA/OPPT determined that the major 

source of exposure to HBCD for human health and the environment was via HBCD dust and/or 

HBCD in dust generated during the manufacture and processing of HBCD, and the processing 

and use of products containing HBCD. HBCD in the form of dust or attached to particulates has 

been measured in indoor domestic and commercial environments, therefore there may be risks 

to consumers. Preliminary exposure calculations for the US population suggest that the 

methodology used in available assessments underestimates consumer exposure to HBCD from 

dust for US consumers. Of particular interest for evaluation are toddlers whose exposure to 

HBCD from dust in non-residential microenvironments contributes to their total HBCD exposure 

(Abdallah and Harrad, 2011). HBCD may also make its way into the outdoor environment by 

transportation through the air and/or washed down the drains (or storm drains) to enter 

waterways. 

These exposure scenarios have been considered in risk assessments conducted by other 

countries and the toxicity and risk of HBCD to aquatic organisms and human health have been 

assessed and summarized in several publications (EC, 2008; Environment CA and Health CA, 

2011; EPA, 2008a, 2014b; NICNAS, 2012; OECD, 2007). However, it is unknown how these 

conclusions apply to current HBCD manufacture, processing, use and exposure in the US. 

Therefore, EPA plans to evaluate information in the non-US published risk assessments to 

determine whether data from other countries are relevant and applicable to US exposures, and 

where appropriate, supplementing these risk assessments with current and US specific 

information. 

 

1

 Generally followed guidance outlined for the High Production Volume Challenge Program at: 

http://www.epa.gov/chemrtk/pubs/general/datadfin.htm and 

http://www.epa.gov/champ/pubs/hpv/Methodology%20for%20HBP%20under%20ChAMP_March%202009.pdf

and EPA Risk Assessment Guidance at: http://www.epa.gov/raf/
Page 11 of 97 

The results of problem formulation as illustrated in the conceptual model and described under 

the assessment questions indicate that: 

• There is the potential for occupational exposure to HBCD during HBCD manufacture and 

processing and polystyrene foam manufacture and processing. 

• There is potential for general population exposure to HBCD from releases to the 

environment (air, water, soil and fish consumption). 

• There is potential for environmental exposure in water, sediment and soil to HBCD from 

releases to the environment. 

• There is potential for consumer exposure to HBCD from the use of consumer products in 

indoor environments. 

In summary, as a result of problem formulation, EPA/OPPT plans to evaluate current risk 

assessments and conduct additional risk analysis on potential worker, general population, 

consumer and environmental exposures under the TSCA Existing Chemicals Program using 

existing data and methods. EPA/OPPT plans to review and evaluate available exposure (See 

Section 2.4 and Appendix C) and hazard benchmarks (Section 2.5, Appendix D and Appendix E) 

and to evaluate the potential non-cancer risk to humans using a margin of exposure approach 

and potential risks to environment using a hazard quotient approach. 

1 INTRODUCTION 

As a part of EPA’s comprehensive approach to enhance the Agency’s management of existing 

chemicals, in March 2012 EPA/OPPT identified a work plan of chemicals for further assessment 

under the Toxic Substances Control Act (TSCA)2. After gathering input from stakeholders, 

EPA/OPPT developed criteria used for identifying chemicals for further assessment3

. The 

criteria focused on chemicals that meet one or more of the following factors: (1) potentially of 

concern to children’s health (for example, because of reproductive or developmental effects); 

(2) neurotoxic effects; (3) persistent, bioaccumulative, and toxic (PBT); (3) probable or known 

carcinogens; (4) used in children’s products; or (5) detected in biomonitoring programs. Using 

this methodology, EPA/OPPT identified a TSCA Work Plan of chemicals as candidates for risk 

assessment in the next several years. In the prioritization process, the Cyclic Aliphatic Bromides 

Cluster, specifically hexabromocyclododecane (HBCD), was identified for assessment based on 

its high production volume and PBT characteristics (persistent, bioaccumulative and toxic). 

EPA/OPPT is performing risk assessments on chemicals in the work plan. If an assessment 

identifies unacceptable risks to humans or the environment, EPA/OPPT will pursue risk 

reduction. The target audience for this risk assessment is primarily EPA risk managers; however, 

it may also be of interest to the broader risk assessment community as well as US stakeholders 

interested in HBCD. The information presented in the risk assessment may be of assistance to 

 

2 http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html 

3 http://www.epa.gov/oppt/existingchemicals/pubs/wpmethods.pdf
Page 12 of 97 

other federal, state, and local agencies as well as to members of the general public who are 

interested in the risks of HBCD. 

The initial step in EPA/OPPT’s risk assessment development process, which is distinct from the 

initial prioritization exercise, includes scoping and problem formulation. During these steps 

EPA/OPPT reviews currently available data and information, including but not limited to, 

assessments conducted by others (e.g., authorities in other countries), published or readily 

available reports and published scientific literature. During scoping and problem formulation 

the more robust review of the factors influencing initial prioritization may result in refinement – 

either addition/expansion or removal/contraction – of specific hazard or exposure concerns 

previously identified in the prioritization methodology. 

This document includes the results of scoping and problem formulation and initial assessment 

for HBCD. During problem formulation, EPA/OPPT identified available exposure and hazard 

data, and characterized potential exposures, receptors and effects. EPA/OPPT developed a 

conceptual model (Figure 2-1) and analysis plan (Section 2.6.2) as a result of problem 

formulation. 

1.1 Scope of the Assessment 

The members of the cyclic aliphatic bromides cluster are the brominated flame retardants 

(BFR): Hexabromocyclododecane (HBCD; CASRN 25637-99-4) 

1,2,5,6,9,10-Hexabromocyclododecane (1,2,5,6,9,10-HBCD; CASRN 3194-55-6) 

1,2,5,6-Tetrabromocyclooctane (CASRN 3194-57-8)4

EPA prioritized the different BFR chemicals and grouped them into different clusters based on 

structure. The cyclic aliphatic bromide cluster included chemicals that contain a ring of 6 to 12 

saturated carbon atoms with different bromine atoms replacing some of the H atoms on the 

ring or attached in sidechains. 

Figure 1-1: Generic Structure of Cyclic Aliphatic Bromides 

Chemicals considered for this cluster were: 1,2-Dibromo-4-(1,2-dibromoethyl) cyclohexane 

[CASRN: 3322-93-8], 1,2,3,4,5,6-hexabromocyclohexane [CASRN: 1837-91-8], 1,2,3,4,5-

Pentabromo-6-chlorocyclohexane [CASRN: 87-84-3] and 1,2,5,6-tetrabromocyclooctane 

[CASRN: 3194-57-8]. One other chemical, Accession number 27248, with generic name 

polybromocycloalkane would be a member of this Work Plan of chemicals; however, no 

 

4

 No domestic uses were identified for 1,2,5,6-Tetrabromocyclooctane (CASRN 3194-57-8). This flame retardant is 

not functional in current EPS and XPS manufacturing processes. Its thermal stability does not meet operating 

temperature requirements for the manufacture of XPS foam (EPA, 2014b). 
Page 13 of 97 

production volume has been reported since 1977. Therefore, these chemicals were rejected, 

along with the individual 1,2,5,6,9,10-HBCD diastereomers, because they were either not on 

the TSCA Inventory or were not manufactured at sufficient production volume to be reported in 

the IUR/CDR data collection. 

 

Two HBCD commercial chemicals meet this cluster criteria and are the subject of this 

assessment. These are the only two chemicals being considered for problem formulation in this 

work plan which differs from the action plan (EPA, 2010a) inclusion criteria. 

• Hexabromocyclododecane [CASRN 25637-99-4] is produced as a mixture of 16 possible 

isomers of 1,2,5,6,9,10-hexabromocyclododecane from the bromination of 1,5,9-

cyclododecatriene. HBCD is the only member of this cluster that is on the TSCA 

Inventory that has a significant production volume (as reported in the IUR and CDR).

• 1,2,5,6,9,10-hexabromocyclododecane [CASRN 3194-55-6] is a mixture of three main 

diastereomers of the 16 possible 1,2,5,6,9,10-hexabromocyclododecane isomers. Each 

individual isomer in this HBCD cluster member contains a ring of 12 saturated carbon 

atoms with 6 bromine atoms replacing 6 hydrogen atoms. Each isomer has a molecular 

formula of C12H18Br6. The three most common individual diastereomers are 

designated as alpha-, beta-, and gamma-HBCD and each has an individual CAS Registry 

Number (as do all 16 isomers)5. 

For the purposes of this assessment, the use of “HBCD” refers to either CASRN (25637-99-4 and 

3194-55-6), or both. In addition, the conclusions drawn for this assessment will be applicable to 

both CASRNs. 

Section 2.6.1 presents the conceptual model developed by EPA/OPPT for HBCD. Using available 

tools and approaches, the Agency identified the relevant TSCA use of HBCD for this assessment 

is its use as flame retardants in EPS and XPS products found in commercial and residential 

environments. Its use in HIPS is not being assessed because the level of HBCD in HIPS in the US 

is unknown, it is not used in typical consumer products (e.g. computer or TV chassis), its use in 

other consumer products (e.g. electrical appliances) is enclosed limiting potential exposure and 

a low risk to consumers was indicated in available risk assessments. Consumer exposure to 

HBCD in textile finishings is not being assessed because it was considered low risk by the CPSC 

in upholstered furnishings (CPSC, 2001), it was not reported to be used in consumer fabrics or 

textiles in the 2012 CDR (EPA, 2012a) and the extent of institutional (e.g. prisons), military or 

aviation use is unknown (EPA, 2012e). 

EPA determined that the major source of exposure to HBCD for human health and the 

environment was via HBCD dust and/or HBCD in dust generated during the manufacture and 

processing of HBCD, and the processing and use of products containing HBCD. HBCD in the form 

of dust or attached to particulates has been measured in indoor domestic and commercial 

 

5

 This is significant because much of the data are reported for the individual alpha, beta, and gamma isomers 

rather than for the two commercial products. 
Page 14 of 97 

environments, therefore there may be risks to consumers. Preliminary exposure calculations 

for the US population suggest that the methodology used in available assessments 

underestimates consumer exposure to HBCD from dust for US consumers. Of particular interest 

for evaluation are toddlers whose exposure to HBCD from dust in non-residential 

microenvironments contributes to their total HBCD exposure (Abdallah and Harrad, 2011). 

HBCD may also make its way into the outdoor environment by transportation through the air 

and/or washed down the drains (or storm drains) to enter waterways.

These exposure scenarios have been considered in risk assessments conducted by other 

countries and the toxicity and risk of HBCD to aquatic organisms and human health have been 

assessed and summarized in several publications (EC, 2008; Environment CA and Health CA, 

2011; EPA, 2008a, 2014b; NICNAS, 2012; OECD, 2007). However, it is unknown how these 

conclusions apply to current HBCD manufacture, processing, use and exposure in the US. 

Therefore, EPA plans to evaluate information in the non-US published risk assessments to 

determine whether data from other countries are relevant and applicable to those in the US, 

and where appropriate, supplement these risk assessments with current and US specific 

information. 

1.2 Regulatory and Assessment History 

The regulatory and assessment history of HBCD in the US and internationally are summarized in 

Table_Apx A-1. 

United States - National 

HBCD was sponsored in the HPV Challenge Program by BFRIP (BFRIP, 2001). Subsequently, 

EPA/OPPT prepared a risk based prioritization document in 2008 (EPA, 2008a) which concluded 

that there was a high concern for potential risk to aquatic organisms, a medium concern for 

potential risk to the general population from environmental releases and a high concern for 

potential risk to workers, consumers and children. In 2010, EPA/OPPT prepared an action plan 

for HBCD (EPA, 2010a). Subsequently, HBCD has been nominated for listing on the Toxic 

Releases Inventory (TRI; in review 2014) and is subject to rulemaking for use in textiles (EPA, 

2012e). In addition, OPPT/DfE (OPPT Design for the Environment) published a flame retardant 

alternatives assessment for HBCD in 2014 (EPA, 2014). 

 

HBCD is currently on the EPA Integrated Risk Information System (IRIS) program agenda. The 

anticipated date for a completed assessment has not yet been determined (EPA, 2015c). HBCD 

is not regulated in drinking water under the National Primary Drinking Water Regulations (EPA, 

2015b) and is not on the Contaminant Candidate List (CCL) (EPA, 2015a). Published risk 

assessments indicate low risk to the general population from drinking water exposure (EC, 

2008; Environment CA and Health CA, 2011; NICNAS, 2012). HBCD is under consideration for 

inclusion in the NHANES human bio-monitoring program. 
Page 15 of 97 

In 2006, the Consumer Product Safety Commission (CPSC) assessed the risk of exposure to 

HBCD in residential upholstered furniture (CPSC, 2001) and concluded that HBCD did not 

present a hazard to consumers, as defined by the Federal Hazardous Substances Act (FHSA). 

The Occupational Safety and Health Administration (OSHA) has not established occupational 

exposure limits for HBCD. 

United States – States 

In California, HBCD is listed as an initial informational candidate under California’s Safer 

Consumer Products regulations (DTSC, 2010), on the state’s Proposition 65 list (OEHHA, 2007) 

and is designated a priority chemical for biomonitoring; however, California has not yet started 

biomonitoring HBCD (SGP, 2014). In Maine, Minnesota and Washington, HBCD is considered a 

chemical of high concern (DEP, 2013; MDH, 2013; WSDE, 2013). Oregon considers HBCD a 

priority persistent pollutant (DEQ, 2010a, 2011) and publishes use, exposure pathways and 

release data for HBCD under this program (DEQ, 2010b). 

International 

HBCD is of international concern because of its PBT properties. The toxicity of HBCD to aquatic 

organisms and human health have been assessed and summarized in several publications (EC, 

2008; Environment CA and Health CA, 2011; EPA, 2008a, 2014b; NICNAS, 2012; OECD, 2007). 

HBCD was added to ECHA’s list of Substances of Very High Concern (SVHCs) on October 28, 

2008 (ECHA, 2008). Risk assessments have been published by Australia (NICNAS, 2012), Canada 

(Environment CA and Health CA, 2011) and the European Union (EC, 2008). The conclusions 

from these assessments are as follows: 

Occupational, General Population and Consumer Exposure 

In the Health Canada assessment, the margin of exposure for neurobehavioral effects in infants 

and children was determined using the LOAEL (0.9 mg/kg-day) from a 90-day study in mice 

(Eriksson et al., 2006) (Environment CA and Health CA, 2011). This study was not used by the 

European Commission or the Australian Government (EC, 2008; NICNAS, 2012). For 

reproductive effects, all three assessments used the NOAEL (10 mg/kg-day) from the twogeneration study in rats (Ema et al., 2008). In addition, the European Commission used the 

NOAEL (22.9 mg/kg-day) from the 28-day study in rats (van der Ven et al., 2006). All three risk 

assessments concluded that the risk to general population and consumers was of low concern. 

The occupational risk conclusions vary in different countries due to variations in exposure (e.g. 

HBCD is not manufactured in Australia) and the risk varies with the activity associated with the 

extent of exposure to HBCD; low to high, depending on the activity relevant to each country. 

Environmental Exposure 

HBCD is persistent and bioaccumulative and is considered a risk to the environment in all three 

published risk assessments (EC, 2008; Environment CA and Health CA, 2011; NICNAS, 2012). In 

May 2013, HBCD was added to the United Nation’s Stockholm Convention list of Persistent 
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Organic Pollutants (Stockholm Convention, 2013). The chemical is scheduled to be eliminated 

by November 2014 with specific exemptions for production and uses in expanded or extruded 

polystyrene building insulation. As required by the convention, parties that use these 

exemptions must register with the secretariat and the exemptions will expire in November 

2019. 

Currently, under the Commission for Environmental Cooperation (CEC), Canada, Mexico and the 

US are evaluating the presence and migration of flame retardants, including HBCD, from 

consumer products (CEC, 2015). The information gathered from this effort will inform exposure 

assessors and risk managers and the executive summary of the final report(s) will be available 

to the public. 

2 PROBLEM FORMULATION 

Problem formulation aims to determine the major factors to be considered in an assessment, 

including exposure pathways, receptors and health endpoints (EPA, 1998a, 2014c). Accordingly, 

this problem formulation summarizes the exposure pathways, receptors and health endpoints 

EPA/OPPT considered to determine whether to conduct further risk analysis and what 

exposure/hazard scenarios to include in a potential risk assessment. To make this 

determination, EPA/OPPT conducted a preliminary data review to identify available fate, 

exposure and hazard data and determine its likely suitability for quantitative analysis and to 

identify exposure pathways, receptors and health endpoints for quantitative analysis. 

The outcome of this evaluation is summarized in a conceptual model (Figure 2-1) that illustrates 

the exposure pathways, receptors and effects that were considered for potential risk 

assessment. An analysis plan is developed if the results of problem formulation indicate the 

need for further analysis. 

2.1 Physical and Chemical Properties 

The physical-chemical properties of HBCD are shown in Table 2-1. Commercial preparations of 

HBCD may contain some impurities, such as tetrabromocyclododecene or other isomeric HBCDs 

(UNEP, 2010) which are not separately included in this problem formulation. 
Page 17 of 97 

Table 2-1: Select Physical-Chemical Properties * 

Properties a

1,2,5,6,9,10-Hexabromocyclododecane 

HBCD 

Melting Point 175 – 195 °C 

Boiling Point > 200 °C [decomposes] b

Vapor Pressure 6.27 E-5 Pa at 21°C 

Water Solubility 66 μg/L at 20°C c

Octanol Water Partition 

Coefficient (Log Kow)

5.625 at 25 °C 

*PCHEM Properties reported in the HPV Robust Summary (BFRIP, 2001) are measured values from a composite of 

commercial products from 3 different manufacturers.

aHPV Data Summary and Test Plan for Hexabromocyclododecane (HBCD) CASRN 3194-55-6 

bEC HBCD RAR (EC, 2008) 

c

Sum of solubilities for 3 major isomers [alpha, beta, and gamma] in commercial product (ECHA, 2008) 

2.2 Production Volume and Uses 

This section discusses the production volume and uses of the cyclic aliphatic bromides cluster 

chemicals and is organized as follows: 

• The 2012 Chemical Data Reporting (CDR) production, import, and export volumes for 

these chemicals are listed in Appendix B. 

• Additional details on production volume for HBCD can be found in Section 2.2.1. 

• Use information can be found in Section 2.2.2. 

• Future market trends are discussed in Section 2.2.3. 

2.2.1 Production Volume 

EPA/OPPT’s 2012 public Chemical Data Reporting (CDR) database (EPA, 2012a), formerly the 

Inventory Update Reporting (IUR) database includes national-level production volume data; 

however, the 2012 public CDR database provides limited information on the domestic 

production volumes of HBCD. For both CAS numbers, site-specific production volumes and 

national level production volumes were withheld as TSCA Confidential Business Information 

(CBI) for the 2011 reporting year (EPA, 2012a). Therefore, EPA/OPPT proposes to assess the 

production volume of HBCD based on the best publicly available production volume data which 

is the historical IUR and CDR data presented in Appendix B . EPA/OPPT assumes that current 

Br

Br

Br

Br

Br Br
Page 18 of 97 

production volumes are equal to the most recently reported production volumes (the 2002 and 

2006 data for CASRNs 25637-99-4 and 3194-55-6, respectively). 

For the 2011 reporting year, the data indicate that two sites currently import at least one of the 

chemicals and that three sites domestically manufacture the chemicals. However, according to 

the US International Trade Commission, the US imported 92,270 pounds of HBCD (CASRN 

25637-99-4) in 2012 (USITC, 2013). This volume does not include HBCD imported as part of an 

article. Three sites reported export volumes as CBI, and two sites reported no exports (EPA, 

2012a). 

Five sites are identified by the 2012 CDR database as manufacturers or importers of HBCD: 

BASF Corporation, Albemarle Corporation, The Dow Chemical Company, and two CBI sites (EPA, 

2012a). Albemarle manufactures HBCD flame retardants under the Saytex®HP-900 trade name 

(Albemarle Corporation, 2000). Both Dow and BASF indicate in the CDR data that they are 

importers; however, trade names of the BASF or Dow Chemical products that use or contain 

HBCD could not be found in a literature search. For more detailed information on 

manufacturers of HBCD who reported for the 2012 CDR collection period, see Appendix B. 

2.2.2 Uses 

2.2.2.1 Use in Expanded Polystyrene Foam (EPS) and Extruded

Polystyrene Foam (XPS) 

HBCD is used as a flame retardant in polystyrene foam, textiles, and high impact polystyrene. 

The chemical has been in production since the 1960s although there is limited data about the 

historical use of HBCD in products. 

The main use of HBCD in the US, the EU, Japan, and Switzerland is as a flame retardant in 

expanded polystyrene foam (EPS) and extruded polystyrene foam (XPS) (UNEP, 2010; Weil and 

Levchik, 2009). Use in EPS and XPS accounts for 95 percent of all HBCD applications and began 

in the 1980s (EPA, 2014b; UNEP, 2010). EPS and XPS are used in the US for thermal insulation 

boards and laminates for sheathing products used in the building and construction industry. In 

addition, EPS is used to provide protection from moisture, prevent freezing, provide a stable fill 

material, and create high-strength composites in construction applications. XPS foam board is 

used mainly for roofing applications and architectural molding. HBCD is used in both types of 

foams, because it is highly effective at low-use levels, and therefore maintains the insulation 

properties of the EPS and XPS foam (Morose, 2006). EPS boards contain approximately 0.5 

percent HBCD by weight in the final product while XPS boards contain 0.5 to 1 percent HBCD by 

weight (Extruded Polystyrene Foam Association, 2011; Morose, 2006). 

The National Institute of Heath’s (NIH) Household Products Database lists HBCD as an 

ingredient in several extruded and foam insulation products, all of which are manufactured by 

Owens Corning for use in the US. Currently, Owens Corning lists HBCD in two of its products: 
Page 19 of 97 

Foamular® Extruded Polystyrene Insulation and Foamular® Extruded Polystyrene Insulation - 

Zero Ozone Depletion Formula, at levels between 0.5 and 1.0 percent (Owens Corning, 2005). 

The Australian Department of Health and Aging reports that EPS resins are also used in 

industrial packaging including packaging durable goods and beanbag fill (NICNAS, 2012). 

Historic data indicate that EPS was used in packaging in North America (Kinshore, 2007), 

however EPA/OPPT was unable to confirm if this is a current use of HBCD in the US. It should be 

noted that uses of polystyrene foam in consumer products, such as packaging, generally do not 

require the use of a flame retardant (EPA, 2014b). 

2.2.2.2 Use in Textiles 

In the US, HBCD was historically used as a flame retardant in the back coating of textiles. 

However, supported by information gathered from research, industry, and consumer product 

organizations, EPA/OPPT believes that HBCD is no longer used in consumer textile applications 

outside of the auto industry. EPA/OPPT received information from a group of textile 

formulators that the end uses of HBCD-containing textiles are for military, institutional, and 

aviation applications such as durable carpet tiles for hospitals or prisons (EPA, 2012e; Friddle, 

2011). Use in this application is quite small; in 2005 only 1 percent of total production volume 

of HBCD was used in textiles in the US (EPA, 2012e). HBCD is typically found in textile back 

coatings at levels of 10-25 percent (Harscher, 2011). 

In Europe, only 2 percent of HBCD was used in textile applications in 2007 (ECHA, 2009). 

2.2.2.2.1 Use in Automotive Textiles 

Within the US auto industry, EPA/OPPT found that a small amount of HBCD is used in floor 

mats, headliners, and possibly other interior fabrics in automobiles made or imported to the US 

(EPA, 2012e). 

HBCD is currently regulated under Annex XIV of European Union’s Regulation on Registration, 

Evaluation, Authorisation and Restriction of Chemicals (REACH), which sets a “sunset date” for 

the use of the chemical of August 21, 2015. In response to the REACH regulation, the auto 

industry has formed a consortium to help US manufacturers understand the new requirements; 

develop tools, processes and best practices; and coordinate compliance efforts. The consortium 

consists of five North American sponsoring companies, Chrysler, Ford, General Motors, Honda, 

and Toyota (AIAG, 2011). It is likely that as companies discontinue the use of HBCD in European 

cars to comply with the REACH regulation, they will discontinue its use in North American 

automobiles as well. 
Page 20 of 97 

2.2.2.2.2 Historic Use in Textiles 

HBCD was historically used as a flame retardant in the US in the back-coating of textiles, 

upholstered furniture, draperies, wall coverings, and interior textiles such as roller blinds 

(ECHA, 2009; Morose, 2006). The majority of HBCD used in textiles was for upholstered 

furniture, because textiles treated with the chemical meet the stringent fire safety laws of the 

United Kingdom (UK) and California (Morose, 2006). 

In the 2006 IUR data, one manufacturer/importer of HBCD (CASRN 3194-55-6) reported the use 

of the chemical substance under the NAICS code for textile and fabric finishing mills (EPA, 

2006a). For this use, less than 1 percent of the total production volume of the chemical 

substance was in consumer and commercial products. The reporting does not distinguish 

between commercial and consumer use (EPA, 2006a). 

EPA/OPPT conducted research to determine whether HBCD was used in textile applications for 

end products sold to consumers in the US. In 2010, an HBCD expert with the Consumer Product 

Safety Commission (CPSC) expressed to EPA/OPPT his understanding that HBCD is used only in 

non-consumer textiles such as firefighters' suits (EPA, 2012e). In 2011, EPA/OPPT requested 

information from current and former manufacturers of HBCD. The responses indicated that 

only one manufacturer sells HBCD for textile uses. The company did not know whether the end 

use of any of those textiles is a consumer article (EPA, 2012e). Additionally, a representative of 

the furniture manufacturing company Herman Miller told EPA/OPPT that HBCD is not in its 

products (EPA, 2012e). HBCD was not reported to be used in fabrics or textiles in the 2012 CDR 

(EPA, 2012a). 

2.2.2.3 Use in High Impact Polystyrene (HIPS) 

In both the US and Europe, HBCD is used as a flame retardant in high impact polystyrene (HIPS) 

for electrical and electronic appliances such as audio-visual equipment, refrigerator lining, and 

some wire and cable applications (ECHA, 2009; Morose, 2006). Use in television sets is the 

predominant application of HIPS (Weil and Levchik, 2009). HBCD is found in HIPS products in 

levels of 1-7% by weight (EC, 2008). Similar data for the US are not available. 

2.2.2.4 Other Identified Uses 

The Australian Department of Health and Aging also reports that minimal amounts of HBCD are 

imported into the country already incorporated into various articles such as inkjet printers, 

projectors, scanners, ventilation units for offices, compact fluorescent lights, and LCD digital 

audiovisual systems (NICNAS, 2012). There are no data to indicate that HBCD is used in the US 

for these uses. 
Page 21 of 97 

2.2.2.5 Summary of All Uses 

2.2.2.5.1 Summary of CDR Information 

Appendix B summarizes the HBCD use data as reported in the 2012 CDR. This Appendix also 

presents information on potential end uses of the chemical beyond what is reported in the 

CDR. The information is based on additional sources as described in the preceding sections of 

the report. 

2.2.2.5.2 Summary of EU Data 

Table_Apx B-4 provides a summary of HBCD uses and potential end products as presented in 

the EU risk assessment report (EC, 2008). Although the EU market and industry for HBCD are 

considered to be similar to those in the US, differences do exist in building technologies, 

climate, and consumption patterns, limiting the comparison of the two markets.

2.2.3 Future Market Trends 

EPA/OPPT expects future use of HBCD to decrease worldwide as the result of forthcoming 

international regulations. HBCD is listed under Annex XIV of European Union’s REACH, which 

sets a “sunset date” for August 21, 2015. After this date, only persons with approved 

authorization applications may continue to use the chemical (BSEF, 2012). In addition, in May of 

2013, the Conference of the Parties (COP) to the Stockholm Convention on Persistent Organic 

Pollutants (Convention) decided to list HBCD on the Convention’s “elimination” annex, with 

specific exemptions for production and use for expanded polystyrene and extruded polystyrene 

in buildings for parties listed in the register of specific exemptions for the substance. The 

specific exemptions can last up to 5 years and, subject to approval by the COP, can be renewed 

for a period of up to 5 years. However, the US is not a party to the Stockholm Convention and 

therefore this action is not applicable to the US. 

Given that HBCD is going to be phased out for some uses in the majority of the world, including 

the EU, Canada, Australia, and most of Asia, it is likely that global processors and users of HBCD 

will work towards phasing out the chemical rather than endure the cost of maintaining a 

separate supply chain for the US. It is expected that the Stockholm Convention may incentivize 

US processors, manufacturers, and importers to consider alternatives to HBCD for some 

applications, which may impact future demand growth for the chemical. 

2.3 Fate and Transport 

The environmental fate of HBCD has been summarized in several publications (EC, 2008; 

Environment CA and Health CA, 2011; EPA, 2008a, 2014b; NICNAS, 2012; OECD, 2007). A 

general overview of persistence and bioaccumulation is presented below. Additional details can 

be found in Appendix D. 
Page 22 of 97 

HBCD is persistent in environmental media. It is expected to be stable to hydrolysis and direct 

photolysis. Measured aerobic biodegradation half-lives either range up to months, or are 

greater than months. Anaerobic biodegradation may be more rapid but in anaerobic conditions 

degradation is also slow with half-lives ranging to months or greater. HBCD is expected to sorb 

to particulates and sediments and have limited mobility in soil. It is expected to volatilize to 

some extent from soils and water surfaces. In the atmosphere, HBCD is expected to occur 

primarily as particulates and may undergo long range transport. It will be removed from the 

atmosphere by wet or dry deposition, and has an estimated vapor phase half-life of 2.1 days for 

reaction with hydroxyl radicals. HBCD is highly bioaccumulative with measured fish 

bioconcentration factor (BCF) values of greater than 18,000. 

2.4 Exposures 

2.4.1 Releases to the Environment 

HBCD is manufactured or imported as a powder or pellets (EPA, 2012a) and incorporated into a 

polymer matrix, including polystyrene foam, as an additive that is incorporated into the matrix 

(EC, 2008). The life cycle of HBCD includes the manufacture and processing of HBCD followed by 

the commercial and consumer use, service life, and disposal of products that contain HBCD (EC, 

2008; Stockholm Convention, 2010). HBCD is released to the environment throughout the life 

cycle (EC, 2008; EPA, 2014; Stockholm Convention, 2010). 

TRI data are not yet available for HBCD, but releases from industrial sites to waste water 

treatment plants (WWTP), surface water, air and landfill are expected (EC, 2008; Environment 

Canada, 2011; NICNAS, 2012). HBCD is expected to remain largely immobile in landfills (EPA, 

2014) and therefore industrial releases to water and air are of greater interest to EPA/OPPT 

than industrial releases to landfills. Sawing of EPS or XPS during commercial and consumer use 

results in release of HBCD (EC, 2008). Emissions of HBCD from EPS and XPS and wear of these 

products result in release of HBCD during their service life (EC, 2008). The total of releases of 

HBCD from construction sites to air or surface water from professional use of EPS or XPS is large 

in comparison with the total releases to each of these media from the manufacture of HBCD or 

processing of HBCD (to make EPS and XPS) (EC, 2008). However, releases from construction 

sites are dispersed and therefore are likely to be lower than industrial releases on a per-site 

basis. Disposal of EPS and XPS may result in releases to the environment as a result of 

demolition of buildings or material that is left on or in the soil (EPA, 2014); EPA/OPPT believes 

these releases are likely to be lower than industrial releases on a per-site basis. 

Manufacturing and processing steps to be assessed are summarized in Appendix C. 
Page 23 of 97 

2.4.2 Presence in the Environment 

2.4.2.1 Surface Water 

Studies of surface water in the US are limited to a study of suspended sediment from the 

Detroit River, a highly industrialized area. The maximum measured concentration in suspended 

sediment was 3.7 μg/kg dw (Marvin et al., 2006) with similar values measured in China and 

Sweden (Arnot et al., 2009; He, S. et al., 2013). HBCD was identified in lakes, tributaries and 

streams in China and the UK with measured concentrations in the ng/L levels (BRE, 2009; 

Harrad et al., 2009; MOE, 2000, 2005). Measurements of marine water were not found, and 

these values would be expected to be low. Geographically and temporally distributed 

monitoring data of this cluster in US surface waters were not found. 

2.4.2.2 Wastewater 

HBCD in wastewater influent (dissolved phase) at sewage treatment plants in South Africa and 

the UK were measured at concentrations of ng/L to <1 μg/L levels (Chokwe et al., 2012; De Boer 

et al., 2002). Measurements of the suspended phase of influent from sewage treatment plants 

in the UK and Netherlands were as high as 3800 μg/kg dw (De Boer et al 2002, Morris et al., 

2004). Measurements of suspended phase in effluent were as high as 18 μg/kg dw (Morris et 

al., 2004). Measured concentrations of HBCD in wastewater in the US are not available. 

2.4.2.3 Sludge 

Measurements of HBCD levels in sludge have been made throughout Europe (Covaci et al., 

2006; De Boer et al., 2002; Gorga et al., 2013; Guerra et al., 2010; Morris et al., 2004) and Asia 

(Feng et al., 2012; Hwang et al., 2012) with values ranging from non-detect (detection limit = 4 

ng/g) at a WWTPs in Spain (Gorga et al., 2013)(Guerra et al., 2010) to as high as 29 mg/kg dw in 

industrial sludge from Korea (Hwang et al., 2012). A study in the US of processed sludge from 

activated sludge-type secondary treatment facility treating domestic & industrial waste 

(including automotive interior manufacturer) found comparatively high levels of HBCD, on the 

order of g/kg (La Guardia et al., 2010). Samples analyzed from the EPA 2001 National Sewage 

Sludge Survey showed approximately 20 ug/kg HBCD (Venkatesan and Halden, 2014). 

2.4.2.4 Soil 

Soil sampling is limited to measurements from Sweden (Arnot et al., 2009), Germany and 

Belgium (Arnot et al., 2009; Covaci et al., 2006), and throughout Asia (Eguchi et al., 2013; Li et 

al., 2012b; Wang et al., 2013) with the highest values (μg/kg dw) found in the soil near a HBCD 

manufacturing plant in the Laizhou Bay area. Studies with measured levels of HBCD in soils in 

the US were not available. 
Page 24 of 97 

2.4.2.5 Sediment 

Sediment measurements have been made in numerous countries throughout the world 

including Asia, South America, North America, Europe and South Africa (Al-Odaini et al., 2013; 

Arnot et al., 2009; Baron et al., 2013; Canton et al., 2008; Covaci et al., 2006; De Boer et al., 

2002; de Boer et al., 2004; Feng et al., 2012; Guerra et al., 2012; Harrad et al., 2009; He, M.-J. et 

al., 2013; Klosterhaus et al., 2012; La Guardia et al., 2012; La Guardia et al., 2013; Li et al., 2013; 

Li et al., 2012b; Managaki et al., 2012; MOE, 2000, 2005; Morris et al., 2004; Xu et al., 2013; 

Zhang et al., 2013) with the highest value (>300 mg/kg dw) found at the Yadkin River at the 

outfall downstream from a textile facility in North Carolina, US (La Guardia et al., 2012). 

2.4.2.6 Biota 

HBCD has been reported in several fresh water and marine species throughout North America. 

In the US, carp from the Hyco River in Virginia were reported with mean HBCD levels of 4640 

μg/kg lipid weight (Chen et al., 2011). HBCD was also measured in the blubber or liver of various 

marine mammals: Bottlenose dolphin (Johnson-Restrepo et al., 2008), Bull shark (JohnsonRestrepo et al., 2008), Atlantic Sharpnose shark (Johnson-Restrepo et al., 2008), White Sided 

dolphin (Peck et al., 2008), and California sea lions (Stapleton et al., 2006) with the highest 

mean concentration of 130 μg/kg lipid weight reported in the White Sided dolphin (Peck et al., 

2008). Similarly, HBCD has been detected in the blubber or liver of marine species (Budakowski 

and Tomy, 2003; Muir et al., 2006; Tomy et al., 2009) and in whole or the muscle of fresh water 

fish in Canada (Law et al., 2006a; Tomy et al., 2008). 

2.4.3 Occupational Exposure 

EPA/OPPT considers inhalation and dermal exposure to be important exposure pathways for 

workers. Sometimes, the inhalation of air-suspended particulate matter that is subsequently 

trapped in mucous and moved from the respiratory system to the gastrointestinal tract (EPA, 

2011b) is a contributor to aggregate exposures. This will be referred to here as incidental 

ingestion of inhaled particulates. 

HBCD is manufactured as a powder at two US sites and is imported as pellets at two other sites. 

The processing of HBCD for the manufacture of EPS and XPS and the subsequent commercial 

use of these products by workers is described in EC (2008) and EPA (2014b). Industrial and 

commercial workers are potentially exposed to HBCD (EC, 2008; Kuo et al., 2014; NICNAS, 2012; 

Zhang et al., 2012). Exposure monitoring data for workers in the US is not available in the 

scientific literature. The number of potentially exposed industrial workers in the US is estimated 

to be less than 2100 (EPA, 2012a). 

The greatest potential for occupational exposure is expected at industrial sites. Inhalation 

exposure concentrations of HBCD dust in the form of inhalable particles for workers handling 

standard grade HBCD powder at sites for the manufacture or processing (for the manufacture 

of XPS or EPS) of HBCD are in the range of 0.1 to 2.5 mg/m3

 (EC, 2008). For dermal exposures, 
Page 25 of 97 

the exposure range is 84 to 840 mg/day of HBCD dust (EC, 2008). Workers who cut EPS or XPS 

boards (e.g., at construction sites) are potentially exposed to HBCD via inhalation at much lower 

concentrations of HBCD in air in the form of respirable particles (Kuo et al., 2014; Zhang et al., 

2012). 

2.4.4 General Population Exposure 

2.4.4.1 Ambient Air 

The concentrations of HBCD are generally higher indoors than outdoors. However, spatial 

variation is likely with proximity to point sources. Concentrations are generally reported in 

picograms/m3. Samples have been collected in a wide variety of locations including remote 

locations in the arctic far removed from sources indicating long-range transport. Some studies 

characterized vapor and particulate phase of HBCD with HBCD most often reported in the 

particulate phase (Abdallah et al., 2008b; Alaee et al., 2003; Li et al., 2012a; Takigami et al., 

2009a; Tue et al., 2013). 

2.4.4.2 Drinking Water 

Measured concentrations of HBCD in drinking water are limited to one study in the UK (BRE, 

2009) where sampling from main water inlet and borehole water indicated concentration of 5-

16 μg/L and samples of process water from the Netherlands were an order of magnitude lower. 

Monitoring studies identifying HBCD in drinking water in the US are not readily available. 

2.4.4.3 Fish Consumption 

Measured concentrations of HBCD in fish are reported throughout the world, typically in the 

μg/kg range and are expected to vary spatially and temporally (Law et al., 2014). Fewer studies 

are available in the US and Canada (Arnot et al., 2009; Covaci et al., 2006; Ismail et al., 2009; 

Klosterhaus et al., 2012). 

2.4.4.4 Biomonitoring 

While fewer studies have characterized HBCD levels in humans compared to wildlife, several 

studies have shown detection in human breast milk, blood, adipose tissue and hair in the US 

and other countries. HBCD has been detected in breast milk at ng/gram lipid levels. (Arnot et 

al., 2009; Carignan et al., 2012; Covaci et al., 2006; Croes et al., 2012; Devanathan et al., 2012; 

Malarvannan et al., 2013; Marvin et al., 2011; Pratt et al., 2013; Shi et al., 2013). Two studies 

have detected HBCD in adipose tissue (Arnot et al., 2009; Johnson-Restrepo et al., 2008). HBCD 

has also been detected in human blood at ng/g lipid levels (Arnot et al., 2009; Covaci et al., 

2006; de Winter-Sorkina et al., 2006; Kiciński et al., 2012; Kim et al., 2013; WWF, 2004). 
Page 26 of 97 

2.4.5 Consumer Exposures 

Consumer exposure to HBCD may include inhalation exposure, dermal exposure through direct 

skin contact with HBCD on the surface of objects or articles, incidental ingestion of inhaled 

particulates (see 2.4.3), and incidental ingestion of indoor settled dust via hand-to-mouth 

behaviors. 

Based on HBCD’s relatively low vapor pressure and relatively high octanol-air partition 

coefficient, it is likely to preferentially partition to smaller suspended particles in the air and 

larger settled particles in dust (Blanchard et al., 2014; Law et al., 2014). HBCD has been 

detected in the dust of residences, commercial buildings, automobiles, and airplanes both in 

the US and other countries. The available assessments have addressed data relevant to US 

exposure scenarios up to and including 2011. 

Concentrations vary widely across different microenvironments and within microenvironments 

and are generally reported in the nanograms/gram or micrograms/gram range (Abdallah et al., 

2008a; Abdallah and Harrad, 2010; Ali et al., 2012; Allen et al., 2013a; Allen et al., 2013b; 

Bjorklund et al., 2012; Covaci et al., 2006; D'Hollander et al., 2010; de Wit et al., 2012; Dodson 

et al., 2012; Harrad et al., 2010; Johnson et al., 2013; Kalachova et al., 2012; Kopp et al., 2012; 

Kukučka P*, 2013; Ni and Zeng, 2013; Sahlström et al., 2012; Shoeib et al., 2012; Stapleton et 

al., 2008a; Stapleton et al., 2009; Stapleton et al., 2014; Takigami et al., 2008, 2009a; Thuresson 

et al., 2012; Tue et al., 2013; van den Eede et al., 2012; Wang et al., 2013). HBCD was detected 

at nanogram levels in handwipe samples in a recent study (Stapleton et al., 2014). HBCD has 

also been also detected in indoor air. Concentrations are generally reported in picograms/m3 

(Abdallah et al., 2008b; Abdallah and Harrad, 2010; de Wit et al., 2012; Ni and Zeng, 2013; Tue 

et al., 2013). 

2.5 Hazard Endpoints 

2.5.1 Ecological Hazard 

The ecological hazard of HBCD has been summarized in several publications (EC, 2008; 

Environment CA and Health CA, 2011; EPA, 2008a, 2014b; NICNAS, 2012; OECD, 2007). A 

general overview is presented below. Additional details and tabulated data summaries can be 

found in Appendix D. 

HBCD has been tested for acute and chronic aquatic toxicity, soil organisms, sediment 

organisms, avian species, and terrestrial plants. EPA/OPPT concludes that HBCD is hazardous to 

the environment. This conclusion is based on the potential for bioaccumulation (fish 

bioconcentration factor [BCF]=8,974–18,100) and biomagnification (fish biomagnification factor 

[BMF]=4.3–9.1), observed acute toxicity values as low as 0.009 mg HBCD/L (72-hour EC50) in the 

marine algae, Skeletonema costatum, that indicates high aquatic toxicity to plants, a chronic 

aquatic toxicity value of 0.0042 mg HBCD/L (maximum acceptable toxicant concentration, 

MATC) in Daphnia magna that indicates high chronic aquatic invertebrate toxicity, and reduced 
Page 27 of 97 

chick survival in Japanese quails (Coturnix coturnix japonica) at 15 ppm in diet (2.1 mg HBCD/kgbody weight/day) that indicates high terrestrial toxicity (Drottar and Krueger, 1998, 2000; Law 

et al., 2006b; MOEJ, 2009; Walsh et al., 1987). 

2.5.2 Human Health Hazard 

The human health hazard of HBCD has been summarized in several publications (EC, 2008; 

Environment CA and Health CA, 2011; EPA, 2008a, 2014b; NICNAS, 2012; OECD, 2007). A 

general overview is presented below. Additional details and tabulated data summaries can be 

found in Appendix E. 

For humans, there is a potential for oral, inhalation and dermal exposure. Available 

toxicokinetics data in rodents indicate that HBCD is moderately absorbed via the 

gastrointestinal tract, metabolized, and distributed to a number of tissues, with preferential 

distribution and accumulation of unchanged HBCD in fatty tissue. Elimination of HBCD is 

predominantly via feces (as unchanged parent compound), but is also eliminated in the urine 

(as secondary metabolites). The acute hazard concern is low via the oral, dermal and inhalation 

routes. The chronic hazard concern is based on reproductive effects which are described in 

detail in Appendix E. There is also some evidence of neurodevelopmental toxicity suggestive of 

hearing impairment, however, it is difficult to determine if the effect is due to developmental 

exposure to HBCD, a result of repeated-dose exposure, or a combination of the two. Available 

data suggest that HBCD is not genotoxic. No adequate carcinogenicity studies are available 

(EPA, 2014b). Existing assessments have also concluded, based on genotoxicity information and 

one limited lifetime study, that HBCD is not carcinogenic (NICNAS, 2012; TemaNord, 2008) or 

that further study of carcinogenicity is not warranted (EC, 2008; OECD, 2007). However, the 

only available dietary study evaluating the carcinogenic potential of HBCD in mice is not 

considered adequate to draw conclusions regarding carcinogenicity (EC, 2008; Environment CA 

and Health CA, 2011; EPA, 2014b; OECD, 2007). Given this data gap, EPA’s HBCD assessment 

will not include carcinogenicity assessment. 

2.6 Results of Problem Formulation 

The results of problem formulation are a conceptual model, key assessment questions and an 

analysis plan for human health and the environment (EPA, 1998a, 2014b). 

2.6.1 Conceptual Model 

During problem formulation, a conceptual model (see Figure 2-1) was developed to identify 

important sources, pathways, and receptors of exposure (See Sections 2.3 and 2.4). Potential 

exposures to HBCD (derived from the manufacture, processing and use of HBCD-containing 

polystyrene products) in homes, offices, the environment, and occupational settings were 

linked to hazard endpoints in human and non-human receptors. 
Page 28 of 97 

Figure 2-1: Conceptual Model for HBCD 

In the conceptual model, the schematic depicts the pathways (denoted by arrows) of potential 

exposure to HBCD and HBCD dust generated during the manufacture and processing of HBCD 

and use of HBCD containing products. The solid lines denote the exposure pathways considered 

likely and with available exposure and hazard data to assess them. The dashed lines designate 

pathways which are of unknown significance i.e. uncertain, have limited data or which are not 

quantifiable. The shaded boxes indicate elements proposed for assessment while the unshaded 

boxes indicate elements lacking adequate data for assessment. These scenarios are elaborated 

in Table 2-2.

Table 2-2: Summary of Use/Exposure Scenarios Considered for Assessment 

# USE/EXPOSURE 

SCENARIO 

CONSIDERED 

POTENTIAL 

ROUTE OF 

EXPOSURE 

PROPOSED 

FOR 

ASSESSMENT 

RATIONALE/LIMITATIONS/ 

UNCERTAINTIES 

1 Worker exposure 

to HBCD during 

manufacturing and 

processing 

ORAL –

Unintended 

oral exposure 

via the 

incidental 

ingestion of 

inhaled 

particles of 

HBCD and 

HBCD in dust 

YES Risk identified for HBCD handling in occupational 

settings in non-US assessments 
Page 29 of 97 

# USE/EXPOSURE 

SCENARIO 

CONSIDERED 

POTENTIAL 

ROUTE OF 

EXPOSURE 

PROPOSED 

FOR 

ASSESSMENT 

RATIONALE/LIMITATIONS/ 

UNCERTAINTIES 

DERMAL NO Experimental data for reliable route extrapolation 

from oral to inhalation & dermal routes are not 

available 

2 General 

population 

exposure from 

HBCD resulting 

from releases to 

the environment

ORAL – 

Ingestion of 

HBCD particles 

YES No TRI data 

ORAL – Fish 

Consumption 

YES Low risk in available non-US assessments; 

confirm low risk using US data 

ORAL – Drinking 

Water 

NO Low risk in available non-US assessments; 

No US drinking water monitoring data 

ORAL – Food 

other than fish 

from ambient 

water 

NO Low risk in available non-US assessments; 

Not regulated under TSCA 

INHALATION NO Low risk in available non-US assessments 

3 Ecological 

Receptors 

WATER YES Available US monitoring data and 

estimated/modeled releases from industrial sites 

SEDIMENT YES Available US monitoring data and 

estimated/modeled releases from industrial sites 

SOIL YES Available US monitoring data and 

estimated/modeled releases from industrial sites 

4a Consumer 

exposure to HBCD 

from the use of 

consumer 

products in indoor 

environments 

ORAL – 

Incidental 

ingestion of 

inhaled 

particles of 

HBCD in dust 

Hand-to-mouth 

exposure of 

HBCD from dust 

YES Data available for oral exposures only 

4b Consumer 

exposure to HBCD 

from the use of 

consumer 

products in indoor 

environments 

INHALATION 

DERMAL 

NO Experimental data for reliable route extrapolation 

from oral to dermal route is not available. 

Inhalation of neat HBCD potentially released from 

products is expected to contribute less to overall 

exposure than the ingestion pathway due to low 

volatility. 

4c Consumer 

exposure to HBCD 

from use of EPS/ 

XPS commercial 

products.

ORAL 

INHALATION 

DERMAL 

NO Exposure considered insignificant and not assessed 

in EURAR; 

Risk to workers low in NICNAS; 

The HBCD content of these boards 1-5%; 

EPS/XPS boards may generate dust during cutting 

during construction, renovations or DIY projects. 

Consumer dust exposure captured in “1.0” above; 

Experimental data for reliable route extrapolation 

from oral to dermal route is not available. 

Inhalation of neat HBCD potentially released from 

products is not expected due to low volatility. 
Page 30 of 97 

# USE/EXPOSURE 

SCENARIO 

CONSIDERED 

POTENTIAL 

ROUTE OF 

EXPOSURE 

PROPOSED 

FOR 

ASSESSMENT 

RATIONALE/LIMITATIONS/ 

UNCERTAINTIES 

4d Consumer 

exposure to HBCD 

in specific articles 

made with high 

impact 

polystyrene (HIPS) 

ORAL 

INHALATION 

DERMAL 

NO Low risk in available non-US assessments; 

Level of HBCD in HIPS in the US is unknown; 

Not used in typical consumer products (computer 

or TV chassis); 

Use in other consumer products (e.g. electrical 

appliances) is enclosed limiting potential exposure

4e Consumer 

exposure to HBCD 

in textile finishings

DERMAL NO Low risk in available non-US assessments; 

Low risk in CPSC study with furnishings; 

In the 2012 CDR, HBCD was not reported to be 

used in consumer fabrics or textiles; 

The extent of HBCD institutional (e.g. prisons), 

military or aviation use is unknown. 

EPA developed four key questions from the conceptual model.

1. Are there risks to workers exposed to HBCD during manufacturing and processing of 

HBCD for the manufacture of EPS and XPS? 

HBCD has been assessed globally (EC, 2008; Environment CA and Health CA, 2011; NICNAS, 

2012). For human health, the toxicological point of departure (POD; NOAEL for the twogeneration toxicity study) used in the published risk assessments (EC, 2008; Environment CA 

and Health CA, 2011; NICNAS, 2012) to calculate the margin of exposure (MOE) is based on a 

study that EPA would consider adequate for the oral route of exposure. No chronic hazard data 

are available for the dermal and inhalation routes of exposure. To address these exposure 

scenarios and minimize uncertainty in the risk conclusions, EPA uses physiologically-based 

pharmacokinetic (PBPK) modeling for route-to-route extrapolation; however, these data are 

not robust for HBCD. Therefore, EPA/OPPT proposes to evaluate the methodology used in the 

published risk assessments, confirm the study used for the POD, and in conjunction with 

EPA’s assessment of the exposure of workers in the US (Section 2.6.2), determine if there are 

risks to workers. 

2. Are there risks to the general population from HBCD released to the environment during 

the lifecycle of HBCD? 

Releases of HBCD to air, including releases to air during manufacture and processing of EPS and 

XPS, are expected to partition to particulate matter and deposit in the environment (water and 

soil) and is expected to be bioaccumulated up the food chain. Therefore, for the general 

population, exposures to HBCD are expected to occur indirectly through water or fish 

consumption. 

Drinking Water: No monitoring data for HBCD in drinking water are available. However, 

published risk assessments indicate low risk to the general population from drinking water 

exposure. 
Page 31 of 97 

Fish Consumption: 

• For the general population, available risk assessments (EC, 2008; Environment CA and 

Health CA, 2011; NICNAS, 2012) concluded that risk to general population from 

consumption of HBCD in fish is low. In addition, the Canadian assessment included 

sensitive subpopulations such as indigenous populations (Nunavut) and nursing infants 

and concluded that risks to these populations is low. 

• However, recent publications (Abdallah and Harrad, 2011; Aylward and Hays, 2011; 

Carignan et al., 2012; Gheorghe et al., 2013; Kalachova et al., 2012) containing 

additional information warrant evaluation. 

A biomonitoring-based risk assessment (Aylward and Hays, 2011) (i.e., based on HBCD 

concentrations found in breast milk and serum) indicated that the margins of exposure (MOE) 

were greatly in excess of target values, suggesting that the risk to the general population is low. 

3. Are there risks to ecological receptors from HBCD found in the environment? 

Available risk assessments (EC, 2008; Environment CA and Health CA, 2011; NICNAS, 2012) 

concluded that HBCD poses a risk to the environment. EPA/OPPT plans to evaluate the 

potential risk to the environment based on US release estimates and exposure. 

4. Are there risks to consumers from HBCD found in household dust? 

Dust: Available risk assessments (EC, 2008; Environment CA and Health CA, 2011; NICNAS, 

2012) concluded that risk to consumers from exposure to HBCD in household dust is low. These 

assessments included hand-to-mouth transfer of dust by children. Preliminary evaluation of 

recent data for the US population suggest that the available assessments underestimate 

consumer exposure to HBCD from dust for US consumers. In addition, for toddlers, exposure to 

HBCD from dust in other microenvironments, such as vehicles and childcare environments, 

may contribute to their total HBCD exposure (Harrad and Abdallah, 2011). Therefore, 

EPA/OPPT plans to evaluate the methodology used in the published risk assessments, confirm 

the study used for the hazard assessment and in conjunction with the current and aggregate 

exposure information relevant to the US population, assess potential risks to US consumers. 

2.6.2 Analysis Plan 

Based on problem formulation EPA/OPPT plans to conduct the following additional analyses. 

2.6.2.1 Workers 

EPA/OPPT plans to evaluate the applicability of data for worker exposure to HBCD through 

manufacturing and processing for the manufacture of EPS and XPS reported in EC (2008) and 

NICNAS (2012) to US occupational exposure scenarios. If the available data are not applicable, 

develop estimates of occupational exposures based on modeling and assumptions (e.g. 

approaches used in the new chemicals program). 
Page 32 of 97 

2.6.2.2 Risks to General Population and Environmental Biota (aquatic, 

terrestrial and avian) 

Robust monitoring datasets for US locations do not exist. EPA/OPPT plans to use estimates of 

releases to the environment during HBCD manufacture and processing for the manufacture of 

EPS and XPS from manufacturing, processing and use to estimate surface water, sediment and 

soil concentrations. EPA/OPPT does not plan to consider degradation losses but may consider 

partitioning. 

EPA/OPPT plans to estimate releases to the environment from industrial sites based on CDR 

(EPA, 2012a) data on production volume and number of sites and emission factors (i.e. ‘loss 

factors’)6 reported in various HBCD risk assessment reports (EC, 2008; Environment CA and 

Health CA, 2011; NICNAS, 2012). EPA/OPPT will assume emission factors for releases from 

manufacturing and processing, in processes in other countries, are applicable to the US. 

The release factor of a chemical is dependent on the design and operation of a chemical 

process. EPA/OPPT assumes the basic process design and operation of the processes for the 

manufacture or processing of HBCD in the US to be similar to those of the corresponding 

processes in other countries. The descriptions of the processes for the manufacture of EPS resin 

beads, the manufacture of foamed plastics including EPS and XPS, and plastics compounding in 

general that are reported in the literature (Burkhardt et al., 2011; EPA, 2014b; Maul et al., 

2007; Suh, 2000) are similar to descriptions reported in EC (2008) and NICNAS (2012) of the 

corresponding processes. EPA/OPPT’s compilation of the non-site specific emission factors 

reported in EC (2008), NICNAS (2012) and Environment CA and Health CA (2011) is given in 

Table_Apx C-2 in Appendix C. EPA/OPPT’s preliminary estimate of the values of input variables 

for the assessment of releases is reported in Table_Apx C-3; EPA/OPPT plans to assess a range 

of release values from the ranges of input variables given in this table. 

Additionally, EPA/OPPT may consider other available information to assess releases and 

concentrations to other media (i.e. air). For a discussion of the approach for how air releases 

could be modeled to estimate concentrations in nearby media see EPA/OPPT’s TBBPA problem 

formulation document 

(http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html). However, there will be 

important differences in the assessments because site-specific modeling parameters were used 

with TBBPA and those are not likely to be available for HBCD industrial sites. 

Mathematical modeling approaches may be necessary to yield exposure estimates. EPA/OPPT 

will consider the use of sensitivity analyses to determine key elements of uncertainty. 

EPA/OPPT plans to estimate MOE for fish consumption (including sensitive populations) using 

US exposure information not captured in previous assessments and modeled fish ingestion 

(EPA, 2007) from release estimates. EPA/OPPT is considering values for adult general 

population consumption typically used by EPA Office of Water (e.g., 22 g/day for adults in the 

 

6

 Ratio of amount of chemical released to amount manufactured or processed 
Page 33 of 97 

general population and 142.5g/day for subsistence fishers in the absence of local or similar fish 

ingestion data). Based on NHANES data from 2003 to 2010 (EPA, 2014a), this value represents 

the 90th percentile consumption rate of freshwater and estuarine fish for the US adult 

population 21 years of age and older. 

EPA/OPPT will identify hazard endpoints and benchmarks from published assessments (EC, 

2008; Environment CA and Health CA, 2011; NICNAS, 2012) and data sources (See Appendix D 

and Appendix E). EPA/OPPT will calculate non-cancer risks using MOE or HQ approaches. 

2.6.2.3 Consumers 

Mathematical modeling approaches may be necessary to yield exposure estimates. EPA/OPPT 

will consider the use of sensitivity analyses to determine key elements of uncertainty. 

EPA/OPPT plans to use available or modeled (to be determined) data relevant to US exposure 

scenarios to estimate consumer exposure using available or modeled data relevant to US 

exposure scenarios with particular emphasis on sensitive populations (e.g. toddlers exposed in 

microenvironments). 

Consumer exposures to HBCD will be evaluated based on incidental ingestion of dust (as 

described above), and incidental ingestion of indoor settled dust via hand-to-mouth behaviors. 

Oral exposure by incidental ingestion of house dust and hand-to-mouth transfer can be 

quantified based on US values of monitored house dust. Several recent studies of house dust 

are available which are expected to be representative of US households. The EPA Exposure 

Factors Handbook (EPA, 2011b) can be utilized to determine typical quantities of dust ingested 

and time-activity patterns. 

EPA/OPPT will identify hazard endpoints and benchmarks from published assessments (EC, 

2008; Environment CA and Health CA, 2011; NICNAS, 2012) and data sources (See Appendix E). 

EPA/OPPT will calculate non-cancer risks using MOE. 

Aggregate oral exposures will be assessed considering hand-to-mouth dust ingestion, incidental 

ingestion of dust and high-end fish consumption. 

Conclusion 

EPA/OPPT plans to evaluate potential risk to workers, the general population, consumers and 

environmental biota under the TSCA Existing Chemicals Program using existing data and 

methods. EPA/OPPT plans to review and evaluate available exposure and hazard benchmarks 

and determine margins of exposure to evaluate the potential risk from human and 

environmental exposure to HBCD. EPA/OPPT plans to estimate releases to the environment 

from industrial sites based on CDR (EPA, 2012a) data on production volume and number of sites 

and emission factors (i.e. ‘loss factors’)7

 reported in various HBCD risk assessment reports (EC, 

2008; Environment CA and Health CA, 2011; NICNAS, 2012). 

 

7

 Ratio of amount of chemical released to amount manufactured or processed 
Page 34 of 97 

2.6.3 Sources and Pathways Excluded From Further Assessment 

Several scenarios were identified where exposure to HBCD is expected to be low or unknown, 

and where further analysis is not recommended by EPA/OPPT under TSCA: 

• Exposure from HBCD in landfills is not being assessed due to uncertainties in release 

from these sites. 

• General population exposure from HBCD in drinking water is not being assessed because 

drinking water monitoring data for the US are not available and conclusions from 

available risk assessments indicate a low concern from this exposure pathway (EC, 2008; 

Environment CA and Health CA, 2011; NICNAS, 2012). 

• Consumer exposure to HBCD in HIPS is not being assessed because the level of HBCD in 

HIPS in the US is unknown, it is not used in typical consumer products (e.g. computer or 

TV chassis), its use in other consumer products (e.g. electrical appliances) is enclosed 

limiting potential exposure and a low risk to consumers was indicated in available risk 

assessments. 

• Consumer exposure to HBCD in textile finishings is not being assessed because it was 

considered low risk by the CPSC in upholstered furnishings (CPSC, 2001), it was not 

reported to be used in consumer fabrics or textiles in the 2012 CDR (EPA, 2012a) and 

the extent of institutional (e.g. prisons), military or aviation use is unknown. 

• There are no adequate toxicological data based on inhalation or dermal exposures or a 

PBPK model readily available for route-to-route extrapolation. Therefore EPA/OPPT will 

not assess inhalation or dermal contact in this assessment. However, EPA is considering 

the quantification of incidental ingestion of particulates that would result from exposure 

to HBCD dust in occupational settings. A similar approach will be used to address 

consumer exposure to HBCD in dust. 

2.6.4 Uncertainties and Data Gaps 

2.6.4.1 Exposure Assessment 

2.6.4.1.1 Releases to the Environment 

The major uncertainties in EPA’s proposed approach are the following: 

Production and Processing Volumes and Number of Sites: 

HBCD production and processing volumes are uncertain because CDR information on current 

production, export and import volumes is CBI. EPA will assume the HBCD production volume to 

be in a range of values that is derived from the most recent publically reported CDR information 
Page 35 of 97 

and will assume the processing volume to be equal to the production volume. Refer to 

Table_Apx C-3 for EPA’s preliminary values for production and processing volumes. 

The number of sites for most processing steps is uncertain. EPA will estimate the number of 

sites based on CDR data which is data on ranges of number of sites. Furthermore, the 

processing and product descriptions reported in CDR are general and preclude an accurate 

determination of specific processing steps. Refer to Table_Apx C-1 for EPA’s preliminary 

assessment of the number of sites. The share of the HBCD production volume that is processed 

to manufacture XPS using HBCD powder or HBCD masterbatch is unknown. 

2.6.4.1.2 Occupational Exposure 

Exposure monitoring data for workers in the US are not available in the scientific literature. The 

greatest potential for occupational exposure is expected at industrial sites. Maximum exposure 

occurs while workers load or unload HBCD powder or pellets (EC, 2008), which is a worker 

activity that EPA expects in the US. Data are available for inhalation and dermal exposures to 

workers (EC, 2008). Workers who cut EPS or XPS boards (e.g., at construction sites) are 

potentially exposed to HBCD via inhalation at much lower concentrations of HBCD in air in the 

form of respirable particles. 

There is no PBPK model readily available for route-to-route extrapolation. EPA/OPPT has 

identified this as a critical data gap since the exclusion of dermal and inhalation exposure 

routes will result in the underestimation of risks. 

2.6.4.1.3 General Population and Consumer Exposure 

Some of the available measured environmental concentrations were outside the US and it is 

not clear how representative they are of exposure scenarios within the US. Significant 

uncertainties may exist in a quantitative evaluation. There are limited US surface water, 

sediment, and soil measurements. 

Available monitoring data may not be representative of concentrations in the environment 

across all areas of the US. There are very limited data of HBCD in fish from the US and it is 

uncertain if concentrations in fish in Canada and abroad would be similar to the US. Fish 

ingestion exposures will need to be modeled based on releases to the environment from 

manufacturing/processing/use. Exposure factors exist for fish consumption, however there 

would be uncertainty in determining the concentration of HBCD in edible fish. If specific 

receiving waters are not identified, there will be uncertainty in the amount of dilution that may 

occur. EPA/OPPT will clearly document the uncertainty and limitations associated with the fish 

consumption analyses. 

Modeled releases to water from industrial facilities may result in the over- or under-estimation 

of concentrations in the aquatic environment. Modeling default values will need to be modified 
Page 36 of 97 

(e.g., fish consumption) to account for high-end consumption. EPA/OPPT will consider the use 

of sensitivity analyses to determine key elements of uncertainty. 

The concentration of HBCD in indoor air or dust in offices or workplaces may be greater than in 

homes. There are uncertainties using existing methodologies to estimate exposure for the 

different sub-environments. Incidental ingestion of dust by adults is expected to be low 

whereas ingestion of dust through incidental ingestion or hand to mouth behavior is expected 

to be higher for small children due to their activity patterns and increased proximity to indoor 

areas where dust may gather. Concentrations of HBCD in dust are likely to vary by 

microenvironment and will need to be a consideration in exposure estimations. 

It is not possible to develop source-to-dose exposure models with currently available 

information. Sources such as dust and presence in fish must be considered integrative metrics 

for the purposes of exposure assessment. Source-to-dose models are absent or limited for most 

of the identified exposure scenarios, therefore linking the exposure to specific products or the 

use patterns of any one product will be challenging. 

2.6.4.2 Ecological Endpoints 

Overall, adequate aquatic toxicity data are available to characterize the hazard to the 

environment for HBCD. 

2.6.4.3 Human Health Endpoints 

Toxicokinetics (by the oral route), acute, repeated-dose, developmental, and reproductive 

toxicity data are available to characterize the potential human health hazard of HBCD. 

Although no standard neurotoxicity or developmental neurotoxicity studies on HBCD are 

available, information on neurotoxicity was obtained from Functional Observational Battery, 

locomotor activity evaluations, neurobehavioral testing, surface righting reflex, negative 

geotaxis reflex, mid-air righting reflex, and brainstem auditory evoked potentials (BAEPs) in 

several repeated-dose and reproductive toxicity studies. Several assays testing for genotoxicity, 

and irritation/sensitization are also available. The only available dietary study evaluating the 

carcinogenic potential of HBCD in mice is not considered adequate to draw conclusions 

regarding carcinogenicity (EC, 2008; Environment CA and Health CA, 2011; EPA, 2014b; OECD, 

2007). EPA agrees with these conclusions and therefore in its HBCD assessment will not 

consider carcinogenicity to be an endpoint of concern. 

Neither a complete mechanistic PBPK model for HBCD, nor a PBPK model for humans is 

available. This precludes the use of a model for cross-route or cross-species extrapolation. 

There is no PBPK model readily available for route-to-route extrapolation. Exclusion of dermal 

and inhalation exposure routes will result in the underestimation of risks. The lack of a lifetime 

exposure study and/or adequate assessment of carcinogenicity increases uncertainty in EPA’s 

assessment of long-term exposures to HBCD. Therefore, inhalation, dermal and lifetime 

exposure assessment data gaps add uncertainty to EPA’s risk assessment of HBCD. 
Page 37 of 97 

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APPENDICES 

Appendix A Regulatory and Assessment History 

Table_Apx A-1: Regulatory and Assessment History of HBCD8

COUNTRY/ORGANIZATION ASSESSMENT 

UNITED STATES Environmental Protection Agency 

• Office of Environmental Information - Proposed HBCD for listing to the Toxic Release 

Inventory (TRI) Program (2014). For current list of chemicals see: 

http://www2.epa.gov/toxics-release-inventory-tri-program/tri-listed-chemicals

• Office of Research and Development – Draft Toxicological Review Scoping Document to 

support an IRIS assessment 

(http://www.ecy.wa.gov/programs/wq/swqs/IRISAgendaChemicals.pdf)

• Office of Pollution Prevention and Toxics (OPPT) – Flame retardant alternatives to 

hexabromocyclododecane (2014) 

 (http://www.epa.gov/dfe/pubs/projects/hbcd/hbcd-full-report-508.pdf) 

• OPPT - Proposed SNUR (Mar 2012) to designate manufacture or processing of HBCD for 

use as a flame retardant in consumer textiles as a significant new use

• OPPT Action Plan for HBCD (2010) (all congeners; 

http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/RIN2070-

AZ10_HBCD%20action%20plan_Final_2010-08-09.pdf)

• OPPT Risk Based Prioritization (RBP) including Hazard Characterization (2008) 

(http://www.epa.gov/chemrtk/hpvis/rbp/HBCD.3194556.Web.RBP.31308.pdf) for CASRNs 

3194-55-6 and 25637-99-4

• OPPT – CASRN 3194-55-6 (2001) High Production Volume Challenge Program test plan and 

robust summaries submission 

(http://www.epa.gov/chemrtk/pubs/summaries/cyclodod/c13459cv.pdf)

Occupational Safety and Health Administration (OSHA) 

• No occupational exposure limits (OSHA PEL, NIOSH REL, ACGIH TLV) are established 

(www.osha.gov) 

Consumer Product Safety Commission (CPSC) 

• CPSC staff exposure and risk assessment of flame retardant chemicals in residential 

upholstered furniture (2001) (http://www.cpsc.gov/en/)

• CPSC staff preliminary risk assessment of flame retardant (FR) chemicals in upholstered 

furniture foam (2006) (http://www.cpsc.gov/en/)

• Quantitative assessment of potential health effects from the use of fire retardant (FR) 

chemicals in mattresses (2006) (http://www.cpsc.gov/en/)

State – California 

• HBCD is listed as an informational initial candidate chemical under California’s Safer 

Consumer Products regulations. (DTSC, 2010) (http://www.dtsc.ca.gov/SCP/ChemList.cfm) 

• HBCD is listed on the state’s Proposition 65 list because it is known to cause cancer or 

birth defects or other reproductive harm (OEHHA, 2007, 2014). 

(http://oehha.ca.gov/) (http://oehha.ca.gov/prop65/prop65_list/files/P65single050214.pdf) 

 

8

 The risk assessment conclusions summarized in the table are selected conclusions from the reports that address 

the pertinent US exposure scenarios and should not be construed as EPA’s conclusions. EPA refers the reader to 

the full reports for detailed explanations of the context of the conclusions reached in all risk assessments. 
Page 62 of 97 

COUNTRY/ORGANIZATION ASSESSMENT 

• California lists HBCD as a designated and priority chemical for biomonitoring. However, 

California has not yet started biomonitoring HBCD (SGP, 2014). 

(http://www.biomonitoring.ca.gov/chemicals/chemicals-biomonitored-california) 

State – Maine 

• Maine classifies HBCD as a chemical of high concern (DEP, 2013). 

(http://www.maine.gov/dep/safechem/highconcern/)

State – Minnesota 

• Minnesota classifies HBCD as a chemical of high concern (MDH, 2013). 

(http://www.health.state.mn.us/divs/eh/hazardous/topics/toxfreekids/chclist/mdhchc2013.pdf)

State - Oregon 

• The Oregon Department of Environmental Quality lists HBCD as a priority persistent 

pollutant (DEQ, 2010a, 2011). 

(http://www.deq.state.or.us/wq/SB737/docs/LegRpAtt20100601.pdf) 

(http://www.deq.state.or.us/wq/SB737/)

• Oregon posts use, exposure pathways and release data for HBCD under this program (DEQ, 

2010b). (http://www.deq.state.or.us/wq/SB737/docs/LegRpAtt420100601.pdf)

State – Washington 

• Washington classifies HBCD as a chemical of high concern to children (WSDE, 2013).

(http://www.ecy.wa.gov/programs/swfa/cspa/chcc.html)

CANADA • HBCD meets Canada’s regulatory criteria for persistence and bioaccumulation potential. 

(http://www.ec.gc.ca/ese-ees/default.asp?lang=En&n=7882C148-1#a4)

• On November 1, 2012, Canada added HBCD to Schedule 1 of CEPA 1999 (Virtual 

Elimination List). Proposed risk reduction measures would prohibit the manufacture, 

import, use, sale, and offer for sale of HBCD and products containing HBCD. 

(http://www.ec.gc.ca/lcpe-cepa/eng/regulations/detailReg.cfm?intReg=82)

• Health Canada (Health CA) and Environment Canada (ENV CA) have published a screeninglevel assessment. (http://www.ec.gc.ca/ese-ees/default.asp?lang=En&n=7882C148-1#a4)

EUROPEAN UNION • HBCD is listed as a substance of very high concern (SVHC) and it is also listed under Annex 

XIV (Authorisation list) of European Union’s REACH. After August 21, 2015, only persons 

with approved authorization applications may continue to use the chemical. 

(http://echa.europa.eu/candidate-list-table) 

(http://echa.europa.eu/documents/10162/13640/prioritisation_hbccd_en.pdf) 

• The European Chemicals Agency (ECHA) is currently considering two applications to 

authorize the use of HBCD: (i) formulation of flame retarded expanded polystyrene (EPS) to 

solid unexpanded pellets using HBCD as the flame retardant additive (for onward use in 

building applications); and (i) manufacture of flame retarded expanded polystyrene (EPS) 

articles for use in building applications. 

(http://echa.europa.eu/documents/10162/18584504/afa_opinion_hbcdd_use_2_en.pdf) 

• HBCD is recommended to be reviewed for the EU Directive’s list of banned substances 

under the restriction of hazardous substances (RoHS) in electrical and electronic 

equipment. 

(http://ec.europa.eu/environment/waste/weee/pdf/hazardous_substances_report.pdf) 

• The WEEE (Waste Electrical and Electronic Equipment) directive in the European Union 

requires the separation of plastics containing brominated flame retardants prior to 

recycling. (http://ec.europa.eu/environment/waste/weee/index_en.htm)

• The European Commission published a European Union Risk Assessment Report (EC, 2008)

on HBCD. (http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_093.pdf)

AUSTRALIA • HBCD is listed as a Priority Existing Chemical. (http://www.nicnas.gov.au/chemicalinformation/pec-assessments)
Page 63 of 97 

COUNTRY/ORGANIZATION ASSESSMENT 

• Australia (National Industrial Chemicals Notification and Assessment Scheme) has prepared 

a risk assessment for HBCD. 

(http://www.nicnas.gov.au/Publications/CAR/PEC/PEC34/HBCD_Report_June_2012_PDF.pdf)

JAPAN • HBCD is subject to mandatory reporting requirements in Japan under the Chemical 

Substances Control Law (CSCL), specifically Japan requires type III monitoring for all 

substances that may interfere with the survival and/or growth of flora and fauna.

(http://www.meti.go.jp/policy/chemical_management/english/cscl/files/about/150408Progres.pdf) 

STOCKHOLM CONVENTION 

ON PERSISTENT ORGANIC 

POLLUTANTS (POPs) 

• In May 2013, HBCD was added to the United Nation’s Stockholm Convention list of 

Persistent Organic Pollutants. The chemical is scheduled to be eliminated by November 

2014 with specific exemptions for production and uses in expanded or extruded 

polystyrene building insulation. As required by the convention, parties that use these 

exemptions must register with the secretariat and the exemptions will expire in November 

2019. (http://chm.pops.int/default.aspx)

ORGANISATION FOR 

ECONOMIC COOPERATION AND 

DEVELOPMENT (OECD) 

• Published SIDS Initial Assessment Profile (SIAP) and SIAR in 2007 for CASRNs 3194-55-6 and 

25637-99-4. (http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?key=39a31bc9-3719-

4c55-a7d4-a8bbdd9afe04&idx=0) 

(http://webnet.oecd.org/HPV/UI/handler.axd?id=ea58ac11-e090-4b24-b281-

200ae351686c) 
Appendix B Uses Supplement Tables 

Table_Apx B-1: 2012 CDR Production Data (Data Reported for 2011) 

CASRN Manufacturing Site Domestic Manufacturing Imported Volume Exported (lbs) Volume Used on the Site (lbs)1

2010 

Produ

Volu

(impo

manufa

25637-99-4 CBI CBI ND CBI 0 CB

CBI CBI ND 0 0 CBBASF Corporation 100 Campus Drive Florham Park, NJ 07932 

ND CBI CBI CBI CB

3194-55-6 Albemarle Corporation 

1550 Hwy. 371 W. Magnolia, AR 71753 

CBI ND CBI CBI CB

The Dow Chemical Company 2020 Dow Center Midland, MI 48674 

ND CBI 0 N/A CB

1The total volume (domestically manufactured and imported) of the chemical used at the reporting site. This number represents the volume of the 

leave the manufacturing site. CBI = Confidential Business Information ND = No Data; the company did not provide the requested information. N/A = Not Applicable; the imported chemical was never physically at the site. “Withheld” in the CDR public database indicates that the national production volume of a chemical was unable to be aggregated in order to protec
Page 65 of 97 

Table_Apx B-2: Historic IUR and CDR Production Volumes 

CASRN Year 1986 1990 1994 1998 2002 2006 2

25637-99-4 10K - 500K No Reports No Reports 10K - 500K 10K - 500K No Reports 

3194-55-6 >1M - 10M >1M - 10M >10M - 50M >10M - 50M >10M - 50M 10 to < 50M 

1The total volume (domestically manufactured and imported) of the chemical used at the reporting site. This number represents the volume of the 

leave the manufacturing site. CBI = Confidential Business Information “Withheld” in the CDR public database indicates that the national production volume of a chemical was unable to be aggregated in order to prote

Table_Apx B-3: Summary of 2011 CDR Production Volume and Use Information 

CAS 

Number 

Industrial 

Sector 

Reported in 

CDR 

Description 

of 

Industrial 

Use 

Commercial or Consumer 

Product Category Potential End Product 2011 PV 

25637-99-4 

Plastics 

Material and 

Resin 

Manufacturing 

Flame 

retardant 

in electrical 

and 

electronic 

equipment 

Plastic and Rubber 

Products not Covered 

Elsewhere (Commercial 

and Consumer use) 

• Electric housings for VCR 

• Electrical and electronic 

equipment (e.g., distribution boxes for electrical lines) 

• Video cassette housings 

CBI 

Construction 

Flame 

retardant 

in 

insulation 

boards 

Building/Construction 

Materials Not Covered 

Elsewhere (Commercial 

and Consumer use) 

• Construction, insulation boards 

(packaging material) 

• Insulation boards (against cold 

or warm) of transport vehicles (e.g., lorries and caravans) 

• Insulation boards in building 

constructions, e.g. houses’ walls, cellars and indoor ceilings and ”inverted roofs” (outdoor) 

• Insulation boards against frost 

heaves of road and railway embankments 

CBI 

Building/Construction 

Materials Not Covered 

Elsewhere (Commercial 

use) 

CBI 
Page 66 of 97 

CAS 

Number 

Industrial 

Sector 

Reported in 

CDR 

Description 

of 

Industrial 

Use 

Commercial or Consumer 

Product Category Potential End Product 2011 PV 

3194-55-6 Utilities 

Flame 

retardant 

in 

insulation 

boards 

Building/Construction 

Materials Not Covered 

Elsewhere (Consumer use) 

• Construction, insulation boards 

(packaging material) 

• Insulation boards in building 

constructions, e.g., houses’ walls, cellars and indoor ceilings and ”inverted roofs” (outdoor) 

CBI 

Building/Construction 

Materials Not Covered 

Elsewhere (Commercial 

use) 

• Construction, insulation 

boards,(packaging material) 

• Insulation boards (against cold 

or warm) of transport vehicles (e.g., lorries and caravans) 

• Insulation boards in building 

constructions e.g. houses’ walls, cellars and indoor ceilings and ”inverted roofs” (outdoor) 

• Insulation boards against frost 

heaves of road and railway embankments 

CBI 

Note: 1) Plastic and rubber products with consumer/commercial categories in the CDR data include: 

• Food packaging 

• Toys, playground, and sporting equipment 

2) Building and construction materials with consumer/commercial categories in the CDR data include: 

• Building/construction materials - wood and engineered wood products

CBI = Confidential Business Information PV = Production Volume 
Page 67 of 97 

Table_Apx B-4: Uses of HBCD as Listed in the 2008 EU Risk Assessment 

Material1 Use/ Function1

Percent of 

HBCD 

Production 

Volume2 

End Products1 Ongoing Use in the Unite

EPS Insulation 45% 

Construction, insulation boards (packaging material) Yes; based on use in cons

in 2012 CDR data2 

Packaging material (minor use and not in food packaging) 

Unknown; it is unclear if tUS, and uses of polystyrenproducts generally do not 

retardant3 

Insulation boards (against cold or warm) of transport vehicles (e.g., lorries and caravans) 

Possibly; based on use in CDR data2

Insulation boards in building constructions e.g. houses’ walls, cellars and indoor ceilings and “inverted roofs” (outdoor) 

Yes; based on use in consin 2012 CDR data2

Insulation boards against frost heaves of road and railway embankments 

Possibly; based on use in CDR data2

XPS Insulation 51% 

Construction, insulation boards Yes; based on use in cons

in 2012 CDR data2

Insulation boards (against cold or warm) of transport vehicles (e.g. lorries and caravans) 

Possibly; based on use in CDR data2

Insulation boards in building constructions e.g. houses’ walls, cellars and indoor ceilings and “inverted roofs” (outdoor) 

Yes; based on use in consin 2012 CDR data2

Insulation boards against frost heaves of road and railway embankments 

Possibly; based on use in CDR data2

HIPS 

Electrical 

and 

electronic 

parts 

2% 

Electric housings for VCR Possibly, based on use in 

CDR2 

Electrical and electronic equipment, e.g., distribution boxes for electrical lines 

Possibly, based on use in CDR2

Video cassette housings Possibly, based on use in 

CDR2
Page 68 of 97 

Material1 Use/ Function1

Percent of 

HBCD 

Production 

Volume2 

End Products1 Ongoing Use in the Unite

Polymer 

dispersion 

on cotton 

or cotton/ 

synthetic 

blends 

Textile 

coating 

agent 

2% 

Upholstery fabric Historic Use in the US4

Bed mattress ticking Historic Use in the US4Flat and pile upholstered furniture (residential and commercial furniture) 

Historic Use in the US4

Upholstery seating in transportation Possibly, based industry rDraperies, and wall coverings Historic Use in the US4Interior textiles e.g. roller blinds Historic Use in the US4Automobile interior textiles Possibly, based industry r

Note: The uses in this table describe recorded HBCD applications for both the US and other countries. Given that HBCD will be phased out internation

Stockholm Convention, it is unclear to what extent HBCD is currently used in these applications outside of the US. Sources: 

1) EC, 2008 

2) EPA, 2012a 

3) EPA, 2014 

4) EPA, 2012e
Appendix C Exposure Supplement Tables 

Table_Apx C-1: 2012 CDR Data (Data Reported for 2011) for Release Assessment 

Table Line 

Number 

Manufacture / Import Industrial Processing / Use 

Site Identity Max 

Concentration and 

Physical Form 

Processing Use Processing Sector Function % PV Numbe

of Sites 

1 

CBI 90%+; Dry Powder 

or Other Solid 

Processing-incorporation 

into formulation, mixture, or 

reaction product 

Plastics Material 

and Resin 

Manufacturing 

Flame 

retardants 50 < 10 

2 Processing-incorporation into article Construction Flame retardants 50 < 10 3 BASF, Florham 

Park, NJ 1 to < 30%; Pellets / Large Crystals 

Processing-incorporation 

into article Construction Other CBI 10 to 24 

4 Processing-incorporation into article Plastics Material and Resin Manufacturing Other CBI 25 to 99 5 Albemarle 

Corporation, 

Magnolia, AR 90%+; Dry Powder 

Processing-incorporation 

into article Utilities Flame retardants NKRA 10 to 24 

6 

Processing-incorporation 

into formulation, mixture, or 

reaction product 

Utilities Flame retardants NKRA 10 to 24 

7 

The Dow 

Chemical 

Company, 

Midland, MI 

60 to < 90%; 

Pellets / Large 

Crystals 

Not Reported 

CBI = Confidential Business Information NKRA = Not Known or Reasonably Ascertainable PV = Production Volume 
Page 70 of 97 

Table_Apx C-2: Compilation of Release Factors and Other Release-Related Information in Various Risk Assessments 

Operation 

(Manufacture or 

Processing Step) 

Reference Release Media Loss Factor (Emission Factor) Number 

Value Description Value 

Manufacture of EPS resin beads that contain HBCD (also referred to as “formulation of EPS compound” (EC, 2008) or “compounding raw HBCD into resins” (NICNAS, 2012)) 

EC (2008)

water 7.6E-06 

This is the emission factor for a generic site and was determined based on the 90th percentile of measurements 

of concentration in the effluent from the on-site sewer treatment plants of 9 of the total of 13 sites. 300 

This is thsite and accordanassessmSite-specrange of exceptioequal to 

air 7.3E-06 

This is the emission factor for a generic site and is equal to the maximum emission factor calculated from site-specific data that pertain to three processing steps including 

formulation of EPS and XPS compounds. 

NICNAS (2012) 

water 6.8E-03 

These values are reasonable worst case values that are the sums of emission factors for handling and compounding solid flame retardants with particle sizes <40 μm that are also of relatively high volatility as reported in OECD (2004b). 

150 This is a 

air 2.5E-04 

Manufacture of EPS that contains HBCD (also referred to as “industrial use of EPS compound” (EC, 2008) or “conversion or processing of polymeric resin into EPS foam products” (NICNAS, 2012)) 

EC (2008)

water 3.0E-05 

These are the emission factors for the generic site and are reported in OECD (2004b) as the emission factors for organic flame-retardants of relatively low volatility in partially open plastics conversion processes. 

300 

This is thsite and accordan

air 3.0E-05 assessm

NICNAS (2012) 

water 1.6E-03 

These emission factors are weighted averages of emission factors for organic flame of relatively high volatility in closed plastics conversion processes that are reported in OECD (2004b). The emission factors that were averaged include values for high process temperature and low

plastics production volume. 

200 This is an 

air 1.6E-03 

Compounding of Polystyrene Resin to Produce XPS Masterbatch containing HBCD (also referred to as “formulation of XPS compound for the manufacture of 

EC (2008) water 7.4E-06 This is the emission factor for a generic site and is equal to 

the maximum of emission factors calculated from sitespecific data for three sites. 

300 

This is thsite and accordanassessm

air 7.3E-06 This is the emission factor for a generic site and is equal to 

the maximum emission factor calculated from site-specific data that pertain to three processing steps including formulation of EPS and XPS compounds. 
Page 71 of 97 

Operation 

(Manufacture or 

Processing Step) 

Reference Release Media Loss Factor (Emission Factor) Number 

Value Description Value 

flame retarded XPS” (EC, 2008) 

Environment CA and Health CA (2011) 

water 6.6E-03 This is the emission factor for a generic site and is the sum 

of emission factors for handling and compounding organic solid flame retardants with particle sizes <40 μm that are of 

relatively medium volatility as reported in OECD (2004b). 

60 or 

200 

These vaare funcrate, and accordanassessm

Manufacture of XPS using XPS Masterbatch containing HBCD 

EC (2008) 

water 2.6E-05 

These are the emission factors for the generic site and are equal to the maxima of the emission factors that were derived from site-specific data but were not explicitly reported. EPA calculated these factors, each of which is equal to the ratio of total annual releases from 13 sites for which site-specific data was not reported and the total 

annual processing rate for these sites. 

1 

This valureasonanumber generic sare in th

air 5.8E-05 300 

The numgeneric sspecific v15 to 30
Page 72 of 97 

Table_Apx C-3: Preliminary Values of Input Variables for Calculation of the Range of Release Rates from Manufacturing Sites of Each Processing Step 

Operation 

(Manufacture or 

Processing Step) 

Processing Rates 

as Fractions of the 

HBCD 

Manufacturing 

Rate1

Manufacturing or Processing 

Rate (kg/yr)2

Number of Sites3 Number of 

Release 

Days4

The Minimum and 

Compiled5 and Ca

Each Medium of Re

per kg of HBCD ma

lower limit of 

range 

upper limit of 

range 

minimum maximum water 

min max 

manufacture of HBCD Not Applicable 4.540.E+06 2.290.E+07 3 250 1.2E-07 4.0E-0manufacture of EPS resin beads 0.45 2.043.E+06 1.031.E+07 1 4 250 7.6E-06 6.8E-0manufacture of EPS 0.45 2.043.E+06 1.031.E+07 5 15 250 3.0E-05 1.6E-0manufacture of XPS using HBCD powder 

0.51 2.316.E+06 1.168.E+07 6 18 1 (water) 250 (air) 1.0E-05 1.0E-0

compounding of polystyrene resin to produce XPS masterbatch containing HBCD 0.51 2.316.E+06 1.168.E+07 10 29 250 7.4E-06 6.6E-0manufacture of XPS using XPS masterbatch containing HBCD 0.51 2.316.E+06 1.168.E+07 10 24 1 (water) 250 (air) 2.6E-05 

Note: 

1) The share of production volume that is processed to manufacture of EPS or XPS is reported in Table_

of production volume that is processed to manufacture of XPS using HBCD powder or HBCD masterb

therefore EPA will conservatively assume this share is equal to the total share that is processed to m
Page 73 of 97 

2) EPA estimated the lower-end of the current range of production volumes by summing the lower-end

production volumes for CAS number 25637-99-4 reported in 2002 and CAS number 3194-55-6 repor

given in Table_Apx B-2. EPA estimated the upper-end of the current range of production volume by 

ends of these two ranges. 

3) The number of sites was estimated from data reported in EPA (2014b) and Table_Apx C-1. 

4) EPA estimated the number of release days to be equal to 250 assuming each facility has an operatio

days per week and 50 weeks per year, allowing for two-week annual downtime for maintenance. Th

number of release days given Table_Apx C-2 are of similar magnitude. The exceptions are the valuewater from the manufacture of XPS using HBCD powder and XPS using XPS masterbatch; EPA assess

parameters to be 1 day per year in consideration of the data presented in Table_Apx C-2. 

5) The compilation of non-site specific release factors is given in Table_Apx C-2. 

6) EPA calculated release factors for HBCD manufacturing and the manufacture of XPS using HBCD pow

reported in EC (2008) because non-site specific release factors are not reported for these two opera
Appendix D Environmental Hazard Study Summaries 

D-1 Persistence in Environmental Media 

D-1-1 Air and Water 

HBCD does not absorb light in the UV/Visible frequencies so is not expected to undergo direct 

photolysis in air or water (Zhou et al., 2014). Kajiwara et al (Kajiwara and Takigami, 2013) 

studied photolysis of HBCD on textiles (4% by wt.) and reported “no substantial loss of any of 

the HBCD diastereomers during the entire exposure period (371 days)” confirming that 

photolytic degradation did not occur.Indirect photolysis with methane as a co-solvent has been 

observed to result in debromination (Zhou et al., 2012) and indirect photolysis with Fe(III) and 

H2O2 also can occur (Zhou et al., 2014). 

Although HBCD is expected to exist primarily in the particulate phase in the atmosphere, a 

small percentage is expected to exist in the vapor phase based on its vapor pressure (Bidleman, 

1988; CMA, 1997; Covaci et al., 2006). HBCD in the vapor phase can be degraded by reaction 

with hydroxyl radicals in the atmosphere with an estimated rate constant of 

5.01×10-12 cm3

/molecules-sec at 25 °C corresponding to an atmospheric half-life of 2.1 days 

(EPA, 1993, 2011a). HBCD associated with particulates is expected to be removed from the 

atmosphere through wet or dry deposition. Removal rates are unknown and the widespread 

detection of HBCD in air samples and biota from remote locations far from release locations 

indicate that long-range atmospheric transport occurs (Covaci et al., 2006; EPA, 2010a; Ueno et 

al., 2006). 

D-1-2 Soil, Sediment and Sludge 

Based on an estimated Koc value of 7.6×104

 HBCD is expected to be fairly immobile in soil and to 

bind strongly to soil, sediment, and suspended organic matter. It may undergo abiotic and 

microbial degradation while associated with solids. The limited data available show that 

biodegradation is slow and that anaerobic processes may be faster than aerobic. 

A soil simulation test was conducted according to OECD TG 307 for commercial HBCD (BFRIP, 

2001; EC, 2008). Activated sludge was inoculated with soil and HBCD at a nominal 

concentration of 34-89 μg/kg dry weight for 120 days. The disappearance half-life was 63 days 

in aerobic soil and >120 days in abiotic aerobic controls. In the anaerobic soil, the half-life was 7 

days compared to 82 days in abiotic anaerobic controls. 

A closed bottle screening-level test for ready biodegradability (OECD TG 301D) was performed 

using an initial HBCD concentration of 7.7 mg/L and an activated domestic sludge inoculum 

(BFRIP, 2001; EC, 2008). No biodegradation was observed (0% of the theoretical oxygen 

demand) over the test period of 28 days. Gerecke et al (Gerecke et al., 2006) studied 
Page 75 of 97 

degradation of BFRs, including HBCD, under anaerobic conditions in digested sewage sludge. 

They reported a half-live for a technical HBCD mixture of 0.66 days. They found no statistically 

significant enantioselective degradation of alpha-, beta-, or gamma-HBCD. The reported 

reduction in concentration the HBCD mixture decreased in sterile controls at a rate 50 times 

slower in incubations under non-sterile conditions.

A water-sediment OECD TG 308 study for commercial HBCD with a nominal concentration of 

34-89 μg/kg dry weight found that aerobic half-lives were 11-32 days in aerobic sediments and 

30-190 days in abiotic aerobic controls (BFRIP, 2001; EC, 2008). In the anaerobic sediments, 

disappearance half-lives were 1.1-1.5 days compared to 9.9-10 days in abiotic anaerobic 

controls. 

Davis et al (2006) studied degradation of 14C radiolabeled HBCD with sludge, sediment, and soil

simulation tests with initial concentrations of HBCD of 3.6-4.2 mg/L in the sludge systems and 

3.0-4.7 mg/kg dry weight in the sediment and soil systems. As shown in Table_Apx D-1 below, 

they observed decrease in total initial radioactivity in the viable systems and abiotic controls. 

Table_Apx D-1: Percent Decrease in Total Initial Radioactivity in Viable Systems and Abiotic Controls 

During Sludge, Sediment, and Soil Simulation Tests Using 14C-labeled HBCD 

Compartment Viable System Abiotic Control Time Period 

Anaerobic digester sludge 87% 84% 60 days 

Aerobic activated sludge 21% 15% 65 days 

Anaerobic freshwater 

sediment 

61% 33% 112-113 days 

Aerobic freshwater sediment 44% 15% 112 days 

Aerobic soil 10% 6% 112 days 

Source: (BFRIP, 2001; Davis et al., 2006; EC, 2008)

HBCD degradation observed in these tests was attributed to abiotic reductive dehalogenation. 

Degradation proceeded through a stepwise process to form TETRABROMOCYCLODODECENE,

DIBROMOCYCLODODECADIENE, AND 1,5,9-CYCLODODECATRIENE (See 

Figure_Apx 2.6.4-1). Further degradation of 1,5,9-CYCLODODECATRIENE was not observed. General 

trends observed were increased HBCD degradation under anaerobic conditions compared to 

aerobic conditions and slower degradation of α-HBCD compared to the β- and γ-stereoisomers. 
Page 76 of 97 

Figure_Apx 2.6.4-1: Stepwise Reductive Dehalogenation of HBCD 

D-1-3 Water and Wastewater 

HBCD is not expected to undergo hydrolysis in environmental waters because of its low 

solubility and lack of hydrolyzable functional groups. Based on the studies described above it is 

not expected to be readily degradable in WWTPs and is expected to be persistent in surface and 

groundwater. It may undergo indirect photolysis or abiotic degradation catalyzed by iron or 

organic matter and can be biodegraded slowly under aerobic and anaerobic conditions. 

Degradation rates in the environment are expected to be slower than those in lab studies. This 

is consistent with environmental observations. For example the detection of HBCD at 

concentrations ranging from 112 to 70,085 μg/kg dry weight in sediment at locations near a 

production site in Aycliffe, UK collected two years after the facility was closed down 

demonstrates the persistence of this substance in the environment (EC, 2008). 

D-1-4 Bioaccumulation 

High bioconcentration of HBCD in aquatic organisms has been observed in fish. Veith et al. 

(Veith et al., 1979) measured a BCF of 18,100 for HBCD in fathead minnows. In a flow-through 

bioconcentration test, BCF values of 8974 and 13,085 were determined for HBCD in rainbow 

trout (EC, 2008). These BCF values indicate that HBCD has a very high potential to 

bioconcentrate in aquatic organisms. The widespread detection of this substance in aquatic 

organisms also suggests that HBCD bioconcentrates in the environment (Covaci et al., 2006; EC, 

2008). Biomagnification of HBCD in the aquatic food web has also been reported based on 

measurements in invertebrates, fish, birds, and marine mammals, with the highest levels of 

HBCD measured in seals and porpoises (Covaci et al., 2006; EC, 2008; EPA, 2010a). Higher 

concentrations of HBCD were measured in eggs from wild peregrine falcons feeding on birds 

from terrestrial food webs in southwestern Sweden than in the eggs of captive falcons feeding 

on domestic chickens, indicating that HBCD bioaccumulation in terrestrial food chains may also 

be important (EPA, 2010a; Lindberg et al., 2004). Bioaccumulation may be isomer specific with 

γ-HBCD is the dominant stereoisomer present in commercial HBCD formulations (>75%) 
Page 77 of 97 

(Becher, 2005). Similar proportionality is observed with HBCD stereoisomers detected in 

environmental media (Covaci et al., 2006). However, in living organisms, α-HBCD is the 

predominant stereoisomer, accounting for 70-90% of all HBCD detected (Covaci et al., 2006). 

The reason for the difference in HBCD composition found in the environment compared to that 

found in living organisms is unknown. Possible explanations include different rates of 

bioconcentration for the α- and γ- stereoisomers or different rates of metabolism within 

organisms (Covaci et al., 2006; EC, 2008).

D-2 Toxicity to Aquatic Organisms 

The toxicity to aquatic organisms has been summarized in several publications (EC, 2008; 

Environment CA and Health CA, 2011; EPA, 2008a, 2014b; NICNAS, 2012; OECD, 2007). 

Guideline studies in freshwater fish, daphnia, and green algae mostly reported no lethal or 

sublethal effects at concentrations approaching saturation (Calmbacher, 1978; EPA, 2014b; 

Graves and Swigert, 1997a, 1997b; Roberts and Swigert, 1997; Siebel-Sauer and Bias, 1990). 

D-2-1 Aquatic Plant Toxicity 

The toxicity to aquatic plants is summarized below and presented in Table_Apx D-2. The study 

denoted with an asterisk is proposed for use by EPA/OPPT for risk assessment. Those studies 

not considered adequate for risk assessment by EPA/OPPT are shaded in the table. 

Green algae (Selanastrum capricornutum) were exposed to nominal test concentrations of 

HBCD ranging from 1.5 to 6.8 μg HBCD/L (Roberts and Swigert, 1997). The mean measured 

concentration of HBCDs (3.7 μg HBCD/L) at the maximum nominal test concentration of 6.8 μg 

HBCD/L (with solvent) was similar to the independently measured water solubility limit (8.6 

μg/L). No effects were observed at any test concentration. Another freshwater aquatic plant 

study reported that green algae (S. subspicatus) had no effects at nominal test concentrations 

ranging from 7.8 to 500 mg HBCD/L (Siebel-Sauer and Bias, 1990). However, the actual 

concentrations of HBCD in test solution are unknown. No effects were observed at the highest 

tested concentration. 

Adverse effects observed following exposure were found in studies with the estuarine/marine 

algae species Skeletonema costatum (Desjardins et al., 2004, 2005; Walsh et al., 1987). Walsh et 

al. (1987) reported measured 72-hour EC50 values in S. costatum ranging from 0.009 to 0.012 

mg HBCD/L based on reduced growth rate in five different types of saltwater media. The study 

also tested two species, Chlorella sp. and Thalassiosira pseudonana, that were found to be less 

sensitive. Desjardins et al. (2005) further substantiated observed toxicity in S. costatum when a 

single saturated solution of 0.0545 mg HBCD/L (without a solvent) resulted in 51% growth 

inhibition after 72 hours of exposure. Desjardins et al. (2004) also reported 19, 21, and 7.3% 

inhibition of cell density, biomass, and growth rate, respectively, following exposure of S. 

costatum to 0.041 mg HBCD/L (with a solvent), the only concentration tested, for 72 hours. 
Page 78 of 97 

Table_Apx D-2: Toxicity of HBCD to Aquatic Plants 

Test Species Fresh/ Salt 

Water 

Duration EndpointConc. 

(mg/L) 

Test 

Analysis 

Effect References 

Green algae (Selanastrum 

capricornutum) 

Fresh 96-hour EC50 >0.0037 Static, 

Measured

Biomass/Growth 

rate 

Roberts and 

Swigert, 1997 

Green algae (S. 

subspicatus) 

Fresh 96-hour EC50 >500 Static, 

Nominal 

Siebel-Sauer and 

Bias, 1987 

Algae (S. costatum) Marine 72-hour EC50 >0.041 Static, 

Measured

Desjardins et al., 

2004 

Algae (S. costatum) Marine 72-hour EC50 >0.01 Static, 

Measured

Growth inhibition Desjardins et al., 

2005 

Algae (S. costatum) Marine 72-hour EC50 0.052 Static, 

Measured

*Algae (S. costatum) Marine 72-hour EC50 0.009-

0.012 

Static, 

Measured

Growth rate Walsh et al., 

1987 

Algae (Thalassiosira 

pseudonana) 

Marine 72-hour EC50 0.05-0.37 Static, 

Measured

Algae (Chlorella Sp.) Marine 72-hour EC50 >1.5 Static, 

Measured

* The study denoted with an asterisk is proposed for use by EPA/OPPT for risk assessment. 

Shaded studies will not be used to evaluate the risk of HCBD because inadequate test methods or 

incomplete information were provided for the study.

D-2-2 Aquatic Invertebrate Toxicity 

The toxicity to aquatic invertebrates is summarized below and presented in Table_Apx D-3. The 

study denoted with an asterisk is proposed for use by EPA/OPPT for risk assessment. Those 

studies not considered adequate for risk assessment by EPA/OPPT are shaded in the table. 

Water fleas, (Daphnia magna; 10 animals per replicate) were exposed to nominal 

concentrations of 0.0015, 0.0022, 0.0032, 0.0046 and 0.0068 mg/L HBCD under flow through 

conditions for 48 hours (Graves and Swigert, 1997a). On day 0, mean measured exposure 

concentrations were 0.0021, 0.0018, 0.0018, 0.0026 and 0.0031mg/L and on day two, the mean 

measured exposure concentrations were 0.0024, 0.0017, 0.0023, 0.0015, and 0.0034 mg/L. The 

reported 48-hr EC50 was >0.0032 mg/L. 

Jatzek (Jatzek, 1990) reported a lowest-observed-effect-concentration (LOEC) of 10 mg HBCD/L 

and an EC50 of 146.34 mg HBCD/L for daphnia immobility based on nominal test concentrations 

that greatly exceeded measured water solubility values for HBCD (0.0488, 0.0147, and 0.0021 

μg/L for α-, β-, and γ-HBCD); however, because the appearance of the test solutions was not 

reported, it is possible that reduction in daphnid swimming was related to the presence of 

insoluble material at higher concentrations. 

For chronic toxicity, hazard was determined based on reduced size (length) of surviving young 

daphnids, resulting in a measured MATC of 0.0042 mg HBCD/L (Drottar and Krueger, 1998). 
Page 79 of 97 

This study used a flow-through test system and reported additional effects, including decreased 

reproductive rate and decreased mean weight of surviving young at 0.011 mg HBCD/L. 

Mortality of adult daphnids in HBCD treatment groups was not significantly different from 

control mortality. 

Sublethal effects to invertebrates following chronic exposure were found in supporting studies 

that assessed endpoints beyond those evaluated in guideline studies. In invertebrates, 

degenerative changes in the gills of clams (Macoma balthica), manifested by the increased 

frequency of nuclear and nucleolar abnormalities and the occurrence of dead cells, were 

observed at nominal concentrations of 0.1 mg HBCD/L (50-day LOEC) (Smolarz and Berger, 

2009). 

Table_Apx D-3: Toxicity of HBCD to Aquatic Invertebrates 

Test Species Fresh/ Salt 

Water 

Duration Endpoint Conc. 

(mg/L) 

Test 

Analysis 

Effect References 

Aquatic Invertebrates – Acute Toxicity

*Water flea 

(Daphnia magna) 

Fresh 48-hour EC50 >0.0032 Flowthrough, 

Measured

Immobilization Graves and 

Swigert, 1997a 

Water flea 

(D. magna Straus) 

Fresh 48-hour EC50 146.34 

Exceed WS

Static, 

Nominal 

Immobilization Jatzek, 1990 

Aquatic Invertebrates – Chronic Toxicity

Clam (Macoma balthica) Marine 50-day LOEC 0.1 Static, 

Nominal 

degenerative 

changes in the 

gills manifested 

by the increased 

frequency of 

nuclear and 

nucleolar 

abnormalities and 

the occurrence of 

dead cells 

Smolarz and 

Berger, 2009 

*Water flea 

(Daphnia magna) 

Fresh 21-day LOEC 0.0056 

mg/L 

Flowthrough, 

Measured

reduced length of 

surviving young 

Drottar and 

Krueger, 1998 

NOEC 0.0031 

mg/L 

* The study denoted with an asterisk is proposed for use by EPA/OPPT for risk assessment. 

Shaded studies will not be used to evaluate the risk of HCBD because inadequate test methods or 

incomplete information were provided for the study.

Toxicity studies for sediment organisms are summarized in Table_Apx D-4. The study denoted 

with an asterisk is proposed for use by EPA/OPPT for risk assessment. Those studies not 

considered adequate for risk assessment by EPA/OPPT are shaded in the table. 
Page 80 of 97 

In two prolonged sediment toxicity tests (Thomas et al., 2003a, 2003b) with Hyalella azteca

exposed to spiked sediment in the presence of 2 or 5% TOC, no effects were seen at the highest 

concentration tested (1000 mg HBCD/kg dry weight sediment). Results of a non-GLP rangefinding test were submitted in conjunction with the definitive tests that showed reduced 

survival of H. azteca at 500 mg HBCD/kg dry weight sediment in the presence of 2 or 5% TOC. 

In another study, Lumbriculus variegatus were tested at nominal test concentrations of 0.05, 

0.5, 5, 50, and 500 mg HBCD/kg dry weight sediment. Corresponding measured concentrations 

were ND, 0.2, 3.1, 28.7, 303.2 mg HBCD/kg dry weight. No HBCD was detected in the overlaying 

water or in the pore water. Study details were excerpted from a secondary source (Oetken et 

al., 2001). 

Table_Apx D-4: Toxicity of HBCD to Sediment Organisms 

Test Species Fresh/ Salt 

Water Duration Endpoint

Conc. Test 

Analysis Effect References 

*Amphipod (Hyalella 

azteca) 

Fresh 28-day LOEC 500 mg/kg dwt 

sediment 

Flowthrough, 

Measured 

reduced 

survivability 

Thomas et al., 

2003a, b 

NOEC 100 mg/kg dwt

sediment 

Amphipod (H. azteca) Fresh 28-day NOEC 1,000 mg/kg 

dwt sediment 

Flowthrough, 

Measured 

Unspecified Thomas et al., 

2003b 

*Amphipod (H. azteca) Fresh 28-day NOEC 1,000 mg/kg 

dwt sediment 

Flowthrough, 

Measured 

Unspecified Thomas et al., 

2003a 

Chironomid 

(Chironomus riparius) 

Fresh 28-day No 

Dose 

Not doseresponsive N/A Not doseresponsive Thomas et al., 

2003a 

Lumbriculus variegatus Fresh 28-day LOEC 28.7 mg/kg dwt 

sediment 

Static, 

Measured 

reduction in 

worm number

Oetken et al., 

2001 

NOEC 3.1 mg/kg dwt 

sediment 

* The study denoted with an asterisk is proposed for use by EPA/OPPT for risk assessment; N/A = not 

applicable 

Shaded studies will not be used to evaluate the risk of HCBD because inadequate test methods or 

incomplete information were provided for the study.

D-2-3 Fish Toxicity 

The toxicity to fish is summarized below and presented in Table_Apx D-5. The study denoted 

with an asterisk is proposed for use by EPA/OPPT for risk assessment. Those studies not 

considered adequate for risk assessment by EPA/OPPT are shaded in the table. 
Page 81 of 97 

Acute Effects 

Rainbow trout (Oncorhynchus mykiss) were exposed to mean measured concentration of 

HBCDs of 0.00075, 0.0015, 0.0023, 00.23 and 0025 mg/L (with solvent) under flow through 

conditions for 96 hours. No effects were observed at any test concentration (Graves and 

Swigert, 1997b). 

Bluegill sunfish (Lepomis macrochirus) were exposed to nominal concentrations ranged from 10 

to 100 mg/L under static conditions for 96 hours. These test concentrations exceeded the test 

substance water solubility. A white flocculate was formed on the surface of the water in all test 

solutions. No effects were seen at the highest test concentration of 100 mg/L (Calmbacher, 

1978)(Calmbacher, 1978). 

Acute effects observed following acute exposure were found in a 96-hour test with zebrafish 

embryos (Deng et al., 2009). In a 96-hour toxicity study with zebrafish embryos, increased 

malformation rate was observed at a nominal concentration of 0.1 mg HBCD/L and decreased 

survival and increased heart rate were observed at a nominal concentration of 0.05 mg HBCD/L 

(lowest concentration tested); an EC50 or LC50 value was not reported (Deng et al., 2009). 

Chronic Effects 

A chronic study in rainbow trout conducted following EPA recommended guidelines, found no 

effects at concentrations approaching saturation (Drottar et al., 2001). No effects were 

observed in European flounder (Platichthys flesus) following 78 days of diet or sediment 

exposure to maximum concentrations of 3000 μg HBCD/g lipid in food and 8000 μg HBCD/g 

total organic carbon (TOC), respectively (Kuiper et al., 2007). 

Sublethal effects to fish following chronic exposure were found in supporting studies that 

assessed endpoints beyond those evaluated in guideline studies. Effects observed in fish 

include increased formation of reactive oxygen species (ROS) resulting in oxidative damage to 

lipids, proteins, and DNA, decreased antioxidant capacities in fish tissue (e.g., brains, 

hepatocytes, or erythrocytes), and increasing levels of ethyoxyresorufin-O-deethylase (EROD, 

detoxification enzyme) and pentoxyresorufin-O-deethylase (PROD, detoxification enzyme) 

levels in hepatocytes of fish exposed to the nominal concentration of ≥0.1 mg HBCD/L 

(corresponds to ~0.2 mg HBCD/g whole fish [wet weight]) for 42 days (Zhang et al., 2008). 

Indications of endocrine disruption were reported following dietary exposure to HBCD that 

impacted the thyroid system of juvenile rainbow trout (Oncorhynchus mykiss). Each of the 

diastereoisomers of HBCD (administered separately via diet at concentrations of 5 ng/g of α-, 

β-, or γ-HBCD) disrupted thyroid homeostasis, as indicated by lower free circulating 

triiodothyronine (T3) and thyroxine (T4) levels (Palace et al., 2010; Palace et al., 2008). 
Page 82 of 97 

Table_Apx D-5: Toxicity of HBCD to Fish 

Test Species Fresh/ Salt 

Water 

Duration Endpoint Conc. 

(mg/L) 

Test 

Analysis 

Effect References 

Fish – Acute Toxicity

Bluegill sunfish (Lepomis 

macrochirus) 

Fresh 96-hour LC50 >100 Static, 

Nominal 

Mortality Calmbacher, 

1978 

*Rainbow trout 

(Oncorhynchus mykiss) 

Fresh 96-hour LC50 >0.0025 Flowthrough, 

Measured

Mortality Graves and 

Swigert, 1997b 

Zebra fish embryos 

(Danio rario) 

Fresh 96-hour LC50 0.05 Static, 

Nominal 

decreased 

survival, reduced 

heart rate 

Deng et al., 2009

Fish – Chronic Toxicity

Rainbow trout 

(Oncorhynchus mykiss) 

Fresh 88-day NOEC 0.0037 Flowthrough, 

Measured

No effects Drottar et al., 

2001 

Rainbow trout 

(Oncorhynchus mykiss) 

 28-day Intraperitoneal 

injection 

using 50 

and<500 

mg/kg-bw

Significant 

catalase activity 

at 50 and<500 

mg/kg-bw; EROD 

activity; LSI 

increase; No 

effects on blood 

plasma, 

vitellogenin levels 

or DNA adducts 

formation. 

(Ronisz et al., 

2004) 

Chinese rare minnow 

(Gobiocypris rarus) 

Fresh 42-day LOEC 0.1 Static, 

Nominal 

DNA damage in 

erythrocytes; 

induction of 

EROD and PROD 

in hepatocytes; 

ROS formation in 

brain tissue 

Zhang et al., 

MATC 0.032 2008 

European flounder 

(Platichthys flesus) 

Fresh 78-day NOEC 8,000 μg/g 

TOC 

Sediment 

exposed 

No effects on 

behavior, 

survival, growth 

rate, relative liver 

and gonad 

weights 

Kuiper et al., 

2007 

3000 μg/g 

lipid in 

muscle 

Diet 

exposed 

*Rainbow trout (O. 

mykiss) 

Fresh 32-day LOEC 5 ng/g of 

α-, β-, or γHBCD 

Diet 

exposed 

thyroid effects Palace et al., 

2010 

* The study denoted with an asterisk is proposed for use by EPA/OPPT for risk assessment. 

Shaded studies will not be used to evaluate the risk of HCBD because inadequate test methods or 

incomplete information were provided for the study.
Page 83 of 97 

D-3 Toxicity to Terrestrial Organisms 

D-3-1 Terrestrial Plant Toxicity 

Available toxicity studies for terrestrial plants are summarized in Table_Apx D-6. 

Studies using monocot and dicot plant species exhibited no toxicity up to the maximum test 

concentration of 5,000 mg HBCD/kg soil (Porch et al., 2002). 

Table_Apx D-6: Toxicity of HBCD to Terrestrial Plants 

Test Species Duration End-point Conc. Test 

Analysis 

Effect References 

Corn (Zea mays) 21-day NOEC >5,000 mg 

HBCD/kg soil 

Nominal No treatmentrelated effects 

on emergence, 

survival or 

growth 

Porch et al., 2002 

Cucumber (Cucumis 

sativa) 

Onion (Allium cepa) 

Ryegrass (Lolium 

perenne) 

D-3-2 Soil Invertebrate Toxicity 

The available toxicity study in soil organisms summarized below and presented in Table_Apx 

D-7 is adequate for risk assessment*. 

Aufderheide et al., (Aufderheide et al., 2003) reported an EC10 and no-observed-effectconcentration (NOEC) values of 21.6 and 128 mg HBCD/kg dry soil, respectively, based on 

reproductive effects in earthworms following 56 days of exposure. High variability in the data at 

the lower test concentrations (as indicated in ECB, 2008) resulted in wide confidence limits for 

the EC10, differences from the control that were not significant, and a NOEC that was greater 

than the EC10. Two worms from the lowest test concentrations were lost during the study and 

treated as dead (as reported in ECB, 2008), which may have contributed to the high variability 

by reducing the sample size at the lowest test concentration; however, study details, data 

tables, and statistical methodology were not available. 

Table_Apx D-7: Toxicity of HBCD to Terrestrial Invertebrates 

Test Species Duration End-point Conc. Test 

Analysis 

Effect References 

*Earthworm (Eisenia 

fetida)

56-day EC10 21.6 mg 

HBCD/kg dry 

soil 

Nominal, 

Static, Soil

reproduction Aufderheide et al., 2003 

NOEC 128 mg 

HBCD/kg dry 

soil 
Page 84 of 97 

D-3-3 Avian Toxicity 

Available toxicity studies to avian species are summarized in Table_Apx D-8. 

Japanese quail eggs exposed for 6 weeks to an isomeric mixture of HBCD in the diet 

experienced a reduction in hatchability at all tested concentrations (12–1000 ppm) (MOEJ, 

2009). Additional effects included a significant reduction in egg shell thickness starting at 125 

ppm, decreases in egg weights and egg production rates starting at 500 ppm, increases in 

cracked eggs starting at 500 ppm, and adult mortality at 1000 ppm. A subsequent test, 

conducted at lower dietary concentrations, determined a lowest-observed-adverse-effect-level 

(LOAEL) and no-observed-adverse-effect-level (NOAEL) values of 15 and 5 ppm, respectively, 

based on significant reduction of survival of chicks hatched from eggs of HBCD-fed quails 

(MOEJ, 2009). In another study, a number of effects were reported in American Kestrels 

exposed in ovo to 164.13 ng HBCD/g wet weight (Kobiliris, 2010). 

Table_Apx D-8: Toxicity of HBCD to Avian Species 

Test Species Duration End-point Conc. Test 

Analysis 

Effect References 

Japanese quail 

(Coturnix coturnix 

japonica) 

6-week LOAEL 125 ppb Diet 

exposed 

reduction in 

hatchability 

MOEJ, 2009 

15 ppm (2.1 

mg/kg body 

wt/day 

reduced chick 

survival 

5 ppm 

American kestrel

(Falco sparverius) 

 LOAEL 164.3 ng/g wet 

weight of egg 

In ovo 

exposed 

reduced 

corticosterone 

response in male 

nestling kestrels, 

reduced flying 

activities in 

juvenile males, 

delayed 

response time to 

predator 

avoidance in 

juvenile females 

Kobiliris, 2010 
Page 85 of 97 

Appendix E Human Health Hazard Study Summaries 

E-1 Toxicokinetics 

For humans, there is a potential for oral, inhalation and dermal exposure. Available 

toxicokinetics data in rodents indicate that HBCD is moderately absorbed via the 

gastrointestinal tract, metabolized, and distributed to a number of nonfat tissues including 

blood, muscle, and the liver, where it accumulates unchanged (Arita et al., 1983; Brandsma et 

al., 2009; Hakk et al., 2012; Reistad et al., 2006; Sanders et al., 2013; Szabo et al., 2010; Szabo et

al., 2011b; van der Ven et al., 2009; van der Ven et al., 2006; Yu and Atallah, 1980). Elimination 

of HBCD is predominantly via feces (as the parent compound), but it is also eliminated in urine 

(as secondary metabolites) (Arita et al., 1983; Yu and Atallah, 1980; Szabo et al., 2010). In 

humans, HBCD has been detected in breast milk, adipose tissue, blood, and both maternal and 

umbilical serum (Abdallah and Harrad, 2011; Antignac et al., 2008; Covaci et al., 2006; 

Fangstrom et al., 2008; Fangstrom et al., 2005; Johnson-Restrepo et al., 2008; Kakimoto et al., 

2008; Meijer et al., 2008; Rawn et al., 2014; Thomsen et al., 2007; Weiss et al., 2006) 

E-2 Acute Toxicity Studies 

Several acute toxicity studies in rats and rabbits by the oral, dermal, and inhalation routes with 

HBCD are available (BASF, 1990; Gulf South Research Institute, 1988; IRDC, 1977, 1978a, 1978b; 

Lewis and Palanker, 1978; Momma et al., 1993). The acute toxicity of HBCD is low via the oral 

route in rats and low via the dermal route in rabbits (Lewis and Palanker, 1978), with LD50 

values >680 mg/kg-bw. Acute inhalation exposure to HBCD resulted in some minor symptoms 

(such as eye squint, slight dyspnea, salivation, lacrimation, and nasal discharge), but no LC50 has 

been identified. 

The acute toxicity of HBCD is summarized in Table_Apx E-1 (oral) and Table_Apx E-2 

(inhalation). 

Table_Apx E-1: Acute Oral Toxicity of HBCD 

Species/strain/

test 

Exposure Result Notes Reference 

Rat/Charles 

River/LD50

Single gavage (corn 

oil) 

LD50 >10,000 

mg/kg 

No mortality; transient hypoactivity 

and diarrhea; corneal opacity and 

ptosis in 3/5 males, which did not 

resolve by end of 14-day 

observation. 

IRDC, 1977 

Rat/Charles River 

CD/ LD50 test of 

HBCD residue 

Single gavage (corn 

oil) 

LD50 = 1258 

mg/kg (male); 

680 mg/kg 

(female) 

Tested Firemaster 100; increased 

activity, eye squint, dyspnea, 

lacrimation, and nasal discharge. 

IRDC, 1978a 
Page 86 of 97 

Species/strain/

test 

Exposure Result Notes Reference 

Weight loss in all animals; recovery 

noted by conclusion of study. 

Mouse/NR/LD50 Single gavage (30% 

aqueous tragacanth)

LD50 >6,400 

mg/kg; data 

not shown 

7-day observation period; increasing 

apathy, trembling and late 

mortalities; peritonitis at necropsy. 

BASF, 1990 

Rat/SpragueDawley/limit test 

of HBCD bottoms 

Single gavage (corn 

oil) 

LD50 >5,000 

mg/kg; clinical 

signs 

This study tested HBCD bottoms 

described as black solids, 

lacrimation, and facial swelling 

resolved by post-exposure day 4; no 

gross lesions were observed. 

Pharmakon 

Research 

International 

Inc., 1990 

Rat/NR/LD50 test Single gavage (corn 

oil) 

LD50 >10,000 

mg/kg 

No significant changes observed. Gulf South 

Research 

Institute, 1988

Abbreviations: NR, not reported 

Table_Apx E-2: Acute Inhalation Toxicity of HBCD 

Species/strain/test Exposure Result Notes Reference 

Rat/Charles River/LD50 4-hr exposure to 

Firemaster 100 dust: 

202.14 mg/L 

No mortality; 

slight dyspnea at 

the end of 

exposure only 

All rats gained weight over 

the observation period, but 

no control data were 

reported. 

IRDC, 1977 

Rat/Wistar/limit test 1-hr exposure to 

200 mg/L GLS-S6-

41A (highest 

possible 

concentration) 

No mortality; no 

clinical signs 

All rats gained weight over 

the observation period, but 

no control data were 

reported. 

Lewis and Palanker, 

1978 

Rat/Charles River/LC50

test of Firemaster 100 

residue (liquid) 

4-hr exposure to 

Firemaster 100 

residue: 22.9 mg/L 

One death (female, Day 3 post-exposure); 

dyspnea, salivation, lacrimation, and nasal 

discharge during exposure, resolved by Day 3; 

significant body weight loss through Day 3, but 

beginning to recover by Day 14 post exposure; 

signs of nasal and lung irritation at gross 

necropsy of rat that died. 

IRDC, 1978b 

Rat/NR/LC50 test 1 hr. whole-body 

inhalation exposure 

to GLS-S6-41A 

LC50 >200 mg/L No significant effects 

observed. 

Gulf South Research 

Institute, 1988 

Abbreviations: NR, not reported 

E-3 Repeated-Dose Toxicity Studies 

Short-term and subchronic toxicity studies on HBCD are available and summarized Table_Apx 

E-3. In these studies, HBCD demonstrated effects on the thyroid and liver (Chengelis, 2002; 
Page 87 of 97 

Chengelis, 1997, 2001; van der Ven et al., 2006). However, most of these effects were not 

significant after a recovery period of 14 days and 28 days, respectively (Chengelis, 2002; 

Chengelis, 1997, 2001). Older short-term and chronic toxicity studies using an HBCD product 

that is no longer manufactured concluded that observed liver findings were adaptive rather 

than adverse (Zeller and Kirsch, 1969, 1970). Developmental behavioral defects were observed 

in 3-month old mice after a single oral exposure on postnatal day (PND) 10 (Eriksson et al., 

2006). 

This following summary is extracted from the hazard characterization found in the supporting 

documents for Initial Risk-Based Prioritization of High Production Volume Chemicals (EPA, 

2008a): 

The potential toxicity from repeated oral exposure to HBCD was assessed in a variety of studies 

in laboratory animals. Liver effects were observed in several studies but based on the 

inconsistency of effects between studies and sexes, and lack of dose-response, it is not clear if 

the observed effects are treatment-related. Effects on the thyroid (one or both sexes) were 

observed at moderate to high doses in some repeated-dose studies but not others, but could 

be due to the fact that the thyroid system was not thoroughly studied in the early studies. More 

recent studies showed increased thyroid weights in females only. One study indicates 

decreased serum T4 and increased serum TSH in both sexes, whereas another study only shows 

effects in females. Taken together, however, the data are suggestive of possible treatmentrelated thyroid effects in adult animals. Several recent in vivo and in vitro studies have been 

conducted to try and elucidate the possible mechanisms for both the observed liver and 

thyroid effects, but with no clear conclusions. Functional observation battery and motor activity 

evaluations in adult animals showed no evidence of neurotoxicity. 

Table_Apx E-3: Repeated-Dose Toxicity of HBCD 

Species/strain Exposure Result Notes Reference 

Sprague-Dawley rats 28-days Liver weight 

increase from the 

lowest dose (940 

mg/kg-day) in both 

sexes. Thyroid 

hyperplasia from 

the lowest dose 

(940 mg/kg-day) in 

both sexes. 

The authors attributed the 

increased liver weight to 

hyperactivity as a result of 

increased thyroid activity 

and concluded the 

increased liver weights 

were not pathologic. 

NOAEL = 940 mg/kg-day. 

Zeller and Kirsch, 

1969 

Sprague-Dawley rats 90-days Liver weight 

increases from the 

lowest dose (120 

mg/kg-day) in both 

sexes. No 

histopathological 

effects in thyroid 

were reported. 

Demonstrates a low order 

of toxicity and may reflect 

a reversible adaptive 

change. Data supports 

that the liver and thyroid 

glands are targets. 

Zeller and Kirsch, 

1970 
Page 88 of 97 

Species/strain Exposure Result Notes Reference 

Sprague-Dawley rats 28-days Liver weight 

increase in females 

from the lowest 

dose (125 mg/kgday) and in males 

from the mid dose 

(350 mg/kg-day). No 

histological effects 

observed in the 

thyroid in either sex.

The effects on the liver 

especially in female rats 

indicate a LOAEL of 125 

mg/kg-day. 

Chengelis, 1997 

Sprague-Dawley rats 90 days Liver weight 

increase from the 

lowest dose (100 

mg/kg-day) in both 

sexes. 

Thyroid weight was 

increased from the middose in females (300 

mg/kg-day), but not in 

males. Serum T4 was 

decreased and TSH 

increased in all dose 

groups of both sexes. 

LOAEL of 100 mg/kg-day 

based on increases in liver 

weights and changes in 

thyroid serum 

concentrations. 

Chengelis, 2001 

Wistar rats 28 days Liver weight 

increases in females 

at 23 mg/kg-day 

Most sensitive endpoint 

was a 10% increase in 

thyroid weight in females 

at 3 mg/kg-day. 

Van der Ven et al., 

2006 

E-4 Reproductive and Developmental Toxicity Studies 

The available toxicity data for HBCD also includes evidence of reproductive, developmental, and 

neurological toxicity in rats and mice which are summarized in Table_Apx E-4 and Table_Apx 

E-5. An exposure-response array for reproductive and developmental toxicity is presented in 

Figure_Apx 2.6.4-2 and for neurological effects is presented in Figure_Apx 2.6.4-3. 

Information on the developmental and reproductive toxicity of HBCD comes from a singlegeneration reproductive toxicity study (van der Ven et al., 2009), a study incorporating 

gestational and post-natal exposure (Saegusa et al., 2009), a two-generation reproduction 

toxicity study (Ema et al., 2008), a gestational exposure study (Murai et al., 1985), and a 

neurotoxicity study of adult mice neonatally exposed to HBCD (Eriksson et al., 2006). 
Page 89 of 97 

Table_Apx E-4: Reproductive and Developmental Toxicity of HBCD* 

Species/strain Exposure Result Notes Reference 

Wistar rats One full 

spermatogenic or 

two full estrous 

cycles (males: 70 d 

prior to mating; 

females: 14 d prior 

to mating) and 

continued during 

pregnancy and 

lactation for a total 

of 11 wks post 

weaning 

No exposure related 

changes in 

reproductive 

parameters, 

including mating 

success, time to 

gestation, gestation 

duration, number of 

implantation sites, 

litter size, and sex 

ratio. 

NOAEL ~ 100 mg/kg-day 

(highest dose tested) 

Van der Ven et al., 

2009 

Crl:CD(SD) rats 10 wks prior to 

mating and through 

gestation, lactation, 

and for two 

generations (multigeneration 

reproductive 

toxicity study) 

A significant 

decrease in the 

number of 

primoridal follicles 

in the ovary; 

decreased size of 

the thyroid follicles 

in both sexes and an 

increase in pup 

mortality during 

lactation 

LOAEL ~ 101 mg/kg-day 

NOAEL ~ 10 mg/kg-day 

Ema et al., 2008 

Wistar rats GD 0-20 No significant 

changes in the 

number of implants, 

resorptions, live or 

dead fetuses or 

external, visceral or 

skeletal anomalies 

NOAEL ~ 750 mg/kg-day 

(highest dose tested) 

Murai et al., 1985 

Crj:CD(SD)IGS rats GD 10–PND 20 

(weaning) 

No exposure-related 

changes in 

reproductive 

parameters; 

however, increased 

thyroid weight and 

decreased serum T3

in male offspring at 

~146 mg/kg-day 

NOAEL ~ 1505 mg/kg-day 

(highest dose tested) 

Saegusa et al., 2009 

Wistar rats See Van der Ven et 

al., 2009 

Effect on Brainstem 

Auditory Evoked 

Potentials (BAEPs) 

observed in the low 

frequency range 

and only in male offspring (see text) 

Neurobehavioral 

assessment of the rats in 

the Van der Ven et al., 

2009 study. 

Lilienthal et al., 

2009 

 *Only studies considered adequate for risk assessment are presented in the table. 
Page 90 of 97 

Signs of developmental toxic effects in Wistar rats included immune system effects, indications 

of liver toxicity, and decreases in bone mineral density at very low doses, i.e., <1.3 mg/kg-day 

(van der Ven et al., 2009); however, the authors noted that the vehicle used (corn oil) may have 

affected observations at higher doses, including: increased mortality during lactation, 

decreased liver weight in males, decreased adrenal weight in females, decreased plasma 

cholesterol in females, and other immunological markers of toxicity. Saegusa et al. (2009) 

observed an increased relative thyroid weight and decreased triiodothyronine (T3) levels in F1 

male Sprague-Dawley rats at postnatal week (PNW) 11 following dietary exposure to 1,000 ppm 

(approximately 146.3 mg/kg-day) HBCD. Saegusa et al. (2009) also reported a significant 

reduction in the number of CNPase-positive oligodendrocytes at 10,000 ppm (approximately 

1,504.8 mg/kg-day). Developmental toxicity was not observed in F1 Wistar rats following 

dietary exposure to HBCD during gestation (Murai et al., 1985). 

Ema et al. (2008) reported a reduced viability index on Day 4 and Day 21 of lactation among 

second generation (F2) offspring at 15,000 ppm (approximately 1,363 mg/kg-day). Ema et al. 

(2008) observed additional developmental effects at doses as low as 1,500 ppm (approximately 

115 and 138 mg/kg-day for F1 males and females, respectively), including: an increase in 

dihydrotestosterone (DHT) in F1 males and an increased incidence of animals with decreased 

thyroid follicle size in both sexes and generations. These authors reported no effects on sexual 

development indicated by anogenital distance, vaginal opening, or preputial separation among 

F1 or F2 generations. 

Reproductive toxic effects have also been observed in Ema et al. (2008). A decrease in the 

number of primordial follicles in first generation (F1) female Crl:CD(SD) rats at 1,500 ppm 

(approximately 138 mg/kg-day) and a significant increase in the number of litters lost in the F1 

generation at 15,000 ppm (approximately 1,363 mg/kg-day) were reported. No other 

treatment-related adverse effects were reported in any generation for indicators of 

reproductive health, including: estrous cyclicity, sperm count and morphology, copulation 

index, fertility index, gestation index, delivery index, gestation length, number of pups 

delivered, number of litters, or sex ratios. 

Neither van der Ven et al. (2009) nor Saegusa et al. (2009) observed reproductive effects at the 

doses tested (up to 100 mg/kg-day in Wistar rats and approximately 1,504.8 mg/kg-day in 

Sprague-Dawley rats, respectively). 

No standard neurotoxicity or developmental neurotoxicity studies on HBCD are available. 

Information on neurotoxicity was obtained from Functional Observational Battery, locomotor 

activity evaluations, neurobehavioral testing, surface righting reflex, negative geotaxis reflex, 

mid-air righting reflex, and brainstem auditory evoked potentials (BAEPs) in several repeateddose and reproductive toxicity studies. 

For example, in a subacute toxicity study, HBCD was administered orally by gavage in corn oil to 

Sprague-Dawley Crl:CD BR rats for 28 days at doses of 0, 125, 350, or 1,000 mg/kg-day (6 
Page 91 of 97 

rats/sex/dose in 125 and 350 mg/kg-day groups and 12 rats/sex/dose in the control and 1,000 

mg/kg-day groups) (Chengelis, 1997). At the end of 28 days, 6 rats/sex/dose were necropsied, 

while the remaining rats in the control and 1,000 mg/kg-day groups were untreated for a 14-

day recovery period prior to necropsy. Functional Observational Battery and motor activity 

evaluations were carried out prior to study initiation, during the last week of HBCD 

administration (Week 3), and during the recovery period (Week 5). No changes in the 

Functional Observational Battery and motor activity tests were reported. 

In another subchronic toxicity study, (Chengelis, 2002; Chengelis, 2001) administered HBCD by 

oral gavage in corn oil daily to Crl:CD(SD)IGS BR rats (15/sex/dose) at dose levels of 0, 100, 300, 

or 1,000 mg/kg-day for 90 days. At the end of 90 days, 10 rats/sex/dose were necropsied, while 

the remaining rats were untreated for a 28-day recovery period prior to necropsy. Functional 

Observational Battery and locomotor activity evaluations were carried out on 5 

animals/sex/dose prior to study initiation, during the last week of HBCD administration (Week 

13), and during the recovery period. There were no treatment-related effects on Functional 

Observational Battery and locomotor activity observed. 

In a one-generation study that included additional immunological, endocrine and 

neurodevelopmental endpoints, van der Ven (2009) exposed Wistar rats (10/sex/dose) to a 

composite mixture of technical-grade HBCD in the diet at concentrations resulting in doses of 

0.1, 0.3, 1.0, 3.0, 10, 30, or 100 mg/kg-day. This study followed OECD Guidelines 415 and 407 

(OECD, 1983, 1995). Just prior to the end of the study, at approximately 8 weeks of age, the 

remaining F1 pups were assigned to separate groups for necropsy (5/sex/dose), immunological 

testing (4 males/dose), or neurobehavioral testing (6/sex/dose plus additional males and 

females from selected dose groups). Lilienthal et al. (Lilienthal et al., 2009) reported the results 

of the neurobehavioral assessment from the one-generation study conducted by van der Ven et 

al. (2009). Lilienthal et al. (2009) examined 110 day-old F1 rats for haloperidol-induced 

catalepsy to determine possible effects of HBCD on the dopaminergic system. One month after 

the catalepsy measurements, brainstem auditory evoked potentials (BAEPs) to broadband click 

and frequency-specific tone stimuli were recorded in males and females to examine potential 

effects on auditory functions. The study authors concluded that the observed dose-dependent 

decreases in latencies may be due to HBCD-related effects on dopaminergic activity or to HBCDrelated induction of metabolizing liver enzymes resulting in enhanced metabolism of 

haloperidol. HBCD-related effects on BAEP were observed in the low frequency range and only 

in male offspring. The study authors hypothesized that HBCD exerts a cochlear effect on males 

based on the results of the BAEPs. The authors noted that an alternative explanation could be 

HBCD-induced changes in retinoids, which may be involved in development of the inner ear. 

Too little information is available in this study to determine the significance of its findings. 

Finally, in a two-generation reproductive toxicity study, Ema et al. (2008) administered HBCD to 

Crl:CD(SD) rats conducted according to OECD Guideline 416 (OECD, 2001), US EPA Guidelines 

(EPA, 1991, 1996), and good laboratory practices (GLP). Groups of male and female rats 
Page 92 of 97 

(24/sex/dose) were fed HBCD (as a mixture of α-HBCD, β -HBCD, and γ-HBCD with proportions 

of 8.5, 7.9, and 83.7%, respectively) in the diet at concentrations of 0, 150, 1,500, or 15,000 

ppm from 10 weeks prior to mating through mating, gestation, and lactation. Reproductive and 

developmental milestones were monitored, including: surface righting reflex, negative geotaxis 

reflex, mid-air righting reflex, and anogenital distance. F2 females exposed to 15,000 ppm HBCD 

completed the mid-air righting reflex (76.9%) than control F2 females (100%). These findings 

were not consistent over generations or sexes and were not considered treatment related. No 

other effects of HBCD exposure on the development of reflexes were observed in either F1 or 

F2 progeny. 

An additional study on the neurotoxicity of HBCD is available. Eriksson et al. (2006) observed 

effects on spontaneous motor behavior, learning, and memory in adult NMRI mice following 

exposure to HBCD on postnatal day (PND) 10. At 0.9 mg/kg, the authors reported significantly 

reduced mean locomotor activity. However, this study was not conducted according to current 

guidelines (EPA, 1998b) and GLP, therefore EPA reserves judgment on the significance of these 

findings. The authors used too few dose groups and the behavioral alterations were induced at 

doses that did not produce clinical signs or affect weight gain. Additionally, effects due to litter 

size were not considered. However, this study did demonstrate good repeatability for control 

values and for relevant active substances tested several times. 

Figure_Apx 2.6.4-2: Exposure-Response Array for Developmental and Reproductive Toxicity Studies of 

HBCD 
Page 93 of 97 

Table_Apx E-5: Summary of Effects in Parental and F1 Rats After Dietary, Gestational, Lactational and 

Postnatal Exposure to HBCD 

HBCD (ppm in diet) 

MalescFemalesc

Generation 0 100 1,000 10,000 0 100 1,000 10,000 

F0 

Thyroid

Relative weight (mg/100 

g BW) 

ND ND ND ND 5.73 6.75 6.30 7.47*

Histopathology: diffuse 

follicular cell hypertrophy 

(±/+/++/+++)a

ND ND ND ND 3/10

(0/3/0/0)b

5/10 

(2/3/0/0) 

6/10 

(1/3/2/0)

9/10#

(0/3/4/2)§§

F1 

Relative organ weights, PND 20 

Liver (g/100 g BW) 3.68 3.82 3.98 4.66* 3.77 3.83 4.01 4.83*

Relative organ weights, PNW 11 

Liver (g/100 g BW) 3.45 3.81** 3.58 3.53 3.35 3.59 3.44 3.30 

Thyroid (mg/100 g BW) 4.85 5.66 5.78* 6.20** 8.20 6.84 7.35 7.72 

Epididymides (mg/100 g 

BW) 

0.23 0.21* 0.22 0.21 NA NA NA NA 

Thyroid-related hormones 

PND 20 

T3 (ng/ml) 1.09 1.13 1.06 0.93** ND ND ND ND 

T4 (μg/dl) 4.39 4.20 4.78 4.20 ND ND ND ND 

TSH (ng/ml) 5.40 6.66 6.07 7.00* ND ND ND ND 

PNW 11 

T3 (ng/ml) 0.96 0.93 0.88* 0.89** ND ND ND ND 

T4 (μg/dl) 4.77 4.84 5.21 5.20 ND ND ND ND 

TSH (ng/ml) 4.74 5.81 5.36 4.96 ND ND ND ND 

Histopathology 

PND 20 

Liver: Vacuolar 

degeneration, liver 

cells, diffuse (+/++)a

0/10 0/10 0/10 6/10* 

(6/0)

0/10 0/10 0/10 6/10*

 (0/6)§§

PNW 11

Adrenal: Vacuolar 

degeneration, diffuse, 

cortical cells (+/++)a

0/10 0/10 0/10 4/10*

(2/2)§

ND ND ND ND

Abbreviations: BW, body weight; PND, postnatal day; ppm, parts per million; PNW, postnatal week; ND, no data; NA, not 

applicable; aGrade of change: (±) minimal; (+) slight; (++) moderate; (+++) severe; bNumber of animals with each grade; cn=10 

rats/sex/group; * Significantly different from the controls by Dunnett’s test or Dunnett-type rank-sum test (p<0.05) 

** Significantly different from the controls by Dunnett’s test or Dunnett-type rank-sum test (p<0.01) 

# Significantly different from the controls by Fisher’s exact probability test (p<0.05) 

§

 Significantly different from the controls by Mann-Whitney’s U-test (p<0.05) 

§§ Significantly different from the controls by Mann-Whitney’s U-test (p<0.01) 

Source: (Saegusa et al., 2009) 
Page 94 of 97 

Figure_Apx 2.6.4-3: Exposure-Response Array for Neurological Effects of HBCD 

Source: (EPA, 2014d) 

E-5 Skin Irritation and Sensitization Studies 

The available literature indicates that HBCD is not a dermal irritant in guinea pigs at 

concentrations up to 0.5 mL, but one study found HBCD to be a mild skin allergen (Momma et 

al., 1993). Acute eye irritation studies in rabbits showed HBCD to be a mild transient ocular 

irritant (Gulf South Research Institute, 1988). 

E-6 Genotoxicity and Cancer Studies 

A limited number of studies investigated the genotoxicity of HBCD. These studies, summarized 

in Table_Apx E-6, indicate that HBCD is not likely to be genotoxic. 

The majority of these studies were standard Ames tests for detecting mutagenic potential in 

Salmonella typhimurium (S. typhimurium). Most Ames tests conducted with HBCD yielded 

negative results (Huntington Research Center, 1978; IBT, 1990; Litton Bionetics Inc, 1990; 

Pharmakoligisches Institute, 1978; SRI, 1990; Zeiger et al., 1987). Two Ames tests showed 

positive, dose-dependent results for strain TA1535; one for TA1535 only using a liquid residue 

of HBCD in DMSO (IBT, 1990); and one for strains TA1535 and TA100 using an unidentified 
Page 95 of 97 

mixture characterized only as HBCD bottoms in acetone (Ethyl Corporation, 1985a). Both of 

these strains detect reversions by base pair substitution. However, the Ames tests in the strains 

that were positive in these two studies (TA1535 and TA100) were negative in the other studies 

cited above. 

In mammalian systems, a reverse mutation assay with Chinese hamster ovary (CHO) Sp5 and 

SPD8 cell lines exposed to HBCD yielded positive results (Helleday et al., 1990). A test of 

unscheduled DNA synthesis with rat hepatocytes exposed to HBCD bottoms was also positive 

with a dose-response relationship (Ethyl Corporation, 1985b). The reverse mutation assay in 

CHO cells (Helleday et al., 1999) and the unscheduled DNA synthesis assay in F344 hepatocytes 

(Ethyl Corporation, 1985b) were not repeated by any other group. 

Several assays performed to determine the genotoxicity of HBCD were negative even when 

testing at cytotoxic concentrations, including: one in yeast (Litton Bionetics Inc., 1990), one 

detecting chromosomal aberrations in human peripheral lymphocytes in vitro (Microbiological 

Associates Inc, 1996), and one in vivo mouse micronucleus test following intraperitoneal 

injection of HBCD (BASF, 2000). Several previous assessments have concluded that based on 

the lack of mutagenicity in vitro and in vivo, HBCD does not have genotoxic potential in vitro or 

in vivo (EC, 2008; Environment CA and Health CA, 2011; NICNAS, 2012; OECD, 2007). EPA agrees 

with this conclusion. 

Existing assessments have also concluded, based on genotoxicity information and one limited 

lifetime study, that HBCD is not carcinogenic (NICNAS, 2012; TemaNord, 2008) or that further 

study of carcinogenicity is not warranted (EC, 2008; OECD, 2007). However, the only available 

dietary study evaluating the carcinogenic potential of HBCD in mice is not considered adequate 

to draw conclusions regarding carcinogenicity (EC, 2008; Environment CA and Health CA, 2011; 

EPA, 2014b; OECD, 2007). Given this data gap, EPA’s HBCD assessment will not include 

carcinogenicity assessment. 
Page 96 of 97 

Table_Apx E-6: Genotoxicity of HBCD 

Test/species/strain/ 

route 

Test doses 

(per plate)a

Resultsb

–S9 +S9 Notes Reference 

Eukaryotic systems, in vitro

S. typhimurium TA98, 

TA100, TA1537 

3,000 μg 

in DMSO – – 

Doses ≥1,000 μg were partially 

insoluble. 

Pharmakologisches 

Institute, 1978 

S. typhimurium TA98, 

TA100, TA1535, 

TA1537, TA1538 

250 μg 

(Firemaster, FM100, Lot 53, white 

powder) 

in DMSO 

– – 

Doses ≥250 μg were insoluble. IBT, 1990 

1,000 μg (FM100, Lot 3322, 

liquid residue) 

in DMSO 

– 

+ 

(TA1535 

only) 

Positive in TA1535 at highest 

dose only; lower doses showed 

positive trend with dose. 

S. typhimurium TA98, 

TA100, TA1535 

10,000 μg 

in DMSO – – 

Insoluble at 10,000 μg. Huntingdon 

Research Center, 

1978 

S. typhimurium TA98, 

TA100, TA1535, 

TA1537 

10,000 μg 

in DMSO – – 

 Zieger et al., 

1987 

S. typhimurium TA98, 

TA100, TA1535, 

TA1537, TA1538 

5,000 μg 

in DMSO _ _ 

 SRI, 1990 

S. typhimurium TA98, 

TA100, TA1535, 

TA1537 

50 μg 

(HBCD bottoms ) 

in acetone + 

(TA1535 

and 100 

only) 

+ 

(TA100 

only) 

No cytotoxicity observed. Doseresponse only in TA1535 (–S9) 

≥100 μg/plate. TA100 positive at 

highest dose only (5,000 

ug/plate). All doses had a black 

precipitate thought to be 

carbon. 

Ethyl 

Corporation, 

1985a 

S. typhimurium TA98, 

TA100, TA1535, 

TA1537, TA1538 

50 μg 

– – 

 Litton Bionetics, 

1990 

Prokaryotic non-mammalian systems, in vitro

Saccharomyces 

cerevisiae D4

50 μg 

– – 

 Litton Bionetics, 

1990 

Mammalian systems, in vitro

Chromosomal 

aberration test 

In human peripheral 

blood lymphocytes 

750 μg/mL (-S9) 

and 

250 μg/mL (+S9) 

in DMSO – (T) – (T) 

Doses 750 – 2,500 were partially 

insoluble, and fully insoluble 

>2,500 μg/mL. Repeated test for 

two harvest time points: 20 hr (-

S9) or 4 hr (+S9) incubations, and 

20 or 44 hr incubations (-S9 and 

+S9). 

Microbiological 

Associates, 1996
Page 97 of 97 

Test/species/strain/ 

route 

Test doses 

(per plate)a

Resultsb

–S9 +S9 Notes Reference 

Unscheduled DNA 

Synthesis 

rat/F344 

male/primary 

hepatocytes

5 – 1,000 μg/well

in acetone 

(HBCD bottoms) 

+ NA 

Five highest doses (from 5 

μg/well) showed an increased 

response with dose over solvent 

control, but only four highest 

were statistically significant (χ2

). 

Highest dose (1,000 μg/well) was 

cytotoxic. 

Ethyl 

Corporation, 

1985b 

Reversion assay 

CHO/V79/Sp5 and 

SPD8 

Intragenic 

recombination at hprt

locus in Sp5 (nonhomologous 

recombination) and 

SPD8 (homologous 

recombination) 

duplication cell lines 

3–20 μg/mL 

in DMSO 

+ NA 

A statistically significant increase 

in reversion frequency was 

observed in both assays in the 

highest dose group as 

determined by linear regression 

analysis. 

Helleday et al., 

1999 

Mammalian systems, in vivo

Micronucleus test 

mouse/NMRI/intraper

itoneal injection

2,000 mg/kg 

in DMSO – (T) NA 

 BASF, 2000 

a

Lowest effective dose for positive results; highest dose tested for negative results. 

b+ = positive, ± = equivocal or weakly positive, – = negative, T = cytotoxicity, NA = not applicable, ND = no data.