FLAME RETARDANT ALTERNATIVES FOR

HEXABROMOCYCLODODECANE (HBCD) 

FINAL REPORT

June 2014 

EPA Publication 740R14001
Executive Summary

This report provides information on hexabromocyclododecane (HBCD; CASRN 25637-99-4; 

3194-55-6) used as a flame retardant in polystyrene building insulation, possible substitutes, and 

alternative materials. The report was developed by the U.S. Environmental Protection Agency 

(EPA) with input from a partnership of stakeholders from business, government, academia, and 

environmental organizations. According to technical experts on the Partnership, between 2011 

and 2014 there were only three viable flame retardant alternatives to HBCD for use in expanded 

and extruded polystyrene foam (EPS and XPS) insulation under current manufacturing 

processes. Alternative materials are also available as substitutes to HBCD-containing insulation. 

These alternatives may require additive flame retardants or other treatment to meet fire safety 

requirements. This report:

1) Identifies viable and non-viable flame retardant alternatives for HBCD in polystyrene 

building insulation foam;

2) Describes uses and provides an overview of end-of-life scenarios and exposure to HBCD;

3) Provides hazard profiles for HBCD and the three chemical alternatives; and

4) Provides an overview of relevant alternative materials.

Based on DfE AA criteria and guidance, the hazard profile of the butadiene styrene brominated 

copolymer (CASRN 1195978-93-8) shows that this chemical is anticipated to be safer than 

HBCD for multiple endpoints. Due to its large size, lack of low molecular weight (MW) 

components, and un-reactive functional groups, human health and ecotoxicity hazard for this 

polymer are measured or predicted to be low, although experimental data were not available for 

all endpoints. In general the exposure potential to the butadiene styrene brominated copolymer is 

expected to be lower than the other chemicals in this assessment because it is a large polymer 

and is unlikely to be released from the polystyrene. However, this alternative is inherently 

persistent and its long-term behavior in the environment is not currently known. Chemical 

suppliers have commercialized this polymer, and polystyrene manufacturers are testing it in their 

products to ensure that the polystyrene will meet all performance standards. The hazard 

designations for this alternative are based upon high MW formulations of the polymer, where all 

components have a MW >1,000. The polymer is regulated with a Significant New Use Rule that 

was finalized in June 2013. Manufacture (or import) of the polymer requires notification to EPA 

except in these cases: (1) the MW of the polymer is in the range of 1,000 to 10,000 daltons, or 

(2) the MW of the polymer is ≥10,000 daltons and less than 5 percent of the particles are in the 

respirable range of 10 microns or less (U.S. EPA 2013).

The hazard profiles of the tetrabromobisphenol A (TBBPA)-bis brominated ether derivative 

(CASRN 97416-84-7) and TBBPA bis(2,3-dibromopropyl) ether (CASRN 21850-44-2) show 

that these chemicals have limited data sets for human health endpoints and hazard designations 

show a potential for toxicity. These two chemicals are also anticipated to have High potential for 

bioaccumulation.

Background

In August 2010, EPA released the HBCD Action Plan. The Action Plan summarized hazard, 

exposure, and use information regarding environmental and health risks associated with HBCD. 

ii
HBCD is a flame retardant that has been found to have persistent, bioaccumulative, and toxic 

(PBT) characteristics. HBCD use as a flame retardant in EPS and XPS accounts for more than 

95% of HBCD applications. EPS and XPS are used as rigid foam insulation in the building and 

construction industry. A small volume of HBCD is used in textiles and high-impact polystyrene 

(HIPS).

As part of the Agency’s efforts to manage chemical risks, the Action Plan called upon the Design 

for the Environment (DfE) Program to conduct an alternatives assessment for HBCD. A DfE

Alternatives Assessment identifies and compares potential alternatives that can be used as 

substitutes to replace chemicals that the Agency has designated for action. DfE alternatives 

assessments provide information on functional class, intrinsic hazard, exposure properties, and 

environmental fate for chemical alternatives. The information in DfE alternatives assessments 

can influence the selection of safer, more sustainable alternatives when combined with other 

information that is not the focus of DfE Alternatives Assessments, such as performance and cost.

Goal of the Partnership and Report

DfE convened a multi-stakeholder partnership to assess the potential human health and 

environmental hazards of HBCD and its alternatives for use in EPS and XPS foam. The 

information presented in this report is based on the Partnership’s knowledge and the DfE 

Program’s research. Chapter 1 of the report provides background information on HBCD and 

defines the report’s purpose and scope. Chapter 2 discusses the uses, end-of-life scenarios, and 

exposure potential of HBCD. Chapter 3 offers background information on flame retardants and 

outlines which flame retardants are and are not included in the alternatives assessment. Chapter 4

explains the hazard evaluation methodology and includes the hazard profiles for HBCD and the 

three identified alternatives. Chapter 5 summarizes the results of the assessment, discusses 

considerations for selecting flame retardants and includes an overview of alternative materials. 

Since the primary use for HBCD is in EPS and XPS foam insulation, the project scope does not 

include alternatives to HBCD for its minor uses in textiles and HIPS. Alternatives to HBCD for 

these uses are included in a separate DfE Alternatives Assessment for decabromodiphenyl ether 

(decaBDE). Flame retardant performance and costs of HBCD and the three alternatives were not 

assessed in-depth in this report.

Results

Members of the Partnership identified many chemicals as potential alternatives; however, only

three chemicals were identified as viable alternatives to HBCD in EPS and XPS foam: a 

butadiene styrene brominated copolymer (CASRN 1195978-93-8), a TBBPA-bis brominated 

ether derivative (CASRN 97416-84-7), and TBBPA bis(2,3-dibromopropyl) ether (CASRN 

21850-44-2). Only three alternatives were identified for evaluation in this report because flame 

retardants for EPS and XPS foam must allow the material to comply with fire safety codes while

not compromising the performance of the foam. All three alternatives are brominated. No nonbrominated flame retardants are known to be compatible in polystyrene manufacturing and 

associated flame tests. Figure ES-1 summarizes the hazard information for HBCD and the three

alternatives assessed. Few measured experimental data were available for the TBBPA-bis 

brominated ether derivative; therefore, estimated hazard designations were determined using 

TBBPA bis(2,3-dibromopropyl ether) (CASRN 21850-44-2) as an analog. 

iii
The human health endpoints evaluated in DfE alternatives assessments include acute toxicity, 

carcinogenicity, genotoxicity, reproductive toxicity, developmental toxicity, neurotoxicity, 

repeated dose toxicity, skin sensitization, respiratory sensitization, eye irritation, and dermal 

irritation. HBCD has been assigned a High hazard designation for developmental neurotoxicity, a 

Moderate hazard designation for reproductive toxicity and repeated dose toxicity, and an 

estimated Moderate hazard designation for carcinogenicity and neurotoxicity; other health 

endpoints have Low or Very Low hazard designations. The butadiene styrene brominated 

copolymer has Low hazard designations (either measured or estimated) for most human health 

endpoints due to its high MW and limited potential for absorption; there is one Moderate hazard 

designation for the eye irritation endpoint based on experimental data. The TBBPA-bis 

brominated ether derivative and TBBPA bis(2,3-dibromopropyl) ether have a Moderate hazard 

designation for carcinogenicity, mutagenicity, reproductive toxicity, developmental toxicity, and 

repeated dose toxicity based on potential alkylating properties. Low hazard designations have 

been assigned to these similar substances for acute toxicity, neurotoxicity, skin sensitization and 

irritation.

The ecotoxicity endpoints evaluated in DfE alternatives assessments include acute and chronic 

aquatic toxicities. HBCD is aquatically toxic and has Very High hazard designations for both 

acute and chronic aquatic toxicity. Aquatic toxicity for the three alternatives is Low, driven by 

their lack of appreciable water solubility leading to “no effects at saturation” (NES). Ecotoxicity 

data for terrestrial species was limited, and thus the potential for impacts on high trophic level 

and terrestrial wildlife from HBCD and its alternatives or associated degradation products is 

unclear.

The environmental fate of HBCD and the three alternatives is described primarily in terms of 

persistence and bioaccumulation potential. All three chemicals have High or Very High

persistence designations, a quality typical for the majority of flame retardants. Long-term fate of 

the three alternatives in the environment is not well understood. The butadiene styrene 

brominated copolymer is estimated to have Low bioaccumulation potential due to its size 

(average MW >1,000 daltons) and lack of low MW components, while HBCD, the TBBPA-bis 

brominated derivative, and TBBPA bis(2,3-dibromopropyl) ether have Very High, High, and 

High potential for bioaccumulation. 

Under conditions where fire or incineration occurs, a halogenated substance may: contribute to 

halogenated dibenzodioxin and dibenzofuran formation, increase the generation of PAHs, and 

impact fire parameters such as smoke and carbon monoxide (Sidhu, Morgan et al. 2013). 

However, combustion reactions are complex and variable and make inclusion of combustion byproducts in hazard assessment challenging. Both halogenated and non-halogenated flame 

retardants may yield other toxic by-products that would need to be compared, not only 

halogenated dioxins and furans. For these reasons, the pyrolysis transformation products are not 

assessed in this report.

In addition to the chemical hazard assessment of HBCD and its alternatives, Chapter 5 of the 

report includes general information about alternative insulation materials. These technologies

include rigid board alternatives (e.g., similar to EPS and XPS), alternatives for certain functional 

uses (e.g., blanket insulation, foamed-in-place insulation), and specialty and emerging alternative 

iv
materials (e.g., aerogel, carbon foam). The report does not assess these materials, does not 

compare them to EPS or XPS, and does not assess flame retardancy needs for each of these 

materials.

How to Use This Report

The intended audience for the report includes, but is not limited to, chemical manufacturers, 

product manufacturers, retailers, consumers, non-governmental organizations (NGOs),

consultants, and state and federal regulators. Three possible uses of this report include: 

identification of potential substitutes; selection of alternative chemicals based on comparative 

hazard assessment; and use of hazard information for further analysis and decision-making.

This report allows stakeholders interested in chemical substitution to identify functional 

substitutes for HBCD in EPS and XPS foam. The list of potential alternatives introduced in 

Chapter 3 includes chemicals identified by stakeholders as viable, functional alternatives, as well 

as chemicals that are not considered functional alternatives. Decision-makers can understand and 

compare the hazard concerns associated with the four chemicals using the profiles in Chapter 4. 

The inclusion of a chemical in this assessment does not indicate environmental- or health-based 

preferability. Manufacturers considering the potential functional alternatives in this report will 

likely also conduct performance testing to confirm an alternative’s performance in their product.

Although outside of the report scope, decision makers should also consider the human health and 

environmental impacts of insulation’s non-flame retardant additives (e.g., synergists and 

stabilizers) discussed in Chapter 2 of the report.

Chapter 4 describes the hazard criteria, data interpretation, and information used to assign hazard 

values in each category. The chapter provides a human health and environmental profile for each 

chemical that is based on empirical data, and enhanced with modeling and expert judgment to fill 

data gaps. Where toxicity is estimated in the absence of measured data, DfE encourages users to 

be conservative in the interpretation of the hazard profiles. Chemicals used at high volumes, or 

likely to be in the future, should be of high priority for further empirical testing. 

The information in this report can be used to inform or supplement further analyses such as risk 

assessments or life-cycle assessments (LCAs) on preferred alternative chemicals. The criteria 

used to develop the hazard assessments in this report can also be used to inform green chemistry 

design, if availability of safer alternatives is limited.

v
ES-1 Hazard Summary for HBCD and Alternatives

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) were 

assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from predictive models and/or professional judgment.

This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion byproducts are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the table.

d This hazard designation would be assigned MODERATE for a potential for lung overloading if >5% of the particles are in the respirable range as a result of dust forming operations.

§ Based on analogy to experimental data for a structurally similar compound.

¥ Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many flame retardants that 

may partition to sediment and particulates.

Chemical

For full chemical name and relevant trade 

names see the hazard profiles in Section 4.8 CASRN

Human Health Effects Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicityGenotoxicityReproductiveDevelopmentalNeurologicalRepeated DoseSkin SensitizationRespiratory Sensitization1Eye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Hexabromocyclododecane (HBCD)

25637-99-4; 

3194-55-6 L M L M H M M L VL VL VH VH H VH

Butadiene styrene brominated copolymer¥

Br

Br

Br

Br

* *

x y z x

1195978-93-8 L L L L L L Ld L M L L L VH L

TBBPA-bis brominated ether derivative¥

97416-84-7 L§ M§ M§ M§ M§ L M§ L§ L L L L H H

TBBPA bis(2,3-dibromopropyl) ether¥

O

Br O Br

Br

Br

Br Br

Br

Br 21850-44-2 L M M M M L M L L L L L VH H

1 At this time, there are no standard test methods for respiratory sensitization and no test data; as a result there was no designation for this endpoint.

Br

Br

O Br

O

Br

Br

Br

Br Br

Br Br

Br Br

Br

Br

vi
Table of Contents

Executive Summary...................................................................................................................... ii

1 Introduction........................................................................................................................ 1-1

1.1 Background .................................................................................................................. 1-1

1.2 Purpose of the Flame Retardant Alternatives Assessment........................................... 1-3

1.3 Scope of the Flame Retardant Alternatives Assessment.............................................. 1-3

1.4 DfE Alternatives Assessments as a Risk Management Tool ....................................... 1-4

2 HBCD Uses, End-of-Life, and Exposure ......................................................................... 2-1

2.1 Uses of HBCD ............................................................................................................. 2-1

2.1.1 Building and Construction ............................................................................... 2-2

2.1.2 Other Uses........................................................................................................ 2-7

2.2 End-of-Life Scenarios.................................................................................................. 2-9

2.2.1 Reuse and Recycling........................................................................................ 2-9

2.2.2 Landfilling...................................................................................................... 2-10

2.2.3 Incineration .................................................................................................... 2-10

2.3 HBCD Exposure ........................................................................................................ 2-10

2.3.1 Human Exposures.......................................................................................... 2-11

2.3.2 Environmental Exposures.............................................................................. 2-12

3 Background on Flame Retardants ................................................................................... 3-1

3.1 General Information on Flame Retardants................................................................... 3-1

3.1.1 Flame Retardant Classification ........................................................................ 3-2

3.1.2 Flammability Tests........................................................................................... 3-4

3.2 Brominated Flame Retardants for Polystyrene ............................................................ 3-5

3.3 Flame Retardants Included in this Assessment............................................................ 3-6

3.4 Flame Retardants Not Included in this Assessment..................................................... 3-7

3.4.1 Specific Chemicals that were Excluded from this Assessment ....................... 3-7

4 Hazard Evaluation of HBCD and Alternatives............................................................... 4-1

4.1 Toxicological and Environmental Endpoints............................................................... 4-1

4.1.1 Definitions of Each Endpoint Evaluated Against Criteria ............................... 4-1

4.1.2 Criteria ............................................................................................................. 4-4

4.1.3 Endpoints Characterized but Not Evaluated .................................................... 4-8

4.2 Data Sources and Assessment Methodology ............................................................... 4-9

4.2.1 Identifying and Reviewing Measured Data ..................................................... 4-9

4.2.2 Hierarchy of Data Adequacy.......................................................................... 4-11

4.2.3 Assessment of Polymers ................................................................................ 4-12

4.3 Importance of Physical and Chemical Properties, Environmental Transport, and 

Biodegradation ........................................................................................................... 4-12

4.4 Evaluating Human Health Endpoints......................................................................... 4-19

4.4.1 Endpoints Characterized and Evaluated Against Criteria Based on Measured 

Data ................................................................................................................ 4-19

4.4.2 SAR – Application of SAR and Expert Judgment to Endpoint Criteria........ 4-20

4.5 Evaluating Environmental Toxicity and Fate Endpoints........................................... 4-21

4.5.1 Aquatic Toxicity ............................................................................................ 4-21

4.5.2 Bioaccumulation ............................................................................................ 4-23

4.5.3 Environmental Persistence............................................................................. 4-24

vii
4.6 Endocrine Activity ..................................................................................................... 4-26

4.7 Hazard Summary Table ............................................................................................. 4-33

4.8 Hazard Profiles........................................................................................................... 4-34

Hexabromocyclododecane (HBCD).................................................................. 4-34

Butadiene styrene brominated copolymer ....................................................... 4-107

TBBPA-bis brominated ether derivative ......................................................... 4-126

TBBPA bis(2,3-dibromopropyl) ether............................................................. 4-146

5 Summary of Hazard Assessments, Considerations for Selecting Flame Retardants, and 

an Overview of Alternative Materials...................................................................................... 5-1

5.1 Considerations for Selecting Flame Retardants........................................................... 5-1

5.1.1 Hazard Considerations..................................................................................... 5-1

5.1.2 Social Considerations....................................................................................... 5-4

5.1.3 Performance and Cost Considerations............................................................. 5-6

5.2 Alternative Materials.................................................................................................... 5-7

5.2.1 Rigid Board Alternatives ................................................................................. 5-9

5.2.2 Alternatives for Certain Functional Uses....................................................... 5-10

5.2.3 Specialty and Emerging Alternative Materials.............................................. 5-12

viii
List of Acronyms and Abbreviations

ACR Acute to chronic ratio

AIM Analog Identification Methodology

ASTM American Society for Testing and Materials

ATSDR Agency for Toxic Substances and Disease Registry

BAF Bioaccumulation Factor

BEARHFTI California Bureau of Electronic and Appliance Repair, Home Furnishings and 

Thermal Insulation

BCF Bioconcentration Factor

C&D Construction and demolition

CDR Chemical Data Reporting

CFC Chlorofluorocarbon

ChV Chronic value

CPSC Consumer Product Safety Commission

DecaBDE Decabromodiphenyl ether

DfE Design for the Environment

EC50 Half maximal effective concentration

ECOSAR Ecological Structure Activity Relationships

EDSP Endocrine Disruptor Screening Program

Eh Redox potential

EIFS Exterior Insulating and Finishing System

EPA U.S. Environmental Protection Agency

EPI Estimation Programs Interface

EPS Expanded polystyrene foam

FPQA Food Quality Protection Act

FPSF Frost Protected Shallow Foundation

FM Factory Mutual

GHS Globally Harmonized System of Classification and Labeling of Chemicals

HBr Hydrogen bromide

HFC Hydrofluorocarbon

HIPS High-impact polystyrene

HPV High production volume

HSDB Hazardous Substances Data Bank

IARC International Agency for Research on Cancer

IBC International Building Code

ICF Insulating Concrete Form

IRC International Residential Code

IRIS Integrated Risk Information System

IUR Inventory Update Reporting

Koa Octanol/air partition coefficient

Koc Soil adsorption coefficient

Kow Octanol/water partition coefficient

LC50 Median lethal concentration

LCA Life-cycle assessment

LD50 Median lethal dose

ix
LFL Lower limit of flammability

LOAEL Lowest observed adverse effect level

LOEC Lowest observed effect concentration

LRTAP Long-Range Transboundary Air Pollution

MDI Methylene diphenyl diisocyanate

MF Molecular formula

MITI Ministry of International Trade and Industry

MSDS Material Safety Data Sheet

MW Molecular weight

NES No Effects at Saturation

NFPA National Fire Protection Association

NGO Non-governmental organization

NICNAS National Industrial Chemicals Notification and Assessment Scheme

NIST National Institute of Standards and Technology

NOAEL No observed adverse effect level

NOEC No observed effect concentration

NTP National Toxicology Program

OECD Organisation for Economic Co-operation Development

P2 Pollution Prevention

PBDE Polybrominated diphenyl ether

PBT Persistent, bioaccumulative, and toxic

PET Polyethylene terephthalate

pMDI Polymeric methylene diphenyl diisocyanate

POP Persistent organic pollutant

POPRC Persistent Organic Pollutants Review Committee

QSAR Quantitative Structure Activity Relationships

RDP Resorcinol-bis-diphenyl phosphate

REACH Registration, Evaluation, Authorisation and Restriction of Chemical Substances 

SAR Structure Activity Relationship

SIAP Screening Information Dataset Initial Assessment Profile

SF Sustainable Futures

SIP Structural Insulated Panel

SNUR Significant New Use Rule

SPF Spray polyurethane foam

TBBPA Tetrabromobisphenol A

TCPP Tris(chlorpropyl) phosphate

TDI Toluene diisocyanate

TSCA Toxic Substances Control Act

UBC Uniform Building Code

UFL Upper limit of flammability

UL Underwriters Laboratories

UNECE United Nations Economic Commission for Europe

XPS Extruded polystyrene foam

x
1 Introduction

1.1 Background

As part of its effort to enhance the safety of chemicals, the U.S. Environmental Protection 

Agency (EPA) has taken steps to identify chemicals that may pose environmental and health 

concerns. Between 2009 and 2011, EPA developed action plans that considered both potential 

regulatory and voluntary actions. In August 2010, EPA released the Hexabromocyclododecane 

(HBCD) Action Plan1. This Action Plan summarized hazard, exposure, and use information to 

help evaluate the environmental and health risks associated with HBCD2.

HBCD is a brominated flame retardant found worldwide in the environment and wildlife. Human 

exposure is evidenced from its presence in breast milk, adipose tissue, and blood. It 

bioaccumulates and biomagnifies in the food chain. It persists and is transported long distances 

in the environment, and is highly toxic to aquatic organisms. HBCD also presents potential 

human health concerns based on animal test results indicating potential reproductive, 

developmental, and neurological effects.

HBCD is a flame retardant most commonly used in expanded polystyrene foam (EPS) and 

extruded polystyrene foam (XPS). EPS and XPS are used as insulation in the building and 

construction industry. HBCD is also used in materials such as textile back coatings on 

institutional carpet tiles or upholstery and some military fabrics (U.S. EPA 2012). A minor use of 

HBCD is in high-impact polystyrene (HIPS) for electrical and electronic applications such as 

audio-visual equipment, refrigerator linings, and in wire and cable (U.S. EPA 2010).

The Action Plan stated EPA’s intent to conduct this Design for the Environment (DfE) Program 

alternatives assessment: Flame Retardant Alternatives for Hexabromocyclododecane (HBCD). 

DfE’s Alternatives Assessment Program helps industries choose safer chemicals and provides a 

basis for informed decision-making by developing an in-depth comparison of potential human 

health and environmental impacts of chemical alternatives. DfE convened a multi-stakeholder 

partnership to help select and evaluate flame retardant alternatives to HBCD and develop this 

report. Partnership representatives from industrial, academic, governmental, and nongovernmental organizations (NGOs) engaged with DfE to provide input from a variety of 

different viewpoints. The chemical alternatives chosen for this report were included because they 

were identified by stakeholders as potential functional alternatives. Including these alternatives 

does not indicate that EPA considers them to be preferable in terms of environmental or health 

hazard, or any other metric. This report did not evaluate efficacy of these alternatives which may 

be related to specific material and product applications and related standards. Stakeholders 

provided professional judgment about whether chemicals are likely to meet flammability tests in 

1 The Hexabromocyclododecane (HBCD) Action Plan is available online at: 

http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/hbcd.html. 2 HBCD should not be confused with hexachloro-1,3-butadiene (HCBD). For information about HCBD, see 

http://www.epa.gov/opptintr/chemtest/pubs/hexchbut.html.

1-1

 
EPS and XPS. The report does provide information that will enable more informed selection of 

alternative flame retardants to HBCD for EPS and XPS.

Several international governmental entities have begun to take actions towards regulating HBCD 

in recent years, including the United Nations Economic Commission for Europe (UNECE) 

Convention on Long-Range Transboundary Air Pollution (LRTAP) (United Nations Economic 

Commission for Europe 2011), the Stockholm Convention on Persistent Organic Pollutants 

(POPs) (Stockholm Convention on Persistent Organic Pollutants 2008), the European Union 

(European Chemicals Agency 2011), Canada (Environment Canada 2010), and Australia 

(Australian Department of Health and Aging: National Industrial Chemicals Notification and 

Assessment 2008). In the United States, the HBCD Action Plan proposed several regulatory 

actions to manage the risk that may be presented by HBCD (U.S. EPA 2010). As the regulation 

of HBCD is considered in the U.S. and internationally, this alternatives assessment will be an 

important resource both in reporting on the environmental and human health profiles of HBCD 

alternatives and in helping product manufacturers select safer alternative flame retardants. The 

information will help reduce the potential for the unintended consequences that could result if 

functional but poorly understood or more hazardous alternatives are chosen as chemical 

substitutes to HBCD.

HBCD is a category of brominated flame retardants, consisting of 16 possible isomers. It has a 

molecular formula (MF) of C12H18Br6 and its structure consists of a ring of 12 carbon atoms to 

which 18 hydrogen and six bromine atoms are bound. HBCD may be designated as a nonspecific mixture of all isomers (Hexabromocyclododecane; CASRN: 25637-99-4) or as a 

mixture of three main diastereomers (1,2,5,6,9,10-hexabromocyclododecane; CASRN: 3194-55-

6). Both mixtures are listed on the Toxic Substances Control Act (TSCA) Inventory and have 

substantial use in U.S. commerce (10-50 million pounds in 2005). A representative structure of 

HBCD is shown in Figure 1-1 below. 

Figure 1-1. Representative Structure of HBCD

HBCD is an effective flame retardant for building insulation materials and does not compromise 

the physical properties of the foam. HBCD is uniquely suited for use in EPS and XPS foam due 

to its effectiveness at low concentration levels, compatibility with current manufacturing 

processes and chemicals, and low water solubility. Alternatives to HBCD must meet the same 

functional requirements; there are currently few viable3 alternatives to HBCD for EPS or XPS. 

3 Viability refers to the functional performance of a chemical as a flame retardant in EPS and XPS foam, not the 

environmental preferability of the chemical nor other product performance criteria.

Br Br

Br Br

Br

Br

1-2

 
Alternatives to HBCD have been discussed previously in reports published by the European 

Commission and the University of Massachusetts at Lowell (Morose 2006; IOM Consulting 

2009). These assessments looked at alternatives to HBCD for its uses in building insulation, 

textile back coatings, and HIPS applications, and identified flame retardant alternatives as well 

as alternative forms of insulation to the use of HBCD in building insulation. This EPA report 

provides new and updated information on chemical flame retardant alternatives to HBCD in its 

primary use as a flame retardant for insulation foam.

1.2 Purpose of the Flame Retardant Alternatives Assessment

The purposes of this assessment are to: (1) identify viable alternatives for HBCD in EPS and 

XPS; (2) evaluate the human health and environmental profiles of HBCD and its alternatives; 

and (3) inform decision making as organizations choose safer alternatives to HBCD. Within DfE 

Alternatives Assessments, chemicals are not ranked for preferability, rather the information

provided is intended for use by decision-makers, who will combine our assessment with other 

information to inform the selection of safer, more sustainable alternatives.

1.3 Scope of the Flame Retardant Alternatives Assessment

The Action Plan issued for HBCD in 2010 called for EPA to conduct a DfE multi-stakeholder 

alternatives assessment to aid users in selecting safer alternatives to HBCD. 

Since the primary use for HBCD is for EPS and XPS foam insulation, the project scope did not 

include alternatives to HBCD for its minor uses in textile back coatings and HIPS used in 

electronics housings and focused on primary uses. Stakeholders interested in alternatives for 

these uses may refer to DfE’s Partnership on Alternatives to Decabromodiphenyl Ether

(decaBDE).

4 The decaBDE report considers alternative flame retardants for a wider range of 

polymers and applications, including electronics housings and textiles, for which both decaBDE 

and HBCD have been used in the past.

The assessment provides hazard information (human toxicity, ecotoxicity, environmental fate) on 

flame retardants that were selected for evaluation in this report as potentially viable alternatives 

to HBCD. Viable alternatives are those that may have similar performance and function to 

HBCD when used in EPS and XPS building insulation. While the assessment will not attempt to 

include comprehensive life-cycle assessment (LCA) information, it will, by both inclusion and 

reference, note relevant life-cycle considerations, describe other relevant information, and 

provide a general overview of potential alternative materials that may aid in the selection of 

alternatives to insulation containing HBCD. An in-depth comparison of potential human health 

and environmental impacts was not done for the alternative insulation materials described in 

Section 5.2. The information provided by this Partnership will help stakeholders select preferable 

alternatives to HBCD; however, the report will not recommend specific flame retardants or 

alternative materials. 

4 http://www.epa.gov/dfe/pubs/projects/decaBDE/index.htm

1-3

 
The report is organized as follows:

• Chapter 1 (Introduction): This chapter provides background on the Flame Retardant 

Alternatives to HBCD project, including the purpose and scope of the Partnership and of 

this report.

• Chapter 2 (HBCD Uses, End-of-Life, and Exposure): This chapter describes the 

insulation products in which HBCD is used and the potential associated exposure 

pathways along each stage of the life cycle of the flame retardant in the products.

• Chapter 3 (Background on Flame Retardants): This chapter describes chemical flame 

retardants generally, as well as those specific to this assessment and provides technical 

information about flammability standards.

• Chapter 4 (Hazard Evaluation of HBCD and Alternatives): This chapter explains the 

chemical assessment method used in this report and summarizes the assessment of 

hazards associated with each flame retardant chemical.

• Chapter 5 (Summary of Hazard Assessments, Considerations for Selecting Flame 

Retardants and an Overview of Alternative Materials): This chapter includes a summary 

of the human health, environmental, social, performance, and cost considerations for 

selecting alternative flame retardants. It also includes an overview of information on 

alternative insulation materials, although the Partnership does not provide a direct 

comparison of these materials to EPS and XPS foam.

1.4 DfE Alternatives Assessments as a Risk Management Tool

Among other actions, the Agency chose to conduct a DfE Alternatives Assessment as a risk 

management tool for HBCD in EPA’s HBCD Action Plan. The Agency chose this tool to inform 

the chemical substitution that may occur as an outcome of other activities described in the Action 

Plan. DfE Alternatives Assessments provide information on the environmental and human health 

profiles of chemicals that may be used as substitutes so that industry and other stakeholders can 

use this information, in combination with analysis of cost, performance, and other factors, to 

make informed choices about alternatives.

DfE Alternatives Assessments along with LCAs, risk assessments, and other tools can be used to 

improve the sustainability profiles of chemicals and products. These tools, which can be 

complementary, should be selected according to the risk management need. DfE Alternatives 

Assessments establish a foundation that other tools can build on.

The focus of this DfE Alternatives Assessment report is to compare the intrinsic properties of 

chemicals within the same functional use group (e.g., solvent, surfactant, flame retardant, ink 

developer) and to evaluate alternatives across a consistent and comprehensive set of hazard 

endpoints. Information about chemical hazards derived from this type of comparative chemical 

hazard assessment can be used by decision-makers to help them select safer alternative 

chemicals.

1-4
Risk assessment and DfE Alternatives Assessment are both based on the premise that risk is a 

function of hazard and exposure. Risk assessment characterizes the nature and magnitude of 

hazard and exposure from chemical contaminants and other stressors. 

DfE’s “functional use” approach to alternatives assessment orients chemical evaluations within a 

given product type and functionality. Under this approach, factors related to exposure scenarios, 

such as physical form and route of exposure, are generally constant within a given functional use 

analysis and would fall out of the comparison. DfE Alternatives Assessments consider intrinsic 

properties of chemical substitutes that affect exposure potential, including absorption, 

persistence, and bioaccumulation. Under this approach, the health and environmental profiles in 

the alternatives assessments become the key variables and sources of distinguishing 

characteristics. Exposure attributes, including significant differences in environmental fate and 

transport based on persistence, bioaccumulation, and physical properties, are considered and 

discussed in Chapters 4 and 5.

DfE Alternatives Assessments are most useful in identifying safer substitutes when available 

alternatives meet performance requirements and are expected to present lower hazards for human 

health and the environment. During decision-making, risk assessment or LCA could be applied 

to the lower-hazard or potentially preferable alternatives to complement the alternatives 

assessment findings. Alternatives assessments can also identify the characteristics of a safer 

alternative and guide innovation and product development, especially when clearly preferable 

alternatives are not available. 

The DfE Alternatives Assessment approach is aligned with green chemistry principles.

5 The 

relationship to two of those principles is especially noteworthy:

• Principle 4: Designing Safer Chemicals -- “Design chemical products to affect their 

desired function while minimizing their toxicity,” and

• Principle 10: Design for Degradation -- “Design chemical products so they break down 

into innocuous products that do not persist in the environment.”

DfE incorporates these two green chemistry principles and applies them in its assessment of 

chemical hazard and fate in the environment. This approach enables identification of safer 

substitutes that emphasize greener chemistry and points the way to innovation in safer chemical 

design where hazard becomes a part of a performance evaluation.

5 http://www.epa.gov/sciencematters/june2011/principles.htm

1-5

 
References

Australian Department of Health and Aging: National Industrial Chemicals Notification and 

Assessment. (2008). "Priority Existing Chemical Assessment Reports." Retrieved May 

17, 2011, from http://www.nicnas.gov.au/publications/CAR/PEC.asp.

Environment Canada. (2010). "Risk Management Scope for Cyclododecane,1,2,5,6,9,10 –

hexabromo-(Hexabromocyclododecane; HBCD) Chemical Abstract Service Registry 

Number (CAS RN): 3194-55-6." Retrieved May 17, 2011, 

from http://www.ec.gc.ca/ese-ees/default.asp?lang=En&n=5F5A32FB-1.

European Chemicals Agency. (2011). "Candidate List of Substances of Very High Concern for 

Authorisation." Retrieved May 17, 2011, 

from http://echa.europa.eu/chem_data/authorisation_process/candidate_list_en.asp.

IOM Consulting (2009). Data on manufacture, import, export, uses, and releases of HBCDD as 

well as information on potential alternatives to its use, Report prepared for European 

Chemicals Agency (ECHA).

Morose, G. (2006). An Overview of Alternatives to Tetrabromobisphenol A (TBBPA) and 

Hexabromocyclododecane (HBCD). University of Massachusetts Lowell, Lowell Center 

for Sustainable Production.

Stockholm Convention on Persistent Organic Pollutants. (2008). "Chemicals under Review." 

Retrieved May 17, 2011, 

from http://chm.pops.int/Convention/POPs%20Review%20Committee/Chemicals/tabid/7

81/language/en-US/Default.aspx.

U.S. EPA (2010). Hexabromocyclododecane (HBCD) Action Plan.

U.S. EPA (2012). Significant New Use Rule for Hexabromocyclododecane and 1,2,5,6,9,10-

Hexabromocyclododecane. 77 FR 17386-17394.

United Nations Economic Commission for Europe. (2011). "Convention on Long-range 

Transboundary Air Pollution." Retrieved May 17, 2011, 

from http://www.unece.org/env/lrtap/lrtap_h1.htm.

1-6
2 HBCD Uses, End-of-Life, and Exposure 

Hexabromocyclododecane (HBCD) is most commonly used in expanded polystyrene foam 

(EPS) and extruded polystyrene foam (XPS) produced for the building and construction industry 

to meet fire safety standards. HBCD also has minor uses as a flame retardant in textile back 

coatings and high-impact polystyrene (HIPS) used in electronics housings. As stated in Chapter 

1, this alternatives assessment focuses on HBCD in EPS and XPS foam insulation and does not 

include alternatives to HBCD for its uses in textile back coatings and HIPS. Information on 

flame retardants in textile back coatings and HIPS can be found in Design for the Environment 

(DfE)’s Partnership on Alternatives to Decabromodiphenyl Ether (decaBDE)6.

Chapter 2 presents the uses of HBCD with descriptions of EPS and XPS (Section 2.1), an 

overview of end-of-life scenarios for insulation (Section 2.2), and a summary of information 

pertaining to human and environmental exposure to HBCD (Section 2.3).

2.1 Uses of HBCD

Figure 2-1 shows the proportions of HBCD use in polystyrene foam, textile back coatings and 

HIPS in the European Union (EU). In 2001, the world market demand for HBCD was 16,700 

tons, or 33.4 million pounds, 57% of which was attributed to Europe (Janak, Covaci et al. 2005). 

According to the Toxic Substances Control Act (TSCA) Inventory Update Reporting (IUR), a 

volume between 10 and 50 million pounds of HBCD was manufactured or imported in the U.S. 

in 2005 (U.S. EPA 2006). In the most recent TSCA reporting for 2011, now called Chemical 

Data Reporting (CDR), the volume of HBCD manufactured or imported in the U.S. was claimed 

confidential and cannot be described in this report (U.S. EPA 2013). More precise data for 

HBCD uses are available for the EU, where 96% of HBCD is used in EPS and XPS foam. Figure 

2-1 reflects data for European markets, as similar information for the U.S. is not available. 

Although the EU market and industry for HBCD are considered to be similar to those in the U.S., 

differences do exist in building technologies, climate, and consumption patterns, limiting the 

comparison of the two markets.

The application of HBCD in EPS and XPS is discussed in Section 2.1.1 of this assessment; 

Section 2.1.2 provides a summary of the minor uses of HBCD in textiles and HIPS.

6 www.epa.gov/dfe/pubs/projects/decaBDE/index.htm

2-1

 
Figure 2-1. Profile of HBCD Uses in European Markets for 2006/2007

(European Chemicals Agency 2009)

2.1.1 Building and Construction

Important properties of EPS and XPS include their energy efficiency, long-term performance 

(50-100 years), compressive strength, high moisture resistance and resistance to water 

absorption, versatility, durability, reusability, imperviousness to mold growth and 

microbiological, degradation, availability, and cost-effectiveness (EPS Industry Alliance 2011a; 

Extruded Polystyrene Foam Association 2011a; Fabian 2011).

EPS and XPS are used in buildings for insulation as well as to provide a moisture barrier, protect

against damage from freezing, provide a stable fill material, and create high strength composite

materials (Morose 2006). Typical applications include insulation in: attics, ceilings, roofs, walls,

flooring, below grade applications, transportation, and cold storage (EPS Industry Alliance 

2009a; EPS Industry Alliance 2011b; Extruded Polystyrene Foam Association 2011a; Extruded 

Polystyrene Foam Association 2011b). Other uses of polystyrene foam in consumer products

(e.g., packaging) generally do not require the use of a flame retardant (European Commission 

2008; EPS Industry Alliance 2011b). The use of HBCD in non-insulation applications of

polystyrene foam was outside the scope of this alternatives assessment and was not researched.

XPS

51% EPS

45%

Textile

2%

Other (including 

HIPS)

2%

2-2
Performance requirements for EPS and XPS foam used as thermal insulation are governed by 

American Society for Testing and Materials (ASTM) C578, Standard Specification for Rigid, 

Cellular Polystyrene Insulation.

7 In 

general, the performance requirements of 

foam insulation vary depending on the 

density of the foam. The ASTM C578 

standards differentiate between 

classifications of insulation foam based on 

density and compressive strength. Table 

2-1 below gives a broad range of 

properties covering the breadth of foam

densities and compressive strengths cited 

in ASTM C578. The requirements are 

defined as follows:

• Density: Mass per unit volume.

• R-value: Thermal resistance. 

Higher R-values indicate a better 

ability to resist the flow of heat.

• Compressive strength: The 

compaction force (load per unit 

area) a material can withstand for 

a given change in dimensions 

(typically 10% reduction in 

thickness).

• Flexural strength: The breaking 

load applied to the neutral axis of 

a beam.

• Water vapor transmission rate:

The steady state water vapor flow 

in unit time through unit area of a 

body, normal to specific parallel 

surfaces, under specific conditions 

of temperature and humidity at 

each surface.

• Water absorption: Percentage, by volume, of water remaining within the specimen 

after immersion in water for a specified time.

• Dimensional stability: The ability of a material to maintain its original size, shape, and 

dimensions in response to thermal and humid aging.

• Oxygen index: The percent of oxygen necessary to support combustion of a polymer.

7 Likewise, ASTM D6817 applies to polystyrene foams in geotechnical engineering applications (“geofoam”). See

http://www.astm.org/Standards/D6817.htm. 

Typical Applications of EPS and/or XPS:

• Attics and Ceilings

• Roofs

o Membrane roofs

o Recovery/reroofing

o Vegetative roofs

• Walls

o Continuous insulation

o Exterior Insulating and Finishing 

Systems (EIFS)

o Garage door panels

o Insulating Concrete Forms (ICFs)

o Masonry cavity walls

o One-coat stucco panels

o Precast concrete

o Steel Stud insulation

o Structural Insulated Panels (SIPs)

• Flooring

• Below grade applications

o Frost Protected Shallow 

Foundations (FPSF)

o Geofoam

o Geotechnical fill & stabilization

o Highway insulation

• Cold Storage/Low temperature buildings

• Transportation

o Recreational vehicle panels

o Shipping containers

(EPS Molders Association, 2009a, 2011b; 

Extruded Polystyrene Foam Association, 2011a, 

2011b)

2-3

 
• Flame spread index: The index rate expressed in distance and time at which a material 

will propagate flame on its surface.

• Smoke development index: An index indicating the potential for smoke generation 

during fire propagation.

Table 2-1. ASTM C578 Requirements for EPS and XPS Foam

Unit EPS XPS

Classification Type XI, I, VIII, II, IX, XIV, XV XII, X, XIII, IV, VI, VII, V

Minimum Density lbs per ft3 (pcf) 0.70, 0.90, 1.15, 1.35, 1.80, 

2.40, 3.00

1.20, 1.30, 1.60, 1.55, 1.80, 

2.20, 3.00

Compressive strength lbs per in2 (psi) 5.0, 10.0, 13.0, 15.0, 25.0, 

40,0, 60.0

15.0, 15.0, 20.0, 25.0, 40.0, 

60.0, 100.0

Performance Requirement

R-value F-ft2-h/BTU (75°F) 3.1-4.3 4.6-5

Flexural strength lbs per in2 (psi) 10-75 40-100

Water vapor transmission rate Perm per inch 2.5-5.0 1.1-1.5

Water absorption % 2.0-4.0 0.3-1.0

Dimensional Stability % 2 2

Oxygen index % >24 >24

Flame spread index Unitless index <75 <75

Smoke development index Unitless index <450 <450

(International Code Council 2011a; International Code Council 2011b; American Society for Testing and Materials 

2012)

To help ensure safety of occupants, building codes in the U.S. require use of materials that 

reduce the risk of fire. Flame retardants are used in EPS and XPS to raise ignition temperatures 

and to reduce the rate of burning, flame spread, and smoke, in turn potentially allowing building 

occupants more time to escape a life-threatening fire. HBCD is used because of its ability to 

impart flame retardancy at low concentrations (at a typical loading of 0.5% by weight in EPS 

(EPS Industry Alliance 2009b), 0.5-1% by weight in XPS (Extruded Polystyrene Foam 

Association 2011a), without the loss of thermal and physical property performance. HBCD is 

compatible with both EPS and XPS manufacturing processes (described in more detail below). 

Other valued characteristics include its low water solubility and retention in the foam, such that 

its fire safety contribution is maintained for decades, even after extended water contact (EPS 

Industry Alliance 2011a; Extruded Polystyrene Foam Association 2011a; Fabian 2011). 

Alternatives to HBCD in EPS and XPS foam must be able to meet fire safety and other 

regulatory requirements while avoiding negative impacts on human health and the environment, 

maintaining the thermal and physical properties of the material, being compatible with 

manufacturing processes, and being economically viable (EPS Industry Alliance 2011a; 

Extruded Polystyrene Foam Association 2011a; Fabian 2011). The EPS industry is making 

efforts to move away from the use of HBCD in building products and to implement alternatives 

by developing a test program to ensure that a new polymeric flame retardant complies with 

building code fire performance requirements for EPS applications in Canada and the U.S. (EPS 

Industry Alliance 2012). After commercial quantities of alternatives become available, in-house 

testing and quality control measures will be independently verified through third-party 

certification programs (EPS Industry Alliance 2012; ICC Evaluation Service 2012).

The remainder of this section discusses the manufacturing processes used to make EPS and XPS 

foam containing HBCD.

2-4
Manufacture of Expanded Polystyrene (EPS)

EPS is a rigid foam insulation produced by expansion and molding of expandable polystyrene 

resin beads. To manufacture EPS, first a polystyrene resin is produced via suspension 

polymerization by chemical manufacturers. Suspension polymerization is a polymerization 

process that uses agitation and suspending agents to suspend monomer and polymer particles 

(U.S. EPA 1997). The production of EPS resin beads for insulation is done by a limited number 

of chemical companies at a small number (<5) of production sites in the U.S. HBCD and a 

blowing agent, usually pentane, are added to the 

resin during the polymerization process. 

Synergists are often used with HBCD in EPS 

foam to allow the concentration of HBCD to be 

reduced, as is discussed in more detail below. 

There is also a less economical two-step 

technology for manufacturing EPS resin that for 

the most part has been replaced with the one-step 

process described here (Grant 2011).

The expandable resin is sold and transported to 

molders to create EPS foam. At the molding 

plant, the polystyrene resin is first expanded into 

foam beads via the direct application of steam, 

which causes the blowing agent in the resin to expand. Following an aging/maturing step of 

approximately 2 to 24 hours, the expanded foam beads are molded into rigid closed-cell foam. 

This process produces blocks of foam which are cut to desired shapes (such as insulation board) 

and thicknesses with hot wires (COWI 2011; EPS Industry Alliance 2011a). Alternatively, the 

expanded foam beads may be molded into custom shapes to produce rigid foam construction 

elements, such as ICFs. This process typically takes place at temperatures of 120°C (COWI 

2011) or below. Trim scrap from the cutting operation can be recycled into the molding 

operation under controlled conditions while maintaining required properties. Molding plants are 

typically strategically located around the country to minimize the shipping costs of transporting 

the lightweight foams to end users. Additional information and resources regarding EPS foam 

and its manufacture may be found from chemical manufacturers, processors and formulators, and 

industrial association websites.

Figure 2-2. EPS Insulation

2-5
Manufacture of Extruded Polystyrene (XPS)

XPS is a rigid foam insulation board produced by an extrusion process. To manufacture XPS, 

polystyrene resin granules and additives, including blowing agents (typically hydrofluorocarbons

(HFCs)) and flame retardants (i.e., HBCD), are mixed in an 

extruder. The resulting mixture is melted at high pressure 

and high temperatures (ranging from 180-230°C) into a 

viscous plastic fluid. Due to these high processing 

temperatures, HBCD is stabilized with chemical additives 

to limit effects of any HBCD decomposition during 

manufacture, as is discussed in more detail below. Next, 

the viscous fluid is forced through a die, expanded into a 

foam and shaped. The foamed mixture is cooled into 

continuous sheets (boards) of closed-cell insulation. The 

boards are cut to size and production waste is reprocessed 

(Wilson 2005; COWI 2011; Extruded Polystyrene Foam 

Association 2011a; Fabian 2011). Additional information 

and resources regarding XPS foam and its manufacture 

may be found from chemical manufacturers, processors and formulators, and their industrial 

association websites.

Synergists and Stabilizers used with HBCD in EPS and XPS

Synergists are often used with HBCD for the manufacture of EPS and stabilizers are used with 

HBCD in the manufacture of XPS. The Partnership discussed these additives but U.S. 

Environmental Protection Agency (EPA) did not include them in the hazard assessment (see 

Chapter 4) for several reasons: the additives were outside of the project scope that focuses on 

alternatives to HBCD; a comprehensive hazard assessment would require inclusion of the many 

different additives (beyond only synergists and stabilizers) that may be present in EPS and XPS 

foam; and as the transition to HBCD alternatives has not yet occurred, there is not certainty as to 

the synergists and stabilizers likely to be used with the alternatives. However, users of HBCD 

alternatives are encouraged to conduct hazard assessments on additives used with flame 

retardants to select the safest functional chemistries. The paragraphs that follow provide general 

information about synergists and stabilizers used with HBCD in EPS and XPS foam, 

respectively.

In EPS foam, synergists are often used along with HBCD for economic reasons, as they enable 

the concentration of HBCD to be reduced (Arch 2011). Synergists are typically added to the EPS 

resin by the EPS resin manufacturer; HBCD is generally not sold with synergists added. 

Common synergists used with HBCD in EPS foam are:

• 2,3-dimethyl-2,3-diphenyl butane (sold as Perkadox 30); and,

• dicumyl peroxide.

Synergists are typically not used with HBCD in XPS foam because most types (e.g., peroxides) 

are unstable at the high processing temperatures of the XPS manufacturing process (Arch 2011).

Figure 2-3. XPS Insulation

2-6
As was noted above, HBCD must be stabilized during the XPS manufacturing process because it 

may decompose at the high processing temperatures. Chemical manufacturers sell a stabilized 

grade of HBCD for use in the XPS manufacturing process. Commonly used thermal stabilizers 

for HBCD in XPS foam are:

• hydrotalcite;

• dibutyl tin maleate; and

• zeolites.

Other chemicals that have been proposed in the literature as stabilizers for XPS foam include:

• aminocrotonic acid esters;

• epoxy derivatives;

• metals;

• organotins;

• polymeric acrylic binders; and

• talc.

(Hahn, Hinselmann et al. 1981; Books and Landry 1998; Hallenback, Doumen et al. 2001; 

Maxwell 2008; Stobby 2008; Weil and Levchik 2009).

The formulations of stabilizers in the literature ranged from 0.1 to 30 weight percent based on 

the weight of the flame retardant (Hahn, Hinselmann et al. 1981; Books and Landry 1998; 

Hallenback, Doumen et al. 2001; Maxwell 2008; Stobby 2008). Available product literature 

about the butadiene styrene brominated copolymer indicates that the same stabilizers used with 

HBCD may also be used with the alternatives (Great Lakes Solutions 2011).

2.1.2 Other Uses

The remainder of this section includes information on the uses of HBCD in textiles and HIPS. 

Although the report only assesses alternatives for HBCD in insulation, this information is 

provided as background for the reader.

HBCD in Textiles

In the U.S., producers reported that less than 1% of the total HBCD used for commercial and 

consumer purposes in 2005 was used in the fabrics and textiles sector (U.S. EPA 2012). Based 

on information submitted to EPA, it is likely that HBCD use in textiles in the U.S. is restricted to 

use by the automotive industry and use in non-consumer textile applications (e.g., institutional, 

military, and aviation), such as firefighters’ suits (U.S. EPA 2012). EPA has proposed a 

Significant New Use Rule (SNUR) under TSCA Section 5(a)(2), which would designate the 

manufacture (which includes import) or processing of HBCD for use in consumer textiles as a 

significant new use, requiring manufacturers, importers and processors to notify EPA before 

manufacturing or processing HBCD for this use. In the EU, only 2% of HBCD is used in textile 

back coatings in applications such as flat and pile upholstered furniture, upholstery seating in 

2-7
transportation, draperies, wall coverings, and automobile interior textiles and car cushions 

(European Chemicals Agency 2009).

The global automotive industry uses HBCD in floor mats, roof interior coverings, and other 

interior fabrics of motor vehicles (U.S. EPA 2012). Additionally, in Europe it has been noted that 

EPS may be used in children’s car seats or for insulation for transport vehicles (European 

Commission 2008). The EPS used in children’s car seats may contain HBCD, as is evidenced by 

the bromine content found in tested car seats (Gearhart, Posselt et al. 2008). Some automakers 

plan to phase out these uses of HBCD in 2015, due to the addition of HBCD to the Annex XIV 

List of Substances Subject to Authorisation under the EU’s Registration, Evaluation, 

Authorisation and Restriction of Chemical Substances (REACH) regulations.

For use in textiles, HBCD is formulated into polymer-based dispersions (e.g., acrylic or latex) of 

variable viscosity, which are then processed in the textile finishing industry (Harscher 2011). As 

HBCD is applied to textiles as a surface coating, it may be released during textile wear and 

washing (European Commission 2008). Antimony trioxide is often used as a synergist in 

combination with HBCD in the flame retardation of textiles (European Commission 2008). The 

typical loading of HBCD in textile back coatings is 10-25% (Harscher 2011).

The use of HBCD in textile back coatings is a source of HBCD in the environment. HBCD is 

expected to have greater mobility from textile coatings, where it is used in a surface coating, 

compared to EPS and XPS, where it is dispersed throughout the polymer matrix (European 

Commission 2008). Additionally, the HBCD particle size for textile applications is smaller than 

that used for insulation, which poses the potential of deep lung particulate exposure (Rozman 

and Klaassen 2001). The EU risk assessment of HBCD published in 2008 (European 

Commission 2008) estimated releases of HBCD during its production, formulation, and use in 

EPS, XPS, textiles, and HIPS. These estimates indicated that textile-related releases may 

constitute a significant share (approximately 86%) of total HBCD releases to the environment, 

however, textiles only accounted for 11% of the overall use of HBCD in Europe at the time of 

the study (European Commission 2008). Thus, EPS, XPS, and HIPS applications of HBCD only 

represented 14% of the releases despite accounting for 89% of the HBCD used. Industry 

information indicates that the use of HBCD in textiles in Europe has declined in recent years to 

2% of total HBCD use (see Figure 2-1) (IOM Consulting 2009). For information on potential 

alternatives to HBCD in textile back coatings, refer to An Alternatives Assessment For The 

Flame Retardant Decabromodiphenyl Ether (DecaBDE)8, which assessed alternatives for this 

use.

HBCD in HIPS

The use of HBCD in HIPS accounts for approximately 2% of HBCD usage in the EU (European 

Chemicals Agency 2009). Similar data for the U.S. are not available. HBCD is used as a flame 

retardant in HIPS enclosures for audio/video equipment and other appliances, typically in “Glow 

Wire” and Underwriters Laboratories (UL) 94 V2 rated applications (Harscher 2011). The use of 

8 www.epa.gov/dfe/pubs/projects/decaBDE/index.htm

2-8

 
HBCD in these products allows for lower load levels, lower specific gravity, and non-antimony 

trioxide formulations (Harscher 2011). To use HBCD in HIPS, HIPS pellets are mixed with 

HBCD and other ingredients in an extruder; the resulting pellets then undergo granulation 

processes (European Commission 2008). The typical loading of HBCD in HIPS is 1-7% 

(European Commission 2008). For information on potential alternatives to HBCD in HIPS, refer 

to An Alternatives Assessment For The Flame Retardant Decabromodiphenyl Ether 

(DecaBDE)9, which assessed alternatives for this use.

2.2 End-of-Life Scenarios

There are multiple end-of-life pathways for insulation products including reuse, recycling, 

landfilling or incineration. The manner in which a product is handled after use contributes to its 

environmental and human health impacts. The following sections consider end-of-life issues for 

insulation materials containing HBCD. As insulation boards comprise the majority of waste 

containing HBCD (Dawson 2011), they are the focus of this section.

For insulation materials, the end-of-life usually occurs when the building is altered, demolished 

(U.S. Department of the Interior n.d.), or burned down. During demolition, HBCD may be 

released in dust (European Commission 2008; Sall 2010). Common demolition techniques 

include implosion with explosives, use of a crane and wrecking ball, or deconstruction of the 

structure (European Commission 2008). Construction and demolition (C&D) debris in the U.S. is 

estimated to total approximately 160 million tons per year (U.S. EPA 2009). The amount of XPS 

and EPS insulation in this waste is unknown. In Europe, HBCD use in insulation began in the 

1980s; therefore, the volume of waste containing HBCD is expected to increase after 2025, as 

buildings containing insulation flame retarded with HBCD are refurbished or demolished (Sall 

2010).

Additionally, in some cases, insulation used on or under the soil may be left in the environment 

after use. For example, polystyrene insulation may be used under parking decks, rails, roads, or 

exterior insulation of cellars (European Commission 2008). Insulation used for these purposes 

often remains in the ground after its intended use is over (European Commission 2008).

The Agency’s concern about HBCD stems largely from its persistent, bioaccumulative, and toxic 

(PBT) characteristics. HBCD bioaccumulates and biomagnifies in the food chain (U.S. EPA 

2010). Along with its high toxicity towards aquatic organisms, it persists and is transported long 

distances in the environment and is associated with human health concerns (U.S. EPA 2010).

2.2.1 Reuse and Recycling

The end-of-life for EPS and XPS often comes when buildings are demolished or altered. 

However, EPS and XPS insulation may remain functional as insulation even after a building is 

taken out of service. Polystyrene insulation can therefore be salvaged and reused, although the 

board must be protected and not broken during removal (Wilson 2005; U.S. Department of the 

9 www.epa.gov/dfe/pubs/projects/decaBDE/index.htm

2-9

 
Interior n.d.). For example, during the re-roofing of the Dallas Fort Worth International Airport, 

approximately 90% of existing XPS material had maintained its thermal and physical properties 

over the past 17 years and was reused (Owens Corning 2007).

Additionally, polystyrene insulation board may be recycled into new polystyrene boards or other 

applications (European Commission 2008; Sall 2010). Polystyrene is easier to recycle compared 

to other foam insulation materials because it can be melted and reformed with minimal chemical 

modification (U.S. Department of the Interior n.d.). To do so, the polystyrene is melted and reexpanded into insulation or packaging (Wilson 2005). For example, used EPS insulation boards 

may be ground up and molded with virgin EPS to form new boards (European Commission 

2008). Similarly, XPS may also be melted and reused in the manufacture of new insulation board 

(Herrenbruck n.d.). Due to the use of flame retardants (i.e., HBCD), as well as the dust and dirt 

accumulated during use and removal, used EPS and XPS can typically only be recycled into 

building insulation, and cannot be recycled into non-building applications, such as packaging 

(U.S. Department of the Interior n.d.). Although there is some recycling of polystyrene insulation 

in Europe – for example, Germany collects used polystyrene and recycles it into building 

insulation on a national level (European Commission 2008) – it is unclear to what extent the 

recycling of EPS and XPS takes place in the U.S. (Herrenbruck n.d.).

2.2.2 Landfilling

In the U.S., the majority of C&D waste is disposed of in municipal solid waste landfills or C&D 

landfills (U.S. EPA 1998; Dawson 2011; Sustainable Sources 2012). In landfills, weathering and 

degradation (via UV light, microorganisms, and physical impact) will cause these materials to 

release HBCD over time to the soil, and to a lesser extent to water and air (European 

Commission 2008; Environment Canada 2011b). However, HBCD is expected to remain largely 

immobile in landfills, due to its tendency to sorb to organic matter in particles and its low water 

solubility (Environment Canada 2011a). Therefore, the potential for groundwater contamination 

from landfill seepage is unlikely due to HBCD’s physical-chemical properties and evidence that 

the chemical may undergo anaerobic biodegradation (Environment Canada 2011b).

2.2.3 Incineration

Insulation boards containing HBCD may also be incinerated, although this process is not 

commonly used in the U.S. (Herrenbruck n.d.). Although HBCD should be destroyed at the high 

temperatures found in properly functioning incinerators, releases of potentially hazardous 

combustion by-products such as polybrominated dibenzo-p-dioxins and dibenzofurans may 

occur from uncontrolled burns, accidental fires, and improperly functioning incinerators 

(Birnbaum, Staskal et al. 2003; Weber and Kuch 2003; Environment Canada 2011b). Recent 

studies also show that HBCD-containing EPS and XPS can be incinerated in advanced municipal 

solid waste incinerators with a very high destruction efficiency for HBCD (Plastics Europe 

2014).

2.3 HBCD Exposure

Exposure can occur at many points in the life cycle of a flame retardant chemical. HBCD may be 

released to air, water, soil, and sediment during manufacture, processing, transportation, use, 

2-10
improper handling, improper storage or containment, product usage, and disposal of the 

substance or products containing the substance. HBCD has also been shown to be persistent and 

to bioaccumulate and biomagnify in food chains (U.S. EPA 2010). Occupational exposures may 

occur during raw material extraction, chemical and product manufacturing, handling of material 

containing HBCD (e.g., handling of insulation during installation and renovation of buildings), 

and product end-of-life (i.e., reuse, refurbishing, recycling, incinerating, landfilling, building 

demolition, or fire). Consumers have the potential to be exposed to HBCD while the flame 

retarded product is in use (e.g., releases to the air from flame retarded textiles), however the 

magnitude of this exposure is highly uncertain (IOM Consulting 2009). A quantitative exposure 

assessment is outside the scope of this project. For an overview of exposure considerations and 

routes of exposure, refer to Chapter 5 of the An Alternatives Assessment For The Flame 

Retardant Decabromodiphenyl Ether (DecaBDE). Additionally, EPA’s Exposure Factors 

Handbook10 provides information on various physiological and behavioral factors commonly 

used in assessing exposure to environmental chemicals. 

2.3.1 Human Exposures

Based on the uses of HBCD, humans may be exposed during its production, industrial use, from 

the use of products containing HBCD, and indirectly from household dust or the environment via 

food, soil, water, and air (European Commission 2008). The human population can be exposed to 

HBCD by inhaling airborne dust, ingestion, dermal contact (European Commission 2008) and, 

although unlikely, by inhaling vapor. It should be noted that HBCD exposure studies generally 

do not compare exposure resulting from the use of flame-retarded insulation to that from other 

uses (e.g., textiles), however, one study did indicate that the HBCD releases from insulation are 

minor in comparison to textile applications (European Commission 2008).

The primary occupational exposure to HBCD is through inhaling airborne dust (European 

Commission 2008). Ingestion may occur as a result of inhaling dust but is not expected to be a 

relevant route of occupational exposure (European Commission 2008). Workers may also be 

exposed through dermal deposition of airborne dust or direct handling of the chemical or 

products during chemical and product manufacturing and during construction (European 

Commission 2008). For insulation applications, HBCD is typically manufactured as a standard 

grade powder or granule with mean particle sizes that are not respirable (European Commission 

2008). However, an occupational exposure study at an industrial plant in Europe producing EPS 

reported measured elevated airborne dust levels and measured HBCD in the blood of workers 

(Thomsen, Molander et al. 2007). Occupational HBCD exposure may also occur as a result of 

thermal cutting of EPS and XPS at production plants and construction sites. XPS is not typically 

thermally cut at production plants or construction sites. When XPS is cut at production plants, 

fan extraction is supplied and worker exposure is mitigated due to restricted access to the area 

during cutting. One small-scale simulation study suggests that over 60% of the HBCD particles 

released during the thermal cutting of EPS and XPS would penetrate the alveolar region of a 

worker’s lung (Zhang, Kuo et al. 2012). No readily available HBCD occupational exposure 

information – including biomonitoring data – was found for U.S. workers (U.S. EPA 2010). 

10 Available at http://www.epa.gov/ncea/efh/pdfs/efh-complete.pdf.

2-11

 
HBCD is incorporated at high temperatures and/or pressures in EPS and XPS manufacturing. In 

EPS, it is dissolved chemically in styrene monomer in a reactor. In XPS, it is added to viscous, 

molten polystyrene in an extruder. Room temperature solid state diffusion of HBCD out of 

polystyrene foams would be expected to be very slow and very low. Since HBCD is an additive 

flame retardant, it can potentially be released from its end products over time, as it is not 

chemically bound to the polymer matrix (Environment Canada 2011b). 

HBCD has been detected in human adipose tissue, milk, and blood and has been shown to cross 

the placenta (Covaci, Gerecke et al. 2006; Johnson-Restrepo, Adams et al. 2008; Meijer, Weiss 

et al. 2008; Arnot, McCarty et al. 2009). General population exposure to HBCD is likely from its 

presence in food (e.g., fish and shellfish) due to biomagnification in food chains (Heibl and 

Vetter 2007; Fernandes, Dicks et al. 2008; van Leeuwen and de Boer 2008), outdoor air, 

particularly near sites where HBCD or HBCD flame retarded materials are produced (Covaci, 

Gerecke et al. 2006), and indoor air (Law, Herzke et al. 2008). HBCD has also been detected in 

indoor dust (Covaci, Gerecke et al. 2006; Law, Herzke et al. 2008; Roosens, Abdallah et al. 

2009). If HBCD is present in household (e.g., furniture upholstery) and/or automotive (e.g., 

textiles in vehicles) applications, children could be exposed, especially given children’s 

increased potential exposure via dust, mouthing behavior (e.g., object-to-mouth), and hand-tomouth ingestion pathways (U.S. EPA 2010). While biomonitoring data for HBCD in children are 

not available, studies of other brominated flame retardants have found higher exposures in 

children than adults (Center for Disease Control and Prevention 2009; Toms, Sjödin et al. 2009).

2.3.2 Environmental Exposures

HBCD is not known to occur naturally, but may be released to air, water, soil, and sediment 

during manufacture, processing, transportation, use, improper handling, improper storage or 

containment, product usage, and disposal of the substance or products containing the substance 

(Environment Canada 2011a). Studies suggest that a significant portion of HBCD in the 

environment is released from textiles. As was noted in Section 2.1.2, the EU’s 2008 risk 

assessment of HBCD (European Commission 2008) estimated releases of HBCD during its 

various life-cycle stages, finding that textile-related releases may constitute a significant share 

(approximately 86%) of total HBCD releases to the environment in Europe. Information from the 

United Kingdom indicates that the primary sources of HBCD in the environment are from 

fugitive emissions during its manufacture and use in subsequent products, potentially from 

leaching in landfills, and from incinerator emissions (United Kingdom Environment Agency 

2009). Because HBCD is not covalently bound to the polymer, it is possible that it may migrate 

out of consumer or industrial end-use products into the indoor and/or outdoor environment 

(Environment Canada 2011a). It should be noted that HBCD exposure studies generally do not 

compare exposure resulting from the use of flame-retarded insulation to exposure resulting from 

other uses (e.g., textiles).

Limited data are available on the degradation of HBCD in soil, water, or sediment (U.S. EPA 

2010). However, HBCD has been detected in biota over large areas and in remote locations (U.S. 

EPA 2010). The frequent detection of HBCD over a large geographic area, with increasing 

occurrence in remote locations such as the Arctic, where no demonstrable local sources exist that 

can account for these exposures, suggests that HBCD is persistent and undergoes long-range 

atmospheric transport (UNEP 2009).

2-12
HBCD has been measured in air and sediment in the Arctic, Scandinavian countries, North 

America and Asia (Covaci, Gerecke et al. 2006; Arnot, McCarty et al. 2009; UNEP 2009). 

HBCD has also been measured in marine and arctic mammals, freshwater and marine fish, 

aquatic invertebrates, birds and bird eggs, polar bears, and one plant species (Covaci, Gerecke et 

al. 2006; Arnot, McCarty et al. 2009; UNEP 2009). The majority of these studies are European; 

some are from North America, and a few are from Asia. Additionally, studies have shown that 

HBCD is bioavailable and bioaccumulative (Veith, Defoe et al. 1979; Drottar, MacGregor et al. 

2001; Tomy, Budakowski et al. 2004). For example, a monitoring study by De Boer et al. (2002)

included a wide variety of biota (invertebrates, fish, birds, and marine mammals) and showed 

that HBCD bioaccumulates easily and biomagnifies in food chains.

2-13
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brominated flame retardants in Scottish shellfish: methodology, occurrence and human 

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2-15
Heibl, J. and W. Vetter (2007). "Detection of hexabromocyclododecane and its metabolite 

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well as information on potential alternatives to its use, Report prepared for European 

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hexabromocyclododecanes (HBCDs) in tissues of humans, dolphins, and sharks from the 

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Law, R. J., D. Herzke, et al. (2008). "Levels and trends of HBCD and BDEs in the European and 

Asian environments, with some information for other BFRs." Chemosphere 73: 223-241. 

Maxwell, K. (2008). Flame Retardant Extruded Polystyrene Foam Compositions. U.S. Patent US 

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Meijer, L., J. Weiss, et al. (2008). "Serum concentrations of neutral and phenolic organohalogens 

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42(9): 3428-3433. 

Morose, G. (2006). An Overview of Alternatives to Tetrabromobisphenol A (TBBPA) and 

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2-16
Extruded Polystyrene Foam (XPS) containing Hexabromocyclododecane (HBCD) as a 

flame-retardant by co-incineration in the Würzburg Municipal Solid Waste Incinerator. 

Technical Summary Report.

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via Dust Ingestion, but not Diet, Correlates with Concentration in Human Serum—

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Toms, L.-M. L., A. Sjödin, et al. (2009). "Serum Polybrominated Diphenyl Ether (PBDE) Levels 

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2298-2303. 

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U.S. EPA (2012). Significant New Use Rule for Hexabromocyclododecane and 1,2,5,6,9,10-

Hexabromocyclododecane. 77 FR 17386-17394.

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2-18
3 Background on Flame Retardants

This chapter includes background information on flame retardants. Section 3.1 includes 

background on types of flame retardants and flammability test requirements. Section 3.2 presents 

information regarding flame retardants for polystyrene, Section 3.3 presents the flame retardants 

included in this assessment, and Section 3.4 discusses those flame retardants that were 

considered but excluded from the assessment. 

3.1 General Information on Flame Retardants

Flame retardants are chemicals used to reduce risk of fire through reducing the ignitability of 

materials and/or the heat generated from materials. For polymers, the simplest way, in theory, of 

decreasing flammability is to design the polymer so that it is thermally stable. Thermally stable 

polymers are less likely to decompose into combustible gases under heat stress and thus often 

have higher ignition resistances. Because thermally stable polymers are often difficult and 

expensive to process, manufacturers use other means, such as adding flame retardant chemicals, 

to impart flame retardant properties to materials. Since there are a large number of flame 

retardants on the market and they often can be a cost-effective solution for providing fire safety, 

these chemicals are used in a broad range of products. 

As plastics have become an integral part of modern life, fire risk is perceived to be elevated 

because plastics can burn hotter and faster than traditional materials such as wood (Underwriters 

Laboratories 2012). Flame retardants, which are often added to meet flammability standards, 

inhibit combustion and therefore contribute to a reduced fire risk when added to flammable 

plastics. However, some flame retardants are associated with environmental hazards e.g., 

polybrominated diphenyl ethers (PBDEs) (U.S. EPA 2003b; U.S. EPA 2003a; U.S. EPA 2004; 

U.S. EPA 2008; U.S. EPA 2012) and contribute to hazardous by-products from a smoldering or 

fully engaged fire (e.g., carbon monoxide and smoke (Nelson 1998; Peck 2011)) when inhibiting 

combustion. Some halogenated flame retardants will yield additional hazardous by-products 

(e.g., halogenated dioxins and furans) during incomplete combustion (Sidhu, Morgan et al. 

2013). This incomplete combustion is too complex and variable for all potential combustion byproducts to be adequately included in this report. Both halogenated and non-halogenated flame 

retardants may yield other toxic by-products that have not been identified in this report.

The use of flame retardants can be viewed as a risk-risk trade-off. Plastic product manufacturers 

are challenged with using chemical additives that reduce fire risk and may increase 

environmental risk. There are two risk reduction arguments put forth by the stakeholders of this 

Partnership. They are summarized here in simple terms: (1) flame retardants reduce fire risk and 

reduce smoke and toxicity caused by uninhibited fires thus enabling the use of beneficial plastic 

products, and (2) flame retardants increase environmental risk because they release from plastics 

into house dust and contribute to the toxicity of combustion by-products when they burn while 

not significantly increasing egress time from buildings during fires. One important approach in 

addressing this risk-risk trade-off is identifying the least hazardous flame retardant additives 

available for a given polymer-product combination. This report provides the environmental 

information necessary for product manufacturers to identify the flame retardants with the lowest 

hazard for their products. Although an analysis of fire safe assemblies that do not require 

3-1
additive flame retardants is outside of the scope of this report, Chapter 5 provides a general 

overview of alternative insulation materials and the applications in which they may be used.

Fire occurs in three stages: (1) thermal decomposition, where the solid, or condensed phase, 

breaks down into gaseous decomposition products as a result of heat, (2) combustion chain 

reactions in the gas phase, where thermal decomposition products react with an oxidant (usually 

air) and generate more combustion products, which then propagate the fire and release heat, and 

(3) transfer of the heat generated from the combustion process back to the condensed phase to 

continue the thermal decomposition process (Hirschler 1992; Beyler and Hirschler 2002).

Those flame retardants which act in the gas phase do so by interacting with substances that are 

volatile. To function in the gaseous phase this way, these flame retardants themselves must 

become volatile and react with the substances that are being released from a product in turn 

making the volatile substances no longer combustible. Flame retardants that act in the condensed

phase do so by forming a solid char, a glassy layer that acts by isolating the substrate from 

combustion, which interferes with the transfer of heat from the gas phase to the condensed phase

and reduces the combustibility of the gases. The primary physical mode of flame retardancy is to 

reduce heat generation by forming a non-combustible layer or “diluting” the organic combustible 

material through the generation of water vapor and preventing the continued progression of the 

fire (Posner and Boras 2005). Therefore, in either state, flame retardants will act to decrease the 

release rate of heat (Hirschler 1994), thus reducing the burning rate, flame spread, and/or smoke 

generation (Morose 2006a). Flame retardant modes of action are further discussed in Chapter 3 

of the report Flame-Retardant Alternatives for Decabromodiphenyl Ether (decaBDE)

11. 

3.1.1 Flame Retardant Classification

Flame retardants are generally incorporated throughout a polymeric material, although they can 

also be coated on the external surface of the polymer to form a protective barrier. Flame 

retardants can be broadly classified into two types according to the method of incorporation into 

the polymer:

• Reactive: Reactive flame retardants are incorporated into the polymer during

compounding and will become a permanent part of the polymer structure – i.e., the 

chemically-bound reactive flame retardant chemicals cease to exist as separate chemical 

entities. Compared to an additive flame retardant, reactive flame retardants can have a 

greater effect on a polymer’s physical-chemical properties.

• Additive: Additive flame retardants are also incorporated into the polymer during 

compounding and may interact with the polymer, but they remain as an independent 

chemical species. Because they are not chemically bound to the polymer, additive flame 

retardants have a potential to migrate out of the polymer under certain conditions over 

time. Therefore plastic formulators must take this into account to avoid reducing polymer 

fire safety or causing exposure to humans and releases to the environment. A far greater 

number of additive flame retardants are offered for polymers compared to the number of 

11 http://www.epa.gov/dfe/pubs/projects/decaBDE/index.htm

3-2

 
reactive flame retardants. Additive flame retardants are far more versatile because 

commodity plastics are made for many applications, not just those requiring flame 

retardants, and they can be incorporated into the product up until the final stages of 

manufacturing.

Due to the various physical and chemical properties of flame retardant chemicals, most are used 

exclusively as either reactive or additive flame retardants. Both reactive and additive flame 

retardants can significantly change the properties of the polymers into which they are 

incorporated. For example, they may change the viscosity, flexibility, density, electrical 

properties, tensile strength, and flexural strength; they may also increase the susceptibility of the 

polymers to photochemical and thermal degradation. 

Flame retardants can also be classified into four main categories according to chemical 

composition (IPC 2003; Morose 2006a):

• Halogenated: Halogenated flame retardants are primarily based on chlorine and bromine. 

Hexabromocyclododecane (HBCD) and the three alternatives assessed in this report 

contain bromine. In 2006, brominated compounds represented approximately 18% by 

volume of the global flame retardant consumption (Cusack 2007). Typical halogenated 

flame retardants are halogenated aliphatic and aromatic compounds, halogenated 

polymeric materials, and halogenated paraffins. Some halogenated flame retardants also 

contain other elements, such as phosphorus or nitrogen. The effectiveness of halogenated 

additives is due to their interference with volatile substances that are created in the 

combustion process, decreasing their combustibility (see Section 3.2 for more detail). 

• Inorganic: This category includes inorganic flame retardants and flame retardant 

synergists such as silicon dioxide, metal hydroxides (e.g., aluminum hydroxide and 

magnesium hydroxide), antimony compounds (e.g., antimony trioxide), boron 

compounds (e.g., zinc borate – which is often used as a synergist for both halogenated 

and non-halogenated flame retardants), and other metal compounds (molybdenum 

trioxide). As a group, these flame retardants represented the largest fraction (about 46-

52%) of total flame retardants consumed in 2006 because they require high loading levels 

to impact the desired fire safety (Cusack 2007). Antimony trioxide is invariably used as a 

synergist for halogenated flame retardants since by itself antimony oxide has little flame 

retardant effect in the presence of most burning polymers. Inorganic synergists are 

sometimes used with HBCD. 

• Phosphorus-based: This category represented about 16% by volume of the global 

consumption of flame retardants in 2006 and includes organic and inorganic phosphates, 

phosphonates, and phosphinates as well as red phosphorus, covering a wide range of 

phosphorus compounds with different oxidation states (Cusack 2007). There are also 

halogenated phosphate esters, often used as flame retardants for polyurethane foams or as 

flame retardant plasticizers, but not commonly used in electronics applications (Hirschler 

1998; Green 2000; Weil and Levchik 2004). None of the potential HBCD alternatives 

identified in this assessment are phosphorus-based.

3-3
• Nitrogen-based: These flame retardants include melamine and melamine derivatives 

(e.g., melamine cyanurate, melamine polyphosphate). Nitrogen compounds were 

estimated to account for 3% of global flame retardant consumption in 2006 (Cusack 

2007). Nitrogen-containing flame retardants are often used in combination with 

phosphorus-based flame retardants, often with both elements in the same molecule. None 

of the potential HBCD alternatives identified in this assessment are nitrogen-based.

3.1.2 Flammability Tests 

HBCD is used as a flame retardant in polystyrene insulation foam to allow the foam to meet the 

fire safety requirements of various building codes, as set by national, state, county or municipal 

regulations. Flammability standards are developed by a variety of entities, including national 

regulatory agencies such as the Consumer Product Safety Commission (CPSC), state regulatory 

agencies such as the California Bureau of Electronic and Appliance Repair, Home Furnishings 

and Thermal Insulation (BEARHFTI), or for-profit companies such as Underwriters Laboratories

(UL). 

In the U.S., building codes are adopted at the state or municipal level and not at the federal level 

(Morose 2006b; Grant 2011). The American Society for Testing and Materials (ASTM) E5 

committee is responsible for developing voluntary consensus fire standards for materials, 

products, and assemblies that are often incorporated into state or municipal regulations. 

Specifically, ASTM standard E84 (Standard Test Method for Surface Burning Characteristics of 

Building Materials) is the overarching flammability test for building materials in the U.S. 

(Harscher 2011). ASTM E84 assesses the flame spread and smoke development of building 

materials by employing the Steiner Tunnel Test to compare the flame spread and smoke 

development against standard materials (Weil and Levchik 2009; Harscher 2011). Expanded 

polystyrene (EPS) and extruded polystyrene (XPS) foam also generally must meet the 

requirements of ASTM C578 (Standard Specification for Rigid, Cellular Polystyrene Thermal 

Insulation), as well as comply with the International Building Code (IBC) and International 

Residential Code (IRC) (EPS Industry Alliance 2011; Extruded Polystyrene Foam Association 

2011). 

Other flammability tests apply to EPS and XPS insulation foam containing HBCD in specific 

building assemblies. A partial list of these tests includes:

• ASTM D2863 (Standard Test Method for Measuring the Minimum Oxygen 

Concentration to Support Candle-Like Combustion of Plastics)

• ASTM E119 (Standard Test Methods for Fire Tests of Building Construction and 

Materials)

• ASTM E1354 (Standard Test Method for Heat and Visible Smoke Release Rates for 

Materials and Products Using an Oxygen Consumption Calorimeter)

• Factory Mutual (FM) 4450 (Approval Standard for Class 1 Insulated Deck Roofs)

• FM 4470 (Approval Standard for Single-Ply, Polymer-Modified Bitumen Sheet, Built-Up 

Roof (BUR) and Liquid Applied Roof Assemblies for use in Class 1 and Noncombustible 

Roof Deck Construction)

• FM 4880 (Approval Standard for Class 1 Fire Rating of Insulated Wall or Wall and 

Roof/Ceiling Panels, Interior Finish Materials or Coatings and Exterior Wall Systems)

3-4
• National Fire Protection Association (NFPA) 225 (Model Manufactured Home 

Installation Standard)

12

• NFPA 286 (Standard Methods of Fire Tests for Evaluating Contribution of Wall and 

Ceiling Interior Finish to Room Fire Growth)

• Uniform Building Code (UBC) Standard 42-1 (Flame Spread and Smoke Development)

13

• UL 94 (Standard for Safety of Flammability of Plastic Materials for Parts in Devices and 

Appliances Testing)

3.2 Brominated Flame Retardants for Polystyrene

At this time, brominated flame retardants are the only commercially and technically viable 

options for polystyrene foam insulation. Flame retardants for EPS and XPS must be compatible 

with manufacturing processes, allow the material to comply with fire safety codes, and not 

compromise the physical properties of the foam (Environment Canada 2011; EPS Industry 

Alliance 2011; Extruded Polystyrene Foam Association 2011). HBCD has been the flame 

retardant of choice for EPS and XPS because it imparts flame retardance at low concentrations 

without compromising the physical properties (e.g., thermal resistance) of the foam (EPS 

Industry Alliance 2009; Environment Canada 2011; Extruded Polystyrene Foam Association 

2011). Based on currently available technology, using non-brominated flame retardants in 

polystyrene foam would require much higher concentrations of the flame retardant, which can

alter the physical properties of the foam (IOM Consulting 2009).

Brominated flame retardants have the ability to interact with partial oxidation reactions that 

occur in the gas phase during the combustion of polystyrene, which leads to the extinction of the 

flame (Kaspersma, Doumen et al. 2002). Bromine-containing compounds form hydrogen 

bromide (HBr) and prompt the formation of hydrogen gas from radical hydrogen (Beach, 

Rondan et al. 2008). In addition to its ability to exhibit flame retardancy in the gas phase, HBCD 

has also been found to aid in polystyrene degradation through condensed-phase activity (Beach, 

Rondan et al. 2008). 

12 Based on ASTM E84. 13 ibid

Figure 3-1. Bromine Interaction Mechanism

HBr + OH• → H2O + Br•

HBr + •O• → OH• + Br•

HBr + H• ↔ H2 + Br•

HBr + RCH2• ↔ RCH3 + Br•

RBr ↔ R• + Br•

Source: Kaspersma, Doumen et al. 2002

3-5

 
Although all halogens are capable of 

capturing free radicals produced during 

the combustion of polystyrene, the ability 

to do so effectively increases with the size 

of the halogen (F<Cl<Br<I) (Alaee, Arias 

et al. 2003). Fluorinated compounds are 

not used as flame retardants because they 

are very stable and decompose at very 

high temperatures, delaying the activation 

of the flame retardant’s mechanism 

(Alaee, Arias et al. 2003). Iodine-based 

compounds are also not widely used 

because they decompose at slightly 

elevated temperatures and are unstable 

(Alaee, Arias et al. 2003). Brominated 

compounds, however, have a higher 

trapping efficiency and lower 

decomposing temperature than 

chlorinated compounds, making them 

ideal components in flame retardants 

(Alaee, Arias et al. 2003). 

3.3 Flame Retardants Included in this 

Assessment

With the assistance of the multistakeholder partnership, U.S. 

Environmental Protection Agency (EPA) 

identified three alternatives to HBCD that 

fit the scope of this project: viable 

alternatives to HBCD for use in EPS and 

XPS foam insulation (see Chapter 1). A 

list of potential alternatives to HBCD was 

compiled based on information in open 

literature (Morose 2006b; Weil and 

Levchik 2009; pinfa 2011) and discussion 

with experts in chemical manufacturing 

and product development in industry, 

government, and academia. Through these 

discussions, the three alternatives shown 

in Table 3-1 were identified as potentially 

viable for use in EPS and XPS. Section 

3.4 discusses other flame retardants that 

were considered but not included in the 

assessment. As was discussed in Chapter 

1, while the project scope does not include 

alternatives to HBCD for its minor uses in textile back coatings and high-impact polystyrene 

Chemical Alternatives and the Toxic Substances 

Control Act

EPA’s Design for the Environment (DfE) program is 

administered by the Office of Pollution Prevention and 

Toxics (OPPT), which is charged with the implementation 

of the Toxic Substances Control Act (TSCA) and the 

Pollution Prevention Act (PPA).

 

Central to the administration of TSCA is the management 

of the TSCA Inventory. Section 8 (b) of TSCA requires 

EPA to compile, keep current, and publish a list of each 

chemical substance that is manufactured or processed in 

the United States. Companies are required to verify the 

TSCA status of any substance they wish to manufacture or 

import for a TSCA-related purpose. For more information, 

please refer to the TSCA Chemical Substance Inventory 

website: 

http://www.epa.gov/opptintr/existingchemicals/pubs/tscain

ventory/basic.html

TSCA and DfE Alternatives Assessments

Substances selected for evaluation in a DfE Alternatives 

Assessment generally fall under the TSCA regulations and 

therefore must be listed on the TSCA inventory, or be 

exempt or excluded from reporting before being 

manufactured in or imported to, or otherwise introduced in 

commerce in, the United States. For more information see 

http://www.epa.gov/oppt/newchems/pubs/whofiles.htm.

To be as inclusive as possible, DfE Alternatives 

Assessments may consider substances that may not 

have been reviewed under TSCA and therefore may not 

be listed on the TSCA inventory. DfE has worked with 

stakeholders to identify and include chemicals that are of 

interest and likely to be functional alternatives, regardless 

of their TSCA status. Chemical identities are gathered 

from the scientific literature and from stakeholders and, for 

non-confidential substances, appropriate TSCA identities 

are provided.

Persons are advised that substances, including DfE 

identified functional alternatives, may not be introduced 

into US commerce unless they are in compliance with 

TSCA. Introducing such substances without adhering to 

the TSCA provisions may be a violation of applicable law. 

Those who are considering using a substance discussed in 

this report should check with the manufacturer or importer 

about the substance’s TSCA status. If you have questions 

about reportability of substances under TSCA, please 

contact the Industrial Chemistry Branch at 202-564-8740.

3-6
(HIPS) used in electronics housings, stakeholders interested in alternatives for these uses may 

refer to the flame retardants assessed in An Alternatives Assessment For The Flame Retardant 

Decabromodiphenyl Ether (DecaBDE)14.

Table 3-1. Summary of Chemicals for Assessment 

Chemical Name CASRN Status

Hexabromocyclododecane (HBCD) 25637-99-4; 

3194-55-6

Action Plan chemical. Included for comparative 

purposes.

Benzene, ethenyl-, polymer with 1,3 

butadiene, brominated; “butadiene 

styrene brominated copolymer”

1195978-93-8

Announced by The Dow Chemical Company and Great 

Lakes Solutions, A Chemtura Business on March 29, 

2011 (Great Lakes Solutions, A Chemtura Business 

2011). The chemical has also been licensed to ICL-IP 

and Albemarle. 

Benzene, 1,1'-(1-

methylethylidene)bis[3,5-dibromo-4-

(2,3-dibromo-2-methylpropoxy)]; 

“TBBPA-bis brominated ether 

derivative”

97416-84-7 Proposed as an alternative by a chemical manufacturer.

Tetrabromobisphenol A Bis (2,3-

dibromopropyl) Ether 21850-44-2

This flame retardant was submitted as an alternative to 

HBCD to the Stockholm Persistent Organic Pollutants 

Review Committee (POPRC) (Lorenzi and Garlaschi 

2013).

3.4 Flame Retardants Not Included in this Assessment

In addition to the chemicals listed in Table 3-1, the Partnership considered other flame retardants 

for the assessment, including individual chemicals and materials. Section 3.4.1 describes 

chemicals that were identified as possible alternatives to HBCD and the reasons they were 

excluded from the assessment. 

3.4.1 Specific Chemicals that were Excluded from this Assessment

The chemicals listed in this section were identified as possible alternatives to HBCD, but were 

not included in the alternatives assessment. Reasons for exclusion included:

• The chemical is not a flame retardant, but rather a blend of flame retardants and other 

additives intended to improve the performance of certain flame retardants through 

synergistic mixtures;

• Not functional in typical EPS and/or XPS manufacturing processes; and

• Interferes with ability of EPS and/or XPS to meet building codes or flammability standards.

A summary of the chemicals that were discussed but not included in this assessment is listed in 

Table 3-2 along with the reason for exclusion. It is possible that there are alternatives that the 

Partnership was not aware of or were under development at the time this report was compiled; 

therefore, Table 3-1 and Table 3-2 may not list all of the possible alternatives to HBCD.

14 http://www.epa.gov/dfe/pubs/projects/decaBDE/index.htm

3-7

 
Table 3-2. Chemicals Considered but Not Included in the Final Alternatives Assessment1

Chemical Name CASRN Reason for Exclusion

Brominated Flame Retardants

Tetrabromocyclooctane 31454-48-5; 

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.

Dibromoethyldibromocyclohexane 3322-93-8 Polystyrene manufacturers have noted insufficient thermal stability and an inferior persistent, 

bioaccumulative, and toxic (PBT) chemical assessment.

Chloropentabromocyclohexane 87-84-3

The manufacture of this flame retardant was discontinued in favor of HBCD due to an inferior 

environmental health and safety profile. This flame retardant may also interfere with the styrene 

polymerization process, resulting in a product with a lower average molecular weight (MW) and more 

residual unreacted styrene in the product. The resulting foam will lack the strength to meet building code 

requirements.

Cinnamalacetophenone tetrabromide N/A1

This flame retardant was used for a time but discontinued. Its chemical structure is similar to that of 1,2-

dibromoalkyl ketones. Referring to the patent literature, EPA identified this CAS name as expected to be 

1-Pentanone, 2,3,4,5-tetrabromo-1,5-diphenyl-; CASRN 31611-84-4.

Hexabromohexene 125512-87-0

This flame retardant is recommended in patents as a potential alternative, but there is no information 

indicating that it is currently used by industry. It is also similar in structure to 

chloropentabromocyclohexane, so it may also interfere with the styrene polymerization process.

1,2-Dibromoalkyl ketones N/A1

This flame retardant is recommended in patents as a potential alternative, but there is no information 

indicating that it is currently used by industry. Polystyrene foam manufacturers have observed 

insufficient functionality.

1,1,2,3,4,4-Hexabromo-2-butene 72108-73-7; 

36678-45-2

This flame retardant is recommended in patents as a potential alternative, but there is no information 

indicating that it is currently used by industry. This flame retardant may also interfere with the styrene 

polymerization process, resulting in a product with a lower average MW and more residual unreacted 

styrene in the product. The resulting foam will lack the strength to meet building code requirements.

bis(2,3-dibromopropyl) 

tetrabromophthalate N/A1

This flame retardant is not as effective per unit weight as other alkyl halides and polystyrene foam 

manufacturers have observed insufficient flame retardant activity. Referring to the patent literature, EPA 

identified this CAS name as 1,2-Benzenedicarboxylic acid, 3,4,5,6-tetrabromo-, 1,2-bis(2,3-

dibromopropyl) ester; CASRN 214216-08-7.

2,4,6-Tribromophenyl allyl ether 3278-89-5

This flame retardant is recommended in patents as a potential alternative. It is not a potential alternative 

for the use of HBCD in XPS foam because of its poor thermal stability at operating temperatures. It is not 

a cost-effective alternative in EPS because it is only viable in the less-economic two-step manufacturing 

process. This flame retardant may also interfere with the styrene polymerization process, resulting in a 

product with a lower average MW and more residual unreacted styrene in the product, resulting in foam

that will lack the strength to meet building code requirements.

bis(allyl ether) of 

tetrabromobisphenol A 25327-89-3

This flame retardant is recommended in patents as a potential alternative, but in general only has limited 

use and availability. It does not work well in XPS manufacturing processes, and for EPS is only viable in 

the less-economic two-step manufacturing process. The lower brominated content and mixture of 

aliphatic and aromatic bromine affects the efficiency of the material. 

3-8
Chemical Name CASRN Reason for Exclusion

N-(2,3-dibromopropyl)-4,5-

dibromotetrahydrophthalimide 93202-89-2 This flame retardant is recommended in patents as a potential alternative, but feedback from polystyrene foam manufacturers indicated problems with its use, including insufficient flame retardant activity. 

Dialkyl tetrabromophthalate N/A1

This flame retardant is recommended in patents as a potential alternative, but polystyrene foam 

manufacturers have observed insufficient flame retardant activity. It is also known to have mutagenic 

affects. Referring to the patent literature, EPA identified this CAS name as 1,2-Benzenedicarboxylic acid, 

3,4,5,6-tetrabromo-, 1,2-bis(2-ethylhexyl) ester; CASRN 26040-51-7.

tris(2,3-dibromopropyl) phosphate 126-72-7 This flame retardant was used for a time but discontinued due to its mutagenicity. 

Blends

Aluminum Hydroxide/Alumina 

Trihydrate (ATH) (recommended 

with further addition of phosphorus 

or brominated FRs)

21645-51-2

This flame retardant will require high loading in EPS and XPS. It has also already been assessed in 

Design for the Environment (DfE)’s An Alternatives Assessment For The Flame Retardant 

Decabromodiphenyl Ether (DecaBDE).

Brominated anionic styrene polymer 

+ bis(pentabromophenyl) ethane

N/A1 + 

84852-53-9

These blends are synergistic mixtures used to improve performance of certain FRs. They are not potential 

alternatives to HBCD.

Bromoaliphatic FR + a more 

thermally stable bromine compound 

with an aromatic, vinylic, or 

neopentyl structure

N/A1

Halogenated FR + P-N compound N/A1

Elemental sulfur + phosphorus 

additive

7704-34-9 + 

7723-14-0

Graphite particles (halogenated FR 

and (optional) antimony oxide, or 

with a phosphorus FR)

N/A1

Graphite is used to increase thermal properties rather than for flame retardancy. Expandable graphite has 

been used as a flame retardant in some polymers but is not expected to impart flame retardancy in EPS 

and XPS.

Epoxy resin containing reacted-in 

DOPO and phosphoric acid N/A1 This flame retardant is unlikely to be a functional alternative in EPS and XPS due to insufficient flame retardant activity.

Other Classes

Nano-particle coatings N/A1

At low loading levels, these nanoparticle fire retardant coatings significantly reduce polyurethane foam 

flammability and can result in self-extinguishing fire behavior. National Institute of Standards and 

Technology (NIST) is evaluating this fire retardant technology that may have potential for XPS. The EPS 

industry processes material with hot wires, and particles that do not melt tend to create problems during 

this step.

Thiophosphates and 

dithiophosphates N/A1 Polystyrene foam manufacturers observed insufficient flame retardant activity.

Flame resistant barrier - coating, 

laminate, foil N/A1

Back coatings may not work with polystyrene foam because they will interfere with the ability of the 

foam to recede away from the fire. Additionally, the coating levels necessary to pass flammability tests 

are not economical. 

Boric acid + binder N/A1 This chemical is used as a smoke suppressant rather than as a flame retardant. It should also be noted that 

3-9
Chemical Name CASRN Reason for Exclusion

boric acid is a substance of very high concern in the European Union (EU).

Dimethyl methyl phosphonate 

(DMMP) 756-79-9 This chemical is too volatile for polystyrene foam.

Hypophosphite, calcium salt (with 

synergists) 7789-79-9 Polystyrene manufacturers have noted insufficient flame retardant activity.

Magnesium dihydroxide 1309-42-8

This flame retardant is not viable for polystyrene foam because it is not soluble and would require high 

loadings. It has also already been assessed in Design for the Environment (DfE)’s Flame Retardants in 

Printed Circuit Boards Partnership and the Flame Retardant Alternatives for DecaBDE Partnership.

Source: Personal Communication with members of the Partnership on Flame Retardant Alternatives for HBCD. 1 A specific CASRN was not suitable for entries that cover a general group or larger class of chemicals.

3-10
References

Alaee, M., P. Arias, et al. (2003). "An overview of commercially used brominated flame 

retardants, their applications, their use patterns in different countries/regions and possible 

modes of release." Environ Int 29: 683-689. 

Beach, M. W., N. G. Rondan, et al. (2008). "Studies of degradation enhancement of polystyrene 

by flame retardant additives." Polymer Degradation and Stability 93: 1664-1673. 

Beyler, C. L. and M. M. Hirschler (2002). Thermal Decomposition of Polymers. In SFPE 

Handbook of Fire Protection Engineering, DiNenno, P.J.

Cusack, P. (2007). Novel coated fillers enhance flame-retardant properties. Plastic Additivies 

and Compounding.

Environment Canada (2011). Proposed Risk Management Approach for 

Hexabromocyclododecane (HBCD).

EPS Industry Alliance. (2009). "HBCD Use & Application in EPS Foam Insulation." Retrieved 

September 28, 2011, 

from http://www.epsmolders.org/PDF_FILES/HBCD_Fact_Sheet_final_web.pdf.

EPS Industry Alliance (2011). HBCD Use in Polystyrene Foam Insulation. Presentation to U.S. 

Environmental Protection Agency, Washington, DC.

Extruded Polystyrene Foam Association (2011). Extruded Polystyrene Foam (XPS) Thermal 

Insulation Overview. Presentation to U.S. Environmental Protection Agency, 

Washington, D.C.

Grant, T. (2011). Construction Codes. Email to Emma Lavoie.

Great Lakes Solutions, A Chemtura Business (2011). Emerald 3000.

Green, J. (2000). Chapter 5: Phosphorus-containing flame retardants. Fire Retardancy of 

Polymeric Materials, Grand, A.F., Wilkie, C.A. New York, Marcel Dekker: 147.

Harscher, M. (2011). Uses of Hexabromocyclododecane (HBCD); Flammability Standards. 

Design for the Environment Kick-Off Meeting, Crystal City, VA.

Hirschler, M. M. (1992). Fire hazard and fire risk assessment; ASTM STP 1150. Amer. Soc. 

Testing and Materials, Philadelphia, PA.

Hirschler, M. M. (1994). Fire Retardance, Smoke Toxicity and Fire Hazard. Proceedings of 

Flame Retardants ‘94, London, UK.

Hirschler, M. M. (1998). Fire Performance of Poly(Vinyl Chloride) - Update and Recent 

Developments. Proceedings of Flame Retardants '98, London, UK, Interscience 

Communications.

3-11
IOM Consulting (2009). Data on manufacture, import, export, uses, and releases of HBCDD as 

well as information on potential alternatives to its use, Report prepared for European 

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IPC (2003). "IPC White Paper and Technical Report on Halogen-Free Materials Used for Printed 

Circuit Boards and Assemblies, IPC-WP/TR-584,." 

Kaspersma, J., C. Doumen, et al. (2002). "Fire retardant mechanism of aliphatic bromine 

compounds in polystyrene and polypropylene." Polymer Degradation and Stability 77: 

325-331. 

Lorenzi, M. and E. Garlaschi (2013). GC SAM: Alternative to HBCD for XPS. Prepared for 

Ninth meeting of the Persistent Organic Pollutants Review Committee Side Event: 

Alternatives to HBCD - state of play. October 14, 2013.

Morose, G. (2006a). An Investigation of Alternatives to Tetrabromobisphenol A (TBBPA) and 

Hexabromocyclododecane (HBCD) Prepared for: The Jennifer Altman Foundation.

Morose, G. (2006b). An Overview of Alternatives to Tetrabromobisphenol A (TBBPA) and 

Hexabromocyclododecane (HBCD). University of Massachusetts Lowell, Lowell Center 

for Sustainable Production.

Nelson, G. L. (1998). "Carbon Monoxide and Fire Toxicity: A Review and Analysis of Recent 

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32(5): 511-518. 

pinfa (2011). Flame Retardants Product Selector and Regulatory Information.

Posner, S. and L. Boras (2005). Survey and technical assessment of alternative to 

Decabromodiphenyl ether (decaBDE) in plastics. The Swedish Chemicals Inspectorate. 

Stockholm.

Sidhu, S., A. Morgan, et al. (2013). Use of Cone Calorimeter to Identify Selected 

Polyhalogenated Dibenzo-P-Dioxins/Furans and Polyaromatic Hydrocarbon Emissions 

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3-12
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19-5)." Integrated Risk Information System Retrieved November 29, 2012, 

from http://www.epa.gov/iris/subst/0035.htm.

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Applications. Cincinnati, Hanser Publications.

3-13
4 Hazard Evaluation of HBCD and Alternatives

This chapter summarizes the toxicological and environmental hazards of 

hexabromocyclododecane (HBCD) and each of the three alternative chemicals that were

identified as potential functional substitutes for HBCD. Evaluations of chemical formulations 

may also include associated substances (e.g., starting materials, by-products, and impurities) if 

their presence is specifically required to allow that alternative to fully function in the assigned 

role. Otherwise, pure substances were analyzed in this assessment. Users of the alternative 

assessments should be aware of the purity of the trade product they purchase, as the presence of 

impurities may alter the assessment of the alternative. This report is a hazard assessment, not a 

risk assessment. Hazard assessment as a risk management tool is discussed in more detail in 

Section 1.4.

Toxicological and environmental endpoints included in the hazard profiles are discussed in 

Section 4.1 along with the criteria used to evaluate each hazard endpoint. Data sources and the 

review methodology are described in Section 4.2. The report then offers a detailed description of 

the utility of physical-chemical properties in understanding hazard in Section 4.3 and the process 

of evaluating human health and environmental endpoints in Sections 4.4 and 4.5, respectively. A 

discussion of the evaluation of endocrine activity is included in Section 4.6. The characteristics 

of each chemical included in the alternatives assessment are summarized in the comparative 

hazard summary table in Section 4.7. Lastly, the collected data and hazard profile of each 

chemical are presented in Section 4.8.

4.1 Toxicological and Environmental Endpoints

The assessment of endpoints with the intent to create hazard profiles for a Design for the 

Environment (DfE) alternatives assessment follows the guidance of the Alternatives Assessment 

Criteria for Hazard Evaluation (U.S. EPA 2011b). The definitions for each endpoint evaluated 

following these criteria are outlined in Section 4.1.1 and the criteria by which these endpoints are 

evaluated are outlined in Section 4.1.2. Lastly, there are endpoints that DfE characterizes but 

does not assign criteria to, and these are summarized in Section 4.1.3.

4.1.1 Definitions of Each Endpoint Evaluated Against Criteria

Hazard designations for each chemical discussed in this report were made by direct comparison 

of the experimental or estimated data to the DfE Alternatives Assessment Criteria for Hazard 

Evaluation (U.S. EPA 2011b). Table 4-1 provides brief definitions of human health toxicity, 

environmental toxicity and environmental fate endpoints.

4-1
Table 4-1. Definitions of Toxicological and Environmental Endpoints for Hazard Assessment

Endpoint 

Category Endpoint Definition

Human Health 

Effects

Acute Mammalian Toxicity

Adverse effects occurring following oral or dermal 

administration of a single dose of a substance, or multiple 

doses given within 24 hours, or an inhalation exposure of 

4 hours.

Carcinogenicity

Capability of a substance to increase the incidence of 

malignant neoplasms, reduce their latency, or increase

their severity or multiplicity.

Mutagenicity/Genotoxicity

Mutagenicity. The ability of an agent to induce permanent, 

transmissible changes in the amount, chemical properties,

or structure of the genetic material. These changes may 

involve a single gene or gene segment, a block of genes, 

parts of chromosomes, or whole chromosomes. 

Mutagenicity differs from genotoxicity in that the change 

in the former case is transmissible to subsequent cell 

generations.

Genotoxicity. The ability of an agent or process to alter 

the structure, information content, or segregation of DNA, 

including those which cause DNA damage by interfering 

with normal replication process, or which in a nonphysiological manner (temporarily) alter its replication. 

Reproductive Toxicity The occurrence of biologically adverse effects on the 

reproductive systems of females or males that may result 

from exposure to environmental agents. The toxicity may 

be expressed as alterations to the female or male 

reproductive organs, the related endocrine system, or 

pregnancy outcomes. The manifestation of such toxicity 

may include, but is not limited to: adverse effects on 

onset of puberty, gamete production and transport, 

reproductive cycle normality, sexual behavior, fertility, 

gestation, parturition, lactation, developmental toxicity, 

premature reproductive senescence or modifications in 

other functions that were dependent on the integrity of the 

reproductive systems.

Developmental Toxicity

Adverse effects in the developing organism that may 

result from exposure prior to conception (either parent), 

during prenatal development, or postnatally to the time of 

sexual maturation. Adverse developmental effects may be 

detected at any point in the lifespan of the organism. The 

major manifestations of developmental toxicity include: 

(1) death of the developing organism, (2) structural 

abnormality, (3) altered growth, and (4) functional 

deficiency. 

Neurotoxicity

An adverse change in the structure or function of the 

central and/or peripheral nervous system following 

exposure to a chemical, physical, or biological agent.

4-2
Endpoint 

Category Endpoint Definition

Repeated Dose Toxicity

Adverse effects (immediate or delayed) that impair 

normal physiological function (reversible and irreversible) 

of specific target organs or biological systems following 

repeated exposure to a chemical substance by any route 

relevant to humans. Adverse effects include biologically 

significant changes in body and organ weights, changes 

that affect the function or morphology of tissues and 

organs (gross and microscopic), mortality, and changes in 

biochemistry, urinalysis, and hematology parameters that 

are relevant for human health; may also include 

immunological and neurological effects.

Respiratory Sensitization Hypersensitivity of the airways following inhalation of a

substance.

Skin Sensitization

A cell-mediated or antibody-mediated allergic response 

characterized by the presence of inflammation that may 

result in cell death, following an initial induction exposure 

to the same chemical substance, i.e., skin allergy.

Eye Irritation/Corrosivity Irritation or corrosion to the eye following the application 

of a test substance.

Dermal Irritation/Corrosion

Dermal irritation - reversible damage to the skin following 

the application of a test substance for up to 4 hours. 

Dermal corrosion - irreversible damage to the skin 

namely, visible necrosis through the epidermis and into 

the dermis following the application of a test substance for 

up to 4 hours.

Environmental 

Toxicity 

Environmental toxicity refers to adverse effects observed in living organisms that typically inhabit 

the wild; the assessment is focused on effects in three groups of surrogate aquatic organisms 

(freshwater fish, invertebrates, and algae).

Aquatic Toxicity (Acute) The property of a substance to be injurious to an organism 

in a short-term (days), aquatic exposure to that substance.

Aquatic Toxicity (Chronic)

The property of a substance to cause adverse effects to 

aquatic organisms during aquatic exposures which were 

determined in relation to the life cycle of the organism. 

Environmental 

Fate

Environmental Persistence

The length of time the chemical exists in the environment, 

expressed as a half-life, before it is destroyed (i.e., 

transformed) by natural or chemical processes. For 

alternative assessments, the amount of time for complete 

assimilation (ultimate removal) is preferred over the initial 

step in the transformation (primary removal).

Bioaccumulation The process in which a chemical substance is absorbed in 

an organism by all routes of exposure as occurs in the 

natural environment (e.g., dietary and ambient 

environment sources). Bioaccumulation is the net result of 

competing processes of chemical uptake into the organism 

at the respiratory surface and from the diet and chemical 

elimination from the organism including respiratory 

exchange, fecal egestion, metabolic biotransformation of 

the parent compound, and growth dilution.

4-3
The hazard profile for each chemical contains endpoint-specific summary statements (see

Section 4.8). For each of the endpoints listed in Table 4-1, these summary statements provide the 

hazard designation, the type of data (experimental or estimated) and the rationale. The endpoint 

summaries may also include explanatory comments, a discussion of confounding factors or an 

indication of the confidence in the data to help put the results in perspective.

4.1.2 Criteria

Table 4-2 summarizes the criteria that were used by DfE to interpret the data presented in the 

hazard profiles. The same criteria are used to evaluate hazard for all alternatives assessments 

conducted by DfE since 2011. These criteria, collectively known as DfE Alternatives Assessment 

Criteria for Hazard Evaluation, underwent Agency-wide and public comment, and were 

finalized in 2011 (U.S. EPA 2011b). A hazard designation for each human health endpoint was 

not given for each route of exposure but rather was based on the exposure route with the highest 

hazard designation. Data may have been available for some or all relevant routes of exposure. 

The details as to how each endpoint was evaluated are described below and in the DfE full 

criteria document, DfE Alternatives Assessment Criteria for Hazard Evaluation, available 

at: http://www.epa.gov/dfe/alternatives_assessment_criteria_for_hazard_eval.pdf.

4-4
Table 4-2. Criteria Used to Assign Hazard Designations

Endpoint Very High High Moderate Low Very Low

Human Health Effects

Acute mammalian toxicity

Oral median lethal dose 

(LD50) (mg/kg) ≤50 >50–300 >300–2000 >2000 –

Dermal LD50 (mg/kg) ≤200 >200–1000 >1000–2000 >2000 –

Inhalation median lethal 

concentration (LC50) -

vapor/gas

(mg/L)

≤2 >2–10 >10–20 >20 –

Inhalation LC50 - dust/mist/

fume (mg/L) ≤0.5 >0.5–1.0 >1–5 >5 –

Carcinogenicity

Carcinogenicity

Known or 

presumed 

human 

carcinogen

Equivalent to 

Globally 

Harmonized 

System of 

Classification 

and Labeling of 

Chemicals 

(GHS) 

Categories 1A 

and 1B

Suspected 

human 

carcinogen 

Equivalent to 

GHS Category 

2

Limited or 

marginal 

evidence of 

carcinogenicity 

in animals

And inadequate 

evidence in 

humans

Negative studies 

or robust 

mechanismbased Structure

Activity 

Relationship 

(SAR)

As described 

above

–

Mutagenicity/Genotoxicity

Germ cell mutagenicity

GHS Category 

1A or 1B: 

Substances 

known to 

induce heritable 

mutations or to 

be regarded as 

if they induce 

heritable 

mutations in the 

germ cells of 

humans 

GHS Category 

2: Substances 

which cause 

concern for 

humans owing 

to the 

possibility that 

they may 

induce heritable 

mutations in the 

germ cells of 

humans 

OR

Evidence of 

mutagenicity 

supported by 

positive results 

in in vitro OR in 

vivo somatic 

cells of humans 

or animals 

Negative for 

chromosomal 

aberrations and 

gene mutations, 

or no structural 

alerts. 

--

4-5
Endpoint Very High High Moderate Low Very Low

Mutagenicity and 

genotoxicity in somatic 

cells

Evidence of 

mutagenicity 

supported by 

positive results 

in in vitro AND 

in vivo somatic 

cells and/or 

germ cells of 

humans or 

animals

Reproductive toxicity

Oral (mg/kg/day) – <50 50–250 >250-1000 >1000

Dermal (mg/kg/day) – <100 100–500 >500-2000 >2000

Inhalation - vapor, gas 

(mg/L/day) – <1 1–2.5 >2.5-20 >20

Inhalation - dust/mist/fume 

(mg/L/day) – <0.1 0.1–0.5 >0.5-5 >5

Developmental toxicity

Oral (mg/kg/day) – <50 50–250 >250-1000 >1000

Dermal (mg/kg/day) – <100 100–500 >500-2000 >2000

Inhalation - vapor, gas 

(mg/L/day) – <1 1–2.5 >2.5-20 >20

Inhalation - dust/mist/fume 

(mg/L/day) – <0.1 0.1–0.5 >0.5-5 >5

Neurotoxicity

Oral (mg/kg/day) – <10 10–100 >100 –

Dermal (mg/kg/day) – <20 20–200 >200 –

Inhalation - vapor, gas 

(mg/L/day) – <0.2 0.2–1.0 >1.0 –

Inhalation - dust/mist/fume 

(mg/L/day) – <0.02 0.02–0.2 >0.2 –

Repeated-dose toxicity

Oral (mg/kg/day) – <10 10–100 >100 –

Dermal (mg/kg/day) – <20 20–200 >200 –

Inhalation - vapor, gas 

(mg/L/day) – <0.2 0.2–1.0 >1.0 –

Inhalation - dust/mist/fume 

(mg/L/day) – <0.02 0.02–0.2 >0.2 –

Sensitization

Skin sensitization –

High frequency 

of sensitization 

in humans 

and/or high 

potency in 

animals (GHS 

Category 1A)

Low to moderate 

frequency of 

sensitization in 

human and/or 

low to moderate 

potency in 

animals (GHS 

Category 1B)

Adequate data 

available and not 

GHS Category 

1A or 1B

–

4-6
Endpoint Very High High Moderate Low Very Low

Respiratory sensitization –

Occurrence in 

humans or 

evidence of 

sensitization in 

humans based 

on animal or 

other tests 

(equivalent to 

GHS Category 

1A and 1B)

Limited 

evidence 

including the 

presence of 

structural alerts

Adequate data 

available 

indicating lack 

of respiratory 

sensitization

–

Irritation/corrosivity

Eye irritation/corrosivity

Irritation 

persists for 

>21 days or 

corrosive

Clearing in 8–

21 days, 

severely 

irritating

Clearing in 

≤7 days, 

moderately 

irritating

Clearing in 

<24 hours, 

mildly irritating

Not irritating

Skin irritation/corrosivity Corrosive

Severe 

irritation at 

72 hours

Moderate 

irritation at 

72 hours

Mild or slight 

irritation at 

72 hours

Not irritating

Endocrine activity

Endocrine Activity For this endpoint, High/Moderate/Low etc. characterizations will not apply. A 

qualitative assessment of available data will be prepared.

Environmental Toxicity and Fate

Aquatic toxicity

Acute aquatic toxicity –

LC50 or half maximal 

effective concentration 

(EC50) (mg/L)

<1.0 1–10 >10–100

>100 or No 

Effects at 

Saturation

(NES)

–

Chronic aquatic toxicity –

lowest observed effect 

concentration (LOEC) or 

chronic value (ChV)

(mg/L)

<0.1 0.1–1 >1–10 >10 or NES –

Environmental persistence

Persistence in water, soil, 

or sediment

Half-life 

>180 days or 

recalcitrant

Half-life of 60–

180 days

Half-life <60 

but ≥16 days

Half-life 

<16 days OR 

passes Ready 

Biodegradability 

test not 

including the 

10-day window. 

No degradation 

products of 

concern.

Passes Ready 

Biodegradability 

test with 10-day 

window. No 

degradation 

products of 

concern.

Persistence in air (half-life 

days)

For this endpoint, High/Moderate/Low etc. characterizations will not apply. A 

qualitative assessment of available data will be prepared.

4-7
Endpoint Very High High Moderate Low Very Low

Bioaccumulation 

Bioconcentration Factor 

(BCF)/Bioaccumulation 

Factor (BAF)

>5000 5000–1000 <1000–100 <100 –

Log BCF/BAF >3.7 3.7–3 <3-2 <2 –

Very High or Very Low designations (if an option for a given endpoint in Table 4-2) were assigned only when there were experimental data 

located for the chemical under evaluation. In addition, the experimental data must have been collected from a well conducted study specifically 

designed to evaluate the endpoint under review. If the endpoint was estimated using experimental data from a close structural analog, by 

professional judgment, or from a computerized model, then the next-level designation was assigned (e.g., use of data from a structural analog 

that would yield a designation of very high would result in a designation of high for the chemical in review). One exception is for the estimated 

persistence of polymers with an average molecular weight (MW) >1,000 daltons, which may result in a Very High designation. 

4.1.3 Endpoints Characterized but Not Evaluated

Several additional endpoints were characterized, but not evaluated against hazard criteria. This is 

because the endpoints lacked a clear consensus concerning the evaluation criteria (endocrine 

activity), data and expert judgment were limited for industrial chemicals (persistence in air, 

terrestrial ecotoxicology), or the information was valuable for the interpretation of other toxicity 

and fate endpoints (including toxicokinetics and transport in the environment).

Table 4-3. Definitions of Endpoints and Information Characterized but Not Evaluated Against Hazard 

Criteria

Toxicological Endpoint Definition

Toxicokinetics

The determination and quantification of the time course of absorption, distribution, 

biotransformation, and excretion of chemicals (sometimes referred to as 

pharmacokinetics). 

Biomonitoring 

Information

The measured concentration of a chemical in biological tissues where the analysis 

samples were obtained from a natural or non-experimental setting. 

Environmental Transport

The potential movement of a chemical, after it is released to the environment, within 

and between each of the environmental compartments, air, water, soil, and sediment. 

Presented as a qualitative summary in the alternative assessment based on physicalchemical properties, environmental fate parameters, and simple volatilization models. 

Also includes distribution in the environment as estimated from a fugacity model1.

Persistence in Air

The half-life for destructive removal of a chemical substance in the atmosphere. The 

primary chemical reactions considered for atmospheric persistence include hydrolysis, 

direct photolysis, and the gas phase reaction with hydroxyl radicals, ozone, or nitrate 

radicals. Results are used as input into the environmental transport models.

Immunotoxicology

Adverse effects on the normal structure or function of the immune system caused by 

chemical substances (e.g., gross and microscopic changes to immune system organs, 

suppression of immunological response, autoimmunity, hypersensitivity, 

inflammation, and disruption of immunological mechanistic pathways).

Terrestrial Ecotoxicology

Reported experimental values from guideline and nonguideline studies on adverse 

effects on the terrestrial environment. Studies on soil, plants, birds, mammals, 

invertebrates were also included.

Endocrine Activity

A change in endocrine homeostasis caused by a chemical or other stressor from 

human activities (e.g., application of pesticides, the discharge of industrial chemicals 

to air, land, or water, or the use of synthetic chemicals in consumer products.) 1

A fugacity model predicts partitioning of chemicals among air, soil, sediment, and water under steady state 

conditions for a default model “environment” (U.S. EPA 2012c).

4-8
4.2 Data Sources and Assessment Methodology

This section explains how data were collected (Section 4.2.1), prioritized, and reviewed (Section 

4.2.2) for use in the development of hazard profiles. High-quality experimental studies lead to a 

thorough understanding of behavior and effects of the chemical in the environment and in living 

organisms. Analog approaches and SAR-based estimation methods are also useful tools and are 

discussed throughout this section. Information on how the alternative butadiene styrene 

brominated copolymer included in this assessment differs from discrete chemicals in terms of 

how it was evaluated is presented in Section 4.2.3.

4.2.1 Identifying and Reviewing Measured Data

For each chemical assessed, data were collected in a manner consistent with the High Production 

Volume (HPV) Chemical Challenge Program Guidance (U.S. EPA 1999b) on searching for 

existing chemical information. This process resulted in a comprehensive search of the literature 

for available experimental data. For chemicals well characterized by experimental studies, this 

usually resulted in the collection of recent high-quality reviews or peer-reviewed risk 

assessments. These were supplemented by primary searches of scientific literature published 

after these secondary sources were released, which is explained in greater detail below. For 

chemicals that are not as well characterized, that is, where these secondary sources were not 

available or lacked relevant or adequate data, a comprehensive search of the primary scientific 

literature was done. Subsequently, these searches led to the collection and review of articles from 

the scientific literature, industrial submissions, encyclopedic sources, and government reports. In 

addition, data presented in EPA public databases (e.g., integrated risk information system (IRIS); 

the High Production Volume Information System) and confidential databases were obtained for 

this project. Generally, foreign language (non-English) reports were not used unless they 

provided information that was not available from other sources.

Chemical assessments were performed by first searching for experimental data for all endpoints 

in Table 4-1. For the three alternatives assessed, high-quality secondary sources were not 

available; therefore, a comprehensive search of the literature was performed to identify 

experimental data. In some cases, confidential studies were also submitted to EPA by chemical 

manufacturers available to support hazard designations. For those chemicals that were expected 

to form stable metabolites or degradation products, searches were performed to identify relevant 

fate and toxicity information for the metabolite or degradation product.

Well Studied Chemicals – Literature Search Strategy

As mentioned above, for chemicals that have been well studied, limited to HBCD in this 

Alternatives Assessment, the literature review focused primarily on the use of secondary sources, 

such as Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profiles or 

EPA’s Integrated Risk Information System (IRIS) assessments. For HBCD, an Australian 

National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (National 

Industrial Chemicals Notification and Assessment Scheme 2012), an Organisation for Economic 

Co-operation Development (OECD) Screening Information Dataset Initial Assessment Profile 

4-9
(SIAP) from 2007 (Organisation for Economic Co-Operation and Development (OECD) 2007), a 

National Academy of Sciences National Research Council (National Research Council 2000)

risk assessment, a European Communities (European Commission 2008; Scientific Committee 

on Health and Environmental Risks (SCHER) 2008b; Scientific Committee on Health and 

Environmental Risks (SCHER) 2008a) assessment, and a Screening Assessment by Environment 

Canada/Health Canada (Environment Canada 2011) were available. Using high-quality 

secondary sources maximized available resources and eliminated potential duplication of effort. 

However, more than one secondary source was typically used to verify reported values, which 

also reduced the potential for presenting a value that was transcribed incorrectly from the 

scientific literature. Although other sources might also contain the same experimental value for 

an endpoint, effort was not focused on building a comprehensive list of these references, as it 

would not have enhanced the ability to reach a conclusion in the assessment. When data for a 

selected endpoint could not be located in a secondary source for an otherwise well studied 

chemical, the primary literature was searched by endpoint and experimental studies were 

assessed for relevant information.

Making Predictions in the Absence of Measured Data

In the absence of primary or secondary data, hazard designations were based on (1) Quantitative 

Structure Activity Relationships (QSAR)-based estimations from the EPA New Chemical 

Program’s predictive methods; (2) analog data; (3) class-based assignments from the EPA 

Chemical Categories document; and (4) expert judgment by EPA subject matter experts.

For chemicals that lacked experimental information, QSAR assessments were made using either 

EPA’s Estimation Programs Interface (EPISuiteTM) for physical-chemical property and 

environmental fate endpoints or EPA’s Ecological Structure Activity Relationships 

(ECOSARTM) QSARs for ecotoxicity. For the cancer endpoint, EPA’s OncoLogic expert system

was consulted, but did not provide results for HBCD or the alternatives because an appropriate 

chemical class was not available within the model to evaluate these chemicals. These estimation 

methods have been automated, and are available for free (U.S. EPA 2012d). Often analog data 

were used to support predictions from models. These approaches were described in the EPA 

Pollution Prevention (P2) Framework and Sustainable Futures (SF) program (U.S. EPA 2005b; 

U.S. EPA 2012c).

For some physical-chemical properties that could not be estimated using EPISuiteTM, such as 

acid/base dissociation constants, other available methods (e.g., the SPARC Performs Automated 

Reasoning in Chemistry (SPARC) website for dissociation constants) were used. All estimation 

methods employed were limited to those freely available in the public domain. 

The methodology and procedures used to evaluate a polymer are described in Section 4.2.3. The 

endpoints for impurities and oligomers with a MW >1,000 daltons were estimated using 

professional judgment and the results assessed for inclusion in the overall hazard designation. 

This process is described, as appropriate, under the corresponding endpoints appearing in Section 

4.3.

When QSAR models were not available, professional judgment was used to identify hazards for 

similar chemicals using the guidance from EPA’s New Chemicals Categories (U.S. EPA 2010b). 

4-10
The categories identify substances that share chemical and toxicological properties and possess 

potential health or environmental concerns (U.S. EPA 2010a). In the absence of an identified 

category, analogs for which experimental data are available were identified using EPA’s Analog 

Identification Methodology (AIM) or by substructure searches of confidential EPA databases

(U.S. EPA 2012a). If a hazard designation was still not available, the expert judgment of 

scientists from EPA’s New Chemical Program would provide an assessment of the physicalchemical properties, environmental fate, aquatic toxicity, and human health endpoints to fill 

remaining data gaps.

4.2.2 Hierarchy of Data Adequacy 

Once the studies were obtained, they were evaluated to establish whether the hazard data were of 

sufficient quality to meet the requirements of the assessment process. The adequacy and quality 

of the studies identified in the literature review are described in the Data Quality field of the 

chemical assessments presented in Section 4.8. The tiered approach described below represents a 

general preferred data hierarchy, but the evaluation of toxicological data also requires flexibility 

based on expert judgment.

1. One or more studies conducted in a manner consistent with established testing 

guidelines

2. Experimentally valid but nonguideline studies (i.e., do not follow established testing 

guidelines)

3. Reported data without supporting experimental details

4. Estimated data using SAR methods or professional judgment based on an analog 

approach

5. Expert judgment based on mechanistic and structural considerations

In general, data were considered adequate to characterize an endpoint if they were obtained using 

the techniques identified in the HPV data adequacy guidelines (U.S. EPA 1999b). Studies 

performed according to Harmonized EPA or OECD guidelines were reviewed to confirm that the 

studies followed all required steps.

Experimental studies published in the open literature were reviewed for their scientific rigor and 

were also compared and contrasted to guideline studies to identify potential problems arising 

from differences in the experimental design. Data from adequate, well-performed, experimental 

studies were used to assign hazard designations in preference to those lacking sufficient 

experimental detail. When multiple adequate studies were available for a given endpoint, any 

discrepancies that were identified within the set of data were examined further and addressed 

using a weight-of-evidence approach that was described in the data entry to characterize the 

endpoint whenever possible. 

When available, experimental data from guideline or well-performed experimental studies were 

preferred (Items 1 and 2 in the hierarchy list). Information from secondary sources such as

Material Safety Data Sheets or online databases (such as the National Library of Medicine’s 

Hazardous Substances Data Bank, Item 3 in the hierarchy list) was considered appropriate for 

some endpoints when it included numerical values for effect levels that could be compared to the 

evaluation criteria. 

4-11
4.2.3 Assessment of Polymers

The methodology and procedures used to assess the polymer (butadiene styrene brominated 

copolymer) in this assessment were slightly different than those used for discrete compounds and 

simple mixtures. Using the literature search techniques discussed above in Section 4.2.1 

experimental data for the polymer were identified for many, but not all, of the endpoints. 

Estimations, using professional judgment as presented in the polymer assessment literature, were 

used in instances where there was an absence of experimental data (Boethling and Nabholz 

1997).

Polymers are a mixture of molecules with a distribution of components (e.g., different chain 

lengths) that depend on the monomers used, their molar ratios, the total number of monomeric 

units in the polymer chain, and the manufacturing conditions. To account for this variation, the 

average MW profile (also referred to as the number average molecular weight MWn) was used in 

the assessment as the individual chains rarely have the same degree of polymerization and 

weight yet their physical, chemical, and environmental properties are essentially identical for the 

purposes of this assessment. The polymer evaluated as an alternative, Butadiene styrene brominated 

copolymer, typically has an average MWs ranging from 60,000 to 160,000 daltons.

4.3 Importance of Physical and Chemical Properties, Environmental Transport, and 

Biodegradation

Physical-chemical properties provide basic information on the characteristics of a chemical 

substance and were used throughout the alternatives assessment process. These endpoints 

provide information required to assess potential environmental release, exposure, and 

partitioning as well as insight into the potential for adverse toxicological effects. The physicalchemical properties are provided in the individual chemical hazard profiles presented in Section 

4.8. For information on how key physical-chemical properties of alternatives can be used to 

address the potential for human and environmental exposure, please refer to Table 4-1. 

Descriptions of relevant physical-chemical properties and how they contribute to the hazard 

assessments are presented below.

Molecular Weight (MW)

MW informs how a chemical behaves in a physical or biological system including bioavailability 

and environmental fate. In general, but not strictly, larger compounds tend to be less mobile in 

biological and environmental systems. Their large size restricts their transport through biological 

membranes and lowers their vapor pressure. Polymers are mixtures that contain a distribution of 

components and typically do not have a unique MW (see also Section 4.2.3). To account for 

variation in these mixtures, the average MW or MWn, determined experimentally (typically 

using high pressure liquid chromatography, viscosity, or light-scattering), is used in the 

assessment of the polymer. The assessment of a polymer also includes analysis of oligomers and 

unchanged monomers (starting materials) that have MW of <1,000 daltons as these can often be 

the highest concern materials (bioavailable substances) in the mixture. The butadiene styrene 

4-12
brominated copolymer evaluated in this assessment is not expected to contain a significant 

amount of oligomers or unchanged monomers based on its method of manufacture.

Melting Point and Boiling Point 

These two properties provide an indication of the physical state of the material at ambient 

temperature. Chemicals with a melting point more than 25°C were assessed as a solid. Those

substances with a melting point less than 25°C and a boiling point more than 25°C were assessed 

as a liquid and those with a boiling point less than 25°C were assessed as a gas. The physical 

state was used throughout the assessment, such as in the determination of potential routes of 

human and environmental exposure, as described in Section 5.2. The melting and boiling points 

were also useful in determining the potential environmental fate, ecotoxicity, and human health 

hazards of a chemical. For example, organic compounds with high melting points generally have 

low water solubility and low rates of dissolution. These properties influence a material’s 

bioavailability and were therefore taken into account in both the assessment process and the 

evaluation of experimental studies. Similarly, chemicals with a low melting point also have a 

higher potential to be absorbed through the skin, gastrointestinal tract, and lungs. 

In the absence of experimental data, the melting point value was not reported and no estimations 

were performed. If a chemical decomposes before it melts, this information was included in the 

assessment. For boiling point, the maximum value reported in the assessment was 300°C for 

high boiling materials including the butadiene styrene brominated copolymer (U.S. EPA 1999b).

A melting point for the butadiene styrene brominated copolymer was not reported as this type of 

material typically reaches a softening point and does not undergo the phase change associated 

with melting (i.e., solid to liquid). 

Vapor Pressure 

Vapor pressure is useful in determining the potential for a chemical substance to volatilize to the 

atmosphere from dry surfaces, from storage containers, or during mixing, transfer, or 

loading/unloading operations (see Section 5.2). In the assessment process, chemicals with a 

vapor pressure less than 1x10-6 mm Hg have a low potential for inhalation exposure resulting 

from gases or vapors. Vapor pressure is also useful for determining the potential environmental 

fate of a substance. Substances with a vapor pressure more than 1x10-4 mm Hg generally exist in 

the gas phase in the atmosphere. Substances with a vapor pressure between 1x10-4 and 1x10-8

mm Hg exist as a gas/particulate mixture. Substances with a vapor pressure less than 1x10-8 mm 

Hg exist as a particulate. The potential atmospheric degradation processes described below in the 

reactivity section generally occur when a chemical exists in the gas phase. Gases in the 

atmosphere also have the potential to travel long distances from their original point of release. 

Materials in the liquid or solid (particulate) phases in the atmosphere generally undergo 

deposition onto the Earth’s surface.

A maximum vapor pressure of 1x10-8 mm Hg was assigned for chemicals without experimental 

data or for those substances that were anticipated by professional judgment to be nonvolatile

(U.S. EPA 1999b). The maximum vapor pressure of 1x10-8 mm Hg was also the default value 

4-13
reported for the vapor pressure of the butadiene styrene brominated copolymer as it has a MW 

>1,000 daltons.

Water Solubility 

The water solubility of a chemical provides an indication of its distribution between 

environmental media, potential for environmental exposure through release to aquatic 

compartments, and potential for human exposure through ingestion of drinking water. Water 

solubility was also used extensively to determine potential human health and ecotoxicity hazards. 

In general, chemicals with water solubility less than 1x10-5 g/L indicate a lower concern for both 

the expression of adverse effects, and potential aquatic and general population exposure due to 

their low bioavailability. However, chemicals with low bioavailability also tend to be more 

environmentally persistent. Low bioavailability is different than no bioavailability, and the two 

should not be used interchangeably.

Within the context of this alternatives assessment, the following descriptors were used according 

to ranges of water solubility values: more than 10,000 mg/L was considered very soluble; 

1,000–10,000 mg/L represents soluble; 100–1,000 mg/L represents moderately soluble, 1–100 

mg/L represents slightly soluble, and less than 1 mg/L represents insoluble, noting that these 

guidelines might not match what is used elsewhere within the scientific literature for other 

disciplines. Chemicals with higher water solubility were more likely to be transported into 

groundwater with runoff during storm events, be absorbed through the gastrointestinal tract or 

lungs, partition to aquatic compartments, undergo atmospheric removal by rain washout, and 

possess a greater potential for human exposure through the ingestion of contaminated drinking 

water. Chemicals with lower water solubility are generally more persistent and have a greater 

potential to bioconcentrate. 

The water solubility of a substance was also used to evaluate the quality of experimental aquatic 

toxicity and oral exposure human health studies as well as the reliability of aquatic toxicity 

estimates. If the water solubility of a substance was lower than the reported exposure level in 

these experiments, then the study was likely to be regarded as inadequate due to potentially 

confounding factors arising from the presence of un-dissolved material. For aquatic toxicity 

estimates obtained using SARs, when the estimated toxicity was higher than a chemical’s water 

solubility (i.e., the estimated concentration in water at which adverse effects appear cannot be 

reached because it was above the material’s water solubility), the chemical was described as 

having NES. An NES designation is equivalent to a Low ecotoxicity hazard designation for that 

endpoint.

Chemicals without experimental data or chemicals that were anticipated by professional 

judgment to be sufficiently insoluble and thus were not bioavailable were assigned a water 

solubility maximum value of 1x10-3 mg/L (U.S. EPA 1999b). A water solubility of 1x10-3 mg/L

is the default value used for discrete organics as well as a non-ionic polymer with a MW >1,000 

daltons according to information contained in the literature concerning polymer assessment 

(Boethling and Nabholz 1997). This assignment is consistent with an analysis of the chemicals 

used in the development of the water solubility estimation program in EPA’s EPISuiteTM

software. The training set for this model included 1,450 chemicals with a MW range 27-628 

4-14
daltons and experimental water solubilities ranging from miscible to 4x10-7 mg/L (Meylan, 

Howard et al. 1996; U.S. EPA 2011h). Given that water solubility decreases with MW, a default 

value of 1x10-3 mg/L is consistent with the limited bioavailability expected for materials with a 

MW >1,000 daltons. 

Octanol/Water Partition Coefficient (Kow)

The octanol/water partition coefficient, commonly expressed as its log value (i.e., log Kow) is 

one of the most useful properties for performing a hazard assessment. The log Kow indicates the 

partitioning of a chemical between octanol and water, where octanol is used to mimic fat and 

other hydrophobic components of biological systems. Chemicals with a log Kow less than 1 are 

highly soluble in water (hydrophilic), while those with a log Kow more than 4 are not very 

soluble in water (hydrophobic). A log Kow more than 8 indicates that the chemical is not readily 

bioavailable and is essentially insoluble in water. In addition, a log Kow greater than 

approximately 8 may be difficult to obtain experimentally.

The log Kow can be used as a surrogate for the water solubility in a hazard assessment and is 

frequently used to estimate the water solubility if an experimental value is not available. It can 

also be used to estimate other properties important to the assessment, including bioconcentration 

and soil adsorption, and is a required input for SAR models used to estimate ecotoxicity values.

 

For chemicals without data, that are not within the domain of EPISuiteTM or that were expected

to be insoluble in water (WS <1x10-3 mg/L), a minimum value of 10 was assigned for the log 

Kow (U.S. EPA 1999b). Insoluble chemicals that could be run through EPISuiteTM software may 

use a log Kow >10 if the result appeared to be valid based on expert review. This assignment is 

consistent with an analysis of the chemicals (“training set”) used in the development of the 

octanol/water partition coefficient estimation program in the EPISuiteTM software. The training 

set for this model included 10,946 chemicals with a MW range 18-720 daltons and experimental 

log Kows ranging from -3.89 to 8.70 (Meylan and Howard 1995; U.S. EPA 2011g). Given that 

log Kow increases with MW, a default value of 10 is consistent with the limited bioavailability 

expected for materials with a MW >1,000 daltons. A maximum log Kow of -2 was used for water 

soluble materials. For most polymers and other materials that are anticipated to be insoluble in 

both water and octanol, the log Kow cannot be measured and it was therefore not listed for the 

butadiene styrene brominated copolymer evaluated in this assessment.

Flammability (Flash Point)

The flash point of a substance is defined as the minimum temperature at which the substance 

emits sufficient vapor to form an ignitable mixture with air. Flash point can be used to identify 

hazards associated with the handling of volatile chemicals. Substances with a flash point above 

37.8°C (100°F) were commonly referred to as non-flammable, as this is the flammability 

definition used in the shipping industry. There are exceptions to this definition such as chemicals 

that may form explosive mixtures in the presence of air. 

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Explosivity

Explosivity refers to the potential for a chemical to form explosive mixtures in air and can be 

defined using the limits of flammability. The lower limit of flammability (LFL) is defined as the 

minimum concentration of a combustible substance that is capable of propagating a flame 

through a homogenous mixture in the presence of an ignition source. The upper limit of 

flammability (UFL) is similarly defined as the highest concentration that can propagate a flame. 

LFLs and UFLs are commonly reported as the volume percent or volume fraction of the 

flammable component in air at 25°C. If the ambient air concentration of the gas (or vapor) is 

between the upper and lower explosion limit, then the material has the potential to explode if it 

comes in contact with an ignition source. Knowledge regarding the explosivity of a given 

material in air is also useful in identifying potential hazards associated with the manufacture and 

use of that material.

pH

The pH scale measures how acidic or basic a substance is on a range from 0 to 14. A pH of 7 is 

neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. This scale is used primarily 

to identify potential hazards associated with skin or eye contact with a chemical or its aqueous 

solutions. The corrosive nature of chemicals that form either strongly basic (high pH) or strongly 

acidic (low pH) solutions are generally likely to result in harm to skin and other biological 

membranes. For corrosive chemicals, some experimental studies, such as biodegradation tests, 

require additional analysis to determine if the tests were performed at concentrations that cause 

harm to microbes in the test (and, therefore, may result in incorrectly identifying a chemical as 

persistent in the environment). For chemicals that form moderately basic or acidic solutions in 

water, the pH of the resulting solution can be used in lieu of a measured dissociation constant. 

None of the chemicals evaluated in this assessment are expected to dissociate in water.

Dissociation Constant in Water (pKA)

The dissociation constant determines if a chemical will ionize under environmental conditions. 

The dissociation constant in water provides the amount of the dissociated and undissociated 

forms of an acid, base, or organic salt in water. Knowledge of the dissociation constant is 

required to assess the importance of the other physical-chemical properties used in the hazard 

assessment. As the percentage of ionization increases, the water solubility increases while the 

vapor pressure, Henry’s Law constant, and octanol/water partition coefficient decrease. For acids 

and bases, the dissociation constant is expressed as the pKA and pKB, respectively. None of the 

chemicals evaluated in this assessment are expected to ionize in water.

Henry’s Law Constant

Henry’s Law constant is the ratio of a chemical’s concentration in the gas phase to that in the 

liquid phase (at equilibrium). In environmental assessments, the Henry’s Law constant is 

typically measured in water at 25°C. The Henry’s Law constant provides an indication of a 

chemical’s volatility from water, which can be used to derive partitioning within environmental 

compartments and the amount of material removed by stripping in a sewage treatment plant. 

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Henry’s Law constant values less than 1x10-7 atm-m3

/mole indicate slow volatilization from 

water to air (the Henry’s Law constant for the volatilization of water from water is 1x10-7 atmm3

/mole) and values more than 1x10-3 atm-m3/mole indicate rapid volatilization from water to 

air. To aid in determining the importance of volatilization, the assessment uses two models based 

on the Henry’s Law constant. These models determine the half-life for volatilization from a 

model river and a model lake. A maximum value of 1x10-8 atm-m3

/mole for the Henry’s Law 

constant was assigned for chemicals without experimental data or for those that were anticipated 

by professional judgment to be nonvolatile. 

Sediment/Soil Adsorption/Desorption Coefficient (Koc)

The soil adsorption coefficient provides a measure of a chemical’s ability to adsorb to the 

organic portion of soil and sediment. This provides an indication of the potential for the chemical 

to leach through soil and be introduced into groundwater, which may lead to environmental 

exposures to wildlife or humans through the ingestion of drinking water drawn from 

underground sources. Chemicals with high soil adsorption coefficients are expected to be 

strongly adsorbed to soil and are unlikely to leach into ground water. The soil adsorption 

coefficient also describes the potential for a chemical to partition from environmental waters to 

suspended solids and sediment. The higher the Koc, the more strongly a chemical is adsorbed to 

soil. Strong adsorption may impact other fate processes, such as the rate of biodegradation, by 

making the chemical less bioavailable. 

The soil adsorption coefficient, Koc, is normalized with respect to the organic carbon content of 

the soil to account for geographic differences. The assignments for the degree that a chemical is 

adsorbed to soil within the context of the assessment were described qualitatively as very strong 

(above 30,000), strong (above 3,000), moderate (above 300), low (above 30), and negligible 

(above 3). When determining the potential for a chemical to adsorb to soil and suspended organic 

matter, the potential for a chemical to form chemical bonds with humic acids and attach to soil 

also needs to be considered, although this process is generally limited to a small number of 

chemical classes.

A maximum value of 30,000 for the Koc was assigned for chemicals without experimental data 

or for those that were anticipated by estimation models or professional judgment to be strongly 

absorbed to soil (U.S. EPA 2005b). A default Koc of 30,000 was also assigned for the butadiene 

styrene brominated copolymer because it has a MW >1,000 daltons. 

Reactivity

The potential for a substance to undergo irreversible chemical reactions in the environment can 

be used in the assessment of persistence. The primary chemical reactions considered in an 

environmental fate assessment are: hydrolysis, photolysis, and the gas phase reaction with 

hydroxyl radicals, ozone, or nitrate radicals. The most important reaction considered in the 

hazard assessment of organic compounds is hydrolysis, or the reaction of a chemical substance 

with water. Because the rate of hydrolysis reactions can change substantially as a function of pH, 

studies performed in the pH range typically found in the environment (pH 5–9) were considered. 

The second reaction considered in the assessment is photolysis, the reaction of a chemical with 

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sunlight. Both hydrolysis and photolysis occur in air, water, and soil, while only hydrolysis was 

considered in sediment. The half-lives for reactive processes, if faster than removal via 

biodegradation, were used to assign the hazard designation by direct comparison to the DfE 

persistence criteria.

For the atmospheric compartment, persistence also includes the evaluation of oxidative gasphase processes. These processes include the reaction with ozone, hydroxyl radicals, and nitrate 

radicals. Since the average concentration of these oxidative species in the atmosphere has been 

measured, the experimental or estimated rate constants were converted to, and reported as, a 

half-life in the assessment using standard pseudo first-order kinetics (U.S. EPA 2011e; U.S. EPA 

2011d).

Environmental Transport

The persistence of a chemical substance is based on determining the importance of removal 

processes that may occur once a chemical enters the environment. As noted in Section 4.3, 

chemicals with a half-life of less than 60 days are expected to be at most a Moderate hazard 

designation for persistence. Persistence does not directly address the pathways in which a 

chemical substance might enter the environment (e.g., volatilization or disposal in a landfill) and 

focuses instead on the removal processes that are expected to occur once it is released into air, 

water, soil, or sediment. Similarly, the persistence assessment does not address what might 

happen to a chemical substance throughout its life cycle, such as disposal during incineration of 

consumer or commercial products. Understanding the environmental transport of a chemical 

substance can help identify processes relevant to environmental assessment. For example, if a 

chemical is toxic to benthic organisms and partitions primarily to sediment, its potential release 

to water should be carefully considered in the selection of alternatives.

Biodegradation

In the absence of rapid hydrolysis or other chemical reactions, biodegradation is typically the 

primary environmental degradation process for organic compounds. Determining the importance 

of biodegradation is, therefore, an important component of the assessment. Biodegradation 

processes are divided into two types. The first is primary biodegradation, in which a chemical 

substance is converted to another substance. The second is ultimate biodegradation, in which a 

chemical is completely mineralized to small building-block components (e.g., CO2 and water). 

DfE persistence criteria use data that are reported as percent of theoretical ultimate degradation

in the guideline Ready Biodegradability test or as a half-life in other experimental studies; both 

of these measurements can be compared directly to the DfE criteria in 4.1.2. When considering 

primary degradation, the assessment process includes an evaluation of the potential for the 

formation of metabolites that were more persistent than the parent materials. Chemical 

substances that undergo rapid primary degradation but only slow ultimate biodegradation were 

considered to have stable metabolites. In the absence of measured data on the substance of 

interest, DfE evaluated the potential for biodegradation for chemicals with a MW <1,000 daltons 

using the EPA EPISuiteTM models. EPISuiteTM estimates the probability for ready biodegradation 

as well as the potential for primary and ultimate removal, as described in Section 4.3. A default 

Very High persistence hazard designation was assigned for the butadiene styrene brominated 

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copolymer according to information contained in the literature concerning polymer assessment 

because it has a MW >1,000 daltons (Boethling and Nabholz 1997).

4.4 Evaluating Human Health Endpoints

After data collection and analysis of the physical-chemical properties for the chemicals being 

assessed the comparison of the data against the hazard criteria can begin. Section 4.4.1 discusses 

how measured data are used to make hazard designations for human health endpoints and 

Section 4.4.2 presents the approach for filling in data gaps to make these hazard designations. 

4.4.1 Endpoints Characterized and Evaluated Against Criteria Based on Measured Data 

This section provides a short description of how measured data were used to designate the level 

of hazard for each endpoint. As a reminder, the criteria for the hazard designations are in Table 

4-2.

For acute mammalian toxicity, LD50s or LC50s were used to assign the hazard designation. Four 

levels of hazard designation have been defined ranging from Low to Very High.

For cancer, the hazard designation was contingent on the level of evidence for increased 

incidence of cancer rather than potency. The definitions applied in DfE criteria are based on 

International Agency for Research on Cancer (IARC) levels of evidence (International Agency 

for Research on Cancer 2006). For example, a designation of Very High concern requires that 

the substance be characterized as a “known or presumed human carcinogen”, whereas a 

designation of Low concern requires either negative studies or robust SAR conclusions. A 

designation of Moderate was applied as a default value when there was an absence of data 

suggesting High carcinogenicity, and an absence of data supporting Low carcinogenicity (i.e., a 

lack of negative studies or weak SAR conclusions).

Similarly, the hazard designation for mutagenicity/genotoxicity was also based on the level of 

evidence rather than potency. Complete data requirements for this endpoint were both gene 

mutation and chromosomal aberration assays. For instances of incomplete or inadequate 

mutagenicity/genotoxicity data, a Low hazard designation cannot be given.

For chronic endpoints, such as reproductive, developmental, neurological, and repeated dose 

toxicities, the hazard designation was based on potency. The evaluation considers both lowest 

observed adverse effect levels (LOAELs) and identification of no observed adverse effect levels 

(NOAELs) when available. The LOAEL and the NOAEL are experimental dose levels, and their 

reliability is dictated by the study design. In studies for which the lowest dose tested resulted in 

an adverse effect (and therefore a NOAEL was not established), and in studies for which the 

highest dose tested was a NOAEL, a conservative approach using professional judgment was 

used to address uncertainty regarding the lowest dose or exposure level that might be expected to 

cause a particular adverse effect. For example, in the absence of an established a NOAEL, an 

identified LOAEL might fall within the range of a Moderate hazard; however, it is uncertain if a

lower dose, such as one that falls within the range of High hazard exists because no lower doses 

were tested. In such cases, professional judgment was applied to assign a hazard designation 

when possible. Some degree of uncertainty was evident in results from studies in which a 

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NOAEL may fall within one hazard range (e.g., Moderate hazard) and the identified LOAEL 

falls within a different hazard range (e.g., Low hazard) because the true LOAEL may fall in 

either category, but there were not enough experimental data points to determine the true 

LOAEL. Professional judgment was also applied to these cases to assign a hazard descriptor 

when possible and the rationale used was described in the assessment. Developmental 

neurotoxicity was considered and was evaluated using the developmental toxicity criteria, which 

are more stringent than the criteria for neurotoxicity, and thus designed to be more protective

(U.S. EPA 2011b).

The criteria for skin and respiratory sensitization, which are immune-based responses, consider 

the frequency and potency of the reactions. For skin sensitization, categories were based on the 

weight of evidence15 from traditional animal bioassays, but in vitro alternative studies were also 

considered. At this time, there are no standard test methods for respiratory sensitization and no 

test data; as a result there was often no designation for this endpoint.

The evaluation of skin and eye irritation and corrosivity were based on the time to recovery. 

4.4.2 SAR – Application of SAR and Expert Judgment to Endpoint Criteria

If measured data pertaining to human health criteria were not available, potential adverse effects 

were estimated with SAR analysis. To make these estimates, DfE relied on the expertise of 

scientists in EPA’s New Chemicals Program who have reviewed thousands of chemicals and 

associated data using these methods. SAR uses the molecular structure of a chemical to infer a 

physicochemical property that can be related to specific effects on human health. These 

correlations may be qualitative (“simple SAR”) or quantitative (QSAR). Information on EPA’s 

use of SAR analysis has been published by U.S. EPA (1994). Public access to free validated 

quantitative SAR models for human health endpoints is far more limited than physical-chemical 

properties, environmental fate parameters, or ecotoxicology. 

Carcinogenicity was assessed using the OncoLogic expert system that provides a qualitative 

result directly applicable to the DfE criteria. For other endpoints that required SAR approaches, 

an analog approach using expert judgment was used as discussed in Section 4.4.2. All estimates 

obtained in this project were reviewed by EPA scientists having appropriate expertise. Estimates 

for the other human health endpoints were based on expert judgment using an analog approach 

and not through the use of computerized SAR methodologies.

Carcinogenicity

The potential for a chemical to cause cancer in humans was estimated using the OncoLogic 

expert system. This program uses a decision tree based on the known carcinogenicity of 

chemicals with similar chemical structures, information on mechanisms of action, short-term 

predictive tests, epidemiological studies, and expert judgment. EPA’s OncoLogic expert system 

15 Generally, weight of evidence is defined as the process for characterizing the extent to which the available data 

support a hypothesis that an agent causes a particular effect (U.S. EPA 1999a; U.S. EPA 2002; U.S. EPA 2005a).

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was consulted, but did not provide results for HBCD or the alternatives because an appropriate 

chemical class was not available for HBCD or the alternatives.

Assessment of Polymers

Estimates for the butadiene styrene brominated copolymer were obtained using information 

contained in the literature concerning polymer assessment based on its MW profile (Boethling 

and Nabholz 1997). The butadiene styrene brominated copolymer had an average MW >1,000 

daltons and no significant amounts of low MW material <1,000 daltons arising from oligomers 

or unreacted monomers based on its method of manufacture. The properties for polymers with an 

average MW >1,000 with no low MW components are generally evaluated as a single high MW 

material. In general, polymers with an average MW >1,000 were not amenable to the available 

SAR estimation methods and based on the literature are assumed to have low to no 

bioavailability. Polymers with MW >1,000 that were not degradable or reactive are also typically 

not bioavailable. Polymers with an average MW >10,000 have the potential for adverse effects 

due to lung overloading when respirable particles are present (less than ten microns). The 

potential for fibrosis or cancer are not assumed with high MW compounds. These methods were 

applied to the butadiene styrene brominated copolymer evaluated in this hazard screening 

assessment. There may be exceptions to the guidelines outlined above and as such this guidance 

should not be held as absolute thresholds. 

4.5 Evaluating Environmental Toxicity and Fate Endpoints

As with endpoints previously mentioned, the preferred method for the evaluation of 

environmental endpoints is the use of experimental data. In their absence, the alternatives

assessment uses computerized QSAR models developed by EPA for the evaluation of 

environmental endpoints that can be directly compared to the DfE criteria. When measured data 

were not available, the aquatic toxicity was estimated using EPA’s ECOSARTM software and the 

persistence designation was estimated using models in EPA’s EPISuiteTM software. The hazard 

designation was determined by applying the criteria to these estimates. As a direct result of the 

design of these models and their direct application to DfE criteria, the evaluation of 

environmental endpoints using experimental or estimated data was discussed together in the 

following subsections.

4.5.1 Aquatic Toxicity

For ecological toxicity, the alternatives assessment focused on the hazard designations for acute 

and chronic studies on freshwater species of algae, invertebrates, and fish, (often referred to as 

the “three surrogate species”). Aquatic toxicity values were reported in the assessment as 

follows:

• Acute (estimated or experimental) - LC50 in mg/L

• Chronic (experimental) - No observed effect concentration (NOEC) in mg/L 

• Chronic (estimated) - ChV, or the geometric mean between the NOEC and the LOEC, in 

mg/L

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Experimental data reported in the alternatives assessment also included information on the 

species tested. Test data on other organisms (e.g., worms) were included in the assessment if data 

were readily available. These data would be evaluated using professional judgment to support 

hazard designations assigned using the three surrogate species; however, they were not used by 

themselves to assign a hazard designation as DfE criteria are not available.

If an experimental or estimated effect level exceeded the known water solubility of a chemical 

substance, or if the log Kow exceeded the estimated ECOSARTM cut-off values for acute and 

chronic endpoints (which are class-specific), NES were predicted for the aquatic toxicity 

endpoints. NES indicates that at the highest concentration achievable, the limit of a chemical’s 

water solubility, no adverse effects were observed (or would be expected). In these cases, a Low 

hazard designation was assigned. The three alternatives evaluated were estimated to display 

NES.

In the case where an experimental aquatic toxicity value was significantly higher than the 

chemical’s water solubility, it was likely the result of a poorly conducted study. In this 

circumstance, which is generally more frequent for formulated products or mixtures, additional 

details were provided in the data quality section to describe why the reported values could not be 

used to assign a hazard designation.

EPA’s ECOSARTM estimation program uses chemical structure to estimate toxicity of a chemical 

substance using class-specific QSARs. ECOSARTM automatically determines all of the classes 

that a chemical substance may belong to and, therefore, may provide a number of different 

ecotoxicity estimates for some or all of the species and durations estimated. Modeled results are

dependent on the functional groups present on the molecule as well as the diversity of chemicals 

with experimental data that were used to build the models (their training set). The hazard profiles 

report every estimated value returned from ECOSARTM. However, the hazard designation was 

based on the most conservative ECOSARTM estimate, unless expert judgment suggested that an 

individual substance was better represented by a specific class based on analysis of the operative 

mode of action. However, if the chemical substance is not anticipated to lie within the domain of 

the class-specific estimates provided by ECOSAR or to undergo the same mode of action of the 

chemicals that appear in their training sets, the narcosis (baseline toxicity) associated with the 

neutral organic class will be used preferentially. Experimental log Kow values were used 

preferentially as input into ECOSARTM. In their absence, estimated log Kow values from 

EPISuiteTM were used. ECOSARTM is maintained and developed as a stand-alone program but is 

also accessible through the EPA EPISuiteTM program after it is installed; therefore the 

Estimations Program Interface (EPI) program was cited for the ECOSARTM values in this report.

The QSARs for ECOSARTM were built using experimental data for several chemical classes. For 

a chemical class to be defined within ECOSARTM, sufficient acute experimental data were 

required to build a QSAR for all three species included in the model. The equations in ECOSAR 

are derived from data for surrogate species of fish, zooplankton, and phytoplankton. While these 

surrogate species can comprise several genera as well as families, the equations are not intended 

to be species specific, but rather estimates of toxicity to the general trophic levels they represent 

(fish, aquatic invertebrates, and aquatic plants). There were instances, however, where sufficient 

experimental data are not available to build a chronic QSAR for some of the three surrogate 

4-22
species. Although not utilized in this alternative assessment an acute value (experimental or 

estimated) would be divided by an acute to chronic ratio (ACR) to arrive at the chronic value if a 

chronic equation did not exist. ACRs of 10 are used for fish and daphnid and an ACR of 4 is

used for algae (Mayo-Bean, Nabholz et al. 2011).

An estimate of NES is the default value used for organics, oligomers, or non-ionic polymers with 

a MW >1,000 daltons in the assignment of aquatic toxicity hazard. In EPA’s New Chemical 

program, aquatic toxicity is not predicted for chemicals with a MW >1,000 daltons as uptake has 

been found to decrease exponentially with MWs >600 daltons (Nabholz, Clements et al. 1993)

due to a decrease in passive absorption through respiratory membranes (Mayo-Bean, Nabholz et 

al. 2011).

4.5.2 Bioaccumulation

Bioaccumulation is a process in which a chemical substance is absorbed in an organism by all 

routes of exposure as occurs in the natural environment, e.g., from dietary and ambient 

environment sources. Bioaccumulation is the net result of the competing processes which

includes uptake, metabolism, and elimination of a chemical in an organism. Bioaccumulation can 

be evaluated using the BAF, the steady state ratio of a chemical in an organism relative to its 

concentration in the ambient environment, where the organism is exposed through ingestion and 

direct contact. Experimental BAFs have not been widely available in the scientific literature and, 

as a result, experimental BCFs are more commonly used to evaluate the bioaccumulation hazard. 

BCFs are defined as the ratio of the concentration of a chemical in an organism to the 

concentration of the chemical in the organism’s surroundings; BCFs are typically measured for 

fish (in water) using guideline studies.

Experimental BAF or BCF values can be compared directly to the DfE criteria for this endpoint 

to assign a hazard designation. The BCF/BAF designations range from <100 for a Low 

designation to >5,000 for a Very High designation (see 4.1.2). If experimental values were 

available for both of these endpoints, and the BCF and BAF were >100 (i.e., above the Low 

designation), the largest factor was used to assign hazard designation. If experimental BCFs 

<100 were available, the estimated upper trophic BAF from EPISuiteTM was used preferentially 

if its use resulted in a more conservative hazard designation and the potential for metabolism was 

accurately accounted for within the model estimates. 

In the absence of experimental data, evaluation of bioaccumulation potential can be done using 

the log Kow and the log octanol/air partition coefficient, Koa, as estimated by EPISuiteTM. 

However, analysis using Koa requires the use of metabolism data for higher trophic, air-breathing 

organisms, which can be difficult to obtain from the scientific literature and cannot be readily 

estimated. BAFs and BCFs from EPISuiteTM were, therefore, typically used for the 

bioaccumulation hazard designation when experimental data were lacking. These values can be 

compared directly to DfE criteria and the most conservative result was used for the hazard 

designation. For chemicals that had estimated bioaccumulation data, available experimental 

monitoring data were used to provide insight into the reliability of the model results. For 

example, an estimated Low bioaccumulation potential may be increased to a Moderate 

designation if a chemical was routinely identified in samples from higher trophic levels, or a 

High designation if the chemical was routinely measured in animals at the top of the food chain. 

4-23
Environmental monitoring data were only available for HBCD and TBBPA bis(2,3-

dibromopropyl) ether.

An estimate of Low is the default value used for discrete organics with a MW >1,000 daltons in 

the assignment of bioaccumulation hazard. This assignment is consistent with an analysis of the 

chemicals used in the development of the bioconcentration and bioaccumulation estimation 

programs in the EPISuiteTM software (U.S. EPA 2011f). The training sets for these models 

included 527 and 421 chemicals, respectively, with a MW range of 68-992 daltons (959 daltons 

for BAF). Given that BCF and BAF reach a maximum and then decrease with increasing log 

Kow, a default value of Low is, in general, consistent with the limited bioavailability expected 

for materials with a MW >1,000 daltons. DfE will use all available well‐conducted studies when 

evaluating bioaccumulation potential for materials with a MW >1,000, including environmental 

biomonitoring data on higher trophic levels. No discrete organic substances with a MW >1,000 

daltons were evaluated in the HBCD alternatives assessment.

The butadiene styrene brominated copolymer has a MW >1,000 daltons, and the default 

bioaccumulation designation of Low was assigned, arising from its predicted limited 

bioavailability (Boethling and Nabholz 1997). 

4.5.3 Environmental Persistence

A chemical’s persistence in the environment is evaluated by determining the type and rate of 

potential removal processes. These removal processes were generally divided into two 

categories: chemical and biological. Of the chemical degradation processes, an evaluation of 

environmental persistence includes the reaction of a chemical with water, also known as 

hydrolysis, because water is ubiquitous in the environment. Hydrolysis rate constants can be 

obtained from the literature or estimated, and the resulting half-lives can be compared directly to 

DfE criteria. For chemicals without hydrolyzable groups, biodegradation tends to be the faster 

degradation process; however, numerous chemicals possess labile groups and these may 

hydrolyze in the environment at significant or even rapid rates. The chemicals assessed are not 

anticipated to hydrolyze under environmental conditions. Direct and indirect photolysis also 

represent other potential chemical degradation processes that are considered in the alternative 

assessment, and they are discussed later in this section.

Biodegradation, the most prevalent biological removal process, was divided into two types. The 

first is primary biodegradation, in which a chemical substance is converted to another substance 

through a single transformation. The second is ultimate biodegradation, in which a chemical is 

completely degraded to CO2, water, mineral oxides (such as phosphates for chemicals containing 

phosphorus). DfE criteria utilize ultimate biodegradation preferentially for the persistence hazard 

designation, although primary removal rates were informative in assigning hazard designations 

particularly for materials that were transformed slowly, and to a lesser extent for those that are 

transformed rapidly.

If ultimate biodegradation data were not available, primary removal data were evaluated. If 

primary removal processes are occurring, then the potential for the formation of degradation 

products that are more persistent than the parent compounds must be considered in the hazard 

designation. When present, the persistent degradation products should be evaluated for fate and 

4-24
toxicity if they are anticipated to result in a different hazard designation relative to the parent 

material. For all four of the chemicals evaluated, the primary biodegradation step is anticipated 

to occur at a slow or negligible rate representing a High or Very High designation when

compared directly to the DfE criteria.

Biodegradation processes can be classified as either aerobic or anaerobic. Aerobic 

biodegradation is an oxidative process that occurs in the presence of oxygen. Anaerobic 

biodegradation is a reductive process that occurs only in the absence of oxygen. Aerobic 

biodegradation is typically assessed for soil and water, while anaerobic biodegradation is 

generally assessed in sediment. For determining the persistence hazard, the importance of both 

aerobic and anaerobic biodegradation as well as partitioning and transport in the environment 

were considered to determine what removal processes were most likely to occur. Anaerobic 

degradation may use any of several electron acceptors depending on their availability in a given 

environment and the prevailing redox potential (Eh). The biodegradative populations that are 

dominant in a given environment vary with the conditions and so do their biodegradative 

capabilities.

One aspect of the assessment is to determine the potential for removal of a chemical substance, 

and especially removal attributable to biodegradation, within a sewage treatment plant and other 

environments. In this assessment, the term “ready biodegradability” refers to a chemical’s 

potential to undergo ultimate degradation in guideline laboratory studies. A positive result in a 

test for ready biodegradability can be considered as indicative of rapid and ultimate degradation 

in most environments including biological sewage treatment plants. Ready tests typically include 

a 10-day window, beginning when the biodegradation parameter (e.g., disappearance of 

dissolved organic carbon from test substance, or theoretical oxygen demand) reaches 10%. The 

10-day window must occur within the 28-day length of the test. If the pass level of the test (60%

for oxygen demand and CO2 production; 70% for dissolved organic carbon disappearance) is 

met in the 10-day window, the chemical received a Very Low hazard designation. Those that did 

not pass the 10-day window criterion but met the pass level in 28 days received a Low hazard 

designation. 

In the absence of a reported half-life, experimental data were also used to approximate half-life 

as appropriate. For example, a chemical that undergoes <5% removal in 30 days would be 

expected to have a half-life >60 days and would be assigned a High persistence concern.

When experimental data on the biodegradation of a chemical substance were not available, the 

potential of that substance to undergo this removal process was assessed from the results of the 

EPISuiteTM models. These models fall into one of four classes: rapid biodegradation models 

based on linear and non-linear regressions that estimate the probability that a chemical substance 

will degrade fast; expert survey models that estimated the rate of ultimate and primary 

biodegradation using semi-quantitative methods; probability of ready biodegradability in the 

OECD 301C test; and probability of rapid biodegradation under methanogenic anaerobic 

conditions (specifically, under conditions of the OECD 311 test). Each of these is discussed in 

the following paragraphs.

4-25
The first models (Biowin 5 and 6) used in the screening assessment estimated ready 

biodegradability in the OECD 301C test and are also known as the Japanese Ministry of 

International Trade and Industry (MITI) models. These models provided the probability that a 

material passes this standardized test. Those chemicals that were estimated to pass the ready 

biodegradability test received a Low persistence designation. If a chemical was not estimated to 

pass the MITI test, the results of the other EPISuiteTM biodegradation models were used.

The rapid biodegradation potential models within EPISuiteTM (Biowin 1 and 2) were useful for 

determining if a chemical substance was expected to biodegrade quickly in the environment. If a 

chemical was likely to biodegrade quickly, it was generally assigned a Low hazard designation 

for persistence. The results of the estimates from these models may be used in concert with the 

semi-quantitative output from a second set of models, which include ultimate and primary 

biodegradation survey models (Biowin 3 and 4) for evaluating persistence. These models 

provided a numeric result, ranging from 1 to 5, which relates to the amount of time required for 

complete ultimate degradation (Biowin 3) and removal of the parent substance by primary 

degradation (Biowin 4) of the test compound. The numeric result from Biowin 3 was converted 

to an estimated half-life for removal that can be compared directly to DfE criteria. If results from 

different models (other than the MITI models) led to a different hazard designation, then the 

ultimate biodegradation model results were used preferentially. If the transport properties 

indicate the potential for the material to partition to sediment, an anoxic compartment, then the 

results of the anaerobic probability model (Biowin 7) will also be evaluated. 

Half-lives for hydrolysis from experimental studies or EPISuiteTM estimates were used in 

preference to biodegradation data when they suggested that hydrolysis is a more rapid removal 

process. Hydrolysis half-lives can then be compared directly to DfE criteria to assign the 

persistence designation. None of the chemicals evaluated are anticipated to undergo hydrolysis 

under environmental conditions.

Photolysis may also be an important environmental removal process. In general, environmental 

removal rates from photolysis do not compete with biodegradation or hydrolysis although there 

are exceptions such as iodides and, to a lesser extent, bromides. Photolysis may be an important 

removal process for chemicals that were not bioavailable because of their limited water 

solubility. Estimation methods for photolysis rates were not available using computerized SAR 

tools. If experimental or suitable analog data were available, the rate of photolysis was evaluated 

relative to other removal processes.

The environmental persistence designation in the four hazard profiles is High or Very High. 

Although these substances can degrade over time, this process is anticipated to occur at a very 

slow rate. The butadiene styrene brominated copolymer has a MW >1,000 and received a Very 

High persistence designation arising from its lack of bioavailability and the absence of chemical 

degradation processes.

4.6 Endocrine Activity

Chemicals included in DfE alternatives assessments were screened for potential endocrine 

activity, consistent with the DfE Alternatives Assessment Criteria. Endocrine activity refers to a 

change in endocrine homeostasis caused by a chemical or other stressor. An endocrine 

4-26
disruptor is an external agent that interferes in some way with the role of natural hormones in 

the body, in a manner causing adverse effects. Relevant data are summarized in the hazard 

assessments for each chemical, located in Section 4.8. Data on endocrine activity were available 

for HBCD, tetrabromobisphenol A (TBBPA) bis (2, 3-dibromopropyl) ether, and for TBBPA-bis 

brominated ether derivative by analogy to the former substance. Endocrine data were 

summarized as a narrative. A unique hazard designation for endocrine activity is not provided for 

this endpoint in Table 4-2 because there is no consensus on what constitutes Low, Moderate or 

High hazard concern. This issue is discussed in greater detail below. 

The document Special Report on Environmental Endocrine Disruption: An Effects Assessment 

and Analysis describes EPA’s activities regarding the evaluation of endocrine disruption (U.S. 

EPA 1997). This report was requested by the Science Policy Council and prepared by EPA’s 

Risk Assessment Forum. This report states that “Based on the current state of the science, the 

Agency does not consider endocrine disruption to be an adverse endpoint per se, but rather to be 

a mode or mechanism of action potentially leading to other outcomes, for example, carcinogenic, 

reproductive or developmental effects, routinely considered in reaching regulatory decisions”

(U.S. EPA 1997). The report also states that “Evidence of endocrine disruption alone can 

influence priority setting for further testing and the assessment of results of this testing could 

lead to regulatory action if adverse effects are shown to occur” (U.S. EPA 1997).

The 1996 Food Quality Protection Act (FQPA) directed EPA to develop a scientifically validated 

screening program to determine whether certain substances may cause hormonal effects in 

humans. In response, EPA established the Endocrine Disruptor Screening Program (EDSP) (U.S. 

EPA 2012b). The EDSP is developing requirements for the screening and testing of thousands of 

chemicals for their potential to affect the endocrine system. When complete, EPA will use these 

screening and testing approaches to set priorities and conduct further testing when warranted. 

The science related to measuring and demonstrating endocrine disruption is relatively new, and 

validated testing methods at EPA are still being developed. 

The EDSP proposes a two-tiered approach that includes initial screening followed by more indepth testing when warranted (U.S. EPA 2011a). The Tier 1 screening battery is intended to 

identify chemicals with the potential to interact with the estrogen, androgen, or thyroid hormone 

systems through any of several recognized modes of action. Positive findings for Tier 1 tests 

identify the potential for an interaction with endocrine systems, but do not fully characterize the 

nature of possible effects in whole animals. Tier 2 testing is intended to confirm, characterize, 

and quantify the effects for chemicals that interact with estrogen, androgen, and thyroid hormone 

systems. These test methods must undergo a four-stage validation process (protocol 

development, optimization/prevalidation, validation, and peer-review) prior to regulatory 

acceptance and implementation. Validation is ongoing for Tier 1 and Tier 2 methods.

16 Once 

validated test methods have been established for screening and testing of potential endocrine 

disruptors, guidance must be developed for interpretation of these test results using an overall 

weight-of-evidence characterization.

16 Information on the status of assay development and validation efforts for each assay in EPA’s EDSP can be found 

at: http://www.epa.gov/oscpmont/oscpendo/pubs/assayvalidation/status.htm.

4-27

 
To assess the data on endocrine activity, DfE applies the weight of evidence approach developed 

by the EDSP (U.S. EPA 2011c). This process integrates and evaluates data, and always relies on 

professional judgment (U.S. EPA 2011c). To evaluate endocrine activity with this weight of 

evidence approach, DfE examined multiple lines of evidence (when available) and considered 

the nature of the effects within and across studies, including number, type, and 

severity/magnitude of effects, conditions under which effects occurred (e.g., dose, route, 

duration), consistency, pattern, range, and interrelationships of effects observed within and 

among studies, species, strains, and sexes, strengths and limitations of the in vitro and in vivo

information, and biological plausibility of the potential for an interaction with the estrogen, 

androgen, or thyroid hormonal pathways.

Test data from both in vitro assays and in vivo studies were included in the hazard profile for 

HBCD. The hazard profile for TBBPA bis(2, 3-dibromopropyl) ether includes summaries of in 

vitro assays, as does the hazard profile for TBBPA-bis brominated ether derivative by analogy to 

the former substance. The results of in vitro assays alone were not generally expected to provide 

a sufficient basis to support a hazard designation for endocrine disruption. EPA expects that in 

vivo evidence would typically be given greater overall influence in the weight of evidence

evaluation than in vitro findings because of the inherent limitations of such assays. Although in 

vitro assays can provide insight into the mode of action, they have limited ability to account for 

normal metabolic activation and clearance of the compound, as well as normal intact 

physiological conditions (e.g., the ability of an animal to compensate for endocrine alterations). 

There were no experimental endocrine activity studies available for the butadiene styrene 

brominated copolymer although based on the large MW and structural groups, it is not expected 

to have endocrine activity due to its limited bioavailability and inability to be readily 

metabolized in the body.

4-28
Chemical Alternatives and the Toxic Substances Control Act

EPA’s Design for the Environment (DfE) program is administered by the Office of Pollution Prevention and 

Toxics (OPPT), which is charged with the implementation of the Toxic Substances Control Act (TSCA) and 

the Pollution Prevention Act (PPA).

 

Central to the administration of TSCA is the management of the TSCA Inventory. Section 8 (b) of TSCA 

requires EPA to compile, keep current, and publish a list of each chemical substance that is manufactured or 

processed in the United States. Companies are required to verify the TSCA status of any substance they wish to 

manufacture or import for a TSCA-related purpose. For more information, please refer to the TSCA Chemical 

Substance Inventory website: http://www.epa.gov/opptintr/existingchemicals/pubs/tscainventory/basic.html

TSCA and DfE Alternatives Assessments

Substances selected for evaluation in a DfE Alternatives Assessment generally fall under the TSCA regulations 

and therefore must be listed on the TSCA inventory, or be exempt or excluded from reporting before being 

manufactured in or imported to, or otherwise introduced in commerce in, the United States. For more 

information see http://www.epa.gov/oppt/newchems/pubs/whofiles.htm.

To be as inclusive as possible, DfE Alternatives Assessments may consider substances that may not have 

been reviewed under TSCA and therefore may not be listed on the TSCA inventory. DfE has worked with 

stakeholders to identify and include chemicals that are of interest and likely to be functional alternatives,

regardless of their TSCA status. Chemical identities are gathered from the scientific literature and from 

stakeholders and, for non-confidential substances, appropriate TSCA identities are provided.

Persons are advised that substances, including DfE identified functional alternatives, may not be introduced 

into US commerce unless they are in compliance with TSCA. Introducing such substances without adhering to 

the TSCA provisions may be a violation of applicable law. Those who are considering using a substance 

discussed in this report should check with the manufacturer or importer about the substance’s TSCA status. If 

you have questions about reportability of substances under TSCA, please contact the Industrial Chemistry 

Branch at 202-564-8740.

4-29
References

Boethling, R. S. and J. V. Nabholz (1997). Environmental Assessment of Polymers under the 

U.S. Toxic Substances Control Act. Ecological Assessment of Polymers Strategies for 

Product Stewardship and Regulatory Programs. J. D. Hamilton and R. Sutcliffe. New 

York, Van Nostrand Reinhold: 187-234.

Environment Canada (2011). Screening Assessment Report on Hexabromocyclododecane.

European Commission (2008). Risk Assessment: Hexabromocyclododecane CAS-No.: 25637-

99-4 EINECS No.: 247-148-4, Final Report May 2008. Luxembourg.

International Agency for Research on Cancer. (2006). "Preamble to the IARC Monographs." 

Retrieved April 17, 2012, 

from http://monographs.iarc.fr/ENG/Preamble/currentb6evalrationale0706.php.

Mayo-Bean, K., K. V. Nabholz, et al. (2011). Methodology Document for the Ecological 

Structure-Activity Relationship Model (ECOSAR) Class Program. Office of Pollution 

Prevention and Toxics. Washington, DC.

Meylan, W. M. and P. H. Howard (1995). "Atom/fragment contribution method for estimating 

octanol-water partition coefficients." J Pharm Sci 84(1): 83-92. 

Meylan, W. M., P. H. Howard, et al. (1996). "Improved method for estimating water solubility 

from octanol/water partition coefficient." Environ Toxicol Chem 15(2): 100-106. 

Nabholz, J. V., R. G. Clements, et al. (1993). Validation of Structure Activity Relationships 

Used by the USEPA’s Office of Pollution Prevention and Toxics for the Environmental 

Hazard Assessment of Industrial Chemcials. Environmental Toxicology and Risk 

Assessment. J. W. Gorsuch, F. J. Dwyer, C. G. Ingersoll and T. W. La Point. 

Philadelphia, American Society for Testing and Materials. 2: 571-590.

National Industrial Chemicals Notification and Assessment Scheme (2012). Priority Existing 

Chemical Assessment Report No. 34: Hexabromocyclododecane. Department of Health 

and Ageing. Sydney.

National Research Council (2000). Toxicological Risks of Selected Flame-Retardant Chemicals. 

Washington, D.C., National Academy Press.

Organisation for Economic Co-Operation and Development (OECD) (2007). 

Hexabromocyclododecane. Screening Information Dataset Initial Assessment Profile 

(SIAP).

Scientific Committee on Health and Environmental Risks (SCHER) (2008a). Risk Assessment 

Report on Hexabromocyclododecane (HBCDD): Environmental Part.

Scientific Committee on Health and Environmental Risks (SCHER) (2008b). Risk Assessment 

Report on Hexabromocyclododecane (HBCDD): Human Health Part.

4-30
U.S. EPA (1994). Joint Project on the Evaluation of (Quantitative Structure Activity 

Relationships. Office of Prevention Pesticides and Toxic Substances. Washington DC, 

EPA 743R-94-001. .

U.S. EPA (1997). Special Report on Environmental Endocrine Disruption: An Effects 

Assessment and Analysis. R. A. Forum. Washington, DC.

U.S. EPA (1999a). Guidelines for Carcinogen Risk Assessment, Review Draft. Office of 

Research and Development. CEA-F-0644.

U.S. EPA (1999b). High Production Volume (HPV) Challenge: Determining the Adequacy of 

Existing Data. Office of Pollution Prevention & Toxics. Washington, DC.

U.S. EPA (2002). A Review of the Reference Dose and Reference Concentration Processes. Risk 

Assessment Forum. December 2002 Final Report. Washington, DC, EPA. EPA/630/P02/002F.

U.S. EPA (2005a). Guidelines for Carcinogen Risk Asessment. Risk Assessment Forum. 

Washington, DC, EPA. EPA/630/P-03/001F.

U.S. EPA (2005b). Pollution Prevention (P2) Framework. Office of Pollution Prevention and 

Toxics. Washington D.C.

U.S. EPA. (2010a). "Chemical Categories Report." Retrieved April 17, 2012, 

from http://www.epa.gov/opptintr/newchems/pubs/chemcat.htm.

U.S. EPA (2010b). TSCA New Chemicals Program (NCP) Chemical Categories. Office of 

Pollution Prevention and Toxics. Washington, DC.

U.S. EPA. (2011a). "Assay Development." Retrieved April 17, 2012, 

from http://www.epa.gov/oscpmont/oscpendo/pubs/assayvalidation/index.htm.

U.S. EPA (2011b). Design for the Environment Program Alternatives Assessment Criteria for 

Hazard Evaluation (version 2.0). Design for the Environment. Washington, DC, Office of 

Pollution Prevention and Toxics 

U.S. EPA (2011c). Endocrine Disruptor Screening Program. Weight of the Evidence: Evaluating 

Results of EDSP Tier 1 Screening to Identify the Need for Tier 2 Testing. Office of 

Chemical Safety and Pollution Prevention. Washington DC, EPA.

U.S. EPA. (2011d). "Estimation Program Interface (EPI) Suite." Retrieved April 18, 2012, 

from http://www.epa.gov/oppt/exposure/pubs/episuite.htm.

U.S. EPA (2011e). On-line AOPWINTM User's Guide.

U.S. EPA (2011f). On-line BCFBAFTM User's Guide.

U.S. EPA (2011g). On-line KOWWINTM User's Guide.

4-31
U.S. EPA (2011h). On-line WSKOWWINTM User's Guide.

U.S. EPA. (2012a). "Analog Identification Methodology (AIM)." Retrieved April 17, 2012, 

from http://www.epa.gov/oppt/sf/tools/aim.htm.

U.S. EPA. (2012b). "Endocrine Disruptor Screening Program (EDSP)." Retrieved April 17, 

2012, from http://www.epa.gov/scipoly/oscpendo/index.htm.

U.S. EPA (2012c). Interpretive Assistance Document for Assessment of Discrete Organic 

Chemicals. Sustainable Futures Summary Assessment. Washington, D.C.

U.S. EPA. (2012d). "Models & Methods." Retrieved April 17, 2012, 

from http://www.epa.gov/oppt/sf/tools/methods.htm.

4-32
4.7 Hazard Summary Table

Table 4-4. Hazard Summary for HBCD and Alternatives

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) were 

assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from predictive models and/or professional judgment.

This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion byproducts are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the table.

d This hazard designation would be assigned MODERATE for a potential for lung overloading if >5% of the particles are in the respirable range as a result of dust forming operations.

§ Based on analogy to experimental data for a structurally similar compound.

¥ Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many flame retardants that 

may partition to sediment and particulates.

Chemical

For full chemical name and relevant trade 

names see the hazard profiles in Section 4.8 CASRN

Human Health Effects Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicityGenotoxicityReproductiveDevelopmentalNeurologicalRepeated DoseSkin SensitizationRespiratory Sensitization1Eye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Hexabromocyclododecane (HBCD)

25637-99-4; 

3194-55-6 L M L M H M M L VL VL VH VH H VH

Butadiene styrene brominated copolymer¥

Br

Br

Br

Br

* *

x y z x

1195978-93-8 L L L L L L Ld L M L L L VH L

TBBPA-bis brominated ether derivative¥

97416-84-7 L§ M§ M§ M§ M§ L M§ L§ L L L L H H

TBBPA bis(2,3-dibromopropyl) ether ¥

O

Br O Br

Br

Br

Br Br

Br

Br 21850-44-2 L M M M M L M L L L L L VH H

1 At this time, there are no standard test methods for respiratory sensitization and no test data; as a result there was no designation for this endpoint.

Br

Br

O Br

O

Br

Br

Br

Br Br

Br Br

Br Br

Br

Br

4-33
4.8 Hazard Profiles

Hexabromocyclododecane (HBCD)

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) were 

assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from predictive models and/or professional judgment.

This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion byproducts are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the table.

Chemical CASRN

Human Health Effects Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicityGenotoxicityReproductiveDevelopmentalNeurologicalRepeated DoseSkin SensitizationRespiratory SensitizationEye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Hexabromocyclododecane (HBCD) 25637-99-4; 

3194-55-6 L M L M H M M L VL VL VH VH H VH

4-34
Hexabromocyclododecane (HBCD)

Representative structure; substitution and stereochemistry not specified

CASRN: 25637-99-4; 3194-55-6

MW: 641.70

MF: C12H18Br6

Physical Forms:

Neat: Solid

Use: Flame retardant

SMILES: BrC1CC(CC(CC(CC(CC(C1)Br)Br)Br)Br)Br (for CASRN 25637-99-4); BrC(C(Br)CCC(Br)C(Br)CCC(Br)C(Br)C1)C1 (for CASRN 3194-55-6)

Synonyms: Cyclododecane, hexabromo- (CA Index Name for CASRN 25637-99-4); Cyclododecane, 1,2,5,6,9,10-hexabromo- (CA Index Name for CASRN 3194-

55-6); HBCD; HBCDD 

Trade Names: BRE 5300 Pyroguard F 800; Bromkal 73-6CD; Pyroguard SR 103; CD 75; Pyroguard SR 103A; CD 75P; Pyrovatex 3887; FR 1206; Safron 5261; FR 

1206HT; Saytex HBCD; HBCD-LM; Saytex HBCD-LM; HBCD-LMS; Saytex HBCD-SF; Myflam 11645; Saytex HP 900; Nicca Fi-None CG 1; SR 103; Nicca FiNone TS 1; SR 104; Nicca Fi-None TS 3; YM 88

Chemical Considerations: This is a discrete organic chemical with a MW <1,000. There are 16 possible hexabromocyclododecane (HBCD) isomers. CASRN

25637-99-4 is assigned to a non-specific mixture of all HBCD isomers and CASRN 3194-55-6 is assigned to the mixture of 1,2,5,6,9,10- HBCD isomers. There are 

differences in the fate, the behavior in the environment and the potential for toxic effects for individual HBCD isomers; therefore, studies identifying specific isomers 

are labeled in this assessment. Technical HBCD is predominantly comprised of three diastereomers (these are isomers that differ only in the three-dimensional 

orientations of the bromine substituents), known as α-, β- and γ- HBCD. Additionally, EPI v 4.1 was used to estimate physical/chemical and environmental fate values 

in the absence of experimental data. EPI-estimated values for HBCD are not isomer specific; the estimations were considered to be applicable to all isomers. 

Measured values from experimental studies were incorporated into the estimations. The overall hazard designations in this profile were determined using a 

conservative approach; each designation was based on the most hazardous material or value in the event that there were multiple adequate, high-quality measured 

values reported.

On August 18, 2010, EPA released an action plan on this brominated flame retardant category, hexabromocyclododecane, which outlined the Agency concerns for 

these chemicals and proposed risk management approaches to address those concerns, including a list of potential future regulatory actions 

(http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/hbcd.html). One such regulatory action has already been initiated. In the spring of 2012, EPA proposed 

a Significant New Use Rule (SNUR) to enable EPA to review future use of HBCD in consumer textiles. If finalized, the rule will require that anyone intending to 

manufacture, import, or process HBCD for use in consumer textiles to notify EPA. The notification would provide EPA with an opportunity to evaluate the health and 

environmental effects of using HBCD in consumer textiles (www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2011-0489-0001). Other regulatory actions 

are being considered.

Br Br

Br Br

Br

Br

4-35
Polymeric: No

Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: Tetrabromocyclododecene, dibromocyclododecadiene and 1,5,9-cyclododecatriene by aerobic and 

anaerobic degradation (ECHA, 2008).

Analog: No analogs

 Endpoint(s) using analog values: Not applicable

Structure: Not applicable

Structural Alerts: Cyclic halogenated hydrocarbons, neurotoxicity; halogenated aliphatic hydrocarbons, potential nephrotoxins (EPA, 2011)

Risk Phrases: R63 - Possible risk of harm to the unborn child; R64 - May cause harm to breastfed babies (NICNAS, 2012)

Hazard and Risk Assessments: A risk assessment was prepared for HBCD by the National Academy of Sciences National Research Council (NAS, 2000) and 

European Communities (EINECS, 2008; SCHER, 2008a; SCHER, 2008b). A Screening Assessment was prepared by Environment Canada/Health Canada 

(Environment Canada, 2011), the Australian National Industrial Chemicals Notification and Assessment Scheme (NICNAS, 2012) and an OECD Screening 

Information Dataset Initial Assessment Profile (SIAP) was completed in 2007 (OECD, 2007). HBCD was also part of the Initial Risk-Based Prioritization of High 

Production Volume Chemicals (HPV) (EPA, 2008).

4-36
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 185-195 (Measured) NAS, 2000 Similar values are consistently

reported in secondary sources. 172-184 to 201-205; 190 (average) 

(Measured) 

EINECS, 2008

180-185 (Measured) NICNAS, 2012

175-195 (Measured) IUCLID, 2000

Boiling Point (°C) >190 (decomposes)

(Measured)

EINECS, 2008; NICNAS, 2012 Value reported in a secondary source.

Vapor Pressure (mm Hg) 4.7x10-7 at 21oC (Measured)

GLP Spinning Rotor Method/OECD TG 

104 and EPA OPPTS 830.7952; reported 

as 6.3x10-5 Pa

HBCD sample consisted of 8.5%, 6.0% 

and 79.1% α-, β- and γ-HBCD 

respectively.

EINECS, 2008; NICNAS, 2012 The method used is not recommended 

for substances with vapor pressures 

<10-4 Pa (or 0.0008 mm Hg). 

However, this value indicates a low 

vapor pressure. 

α-HBCD 7.9×10-11

β-HBCD 4.4×10-11

γ-HBCD 6.3×10-13

at 25 oC Gas saturation method 

(Measured)

Kuramochi et al., 2010 The method used is not recommended 

for substances with vapor pressures 

outside of 7.5×10-10 to 0.008 mm Hg. 

This value indicates a low vapor 

pressure. 

Water Solubility (mg/L) 6.6x10-2 at 20oC (Measured)

GLP Column Elution Method

α-HBCD: 4.8x10-2

β-HBCD: 1.5x10-2

γ-HBCD: 2.1x10-3

EINECS, 2008; NICNAS, 2012 Value reported in a secondary source. 

The value reported is the sum of the 

water solubility values for individual 

diastereomers found in the technical 

mixture.

4-37
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

0.12 (Measured) 

Solubility value of total HBCD

One isomer:

α-HBCD: 1.4x10-2

β-HBCD: 2.8x10-3

γ-HBCD: 1.5x10-3

Mixture of isomers (technical product):

α-HBCD: 8.1x10-2

β-HBCD: 3.3x10-2

γ-HBCD: 1.6x10-3

Direct Coupled Column Linked

Chromatographic Technique

Kuramochi et al., 2007 The value reported is the sum of the 

water solubility values for individual 

diastereomers found in the technical 

mixture.

0.008 (Measured) IUCLID, 2000 Value reported in a secondary source.

3.4x10-3 at 25oC (Measured)

GLP Column Elution Method

EINECS, 2008; NAS, 2000; 

NICNAS, 2012

The measurement was performed on 

the technical product, which was not 

100% pure. The value reported was 

for a single diastereomer (γ-HBCD)

in the mixture.

8.6x10-3 at 25oC (Measured; 

CASRN 3194-55-6)

HSDB, 2011a Value reported in a secondary source; 

sufficient details were not available to 

assess the quality of this study.

Log Kow 5.62 (Measured)

GLP Generator Column Method

EINECS, 2008; NICNAS, 2012 The measurement was performed on 

the technical product, which was not 

100% pure.

4-38
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

One isomer:

α-HBCD: 5.8

β-HBCD: 5.8

γ-HBCD: 6.3

Mixture of isomers (technical product):

α-HBCD: 5.7

β-HBCD: 6.1 

γ-HBCD: 6.3

Slow-stirrer method (Measured)

Kuramochi et al., 2007 Adequate non-guideline study. 

5.81 (Measured) IUCLID, 2000 Value reported in a secondary source.

Flammability (Flash Point) Not flammable (Estimated) EINECS, 2008 Value reported in a secondary source.

Explosivity Not explosive (Estimated) EINECS, 2008 Value reported in a secondary source.

Pyrolysis Decomposition occurs between 240 and 

270°C; study performed in a batch reactor 

with inert and oxidizing atmospheres

Numerous products were identified by 

gas chromatography/mass spectrometry 

(GC/MS), proposed pyrolysis degradation 

products were non-brominated structures 

and brominated structures

Barontini et al., 2001; NICNAS, 

2012

Adequate non-guideline study. 

Potential mechanisms for thermal 

decomposition proposed.

pH Not applicable Professional judgment Does not contain functional groups 

that are expected to ionize under 

environmental conditions.

pKa Not applicable Professional judgment Dissociation is not expected; the 

chemical does not contain ionizable 

functional groups.

4-39
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

HUMAN HEALTH EFFECTS

Toxicokinetics HBCD is readily absorbed following oral administration in rodent studies and is distributed primarily to 

lipid-rich tissues. Smaller amounts of HBCD have been detected in the lungs, kidneys, blood, and brain. 

HBCD and its metabolites are eliminated from the body mainly in the feces (~30 -70%) and in urine (~16%). 

Dermal absorption is estimated to be 4% for fine particles and 2% for granular particles. The overall extent 

of metabolism of technical-grade HBCD is unknown. Three polar metabolites have been detected following 

exposure to γ-HBCD. It has been demonstrated in monitoring studies with volunteers that HBCD may be 

transferred across the placenta to the developing fetus and secreted in breast milk during lactation.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or 

Inhaled

Rats (2 males, 8 females) administered a 

single oral dose of 1.93 mg radiolabeled 

HBCD eliminated 86% of the dose within 

72 hours (70% in feces and 16% in urine)

Absorption is quick from the 

gastrointestinal tract with a half-life of 

2 hours (absorbed fraction not reported); 

elimination is slower in adipose tissue as 

opposed to non-adipose tissue

EPA, 2005; NICNAS, 2012 Reported in a secondary source. 

Authors state that caution is urged in 

interpreting the data due to the small 

sample size and the brief nature of the 

final report. 

Four male Wistar rats orally administered 

500 mg/kg-day HBCD in olive oil for 

5 days

Average daily rate of excretion in the 

feces was 29-37% of the dose; the 

cumulative excretion was constant at 

32-35%; urinary excretion was not 

observed; metabolites were not detected 

in the urine or feces; HBCD was detected 

only in adipose tissue (0.3-0.7 mg/g fat) 

EPA, 2005; NICNAS, 2012 Reported in a secondary source. 

4-40
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

In rodents, HBCD is readily absorbed 

through the gastrointestinal tract with 

highest concentrations in adipose tissue 

and muscle, followed by the liver; it has 

been found in much lower concentrations 

in the lungs, kidneys, blood and brain

Oral absorption estimated to be 50-100%; 

accumulation of α-diastereomer is much 

higher than other diastereomers

Overall extent of metabolism of 

technical-grade HBCD is unknown; 

γ-HBCD is metabolized to form three 

polar metabolites

EU risk assessment concluded 4% dermal 

absorption for fine particles and 2% for 

granular particles

ECHA, 2008 Reported in a secondary source with 

limited study details.

Following continuous exposure (via 

homes, offices and cars), HBCD was 

detected in human adipose tissue and 

blood

HBCD may be transferred across the 

placenta and via breast milk; estimates of 

uptake via breast milk range from 50 to 

100%; intake of HBCD via breast milk is 

1.5 ng/kg body weight/day for 

0-3-month-old babies and 5.6 ng body 

weight/day for 3-12-month-old babies 

Marvin et al., 2011 Reported in a secondary source with 

limited study details. 

4-41
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Acute Mammalian Toxicity LOW: Based on acute oral and dermal LD50 values >2,000 mg/kg in rats and rabbits and an acute 

inhalation LC50 >200 mg/L in rats.

Acute Lethality Oral Rat LD50 >10,000 mg/kg EPA, 2005; NICNAS, 2012 Reported in a secondary source with 

limited study details.

Rat LD50 >6,400 mg/kg EINECS, 2008 Reported in a secondary source. Nonguideline study. Dose and particle 

size not reported; 7-day observation

period.

Dermal Rabbit LD50 >8,000 mg/kg EPA, 2005; NICNAS, 2012 Reported in a secondary source with 

limited study details.

Rabbit LD50 >20,000 mg/kg EINECS, 2008; NICNAS, 2012 Non-guideline study. Too few 

animals were used; clinical signs not 

reported.

Inhalation Rat LC50 >200 mg/L EPA, 2005; NICNAS, 2012 Reported in a secondary source with 

limited study details.

Acute respiratory irritation test in Charles 

River CD rats (5/sex) exposed (wholebody) to 202 mg/L HBCD dust for 

4 hours

Slight dyspnea, which did not persist into 

the 14-day observation period; no deaths 

occurred and there were no signs of 

respiratory tract irritation

EINECS, 2008; NICNAS, 2012 Reported in a secondary source. Nonguideline study. No autopsy was 

performed. According to OECD 

guidelines (436), starting 

concentrations for dust should be 

0.05–5 mg/L.

Carcinogenicity MODERATE: Only one carcinogenicity study was located. In this mouse dietary study, there were 

increases in tumor incidence compared to controls. This study is not adequate to determine a hazard 

designation for the carcinogenicity endpoint due to high tumor incidence in control males. Carcinogenic 

potential cannot be ruled out therefore an estimated Moderate hazard is designated.

OncoLogic Results This compound is not amenable to 

available estimation methods.

4-42
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity (Rat 

and Mouse)

Lifetime (18-month) dietary bioassay in 

B6C3F1 mice (50/sex/dose)

Doses: 0, 100, 1,000 or 10,000 ppm for 

18 months

No adverse effect on mortality, clinical 

signs, body weight or food consumption 

Gross lesions/nodules detected at 

necropsy (hepatocyte swelling, 

degeneration, necrosis, vacuole formation 

and fatty infiltration) were not considered 

dose-related; 

Incidence of hepatocellular tumors were 

reported in males: 14/50, 19/50, 27/50, 

15/50 in the 0, 100, 1,000, and 10,000 

ppm groups, respectively and in females: 

0/50, 1/50, 1/50, 5/50 in the 0, 100, 1,000, 

and 10,000 ppm groups, respectively.

The study author stated that there was no 

correlation between dose and incidence of 

hepatic tumors for both male and female 

mice; the number of tumors in this study 

were within the historical rates of 

spontaneously induced tumors in control 

animals in this strain of mice

Kurokawa et al., 1984; EINECS, 

2008; EPA, 2005; NICNAS, 

2012

Study not conducted according to 

OECD guidelines; this study is not 

adequate to determine a hazard 

designation for the carcinogenicity 

endpoint.

4-43
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

HBCD does not meet criteria (NOHSC, 

2004) for classification as a carcinogen 

(R45, R49, R40)

NICNAS, 2012 Reported in a secondary source.

Combined Chronic 

Toxicity/

Carcinogenicity

No data located.

Genotoxicity LOW: Based on negative results for gene mutations in bacterial cells, a lack of chromosomal aberrations in 

human peripheral blood lymphocyte cells in vitro, and negative results in recombination and mouse 

micronucleus tests.

Gene Mutation in vitro Negative in Salmonella typhimurium 

(strains not specified) in the presence and 

absence of metabolic activation

EPA, 2005; NICNAS, 2012 Reported in a secondary source with 

limited study details.

Gene Mutation in vivo No data located.

Chromosomal 

Aberrations in vitro

Negative, mammalian chromosomal 

aberration test with human peripheral 

blood lymphocytes in the presence and 

absence of metabolic activation

Doses: 10, 19, 38, 75, 150, 300 and 

600 μg/mL

EPA, 2005; NICNAS, 2012 Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines,

and GLP.

DNA Damage and 

Repair

No data located.

Other in vitro Positive, intragenic recombination test in 

Sp5/V79 and SPD8 hamster cells; cell 

lines developed by study authors

Doses: 2-20 μg/mL

EPA, 2005; NICNAS, 2012 Reported in a secondary source. Nonguideline study. Not a standard test 

used by regulatory agencies to assess 

genotoxicity. Reliability and 

predictive ability is unknown. 

Negative, mouse micronucleus test

Doses: 0, 500, 1,000 or 2,000 mg/kg in 

dimethyl sulfoxide (DMSO)

EPA, 2005 Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

4-44
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproductive Effects MODERATE: Based on a LOAEL of 138 mg/kg-day for reduced number of primordial follicles in F1 

females in a two-generation dietary study in rats. There is uncertainty in that reproductive effects may 

occur at doses between the identified NOAEL (14.3 mg/kg-day) and the LOAEL (138 mg/kg-day).Using a 

conservative approach, a MODERATE hazard is designated. There were no treatment-related effects on the 

fertility index, sperm parameters, estrous cyclicity, reproductive organ weights or histopathology in F0 or F1

adults.

4-45
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproduction/ 

Developmental Toxicity 

Screen

Two-generation dietary (HBCD particles 

in ground food) study in Crl:CD (SD) rats 

(24/sex/group)

Doses: 0, 150, 1,500 or 15,000 ppm

Mean daily intake during entire 

administration: 10.2, 101 and 

1,008 mg/kg-day (F0 males); 14, 141 and 

1,363 mg/kg-day (F0 females); 11.4, 

115 and 1,142 mg/kg-day (F1 males); and 

14.3, 138 and 1,363 mg/kg-day (F1 

females)

Delayed eye opening and surface righting 

reflex response (F1 and F2 pups) that 

were not consistent over generations or 

sexes (not considered dose-related)

Decreased number of primordial ovarian 

follicles (30% at 1,500 and 15,000 ppm) 

in F1 generation (control: 316.3 ± 119.5; 

14.3 mg/kg-day: 294.2 ± 66.3; 138 

mg/kg-day: 197.9 ± 76.9).

No significant effects in copulation index, 

gestation index, pre-coital interval, 

number of implantations, delivery index 

or number of pups delivered in either F0

or F1 animals

NOAEL = 14.3 mg/kg-day 

LOAEL = 138 mg/kg-day (based on 

reduced number of primordial ovarian 

follicles in F1 females)

Ema et al., 2008 (as cited in 

EINECS, 2008; NICNAS, 2012)

Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD 416 

guidelines and GLP. HBCD particles 

were mixed with ground dry feed at 

the reported concentrations; 

bioavailability may be dependent on 

particle size and dose. Study does not 

consider litter effects; It is noted that 

the number of primordial cells in 

background control data was 189.5 –

353.4 (mean = 295.6) in 4 studies (10 

females/study) in studies conducted 

in 2005-2006. While the number of 

primordial cells was variable within 

these studies, the 30% treatmentrelated decrease at the 138 mg/kg-day 

dose level compared to controls in 

this study, is a significant decrease; in 

addition, the decrease at 198 mg/kg 

dose suggests a dose-response. 

4-46
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Combined Repeated 

Dose with 

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and 

Fertility Effects

28-Day gavage study in Sprague-Dawley 

rats (10/sex/group)

Doses: 0, 1, 2.5 and 5% (0, 940, 

2,410 and 4,820 mg/kg-day)

Very slight change of numerical 

development of the follicles and ripening 

follicles in the ovaries (4,820 mg/kg); 

normal differentiation in the testes and 

epididymides with undisturbed 

spermiohistogenesis (high-dose males)

No NOAEL/LOAEL reported

Zeller and Kirsch, 1969 (as cited 

in EINECS, 2008; EPA, 2005; 

NICNAS, 2012)

Unpublished laboratory report, 

described in a secondary source. Nonguideline study; EINECS (2008) 

states that this study was not carried 

out in accordance with present 

standards.

4-47
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

90-Day gavage study in Crl:CD(SD) IGS 

rats (15/sex/group)

Doses: 0, 100, 300 and 1,000 mg/kg-day 

No changes to the estrus cycle or to

sperm motility/viability, morphology or 

number

No treatment-related changes in weight or 

microscopic effects in the reproductive 

organs with the exception of an increase 

in mean prostate weight (1,000 mg/kgday) on day 90; relative prostate weight 

was also increased on day 90 compared 

with controls; there were no statistically 

significant differences in prostate weights 

between the control and treated groups 

following the recovery period (28 days 

post exposure) 

NOAEL = 1,000 mg/kg-day (highest dose 

tested

LOAEL = Not established 

Chengelis, 2001 (as cited in EPA, 

2005; NICNAS, 2012)

Unpublished laboratory report, 

described in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

4-48
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Developmental Effects HIGH: Based on a LOAEL of 13.5 mg/kg-day (NOAEL = 0.9 mg/kg) in mice for reduced habituation, 

decreased locomotion, and decreased rearing in neonatal male mice exposed to HBCD on postnatal day 

(PND) 10. In addition, hearing appeared to be impaired at low frequency ranges following exposure to 

HBCD at doses estimated to be as low as 0.2 mg/kg-day (BMD05 = 1.0 mg/kg-day) in adult rats exposed via 

diet from pre-mating to after weaning. Other neurodevelopmental effects occurred at higher doses. Reduced 

density of brain CNPase-positive oligodendrocytes was observed in a dietary study in rats exposed to HBCD 

from gestation day (GD) 10 until postnatal day (PND) 20 at a dose >1,000 mg/kg-day. A LOAEL of 1504.8

mg/kg-day (time weighted average) was identified in this study for thyroid effects (increased thyroid weight 

and decreased serum triiodothyronine [T3] concentrations).There is uncertainty in that these thyroid effects 

may occur at doses between the identified NOAEL (146.3 mg/kg-day) and the identified LOAEL 

(1504.8 mg/kg-day). Benchmark dose (BMD) modeling was conducted to predict at which dose these effects 

could occur. A BMDLSD1 of 73 mg/kg-day for decreased serum T3 levels was predicted, which falls within 

the criteria for a Moderate hazard designation. A dose-dependent increase in F2 pup mortality was also 

observed at 15,000 ppm (1,363 mg/kg-day). Also, in a two-generation dietary study in rats, delayed eye 

opening was observed in F1 and F2 pups; however, this effect was not consistent over generations or sexes 

and was not considered to be dose-related. No developmental effects were observed in two other prenatal 

exposure studies at oral doses ≥ 500 mg/kg-day. 

Reproduction/ 

Developmental Toxicity 

Screen

Dietary study in pregnant Crj:CD rats; 

Doses: 0, 100, 1,000 or 10,000 ppm (0, 

8.1-21.3, 80.7-212.9 or 

803.2-2,231.3 mg/kg-day) from gestation 

day (GD) 10 until postnatal day (PND) 20 

Time-weighted average (TWA) doses: 0, 

14.8, 146.3 and 1,504.8 mg/kg-day

Maternal toxicity: increased relative 

thyroid weights

Trend for an increase in the incidence of 

thyroid follicular cell hypertrophy at 

100 and 1,000 ppm (TWA dose 14.8 and 

146 mg/kg-day, respectively) in dams; 

statistically significant at 10,000 ppm 

Saegusa et al., 2009 Lowest end of maternal exposure 

range used to determine LOAEL and 

NOAEL values for maternal and 

developmental toxicity and thus, 

hazard. 

TWA doses were calculated by 

multiplying the HBCD intake 

(mg/kg-day) by the number of 

inclusive days of exposure for each 

time point. The sum of each time 

point for an individual dietary 

concentration (100, 1,000 and 

12,000 ppm) was divided by the total 

number of inclusive days (33 days) of 

exposure. 

4-49
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

(TWA dose 1,504.8 mg/kg-day)

Developmental toxicity: No 

abnormalities in clinical observation in 

offspring; increased relative liver weight; 

weak hypothyroidism with increased 

thyroid weight, increased incidence of 

thyroid follicular cell hypertrophy, 

increased thyroid stimulating hormone 

[TSH] concentrations and decreased T3 

concentrations at 10,000 ppm (TWA dose 

1,504.8 mg/kg-day); reduced density of 

CNPase-positive oligodendrocytes at 

10,000 ppm (TWA dose 1,504.8 mg/kgday)

Increased thyroid weight and decreased 

serum T3 concentrations when male 

offspring reached adult stage at 

1,000 ppm (TWA dose 146.3 mg/kg-day)

Maternal: 

NOAEL = 1,000 ppm (146.3 mg/kg-day

LOAEL = 10,000 ppm (1504.8 mg/kgday, (based on increased incidence of 

thyroid follicular cell hypertrophy)

Developmental: 

NOAEL = 100 ppm (14.8 mg/kg-day) 

LOAEL = 1,000 ppm (146.3 mg/kg-day, 

based on thyroid effects)

BMDSD1 = 119.68 mg/kg-day (based on 

decreased serum T3 levels)

BMDLSD1 = 73.53 mg/kg-day

Saegusa et al., 2009 (continued)

Dosing administered from gestation 

day (GD) 10 to postnatal day (PND)

20 = GDs 10-20: 0, 8.1, 80.7 and 

803.2 mg/kg-day; PNDs 1-9: 0, 14.3, 

138.7 and 1,404.8 mg/kg-day; PNDs 

9-20: 0, 21.3, 212.9 and 2,231.3 

mg/kg-day (described in study 

report).

In an effort to predict at what dose 

effects would occur, BMD modeling 

was conducted on the datasets for 

changes in serum T3 levels and for 

changes in thyroid weight. The BMD 

and BMDL for a change of 1 standard 

deviation from the control for 

decreased serum T3 levels were 

predicted to be 119.68 and 

73.53 mg/kg-day, respectively (see 

Table 1 at end of profile). 

The data for changes in thyroid 

weight were determined not to be 

suitable for BMD modeling (Table 2).

It is not clear if effects on brain 

CNPase-positive oligodendrocytes

are predictive for functional effects.

Thyroid weights were not recorded 

on PND 20. There is generally a 

typically high variance in TSH levels; 

changes in point measurements of 

4-50
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Saegusa et al., 2009 (continued) thyroid hormone are more indicative 

of altered thyroid function when 

observed with changes in thyroid 

weight and histopathology.

4-51
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Two-generation dietary study in 

Crl:CD(SD) rats (24/sex/group)

Doses: 0, 150, 1,500 or 15,000 ppm

(10-14, 101-141 or 1,008-1,363 mg/kgday)

Mean daily intake during entire 

administration: 10.2, 101 and 

1,008 mg/kg-day (F0 males); 14, 141 and 

1,363 mg/kg-day (F0 females); 11.4, 

115 and 1,142 mg/kg-day (F1 males); and 

14.3, 138 and 1,363 mg/kg-day (F1 

females)

No effect on spontaneous locomotor 

activity (10 min intervals for a total of 60 

min; F1 pups). No difference between 

controls and treated F1 rats on day 1 of 

the T-maze test. On day 3 of T-maze, 

males performed better than controls 

(shorter elapsed time at 1,500 and 15,000 

ppm with fewer errors at 15,000 ppm), 

but no difference between controls and 

females. Delayed eye opening and surface 

righting reflex response (F1 and F2 pups) 

that was not consistent over generations 

or sexes (not considered dose-related); 

dose-dependent pup mortality during 

lactation (F2, 35% at 15,000 ppm)

NOAEL = 138 mg/kg-day

LOAEL = 1,363 mg/kg-day (based on 

increased pup mortality during lactation 

in offspring from F1 dams)

Ema et al., 2008 (as cited in 

EINECS, 2008; NICNAS, 2012)

Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP. HBCD particles were mixed 

with ground dry feed at the reported 

concentrations. Bioavailability may 

be dependent on particle size and 

dose. Study does not consider litter 

effects.

4-52
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Wistar rats were exposed via the diet 

before conception, through mating, 

gestation, lactation and after weaning

Doses: 0, 0.1, 0.3, 1, 3, 10, 30 and 

100 mg/kg-day

There were no treatment-related changes 

in number of implantations, litter size, 

and sex ratio compared to controls

Effects on lower frequency range in 140-

day old male offspring; no progressive 

delays in peak latencies were detected in 

later waves of the brainstem auditory 

evoked potentials (BAEP), suggesting a 

cochlear origin of hearing impairment.

Decreased latencies to movement onset

were reported in all three situations (bar, 

grid, box) used to measure haloperidolinduced cataleptic behavior in 110-day 

old female rats in the 30 and 100 mg/kgday dose groups at testing times 30 and 

60 minutes. The BMD and BMDL for the 

sum of latencies in female rats were 15.6 

and 3.7 mg/kg-day, respectively. Male 

rats exhibited a significant latency only 

for foreleg retraction on the box at the 60 

minute test time (BMD and BMDL = 

10.8 and 3.0 mg/kg-day, respectively)

BMD05 = 1.0

BMDL05 = 0.2 mg/kg-day (based on 

hearing impairment)

Lilienthal et al., 2006, 2009 (as 

cited in EINECS, 2008; 

NICNAS, 2012)

Guideline study. Conducted

according to current EPA, OECD 

Guideline 415. BMD doses were 

calculated by the authors using a 

biologically relevant benchmark 

response of 5% deviation change 

from control; Rats were tested at 110 

and 140 days old for the cataleptic 

and hearing impairment tests, 

respectively. It is difficult to 

determine, however, if the effect is 

due to developmental exposure to 

HBCD, a result of repeated-dose 

exposure, or a combination of the 

two. Due to this uncertainty, this 

study was not used to determine the 

hazard designation; however, the 

results of this study suggest that there 

is potential concern for neurotoxic 

effects.

4-53
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Combined Repeated 

Dose with 

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development Gavage study in pregnant 

Crl:CD(SD)IGS Br rats (25/group) 

Dose: 0, 250, 500 or 1,000 mg/kg-day 

from gestation days (GDs) 6 to 19

No maternal mortality or treatmentrelated effects on clinical signs, body 

weight gain or food consumption

No effects on intrauterine growth/

survival; no treatment-related fetal 

malformations or developmental 

variations.

NOAEL (maternal/developmental): 

1,000 mg/kg-day (highest dose tested)

LOAEL = Not established

Stump, 1999 (as cited in 

EINECS, 2008; EPA, 2005; 

NICNAS, 2012)

Unpublished laboratory report, 

described in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP. There were no effects at the 

highest dose tested; a LOAEL was 

not identified.

4-54
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Dietary study in pregnant rats 

Doses: 0, 0.01, 0.1 or 1% HBCD on 

gestation days (GDs) 0-20; authors 

estimate doses in the feed were equivalent 

to 0, 5, 50 or 500 mg HBCD/kg body 

weight-day

No effects on maternal weight gain or 

food consumption and no gross 

appearance of internal organs 

No adverse effects on corpora lutea, 

implants, resorptions, live fetuses, sex 

ratio or body or placental weight and no 

fetal deaths; no external, skeletal or 

visceral malformations were detected; a 

few skeletal variations were present, but 

were of similar type noted in controls and 

not considered statistically significant

Normal development in neonates carried 

through to 6 weeks of age

NOAEL = 1% (500 mg/kg-day, highest 

dose tested)

LOAEL = Not established

Murai et al., 1985 (as cited in 

EPA, 2005; NICNAS, 2012)

Reported in secondary sources. EPA 

(2005) refers to KEMI, who deemed 

this study to be insufficient. There 

were no effects at the highest dose 

tested; a LOAEL was not identified.

Same study described in EINECS 

(2008) with variations on calculated 

doses:

Doses equivalent to: 0, 7.5, 75 and 

750 mg/kg-day (based on assumption 

that animals mean weight is 200 g 

and food consumption is 15 g/day)

NOAEL (fetal) = 750 mg/kg-day 

NOAEL (maternal) = 75 mg/kg-day 

based on 13% liver weight increase at 

the high dose.

4-55
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Postnatal Development Gavage study in neonatal male NMRI 

mice (8-10/group)

Doses: 0.9 or 13.5 mg/kg dissolved in a 

mixture of egg lecithin and peanut oil on 

PND 10

Reduced habituation with initial 

hypoactivity followed by hyperactivity in 

a novel environment; decreased 

locomotion and rearing during first 

20 minutes with no effects in later 

measurements 

NOAEL = 0.9 mg/kg

LOAEL = 13.5 mg/kg (based on reduced 

habituation, decreased locomotion, and 

rearing)

Eriksson et al., 2006 (as cited in 

EINECS, 2008; NICNAS, 2012)

Reported in a secondary source. Nonguideline study. Study used too few 

dose groups and the behavioral 

alterations were induced at doses that 

did not produce clinical signs or 

affect weight gain. Though the 

Eriksson et al., 2006 study was a nonguideline study, it was adequate to 

use for assessing neurodevelopmental 

effects; exposure occurred during the 

peak period of rapid brain growth and 

the methodology was validated with 

known neurotoxic agents in previous 

studies.

Effects due to litter size were not 

taken into consideration.

4-56
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on structural alert for cyclic halogenated 

aliphatic hydrocarbons and professional judgment. No adverse effects were noted in functional observation 

battery (FOB) and motor activity tests at doses ≤1,000 mg/kg-day (highest dose tested) in adult animals. In 

another study, hearing appeared to be impaired at low frequency ranges following exposure to HBCD at 

doses estimated to be as low as 0.2 mg/kg-day in adult rats exposed from pre-mating to after weaning; 

uncertainty exists as to whether the effects were a result of gestational/developmental exposure or repeated 

dose exposure to HBCD therefore it does not influence the adult neurotoxicity hazard designation.

Neurotoxicity Screening 

Battery

Potential for producing neurotoxicity

(Estimated)

EPA, 2011 Estimated based on structural alert for 

cyclic halogenated aliphatic 

hydrocarbons.

90-Day gavage study in 

Crl:CDC(SD)IGS rats (15/sex/group)

Doses: 0, 100, 300 and 1,000 mg/kg-day 

at a dosage volume of 5 mL/kg in corn 

oil; test article was a composite of three 

lots of commercial HBCD 

No adverse results in functional 

observation battery and motor activity 

tests 

NOAEL = 1,000 mg/kg-day (highest dose 

tested)

LOAEL = Not established 

Chengelis, 2001 (as cited in EPA, 

2005; NICNAS, 2012)

Reported in a secondary source. 

Guideline study performed according 

to current EPA, OECD guidelines and 

GLP.

In vitro plasma membrane uptake study in 

removed brains of male Wister rats

Doses: 2-20 μM 

Inhibition of neurotransmitter uptake into 

synaptosomes, dopamine uptake into 

synaptic vesicles and glutamate uptake at 

low concentrations

Mariussen and Fonnum, 2003 (as 

cited in EINECS, 2008; 

NICNAS, 2012)

Study reported in a secondary source.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Neurodevelopmental Wistar rats were exposed via the diet 

before conception, through mating, 

gestation, lactation and after weaning

Doses: 0, 0.1, 0.3, 1, 3, 10, 30 and 

100 mg/kg-day

There were no treatment-related changes 

in number of implantations, litter size, 

and sex ratio compared to controls

Effects on lower frequency range in 140-

day old male offspring; no progressive 

delays in peak latencies were detected in 

later waves of the brainstem auditory 

evoked potentials (BAEP), indicating a 

cochlear origin of hearing impairment.

Decreased latencies to movement onset

was reported in all three situations (bar, 

grid, box) used to measure haloperidolinduced cataleptic behavior in 110-day 

old female rats in the 30 and 100 mg/kgday dose groups at testing times 30 and 

60 minutes. The BMD and BMDL for the 

sum of latencies in female rats were 15.6 

and 3.7 mg/kg-day, respectively. Male 

rats exhibited a significant latency only 

for foreleg retraction on the box at the 60 

minute test time (BMD and BMDL = 

10.8 and 3.0 mg/kg-day, respectively)

BMD05 = 1.0

BMDL05 = 0.2 mg/kg-day (based on 

hearing impairment)

Lilienthal et al., 2006, 2009 (as 

cited in EINECS, 2008; 

NICNAS, 2012)

Guideline study. Conducted

according to current EPA, OECD 

Guideline 415. BMD doses were 

calculated by the authors using a 

biologically relevant benchmark 

response of 5% deviation change 

from control.

Rats were tested at 110 and 140 days 

old for the cataleptic and hearing 

impairment tests, respectively. It is 

difficult to determine, however, if the 

effect is due to developmental 

exposure to HBCD, a result of 

repeated-dose exposure, or a 

combination of the two. Due to this 

uncertainty, this study was not used 

to determine the hazard designation; 

however, the results of this study 

suggest that there is potential for 

neurotoxic effects.

4-58
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Repeated Dose Effects MODERATE: Based on increased TSH levels in F0 female rats at an oral dose of 14 mg/kg-day (lowest dose 

tested) in a two-generation dietary study. In a developmental study in rat dams exposed from gestation day 

(GD) 10 until postnatal day (PND) 20, increased thyroid weights and increased incidence of thyroid 

follicular cell hypertrophy were observed at 146.3 mg/kg-day (NOAEL= 14.8 mg/kg-day). Repeat dose 

studies reported liver effects including increased liver weights in conjunction with histopathological findings 

in a 90-day gavage study in rats administered 100 mg/kg-day (lowest dose tested) and increased liver weights 

in a 28-day gavage study in rats at a dose of 940 mg/kg-day (lowest dose tested). In the 28-day study, effects 

on the thyroid (microfollicular hyperplasia and increased activity of the thyroid epithelium) also occurred at 

940 mg/kg-day and were attributed to hypermetabolism as a result of increased thyroid activity. No 

significant adverse effects were noted in a 28-day gavage study in rats at doses up to 1,000 mg/kg-day; 

treatment-related liver effects noted in this study were mild, reversible and without effect on the clinical 

condition of the animals or associated with organ damage or diminished function. There is potential for 

nephrotoxicity based on a structural alert for halogenated aliphatic hydrocarbons.

Potential for producing nephrotoxicity 

(Estimated)

EPA, 2011 Estimated based on a structural alert 

for halogenated aliphatic 

hydrocarbons.

4-59
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Two-generation dietary study in 

Crl:CD(SD) rats (24/sex/group)

Doses: 0, 150, 1,500 or 15,000 ppm

(0, 10-14, 101-141 or 1,008-1,363 mg/kgday)

Mean daily intake during entire 

administration: 10.2, 101 and 

1,008 mg/kg-day (F0 males); 14, 141 and 

1,363 mg/kg-day (F0 females); 11.4, 

115 and 1,142 mg/kg-day (F1 males); and 

14.3, 138 and 1,363 mg/kg-day (F1

females)

Increased serum TSH (F0 females at 

150 ppm and F1 females at 15,000 ppm); 

decreased serum follicle stimulating 

hormone (FSH) levels in F0 males and 

increased in F0 females at 15,000 ppm; 

increased dihydrotestosterone (DHT) in 

F1 males (15,000 ppm); increased 

incidence of decreased size of thyroid 

follicular cells in F0 females (1,500 ppm)

No significant differences in serum 

testosterone, estradiol, progesterone or 

luteinizing hormone (LH) levels 

Authors concluded that the effect on TSH 

levels is consistent through dose groups 

and generations, and is considered an 

effect of HBCD-exposure

NOAEL = Not established

LOAEL = 150 ppm (14 mg/kg-day, based 

on increased TSH levels in F0 females; 

lowest dose tested)

Ema et al., 2008 (as cited in 

EINECS, 2008; NICNAS, 2012)

Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP. HBCD particles were mixed 

with ground dry feed at the reported 

concentrations; bioavailability may 

be dependent on particle size and 

dose. Study does not consider litter 

effects.

Uncertainty exists concerning the

extrapolation of the biological 

significance of thyroid effects

between rodents and humans. There 

is uncertainty as to where effects may 

occur as this effect occurred at the 

lowest dose tested. It is possible that 

this effect could occur at a dose 

<10 mg/kg-day. 

4-60
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Dietary study in pregnant Crj:CD rats; 

Doses: 0, 100, 1,000 or 10,000 ppm (0, 

8.1-21.3, 80.7-212.9 or

803.2-2,231.3 mg/kg-day) from gestation 

day (GD) 10 until postnatal day (PND)

20.

Time weighted average (TWA) doses: 0, 

14.8, 146.3 or 1,504.8 mg/kg-day

Dams: increased relative thyroid 

weights; trend for an increase in the 

incidence of thyroid follicular cell 

hypertrophy at 100 and 1,000 ppm (TWA 

dose 14.8 and 146 mg/kg-day, 

respectively); statistically significant at 

10,000 ppm (TWA dose 1,504.8 mg/kgday)

NOAEL = 100 ppm (14.8 mg/kg-day) 

LOAEL = 1,000 ppm (146.3 mg/kg-day, 

based on increased incidence of thyroid 

follicular cell hypertrophy)

Saegusa et al., 2009 Lowest end of maternal exposure 

range used to determine LOAEL and 

NOAEL values for repeated-dose 

toxicity and thus, hazard.

Time weighted average (TWA) doses 

were calculated by multiplying the 

HBCD intake (mg/kg-day) by the 

number of inclusive days of exposure 

for each time point. The sum of each 

time point for an individual dietary 

concentration (100, 1,000 and

12,000 ppm) was divided by the total 

number of inclusive days (33 days) of 

exposure. 

Dosing administered from gestation 

day (GD) 10 to postnatal day (PND)

20 = GDs 10-20: 0, 8.1, 80.7 and 

803.2 mg/kg-day; PNDs 1-9: 0, 14.3, 

138.7 and 1,404.8 mg/kg-day; PNDs

9-20: 0, 21.3, 212.9 and 2,231.3 

mg/kg-day (described in study 

report).

4-61
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

90-Day gavage study in Crl:CD (SD)IGS 

rats (15/sex/group)

Doses: 0, 100, 300 and 1,000 mg/kg-day 

at a dosage volume of 5 mL/kg in corn 

oil; test article was a composite of three 

lots of commercial HBCD 

Increase in liver weight (100 mg/kg-day) 

with mild histopathological findings 

(minimal hepatocellular vacuolation, 

minimal to mild hepatocellular 

hypertrophy). Minimal thyroid follicular 

cell hypertrophy (1,000 mg/kg-day); it is 

not apparent if these changes were related 

to treatment (authors state that changes 

may have been a related to reduced serum 

thyroxine [T4] levels, which is a normal 

physiological response of healthy 

organisms acting to maintain serum T4 

levels in the normal range)

No clinical signs of toxicity and no 

adverse effects on survival, food 

consumption, body weight or 

hematological parameters; no articlerelated ocular lesions; no adverse results 

in functional observation battery and 

motor activity tests; no changes to the 

estrus cycle or to sperm motility/viability, 

morphology or number; no gross lesions

NOAEL = Not established

LOAEL = 100 mg/kg-day (based on 

increased liver weight in conjunction with 

histopathological findings; lowest dose 

tested)

Chengelis, 2001 (as cited in EPA, 

2005; NICNAS, 2012)

Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

Commercial mixture composed of α 

isomer (6.3%), β isomer (9.1%) and γ

isomer (76.9%).

Study authors state that all test 

article-related changes were mild, 

reversible and generally secondary to 

hepatic enzyme induction (which is 

an adaptive not a toxic change) and 

without effect on the clinical 

condition of the animals or associated 

with specific target organ damage or 

diminished function; however, 

changes in liver weight in 

conjunction with histopathological 

can be considered an adverse effect.

4-62
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

28-Day gavage study in Sprague-Dawley 

rats (10/sex/group)

Doses: 0, 1, 2.5 and 5% (0, 940, 

2,410 and 4,820 mg/kg-day)

Increased absolute and relative liver 

weights at all dose levels when compared 

to the control, but no microscopic 

pathology detected. 

Thyroid microfollicular hyperplasia and 

increased activity of the thyroid 

epithelium were reported at 1% 

(940 mg/kg-day); these effects were more 

marked at 2.5% (2,410 mg/kg-day) and 

very marked hyperplastic thyroid tissue 

with adenomatous proliferation and 

thyroid epithelial hyperactivity was 

reported at 5% (4,820 mg/kg-day); not 

specified if these effects occurred in the 

control group; very slight numerical 

development of the follicles and ripening 

follicles in the ovaries (4,820 mg/kg-day)

Effects on the thyroid were attributed to 

hypermetabolism as a result of increased 

thyroid activity, and effects were not 

pathologic according to the study authors

No clinical signs related to treatment or 

changes in any other organ; no change in 

clinical chemistry parameters

Effects on the liver and thyroid were 

Zeller and Kirsch, 1969 (as cited 

in EPA, 2005; NICNAS, 2012)

Non-guideline study; limited study 

details reported in a secondary 

source.

The author’s determination of the 

thyroid effects being non-pathologic 

in nature is based on the study 

author’s judgment.

4-63
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

attributed to hyperactivity and 

hypermetabolism, respectively, and were 

not pathologic according to the study 

authors 

NOAEL = Not established

LOAEL = 1% (940 mg/kg-day, based on 

increased liver weights; lowest dose 

tested)

Zeller and Kirsch, 1969 (as cited 

in EPA, 2005; NICNAS, 2012) 

(continued)

90-Day dietary study in Sprague-Dawley 

rats (20/sex/group)

Doses: 0, 0.16, 0.32, 0.64 and 1.28%

(0, 120, 240, 470 and 950 mg/-day)

Increased incidence of hepatic lipoid 

phanerosis (fatty accumulation) in the 

liver was observed at all doses in a dosedependent manner; however, there were 

no changes in liver clinical chemistry and 

no detectable histological changes; study 

authors noted that these effects were 

transient effects and attributed to 

increased activity in the liver

No adverse clinical signs, changes in 

body weight or clinical chemistry 

parameters; no histological changes in 

any organ (other than the liver)

NOAEL = 950 mg/kg-day (highest dose 

tested)

LOAEL = Not established

Zeller and Kirsch, 1970 (as cited 

in EPA, 2005; NICNAS, 2012)

Unpublished laboratory report 

described in secondary sources. 

Guideline study. Was not conducted 

according to OECD guidelines. It is 

not specified where statistical 

significance for the increased 

incidence of liver effects occurs. 

Based on the limited observations 

reported, the NOAEL is determined 

(with low confidence) to be the 

highest dose tested (950 mg/kg-day). 

4-64
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

28-Day gavage study in Sprague-Dawley 

rats (12 rats [6 of each sex] in the 125 and 

350 mg/kg-day dose groups; 24 rats 

[12 of each sex] in the 1,000 mg/kg-day 

dose group)

Doses: 0, 125, 350 or 1,000 mg/kg-day; 

at conclusion of the study 6 rats/sex in 

control and 1,000 mg/kg-day groups were 

sacrificed and necropsied while the 

remaining animals had a 14 day recovery 

period.

Increased absolute liver weight 

(1,000 mg/kg-day in males, 350 and 

1,000 mg/kg-day in females); increased 

relative liver weight at 28-day sacrifice 

(350 and 1,000 mg/kg-day in males, all 

doses in females)

Effects on the liver were reversible by the 

end of the recovery period; authors 

consider this effect to be an adaptive 

rather than toxic response due to the lack 

of related histopathologic or serum 

chemistry changes

No clinical signs of toxicity and no 

adverse effects on survival, food 

consumption, body weight or 

hematological/serum chemistry values; 

no gross or microscopic lesions that could 

be attributed to the test article; no adverse 

results in functional observation battery 

or motor activity tests 

NOAEL = 1,000 mg/kg-day (highest dose 

tested)

LOAEL = Not established 

Chengelis, 1997 (as cited in EPA, 

2005; NICNAS, 2012)

Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

4-65
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Lifetime (18-month) dietary bioassay in 

B6C3F1 mice (50/sex/dose)

Doses: 0, 100, 1,000 or 10,000 ppm (0, 

13, 130 or 1,300 mg/kg-day for 

18 months

No adverse effect on mortality, clinical 

signs, body weight or food consumption 

Gross lesions/nodules were observed at 

necropsy (hepatocyte swelling, 

degeneration, necrosis, vacuole formation 

and fatty infiltration); however, effects 

were not dose-related

Tumors were sporadic in incidence and 

not related to test article

NOAEL = 1,300 mg/kg-day 

(10,000 ppm; highest dose tested)

LOAEL = Not established

Kurokawa et al., 1984 (as cited in 

EINECS, 2008; EPA, 2005; 

NICNAS, 2012)

Reported in a secondary source. 

Study was not conducted according to 

OECD guidelines.

Skin Sensitization LOW: Based on negative results for skin sensitization in human volunteers and guinea pigs.

Skin Sensitization Negative, patch test with 10% HBCD in 

volunteers

EPA, 2005 Reported in a secondary source. 

Guideline study.

Negative, guinea pigs EPA, 2005; NICNAS, 2012 Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

Negative, mice:

Local lymph node assay with 2, 20 or 

50% w/v HBCD in DMF

EPA, 2005; NICNAS, 2012 Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

4-66
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Positive, guinea pigs

Intra-dermal injection and topical 

application

EINECS, 2008; EPA, 2005; 

NICNAS, 2012

Reported in a secondary source. 

Results are questionable; impurities

unknown). In addition, the study was 

an intra-dermal injection study and

acetone was used as the vehicle in the 

dermal challenge phase of the tests, 

which promotes penetration on 

shaved skin.

Respiratory Sensitization No data located.

Respiratory 

Sensitization

No data located.

Eye Irritation VERY LOW: HBCD is not an eye irritant in rabbits.

Eye Irritation Non-irritant, rabbits EPA, 2005; NICNAS, 2012 Reported in a secondary source with 

limited study details.

Dermal Irritation VERY LOW: HBCD is not a dermal irritant in rabbits or guinea pigs.

Dermal Irritation Non-irritant, rabbits EPA, 2005; NICNAS, 2012 Reported in a secondary source with 

limited study details.

Non-irritant, guinea pigs EINECS, 2008 Reported in a secondary source. 

Guideline study performed according 

to current EPA, OECD guidelines and 

GLP.

4-67
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Endocrine Activity In vivo: Thyroid effects were noted following repeated HBCD in vivo exposure in rats. Increased TSH levels 

were reported in F0 females (14 mg/kg-day) and F1 females (1,363 mg/kg-day) exposed to HBCD in a twogeneration dietary study. In addition, increased size of thyroid follicular cells in F0 females (141 mg/kg-day), 

decreased serum FSH levels in F0 males, increased FSH levels in F0 females and increased DHT in F1 males 

were reported at the highest dose tested (1,008-1,363 mg/kg-day). Increased relative thyroid weights and 

increased incidence of thyroid follicular cell hypertrophy were reported in dams exposed on gestation day 

(GD) 10 until postnatal day (PND) 20 at a dose of 1,504.8 mg/kg-day in a dietary study in rats. Offspring 

developed weak hypothyroidism with increased thyroid weight, increased incidence of thyroid follicular cell 

hypertrophy, increased FSH levels and decreased T3 concentrations at 1,504.8 mg/kg-day. In this same 

study, increased thyroid weight and decreased serum T3 concentrations were reported in adult stage male 

offspring at 146.3 mg/kg-day. Thyroid microfollicular hyperplasia and increased activity of the thyroid 

epithelium were reported at a dose of 940 mg/kg-day in rats following gavage exposure for 28 days. These 

effects were attributed to hypermetabolism based on increased thyroid activity, and no pathological findings 

were noted. Minimal thyroid follicular cell hypertrophy was reported at 1,000 mg/kg-day following a 90-day 

gavage study in rats. In fish, disruption of thyroid axis (lower circular FT4 and higher FT3; increase in 

thyroid epithelial cell height) was evident in γ-HBCD-exposed Oncorhynchus mykiss. Fish fed a α-HBCDenriched diet exhibited altered glucuronyltransferase activity and thyroid epithelial cell heights, and fish fed 

β-HBCD had altered FT4 and FT3 and glucuronyltransferase activity. In contrast, limited potential for 

endocrine disruption of the thyroid hormonal system was noted in Platichthys flesus (flounder) exposed to a 

technical mixture of HBCD (α-, β- and γ-diastereomers) in sediment and food for 78 days. HBCD alone or in 

combination with T3 facilitated very fast tail tip regression in tadpoles in an ex vivo study.

In vitro: HBCD exhibited antiandrogenic, antiprogesteronic and T3-potentiating properties, and a low 

binding of thyroxine to transthyretin (TTR) in rat pituitary cells and rat pituitary tumor GH3 cells, 

activated thyroid receptor in the presence of T3 in human cervical carcinoma cells, and is a pregnane X 

receptor (PXR) agonist in rat and human hepatoma cells. In addition, γ-HBCD is a moderate androgen 

receptor (AR) and progesterone receptor (PR) antagonist in rat pituitary tumor GH3 cells, while there was 

no antagonistic activation detected for aryl hydrocarbon receptor (AhR) and estrogen receptor (ER). 

α-HBCD and γ-HBCD showed T3-enhanced activity in the T-screen assay, and there was no inhibition of 

estradiol (E2) sulfotransferate in rat pituitary tumor GH3 cells. Xenobiotic-metabolizing enzymes and genes 

associated with the TH pathway and lipid regulation were noted to be sensitive to HBCD in an in vitro study 

in chicken hepatocytes. 

4-68
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Representative in vivo studies

28-Day gavage study in Sprague-Dawley 

rats (10/sex/group)

Doses: 0, 1, 2.5 and 5% (0, 940, 

2,410 and 4,820 mg/kg--day)

Thyroid microfollicular hyperplasia and 

increased activity of the thyroid 

epithelium were reported at 1% 

(940 mg/kg-day); these effects were more 

marked at 2.5 % (2,410 mg/kg-day), and 

very marked hyperplastic thyroid tissue 

with adenomatous proliferation and 

epithelial hyperactivity was reported at 

5% (4,820 mg/kg-day); it is not specified 

if these effects occurred in the control 

group

Very slight numerical development of the 

follicles and ripening follicles in the 

ovaries (4,820 mg/kg-day)

Effects on the thyroid were attributed to 

hypermetabolism as a result of increased 

thyroid activity, and effects were not 

pathologic according to the study authors 

No clinical signs related to treatment or 

changes in any other organ; no change in 

clinical chemistry parameters

Zeller and Kirsch, 1969 (as cited 

in EPA, 2005)

Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

4-69
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

90-Day gavage study in 

Crl:CDC(SD)IGS rats (15/sex/group)

Doses: 0, 100, 300 and 1,000 mg/kg-day 

at a dosage volume of 5 mL/kg in corn 

oil; test article was a composite of three 

lots of commercial HBCD 

Minimal thyroid follicular cell 

hypertrophy (1,000 mg/kg-day); it is not 

apparent if these changes were related to 

treatment (authors state that changes may 

have been a related to reduced serum T4 

levels, which is a normal physiological 

response of healthy organisms acting to 

maintain serum T4 levels in the normal 

range)

No adverse changes to the estrus cycle or 

to sperm motility/viability, morphology 

or number

Chengelis, 2001 (as cited in EPA, 

2005)

Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

4-70
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Two-generation dietary study in 

Crl:CD(SD) rats (24/sex/group)

Doses: 0, 150, 1,500 or 15,000 ppm

(10-14, 101-141 or 1,008-1,363 mg/kgday)

Mean daily intake during entire 

administration: 10.2, 101 and 

1,008 mg/kg-day (F0 males); 14, 141 and 

1,363 mg/kg-day (F0 females); 11.4, 

115 and 1,142 mg/kg-day (F1 males); and 

14.3, 138 and 1,363 mg/kg-day (F1

females)

Increased TSH (F0 females at ≥150 ppm 

and F1 females at ≥15,000 ppm); 

decreased serum FSH levels in F0 males 

and increased in F0 females at 

15,000 ppm; increased DHT in F1 males 

(15,000 ppm); increased incidence of 

decreased size of thyroid follicular cells 

in F0 females (1,500 ppm)

No significant differences in serum 

testosterone, estradiol, progesterone or 

LH levels 

Authors conclude that the effect on TSH 

levels is consistent through dose groups 

and generations, and is considered an 

effect of HBCD exposure

Ema et al., 2008 (as cited in 

EINECS, 2008; NICNAS, 2012)

Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

4-71
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Dietary study in pregnant Crj:CD rats; 

Doses: 0, 100, 1,000 or 10,000 ppm (0, 

8.1-21.3, 80.7-212.9 or

803.2-2,231.3 mg/kg-day) from gestation 

day (GD) 10 until postnatal day (PND)

20.

Time weighted average (TWA) doses: 0, 

14.8, 146.3 or 1,504.8 mg/kg-day

Dams: increased relative thyroid 

weights; tendency for increase in the 

incidence of thyroid follicular cell 

hypertrophy at 100 and 1,000 ppm (TWA 

dose 14.8 and 146 mg/kg-day, 

respectively); statistically significant at 

10,000 ppm (TWA dose 1,504.8 mg/kgday)

Offspring: weak hypothyroidism with 

increased thyroid weight, increased 

incidence of thyroid follicular cell 

hypertrophy, increased TSH 

concentrations and decreased T3 

concentrations at 10,000 ppm 

(1,504.8 mg/kg-day); increased thyroid 

weight and decreased serum T3 

concentrations when offspring reached 

adult stage at 1,000 ppm (146.3 mg/kgday)

Saegusa et al., 2009 Lowest end of maternal exposure 

range used to determine LOAEL and 

NOAEL values for maternal and 

developmental toxicity and thus, 

hazard. Study does not consider litter 

effects.

Time weighted average (TWA) doses 

were calculated by multiplying the 

HBCD intake (mg/kg-day) by the 

number of inclusive days of exposure 

for each time point. The sum of each 

time point for an individual dietary 

concentration (100, 1,000 and

12,000 ppm) was divided by the total 

number of inclusive days (33 days) of 

exposure. 

Dosing administered from gestation 

day (GD) 10 to postnatal day (PND)

20 = GDs 10-20: 0, 8.1, 80.7 and 

803.2 mg/kg-day; PNDs 1-9: 0, 14.3, 

138.7 and 1,404.8 mg/kg-day; PNDs

9-20: 0, 21.3, 212.9 and 2,231.3 

mg/kg-day (described in study 

report).

4-72
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

In vivo study in Platichthys flesus

(flounder) exposed to HBCD in sediment 

and food for 78 days; test substance was a 

technical mixture of 10.28, 8.72 and 

81.01% of α-, β- and γ-diastereomers, 

respectively; maximum concentration 

was 446 μg HBCD/g lipid weight (lw)

No adverse effects on behavior. No 

histopathological changes in internal 

organs including liver, spleen, kidney, 

gonads and thyroid gland related to 

HBCD exposure

Limited potential for in vivo endocrine 

disruption of the reproductive and thyroid 

hormonal system 

Kupier et al., 2007 (as cited in 

EINECS, 2008)

Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP.

4-73
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Dietary study in Oncorhynchus mykiss, 

fed either reference diet or three diets 

enriched with α-, β- or γ-HBCD for 

56 days

Test concentrations were 0.47 and 

0.84 ng/g (α- and γ-HBCD, respectively) 

Disruption of thyroid axis most evident in 

γ-HBCD-exposed group (lower circular 

FT4 and higher FT3; increase in thyroid 

epithelial cell height) 

Fish fed the α-HBCD-enriched diet also 

exhibited altered glucuronyltransferase 

activity and thyroid epithelial cell heights 

and the β-HBCD group had altered FT4 

and FT3 and glucuronyltransferase 

activity

Palace et al., 2008 Guideline study. The β-isomer was 

below the detection limit.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Representative ex vivo studies

Ex vivo thyroid hormone disruptive study 

in Xenopus laevis tadpoles

Doses: 1,000 or 10,000 nM HBCD alone 

or 20 nM T3 in combination with 10, 100, 

1,000 or 10,000 nM HBCD

Very fast tail tip regression at 1,000 nM 

HBCD alone or in combination with T3 

during the first 2 days of exposure; no 

further regression during the rest of the 

exposure period; no effect on tail 

regression at doses <1,000 nM

Authors conclude that regression was due 

to cytotoxic activity 

Schriks et al., 2006 (as cited in 

EINECS, 2008) 

Reported in a secondary source. Nonguideline study. Not validated 

according to OECD guidelines and no 

results from metabolic activation 

reported.

4-75
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Representative in vitro studies

In vitro study using rat pituitary cells to 

test potential effects of HBCD as an 

endocrine disruptor

Doses (test for T3 potentiating effect): 

10-12.5 μM (maximum concentration) for 

24 hours in the presence or absence of a 

reference agonist.

Doses (test for potency at act as a thyroid 

hormone receptor (TR) agonist or 

antagonist): 1 μM (maximum 

concentration) for 96 hours in the 

presence or absence of T3 hormone

HBCD exhibited antiandrogenic, 

antiprogesteronic and T3-potentiating 

properties in vitro, and a low binding to 

thyroxine binding to TTR

Hamers et al., 2006 (as cited in 

EINECS, 2008)

Reported in a secondary source. 

EINECS (2008) states: Study not 

validated according to OECD 

guidelines.

In vitro study using human cervical 

carcinoma cells

HBCD activated thyroid receptor in the 

presence of T3 

Fery et al., 2009 Test substance: HBCD containing 

10.3% α, 8.7% β, and 81.0% γHBCD.

In vitro study using rat and human 

hepatoma cells 

HBCD is a pregnane-X-receptor (PXR)

agonist, which may account for disrupted 

thyroid activity 

Fery et al., 2009 Test substance: HBCD containing 

10.3% α, 8.7% β, and 81.0% γHBCD.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

In vitro study using rat pituitary tumor 

GH3 cell line 

Dose: Maximum concentration of 1 μM 

in the presence or absence of T3 hormone 

for 96 hours

Moderate AR and PR antagonistic 

activity was reported for γ-HBCD. Very 

low or no antagonistic activation was 

detected for the other two receptors, AhR 

and ER. α-HBCD and γ-HBCD showed 

T3-enhanced activity at 1 μM in the 

T-screen assay

No inhibition of E2 sulfotransferase

HBCD exhibited antiandrogenic, 

antiprogesteronic and T3-potentiating 

properties in vitro, and a low binding to 

TTR

EINECS, 2008; Marvin et al., 

2011

Non-guideline study. No results from 

metabolic activation reported and not 

validated according to OECD 

guidelines.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

In vitro study in chicken (Gallus 

domesticus) hepatocytes exposed to 

nominal concentrations of 0.001-30 μM 

α-HBCD for 24 or 36 hours

Exposure to ≥1 mM resulted in 

significant upregulation of cytochrome 

P450 2H1 and CYP3A37 at 24 and 

36 hours; significant downregulation of 

transthyretin, thyroid hormone-responsive 

spot 14-α and liver fatty acid-binding 

protein

Results indicate that xenobioticmetabolizing enzymes and genes 

associated with the TH pathway and lipid 

regulation are vulnerable to HBCD

Crump et al., 2008 Guideline study.

Immunotoxicity HBCD exposure resulted in decreased total number of spleen cells, decreased T-helper and natural killer 

(NK) cells and decreased NK cell activity in rats.

Immune System Effects 28-Day gavage study in 7-week-old male 

Wistar rats (5/group)

Doses: 0, 0.3, 1, 3, 10, 30, 100 and 

200 mg/kg- day in corn oil

Decreased total number of cells per 

spleen, T-helper cells and NK cells; 

decreased NK cell activity (general 

decreasing trend, but increased at the high 

dose)

EINECS, 2008 Reported in a secondary source. 

Performed according the current 

OECD guidelines. However, study 

was not GLP and only limited study 

details were reported; data based on a 

small number of animals and only 

males were tested. No changes in 

spleen weight or histopathological 

effects were noted; therefore, the 

toxicological relevance of these 

findings is uncertain.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

ECOTOXICITY

ECOSAR Class Neutral organics

Acute Aquatic Toxicity VERY HIGH: Based on an EC50 of 0.027 mg/L in algae. NES is expected based on physical-chemical 

properties and other experimental and estimated values for fish, daphnia and algae; however, there is some 

indication of toxicity to algae at concentrations that are within the range of water solubility.

Fish LC50 Oncorhynchus mykiss 96-hour LC50

>0.0068 mg/L (nominal) or 

>0.0025 mg/L (mean measured)

EPA, 2005; NICNAS, 2012 Reported in a secondary source. 

Guideline study. Performed according 

to current EPA, OECD guidelines and 

GLP. No toxicity at HBCD’s limit of 

water solubility.

Lepomis macrochirus 96-hour LC50

>100 mg/L (nominal)

EPA, 2005 Reported in a secondary source with 

limited study details. Value exceeds 

water solubility.

Leuciscus idus 96-hour LC50

>10,000 mg/L (nominal)

EPA, 2005 Reported in a secondary source with 

limited study details. Value exceeds 

water solubility.

Fish 96-hour LC50 = 0.30 mg/L

(Estimated)

ECOSAR class: Neutral organics

ECOSAR v1.10

NES: The log Kow of 5.6 for this 

chemical exceeds the SAR limitation 

for the log Kow of 5.0; NES are 

predicted for these endpoints.

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Brachydanio rerio exposed to 0, 0.05, 

0.1, 0.5 and 1.0 mg L for up to 96 hours. 

Cell apoptosis, induction of reactive 

oxygen species (ROS) at 0.1, 0.5 and 

1.0 mg/L.

Exposure to HBCD results in oxidative 

stress and may induce apoptosis through 

involvement of caspases

NOEC = 0.05 mg/L

LOEC = 0.1 mg/L

Deng et al., 2009 Guideline study. Study details taken 

from abstract. This study is for a 

nontraditional endpoint for 

determining hazard designation. In 

addition, NOEC and LOEC values 

are above the limit of water solubility 

and will not be used to determine a 

hazard designation. No effects at 

saturation (NES) are predicted.

Daphnid LC50 Daphnia magna 48-hour EC50

>0.0068 mg/L (nominal) or 

>0.0032 mg/L (mean measured)

EPA, 2005; NICNAS, 2012 Reported in a secondary source. 

Guideline study performed according 

to current EPA, OECD guidelines and 

GLP. No toxicity at HBCD’s limit of 

water solubility; NES.

D. magna 48-hour EC50 = 146 mg/L 

(nominal)

Nominal test concentrations were 0.01-

1,000 mg/L (both below and above the 

water solubility)

EINECS, 2008 Reported in a secondary source. 

Guideline study performed according 

to current EPA, OECD guidelines and 

GLP. Value exceeds water solubility.

4-80
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnia 48-hour LC50 = 0.23 mg/L

(Estimated)

ECOSAR class: Neutral organics

ECOSAR v 1.10

NES: The log Kow of 5.6 for this 

chemical exceeds the SAR limitation 

for the log Kow of 5.0; NES are 

predicted for these endpoints.

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green Algae EC50 Skeletonema costatum 72-hour NOEC 

>0.01 mg/L (>10 μg HBCD)

EC50 = 0.027 mg/L (biomass)

EC50 = 0.052 mg/L (growth rate)

Desjardins et al., 2005; ECHA, 

2008 

Reported in a secondary source with 

limited study details. 

Pseudokirchneriella subcapitata 96-hour 

EC50 >0.0068 mg/L (nominal) or 

>0.0037 mg/L (mean measured)

EPA, 2005; NICNAS, 2012 Reported in a secondary source. 

Guideline study performed according 

to current EPA, OECD guidelines and 

GLP. No toxicity at HBCD’s limit of 

water solubility; NES.

Chlorella sp. 96-hour EC50 >1.5 mg/L EPA, 2005; NICNAS, 2012 Reported in a secondary source with 

limited study details. No toxicity at 

HBCD’s limit of water solubility; 

NES.

S. costatum 72-hour EC50 >0.0093-

0.012 mg/L

EPA, 2005; NICNAS, 2012 Reported in a secondary source with 

limited study details. No toxicity at 

HBCD’s limit of water solubility; 

NES.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

S. costatum 96-hour EC50 >0.0025 mg/L ECHA, 2008 Reported in a secondary source with 

limited study details. The test 

substance was made up of a 

composite of HBCD samples from 

three manufacturers containing 6.0% 

α-, 8.5% β- and 79.1% 

γ-diastereomers; total HBCD was 

93.6% of test substance. There were 

no effects at the highest concentration 

tested.

S. costatum 72-hour EC50 >0.0406 mg/L 

(40.6 μg HBCD/L)

NOEC >0.0406 mg/L (only concentration 

tested)

LOEC = Not identified

Desjardins et al., 2004 (as cited in 

ECHA, 2008; NICNAS, 2012) 

Reported in a secondary source with 

limited study details; LOECs were 

not identified. One test concentration 

at the limit of water solubility; NES.

Thalassiosira pseudonana 72-hour EC50 

>0.05–0.37 mg/L

Walsh et al., 1987 (as cited in 

EPA, 2005; NICNAS)

Reported in a secondary source with 

limited study details. No toxicity at 

HBCD’s limit of water solubility.

Scenedesmus subspicatus 96-hour EC50

>500 mg/L

No effect on growth inhibition

Siebel-Sauer and Bias, 1987 (as 

cited in EINECS, 2008)

Reported in a secondary source. 

Guideline study performed according 

to current EPA, OECD guidelines and 

GLP. Value exceeds water solubility.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae 96-hour EC50 = 0.29 mg/L

(Estimated)

ECOSAR class: Neutral organics

ECOSAR v. 1.10

The estimated effect exceeds the 

water solubility of 0.66 mg/L, but not 

by 10x as required to be considered 

NES by ECOSAR.

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

4-83
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Chronic Aquatic Toxicity VERY HIGH: Based on experimental 21-day LOEC = 0.0056 mg/L and NOEC = 0.0031 mg/L for γ-HBCD 

in Daphnia magna. 

Fish ChV Oncorhynchus mykiss 88-day NOEC 

>0.0037 mg/L (γ-HBCD).

27-Day hatching period; 61 days posthatch showed no effects on hatching 

success, time to swim-up, larval survival, 

fry survival or growth

Drotter et al., 2001; EPA, 2005 Reported in a secondary source. 

Guideline study performed according 

to current EPA, OECD guidelines and 

GLP; LOEC and MATC could not be 

determined due to absence of toxicity, 

but were considered >0.0037 or 

0.0068 mg/L (more than twice 

γ-HBCD’s water solubility). HBCD 

was not chronically toxic to rainbow 

trout at concentrations at or above its 

limit of solubility.

Fish ChV = 0.043 mg/L (Estimated)

ECOSAR class: Neutral organics

ECOSAR v. 1.10 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

4-84
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Chinese rare minnow 14-, 28- and 42-day 

waterborne HBCD exposure to 

0.1-0.5 mg/L 

Induced hepatic enzymes (as measured by 

EROD and PROD)

Induced oxidative stress in fish brain (as 

measured by ROS and TBARS)

28-day LOEC = 0.5 mg/L 

42-day LOEC = 0.1 mg/L 

Zhang et al., 2008 Study details reported in abstract. 

Values exceed water solubility. This 

study is for a non-traditional endpoint 

for determining hazard designation. 

In addition, LOEC values are above 

the limit of water solubility and will 

not be used to determine a hazard 

designation. A NOEC was not 

identified.

Daphnid ChV D. magna 21-day life cycle toxicity test. 

Nominal test concentrations were 0.85, 

1.7, 3.4 and 13.6 μg/L; measured test 

concentrations were 0.87, 1.6, 3.1, 

5.6 and 11 μg/L.

LOEC = 0.0056 mg/L ([0.0042 mg/L 

geometric mean]; reduced mean lengths) 

NOEC = 0.0031 mg/L (γ-HBCD, 

measured)

Drotter and Kruger, 1998 (as 

cited in EINECS, 2008; EPA, 

2005; NICNAS, 2012) 

Reported in a secondary source. 

Guideline study performed according 

to current EPA, OECD guidelines and 

GLP. Within the range of water 

solubility. The test substance was 

made up of a composite of HBCD 

samples from three manufacturers 

containing 6.0% α-, 8.5% β- and 

79.1% γ-diastereomers; total HBCD 

was 93.6% of test substance. Reduced 

lengths, dry weight and fewer young 

observed in daphnia exposed to 0.011

mg/L.

Daphnia ChV = 0.0.059 mg/L

(Estimated)

ECOSAR class: Neutral organics

ECOSAR v. 1.10 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green Algae ChV Green algae ChV = 0.38 mg/L

(Estimated)

ECOSAR class: Neutral organics

ECOSAR v. 1.10 The effect level exceeds the water 

solubility of 0.66 mg/L, but not by 

10x as required to be considered NES 

by ECOSAR. <br>

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Earthworm Subchronic Toxicity Lumbriculus variegates 28-day sediment 

bioassay (spiked and aged sediment)

0.05, 0.5, 5, 50 and 500 mg HBCD/kg 

dwt (nominal)

LOEC = 28.7 mg/kg (rate of emergence)

NOEC = 3.2 mg/kg dwt

Mean number of eggs in F1 generation 

was significantly reduced at highest 

concentration (159 mg/kg dwt)

EINECS, 2008; Oetken et al., 

2001

Performed in contrast with OECD 

Draft Guideline 218, artificial 

sediment with a coarse grain size 

(100-2,000 μm) and other carbon 

sources (stinging-nettle and leaves of 

alder). EINECS states that the results 

for total emergence and emergence 

rate were not considered valid for the 

purpose of risk assessment due to the 

large variations in solvent control.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Avian Toxicity HBCD exposure produced adverse effects on reproduction in birds. In Japanese quail (Coturnix coturnix 

japonica), dietary exposure of HBCD caused a reduction in hatchability of eggs (125 ppm), reduced shell 

thickness (>125 ppm), decreased egg weight and an increase in the number of cracked eggs (500 and 1,000 

ppm). The NOAEC for reproductive performance in this study was determined to be 5 ppm (0.7 mg/kg bwday). In a dietary study in American Kestrels (Falco sparcerius), HBCD exposure resulted in delayed egg 

laying, reduced egg size, thinner egg shells, differential weight loss during embryonic development and 

reduced fertility (concentrations not specified).

Reproductive Toxicity to Birds 6-week dietary study in Japanese quails 

(Coturnix coturnix japonica).

Doses: 0, 125, 250, 500 or 1,000 ppm of 

HBCD (a mixture of isomers: α-, 27%; β-

, 30%; γ-,43%).

Reduction in hatchability at all 

concentrations tested. Reduction in egg 

shell thickness at > 125 ppm. Decreased 

egg weight and egg production rate, 

increase in cracked eggs at 500 and 1,000 

ppm. 

Additional test conducted for 

reproductive performance. Doses: 0, 5, 

15, 45 or 125 ppm.

Reduced survival of chicks at ≥ 15 ppm. 

NOEC (reproductive performance): 5 

ppm (0.7 mg/kg bw-day)

MOEJ, 2009 Limited study details; only abstract is 

available.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Dietary study in American Kestrels 

(Falco sparcerius) fed HBCD and PBDE

Delayed egg laying, smaller eggs, thinner 

eggshells, differential weight loss during 

embryonic development and reduced 

fertility and reproductive success

Fernie et al., 2009 Exposure was to a mixture of HBCD 

and PBDE. There are currently no 

DfE criteria to determine a hazard 

designation for this endpoint.

ENVIRONMENTAL FATE

Transport The transport evaluation for HBCD is based on both estimated and experimental physical and chemical 

properties. HBCD has been found widespread, in many environmental and ecological samples, even in 

remote regions such as the Arctic, where concentrations in the atmosphere and top predators are elevated. 

In the atmosphere, HBCD is expected to exist in both the vapor and particulate phase. Vapor-phase HBCD 

is expected to have limited potential for photodegradation. Particulate-phase HBCD will be removed from 

air by wet or dry deposition. Based on the fugacity models incorporating the available experimental 

property data, HBCD is expected to partition primarily to soil. HBCD is expected to have low mobility in 

soil based on its estimated Koc. Therefore, leaching of HBCD through soil to groundwater is not expected to 

be an important transport mechanism. Estimated volatilization half-lives for a model river and model lake 

indicate that HBCD will have low to moderate potential to volatilize. Volatilization from water surfaces is 

expected to be attenuated by adsorption to suspended solids and sediment in the water column.

Henry’s Law Constant –

HLC (atm-m3/mole)

4.6x10-5 at 25oC (Calculated from 

Measured values)

EPI/Physprop database for 

CASRN 3194-55-6

Derived from measured vapor 

pressure (4.7x10-7 mm Hg) and water 

solubility (8.6x10-3 mg/L) values.

6.0x10-6 at 25oC (Estimated) EPI Value was obtained from the 

measured vapor pressure and water 

solubility.

α-HBCD: 4.8x10-9

β-HBCD: 1.3x10-8

γ-HBCD: 3.5x10-10

(Calculated from Measured values)

Kuramochi et al., 2010 Value was obtained from the 

measured vapor pressure (α-HBCD 

7.9×10-11; β-HBCD 4.4×10-11; 

γ-HBCD 6.3×10-13

) and water 

solubility.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

9.1x104 (Estimated) EPI

Level III Fugacity 

Model

Air = 0.4% (Estimated)

Water = 6.3%

Soil = 54%

Sediment = 39.5%

EPI Values were obtained from the 

measured vapor pressure, log Kow and 

water solubility.

Persistence HIGH: The persistence designation for HBCD is high. HBCD was considered by the Executive Body of the 

United Nations Economic Commission for Europe (UNECE) Convention on Long-Range Trans-boundary 

Air Pollution (LRTAP) to meet the criteria for persistent organic pollutants (POPs) as defined under the 

POPs protocol. HBCD is persistent in the air, and as such, has been detected in remote regions including the 

Arctic, and in sediment layers from the 1960s and 1970s through core sampling studies. HBCD is not 

expected to appreciably degrade under aerobic conditions. Degradation through debromination may occur 

under anaerobic conditions. Experimental studies indicate no degradation after 28 days in a ready 

biodegradation test. Aerobic biodegradation data obtained in soil also suggest high persistence. 

Experimental simulation studies indicate that anaerobic biodegradation of HBCD is possible; however, the 

removal rate suggests high environmental persistence, and sediment core samples show a significantly 

slower apparent decrease of HBCD concentrations with time compared to what would be expected based on 

the half-lives obtained from sediment biodegradation simulation tests. HBCD is not expected to hydrolyze in 

the environment based on experimental and estimated data. No experimental data were available for the 

photolysis of HBCD; however, it is not expected to undergo direct photolysis by sunlight as it does not 

contain chromophores that absorb at wavelengths >290 nm. 

Water Aerobic Biodegradation No degradation after 28 days (Measured) 

OECD Test Guideline 301D

EINECS, 2008; NICNAS, 2012 Values reported in a secondary 

source. Guideline studies performed 

according to current EPA, OECD 

guidelines and GLP.

Approximately 22% degradation after 56 

days; aerobic sludge inherent 

biodegradation study (Measured) 

OECD Test Guideline 302B

EINECS, 2008; NICNAS, 2012

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

87-92% degradation of the three HBCD 

diastereomers after 60 days under 

anaerobic conditions using activated 

sludge (Measured) 

NICNAS, 2012

Volatilization Half-life 

for Model River

10 days (Estimated) EPI Estimation model was calculated 

using all applicable measured input 

values and the Henry’s Law constant 

obtained from the measured vapor 

pressure and water solubility. It 

should be noted that this mechanism 

of HBCD transport should be 

attenuated by the strong sorption 

potential of HBCD to suspended 

material.

Volatilization Half-life 

for Model Lake

122 days (Estimated) EPI Estimation model was calculated 

using all applicable measured input 

values and the Henry’s Law constant 

obtained from the measured vapor 

pressure and water solubility.

Soil Aerobic Biodegradation Half-life of γ-HBCD: 63 days at 20°C 

(Measured)

OECD Test Guideline 307

ECHA, 2008; NICNAS, 2012 Value reported in a secondary source. 

Soil simulation dissipation study 

using sandy loam soil amended with 

sewage sludge.

No degradation after 112 days 

(Measured)

OECD Test Guideline 307

ECHA, 2008; NICNAS, 2012 Reported in a secondary source. Soil 

simulation dissipation study.

Anaerobic 

Biodegradation

Half-life of γ-HBCD: 7 days at 20°C 

(Measured)

OECD Test Guideline 307

EINECS, 2008; NICNAS, 2012 Reported in a secondary source. Soil 

simulation dissipation study using 

sandy loam soil amended with 

sewage sludge.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Half-life: 1.6 days at 37°C (Measured) EINECS, 2008 Reported in a secondary source. Test 

substance was a technical HBCD 

mixture. Performed using sewage 

sludge in anaerobic conditions.

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

Aerobic sediment half-life: 101 days

Anaerobic sediment half-life: 66 days

(Measured)

OECD Test Guideline 308

α-HBCD: 113 days 

β-HBCD: 68 days 

γ-HBCD: 104 days

Study reported a stepwise reductive 

dehalogenation via 

tetrabromocyclododecene and 

dibromocyclododecadiene to 

1,5,9-cyclododecatriene in aerobic and 

anaerobic sediment; further degradation 

beyond 1,5,9-cyclododecatriene was not 

observed

ECHA, 2008 Reported in a secondary source. 

Guideline study; provides supporting 

information concerning the isomer 

profile of HBCD degradation.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Aerobic sediment half-life: 11 days; 

32 days

Anaerobic sediment half-life: 2 days

(γ-HBCD) (Measured)

OECD Test Guideline 308

ECHA, 2008; NICNAS, 2012 Value reported in a secondary source. 

Guideline study. The test 

concentration was too low to allow 

for the quantification of α- and 

β-diastereomers. No mass balance 

could be established during the test. 

The recovery of the test substance 

varied (33-125%), indicating 

problems with the extraction method. 

It is stated that the half-life values 

obtained from this study may 

overestimate the degradability of 

γ-HBCD.

Degraded by abiotic and biotic processes 

in soil and aquatic sediment with reported 

half-lives of 2 days to 2 months

(Measured)

Davis et al., 2005, 2006; EPA, 

2010 

Provides supporting information 

about HBCD degradation.

HBCD was detected in sediment layers 

from the 1960s and 1970s in sediment 

core studies; sediment layers from the 

Stockholm archipelago, approximately 30 

and 40 years old, were found to contain 

HBCD in 25-33% of the concentration 

found in the top layer (approximately 

2,004) (Measured)

ECHA, 2008 Non-guideline sediment core studies 

reported in a secondary source; 

suggests that degradation half-lives 

under field conditions may not be as 

fast as simulation degradation studies 

indicate.

Air Atmospheric Half-life 1.7 days (Estimated) EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional 

judgment

The substance does not contain 

functional groups that would be 

expected to absorb light at 

wavelengths >290 nm.

4-92
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

UV absorbance <240 nm calculated for α, 

β and γ HBCD diastereomers using time 

dependent-density functional theory 

(TD-DFT). 

Zhao et al., 2010 HBCD photodegradation and 

photostereoisomerization trends at 

wavelengths below 240 nm were 

predicted. Based on this report, there 

is potential for degradation of HBCD

by UV light, although it is expected 

to have limited influence on the 

overall rate of removal.

Hydrolysis No degradation after 39 days (Measured) EINECS, 2008 Reported in a secondary source with 

limited study details. The 

measurement was performed on the 

technical product. The detection limit 

of 200 ppm may be too high to be 

reliable. 

Half-life at pH 8: 1.2x1010 years 

Half-life at pH 7: 1.2x1011 years 

(Estimated)

EPI This result is unreliable because this 

substance is outside the domain of the 

EPI HYDROWIN v2.00 estimation 

as no cyclic structures were in the 

alkyl halide training set.

Professional judgment HBCD is not expected to undergo 

hydrolysis in the environment due to 

the lack of functional groups that 

hydrolyze under environmental 

conditions.

Environmental Half-Life >120 days (Estimated) PBT Profiler; EPI;

Professional judgment

Half-life estimated for the 

predominant compartment (soil), as 

determined by EPI and the PBT 

Profiler methodology. This value is 

consistent with available measured 

half-lives.

4-93
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Bioaccumulation VERY HIGH: The bioaccumulation designation for HBCD is based on measured BCF values. Available 

monitoring data demonstrate HBCD being detected in a range of organisms, including higher trophic level 

organisms. 

Fish BCF BCF = 8,974 (Measured)

Oncorhynchus mykiss (whole fish) at a 

nominal concentration of 3.4 μg HBCD/L 

for 70 days long (25-day uptake, 35-day 

depuration); nominal concentrations 

based on γ-isomer

The three stereoisomers of HBCD were 

present in O. mykiss in rough 

approximation to that of the commercial 

product used as test article

Drottar and Kruger, 2000; 

EINECS, 2008; EPA, 2005; 

NICNAS, 2012 

Guideline study performed according 

to current EPA, OECD guidelines and 

GLP.

BCF = 18,100 (Measured)

(steady-state, log BCF 4.26) in 

Pimephales promelas at a mean water 

concentration of 6.2 μg HBCD/L for 

32 days

EINECS, 2008; Veith et al., 1979 Non-guideline study that was 

conducted before the implementation 

of standardized test procedures for 

BCF.

Fish BAF 4,100 (Estimated for 3194-55-6)

350,000 (Estimated for 25637-99-4)

EPI These estimated results are from the 

BCFBAF v3.01 Arnot-Gobas 

method, reporting the upper trophic 

value with an entered measured Log 

KOW value of 5.6.

4-94
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Juvenile rainbow trout (O. mykiss) were 

exposed to three HBCD isomers through 

their diet for 56 days, followed by 112 

days of untreated food 

Steady state was not reached after 56 

days; muscle tissue was sampled 

throughout the study 

α-HBCD: 9.2

β-HBCD: 4.3

γ-HBCD: 7.2

Law, 2006; NICNAS, 2012 The secondary source reported these 

calculated results as BAF values;

however, the original source refers to 

these as BMF values. Despite the 

difference in nomenclature, these 

values from non-guideline studies 

demonstrate that HBCD isomers 

bioaccumulate in fish through dietary 

exposure.

Mammalian BAF 90-Day gavage study in Crl:CD(SD)IGS 

BR rats (20/sex)

Doses: 0 and 1,000 mg technical-grade 

HBCD/kg/day at a dosage volume of 

5 mL/kg for 90 days (Measured)

Relative BAF α-HBCD: 99

Relative BAF β-HBCD: 11

Relative BAF γ-HBCD: 1 

EINECS, 2008 Values were obtained from a 

secondary source provide supporting 

information concerning the isomer 

profile of HBCD bioaccumulation.

Earthworm BAF BAF HBCD: 0.03-0.08 wwt/wwt 

(Measured)

A 28-day study in earthworms exposed to 

concentrations HBCD ranging from 78.5 

to 5,000 mg/kg soil (dwt)

BAF α-HBCD: 0.3-0.8 dwt/wwt

BAF β-HBCD: 0.01-0.04 dwt/wwt

BAF γ-HBCD: 0.005-0.02 dwt/wwt

EINECS, 2008; NICNAS, 2012 Values were obtained from a 

secondary source provide supporting 

information concerning the isomer 

profile of HBCD bioaccumulation.

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Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Metabolism in Fish Metabolite formation was studied in 

juvenile rainbow trout (O. mykiss) liver 

and muscle

Bioisomerization:

Fish exposed to the β-isomer resulted in 

α-isomer and γ-isomer

Fish exposed to the α-isomer resulted in 

no β-isomer and a small amount of 

γ-isomer

Fish exposed to the γ-isomer resulted in a 

linear increase in the α-isomer over the 

first 14 days of depuration and this 

isomer was still found after 112 days 

depuration; no β-isomer was found after 

112 days depuration

NICNAS, 2012 Values were obtained from a 

secondary source and provide 

species-specific isomer profile 

information.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring Detected in lake and river sediment, indoor dust, Arctic atmospheric air, deposition samples, European surface 

waters, point source air, urban air and marine sediment (ECHA, 2008; EINECS, 2008; HSDB, 2011b; NICNAS, 

2012; La Guardia et al., 2012).

Ecological Biomonitoring Detected in the eggs, liver and blood of Arctic marine birds, Baltic Sea guillemot eggs, Arctic sea ice amphipods, 

polar cod, skipjack tuna, polar bear adipose tissue, harbor seal blubber, ringed seal blubber, fish and marine 

mammals in Western Europe, the Baltic Sea and Western Scheldt, U.K. harbor porpoise, plankton, mussels, 

peregrine falcons in Sweden, Sparrow hawk, Atlantic puffin, Atlantic white sided dolphin, bottle nose dolphin, bull 

shark, Grey seal, sea lion, Narwhal, bivalve, gastropod, beluga and ring-billed gulls from the St. Lawrence River, 

Canada (ECHA, 2008, EINECS, 2008, EPA, 2010, NICNAS, 2012, Gentes et al., 2012; La Guardia et al., 2012).

Human Biomonitoring Detected in breast milk, blood plasma and adipose tissue. This chemical was not included in the NHANES 

biomonitoring report (CDC, 2011; ECHA, 2008; HSDB, 2011b; Marvin et al., 2011; NICNAS, 2012).

4-96
Table 1. Summary of benchmark dose model results for decreased serum T3 levels 

in adult stage (PNW 11) male offspring from Sprague-Dawley rats exposed to 

HBCD in the diet from gestation day (GD) 10 – postnatal day (PND) 20 

Model

Test for 

significant 

difference 

p-valuea

Variance

p-valueb

Means

chi-square 

p-valueb

Scaled 

residuals of 

interestc AIC

BMDRD10%

(mg/kgday)BMDLRD10%

(mg/kg-day)

All doses included

Constant variance

Exponential NA

Hille 0.06 0.77 NA

0.000000188 / 

-0.28 -178.58 18.67 7.11

Lineard 0.06 0.77 0.02 0.20 / HD -174.60 2376.16 1189.99

Polynomial (2-degree)d 0.06 0.77 0.02 0.20 / HD -174.60 2376.16 1189.99

Polynomial (3-degree)d 0.06 0.77 0.02 0.20 / HD -174.60 2376.16 1189.99

Powere 0.06 0.77 0.02 0.20 / HD -174.60 2376.16 1189.99

Highest dose dropped

Constant variance

Exponential (model 2) 0.05 0.57 0.38 -0.65 / 0.07 -134.64 119.68 73.53

Exponential (model 3) 0.05 0.57 0.38 -0.65 / 0.07 -134.64 119.68 73.53

Exponential (model 4)

0.05 0.57 NA 4.38E -08 / 2.22E-08 -133.42 39.57 9.73

Hille NA

Lineard 0.05 0.57 0.37 -0.66 / 0.07 -134.63 120.98 75.95

Polynomial (2-degree)d 0.05 0.57 0.37 -0.66 / 0.07 -134.63 120.98 75.95

Powere 0.05 0.57 0.37 -0.66 / 0.07 -134.63 120.98 75.95

Data from Saegusa et al. 2009

AIC = Akaike Information Criterion; BMD = maximum likelihood estimate of the dose associated with the 

selected benchmark response; BMDL = 95% lower confidence limit on the BMD; HD = BMD value is higher than 

the highest dose tested; therefore, only the residual just below the BMD is presented; NA = Model failed to 

generate; SD = standard deviation 

a

Values >0.05 fail to meet conventional goodness-of-fit criteria. b

Values <0.10 fail to meet conventional goodness-of-fit criteria. c

Scaled residuals at doses immediately below and immediately above the benchmark dose. d

Coefficients restricted to be negative.

e

Power restricted to ≥1.

The test for significant difference provided a marginal fit to the data for changes in serum T3 levels in rats. The 

continuous models with constant variance assumed did provide adequate fits to the variance model; however none 

of the models provided an adequate fit to the means. In an attempt to achieve an adequately fit model, the highest 

dose was dropped from the dataset and reapplied to the continuous models with constant variance assumed. After 

dropping the highest dose, all models (linear, polynomial, power, and exponential), with the exception of the Hill 

model, provided adequate fits to both the variance and the means. Among the fit models, the BMDLs differed by 

less than 3-fold, so the model with the lowest AIC was selected (exponential model). BMDs and BMDLs 

associated with a change of one standard deviation were calculated to be 119.68 and 73.53 mg/kg-day, 

respectively. 

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Fit of exponential model (model 2) to data for decreased serum T3 levels in adult stage 

(PNW 11) male offspring from Sprague-Dawley rats exposed to HBCD in the diet from 

gestation day (GD) 10 – postnatal day (PND) 20

Highest Dose Dropped

The BMD and BMDL indicated are associated with a 1 standard deviation change from the control and are 

in units of mg/kg day

4-98
Table 2. Summary of benchmark dose model results for increased relative 

thyroid weight in adult stage (PNW 11) male offspring from Sprague-Dawley 

rats exposed to HBCD in the diet from gestation day (GD) 10 – postnatal day 

(PND) 20

Model

Test for 

significant 

difference 

p-valuea

Variance

p-valueb

Means

chi-square 

p-valueb

Scaled 

residuals of 

interestc AIC

BMDRD10%

(mg/kgday)BMDLRD10%

(mg/kg-day)

Constant variance

Exponential (model 2) 0.01 0.48 0.03 -0.12 / HD 32.47 1518.54 960.56

Exponential (model 3) 0.01 0.48 0.03 -0.12 / HD 32.47 1518.54 960.56

Exponential (model 4)

0.01 0.48 0.23

-0.00004 / 

0.00014 28.89 14.01 0.03

Exponential (model 5)

0.01 0.48 0.23

-0.00004 / 

0.00014 28.89 14.01 0.04

Hille 0.01 0.48 0.29 0.16 / -0.80 28.57 15.85 0.00005

Lineard 0.01 0.48 0.03 -0.12 / HD 32.42 1505.30 913.61

Polynomial (2-degree)d 0.01 0.48 0.03 -0.12 / HD 32.42 1505.30 913.61

Polynomial (3-degree)d 0.01 0.48 0.03 -0.12 / HD 32.42 1505.30 913.61

Powere 0.01 0.48 0.03 -0.12 / HD 32.42 1505.30 913.61

Data from Saegusa et al. 2009

AIC = Akaike Information Criterion; BMD = maximum likelihood estimate of the dose associated with the selected 

benchmark response; BMDL = 95% lower confidence limit on the BMD; HD = BMD value is higher than the highest 

dose tested; therefore, only the residual just below the BMD is presented; NA = Model failed to generate; SD = 

standard deviation 

a

Values >0.05 fail to meet conventional goodness-of-fit criteria. b

Values <0.10 fail to meet conventional goodness-of-fit criteria. c

Scaled residuals at doses immediately below and immediately above the benchmark dose. d

Coefficients restricted to be positive.

e

Power restricted to ≥1.

Models were fit to the data for changes in relative thyroid weight in rats. The continuous models with constant 

variance assumed did provide adequate fits to the variance model. Only the exponential (models 4 and 5) and Hill 

models provided an adequate fit to the means. Among the fit models, the BMDLs differed by less than 2- to 3-fold, so 

the model with the lowest AIC was selected (Hill model). BMDs and BMDLs associated with a change of one 

standard deviation were calculated to be 15.85 and 0.00005 mg/kg-day, respectively. 

The LOAEL for this endpoint was determined to be 146.3 mg/kg-day with a NOAEL of 14.8 mg/kg-day. The BMDL 

of 0.00005 mg/kg-day, as well as the BMDLs from the exponential (models 4 and 5) models fall below the observed 

NOAEL for this endpoint, and do not appear to be valid. 

4-99
Fit of Hill model to data for increased relative thyroid weight in adult stage (PNW 11) male 

offspring from Sprague-Dawley rats exposed to HBCD in the diet from gestation day (GD)

10 – postnatal day (PND) 20

The BMD and BMDL indicated are associated with a 1 standard deviation change from the control and are 

in units of mg/kg day

4-100
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Palace, V.P.; Pleskach, K.; Halldorson, T.; Danell, R.; Wautier, K.; Evans, B.; Alaee, M.; 

Marvin, C.; Tommy, G.T. Biotransformation enzymes and thyroid axis disruption in juvenile 

rainbow trout (Oncorhynchus Mykiss) exposed to hexabromocyclododecane diastereoisomers. 

Environ. Sci. Technol. 2008, 42, 1967-1972. 

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler.

Washington D.C. U.S. Environmental Protection Agency www.pbtprofiler.net.

Saegusa, Y.; Fujimoto, H.; Woo, G. H.; Inoue, K.; Takahashi, M.; Mitsumori, K.; Hirose, M.; 

Nishikawa, A.; Shibutani, M. Developmental toxicity of brominated flame retardants, 

tetrabromobisphenol A and 1,2,5,6,9,10-hexabromocyclododecane, in rat offspring after 

maternal exposure from mid-gestation through lactation. Reprod. Toxicol. 2009, 28, 456-467.

SCHER (Scientific Committee on Health and Environmental Risks). Risk assessment report on 

hexabromocyclododecane (HBCD), human health part, CAS RN 25637-99-4, EINECS No. 247-

148-4. Opinion adopted at SCHER 21st plenary, 15 January 2008a. European 

Commission. http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_076.pdf

(accessed on August 14, 2012).

4-105
SCHER (Scientific Committee on Health and Environmental Risks). Risk assessment report on 

hexabromocyclododecane (HBCD). Environmental part, CAS No.: 25637-99-4, EINECS No.: 

247-148-4. Opinion adopted at SCHER 23rd plenary, 6 May 2008b. European 

Commission. http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_093.pdf

(accessed on August 14, 2012)

Schriks, M.; Zvinavashe, E.; Furlow, J. D.; Murk, A. J., Disruption of thyroid hormone-mediated 

Xenopus laevis tadpole tail tip regression by hexabromocyclododecane (HBCD) and 

2,2',3,3',4,4',5,5',6-nona brominated diphenyl ether (BDE206). Chemosphere 2006, 65 (10), 

1904-1908.

Siebel-Sauer; Bias. Algal growth inhibition test. Hexabromid S. Test report no. 1184/87. 1987. 

1184/87, pp 12. BASF Labor fur Okologie.

Stump, D. A prenatal developmental toxicity study of hexabromocyclododecane (HBCD) in rats. 

Laboratory Study No.: WIL-186009. WIL Research Laboratories, Inc., Ashland, OH. 1999.

Veith, G.D.; Defoe, D.L.; Bergstedt, B.V. Measuring and estimating the bioconcentration factor 

of chemicals in fish. J. Fish Res. Board Can. 1979, 36, 1040-1048.

Walsh, G.E.; Yoder, M. J.; McLaughlin, L.L.; Lores, E.M. Responses of marine unicellular algae 

to brominated organic compounds in six growth media. Ecotoxicol. Environ. Saf. 1987, 14, 215-

222. 

Zeller, H.; Kirsch, P. Hexabromocyclododecane: 28-day feeding trials with rats. BASF. 1969. 

Unpublished laboratory report.

Zeller, H.; Kirsch, P. Hexabromocyclododecane: 90-day feeding trials with rats. BASF. 1970. 

Unpublished laboratory report.

Zhang, X.; Yang, F.; Zhang, X.; Xu, Y.; Liao, T.; Song, S.; Wang, J. Induction of hepatic 

enzymes and oxidative stress in Chinese rare minnow (Gobiocypris rarus) exposed to 

waterborne hexabromocyclododecane (HBCDD). Aquatic Toxicol. 2008, 86, 4-11. 

Zhao, Y.; Zhang, X.; Sojinu, O. Thermodynamics and photochemical properties of alpha, beta, 

and gamma-hexabromocyclododecanes: a theoretical study. Chemosphere. 2010, 80 (2), 150-

156. 

4-106
Butadiene styrene brominated copolymer

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) were 

assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from predictive models and/or professional judgment.

This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion 

by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the 

table.

d This hazard designation would be assigned MODERATE for a potential for lung overloading if >5% of the particles are in the respirable range as a result of dust forming 

operations 

¥ Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many flame retardants 

that may partition to sediment and particulates.

Chemical CASRN

Human Health Effects Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicityGenotoxicityReproductiveDevelopmentalNeurologicalRepeated DoseSkin SensitizationRespiratory Sensitization Eye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Butadiene styrene brominated copolymer¥ 1195978-93-8 L L L L L L Ld L M L L L VH L

4-107
Butadiene styrene brominated copolymer

Br

Br

Br

Br

* *

x y z x

Representative structure

CASRN: 1195978-93-8

MW: 60,000-160,000;

<0.1% <1,000;

<0.1% <500

MF: (C8H9)x(C4H6Br2)y(C4H6Br2)z

Physical Forms:

Neat: Solid

Use: Flame retardant

SMILES: This polymer with MW >1,000 and minimal low MW components is not amenable to SMILES notation.

Synonyms: Benzene, ethenyl-, polymer with 1,3-butadiene, brominated (CA Index Name for CASRN 1195978-93-8); Block copolymer of polystyrene and 

brominated polybutadiene; polymeric FR

Trade Names: Emerald InnovationTM 3000; FR122P

Chemical Considerations: This alternative is a high MW polymer. It was assessed using polymer assessment criteria as described in the literature (Boethling and 

Nabholz, 1997). The hazard designations shown in the table for this alternative are based upon high MW formulations of the polymer, where all components have a 

MW >1,000. Future formulations may contain lower MW oligomers or impurities that have the potential to be persistent, bio-accumulative, and toxic (PBT) and are 

not represented in the hazard designations presented.

This substance is subject to a Significant New Use Rule (SNUR) that was finalized in June 2013 (78 Federal Register 38210). Manufacture (or import) of the polymer 

requires notification to EPA except in these cases: (1) the MW of the polymer is in the range of 1,000 to 10,000 daltons, or (2) the MW of the polymer is ≥10,000 

daltons and less than 5 percent of the particles are in the respirable range of 10 microns or less (EPA, 2013). 

4-108
Polymeric: Yes

Oligomers: The average MW of this polymer ranges from 60,000 to 160,000 daltons with oligomers below 500 or 1,000 expected in negligible amounts. 

Metabolites, Degradates and Transformation Products: None identified.

Analog: No analogs

Endpoint(s) using analog values: Not applicable

Structure: Not applicable

Structural Alerts: None identified

Risk Phrases: Not classified by Annex VI Regulation (EC) No. 1272/2008 (ESIS, 2011)

Hazard and Risk Assessments: None identified

4-109
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) No data located.

Boiling Point (°C) >300 (Estimated) Professional judgment Cutoff value used for large, high MW

solid.

Vapor Pressure (mm Hg) <10-8 (Estimated) Professional judgment; Boethling 

and Nabholz, 1997

Cutoff value for large, high MW

polymers according to polymer 

assessment literature.

Water Solubility (mg/L) No dissolved organic carbon (DOC) was 

detected in water at pH 2, 7 and 9 at 20°C

and pH 7 at 37°C after 24 hours according 

to test guideline OECD 120 with 0.05 and 

0.5 g samples (Measured)

Dow, 2005c OECD test guideline 120 is for solid 

polymers for which the Water 

Solubility OECD 105 test is not 

applicable. For OECD 120, the 

solution/extraction behavior of the 

polymer in water at a range of pH 

values is analyzed.

<10-3 (Estimated) Professional judgment; Boethling 

and Nabholz, 1997

Cutoff value for large, high MW nonionic polymers according to polymer 

assessment literature.

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Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Log Kow No data located; polymers with a 

MW >1,000 are outside the domain 

of the available estimation methods.

Approximately 2 (Measured)

According to Guideline OECD 117; 

calculated for residual solvent from an 

acute invertebrate toxicity study water 

accommodated fraction (WAF) sample.

Dow, 2007a; Dow, 2012 Inadequate, the log KOW is not 

consistent with the structure of the 

material and does not represent the 

polymeric substance. The sample is 

from an acute invertebrate toxicity 

study WAF; polymeric components 

not found in the WAF were not 

evaluated.

Additionally, this study did not 

definitively identify the peak detected 

from the WAF using OECD 117 

“Partition Coefficient (Noctanol/water), High Performance 

Liquid Chromatography (HPLC) 

Method”.

Separate analysis of WAF identified 

the impurities to be solvent present in 

the sample (i.e. 1,2-dichloroethane).

Flammability (Flash Point) Nonflammable (Estimated) Professional judgment No experimental data located; based 

on its use as a flame retardant.

Explosivity Not expected to form explosive mixtures 

with air (Estimated)

Professional judgment No experimental data located; based 

on its use as a flame retardant. 

Pyrolysis DfE assessment methodology indicates 

that chemicals that contain both halogens 

and aromatic rings have the potential to 

form compounds potentially hazardous 

compounds under high temperature 

conditions (Estimated)

Professional judgment Based on analysis of the chemical 

structure.

4-111
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

pH Not applicable Professional judgment Does not contain functional groups 

that are expected to ionize under 

environmental conditions.

pKa Not applicable Professional judgment Does not contain functional groups 

that are expected to ionize under 

environmental conditions.

HUMAN HEALTH EFFECTS

Toxicokinetics There is no absorption expected for any route of exposure. This polymer is large, with a MW >1,000. It is 

expected to have limited bioavailability and is therefore not expected to be readily absorbed, distributed or 

metabolized in the body.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or 

Inhaled

No absorption expected for any route of 

exposure (Estimated)

Professional judgment Estimated based on professional 

judgment.

Acute Mammalian Toxicity LOW: Based on experimental LD50 values >2,000 mg/kg. This polymer is also expected to have limited 

bioavailability and is therefore of low potential for acute mammalian toxicity. 

Acute Lethality Oral Oral, rat LD50 >2,000 mg/kg in Up and 

Down Procedure.

Dow, 2007e Sufficient study details provided.

Oral, mouse LD50 >5,000 mg/kg Dow, 2005a Sufficient study details provided.

Oral, rat LD50 >2,000 mg/kg in Up and 

Down Procedure.

Dow, 2007e Sufficient study details provided.

Dermal Limited bioavailability expected 

(Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment 

Inhalation literature.

Carcinogenicity LOW: This polymer is large, with a MW >1,000. It is expected to have few to no residual monomers. 

Additionally, it is not expected to have crosslinking, swellability, dispersability, reactive functional groups, 

potential for inhalation or hindered amine groups. This chemical therefore has a low potential for 

carcinogenicity. No experimental data located.

OncoLogic Results No data located.

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Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity (Rat 

and Mouse)

Limited bioavailability expected

(Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment

literature.

Combined Chronic 

Toxicity/Carcinogenici

ty

Genotoxicity LOW: This compound did not induce gene mutations in bacteria or cause chromosomal aberrations in 

mammalian cells in vitro. In addition, this polymer is large, with a MW >1,000. It is expected to have limited 

bioavailability; therefore, it has low potential for genotoxicity. 

Gene Mutation in vitro Negative in Ames assay in S. typhimurium

TA98, TA100, TA1535, TA1537, and in 

E. coli WP2uvrA in the presence of 

metabolic activation

Dow, 2005b Sufficient study details and 

supporting data provided.

Gene Mutation in vivo Limited bioavailability expected 

(Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment 

literature.

Chromosomal 

Aberrations in vitro

Negative in rat lymphocyte chromosomal 

aberration test (RLCAT)

Dow, 2006 Sufficient study details and 

supporting data provided.

Chromosomal 

Aberrations in vivo

Limited bioavailability expected 

(Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment 

literature.

DNA Damage and 

Repair

No data located.

Other No data located.

Reproductive Effects LOW: Available experimental data indicate a Low hazard designation. In addition, this polymer is large, 

with a MW >1,000. It is expected to have limited bioavailability; therefore, it has low potential for 

reproductive effects. 

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Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproduction/ 

Developmental 

Toxicity Screen

No reproductive effects were observed in 

combined repeated dose toxicity study (28-

day) with reproductive/developmental 

toxicity screening test in Crl:CD (SD) rats 

orally exposed to 0, 100, 300, or 1,000 

mg/kg-day via gavage.

NOAEL >1,000 mg/kg-day (highest dose 

tested)

Dow, 2007f Sufficient study details and 

supporting data provided; effects on

reproductive and developmental 

functions including organ weights, 

histopathological examinations of 

tissues, litter size, pup survival, sex, 

body weight, and the presence of 

gross external abnormalities were 

evaluated; conducted according to 

OECD guidelines.

Combined Repeated 

Dose with 

Reproduction/ 

Developmental 

Toxicity Screen

Limited bioavailability expected 

(Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment 

literature.

Reproduction and 

Fertility Effects

4-114
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Developmental Effects LOW: Available experimental data also indicate a Low hazard designation. In addition, this polymer is 

large, with a MW >1,000. It is expected to have limited bioavailability; therefore, it has low potential for 

developmental effects. 

Reproduction/ 

Developmental 

Toxicity Screen

No developmental effects were observed in 

combined repeated dose toxicity study (28-

day) with reproductive/developmental 

toxicity screening test in Crl:CD (SD) rats 

orally exposed to 0, 100, 300, or 1,000 

mg/kg-day via gavage. 

Developmental NOAEL >1,000 mg/kgday (highest dose tested)

Dow, 2007f Sufficient study details and 

supporting data provided; effects on 

reproductive and developmental 

functions including organ weights, 

histopathological examinations of 

tissues, litter size, pup survival, sex, 

body weight, and the presence of 

gross external abnormalities were 

evaluated; conducted according to 

OECD guidelines.

Combined Repeated 

Dose with 

Reproduction/ 

Developmental 

Toxicity Screen

Limited bioavailability expected 

(Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment

literature.

Prenatal Development

Postnatal Development

4-115
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Neurotoxicity LOW: This polymer is large, with a MW >1,000. It is expected to have limited bioavailability; therefore, it

has low potential for neurotoxicity. There were no neurological effects reported in a 28-day repeated dose 

toxicity study in rats at doses as high as 1,000 mg/kg-day.

Neurotoxicity 

Screening Battery 

(Adult)

Limited bioavailability expected 

(Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment 

literature.

There were no neurological effects 

observed in a combined repeated dose 

toxicity study (28-day) with reproductive/

developmental toxicity screening test in 

Crl:CD (SD) rats orally exposed to 0, 100, 

300, or 1,000 mg/kg-day via gavage. 

NOAEL >1,000 mg/kg-day (highest dose 

tested)

Dow, 2007f Sufficient study details and 

supporting data provided; effects on 

neurological functions including 

sensory evaluation, rectal 

temperature, grip performance, and 

motor activity were evaluated; 

conducted according to OECD 

guidelines.

Repeated Dose Effects LOW: Based on an experimental NOAEL >1,000 mg/kg-day in rats exposed via gavage for 28 days. This 

polymer is large, with a MW >1,000. It is expected to have limited bioavailability; however, because the

number average molecular weight (MWn) is >10,000, there is the possibility of lung overloading in dust 

forming conditions.

This MWn for this polymer is >10,000; 

potential for irreversible lung damage as a 

result of lung overloading (Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment 

literature.

No adverse effects were observed in a

combined repeated dose toxicity study (28-

day) with reproductive/developmental 

toxicity screening test in Crl:CD (SD) rats 

orally exposed to 0, 100, 300, or 1,000 

mg/kg-day via gavage. 

NOAEL >1,000 mg/kg-day (highest dose 

tested)

Dow, 2007f Sufficient study details and 

supporting data provided; conducted 

according to OECD guidelines.

4-116
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Skin Sensitization LOW: This polymer did not cause skin sensitization in a guideline study.

Skin Sensitization Does not cause skin sensitization in guinea 

pig by Buehler test 

Dow, 2007b Sufficient study details and 

supporting data provided. Conducted 

according to OECD Test Guideline 

406 

Respiratory Sensitization No data located.

Respiratory 

Sensitization

No data located.

Eye Irritation MODERATE: This polymer is mildly irritating to rabbit eyes, with effects clearing within 72 hours post 

instillation.

Eye Irritation Non-irritating (species not specified) Dow, 2011 Limited study details and no 

supporting data provided.

Mildly irritating, rabbits

Single instillation of 20 mg of the test 

substance caused iritis and conjunctivitis, 

clearing within 72 hours.

Dow, 2007c Sufficient study details provided; 

study conducted according to OECD 

guidelines; evaluated by the Draize 

method; irritations may have been 

due to mechanical action (scratching) 

due to the 20 mg instillation of the 

test substance particles.

Dermal Irritation LOW: This polymer is slightly irritating to the skin of rabbits.

Dermal Irritation Slightly irritating in rabbits according to 

OECD Test Guideline 404; caused slight 

erythema that cleared within 24 hours

Dow, 2007d Sufficient study details and 

supporting data provided.

Endocrine Activity This polymer is large, with a MW >1,000. It is not expected to have endocrine activity due to its limited

bioavailability and inability to be readily metabolized in the body.

Limited bioavailability expected 

(Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment 

literature.

Immunotoxicity This polymer is large, with a MW >1,000. It is expected to have limited bioavailability; therefore, it has low 

potential for immunotoxicity.

4-117
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Immune System 

Effects

Limited bioavailability expected 

(Estimated)

Professional judgment; Boethling 

and Nabholz, 1997

Based on polymer assessment 

literature.

ECOTOXICITY

ECOSAR Class Not applicable

Acute Aquatic Toxicity LOW: Non-ionic polymers with MWs >1,000 that do not contain reactive functional groups and are 

comprised of minimal low MW oligomers are estimated to display no effects at saturation (NES). These 

polymers display NES because the amount dissolved in water is not anticipated to reach a concentration at 

which adverse effects may be expressed. Guidance for the assessment of aquatic toxicity hazard results in a

Low hazard designation for those materials that display NES. Experimental data for Daphnia magna indicate 

NES with EC50 values > 1,000 mg/L; these reported values exceed the compound’s water solubility by several 

orders of magnitude.

Fish LC50 NES Professional judgment The large MW, limited 

bioavailability and low water 

solubility suggest that there will be 

NES.

4-118
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid LC50 Daphnia magna 48-hour EL50 > 1,000 

mg/L. EL50 is the effect (immobility)

loading rate resulting in 50% immobility;

24-hour EL50 > 1,000 mg/L;

48-hour no-observed-effect loading rate 

(NOELR) < 1,000 mg/L

(Experimental)

Dow, 2007a Sufficient study details provided; 

study conducted according to OECD 

Test Guideline 202. The reported 

value was determined using a water 

accommodated fraction (WAF) at a 

loading rate of 1,000 mg (only 

concentration tested); the toxicity 

values were determined based on the 

nominal loading rate used to prepare 

the WAF solution. As a result, the 

reported value exceeds this material’s 

water solubility; immobility was 

reported in 10% (3/30) daphnids at 

the test dose (1,000 mg/L) following 

24- and 48- hours of exposure, 

therefore the NOELR is determined 

to be at some concentration less than 

1,000 mg/L. Subsequent evaluation 

determined that the WAF contained 

solvent impurities

NES Professional judgment The large MW, limited 

bioavailability and low water 

solubility suggest that there will be 

NES.

Green Algae EC50 NES Professional judgment The large MW, limited 

bioavailability and low water 

solubility suggest that there will be 

NES.

Chronic Aquatic Toxicity LOW: Non-ionic polymers with a MW >1,000 that do not contain reactive functional groups and are 

comprised of minimal low MW oligomers are estimated to display NES. These polymers display NES because 

the amount dissolved in water is not anticipated to reach a concentration at which adverse effects may be 

expressed. Guidance for the assessment of aquatic toxicity hazard results in a low hazard categorization for 

those materials that display NES.

4-119
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Fish ChV NES Professional judgment The large MW, limited 

bioavailability and low water 

solubility suggest that there will be 

NES.

Daphnid ChV NES Professional judgment The large MW, limited 

bioavailability and low water 

solubility suggest that there will be 

NES.

Green Algae ChV NES Professional judgment The large MW, limited 

bioavailability and low water 

solubility suggest that there will be 

NES.

ENVIRONMENTAL FATE

Transport The negligible water solubility and estimated negligible vapor pressure indicate that this polymer is 

anticipated to partition predominantly to soil and sediment. The estimated Henry’s Law constant of 

<10-8 atm-m3/mole indicates that it is not expected to volatilize from water to the atmosphere. The estimated 

Koc of >30,000 indicates that it is not anticipated to migrate from soil into groundwater and that it has the 

potential to adsorb to sediment.

Henry’s Law Constant 

(atm-m3/mole)

<10-8 (Estimated) Professional judgment; Boethling 

and Nabholz, 1997

High MW polymers are expected to 

have low vapor pressure and are not 

expected to undergo volatilization 

according to polymer assessment 

literature.

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated) Professional judgment; Boethling 

and Nabholz, 1997

Cutoff value used for large, high MW 

polymers. High MW polymers are 

expected to adsorb strongly to soil 

and sediment according to polymer 

assessment literature.

Level III Fugacity 

Model

No data located.

4-120
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Persistence VERY HIGH: This polymer is large, with a MW >1,000. It has negligible water solubility and is expected to 

have poor bioavailability to microorganisms, indicating that neither biodegradation nor hydrolysis are 

expected to be important removal processes in the environment. Additionally, experimental guideline studies 

did not detect anaerobic biodegradation of this polymer after 62 days or degradation by hydrolysis after five 

days at pH 1.2 to 9. Although debromination by photodegradation of polybrominated benzenes has been 

observed, this process is not anticipated to lead to ultimate degradation of the material; also, limited 

debromination is not likely to significantly alter the environmental properties of this material. As a result, a 

half-life for this high MW polymer of >180 days leads to a potential for Very High persistence.

Water Aerobic 

Biodegradation

Recalcitrant (Estimated) Professional judgment; Boethling 

and Nabholz, 1997

High MW synthetic polymers are 

expected to be non-biodegradable 

according to polymer assessment 

literature.

Volatilization Half-life 

for Model River

>1 year (Estimated) Professional judgment Based on the magnitude of the 

estimated Henry’s Law constant.

Volatilization Half-life 

for Model Lake

>1 year (Estimated) Professional judgment Based on the magnitude of the 

estimated Henry’s Law constant.

Soil Aerobic 

Biodegradation

No data located. 

Anaerobic 

Biodegradation

Anaerobic Biodegradation OECD 311 

study exhibited no biodegradation after 62 

days (Measured)

Dow, 2009a Guideline study.

Soil Biodegradation 

with Product 

Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life No data located.

4-121
Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reactivity Photolysis Photodegradation was detected in studies 

using the bulk polymer and the polymer in 

foam; 9,600 ppm water extractable 

bromide was detected from 0.022 g of bulk 

polymer samples by IC-MS after 30 days 

of light exposure from a Xenon arc lamp 

with a UV glass filter limiting wavelengths 

below 290 nm at 28-39°C (Measured)

Dow, 2007h; Dow, 2009c Bromine substituents may be 

susceptible to photolysis in the 

environment; however, this is 

expected to be a relatively slow 

process for a high MW brominated 

polymer and is not anticipated to 

result in the ultimate degradation of 

this substance. 

Hydrolysis Not susceptible to hydrolysis according to 

OECD 111 based on average DOC values 

of: 

1.76 ± 0.51 mg/L at pH 1.2; 

0.81 ± 0.30 mg/L at pH 4; 

1.25 ± 0.35 mg/L at pH 7; 

1.33 ± 0.40 mg/L at pH 9

obtained from 914 ± 112 mg/L of sample 

at 49.9 °C for 5 days (Measured)

Dow, 2007g Guideline study.

Other This polymer is stable in PEG400 for 21 

days; 2.5-250 mg/mL samples analyzed by 

HPLC/RI (Measured)

Dow, 2007i This study demonstrates the stability 

of this compound in PEG400.

Environmental Half-Life >180 days (Estimated) Professional judgment The substance is a high MW 

synthetic polymer and is not 

anticipated to be assimilated by 

microorganisms. Therefore, 

biodegradation is not expected to be 

an important removal process. It is 

also not expected to undergo removal 

by other degradative processes under 

environmental conditions.

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Butadiene styrene brominated copolymer CASRN 1195978-93-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Bioaccumulation LOW: Due to the large size and limited bioavailability of the high MW brominated polymer, it is of low

potential for bioconcentration or bioaccumulation.

Fish BCF <100 (Estimated) Professional judgment; Boethling 

and Nabholz, 1997

Cutoff value for large, high MW, 

insoluble polymers according to

polymer assessment literature.

BAF No data located.

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-123
Boethling RS, Nabholz JV (1997) Environmental assessment of polymers under the U.S. Toxic Substances Control Act. Washington,

DC: U.S. Environmental Protection Agency.

CDC (Centers for Disease Control and Prevention). Fourth National Report on Human Exposure to Environmental Chemicals, 

Updated Tables. Department of Health and Human Services. 

2011. http://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Feb2012.pdf (accessed on September 14, 2012).

Dow. The Dow Chemical Company. Acute oral toxicity screen in mice. PMN number P10-0476. 2005a.

Dow. EH&S data summary for polymeric flame retardant (polymeric FR) issued by the Dow Chemical Company. Dow Chemical 

Company. 2012.

Dow. The Dow Chemical Company. Charles, G; M; Kleinert, K. Salmonella/E. coli reverse mutation screening assay for [confidential 

substance]17 with mammalian S-9 activation. PMN number P10-0476. 2005b.

Dow. The Dow Chemical Company. Charles, G; Schisler, M; Kleinert, K. Evaluation of the alcohol and aqueous extracts of 

[confidential substance]1 in an in vitro chromosomal aberration assay utilizing rat lymphocytes. PMN number P10-0476. 2006.

Dow. The Dow Chemical Company. Marino, T; Hales, C; Najar J. An acute toxicity study with the daphnid, Daphnia magna. PMN 

number P10-0476. 2007a.

Dow. The Dow Chemical Company. Dermal sensitization study in guinea pigs (Buehler method). PMN number P10-0476. 2007b.

Dow. The Dow Chemical Company. Primary eye irritation study in rabbits. PMN number P10-0476. 2007c.

Dow. The Dow Chemical Company. Primary skin irritation study in rabbits. PMN number P10-0476. 2007d.

Dow. The Dow Chemical Company. Acute oral toxicity up and down procedure in rats. PMN number P10-0476. 2007e.

17 At time of submission of study report, the test substance name was claimed confidential. At notice of commencement (NOC) the confidentiality claim on the 

chemical identification was retracted.

4-124

 
Dow. The Dow Chemical Company. Yano, B; Zablotny, C; Murray, J. A combined repeated dose toxicity study with the 

reproduction/developmental toxicity screening test in CRL:CD (SD) rats. PMN number P10-0476. 2007f.

Dow. The Dow Chemical Company. Determination of Hydrolysis Rate Following OECD 111 Guidelines. PMN number P10-0476. 

2007g.

Dow. The Dow Chemical Company. Evaluation of biodegradability in Anaerobic Digester Sludge According to OECD Guideline 311. 

PMN number P10-0476. 2009a.

Dow. The Dow Chemical Company. Evaluation of biodegradability in Anaerobic Digester Sludge According to OECD Guideline 311. 

PMN number P10-0476. 2009b.

Dow. The Dow Chemical Company. Exposure of Polymer Samples to Artificial Sunlight Irradiation. PMN number P10-0476. 2007h.

Dow. The Dow Chemical Company. Exposure of Polystyrene Foam Containing [Confidential substance] polymer to Artificial 

Sunlight Irradiation: Evaluation of [Confidential substance] Stability. PMN number P10-0476. 2009c.

Dow. The Dow Chemical Company. Solution/Extraction behavior in Water following the OECD 120 Guideline. PMN number P10-

0476. 2005c.

Dow. The Dow Chemical Company. Stability study. PMN number P10-0476. 2007i.

Dow. The Dow Chemical Company. Strategic Approach Towards Developing More Environmentally Sustainable Flame Retardants. 

[Presentation] 2011.

EPA (U.S. Environmental Protection Agency). Significant New Use Rules on Certain Chemical Substances. 78 FR 38210-38223.

2013. http://www.gpo.gov/fdsys/pkg/FR-2013-06-26/pdf/2013-15032.pdf (accessed on April 8, 2014). 

ESIS (European chemical Substances Information System). Classification, Labeling and Packaging of Dangerous Substances Annex 

VI to Regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on May 10, 2011). 

4-125
TBBPA-bis brominated ether derivative

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) were 

assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from predictive models and/or professional judgment.

This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion 

by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the 

table.

§ Based on analogy to experimental data for a structurally similar compound. ¥ Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may 

not be adequate for poorly soluble substances such as many flame retardants that may partition to sediment and particulates.

¥ Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many flame retardants 

that may partition to sediment and particulates.

Chemical CASRN

Human Health Effects

Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicityGenotoxicityReproductiveDevelopmentalNeurologicalRepeated DoseSkin SensitizationRespiratory SensitizationEye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

TBBPA-bis brominated ether 

derivative¥ 97416-84-7 L§ M§ M§ M§ M§ L M§ L§ L L L L H H

4-126
TBBPA-bis brominated ether derivative

CASRN: 97416-84-7

MW: 971.68

MF: C23H24Br8O2

Physical Forms:

Neat: Solid

Use: Flame retardant

SMILES: BrCC(Br)(C)COc1c(Br)cc(C(C)(C)c2cc(Br)c(OCC(Br)(C)CBr)c(Br)c2)cc1Br

Synonyms: Benzene, 1,1'-(1-methylethylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)] (CA Index Name for CASRN 97416-84-7); 1,1'-

(Isopropylidene)bis(3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene); 1,1'-Propane-2,2-diylbis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene]; 1,3-

Dibromo-5-[2-[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)phenyl]propan-2-yl]-2-(2,3-dibromo-2-methylpropoxy)benzene; 2,2-Bis[4-(2,3-dibromopropoxy)-3,5-

dibromophenyl] propane. 

Trade Names: PYROGUARD SR-130; SR-130

Chemical Considerations: This is a discrete organic chemical with a MW <1,000. EPI v 4.0 was used to estimate physical/chemical and environmental fate values 

as required. No measured values were incorporated into the estimations.

Br

Br

O

Br

O

Br

Br

Br

Br Br

4-127
Polymeric: No

Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None identified; although this compound contains a TBBPA backbone, degradation of this compound to 

TBBPA has not been demonstrated in a published study. The hazards of the theoretical degradation products were not considered in this hazard assessment.

Analog: TBBPA bis(2,3-dibromopropyl) ether (CASRN 21850-44-2)

Endpoint(s) using analog values: Acute Mammalian Toxicity, Genotoxicity, 

Repeated Dose Effects 

Analog: Confidential analog 

Endpoint(s) using analog values: Acute Mammalian Toxicity, Carcinogenicity, 

Reproductive and Developmental Toxicity, Repeated Dose Effects, Skin 

Sensitization 

Analog Structure: 

Tetrabromobisphenol A bis(2,3-dibromopropyl) ether (CASRN 21850-44-2)

Structural Alerts: Polyhalogenated aromatic hydrocarbons, Immunotoxicity (EPA, 2011a)

Risk Phrases: Not classified by Annex VI Regulation (EC) No. 1272/2008 (ESIS, 2011)

Hazard and Risk Assessments: None identified

Br

Br

O

Br

O

Br

Br

Br

Br

Br

4-128
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) Approximately 115 (Measured) Eurosarm MSDS, 2010 Reported for PYROGUARD SR-130, 

containing approximately 100% 

CASRN 97416-84-7.

Approximately 110 (Measured) DKS, 2012 Reported for the commercial product 

PYROGUARD SR-130 (≥90.4% 

purity of TBBPA-bis brominated 

ether derivative CASRN 97416-84-

7); no study details provided.

Boiling Point (°C) >300 (Estimated by analogy) EPI; EPA, 1999 Decomposition is expected before the 

boiling point is reached based on 

analogy to TBBPA 

bis(2,3-dibromopropyl) ether. This 

value is the cutoff for high boiling 

point compounds according to HPV 

assessment guidance.

260 decomposes (Measured) DKS, 2012 Reported for the commercial product 

PYROGUARD SR-130 (≥90.4% 

purity of TBBPA-bis brominated 

ether derivative CASRN 97416-84-

7); no study details provided.

Vapor Pressure (mm Hg) <3.3x10-6 at 25°C (Measured) ICL-IP, 2011 No experimental details were 

provided; however, this value is 

consistent with expected values based 

on the chemical structure and is 

adequate as an upper limit.

Water Solubility (mg/L) <4.2x10-4 at 25°C (Measured) ICL-IP, 2011 No experimental details were 

provided; however, this value is 

consistent with expected values based 

on the chemical structure and is 

adequate as an upper limit.

4-129
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

<1x103 (Measured) Eurosarm MSDS, 2010 Nonspecific value reported as < 1 g/L 

for PYROGUARD SR-130, 

containing approximately 100% 

CASRN 97416-84-7.

0.020 (Measured) DKS, 2012 Reported for the commercial product 

PYROGUARD SR-130 (≥90.4% 

purity of TBBPA-bis brominated 

ether derivative CASRN 97416-84-

7); no study details provided.

Log Kow 12 (Estimated) EPI; EPA, 1999 Estimated value is greater than the 

cutoff value, >10, according to 

methodology based on HPV 

assessment guidance.

Flammability (Flash Point) Non-flammable (Estimated) Professional judgment No experimental data located; based 

on its use as a flame retardant.

Explosivity Not expected to form explosive mixtures 

with air (Estimated)

Professional judgment No experimental data located; based 

on its use as a flame retardant.

Pyrolysis DfE assessment methodology indicates 

that chemicals that contain both halogens 

and aromatic rings have the potential to 

form potentially hazardous compounds 

under high temperature conditions 

(Estimated)

Professional judgment Based on analysis of the chemical 

structure.

pH Not applicable Professional judgment Does not contain functional groups 

that are expected to ionize under 

environmental conditions.

pKa Not applicable Professional judgment Does not contain functional groups 

that are expected to ionize under 

environmental conditions.

4-130
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

HUMAN HEALTH EFFECTS

Toxicokinetics The toxicokinetic properties of TBBPA-bis brominated ether derivative are estimated based on experimental 

data for the analog TBBPA bis(2,3-dibromopropyl) ether, for a closely related confidential compound, and 

by professional judgment. TBBPA-bis brominated ether derivative is expected to have similar toxicological

properties based on structural similarities to the analogs. As a neat material, TBBPA-bis brominated ether 

derivative is estimated to not be absorbed through the skin and to have poor skin absorption when in 

solution; it is estimated to have poor absorption via the lungs and gastrointestinal tract. An experimental 

study in rats showed that the majority (95%) of the analog, TBBPA bis(2,3-dibromopropyl) ether, was 

rapidly eliminated in the feces following single or multiple oral doses with gastrointestinal absorption slow 

and minimal. However, when absorption did occur through the gastrointestinal tract, the analog TBBPA 

bis(2,3-dibromopropyl) ether was slowly eliminated from the blood, with the liver being the main organ for 

deposition.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or 

Inhaled

Not absorbed through the skin as a neat 

material and poor absorption through skin 

when in solution; poor absorption through 

the lung and gastrointestinal tract; 

expected to be a poor alkylating agent due 

to low water solubility 

(Estimated by analogy)

Professional judgment Based on a closely related 

confidential analog with similar 

structure and functional groups.

4-131
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Following single or repeated (5 or 

10 days) oral administration of 20 mg/kg 

[

14C]-TBBPA bis(2,3-dibromopropyl) 

ether to male F-344 rats, the compound 

was poorly absorbed from the 

gastrointestinal tract and uptake to the 

systemic circulation was considered slow. 

The Cmax (0.6 μg/mL) occurred 7.4 hours 

after dosing. Distribution to the tissues 

accounted for <1% of the dose at 

96 hours, while 95% of the dose (in [14C] 

equivalents) was excreted in the feces 

within 36 hours of administration. 

Elimination in the urine accounted for 

<0.1% of the administered dose, and 1% 

of the dose (as metabolites) was excreted 

in the bile after 24 hours. 

(Estimated by analogy)

Knudsen et al., 2007; Professional 

judgment

Estimated based on data for the 

analog TBBPA 

bis(2,3-dibromopropyl) ether; study 

details reported in primary source.

Acute Mammalian Toxicity LOW: Estimated based on analogy to TBBPA bis(2,3-dibromopropyl) ether. Available experimental oral 

and dermal LD50 values for the analog TBBPA bis(2,3-dibromopropyl) ether are >2,000 mg/kg and an 

inhalation LC50 value for the analog is >20 mg/L.

Acute Lethality Oral Mouse LD50 >20,000 mg/kg

(Estimated by analogy)

IPCS, 1995; Professional 

judgment

Estimated based on data for the 

analog TBBPA 

bis(2,3-dibromopropyl) ether; limited 

study details reported in a secondary 

source.

Dermal Mouse LD50 >20,000 mg/kg

(Estimated by analogy)

IPCS, 1995; Professional 

judgment

Estimated based on data for the 

analog TBBPA 

bis(2,3-dibromopropyl) ether; limited 

study details reported in a secondary 

source.

4-132
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Inhalation Mouse LC50 >87,000 mg/m3 (87 mg/L)

(Estimated by analogy)

Great Lakes Chemical 

Corporation, 1982b; Professional 

judgment

Estimated based on data for the 

analog TBBPA 

bis(2,3-dibromopropyl) ether; limited 

study details reported in a secondary 

source.

Carcinogenicity MODERATE: No data located. Estimated to have potential for carcinogenicity based on the potential for 

alkylation and professional judgment.

OncoLogic Results No data located.

Carcinogenicity (Rat 

and Mouse)

Potential for carcinogenic effects based on 

the potential for alkylation, although this 

compound is expected to be a poor 

alkylating agent due to low water 

solubility

(Estimated by analogy)

Professional judgment Based on a closely related 

confidential analog with similar 

structure and functional groups; 

expected to be a poor alkylating 

agent; however, there is still potential 

for alkylating activity.

Combined Chronic 

Toxicity/ 

Carcinogenicity

No data located.

4-133
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Genotoxicity MODERATE: Estimated based on analogy to TBBPA bis(2,3-dibromopropyl) ether. The analog TBBPA 

bis(2,3-dibromopropyl) ether was mutagenic to Salmonella typhimurium but did not cause chromosomal 

aberrations in Chinese hamster ovary (CHO) cells (in vitro), was negative in an in vivo micronucleus assay in 

mice and did not produce unscheduled DNA synthesis in rats.

Gene Mutation in vitro Positive, Ames assay (standard plate) in 

Salmonella typhimurium strains TA1535 

and TA100 with and without metabolic 

activation and TA98 without metabolic 

activation

(Estimated by analogy)

Great Lakes Chemical 

Corporation, 1982a; Professional 

judgment

Estimated based on data for the 

analog TBBPA 

bis(2,3-dibromopropyl) ether.

Gene Mutation in vivo No data located.

Chromosomal 

Aberrations in vitro

Negative chromosomal aberrations in 

Chinese hamster ovary (CHO) cytogenetic 

assay with and without metabolic 

activation (precipitation was observed at 

the highest concentration) (Estimated by 

analogy)

IPCS, 1995; Professional 

judgment

Estimated based on data for the 

analog TBBPA 

bis(2,3-dibromopropyl) ether.

Chromosomal 

Aberrations in vivo

Negative for micronucleated 

polychromatic erythrocytes in B6C3F1 

mice

(Estimated by analogy)

NTP, 2011; Professional 

judgment

Estimated based on data for the 

analog TBBPA 

bis(2,3-dibromopropyl) ether.

DNA Damage and 

Repair

Negative for unscheduled DNA synthesis 

assay in Sprague-Dawley rats at 10, 50, 

100, 500 and 1,000 μg/mL

(Estimated by analogy)

IPCS, 1995; Professional 

judgment

Estimated based on data for the 

analog TBBPA 

bis(2,3-dibromopropyl) ether.

Other (Mitotic Gene 

Conversion)

No data located.

4-134
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproductive Effects MODERATE: Estimated based on a mechanistic consideration of its potential to act as an alkylating agent 

using professional judgment.

Reproduction/ 

Developmental 

Toxicity Screen

Although this compound is likely to be a 

poor alkylating agent due to low water 

solubility, the potential exists for 

alkylation. Based on mechanistic 

considerations of this potential for 

alkylation, there is potential for 

reproductive effects.

(Estimated by analogy)

Professional judgment Based on a closely related 

confidential analog with similar 

structure and functional groups; 

expected to be a poor alkylating 

agent; however, there is still potential 

for alkylating activity.

Combined Repeated 

Dose with 

Reproduction/ 

Developmental 

Toxicity Screen

No data located.

Reproduction and 

Fertility Effects

No data located.

Developmental Effects MODERATE: Estimated based on a mechanistic consideration of its potential to act as an alkylating agent 

using professional judgment.

Reproduction/ 

Developmental 

Toxicity Screen

Although this compound is likely to be a 

poor alkylating agent due to low water 

solubility, the potential exists for 

alkylation. Based on mechanistic 

considerations of this potential for 

alkylation, there is potential for 

developmental effects.

(Estimated by analogy)

Professional judgment Based on closely related confidential 

analogs with similar structures and 

functional groups; expected to be a 

poor alkylating agent, however, there 

is still potential for alkylating activity.

Combined Repeated 

Dose with 

Reproduction/ 

Developmental 

Toxicity Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

4-135
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Neurotoxicity LOW: Low potential for neurotoxicity estimated based on expert judgment. No data located.

Neurotoxicity 

Screening Battery 

(Adult)

Low potential for neurotoxicity

(Estimated)

Expert judgment Estimated based on expert judgment.

Repeated Dose Effects MODERATE: Estimated based on analogy to a confidential analog. There is also potential for liver toxicity 

as TBBPA-bis brominated ether derivative is a highly brominated compound.

Potential for liver effects based on a 

mechanistic consideration of this highly 

brominated compound

(Estimated by analogy)

Professional judgment Based on a closely related 

confidential analog with similar 

structure and functional groups.

Mice were administered TBBPA 

bis(2,3-dibromopropyl) ether in their diet 

at 200 or 2,000 mg/kg-day for 90 days. 

There were no deaths or gross 

abnormalities

(Estimated by analogy)

IPCS, 1995; Professional 

judgment

Based on the analog TBBPA 

bis(2,3-dibromopropyl) ether; limited 

study details reported in a secondary

source.

Skin Sensitization LOW: No data located. Estimated to have low potential for skin sensitization based a closely related 

confidential analog and professional judgment. There is some potential for skin sensitization based on a 

mechanistic consideration of the potential for alkylation.

Skin Sensitization Potential for skin sensitization based on a 

mechanistic consideration of the potential 

for alkylation, although this compound is 

expected to be a poor alkylating agent due 

to low water solubility

(Estimated by analogy)

Professional judgment Based on a closely related 

confidential analog with similar 

structure and functional groups; 

expected to be a poor alkylating 

agent; however, there is still potential 

for alkylating activity.

Not sensitizing, guinea pigs

(Estimated by analogy)

Submitted Confidential Study Estimated by analogy to a closely 

related confidential analog. Reported 

in a submitted confidential study; 

Study conducted according to GLP.

Respiratory Sensitization No data located.

Respiratory 

Sensitization

No data located.

Eye Irritation LOW: Estimated not to cause eye irritation based on expert judgment. No experimental data located.

4-136
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Eye Irritation Low potential for eye irritation 

(Estimated)

Expert judgment Estimated based on expert judgment.

Dermal Irritation LOW: Estimated not to cause dermal irritation based on expert judgment. No experimental located.

Dermal Irritation Low potential for dermal irritation

(Estimated)

Expert judgment Estimated based on expert judgment.

Endocrine Activity Estimated based on analogy to TBBPA bis(2,3-dibromopropyl) ether. Based on four in vitro assays, the 

analog TBBPA bis(2,3-dibromopropyl) ether can interact with the endocrine system. The analog TBBPA 

bis(2,3-dibromopropyl) ether may have potential estrogenic and transthyretin-binding effects; it appears to 

inhibit sulfation of estradiol (E2), but does not exhibit estrogenic activity via interference with estrogen 

receptors (ER); it does not appear to interfere with aryl hydrocarbon receptor (AhR)-mediated, androgenic 

or progestagenic pathways. The analog TBBPA bis(2,3-dibromopropyl) ether competed with thyroid 

hormone precursor thyroxine (T4) for binding to human transthyretin (TTR), but did not exhibit thyroid 

hormone (T3) mimicking activity.

Negative; did not cause inhibition of 

CYP17 catalytic activity in human H295R 

adrenocortical carcinoma cells

(Estimated by analogy)

Cantón et al., 2006; Professional 

judgment

Based on the analog TBBPA 

bis(2,3-dibromopropyl) ether; data 

taken from primary study.

Positive for estradiol sulfotransferase

(E2SULT)-enzyme inhibition in E2SULT 

assay 

(Estimated by analogy)

Hamers et al., 2006; Professional 

judgment

Based on the analog TBBPA 

bis(2,3-dibromopropyl) ether; data 

taken from primary study.

Negative for agonistic and antagonistic 

interactions with AhR, androgen, 

progesterone and estrogen receptors in 

series of CALUX assays

(Estimated by analogy)

Hamers et al., 2006; Professional 

judgment

Based on the analog TBBPA 

bis(2,3-dibromopropyl) ether; data 

taken from primary study.

Positive for displacement of thyroid 

hormone precursor T4 from plasma 

transport protein in TTR binding assay 

(Estimated by analogy)

Hamers et al., 2006; Professional 

judgment

Based on the analog TBBPA 

bis(2,3-dibromopropyl) ether; data 

taken from primary study.

Negative for potentiating and antagonistic 

activity with T3-mediated cell 

proliferation in T-screen

(Estimated by analogy)

Hamers et al., 2006; Professional 

judgment

Based on the analog TBBPA 

bis(2,3-dibromopropyl) ether; data 

taken from primary study.

4-137
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Immunotoxicity Potential for immunotoxicity based on the presence of the polyhalogenated aromatic hydrocarbons 

structural alert and professional judgment. 

Immune System 

Effects

Potential for immunotoxicity based on the 

presence of the polyhalogenated aromatic 

hydrocarbons structural alert

EPA, 2011a; Professional 

judgment

Estimated based on the presence of a 

structural alert.

ECOTOXICITY

ECOSAR Class Halo Ethers

Acute Aquatic Toxicity LOW: Based on estimated acute toxicity values for fish, Daphnid, and green algae that suggest no effects at 

saturation (NES).

Fish LC50 Fish 96-hour LC50 = 3.01x10-6 mg/L

ECOSAR class: Halo ethers

ECOSAR v. 1.10 NES: The log Kow of 12.4 for this 

chemical exceeds the SAR limitation 

for the log Kow of 8.0; NES are

predicted for these endpoints.

Fish 96-hour LC50 = 3.47x10-7 mg/L

ECOSAR class: Neutral organics

ECOSAR v. 1.10 NES: The log Kow of 12.4 for this 

chemical exceeds the SAR limitation 

for the log Kow of 8.0.; NES are 

predicted for these endpoints.

Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

4-138
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid LC50 Daphnid 48-hour LC50 = 1.33x10-6 mg/L

ECOSAR class: Neutral organics

ECOSAR v. 1.10 NES: The log Kow of 12.4 for this 

chemical exceeds the SAR limitation 

for the log Kow of 8.0; NES are 

predicted for these endpoints.

Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action

relative to narcosis.

Green Algae EC50 Green Algae 96-hour = 1.31x10-6 mg/L 

ECOSAR class: Neutral organics

ECOSAR v. 1.10 NES: The log Kow of 12.4 for this 

chemical exceeds the SAR limitation 

for the log Kow of 8.0; NES are 

predicted for these endpoints.

Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Chronic Aquatic Toxicity LOW: Based on estimated chronic toxicity values for fish, Daphnid, and green algae that suggest NES.

Fish ChV Fish ChV = 1.68x10-7 mg/L

ECOSAR class: Halo ethers

ECOSAR v. 1.10 NES: The log of 12.4 for this 

chemical exceeds the SAR limitation 

for the log Kow of 8.0; NES are 

predicted for these endpoints.

4-139
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Fish ChV = 1.06x10-7 mg/L

ECOSAR class: Neutral organics

ECOSAR v. 1.10 NES: The log Kow of 12.4 for this 

chemical exceeds the SAR limitation 

for the log Kow of 8.0; NES are 

predicted for these endpoints.

Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid ChV Daphnid ChV = 7.33x10-7 mg/L

ECOSAR class: Neutral organics

ECOSAR v. 1.10 NES: The log Kow of 12.4 for this 

chemical exceeds the SAR limitation 

for the log Kow of 8.0; NES are 

predicted for these endpoints.

Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Green Algae ChV Green Algae ChV = 4.59x10-5 mg/L 

ECOSAR class: Neutral organics

ECOSAR v. 1.10 NES: The log Kow of 12.4 for this 

chemical exceeds the SAR limitation 

for the log Kow of 8.0; NES are 

predicted for these endpoints.

Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

ENVIRONMENTAL FATE

4-140
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Transport TBBPA-bis brominated ether derivative is expected to have low mobility in soil based on estimations 

indicating strong absorption to soil. If released to the atmosphere, TBBPA-bis brominated ether derivative is 

likely to exist solely as particulate. Therefore, atmospheric removal will occur through wet or dry deposition 

as opposed to atmospheric oxidation. Based on the Henry’s Law constant, volatilization from water or moist 

soil is not expected to occur at an appreciable rate. Fugacity models indicate that TBBPA-bis brominated 

ether derivative will partition predominantly to soil.

Henry’s Law Constant 

(atm-m3/mole)

<10-8 (Estimated) EPI; Professional judgment Cutoff value for non-volatile 

compounds.

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated) EPI; EPA, 2005 Cutoff value for non-mobile

compounds.

Level III Fugacity 

Model

Air = <1% (Estimated)

Water = 5%

Soil = 95%

Sediment = <1%

EPI These results were obtained without 

incorporating measured values; 

suitable experimental values were not 

available.

Persistence HIGH: High persistence of TBBPA-bis brominated ether derivative is expected. Aerobic biodegradation is 

not expected to be an important removal process, based on analog data. Although anaerobic biodegradation

(by dehalogenation) may occur, the rate is likely to be low, and any such transformation will only lead to 

intermediate products that have essentially the same environmental properties. In other words, if emission to 

the environment occurs at any rate greater than negligible, this substance will accumulate. TBBPA-bis 

brominated ether derivative will exist primarily in the particulate phase in the atmosphere and is not 

expected to undergo removal by gas-phase oxidation reactions; however due to its properties, it is not 

expected to be released or transported to the atmosphere to a significant degree. TBBPA-bis brominated 

ether derivative is not anticipated to undergo removal by hydrolysis, since it does not contain hydrolyzable 

functional groups.

Water Aerobic 

Biodegradation

Recalcitrant (Primary survey model)

Recalcitrant (Ultimate survey model)

EPI Not expected to be an important fate 

process.

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI Based on the magnitude of the 

estimated Henry’s Law constant.

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI Based on the magnitude of the 

estimated Henry’s Law constant.

Soil Aerobic 

Biodegradation

No data located.

4-141
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Anaerobic 

Biodegradation

Probable (Anaerobic-methanogenic 

biodegradation probability model)

EPI Not expected to be an important fate 

process.

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 8.3 hours (Estimated) EPI Estimate for gas-phase process. Given 

that the material is expected to exist 

as a particulate in the atmosphere, the 

rate of this process will be attenuated, 

and it is not expected to be an 

important fate process.

Reactivity Photolysis No data located.

Hydrolysis Not a significant fate process (Estimated) Mill, 2000; Professional judgment The substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions. 

Environmental Half-life >180 days (Estimated) PBT Profiler; EPI Half-life estimated for the 

predominant compartment (soil), as 

determined by EPI and the PBT 

Profiler methodology.

4-142
TBBPA-bis brominated ether derivative CASRN 97416-84-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Bioaccumulation HIGH: High potential for bioaccumulation based on an estimated BAF of 1,600.

Fish BCF <76-94 at a concentration of 0.001 mg/L;

<9-45 at a concentration of 0.01 mg/L in 

Carp (Cyprinus carpio)

According to "Bioconcentration test of 

chemical substances in fish

and shellfish" (Japanese notification, 

Yakushokuhatsu 0331 No.7, Heisei

23.03.29 Seikyoku No.5, Kanpokihatsu 

No.110331009, March 31, 2011;

latest revision, April 2, 2012) and OECD

Test Guideline 305C

(Measured)

DKS, 2012 This test is most appropriately applied 

to organic chemicals with Kow values 

of 1.5-6.0; the experimental set up did 

not include exposure through food.

Reported for the commercial product 

PYROGUARD SR-130 (≥90.4% 

purity of TBBPA-bis brominated 

ether derivative CASRN 97416-84-7).

BAF 1,600 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-143
CDC (Centers for Disease Control and Prevention). Fourth National Report on Human Exposure to Environmental Chemicals, 

Updated Tables. Department of Health and Human Services. 

2011. http://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Feb2012.pdf (accessed on September 14, 2012).

Canón, R. F.; Sanderson, J. T.; Nijmeijer, S.; Bergman, A.; Letcher, R. J.; van den Berg, M., In vitro effects of brominated flame 

retardants and metabolites on CYP17 catalytic activity: a novel mechanism of action? Toxicol. Appl. Pharmacol. 2006, 216 (2), 274-

81.

DKS. Bioconcentration Study of PYROGUARD SR-130 with Carp. Dai-ichi Kogyo Seiyaku Co., Ltd. 2012.

ECOSAR/EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 1.10. U.S. Environmental Protection 

Agency: Washington D.C. http://www.epa.gov/opptintr/exposure/.

EPA (U.S. Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm (accessed on September 17, 2012). 

EPA (U.S. Environmental Protection Agency). Pollution Prevention (P2) Framework. Office of Pollution Prevention and Toxics. 

Washington, DC. 2005.

EPA (U.S. Environmental Protection Agency). Sustainable Futures. Using noncancer screening within the SF Initiative. Washington 

D.C. 2011. http://www.epa.gov/opptintr/sf/pubs/noncan-screen.htm#systemic (accessed on August 30, 2011).

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.0. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/.

ESIS (European chemical Substances Information System) Classification, Labeling and Packaging of Dangerous Substances Annex 

VI to Regulation (EC) No 1272/2008 [Online] 2011. http://esis.jrc.ec.europa.eu/ (accessed on August 30, 2011). 

Eurosarm MSDS. Pyroguard SR 130 Material safety datasheet. Eurosarm Distributor Chemikalii. May 11, 

2010. http://www.eurosarm.cz/web/umkatalogdoc/4050.pdf (accessed on August 30, 2011). 

Great Lakes Chemical Corporation. Ames/Salmonella plate assay report on bis(2,3-dibromopropyl)ether of tetrabromobisphenol A 

with attachments. TSCA Section 8E, OTS0503680. U.S. EPA Doc. No. 8888200436. 1982a.

4-144
Great Lakes Chemical Corporation. Ames/Salmonella plate assay report on bis(2,3-dibromopropyl)ether of tetrabromobisphenol A 

with attachments. TSCA Section 8E, OTS0503680. U.S. EPA Doc. No. 8888200426. 1982b.

Hamers, T.; Kamstra, J. H.; Sonneveld, E.; Murk, A. J.; Kester, M. H.; Andersson, P. L.; Legler, J.; Brouwer, A., In vitro profiling of 

the endocrine-disrupting potency of brominated flame retardants. Toxicol. Sci. 2006, 92 (1), 157-173.

ICL-IP. E-mail correspondence from Joel Tenney at ICL Industrial Products to Emma Lavoie at U.S. Environmental Protection 

Agency, 2011.

IPCS (International Programme on Chemical Safety). Environmental Health Criteria 172. Tetrabromobisphenol A and derivatives. 

1995. http://www.inchem.org/documents/ehc/ehc/ehc172.htm (accessed on January 14, 2011).

Knudsen, G. A.; Jacobs, L. M.; Kuester, R. K.; Sipes, I. G., Absorption, distribution, metabolism and excretion of intravenously and 

orally administered tetrabromobisphenol A [2,3-dibromopropyl ether] in male Fischer-344 rats. Toxicology 2007, 237 (1-3), 158-67.

Mill, T. (2000) Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences. Boca Raton: Lewis Publishers: 355-381.

NTP (National Toxicology Program). Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) National Toxicology Program, 

Department of Health and Human Services. 2011. http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?searchterm=21850-44-

2&fuseaction=ntpsearch.searchresults. 

Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

4-145
TBBPA bis(2,3-dibromopropyl) ether

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) were 

assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from predictive models and/or professional judgment.

This table contains hazard information for each chemical; evaluation of risk considers both hazard and exposure. Variations in end-of-life processes or degradation and combustion 

by-products are discussed in the report but not addressed directly in the hazard profiles. The caveats listed below must be taken into account when interpreting the information in the 

table.

¥ Aquatic toxicity: EPA/DfE criteria are based in large part upon water column exposures which may not be adequate for poorly soluble substances such as many flame retardants 

that may partition to sediment and particulates.

Chemical CASRN

Human Health Effects Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicity Genotoxicity ReproductiveDevelopmentalNeurologicalRepeated DoseSkin SensitizationRespiratory SensitizationEye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

TBBPA bis(2,3-dibromopropyl) ether¥ 21850-44-2 L M M M M L M L L L L L VH H

4-146
TBBPA bis(2,3-dibromopropyl) ether

CASRN: 21850-44-2

MW: 943.62

MF: C21H20Br8O2

Physical Forms:

Neat: Solid

Use: Flame retardant

SMILES: O(c1c(cc(cc1Br)C(c1cc(c(OCC(Br)CBr)c(c1)Br)Br)(C)C)Br)CC(Br)CBr

Synonyms: Benzene, 1,1'-(1-methylethylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)-; 1,1'-(1-Methylethylidene)bis(3,5-dibromo-4-(2,3-

dibromopropoxy))benzene; 1,1'-(1-Methylethylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)]benzene; 1,1'-(Isopropylidene)bis(3,5-dibromo-4-(2,3-

dibromopropoxy)benzene); 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)benzene]; 1,1'-propane-2,2-diylbis[3,5-dibromo-4-(2,3-

dibromopropoxy)benzene]; 2,2-Bis[3,5-dibromo-4(2,3-dibromopropoxy)phenyl]propane; 2,2-Bis[3,5-dibromo-4-(2,3-dibromopropyloxy)phenyl]propane; 2,2-Bis[4-

(2,3-dibromopropoxy)-3,5-dibromophenyl]propane; 3,3’,5,5’-TetrabromobisphenolA bis92,3-dibromopropyl) ether; 4,4’-Isopropylidenebis[2,6-dibromo-1-(2,3-

dibromopropoxy)benzene]; 403AF; Bis(2,3-dibromopropoxy)tetrabromobisphenol A; Bromcal 66.8; Bromkal 66-8; D 5532; Dibromopropydian; FG 3100; FR 720; 

Fire guard 3100; Flame Cut 121K; Flame Cut 121R; GX 5532; Propane, 2,2-bis[3,5-dibromo-4-(2,3-dibromopropoxy)phenyl]-; PE-68; Pyroguard SR 720; SR 720; 

SAYTEX HP-800 A; HP-800 AG; HP-800 AGC; Tetrabromobisphenol A bis(2,3-dibromopropyl ether); Tetrabromobisphenol A bis(2,3-dibromopropyl) ether; 

Tetrabromobisphenol-A-bis-2,3-dibromopropyl ether Tetrabromobisphenol-A-bis-2,3-dibromopropylether; TBBPA-DBPE

Chemical Considerations: This is a discrete organic chemical with a MW below 1,000. EPI v 4.0 was used to estimate physical/chemical and environmental fate 

values as required. Measured values for available endpoints were incorporated into the estimations.

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None identified; although this compound contains a TBBPA backbone, degradation of this compound to 

TBBPA has not been demonstrated in a published study. The hazards of the theoretical degradation products were not considered in this hazard assessment.

Analog: No analog

 Endpoint(s) using analog values: Not applicable

Analog Structure: Not applicable

Structural Alerts: Polyhalogenated aromatic hydrocarbons, immunotoxicity (EPA, 2011).

Risk Phrases: Not classified by Annex I Directive 67/548/European Economic Community & IUCLID (Pakalin et al., 2007).

Hazard and Risk Assessments: Risk assessment complete for TBBPA bis(2,3-dibromopropyl) ether by the European Chemicals Bureau in 2007 (Pakalin et al.,

2007).

Br

Br

O

Br

O

Br

Br

Br

Br

Br

4-147
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 117 (Measured) Tokyo Chemical Industry Co., 

2010; ChemSpider, 2011

Selected value for assessment.

114 (Measured) NICNAS, 2001 Sufficient details were not available 

to assess the quality of this study; 

value reported in a secondary source.

90-100 (Measured) IPCS, 1995; Great Lakes 

Chemical Corporation, 1982a

These reported values may be for a 

commercial mixture.

95 (Measured) Mack, 2004

107.3 (Measured) 

Reported as a range 104.3-116.6 using 

Optical melting determination

ECHA, 2013 Nonguideline, non-good laboratory 

practice (GLP) study reported in a 

secondary source.

113.39 (Measured)

Differential scanning calorimeter

ECHA, 2013 Nonguideline, non-GLP study 

reported in a secondary source.

Boiling Point (°C) Decomposition at >270 (Measured) IPCS, 1995 Decomposition is expected before the 

boiling point is reached. 

Vapor Pressure (mm Hg) 2.2 ± 0.15 × 10-4 at 20°C 

Static test according to Organisation of 

Economic Cooperation and Development 

(OECD) TG 104 (Vapor pressure curve) 

and EU Method A.4 (Vapor Pressure); 

GLP study; Purity of test substance 95.1% 

(Measured)

ECHA, 2013 Guideline study reported for FR-720 

in a secondary source.

<10-8 (Estimated) EPI; EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV

assessment guidance.

4-148
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Water Solubility (mg/L) <10-3 (Estimated) EPI; EPA, 1999 Cutoff value for non-soluble 

compounds according to HPV

assessment guidance.

1×103 (Measured) IPCS, 1995 Inadequate; these values are not 

consistent with a nonpolar, highly 

brominated material with a MW near 

1,000.

<1×103 (Measured) NICNAS, 2001

<0.1 mg/L (Measured) 

Reported as 0.144 μg/L at 20°C using

OECD TG 105 (Water solubility) column 

elution method; GLP-study; 

Radiochemical purity of test substance 

(

14C-TBBPA-DBPE) > 99%.

ECHA, 2013 Cutoff value from a guideline study 

reported in a secondary source.

Log Kow 12 (Estimated) EPI; EPA, 1999 Estimated value is greater than the 

cutoff value, >10, according to 

methodology based on HPV 

assessment guidance.

Flammability (Flash Point) Autoignition: 740°C (Measured) 

Ignition produced orange flame; according 

to IEC 61241-2-1 Method B Minimum 

ignition; GLP study

ECHA, 2013 Nonguideline study; purity of test 

substance TDBPE 720 not stated. 

Reported in a secondary source.

Autoignition: >500 mJ (Measured) 

No ignition was observed; according to 

IEC 61241-2-3 Minimum ignition energy; 

GLP study

ECHA, 2013 Nonguideline; purity of test substance 

TDBPE 720 not stated. Reported in a 

secondary source.

Explosivity Not expected to form explosive mixtures 

with air (Estimated)

Professional judgment No experimental data located; based 

on its use as a flame retardant. 

Pyrolysis No data located.

pH Not applicable Professional judgment Does not contain functional groups 

that are expected to ionize under 

environmental conditions.

4-149
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

pKa Not applicable Professional judgment Does not contain functional groups 

that are expected to ionize under 

environmental conditions.

HUMAN HEALTH EFFECTS

Toxicokinetics TBBPA bis(2,3-dibromopropyl) ether, as a neat material, is estimated not to be absorbed through the skin, 

to have poor skin absorption when in solution, and to have poor absorption via the lungs and 

gastrointestinal tract. An experimental study in rats showed that the majority (95%) of TBBPA bis(2,3-

dibromopropyl) ether is rapidly eliminated in the feces following single or multiple oral doses and 

absorption is slow and minimal. However, if absorbed, TBBPA bis(2,3-dibromopropyl) ether is slowly 

eliminated from the blood, with the liver being the main organ for deposition.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin as a neat 

material and poor absorption through 

skin when in solution; poor absorption 

through the lung and gastrointestinal 

tract. (Estimated by analogy)

Professional judgment Based on closely related 

confidential analogs with similar 

structures, functional groups, and 

physical/chemical properties.

Following single or repeated (5 or 10 

days) oral administrations of 20 mg/kg 

[

14C]-TBBPA bis(2,3-dibromopropyl) 

ether to male F-344 rats, the compound 

was poorly absorbed from the 

gastrointestinal tract and uptake to the 

systemic circulation was considered 

slow. The Cmax (0.6 μg/mL) occurred at 

7.4 hours after dosing. Distribution to the 

tissues accounted for <1% of the dose at 

96 hours while 95% of the dose (in [14C] 

equivalents) was excreted in the feces 

within 36 hours of administration. 

Elimination in the urine accounted for 

<0.1% of the administered dose and 1% 

of the dose (as metabolites) was excreted 

in the bile after 24 hours.

Knudsen et al., 2007; ECHA, 

2013

Study details reported in primary 

source.

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TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Other Male Fischer-344 rats were dosed with 

TBBPA-DBPE by IV administration.

Fecal excretion of [14C] equivalents was 

27% by 36h, 71% by 96h. Urinary 

elimination was minimal (<0.1%). A 

single peak that co-eluted with the 

standard of TBBPA-DBPE was detected 

in extracts of whole blood following IV 

administration. TBBPA-DBPE 

elimination from the blood was slow. 

Kinetic constants following IV dosing 

were: t1/2b: 24.8h; CLb: 0.1mL/min. 

Systemic bioavailability was 2.2%. Liver 

was the major site of disposition.

ECHA, 2013 Well conducted study. Not 

performed according to GLP and 

standard testing guidelines.

Acute Mammalian Toxicity LOW: Based on oral and dermal LD50 values >2, 000 mg/kg and an inhalation LC50 value >20 mg/L. 

Acute Lethality Oral Mouse LD50 >20,000 mg/kg IPCS, 1995 Limited study details reported in a 

secondary source. 

Rat oral LD50 > 2,000 mg/kg ECHA, 2013 Sufficient study details reported in a 

secondary source. GLP study 

conducted using OECD guidelines.

Dermal Mouse LD50 >20,000 mg/kg IPCS, 1995 Limited study details reported in a 

secondary source.

Rat dermal LD50 > 2,000 mg/kg ECHA, 2013 Sufficient study details reported in a 

secondary source. GLP study 

conducted using OECD guidelines.

Inhalation Mouse LC50 >87,000 mg/m3 (87 mg/L) Great Lakes Chemical 

Corporation, 1982b

Limited study details reported in a 

secondary source.

Rat 1 hr-inhalation LC50 >24.4 mg/L;

Whole-body exposure to dust.

ECHA, 2013 Sufficient study details reported in a 

secondary source. 

Carcinogenicity MODERATE: No data located. Estimated to have potential for carcinogenicity based on the potential for 

alkylation and professional judgment. 

OncoLogic Results No data located.

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TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity (Rat 

and Mouse)

There is potential for carcinogenicity 

effects based on a mechanistic 

consideration of the potential for 

alkylation (Estimated)

Professional judgment Based on mechanistic 

considerations.

Combined Chronic 

Toxicity/ 

Carcinogenicity

No data located.

Genotoxicity MODERATE: TBBPA bis(2,3-dibromopropyl) ether was mutagenic to Salmonella typhimurium in one 

assay, while it was negative in other assays in S. Typhimurium and E. coli. This substance was also negative 

for mutagenicity in mouse lymphoma cells. TBBPA bis(2,3-dibromopropyl) ether is also estimated to have 

potential for genotoxicity based on the potential for alkylation. TBBPA bis(2,3-dibromopropyl) ether did 

not cause chromosomal aberrations or sister chromatid exchanges in Chinese hamster ovary (CHO)

cells (in vitro), was negative in an in vivo micronucleus assay in mice and did not produce unscheduled DNA 

synthesis in rats.

Gene Mutation in vitro There is potential for mutagenicity based 

on a mechanistic consideration of the 

potential for alkylation. (Estimated)

Professional judgment Based on closely related 

confidential analogs with similar 

structures and functional groups.

Positive, Ames assay (standard plate) in 

Salmonella typhimurium strains TA1535 

and TA100 with and without metabolic 

activation and TA98 without metabolic 

activation.

Great Lakes Chemical 

Corporation, 1982a; ECHA, 

2013

Sufficient study details reported.

Negative, Salmonella typhimurium

strains TA1535, TA1537, TA100 and 

TA98 and Escherichia coli Wp2uvrA 

with and without metabolic activation.

Submitted confidential study; 

ECHA, 2013

Reported in a submitted confidential 

study; Study conducted according to 

GLP 

Negative, mouse lymphoma L5178Y 

cells with and without metabolic 

activation.

Submitted confidential study; 

ECHA, 2013

Reported in a submitted confidential 

study; Study conducted according to 

GLP 

Gene Mutation in vivo No data located.

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TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Chromosomal 

Aberrations in vitro

Negative chromosomal aberrations in 

Chinese hamster ovary (CHO)

cytogenetic assay with and without 

metabolic activation (precipitation was 

observed at the highest concentration).

IPCS, 1995 Reported in a secondary source.

Negative, sister chromatid exchanges in 

Chinese hamster ovary (CHO) cells with 

and without metabolic activation.

Submitted confidential study Reported in a submitted confidential 

study; Study conducted according to 

GLP 

Chromosomal 

Aberrations in vivo

Negative for micronucleated 

polychromatic erythrocytes in B6C3F1 

mice.

NTP, 2011; ECHA, 2013 Reported in a secondary source.

DNA Damage and 

Repair

Negative for unscheduled DNA synthesis 

assay in Sprague Dawley rats at 10, 50, 

100, 500 or 1,000 μg/mL.

IPCS, 1995 Reported in a secondary source.

Other (Mitotic Gene 

Conversion)

Negative, unscheduled DNA synthesis, 

rat hepatocytes.

Submitted confidential study Reported in a submitted confidential 

study; Study conducted according to 

GLP 

Reproductive Effects MODERATE: Estimated to have potential for reproductive effects based on the potential for alkylation and 

professional judgment.

Reproduction/ 

Developmental Toxicity 

Screen

There is potential for reproductive 

effects based on a mechanistic 

consideration of the potential for 

alkylation (Estimated)

Professional judgment Based on mechanistic 

considerations.

Combined Repeated 

Dose with 

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and 

Fertility Effects

No data located.

4-153
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Developmental Effects MODERATE: Estimated to have potential for developmental effects based on the potential for alkylation 

and professional judgment.

Reproduction/ 

Developmental Toxicity 

Screen

There is potential for developmental 

effects based on a mechanistic 

consideration of the potential for 

alkylation (Estimated)

Professional judgment Based on mechanistic 

considerations.

Combined Repeated 

Dose with 

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity LOW: Estimated not to have potential for neurotoxicity based on expert judgment; no data located.

Neurotoxicity Screening 

Battery (Adult)

Low potential for neurotoxicity.

(Estimated)

Expert judgment Estimated based on expert 

judgment.

Repeated Dose Effects MODERATE: There is potential for liver toxicity because TBBPA bis(2,3-dibromopropyl) ether is a highly 

brominated compound and potential for immunotoxicity associated with polyhalogenated aromatic 

hydrocarbon structure. Located data were insufficient.

Potential for liver effects based on a 

mechanistic consideration of this highly 

brominated compound

(Estimated)

Professional judgment Based on closely related 

confidential analogs with similar 

structures and functional groups.

Mice were administered TBBPA bis(2,3-

dibromopropyl) ether in their diet at 200 

or 2,000 mg/kg-day for 90 days. No 

deaths, or abnormal symptoms observed 

in gross pathological examination.

NOAEL = 2,000 mg/kg-day (highest 

dose tested)

IPCS, 1995; ECHA, 2013 Limited study details reported in a 

secondary source. Reported study 

details were not sufficient to 

evaluate the study quality and were 

considered insufficient to determine 

a hazard designation.

Potential for immunotoxicity based on 

polyhalogenated aromatic hydrocarbons 

structure. 

EPA, 2011; Professional 

judgment

Estimated based on the presence of 

a structural alert.

4-154
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Skin Sensitization LOW: Not a skin sensitizer in guinea pigs. There is potential for skin sensitization based on the potential for 

alkylation.

Skin Sensitization There is potential for skin sensitization 

based on a mechanistic consideration of 

the potential for alkylation.

Professional judgment Based on mechanistic 

considerations.

Not sensitizing, guinea pigs Submitted confidential study; 

ECHA, 2013

Reported in a submitted confidential 

study; Study conducted according to 

GLP 

Respiratory Sensitization No data located.

Respiratory 

Sensitization

No data located.

Eye Irritation LOW: Minimal eye irritation in rabbits clearing within 48 hours.

Eye Irritation Low potential for eye irritation.

(Estimated)

Expert judgment Estimated based on expert 

judgment.

Workers report development of eye 

irritation following exposure to a 

complex mixture of airborne 

contaminants that included TBBPA

bis(2,3-dibromopropyl) ether.

Great Lakes Chemical 

Corporation, 1999

Evidence is based on isolated 

incidents and workers were exposed 

to a complex mixture of airborne 

contaminants while melt processing 

that uses thermoplastic resin 

formulators containing this 

substance as an additive. 

Minimal irritation, rabbits; irritation was 

reversed within 24-48 hours.

Submitted confidential study; 

ECHA, 2013

Reported in a submitted confidential 

study; Study conducted according to 

GLP and OECD guidelines.

Dermal Irritation LOW: Not a skin irritant in rabbits.

Dermal Irritation Low potential for dermal irritation.

(Estimated)

Expert judgment Estimated based on expert 

judgment.

Negative, rabbits Submitted confidential study; 

ECHA, 2013

Reported in a submitted confidential 

study; Study conducted according to 

GLP and OECD guidelines.

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TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Workers report development of dermal 

irritation following exposure to a 

complex mixture of airborne 

contaminants that included TBBPA

bis(2,3-dibromopropyl) ether.

Great Lakes Chemical 

Corporation, 1999

Evidence is based on isolated 

incidents and workers were exposed 

to a complex mixture of airborne 

contaminants while melt processing 

that uses thermoplastic resin 

formulators containing this 

substance as an additive. 

Endocrine Activity Based on 4 in vitro assays, TBBPA bis(2,3-dibromopropyl) ether can interact with the endocrine system. 

TBBPA bis(2,3-dibromopropyl) ether may have potential estrogenic and transthyretin-binding effects. 

TBBPA bis(2,3-dibromopropyl) ether appears to inhibit sulfation of estradiol (E2), but does not exhibit 

estrogenic activity via interference with estrogen receptors (ER). TBBPA bis(2,3-dibromopropyl) ether also 

does not appear to interfere with AhR-mediated, androgenic or progestagenic pathways. TBBPA bis(2,3-

dibromopropyl) ether competed with thyroid hormone precursor thyroxine (T4) for binding to human 

transthyretin (TTR), but did not exhibit thyroid hormone (T3) mimicking activity.

Negative; did not cause inhibition of 

CYP17 catalytic activity in human 

H295R adrenocortical carcinoma cells.

Cantón et al., 2006 Data taken from primary study.

Positive for estradiol sulfotransferase 

(E2SULT)-enzyme inhibition in 

E2SULT assay.

Hamers et al., 2006 Data taken from primary study.

Negative for agonistic and antagonistic 

interactions with aryl hydrocarbon 

(AhR), androgen (AR), progesterone 

(PR), and estrogen (ER) receptors in 

series of CALUX assays. 

Hamers et al., 2006 Data taken from primary study.

Positive for displacement of thyroid 

hormone precursor thyroxine (T4) from 

plasma transport protein in TTR binding 

assay.

Hamers et al., 2006 Data taken from primary study.

Negative for potentiating and 

antagonistic activity with T3-mediated 

cell proliferation in T-screen.

Hamers et al., 2006 Data taken from primary study.

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TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Immunotoxicity Potential for immunotoxicity based on the presence of polyhalogenated aromatic hydrocarbon structure

and professional judgment.

Immune System Effects Potential for immunotoxicity based on 

the presence of polyhalogenated 

aromatic hydrocarbon structure. 

(Estimated)

EPA, 2011; Professional 

judgment

Estimated based on the presence of 

a structural alert.

ECOTOXICITY

ECOSAR Class Halo ethers

Acute Aquatic Toxicity LOW: Based on experimental and estimated acute toxicity values for fish, daphnid, and algae that suggest 

no effects at saturation (NES). 

Fish LC50 Fish 96-hour LC50 = 1.5x10-5 mg/L

(Estimated)

ECOSAR: Halo ethers

ECOSAR version 1.11 NES: The log Kow of 12 for this 

chemical exceeds the structure 

activity relationship (SAR)

limitation for log Kow of 5.0; NES 

are predicted.

Fish 96-hour LC50 = 2.2x10-6 mg/L

(Estimated)

ECOSAR: Neutral organics

ECOSAR version 1.11 NES: The log Kow of 12 for this 

chemical exceeds the SAR 

limitation for log Kow of 5.0; NES 

are predicted. Narcosis classes 

(neutral organics) are provided for 

comparative purposes; DfE 

assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Fish (Oryzias latipes) 96-hour LC50 > 

500 mg/L;

Semi-static conditions.

ECHA, 2013 Sufficient study details reported in a 

secondary source. GLP study 

conducted using OECD and 

Japanese guidelines. The value 

exceeds the estimated water 

solubility; NES are predicted.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Fish (Oncorhynchus mykiss) 96-hour 

LC50 > 100 mg/L;

Static conditions.

ECHA, 2013 Sufficient study details reported in a 

secondary source. GLP study 

conducted using OECD guidelines. 

The value exceeds the estimated 

water solubility; NES are predicted.

Daphnid LC50 Daphnia 48-hour LC50 = 3.01x10-6 mg/L

(Estimated)

ECOSAR: Neutral organics

ECOSAR version 1.11 NES: The log Kow of 12 for this 

chemical exceeds the SAR 

limitation for log Kow of 5.0; NES 

are predicted. Narcosis classes 

(neutral organics) are provided for 

comparative purposes; DfE 

assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnia magna 48-hour EC50 > 100 

mg/L; 

Water accommodated fraction (WAF) 

nominal concentration. 

ECHA, 2013 Sufficient study details reported in a 

secondary source. GLP study 

conducted using OECD guidelines. 

The value exceeds the estimated 

water solubility; NES are predicted.

Green Algae EC50 Green algae 96-hour EC50 = 8.48x10-

5 mg/L

(Estimated)

ECOSAR: Neutral organics

ECOSAR version 1.11 NES: The log Kow of 12 for this 

chemical exceeds the SAR 

limitation for log Kow of 6.4; NES 

are predicted. Narcosis classes 

(neutral organics) are provided for 

comparative purposes; DfE 

assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

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TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae (Pseudokirchneriella 

subcapitata) 48 and 72-hour EC50 

(growth rate/biomass) > 100 mg/L;

WAF nominal concentration.

ECHA, 2013 Sufficient study details reported in a 

secondary source. GLP study 

conducted using OECD guidelines. 

The value exceeds the estimated 

water solubility; NES are predicted.

Chronic Aquatic Toxicity LOW: Based on estimated chronic toxicity values for fish, daphnid and green algae that suggest NES.

Fish ChV Fish ChV = 8.78x10-7 mg/L

(Estimated)

ECOSAR: Halo ethers

ECOSAR version 1.11 NES: The log Kow of 12 for this 

chemical exceeds the SAR 

limitation for log Kow of 8.0; NES 

are predicted.

Fish ChV = 6.6x10-7 mg/L

(Estimated)

ECOSAR: Neutral organics

ECOSAR version 1.11 NES: The log Kow of 12 for this 

chemical exceeds the SAR 

limitation for log Kow of 8.0; NES 

are predicted. Narcosis classes 

(neutral organics) are provided for 

comparative purposes; DfE 

assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action

relative to narcosis.

Daphnid ChV

Daphnid ChV = 3.38x10-6 mg/L

(Estimated)

ECOSAR: Neutral organics

ECOSAR version 1.11 NES: The log Kow of 12 for this 

chemical exceeds the SAR 

limitation for log Kow of 8.0; NES 

are predicted. Narcosis classes 

(neutral organics) are provided for 

comparative purposes; DfE 

assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green Algae ChV Green Algae ChV = 0.00016 mg/L 

(Estimated)

ECOSAR: Neutral organics

ECOSAR version 1.11 NES: The log Kow of 12 for this 

chemical exceeds the SAR 

limitation for log Kow of 8.0; NES 

are predicted. Narcosis classes 

(neutral organics) are provided for 

comparative purposes; DfE 

assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

ENVIRONMENTAL FATE

Transport Evaluation of TBBPA bis(2,3-dibromopropyl) ether transport is based entirely on estimations from 

quantitative structure activity relationships. TBBPA bis(2,3-dibromopropyl) ether is expected to have low 

mobility in soil based on estimations indicating strong absorption to soil. If released to the atmosphere, 

TBBPA bis(2,3-dibromopropyl) ether is likely to exist solely as particulate. As a particulate, atmospheric 

oxidation is not expected to be a significant route of environmental removal. Based on the Henry’s Law 

Constant, volatilization from water or moist soil is not expected to occur at an appreciable rate. Level III 

fugacity models indicate that TBBPA bis(2,3-dibromopropyl) ether will partition predominantly to sediment 

and soil.

Henry’s Law Constant 

(atm-m3/mole)

<10-8 (Estimated) EPI; Professional judgment Cutoff value for nonvolatile 

compounds.

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated) EPI; EPA, 2005 Cutoff value for nonmobile 

compounds.

>30,000 (Measured) 

Reported as log KOC >>5.63at 25°C; 

OECD TG 121: Estimation of Adsorption 

Coefficient on Soil and Sewage Sludge 

(HPLC); GLP-study

ECHA, 2013 Guideline study reported in a 

secondary source, although the 

experimental values were outside the 

scope of the protocol (log KOC 1.5-

5.0); radiochemical purity of test 

substance (TBBPA-bis(2,3-

dibromopropyl ether)) >99%.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

>30,000 (Measured) 

Reported as log KOC values of 6.1 (soil) 

and 7.6 (sludge) at pH 7.0; OECD 

Guideline 121: Estimation of Adsorption 

Coefficient on Soil and Sewage Sludge 

(HPLC); GLP-study

ECHA, 2013 Guideline study reported in a 

secondary source, although the 

experimental values were outside the 

scope of the protocol (log KOC 1.5-

5.0); purity of test substance (FR-720) 

not stated.

Level III Fugacity Model Air: <1% (Estimated)

Water = 5%

Soil = 95%

Sediment: <1%

EPI

Persistence VERY HIGH: High persistence of TBBPA bis(2,3-dibromopropyl) ether is expected as a result of located 

biodegradation studies and the absence of other expected likely removal processes under environmental 

conditions. In the course of a 28-day Japanese Ministry of International Trade and Industry (MITI) test, only 

1% of TBBPA bis(2,3-dibromopropyl) ether was degraded. TBBPA bis(2,3-dibromopropyl) ether will exist 

primarily in the particulate phase in the atmosphere and is not expected to undergo removal by gas phase 

oxidation reactions. It is also not anticipated to undergo removal by hydrolysis.

Water Aerobic Biodegradation 1% after 4 weeks 

OECD 301C; test concentration of 

100 mg/L and concentration of activated 

sludge inoculum of 30 mg/L (Measured)

MITI, 2007 Adequate, guideline study. 

Passes Ready Test: No

Test method: OECD TG 301B: CO2

Evolution Test

1% degradation after 29 days using an 

activated sludge inoculum. (Measured)

ECHA, 2013 Adequate, guideline study reported in 

a secondary source; purity of test 

substance FR-720 is 95%.

Volatilization Half-life for 

Model River

>1 year (Estimated) EPI

Volatilization Half-life for 

Model Lake

>1 year (Estimated) EPI

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TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Soil Aerobic Biodegradation 0% degradation after 120 days in soil; 

OECD TG 307:Aerobic and Anaerobic 

Transformation in Soil; test concentration 

of 70.0 kBq/40 g soil dry weight; GLPstudy (Measured)

ECHA, 2013 Adequate guideline study reported in 

a secondary source with 14C-TBBPADBPE. No transformation products 

were observed; degradation assessed 

with 4 different soil types.

Anaerobic 

Biodegradation

0% degradation after 100 days in natural 

sediment; OECD TG 308: Aerobic and 

Anaerobic Transformation in Aquatic 

Sediment Systems; GLP-study (Measured)

ECHA, 2013 Adequate, guideline study reported in 

a secondary source with 14C-TBBPADBPE.Degradation results assessed 

with 2 sediment types, material mass 

balance was reported for both types: 

1.98% in water and 84.48% in 

sediment.

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 12 hours (Estimated) EPI

Reactivity Photolysis No data located.

Hydrolysis 50%/>1 year at 50°C and pH 4, 7, and 9 

OECD TG 111: Hydrolysis as a function 

of pH and OPPTS 835.21 10: Hydrolysis 

as a function of pH; GLP study

Adequate, guideline study reported in 

a secondary source. Test substance 

purity (PE-68; CASRN 21850-44-2) 

not stated, no degradation was 

observed after 5 days in triplicate 

samples prepared for each pH level. 

The substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions. 

Environmental Half-life >180 days (Estimated) PBT Profiler; EPI Half-life estimated for the 

predominant compartment (soil), as 

determined by EPI and the PBT 

Profiler methodology.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Aquatic mesocosm study; a controlled

source of TBBPA bis(2,3-dibromopropyl) 

ether was applied and analyzed by GC-MS 

over the course of the study. TBBPA 

bis(2,3-dibromopropyl) ether was detected 

in both the particulate and sediment 

compartments. Degradation products were 

detected but not all were identified. 

(Measured)

de Jourdan, et al., 2013 Nonguideline field study providing 

supporting data about the partitioning 

and fate/persistence of this compound 

under environmental conditions.

Bioaccumulation HIGH: Based on an estimated BAF of 12,000 and its detection in Great Lakes Herring gull eggs, potential for 

bioaccumulation is high. 

Fish BCF 3.4 to 43 (15 μg/L concentration) 

<17 to 130 (1.5 μg/L concentration) 

(Measured)

MITI, 2007 Adequate, guideline study.

BAF 12,000 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring TBBPA bis(2,3-dibromopropyl) ether was identified in dust collected near an artificial stream and pond system in 

Berlin, Germany (Harju et al., 2009); in sewage sludge samples from southern China; in sediments from southern 

China (Shi et al., 2009) and in water, sediment and soil along the Liuyang River in China (Qu et al., 2011).

Ecological Biomonitoring Detected in Great Lakes Herring gull eggs (Letcher and Chu, 2010).

Human Biomonitoring This chemical was not included in the National Health and Nutrition Examination Survey biomonitoring report 

(CDC, 2011).

4-163
Cantón, R.; Sanderson, J.; Nijmeijer, S.; et al. In vitro effects of brominated flame retardants and metabolites on CYP17 catalytic 

activity: A novel mechanism of action? Toxicol. Appl. Pharmacol. 2006, 274:274-281.

ChemSpider; Structure-based Chemistry Information. Royal Society of Chemistry: London. 2011. http://www.chemspider.com

(accessed on January 20, 2011).

CDC (Centers for Disease Control and Prevention). Fourth National Report on Human Exposure to Environmental Chemicals, 

Updated Tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/pdf/Updated_Tables.pdf

(accessed on May 10, 2011).

de Jourdan, B.; Hanson, M.; Muir, D.; Solomon, K. Environmental fate of three novel brominated flame retardants in aquatic 

mesocosms. Environ Toxicol Chem. 32(5):1060-1068. 2013.

ECHA (2013). 1,1`-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)benzene]. Registered substances. European Chemicals 

Agency. http://apps.echa.europa.eu/registered/data/dossiers/DISS-d6b26f7d-78a6-4269-e044-00144f67d031/DISS-d6b26f7d-78a6-

4269-e044-00144f67d031_DISS-d6b26f7d-78a6-4269-e044-00144f67d031.html 11/4/2013. 

ECOSAR/EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 1.11. U.S. Environmental Protection 

Agency: Washington D.C. http://www.epa.gov/opptintr/exposure/.

EPA Sustainable Futures. Using noncancer screening within the SF Initiative. U.S. Environmental Protection Agency: Washington 

D.C. http://www.epa.gov/opptintr/sf/pubs/noncan-screen.htm#systemic (accessed on February 09, 2011).

EPA (U.S. Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm (accessed on September 17, 2012). 

EPA (U.S. Environmental Protection Agency). Pollution Prevention (P2) Framework. Office of Pollution Prevention and Toxics. 

Washington, DC. 2005.

EPI (EPIWIN/EPISUITE) Estimation Program Interface for Windows, Version 4.0. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/.

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Great Lakes Chemical Corporation. Letter from Great Lakes Chemical Corporation to U.S. EPA regarding skin and eye irritation in 

workers exposed to bis(2,3,-Dibromopropyl)Ether, Tetrabromobisphenol A-. TSCA Section 8E Report, OTS05573935. U.S. EPA 

Doc. No. 88990000194. 1999.

Great Lakes Chemical Corporation. Ames/Salmonella plate assay report on bis(2,3-dibromopropyl)ether of tetrabromobisphenol A 

with attachments. TSCA Section 8E, OTS0503680. U.S. EPA Doc. No. 8888200436. 1982a.

Great Lakes Chemical Corporation. Ames/Salmonella plate assay report on bis(2,3-dibromopropyl)ether of tetrabromobisphenol A 

with attachments. TSCA Section 8E Report, OTS0503680. U.S. EPA Doc. No. 8888200426. 1982b

Hamers, T.; Kamstra, J.; Sonneveld, E.; et al. In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. 

Toxicol. Sci. 2006, 92(1):157-173.

Harju, M.; Heimstad, E.; Herzke, D.; et al. Current state of knowledge and monitoring requirements - emerging "new" brominated 

flame retardants in flame retarded products and the environment (TA-2462/2008) [Online] Norwegian Pollution Control Authority. 

2009. www.klif.no/publikasjoner/2462/ta2462.pdf (accessed on January 20, 2011). 

IPCS (International Programme on Chemical Safety). Environmental Health Criteria 172. Tetrabromobisphenol A and derivatives. 

1995. http://www.inchem.org/documents/ehc/ehc/ehc172.htm (accessed on January 14, 2011).

Knudsen, G.A.; Jacobs, L.M.; Kuester, R.K.; et al. Absorption, distribution, metabolism and excretion of intravenously and orally 

administered tetrabromobisphenol A [2,3-dibromopropyl ether] in male Fischer-344 rats. Toxicology 2007, 237:158-167.

Letcher, R.; Chu, S. High-sensitivity method for determination of tetrabromobisphenol-S and tetrabromobisphenol-A derivative flame 

retardants in great lakes herring gull eggs by liquid chromatography-atmospheric pressure photoionization-tandem mass spectrometry.

Environ Sci Technol. 2010, 44(22):8615-8621.

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September 17, 2004.

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on the CSCL Japan. Compiled under the supervision of Chemical Products Safety Division, Basic Industries Bureau, Ministry of 

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International Trade & Industry, Japan; Chemicals Inspection & Testing Institute, Japan. Ed.; Japan Chemical Industry EcologyToxicology & Information Center: 2007.

NICNAS (National Industrial Chemicals Notification and Assessment Scheme). Priority Existing Chemical Assessment Report No. 

20. Polybrominated Flame Retardants (PBFRs) [Online] 

2001. http://www.nicnas.gov.au/publications/car/pec/pec20/pec_20_full_report_pdf.pdf. 

NTP (National Toxicology Program). Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) National Toxicology Program, 

Department of Health and Human Services. 2011. http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?searchterm=21850-44-

2&fuseaction=ntpsearch.searchresults. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

Pakalin, S., Cole, T., Steinkellner, J., et al. Review on production processes of decabromodiphenyl ether (DECABDE) used in 

polymeric applications in electrical and electronic equipment, and assessment of the availability of potential alternatives to 

DECABDE. [Online]. 2007. http://ecb.jrc.ec.europa.eu/documents/ExistingChemicals/Review_on_production_process_of_decaBDE.pdf (accessed on January 20, 2011).

Qu, G.; Shi, J.; Wang, T.; et al. Identification of tetrabromobisphenol A diallyl ether as an emerging neurotoxicant in environmental 

samples by bioassay-directed fractionation and HPLC-APCI-MS/MS. Environ. Sci. Technol. 2011, 45(11):5009-5016.

Shi, T.; Chen, S.-J.; Luo, X.-J.; et al. Occurrence of brominated flame retardants other than polybrominated diphenyl ethers in 

environmental and biota samples from southern China. Chemosphere 2009, 74:910-916.

Tokyo Chemical Industry Co., LTD. Safety Data Sheet for 2,2-Bis[3,5-dibromo-4-(2,3-dibromopropoxy)phenyl]propane [Online] 

2010. http://www.tciamerica.com/catalog/B2022.html (accessed on May 31, 2011). 

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5 Summary of Hazard Assessments, Considerations for 

Selecting Flame Retardants, and an Overview of 

Alternative Materials 

This chapter outlines attributes that a decision-maker should consider in choosing an alternative 

to hexabromocyclododecane (HBCD), including hazard, social, performance, and economic 

considerations as they prepare to make substitution decisions. An overview of alternative 

insulation materials and the applications in which they may be used is also included. 

5.1 Considerations for Selecting Flame Retardants

Design for the Environment (DfE) alternatives assessments provide extensive information on 

chemical hazards and discuss other general factors that are relevant to substitution decisions. 

When selecting flame retardants, decision-makers will consider performance and cost in 

combination with the human health and environmental information from this report. 

This alternatives assessment considers three alternatives to HBCD. One of the alternatives, a 

butadiene styrene brominated copolymer, is a polymer with a molecular weight (MW) much 

greater than 10,000 daltons. The other two, a tetrabromobisphenol A (TBBPA)-bis brominated 

ether derivative and TBBPA bis(2,3-dibromopropyl) ether, are large molecules with a MWs

close to 1,000 daltons. All three of these chemicals incorporate bromine as the mechanism for 

fire retardation and are the only known technically viable options for HBCD in polystyrene foam 

insulation. The limited number of alternatives is, at least in part, due to the requirement that 

flame retardants for expanded polystyrene (EPS) and extruded polystyrene (XPS) foam (1) allow 

the material to comply with fire safety codes, (2) not compromise the physical properties of the 

foam, and (3) be compatible with its manufacturing processes and formulas. The availability of 

flame retardants for polystyrene is described in Section 3.2.

5.1.1 Hazard Considerations

There are five general attributes evaluated in this assessment that can inform decision-making 

about the potential hazards associated with chemical alternatives: (1) human health hazard, (2)

ecotoxicity, (3) persistence, (4) bioaccumulation potential, and (5) exposure potential. In general, 

a “safer” chemical alternative has lower potential for human health hazard, lower ecotoxicity,

better degradability, low potential for bioaccumulation, and lower exposure potential compared 

to substances currently used. The hazard assessments are summarized below; readers are 

encouraged to review the individual detailed hazard profiles of each chemical in Chapter 4.

While experimental data were available for almost all hazard endpoints for HBCD (the exception 

is respiratory sensitization), experimental data for some or all of the hazard endpoints for the 

three alternatives were not available or were deemed inadequate. In these cases, hazard values 

were assigned using data for structural analogs, structure activity relationship (SAR) modeling,

and professional judgment based upon physical-chemical properties and knowledge of data for 

similar chemicals. In some cases (e.g., respiratory sensitization), it was not possible to assign 

hazard values due to a lack of data, models, or structural analogs. It should be noted that those

5-1
hazard designations based on estimated effect levels are regarded with a lower level of 

confidence compared to hazard designations based on measured data. Empirical data would 

allow for a more robust assessment that would confirm or refute professional judgment and thus

support a more informed choice of alternatives. Estimated values in the report can, therefore, 

also be used to prioritize data needs. 

Human health hazard: The DfE alternatives assessment criteria (U.S. EPA 2011a) address a 

consistent and comprehensive list of human health hazard endpoints for which DfE has 

established thresholds indicating levels of concern. These endpoints include acute toxicity, 

carcinogenicity, genotoxicity, reproductive toxicity, developmental toxicity, neurotoxicity, 

repeated dose toxicity, skin sensitization, respiratory sensitization, eye irritation, and dermal 

irritation. 

HBCD has a High hazard designation for developmental toxicity, a Moderate hazard designation 

for reproductive and repeated dose effects, and an estimated Moderate hazard designation for 

carcinogenicity and neurotoxicity; other health endpoints have Low or Very Low hazard 

designations. Comparatively, the butadiene styrene brominated copolymer has Low hazard 

designations (either measured or estimated) for all health endpoints arising from its high MW

and limited potential for absorption (U.S. EPA 2012b). The substance is marketed as greater than

60,000 daltons with negligible low MW components. U.S. Environmental Protection Agency 

(EPA) has regulated this polymer with a Significant New Use Rule (SNUR) that was finalized in 

June 2013. Manufacture (or import) of the polymer requires notification to EPA except in these 

cases: (1) the MW of the polymer is in the range of 1,000 to 10,000 daltons, or (2) the MW of 

the polymer is ≥10,000 daltons and less than 5 percent of the particles are in the respirable range 

of 10 microns or less (U.S. EPA 2013). The TBBPA-bis brominated ether derivative and TBBPA 

bis(2,3-dibromopropyl) ether have a Moderate hazard designation for carcinogenicity, 

genotoxicity, reproductive toxicity, developmental toxicity, and repeated dose toxicity; Low

hazard designations were designated for acute toxicity, neurotoxicity, skin sensitization, eye 

irritation, and dermal irritation. Due to a lack of data for the substance, the hazard designations

for the TBBPA-bis brominated ether derivative were all estimated. Available data for the

structurally similar substance, TBBPA bis(2,3-dibromopropyl) ether (CASRN 21850-44-2), and 

a closely related confidential compound were used for the estimations based on analogy. 

Recently, TBBPA has been evaluated in a 2-year carcinogenicity study at the National 

Toxicology Program (NTP) (National Toxicology Program (NTP) 2013b). An updated DfE 

hazard profile for TBBPA may be published in 2014 as part of the report on Flame Retardants in 

Printed Circuit Boards (U.S. EPA 2008). Although derived from TBBPA, there are not any 

carcinogenicity data for TBBPA-bis brominated ether derivative or its analog TBBPA bis(2,3-

dibromopropyl) ether. There is also a lack of data to determine if TBBPA might be a degradation 

product of TBBPA-bis brominated ether derivative. TBBPA bis(2,3-dibromopropyl) ether has 

been nominated for consideration for a 2-year cancer bioassay at NTP (Haneke 2002; National 

Toxicology Program (NTP) 2013a). Respiratory sensitization was not characterized for HBCD or 

the alternatives because no data were located, no suitable estimation methods were available, or 

no structural alerts were identified. 

Ecotoxicity: Ecotoxicity includes adverse effects observed in wildlife. Aquatic organisms have 

historically been the focus of environmental toxicity considerations by industry and government 

5-2
during industrial chemical review. Surrogate species of fish, aquatic invertebrates, and algae are 

traditionally assessed to consider multiple levels of the aquatic food chain. HBCD is aquatically 

toxic. Aquatic toxicity for the three alternatives is low, driven by their lack of appreciable water 

solubility leading to no effects at saturation (NES). This analysis does not consider dietary 

exposure to substances since guideline tests are focused on exposure from the water column. For 

the butadiene styrene brominated copolymer, TBBPA-bis brominated ether derivative and 

TBBPA bis(2,3-dibromopropyl) ether, aquatic toxicity is estimated to be low (NES) based upon 

its physical-chemical properties (poor water solubility and estimated high octanol-water partition 

coefficient (Kow). A number of publications identified the presence of HBCD in a variety of 

terrestrial and aquatic species. There were few terrestrial ecotoxicity studies; these studies were 

not associated with High hazard. Therefore, potential for impacts of HBCD on high trophic level 

and terrestrial wildlife is unclear. The butadiene styrene brominated copolymer is not expected to 

be bioavailable; impacts on wildlife from the TBBPA-bis brominated ether derivative or TBBPA 

bis(2,3-dibromopropyl) ether have not been studied. 

Persistence: Persistence describes the tendency of a chemical to resist degradation and removal 

from environmental settings, such as air, water, soil, and sediment. Chemical flame retardants 

must be stable by design in order to maintain their flame retardant properties. HBCD and the 

TBBPA-bis brominated ether derivative have High persistence designations. The butadiene 

styrene brominated copolymer and TBBPA bis(2,3-dibromopropyl) ether have Very High 

persistence designations. Highly persistent chemicals may ultimately degrade in the right 

environmental conditions, but time to degradation is on the order of months to years and could 

be much longer. An ideal flame retardant would be stable in the material to which it is added and 

have low toxicity, but also be degradable at the end of the material’s use (i.e., persistent in use 

but not after use). This quality has been difficult to achieve for flame retardants. Long-term 

degradation products, though beyond the scope of this assessment, are also important to consider 

as they might be more toxic, bioaccumulative or persistent (PBT) than the parent compound. The 

TBBPA-bis brominated ether derivative and TBBPA bis(2,3-dibromopropyl) ether have a 

tetrabromobisphenol A (TBBPA) backbone. TBBPA-bis brominated ether derivative and 

TBBPA bis(2,3-dibromopropyl) ether could theoretically release TBBPA, however, no 

experimental studies describing this degradation pathway were found. As mentioned on the 

previous page, an updated DfE hazard profile for TBBPA may be published in 2014. HBCD has 

been found to degrade to tetrabromocyclododecene, dibromocyclododecadiene, or 1,5,9-

cyclododecatriene by aerobic and anaerobic processes (Davis, Gonsior et al. 2006).

Bioaccumulation Potential: The ability of a chemical to accumulate in living organisms is 

described by the bioconcentration, bioaccumulation, biomagnification, and/or trophic 

magnification factors. Each of these indices has a different definition and as such, a substance 

that bioaccumulates does not necessarily biomagnify. HBCD was assigned a Very High hazard 

designation for bioaccumulation based on standardized test results for bioconcentration factor

(BCF). Based on structure activity relationships (SARs), the potential for a molecule to be 

absorbed by an organism tends to be lower when the molecule is larger than 1,000 daltons. This 

is reflected in the estimated Low hazard designation for bioaccumulation for the butadiene 

styrene brominated copolymer. The TBBPA-bis brominated ether derivative and TBBPA 

bis(2,3-dibromopropyl) ether have an estimated High bioaccumulation designation based on their

lipophilic log Kow and expected slow rate of metabolism.

5-3
Exposure Potential: For humans, chemical exposure may occur at different points throughout 

the chemical and product life cycle; by dermal contact, by inhalation, and/or by ingestion; and is 

affected by multiple physical-chemical factors. The DfE alternatives assessment assumes 

exposure scenarios to chemicals and their alternatives within a functional use class are roughly 

equivalent. The assessment also recognizes that, in some instances, chemical properties, 

manufacturing processes, chemical behavior in particular applications, or use patterns may affect 

exposure scenarios. Stakeholders should evaluate carefully whether and to what extent 

manufacturing changes, life-cycle considerations, and physical-chemical properties will result in 

different patterns of exposure. Large polymeric flame retardants and those that are reacted into a 

polymer backbone can decrease exposure potential.

Exposure potential can also be impacted by the persistence and bioaccumulation potential of 

chemicals and/or their degradation products. Chemicals with both higher persistence and higher 

bioaccumulation potential generally have a higher potential for exposure than chemicals that do 

not possess both of these attributes. As was described above, all four of the chemicals in this 

assessment were assigned High or Very High persistence potential and all were assigned High or 

Very High bioaccumulation potential except for the butadiene styrene brominated copolymer, 

which, based on its large size and insolubility, has Very High persistence but Low 

bioaccumulation potential. Since the butadiene styrene brominated copolymer and the TBBPAbis brominated ether derivative are new to the market, environmental monitoring or 

biomonitoring information are not available to inform the exposure potential of these two 

alternatives. The higher exposure potential based on higher persistence and higher 

bioaccumulation for the TBBPA-bis brominated ether is supported by data for the analog 

TBBPA bis(2,3-dibromopropyl) ether (CASRN 21850-44-2), a chemical also evaluated in this 

report that has been detected in environmental media (Harju, Heimstad et al. 2009; Shi, Chen et 

al. 2009; Qu, Shi et al. 2011) and gull eggs (Letcher and Chu 2010). In general the exposure 

potential to the butadiene styrene brominated copolymer is expected to be lower than the other 

chemicals in this assessment because it is a large polymer and is unlikely to be released from the 

polystyrene, in addition to its low likelihood of bioaccumulation. However, long-term fate in the 

environment is not understood; degradation products could have greater exposure potential upon 

release of the substance to the environment.

5.1.2 Social Considerations

Social considerations may impact the choice of alternative chemicals. This section highlights

occupational, consumer, and environmental justice considerations. Stakeholders may identify 

additional social considerations for application to their own decision-making processes.

Occupational Considerations: Workers might be exposed to relatively high concentrations of

flame retardant chemicals from direct contact when conducting specific tasks related to 

manufacturing, processing, and application of chemicals. For example, tasks that involve heat 

and pressure where materials are aerosolized as they are mixed and reacted may result in direct 

contact with flame retardant chemicals. Many facilities have established risk management 

5-4
practices, which are required to be clearly communicated to all employees. The National Institute 

for Occupational Safety and Health (NIOSH) has established a hierarchy of exposure control 

practices18. Starting with the most protective, the practices are: elimination, substitution, 

engineering controls, administrative controls, and personal protection. Switching to inherently 

low hazard chemicals can benefit workers by decreasing workplace risks through the best 

exposure control practices: elimination and substitution of hazardous chemicals with safer 

alternatives. 

Consumer and Lifestage Considerations: Consumers are potentially exposed to flame 

retardant chemicals through multiple pathways described in Chapter 2. Exposure research 

provides evidence that people carry body burdens of flame retardants, including HBCD. 

Individuals may also experience disproportionate impacts during certain lifestages resulting from 

higher exposures, increased susceptibility in response to exposure, or both conditions (National 

Academy of Sciences 2008). For example, children may be more susceptible to environmental 

exposures than adults because: 

• Their bodily systems are still developing and exposures may occur during critical 

windows of susceptibility;

• Their bodies may absorb and process chemicals differently due to characteristics such as 

greater permeability of the blood-brain barrier, slower excretion from the kidneys, and 

alterations in the activity of metabolic enzymes;

• They eat more, drink more, and breathe more in proportion to their body size; 

• Their behavior can expose them more to chemicals and organisms, for example, hand-tomouth and object-to-mouth behaviors (Xue, Zartarian et al. 2007); and 

• They may be exposed to chemicals, including HBCD, in human milk (Landrigan, 

Sonawane et al. 2002; Covaci, Gerecke et al. 2006; Arnot, McCarty et al. 2009). 

Prenatal development represents a potential window of susceptibility whereby exposures to 

chemicals in the environment can contribute to adverse pregnancy and developmental outcomes 

(Stillerman 2008). During prenatal development, biological systems are forming, and disruption 

of these processes can have consequences later in life. While the placenta is designed to protect 

the fetus from stressors, including chemical exposures, chemicals (including HBCD) have been 

shown to pass through this organ resulting in prenatal exposures (Myren, Mose et al. 2006; 

Meijer, Weiss et al. 2008).

Environmental Justice Considerations: At EPA, environmental justice concerns refer to 

disproportionate impacts on minority, low-income, or indigenous populations. These 

disproportionate impacts arise because these population groups may experience higher 

exposures, are more susceptible in response to exposure, or experience both conditions. Factors 

that are likely to influence resilience/ability to withstand harm from a toxic exposure can vary 

with sociodemographics (e.g., co-morbidities, diet, metabolic enzyme polymorphisms, etc.) and 

are therefore important considerations. Adverse outcomes associated with exposure to chemicals 

18 http://www.cdc.gov/niosh/topics/engcontrols/

5-5

 
may be disproportionately borne by minority and low income populations. Additional 

information about EPA’s environmental justice policy can be accessed 

at: www.epa.gov/compliance/ej/resources/policy/considering-ej-in-rulemaking-guide-07-

2010.pdf.

Some populations have higher exposures to certain chemicals in comparison to the average 

member of the general population. A recent study has found that Hispanics, non-Hispanic 

African Americans, and non-Hispanic Asians generally experience greater exposure to certain 

chemical components associated with adverse health outcomes than non-Hispanic whites (Bell 

and Ebisu 2012). The same study found that populations with lower socioeconomic statuses 

generally experienced higher estimated exposures to certain chemicals based on education, 

unemployment, poverty, and earnings (Bell and Ebisu 2012). Higher exposures to environmental 

chemicals may also be attributable to atypical product use patterns and exposure pathways. This 

may be due to a myriad of factors such as cultural practices, language and communication 

barriers, and economic conditions. The higher exposures may also be a result of:

• The proximity of these populations to sources that emit the environmental chemical (e.g.,

manufacturing industries, industries that use the chemical as production input, hazardous 

waste sites, etc.);

• Access to and use of consumer products that may result in additional exposures to the 

chemical; or

• Higher employment of these groups in occupations associated with exposure to the 

chemical. 

Finally, certain populations may experience high exposures to toxic chemicals due to geography, 

food sources, and cultural practices. For example, research shows that Alaska Natives are 

disproportionately impacted by certain flame retardants and other persistent organic pollutants

(POPs), both because of atmospheric transport of persistent chemicals and because of the 

biomagnification of chemicals in traditional subsistence food webs (Arctic Monitoring and 

Assessment Program 2009). 

5.1.3 Performance and Cost Considerations

The DfE approach allows companies to examine hazard profiles of potential replacement 

chemicals so they can consider the human health and environmental attributes of a chemical in 

association with cost and performance considerations. This is intended to allow companies to 

develop marketable products that meet performance requirements while reducing risk associated 

with potential hazard and exposure attributes. While DfE does not assess performance 

considerations, these attributes are critical to the overall function and marketability of flame 

retardants.

As was discussed in Chapter 2, the performance requirements for EPS and XPS foam used as 

insulation are governed by the American Society for Testing and Materials (ASTM) C578, 

5-6
Standard Specification for Rigid, Cellular Polystyrene Insulation.

19 In addition to meeting the 

required flammability standards, these requirements include density, R-value, compressive 

strength, flexural strength, water vapor transmission rate, water absorption, and dimensional 

stability. Alternatives must also be compatible with the manufacturing processes for EPS and 

XPS (e.g., the high pressures and temperatures of the XPS manufacturing process). Substituting 

chemicals can involve significant costs, as industries must adapt their production processes and 

have products re-tested for all required performance and product standards. Handling, disposal, 

and treatment costs may also be important considerations when evaluating alternatives. The 

expenses associated with initial alternative substitution may ultimately result in reduced costs 

associated with managing consumer concerns and public perceptions of hazardous chemicals. 

Information on the cost and availability of butadiene styrene brominated copolymer is based on a 

2012 report by the Persistent Organic Pollutants Review Committee (POPRC) (Persistent 

Organic Pollutants Review Committee 2012). According to the POPRC report, cost estimates for 

EPS and XPS containing this flame retardant versus HBCD have been made by various parties. 

One manufacturer does not anticipate EPS containing the butadiene styrene brominated 

copolymer to have a significant impact on its cost competitiveness with other products. 

However, other parties expect that the cost of using the butadiene styrene brominated copolymer 

instead of HBCD in EPS and XPS can lead to cost increases. One party suggests the costs of 

using the alternative are 90% (EPS) to 120% (XPS) higher than when using HBCD. The impact 

of the butadiene styrene brominated copolymer on the price of EPS and XPS will remain unclear 

until the alternative is fully commercialized. Regarding availability, the butadiene styrene 

brominated copolymer is currently commercially available through a single manufacturer but is 

expected to be available through two additional manufacturers in 2014. With this increased 

production capacity, it is anticipated that the butadiene styrene brominated copolymer suppliers 

will have sufficient capacity to replace HBCD in polystyrene foams in three to five years.

Consideration of economic factors is often better addressed by decision-makers within the 

context of their organization. Accurate cost estimations must be company-specific; the impact of 

substituting chemicals on complex product formulations can only be analyzed in-house and a 

company must determine for itself how changes will impact market share or other business 

factors. 

5.2 Alternative Materials

This section is intended to provide a general overview of alternative insulation materials and 

their applications. The Partnership discussed alternative insulation materials and decided to 

include general information on this topic. This section is not a comprehensive comparison of 

alternative insulation materials. Some of these alternative materials may require flame retardants 

that are characterized in other DfE alternatives assessments. However, this section does not 

include a chemical hazard assessment of the alternatives. While this report provides general 

19 Likewise, ASTM D6817 applies to polystyrene foams in geotechnical engineering applications (“geofoam”). See

www.astm.org/search/site-search.html?query=C578#84513999. 

5-7

 
information about these potential alternatives, their inclusion here is informational only. 

Inclusion of a substance or material in a DfE report does not denote environmental preferability. 

There are several insulation characteristics that should be considered when selecting alternative 

insulation materials. These include environmental considerations, material safety considerations, 

performance considerations, and economic considerations, as discussed below.

Environmental Considerations 

Environmental considerations include whether the manufacturing process results in pollution, 

whether the material can be reused or recycled, and the environmental impacts of its end-of-life 

management. Another factor is the source of the insulation raw material: whether it is made 

from recycled or virgin materials and the environmental impacts associated with manufacturing 

the raw materials. It is important to consider the embodied energy of the product, such as the 

energy required to produce and transport materials (Wilson 1995), as well as the full range of 

environmental impacts (Wilson 1995; Wilson 2010a). All of these issues feed into the life-cycle 

considerations that should be taken into account when selecting insulation materials. Full lifecycle assessments (LCAs) are not within the scope of this report.

Material Safety Considerations

The material safety of the alternative insulation material is also a consideration. Insulation 

materials may use or contain hazardous chemicals, such as diisocyanates, or constituents such as 

blowing agents that may contribute to air pollution. Some materials pose health concerns as 

chemicals are released during processing, installation, or emitted throughout the life of the 

product. Whether the material contains PBT chemicals is also important, especially when the 

potential life-cycle impacts of the product are considered. 

Performance Considerations 

As discussed in Section 2.1.1, the primary desired properties of rigid foam and its alternatives 

include R-value, compressive strength, flexural strength dimensional stability, moisture 

resistance, and fire safety (e.g., flame spread index, smoke development index). In addition to 

these primary desired properties, other performance characteristics to consider when selecting 

alternatives include: water vapor transmission (permeance); corrosivity; weight of the material; 

resiliency; resistance to mold growth and microbial degradation; acoustical energy absorption; 

and whether the material can be used in retrofits and/or new construction. It is also important to

note that for some materials, the R-value may decrease over the lifetime of the product 

(Minnesota Sustainable Housing Initiative 2007). Therefore, it is important to consider the 

expected lifespan of the product needed for the application.

Economic Considerations 

Economic considerations, such as whether the material is readily available and its cost, will also 

impact the viability of alternative insulation materials. Return on investment, including payback 

through energy savings and net energy savings potential, are other economic considerations that 

may impact the decision to switch to alternative insulation materials.

The sections that follow provide information about specific insulation materials that could be 

used as substitutes for the functional uses of EPS and XPS. As was discussed in the previous 

5-8
section, the functional use of EPS and XPS is for continuous insulation applications such as in 

walls and roofs on the exterior of buildings. These applications include products such as 

insulating concrete forms (ICFs); structural insulated panels (SIPs); below grade and 

geotechnical applications for foundations and highways; and other dimensional stability or 

strength applications, e.g., insulated cold storage applications.

5.2.1 Rigid Board Alternatives

This section discusses alternative insulation materials identified by stakeholders that are 

available as rigid board and therefore can be used in many of the same applications as EPS and 

XPS. EPS and XPS are types of board insulation, which is typically made from plastic foams or 

fibrous materials, and is available in the form of board sheets (Minnesota Sustainable Housing 

Initiative 2007; U.S. Department of Energy 2008). Other materials readily available as board 

insulation include polyisocyanurate foams, perlite insulation, and mineral wool/rockwool 

insulation. These materials are described below.

Non-flame retarded EPS or XPS is a potential alternative to flame retarded EPS or XPS if used 

in conjunction with a thermal (fire resistant) barrier. In this case, the flame retardancy would be 

provided by a fire resistant covering or coating that isolates the insulation materials within the 

building (Sall 2010). While coatings face several technical and economic hurdles, separate nonadhered coverings that have sufficient flame barrier properties can be used to render the flame 

retardant properties of the insulation unimportant. For example, in some countries, non-flame 

retarded EPS is used in ground or floor insulation below a concrete layer, or in wall cavities with 

thermal barriers (COWI 2011). EPS is readily available with no flame retardants to the food or 

packaging industry. U.S. manufacturers generally only supply building insulation that contain

flame retarded resins so that fire safety and construction codes can be met, and to reduce fire 

hazards of EPS and XPS after manufacturing and during transportation and construction.

Polyisocyanurate foams are manufactured from petrochemical feedstocks and a blowing agent 

(e.g., pentane), and are most commonly available as sprayed foam or board insulation with a 

facer on each surface (Wilson 1995; Wilson 2005; U.S. Department of Energy 2011). 

Polyisocyanurate foams typically use 5-14% by weight tris(chlorpropyl) phosphate (TCPP) as a 

flame retardant to meet building codes (Wilson 2005). The performance requirements for faced 

polyisocyanurate foam board insulation are specified in ASTM C1289. Its thermal resistance, 

which is subject to thermal drift over time, is cited by the National Roofing Contractors 

Association as having an in-service R-value of 5.0 or 5.6 per inch depending on whether the 

board is exposed to heating or cooling conditions (Graham 2010). It is primarily used as roof 

insulation, but is also used in cavity walls and sheathing (Polyisocyanurate Insulation 

Manufacturers Association 2011). Polyisocyanurate foam board insulation used in walls can 

have an R-value as high as 6.5 per inch (The Dow Chemical Company 2013; The Dow Chemical 

Company n.d.). It should be noted that the isocyanates (e.g., methylene diphenyl diisocyanate 

(MDI), polymeric methylene diphenyl diisocyanate (pMDI) and toluene diisocyanate (TDI), or 

other isocyanate oligomers) used in the manufacture of the foam pose human health hazards and 

are the subject of an EPA Action Plan and a separate DfE Best Practices Partnership (U.S. EPA 

2011b).

5-9
Perlite insulation is manufactured from naturally occurring volcanic minerals (Sustainable 

Sources 2011). It is available as a rigid board, but is also often used as loose fill insulation or 

concrete aggregate (Healthy Building Network 2011; Sustainable Sources 2011). Perlite 

insulation is naturally fire resistant and does not require a flame retardant (COWI 2011). The 

performance requirements for perlite insulation are specified in ASTM C728 which lists its Rvalue as 2.7 per inch. It is most often used in roofs and walls, but can be used in all building 

applications, including floors (COWI 2011; Healthy Building Network 2011; Sustainable 

Sources 2011).

Mineral wool/rockwool is available as a semi-rigid or rigid board, batt, and blown-in loose fill 

insulation (Wilson 2005; Sustainable Sources 2011). It is made from recycled steel slag and/or 

basalt rock, uses a phenol-formaldehyde binder (Wilson 2005; Sustainable Sources 2011), and 

contains trace amounts of formaldehyde (ICA Fittings 2011). Formaldehyde poses human health 

hazards. EPA is currently developing regulations to implement the Formaldehyde Standards for 

Composite Wood Products Act. Mineral wool does not require a flame retardant (Ehrlich 2009). 

It has a typical R-value of 4 (Ehrlich 2009). It can be used in cavity walls, roofing, exterior 

insulation, and below grade (Wilson 2005; Ehrlich 2009). 

5.2.2 Alternatives for Certain Functional Uses

This section describes alternative insulation materials identified by stakeholders that may be used 

for certain functional uses of EPS and XPS. These alternatives are generally not available as 

rigid board insulation, but may be used in certain applications where the properties such as 

dimensional stability or compressive strength are not integral to the performance of the 

insulation material. Types of insulation that may fulfill this purpose include:

• Blanket insulation, which is available in batts or rolls and is usually made from glass or 

mineral fibers (U.S. Department of Energy 2008). Blanket insulation is used in 

unfinished walls, foundations, floors, and ceilings and is fitted between studs, joists, and 

beams, or is laid on open horizontal surfaces (U.S. Department of Energy 2011). Blanket 

insulation may be used in place of some applications of board insulation in walls, floors, 

ceilings, and foundations. 

• Foamed-in-place insulation, which is sprayed into cavities, reduces air leaks, and is 

usually made from polyurethane (Minnesota Sustainable Housing Initiative 2007; Wilson 

2010b). Foamed-in-place insulation may be used in place of board insulation in 

applications such as walls or roofs where they can be sprayed to fill and seal cavities. 

• Loose-fill insulation, blown insulation, and sprayed insulation, which are generally 

composed of loose fibers or fiber pellets that are blown into wall cavities or above 

horizontal ceiling surfaces using pneumatic equipment (U.S. Department of Energy 

2008). Applications of loose-fill insulation include wall cavities, attic floors, irregularly 

shaped areas, and fill in around obstructions (U.S. Department of Energy 2008). Similar 

to foamed-in-place insulation, loose-fill, blown, and sprayed insulation may be used in 

place of board insulation in applications such as walls or roofs. 

Alternative insulation materials within the categories of insulation types described above that 

may be used for certain functional uses of EPS and XPS are summarized below.

5-10
Cellulose is used as a type of blown-in loose-fill insulation and is made from recycled 

newspaper (Wilson 1995; COWI 2011). Ammonium sulfate, boric acid, and borax are typically 

used as flame retardants in cellulose insulation to meet building codes (Wilson 2005). It has a 

typical R-value of 3.7 and is not water resistant (Minnesota Sustainable Housing Initiative 2007; 

COWI 2011). There are also health concerns as printer ink in the newsprint may outgas as 

formaldehyde, as well as from inhalation of paper dust during installation (Greenspec 2010). 

Cellulose insulation is most commonly used as a loose-fill insulation in attic and wall cavities 

(Wilson 1993). 

Cementitious foam is used as a foamed-in-place insulation and is made from magnesium oxide 

derived from seawater and talc (Wilson 2005). Cementitious foam does not require a flame 

retardant (Healthy Building Network 2011). It is has a typical R-value of 3.9 (AirKrete Inc 

2009). Cementitous foam is friable, limiting its application (Wilson 2005). Currently, 

cementitious foam is manufactured by a single producer, limiting its distribution to the east coast 

of the United States (Wilson 2005; Healthy Building Network 2011). It is used to insulate walls, 

roofs, and ceilings (AirKrete Inc 2009).

Cotton insulation is available as a batt, and is made either from cotton and polyester mill scraps 

or from post-consumer recycled clothing, most often recycled denim scrap (Wilson 2005). It uses 

borate or ammonium sulfate flame retardants (Wilson 2005). Cotton insulation may absorb water 

and has a typical R-value of 3.4 (Healthy Building Network 2011; U.S. Department of Energy 

2011). It can be used in the typical applications of batt insulation such as in walls, foundations, 

floors, and ceilings (U.S. Department of Energy 2011).

Fiberglass is available as a batt, blown-in loose fill, or semi-rigid board insulation material 

(Minnesota Sustainable Housing Initiative 2007). It is made from silica sand and may contain 

recycled glass content (Wilson 2005). Fiberglass insulation traditionally uses phenol 

formaldehyde binders, although some manufacturers are switching to acrylic or bio-based resins 

(Wilson 2005; Ehrlich 2010). Formaldehyde poses human health hazards and EPA is currently 

developing regulations to implement the Formaldehyde Standards for Composite Wood Products 

Act. Fiberglass does not require a flame retardant, although there are some specialty fiberglass 

batt products with halogenated flame retardants in the paper backing (Healthy Building Network 

2011). It has a typical R-value of 3.2 (Minnesota Sustainable Housing Initiative 2007). It is used 

in masonry walls, cavity walls, roofs, attics, ceilings, and flooring (COWI 2011; Healthy 

Building Network 2011). 

Polyurethane is most commonly available as a foam-in-place insulation (known as Spray 

Polyurethane Foam (SPF)) and is made from mixing two ingredients conventionally known as 

“Side A” and “Side B”. Side A is composed of isocyanates; Side B is a polyol blend that 

contains a refined petroleum (often some bio-based content) with a blowing agent (typically 

either water or chlorofluorocarbons (CFCs)/ hydrofluorocarbons (HFCs) (historically), more 

recently non-ozone depleting/low global warming potential substances) and other additives such 

as surfactants, amines, and flame retardants (Wilson 2005; U.S. Department of Energy 2011; 

U.S. EPA 2012a). Some polyurethane insulations may use some bio-based content, which is 

generally less than 15% of the total content (BioBased Insulation 2012). Polyurethane insulation 

5-11
uses TCPP or resorcinol-bis-diphenyl phosphate (RDP) as a flame retardant to meet building 

codes (Wilson 2005). Polyurethane has an R-value ranging from 3.6 to 7.5 (COWI 2011; U.S. 

Department of Energy 2011). It can be used to insulate cavities, walls, or roofs ("Foam-in-Place 

Polyurethane Insulation" 2008). It should be noted that exposures to diisocyanates (e.g., MDI) 

and other ingredients in SPF that may be found in vapors, aerosols, dust, or on surfaces during 

and for a period after installation may cause adverse health effects such as asthma (U.S. EPA 

2011c). The EPA has issued an Action Plan for MDI and related compounds and performed 

separate DfE Best Practices Partnership on this topic (U.S. EPA 2011b). EPA has also developed 

an informational website addressing concerns for SPF 

use: http://www.epa.gov/dfe/pubs/projects/spf/spray_polyurethane_foam.html.

5.2.3 Specialty and Emerging Alternative Materials 

The insulation materials presented in this section may be functional alternatives to EPS and XPS, 

but are not considered to be currently viable for large scale building applications, and so are 

constrained to specialty applications or limited geographic areas. This information is intended to 

provide context in case changes in manufacturing processes or economies of scale allow these 

products to become viable in the future. 

Specialty and emerging alternative insulation materials identified by stakeholders include:

• Aerogel is available as a rigid board, roll, or loose-fill; and is used to insulate 

underfloors, rainscreens, roofing, cathedral ceilings, and interior walls (Madonik 

2011). It is made from silica gel, polyethylene terephthalate (PET), fiberglass, and 

magnesium hydroxide (COWI 2011). Aerogel is lightweight and has a very high Rvalue of 10, but is costly.

• Carbon foam is a type of rigid board foam made from calcined coke. It is 

manufactured in limited quantities and is used primarily as a specialty insulation in 

the aeronautic, marine, and energy industries (Madonik 2011). 

• Foamglas is a rigid board insulation made from sand, limestone, and soda ash that is 

primarily used for high-temperature industrial applications where extreme heat 

resistance is required but can be used to as insulation in roofs, walls, and belowgrade. There is only one Foamglas manufacturer in the U.S. and Foamglas is costly 

compared to other rigid board insulation products (Wilson 2010c). 

• Phenolic foam is a type of rigid foam and foamed-in-place insulation that may be 

used in roofing, wall cavities, external walls, and floors (COWI 2011). Currently, 

only foamed-in place phenolic insulation is available in the U.S (U.S. Department of 

Energy 2011). Rigid phenolic foams are no longer produced in the U.S. after 

corrosive breakdown products caused construction issues in the early 1990s, although 

they may be imported from Europe and Asia (Smith, Carlson et al. 1993; Schroer, 

Hudack et al. 2012).

• Reflective insulation is a foil-faced insulation material that incorporates a radiant 

barrier (normally highly reflective aluminum) with a kraft paper, plastic film, 

polyethylene bubble, or cardboard backing (U.S. Department of Energy 2012). 

Reflective insulation is used to reduce radiant heat flow across an open space, most 

usefully for downward radiant heat flow, and is typically used between roof rafters, 

5-12
floor joists, and wall studs (U.S. Department of Energy 2008). The rest of the 

insulations described here are designed to reduce thermal heat conduction through 

solid surfaces in any direction. For this reason, reflective insulation is not an 

alternative for EPS and XPS, but rather works best in complement with other forms 

of insulation.

• Agrifiber insulation is manufactured from agricultural waste (e.g., rice hulls, fungal 

mycelia, wheat or rice straw) and is available as board insulation (Healthy Building 

Network 2011; Wilson 2011). Agrifiber typically uses borate as a flame retardant 

(Sustainable Sources 2011). New agrifiber insulations under development using 

mycelium as a binder are reported to have obtained a Class 1 fire rating without use 

of added chemical flame retardants (Wilson 2011). Agrifiber insulation has an Rvalue ranging from 3.0 to 3.5 and is not water resistant; it is currently available only 

in limited SIPs applications (Healthy Building Network 2011; Madonik 2011).

Further information about the alternative materials discussed in this section can be found in 

materials provided by the U.S. Department of Energy20, Environmental Building News21, The 

Pharos Project22, GreenSpec23, manufacturer websites, and the respective trade association 

websites, as well as the references cited above.

20 http://www.energysavers.gov/your_home/insulation_airsealing/index.cfm?mytopic=11510 21 http://www.buildinggreen.com/news/index.cfm 22 http://www.pharosproject.net/ 23 http://www.greenspec.co.uk/insulation-introduction.php

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