&EPA
United States
Environmental Protection
Agency
us.
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.
11
-------
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 non-
brominated 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
TBBPAbis(2,3-dibromopropyl ether) (CASRN 21850-44-2) as an analog.
in
-------
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 by-
products 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.
-------
ES-1 Hazard Summary for HBCD and Alternatives
VL = Very Low hazard L = Low hazard VI = Moderate hazard = 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.
§ 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
Acute Toxicity
Carcinogenicity
Genotoxicity
Reproductive
Developmental
Neurological
Repeated Dose
Skin Sensitization
Respiratory
Sensitization1
Eye Irritation
Dermal Irritation
Aquatic
Toxicity
0)
1
Chronic
Environmental
Fate
Persistence
Bioaccumulation
Hexabromocyclododecane (HBCD)
A^-VB,
25637-99-4;
3194-55-6
L
M
L
JM
H
M
L
VL
VL
VH
VH
H
VH
Butadiene styrene brominated copolymer*
r^s
9 j
Br ,X ,J~~~..
i r ii
1195978-93-8
L
TBBPA-bis brominated ether derivative*
•Vlc^'
97416-84-7
L§
L
*
L
^
L
J*
L
J*
L
L
If
*
L
L§
L
L
L
L
L
L
L
VH
L
H
H
TBBPA bis(2,3-dibromopropyl) ether*
•^x
21850-44-2
L
M
M
M
L
M
L
L
L
L
L
VH
H
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.
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
vn
-------
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
TBBPAbis(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
Vlll
-------
List of Acronyms and Abbreviations
ACR
AIM
ASTM
ATSDR
BAF
BEARHFTI
BCF
C&D
CDR
CFC
ChV
CPSC
DecaBDE
Dffi
EC 50
ECOSAR
EDSP
Eh
EIFS
EPA
EPI
EPS
FPQA
FPSF
FM
GHS
HBr
HFC
HIPS
HPV
HSDB
IARC
roc
ICF
IRC
IRIS
IUR
K0a
LCA
LD50
Acute to chronic ratio
Analog Identification Methodology
American Society for Testing and Materials
Agency for Toxic Substances and Disease Registry
Bioaccumulation Factor
California Bureau of Electronic and Appliance Repair, Home Furnishings and
Thermal Insulation
Bioconcentration Factor
Construction and demolition
Chemical Data Reporting
Chi orofluorocarb on
Chronic value
Consumer Product Safety Commission
Decabromodiphenyl ether
Design for the Environment
Half maximal effective concentration
Ecological Structure Activity Relationships
Endocrine Disrupter Screening Program
Redox potential
Exterior Insulating and Finishing System
U.S. Environmental Protection Agency
Estimation Programs Interface
Expanded polystyrene foam
Food Quality Protection Act
Frost Protected Shallow Foundation
Factory Mutual
Globally Harmonized System of Classification and Labeling of Chemicals
Hydrogen bromide
Hy drofluorocarb on
High-impact polystyrene
High production volume
Hazardous Substances Data Bank
International Agency for Research on Cancer
International Building Code
Insulating Concrete Form
International Residential Code
Integrated Risk Information System
Inventory Update Reporting
Octanol/air partition coefficient
Soil adsorption coefficient
Octanol/water partition coefficient
Median lethal concentration
Life-cycle assessment
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
-------
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 non-
governmental 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 C^HigBre 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 non-
specific 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
Br
Br
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.
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/proiects/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 Alter native 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. 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/june201 l/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-l.
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 hi .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/proiects/decaBDE/index.htm
2-1
-------
Figure 2-1. Profile of HBCD Uses in European Markets for 2006/2007
Other (including
HIPS)
2%
(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 2011 a;
Extruded Polystyrene Foam Association 201 la; 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 201 Ib; Extruded Polystyrene Foam Association 201 la; Extruded
Polystyrene Foam Association 201 Ib). 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 201 Ib). The use of HBCD in non-insulation applications of
polystyrene foam was outside the scope of this alternatives assessment and was not researched.
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 Insulation1 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:
Typical Applications of EPS and/or XPS:
• Attics and Ceilings
• Roofs
o Membrane roofs
o Recovery/reroofmg
o Vegetative roofs
• Walls
Continuous insulation
Exterior Insulating and Finishing
Systems (EIFS)
Garage door panels
Insulating Concrete Forms (ICFs)
Masonry cavity walls
One-coat stucco panels
Precast concrete
Steel Stud insulation
Structural Insulated Panels (SIPs)
Flooring
Below grade applications
o
o
o
o
o
o
o
o
o
o
o
o
o
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.
Frost Protected Shallow
Foundations (FPSF)
Geofoam
Geotechnical fill & stabilization
Highway insulation
• Cold Storage/Low temperature buildings
• Transportation
o Recreational vehicle panels
o Shipping containers
(EPS Molders Association, 2009a, 201 Ib;
Extruded Polystyrene Foam Association, 201 la,
201Ib)
Likewise, ASTM D6817 applies to polystyrene foams in geotechnical engineering applications ("geofoam"). See
http ://www. astm.org/Standards/D6817. htm.
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
Classification Type
Minimum Density
Compressive strength
Performance Requirement
R-value
Flexural strength
Water vapor transmission rate
Water absorption
Dimensional Stability
Oxygen index
Flame spread index
Smoke development index
Unit
Ibs per ft3 (pcf)
Ibs per in2 (psi)
F-ft2-h/BTU (75°F)
Ibs per in2 (psi)
Perm per inch
%
%
%
Unitless index
Unitless index
EPS
XI, I, VIII, II, IX, XIV, XV
0 70 0 90 115 135 1 80
2.40, 3.00
5.0, 10.0, 13.0, 15.0,25.0,
40,0, 60.0
3.1-4.3
10-75
2.5-5.0
2.0-4.0
2
>24
<75
<450
XPS
XII, X, XIII, IV, VI, VII, V
1 20 1 30 1 60 1 55 1 80
2.20, 3.00
15.0, 15.0,20.0,25.0,40.0,
60.0, 100.0
4.6-5
40-100
1.1-1.5
0.3-1.0
2
>24
<75
<450
(International Code Council 201 la; International Code Council 201 Ib; 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 201 la), 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 201 la; Extruded Polystyrene Foam Association 201 la; 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 201 la;
Extruded Polystyrene Foam Association 201 la; 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
Figure 2-2. EPS Insulation
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 201 la). 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.
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
Figure 2-3. XPS Insulation
(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; COWI2011; Extruded Polystyrene Foam
Association 201 la; 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).
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 DecabromodiphenylEther (DecaBDE)%, 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
' www. epa. gov/dfe/pubs/proi ects/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; Sail 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 (Sail
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/proi ects/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; Sail 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 re-
expanded 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 201 Ib). 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 201 la). 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 201 Ib).
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 201 Ib). 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 201 Ib).
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-to-
mouth 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, Sjodin 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 201 la). 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 201 la). 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
-------
References
American Society for Testing and Materials (2012). C578-12a: Standard Specification for Rigid,
Cellular Polystyrene Thermal Insulation. West Conshohocken, PA, ASTM International.
Arch, P. (2011). Synergists. E. Lavoie.
Arnot, J., L. McCarty, et al. (2009). An evaluation of hexabromocyclododecane (HBCD) for
Persistent Organic Pollutant (POP) properties and the potential for adverse effects in the
environment. Submitted to European Brominated Flame Retardant Industry Panel
(EBFRIP).
Birnbaum, L. S., D. F. Staskal, et al. (2003). "Health effects of polybrominated dibenzo-p-
dioxins (PBDDs) and dibenzofurans (PBDFs)." Environ Int 29: 855-860.
Books, J. T. and S. D. Landry (1998). Heat stabilized, flame retardant styrenic polymer foam
compositions. U.S. Patent 5 J17.001.
Center for Disease Control and Prevention (2009). Fourth National Report on Human Exposure
to Environmental Chemicals. Department of Health and Human Services: 316.
Covaci, A., A. C. Gerecke, et al. (2006). "Hexabromocyclododecanes (HBCDs) in the
Environment and Humans: A Review." Environ Sci Technol 40: 3679-3688.
COWI (2011). Alternatives to the Use of Flame Retarded EPS in Buildings, Norwegian Ministry
on the Environment: Climate and Pollution Agency.
Dawson, P. (2011). Update on HBCD Assessment at POPs Review Committee, New Zealand
Ministry for the Environment.
DeBoer, J., C. Allchin, et al. (2002). HBCD and TBBP-A in sewage sludge, sediments and biota,
including interlaboratory study. Ymuiden, The Netherlands, Netherlands Institute for
Fisheries Research (RIVO).
Drottar, K. R., J. A. MacGregor, et al. (2001). Hexabromocyclododecane (HBCD): An early life-
stage toxicity test with the rainbow trout (Oncorhynchus mykiss). Final Report.
Maryland, Wildlife International, Ltd.: 1-102.
Environment Canada (201 la). Proposed Risk Management Approach for
Hexabromocyclododecane (HBCD).
Environment Canada (201 Ib). Screening Assessment Report on Hexabromocyclododecane.
EPS Industry Alliance. (2009a). "EPS Molders Association: EPS Applications." Retrieved
September 27, 2011, from http://www.epsmolders.Org/3.html.
2-14
-------
EPS Industry Alliance. (2009b). "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 (201 la). HBCD Use in Polystyrene Foam Insulation. Presentation to U.S.
Environmental Protection Agency, Washington, DC.
EPS Industry Alliance (201 Ib). Personal Communication: Typical EPS Uses 2011. Email to
Emma Lavoie.
EPS Industry Alliance (2012). Expanded Polystyrene Flame Retardants: Fire Resistance in
Building & Construction Applications. Crofton, MD.
European Chemicals Agency (2009). Background document for hexabromocyclododecane and
all major diastereoisomers identified (HBCDD).
European Commission (2008). Risk Assessment: Hexabromocyclododecane CAS-No.: 25637-
99-4 EINECS No.: 247-148-4, Final Report May 2008. Luxembourg.
Extruded Polystyrene Foam Association (201 la). Extruded Polystyrene Foam (XPS) Thermal
Insulation Overview. Presentation to U.S. Environmental Protection Agency,
Washington, D.C.
Extruded Polystyrene Foam Association. (201 Ib). "XPSA." Retrieved September 27, 2011,
from http://www.xpsa.com/comm/index.html.
Fabian, B. (2011). Extruded Polystyrene Thermal Insulation. Design for the Environment Kick-
Off Meeting, Crystal City, VA.
Fernandes, A., P. Dicks, et al. (2008). "Brominated and chlorinated dioxins, PCBs, and
brominated flame retardants in Scottish shellfish: methodology, occurrence and human
dietary exposure." Mol. Nutr. Food Res. 52: 238-249.
Gearhart, J., H. Posselt, et al. (2008). 2008 Guide to Child Car Seats.
Grant, T. (2011). Personal Communication: Specialty EPS. Email to Emma Lavoie.
Great Lakes Solutions, A Chemtura Business (2011). Emerald 3000.
Hahn, K., K. Hinselmann, et al. (1981). Process for the manufacture of flame retardant
polystyrene foams. U.S. Patent 4.298.702.
Hallenback, D., C. Doumen, et al. (2001). Stabilizer blend for organic polymer compositions;
stabilized polymer compositions and method of stabilizing polymers. U.S. Patent
6.225.387.
Harscher, M. (2011). Uses of Hexabromocyclododecane (HBCD): Flammability Standards.
Design for the Environment Kick-Off Meeting, Crystal City, VA.
2-15
-------
Heibl, J. and W. Vetter (2007). "Detection of hexabromocyclododecane and its metabolite
pentabromocyclodedecane in chicken egg and fish from the official food control." I
Agric. Food Chem. 55: 3319-3324.
Herrenbruck, S. (n.d.). "Performance Across The Board." Retrieved January 23, 2012,
from http://www.greenbuildingsolutions.org/Main-Menu/Home/Modern-Materials-
Archive/Energy-Efficiencv/Perfbrmance- Across-The-Board.html.
ICC Evaluation Service (2012). Public Notification Regarding Qualification of Reformulated
Foam Plastic Insulation to Meet the Requirements of AC 12 (Acceptance Criteria for
Foam Plastic Insulation), Subject AC 12-1012-R1 (MB).
International Code Council (2011 a). International Building Code. Chapter 26: Plastic.
International Code Council (201 Ib). "International Residential Code." Section R316: Foam
Plastic.
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).
Janak, K., A. Covaci, et al. (2005). "Hexabromocyclododecane in Marine Species from the
Western Scheldt Estuary: Diastereoisomer- and Enantiomer-Specific
Accumulation." Environ Sci Technol 39: 1987-1994.
Johnson-Restrepo, B., D. H. Adams, et al. (2008). "Tetrabromobisphenol A (TBBPA) and
hexabromocyclododecanes (HBCDs) in tissues of humans, dolphins, and sharks from the
United States." Chemosphere 70: 1935-1944.
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
2008/0090920 Al.
Meijer, L., J. Weiss, et al. (2008). "Serum concentrations of neutral and phenolic organohalogens
in pregnant women and some of their infants in The Netherlands." Environ Sci Technol
42(9): 3428-3433.
Morose, G. (2006). An Overview of Alternatives to Tetrabromobisphenol A (TBBPA) and
Hexabromocyclododecane (HBCD). University of Massachusetts Lowell, Lowell Center
for Sustainable Production.
Owens Corning (2007). PINK Insulation Shows True Color is Green: FOAMULAR® Extruded
Insulation Recycled After 17 Years on the Job at DFW Airport.
Plastics Europe (2014). End-of-life treatment of HBCD-containing polystyrene insulation foams:
Large-scale demonstration of the treatment of Expanded Polystyrene Foam (EPS) and
2-16
-------
Extruded Polystyrene Foam (XPS) containing Hexabromocyclododecane (HBCD) as a
flame-retardant by co-incineration in the Wiirzburg Municipal Solid Waste Incinerator.
Technical Summary Report.
Roosens, L., M. A. Abdallah, et al. (2009). "Exposure to Hexabromocyclododecanes (HBCDs)
via Dust Ingestion, but not Diet, Correlates with Concentration in Human Serum—
Preliminary Results." Environ Health Perspect. 13 July 2009.
Rozman, K. K. and C. D. Klaassen (2001). Absorption, Distribution, and Excretion of
Toxicants. Casarett and Douirs Toxicology: The Basic Science of Poisons. A. Seils, S.
R. Noujaim and L. A. Sheinis. New York, McGrawHill: 117.
Sail, L. (2010). Exploration of Management Options for Hexabromocyclododencane (HBCD):
Paper for the 8th Meeting of the UNECE CLRTAP Task Force on Persistent Organic
Pollutants, Montreal 18-20, Climate and Pollution Agency in Norway.
Stobby, W. G. (2008). Stabilizer blend for organic polymer compositions; stabilized polymer
compositions and method of stabilizing polymers. U.S. Patent 6,225,387.
Sustainable Sources. (2012). "Construction Waste Recycling." Retrieved January 23, 2012,
from http://constructionwaste.sustainablesources.com/.
Thomsen, C., P. Molander, et al. (2007). "Occupational Exposure to Hexabromocyclododecane
at an Industrial Plant." Environ Sci Technol 41(15): 5210-5216.
Toms, L.-M. L., A. Sjodin, et al. (2009). "Serum Polybrominated Diphenyl Ether (PBDE) Levels
Are Higher in Children (2-5 Years of Age) than in Infants and Adults." Environ Health
Perspect 117(9): 1461-1465.
Tomy, G. T., W. Budakowski, et al. (2004). "Biomagnification of a- and y-
hexabromocyclododecane isomers in a Lake Ontario food web." Environ Sci Technol 38:
2298-2303.
U.S. Department of the Interior (n.d.). Environmental Considerations of Building Insulation.
U.S. EPA (1997). EPA Office of Compliance Sector Notebook Project: Profile of the Plastic
Resin and Manmade Industries. Office of Enforcment and Compliance Assurance.
Washington DC.
U.S. EPA (1998). Characterization of Building-related Construction and Demolition Debris the
the United States.
U.S. EPA (2006). Non-confidential 2006 IUR Database.
U.S. EPA (2009). Buildings and their Impact on the Environment: A Statistical Summary.
U.S. EPA (2010). Hexabromocyclododecane (HBCD) Action Plan.
2-17
-------
U.S. EPA (2012). Significant New Use Rule for Hexabromocyclododecane and 1,2,5,6,9,10-
Hexabromocyclododecane. 77 FR 17386-17394.
U.S. EPA (2013). Non-confidential 2012 Chemical Data Reporting (CDR) information.
UNEP (2009). Summary of the proposal for the listing of hexabromocyclododecane (HBCDD)
in Annex A to the Convention. Stockholm Convention on Persistent Organic Pollutants.
United Kingdom Environment Agency (2009). Hexabromocyclododecane in the Environment.
van Leeuwen, S. P. and J. de Boer (2008). "Brominated flame retardants in fish and shellfish -
levels and contribution offish consumption to dietary exposure of Dutch citizens to
HBCD." Mol. Nutr. Food Res. 52: 194-203.
Veith, G. D., D. L. Defoe, et al. (1979). "Measuring and estimating the bioconcentration factor in
fish." J. Fish Res. Bd. Can. 36: 1040-1048.
Weber, R. and B. Kuch (2003). "Relevance of BFRs and thermal conditions on the formation
pathways of brominated and brominated-chlorinated dibenzodioxins and
dibenzofurans." Environ Int 29(6): 699-710.
Weil, E. D. and S. V. Levchik (2009). Flame Retardants for Plastics and Textiles: Practical
Applications. Cincinnati, Hanser Publications.
Wilson, A. (2005). "Insulation: Thermal Performance is Just the Beginning." Environmental
Building News.
Zhang, H., Y.-Y. Kuo, et al. (2012). "Co-Release of Hexabromocyclododecane (HBCD) and
Nano- and Microparticles from Thermal Cutting of Polystyrene Foams." Environ Sci
Technol 46: 10990-10996.
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 by-
products 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/proj ects/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 El 19 (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 (Standardfor 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). FffiCD 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).
Figure 3-1. Bromine Interaction Mechanism
HBr + OH' -> H2O + BH
HBr + •<> -> OH' + BH
HBr + H' <-> H2 + Br'
HBr + RCH2' <-> RCH3 + Br»
RBr <-> R' + Br«
Source: Kaspersma, Doumen et al. 2002
' Based on ASTME84.
'ibid
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
-------
(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
Hexabromocyclododecane (HBCD)
Benzene, ethenyl-, polymer with 1,3
butadiene, brominated; "butadiene
styrene brominated copolymer"
Benzene, 1,1'-(1-
methylethylidene)bis[3,5-dibromo-4-
(2,3-dibromo-2-methylpropoxy)];
"TBBPA-bis brominated ether
derivative"
Tetrabromobisphenol A Bis (2,3-
dibromopropyl) Ether
CASRN
25637-99-4;
3194-55-6
1195978-93-8
97416-84-7
21850-44-2
Status
Action Plan chemical. Included for comparative
purposes.
Announced by The Dow Chemical Company and Great
Lakes Solutions, A Chemtura Business on March 29,
2011 (Great Lakes Solutions, A Chemtura Business
201 1). The chemical has also been licensed to ICL-IP
and Albemarle.
Proposed as an alternative by a chemical manufacturer.
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.
http ://www. epa. gov/dfe/pubs/proi ects/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
Dibromoethyldibromocyclohexane
Chloropentabromocyclohexane
Cinnamalacetophenone tetrabromide
Hexabromohexene
1,2-Dibromoalkyl ketones
1, l,2,3,4,4-Hexabromo-2-butene
bis(2,3 -dibromopropyl)
tetrabromophthalate
2,4,6-Tribromophenyl allyl ether
bis(allyl ether) of
tetrabromobisphenol A
31454-48-5;
3194-57-8
3322-93-8
87-84-3
N/A1
125512-87-0
N/A1
72108-73-7;
36678-45-2
N/A1
3278-89-5
25327-89-3
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.
Polystyrene manufacturers have noted insufficient thermal stability and an inferior persistent,
bioaccumulative, and toxic (PBT) chemical assessment.
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.
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-l,5-diphenyl-; CASRN 31611-84-4.
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.
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.
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.
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-, l,2-bis(2,3-
dibromopropyl) ester; CASRN 214216-08-7.
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.
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
N-(2,3-dibromopropyl)-4,5-
dibromotetrahydrophthalimide
Dialkyl tetrabromophthalate
tris(2,3-dibromopropyl) phosphate
CASRN
93202-89-2
N/A1
126-72-7
Reason for Exclusion
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.
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-, l,2-bis(2-ethylhexyl) ester; CASRN 26040-5 1-7.
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)
Brominated anionic styrene polymer
+ bis(pentabromophenyl) ethane
Bromoaliphatic FR + a more
thermally stable bromine compound
with an aromatic, vinylic, or
neopentyl structure
Halogenated FR + P-N compound
Elemental sulfur + phosphorus
additive
Graphite particles (halogenated FR
and (optional) antimony oxide, or
with a phosphorus FR)
Epoxy resin containing reacted-in
DOPO and phosphoric acid
21645-51-2
N/A' +
84852-53-9
N/A1
N/A1
7704-34-9 +
7723-14-0
N/A1
N/A1
This flame retardant will require high loading in EPS and XPS. It has also already been assessed in
Design for the Environment (DfE)'sAn Alternatives Assessment For The Flame Retardant
Decabromodiphenyl Ether (DecaBDE) .
These blends are synergistic mixtures used to improve performance of certain FRs. They are not potential
alternatives to HBCD.
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.
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
Thiophosphates and
dithiophosphates
Flame resistant barrier - coating,
laminate, foil
Boric acid + binder
N/A1
N/A1
N/A1
N/A1
At low loading levels, these nanoparticle fire retardant coatings significantly reduce polyurethane foam
flammability and can result in serf -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.
Polystyrene foam manufacturers observed insufficient flame retardant activity.
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.
This chemical is used as a smoke suppressant rather than as a flame retardant. It should also be noted that
3-9
-------
Chemical Name
Dimethyl methyl phosphonate
(DMMP)
Hypophosphite, calcium salt (with
synergists)
Magnesium dihydroxide
CASRN
756-79-9
7789-79-9
1309-42-8
Reason for Exclusion
boric acid is a substance of very high concern in the European Union (EU).
This chemical is too volatile for polystyrene foam.
Polystyrene manufacturers have noted insufficient flame retardant activity.
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, PJ.
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
Chemicals Agency (ECHA).
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
Work." Fire Techonology 34(1): 39-58.
Peck, M. D. (2011). "Structure Fires, Smoke Production, and Smoke Alarms." J Burn Care Res
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
from the Combustion of Circuit Board Laminates. Final Report. Prepared for the U.S.
Environmental Protection Agency.
U.S. EPA. (2003a). "Hexabromodiphenyl ether (CASRN 36483-60-0)." Integrated Risk
Information System Retrieved November 29, 2012,
from http://www.epa.gov/iris/subst/0494.htm.
U.S. EPA. (2003b). "Tetrabromodiphenyl ether (CASRN 40088-47-9)." Integrated Risk
Information System Retrieved November 29, 2012,
from http://www.epa. gov/iri s/sub st/0493. htm.
3-12
-------
U.S. EPA. (2004). "Pentabromodiphenyl ether (CASRN 32534-81-9) " Integrated Risk
Information System Retrieved November 29, 2012,
from http://www.epa.gov/iris/subst/0184.htm.
U.S. EPA. (2008). "2,2',3,3',4,4',5,5',6,6'-Decabromodiphenyl ether (BDE-209) (CASRN 1163-
19-5)." Integrated Risk Information System Retrieved November 29, 2012,
from http://www.epa. gov/iri s/sub st/003 5. htm.
U.S. EPA (2012). Certain Polybrominated Diphenylethers; Significant New Use Rule and Test
Rule. 77 FR 19862.
Underwriters Laboratories (2012) "UL Partners With FDNY and NIST to Advance Firefighter
Safety."
Weil, E. D. and S. Levchik (2004). "A Review of Current Flame Retardant Systems for Epoxy
Resins." Journal of Fire Science 22: 25-40.
Weil, E. D. and S. V. Levchik (2009). Flame Retardants for Plastics and Textiles: Practical
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 $\Q Alternatives Assessment
Criteria for Hazard Evaluation (U.S. EPA 201 Ib). 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 20 lib). 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
Acute Mammalian Toxicity
Carcinogenicity
Mutagenicity/Genotoxicity
Human Health
Effects
Reproductive Toxicity
Developmental Toxicity
Neurotoxicity
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.
Capability of a substance to increase the incidence of
malignant neoplasms, reduce their latency, or increase
their severity or multiplicity.
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 non-
physiological manner (temporarily) alter its replication.
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.
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.
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
Environmental
Toxicity
Environmental
Fate
Endpoint
Repeated Dose Toxicity
Respiratory Sensitization
Skin Sensitization
Eye Irritation/Corrosivity
Dermal Irritation/Corrosion
Definition
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.
Hypersensitivity of the airways following inhalation of a
substance.
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.
Irritation or corrosion to the eye following the application
of a test substance.
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 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)
Aquatic Toxicity (Chronic)
Environmental Persistence
Bioaccumulation
The property of a substance to be injurious to an organism
in a short-term (days), aquatic exposure to that substance.
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.
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).
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 201 Ib). 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
Very Low
Human Health Effects
Acute mammalian toxicity
Oral median lethal dose
(LD50) (mg/kg)
Dermal LD50 (mg/kg)
Inhalation median lethal
concentration (LC50) -
vapor/gas
(mg/L)
Inhalation LC 50 - dust/mist/
fume (mg/L)
<50
<200
<2
<0.5
>50-300
>200-1000
>2-10
XX5-1.0
>300-2000
>1000-2000
>10-20
>l-5
>2000
>2000
>20
>5
-
-
-
Carcinogenicity
Carcinogenicity
Known or
presumed
human
carcinogen
Equivalent to
Globally
Harmonized
System of
Classification
and Labeling of
Chemicals
(GHS)
Categories 1A
and IB
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
mechanism-
based Structure
Activity
Relationship
(SAR)
As described
above
-
Mutagenicity/Genotoxicity
Germ cell mutagenicity
GHS Category
1A or IB'
Substances
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
Mutagenicity and
genotoxicity in somatic
cells
Very High
High
Evidence of
mutagenicity
supported by
positive results
in in vitro AND
in vivo somatic
cells and/or
germ cells of
humans or
animals
Very Low
Reproductive toxicity
Oral (mg/kg/day)
Dermal (mg/kg/day)
Inhalation - vapor, gas
(mg/L/day)
Inhalation - dust/mist/fume
(mg/L/day)
-
-
-
-
<50
<100
<1
<0.1
50-250
100-500
1-2.5
0.1-0.5
>250-1000
>500-2000
>2.5-20
>0.5-5
>1000
>2000
>20
>5
Developmental toxicity
Oral (mg/kg/day)
Dermal (mg/kg/day)
Inhalation - vapor, gas
(mg/L/day)
Inhalation - dust/mist/fume
(mg/L/day)
-
-
-
-
<50
<100
<1
<0.1
50-250
100-500
1-2.5
0.1-0.5
>250-1000
>500-2000
>2.5-20
>0.5-5
>1000
>2000
>20
>5
Neurotoxicity
Oral (mg/kg/day)
Dermal (mg/kg/day)
Inhalation - vapor, gas
(mg/L/day)
Inhalation - dust/mist/fume
(mg/L/day)
-
-
-
-
<10
<20
0.2
0.02
10-100
20-200
0.2-1.0
0.02-0.2
>100
>200
>1.0
>0.2
-
-
-
-
Repeated-dose toxicity
Oral (mg/kg/day)
Dermal (mg/kg/day)
Inhalation - vapor, gas
(mg/L/day)
Inhalation - dust/mist/fume
(mg/L/day)
-
-
-
-
<10
<20
O.2
O.02
10-100
20-200
0.2-1.0
0.02-0.2
>100
>200
>1.0
>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 IB)
Adequate data
available and not
GHS Category
lAorlB
-
4-6
-------
Endpoint
Respiratory sensitization
Very High
-
High
Occurrence in
humans or
evidence of
sensitization in
humans based
on animal or
other tests
(equivalent to
GHS Category
1A and IB)
Limited
evidence
including the
presence of
structural alerts
Low
Adequate data
available
indicating lack
of respiratory
sensitization
Very Low
-
Irritation/corrosivity
Eye irritation/corrosivity
Skin irritation/corrosivity
Irritation
persists for
>21 days or
corrosive
Corrosive
Clearing in 8-
21 days,
severely
irritating
Severe
irritation at
72 hours
Clearing in
<7 days,
moderately
irritating
Moderate
irritation at
72 hours
Clearing in
<24 hours,
mildly irritating
Mild or slight
irritation at
72 hours
Not irritating
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)
Chronic aquatic toxicity -
lowest observed effect
concentration (LOEC) or
chronic value (ChV)
(mg/L)
<1.0
<0.1
1-10
0.1-1
>10-100
>1-10
>100orNo
Effects at
Saturation
(NES)
>10orNES
-
-
Environmental persistence
Persistence in water, soil,
or sediment
Persistence in air (half -life
days)
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.
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
Very Low
Bioaccumulation
Bioconcentration Factor
(BCF)/Bioaccumulation
Factor (BAF)
LogBCF/BAF
>5000
>3.7
5000-1000
3.7-3
<1000-100
<3-2
<100
<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
Toxicokinetics
Biomonitoring
Information
Environmental Transport
Persistence in Air
Immunotoxicology
Terrestrial Ecotoxicology
Endocrine Activity
Definition
The determination and quantification of the time course of absorption, distribution,
biotransformation, and excretion of chemicals (sometimes referred to as
pharmacokinetics).
The measured concentration of a chemical in biological tissues where the analysis
samples were obtained from a natural or non-experimental setting.
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 physical-
chemical properties, environmental fate parameters, and simple volatilization models.
Also includes distribution in the environment as estimated from a fugacity model1.
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.
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).
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.
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.)
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 (EPISuite™) for physical-chemical property and
environmental fate endpoints or EPA's Ecological Structure Activity Relationships
(ECOSAR™) 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 EPISuite™, 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 physical-
chemical 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 physical-
chemical 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" 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 IxlO"4 mm Hg generally exist in
the gas phase in the atmosphere. Substances with a vapor pressure between IxlO"4 and IxlO"8
mm Hg exist as a gas/particulate mixture. Substances with a vapor pressure less than IxlO"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 IxlO"8 mm Hg was assigned for chemicals without experimental
data or for those substances that were anticipated by professional judgment to be nonvolatile
o
(U.S. EPA 1999b). The maximum vapor pressure of 1x10" 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 IxlO"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 IxlO"3 mg/L (U.S. EPA 1999b). A water solubility of IxlO"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 EPISuite™
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 201 Ih). Given that water solubility decreases with MW, a default
value of IxlO"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 EPISuite™ or that were expected
to be insoluble in water (WS 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 EPISuite™ 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 201 Ig). 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.
4-15
-------
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
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 pKe, 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.
4-16
-------
Henry's Law constant values less than IxlO"7 atm-m3/mole indicate slow volatilization from
water to air (the Henry's Law constant for the volatilization of water from water is IxlO"7 atm-
m3/mole) and values more than IxlO"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
O Q
model river and a model lake. A maximum value of 1x10" atm-m /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
4-17
-------
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 gas-
phase 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 201 le; U.S. EPA
20 lid).
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., CC>2 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 EPISuite™ models. EPISuite™ 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
4-18
-------
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 LCsoS 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
4-19
-------
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 201 Ib).
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).
4-20
-------
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 ECOSAR™ software and the
persistence designation was estimated using models in EPA's EPISuite™ 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) - LCso 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
4-21
-------
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 ECOSAR™ 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 ECOSAR™ estimation program uses chemical structure to estimate toxicity of a chemical
substance using class-specific QSARs. ECOSAR™ 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 ECOSAR™. However, the hazard designation was
based on the most conservative ECOSAR™ 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 ECOSAR™. In their absence, estimated log Kow values from
EPISuite™ were used. ECOSAR™ is maintained and developed as a stand-alone program but is
also accessible through the EPA EPISuite™ program after it is installed; therefore the
Estimations Program Interface (EPI) program was cited for the ECOSAR™ values in this report.
The QSARs for ECOSAR™ were built using experimental data for several chemical classes. For
a chemical class to be defined within ECOSAR , 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 offish, 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 EPISuite™ 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 EPISuite™.
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 EPISuite™ 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 EPISuite™ software (U.S. EPA 201 If). 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
KQW, 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 CC>2 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
EPISuite™ 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 EPISuite1 biodegradation models were used.
The rapid biodegradation potential models within EPISuite™ (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 EPISuite™ 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
-------
disrupter 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 Disrupter 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 in-
depth testing when warranted (U.S. EPA 201 la). 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
disrupters, 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/assawalidation/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 201 Ic). This process integrates and evaluates data, and always relies on
professional judgment (U.S. EPA 201 Ic). 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^asic.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/P-
02/002F.
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). TSCANew Chemicals Program (NCP) Chemical Categories. Office of
Pollution Prevention and Toxics. Washington, DC.
U.S. EPA. (201 la). "Assay Development." Retrieved April 17, 2012,
from http://www.epa.gov/oscpmont/oscpendo/pubs/assayvalidation/index.htm.
U.S. EPA (201 Ib). 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 (201 Ic). Endocrine Disrupter 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. (201 Id). "Estimation Program Interface (EPI) Suite." Retrieved April 18, 2012,
from http ://www.epa.gov/oppt/exposure/pubs/episuite.htm.
U.S. EPA (201 le). On-line AOPWIN™ User's Guide.
U.S. EPA (201 If). On-line BCFBAF™ User's Guide.
U.S. EPA (201 Ig). On-line KOWWIN™ User's Guide.
4-31
-------
U.S. EPA (201 Ih). On-line WSKOWWIN™ 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 Disrupter 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 VI = Moderate hazard = 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.
§ 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
Acute Toxicitj
^
Carcinogenicil
Genotoxicity
0)
-*^
a
0
1
Developmenta
Neurological
Repeated Dost
.0
Skin Sensitizal
o "3
•** CS
•II
a
-*^
+*
HH
0)
0
B
*c
•_
hH
13
0)
Q
Aquatic
Toxicity
1
Chronic
Environmental
Fate
Persistence
a
o
Bioaccumulati
Hexabromocyclododecane (HBCD)
Br, B,
X-/
CCT
25637-99-4;
3194-55-6
L
M
L
M
H
M
L
VL
VL
VH
VH
H
VH
Butadiene styrene brominated copolymer*
9
1195978-93-8
L
L
L
L
L
L
L<
L
L
L
L
VH
L
TBBPA-bis brominated ether derivative*
%C^
97416-84-7
L§
^
Af«
I*
*
L
Af«
L§
L
L
L
L
H
H
TBBPAbis(2,3-dibromopropyl) ether ¥
B B^H'^vX
21850-44-2
L
M
M
M
L
M
L
L
L
L
L
VH
H
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.
4-33
-------
4.8 Hazard Profiles
Hexabromocyclododecane (HBCD)
VL = Very Low hazard L = Low hazard = Moderate hazard = High hazard VH = Very High hazard — Endpoints in colored text (VL, L, , 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.
Chemical
CASRN
Human Health Effects
JO
"3
3
'0
'3
O
'8
sS
U
&
o
"o
OJ
o
0)
u
s
0
&
3
0)
1
_0
"3
0)
Q
13
u
B
s
0)
o
Q
•a
0)
"S
0)
8.
0
1
0)
C/5
a
C/5
^g
o -5
||
(2 $
a
HH
0)
0
*C
HH
13
0)
Q
Aquatic
Toxicity
"3
4g
ronic
U
Environmental
Fate
Oj
o
1
0)
0.
=
o
«
"3
3
u
sS
s
Hexabromocyclododecane (HBCD)
25637-99-4'
3194-55-6
L
M
L
H
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: C12H18Br
Physical Forms:
Neat: Solid
Use: Flame retardant
SMILES: BrClCC(CC(CC(CC(CC(Cl)Br)Br)Br)Br)Br (for CASRN 25637-99-4); BrC(C(Br)CCC(Br)C(Br)CCC(Br)C(Br)Cl)Cl (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 Fi-
None 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 anon-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 a-, (3- and y- 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-HO-OPPT-2011-0489-0001). Other regulatory actions
are being considered.
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)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
185-195 (Measured)
172- 184 to 20 1-205; 190 (average)
(Measured)
180-185 (Measured)
175-195 (Measured)
>190 (decomposes)
(Measured)
4.7xlO-7 at 21°C (Measured)
GLP Spinning Rotor Method/OECD TG
104 and EPA OPPTS 830.7952; reported
as 6.3xlO"5 Pa
HBCD sample consisted of 8.5%, 6.0%
and 79.1% a-, (3- and y-HBCD
respectively.
a-HBCD 7.9x10-"
P-HBCD 4.4X10'11
y-HBCD 6.3 xlO'13
at 25 °C Gas saturation method
(Measured)
6.6xlO-2 at 20°C (Measured)
GLP Column Elution Method
a-HBCD: 4.8xlO'2
(3-HBCD: l.SxlO'2
y-HBCD: 2.1xlO'3
NAS, 2000
EINECS, 2008
NICNAS, 2012
IUCLID, 2000
EINECS, 2008; NICNAS, 2012
EINECS, 2008; NICNAS, 2012
Kuramochi et al, 2010
EINECS, 2008; NICNAS, 2012
Similar values are consistently
reported in secondary sources.
Value reported in a secondary source.
The method used is not recommended
for substances with vapor pressures
<10-4Pa(or0.0008mmHg).
However, this value indicates a low
vapor pressure.
The method used is not recommended
for substances with vapor pressures
outside of 7.5xlO"10to 0.008 mmHg.
This value indicates a low vapor
pressure.
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
Log Kow
DATA
0.12 (Measured)
Solubility value of total HBCD
One isomer:
a-HBCD: 1.4xl(r2
(3-HBCD: 2.8xlO'3
y-HBCD: l.SxlO'3
Mixture of isomers (technical product):
a-HBCD: S.lxlO'2
(3-HBCD: 3.3xlO'2
y-HBCD: 1.6xl(r3
Direct Coupled Column Linked
Chromatographic Technique
0.008 (Measured)
3.4xlO'3 at 25°C (Measured)
GLP Column Elution Method
8.6xlO'3 at 25°C (Measured;
CASRN 3 194-55-6)
5.62 (Measured)
GLP Generator Column Method
REFERENCE
Kuramochi et al., 2007
IUCLID, 2000
EINECS, 2008; NAS, 2000;
NICNAS, 2012
HSDB, 201 la
EINECS, 2008; NICNAS, 2012
DATA QUALITY
The value reported is the sum of the
water solubility values for individual
diastereomers found in the technical
mixture.
Value reported in a secondary source.
The measurement was performed on
the technical product, which was not
100% pure. The value reported was
for a single diastereomer (y-HBCD)
in the mixture.
Value reported in a secondary source;
sufficient details were not available to
assess the quality of this study.
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
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
One isomer:
a-HBCD: 5.8
(3-HBCD: 5.8
y-HBCD: 6.3
Mixture of isomers (technical product):
a-HBCD: 5.7
(3-HBCD: 6.1
y-HBCD: 6.3
Slow-stirrer method (Measured)
5.81 (Measured)
Not flammable (Estimated)
Not explosive (Estimated)
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
Not applicable
Not applicable
REFERENCE
Kuramochi et al., 2007
IUCLID, 2000
EINECS, 2008
EINECS, 2008
Barontini et al., 2001; NICNAS,
2012
Professional judgment
Professional judgment
DATA QUALITY
Adequate non-guideline study.
Value reported in a secondary source.
Value reported in a secondary source.
Value reported in a secondary source.
Adequate non-guideline study.
Potential mechanisms for thermal
decomposition proposed.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
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 Y-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 a-diastereomer is much
higher than other diastereomers
Overall extent of metabolism of
technical-grade HBCD is unknown;
y-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 etal., 2011
Reported in a secondary source with
limited study details.
4-41
-------
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6
PROPERTY/ENDPOINT
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
Carcinogenicity
OncoLogic Results
DATA
REFERENCE
DATA QUALITY
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.
Rat LD50> 10,000 mg/kg
Rat LD50 >6,400 mg/kg
Rabbit LD50 >8,000 mg/kg
Rabbit LD50 >20,000 mg/kg
Rat LC50 >200 mg/L
Acute respiratory irritation test in Charles
River CD rats (5/sex) exposed (whole-
body) 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
EPA, 2005; NICNAS, 2012
EINECS, 2008
EPA, 2005; NICNAS, 2012
EINECS, 2008; NICNAS, 2012
EPA, 2005; NICNAS, 2012
EINECS, 2008; NICNAS, 2012
Reported in a secondary source with
limited study details.
Reported in a secondary source. Non-
guideline study. Dose and particle
size not reported; 7-day observation
period.
Reported in a secondary source with
limited study details.
Non-guideline study. Too few
animals were used; clinical signs not
reported.
Reported in a secondary source with
limited study details.
Reported in a secondary source. Non-
guideline study. No autopsy was
performed. According to OECD
guidelines (436), starting
concentrations for dust should be
0.05-5 mg/L.
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.
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
Combined Chronic
Toxicity/
Carcinogenicity
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal
Aberrations in vitro
DNA Damage and
Repair
Other in vitro
DATA
HBCD does not meet criteria (NOHSC,
2004) for classification as a carcinogen
(R45, R49, R40)
REFERENCE
NICNAS, 2012
DATA QUALITY
Reported in a secondary source.
No data located.
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.
Negative in Salmonella typhimurium
(strains not specified) in the presence and
absence of metabolic activation
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 ug/mL
Positive, intragenic recombination test in
Sp5/V79 and SPD8 hamster cells; cell
lines developed by study authors
Doses: 2-20 ug/mL
Negative, mouse micronucleus test
Doses: 0, 500, 1,000 or 2,000 mg/kg in
dimethyl sulfoxide (DMSO)
EPA, 2005; NICNAS, 2012
EPA, 2005; NICNAS, 2012
EPA, 2005; NICNAS, 2012
EPA, 2005
Reported in a secondary source with
limited study details.
No data located.
Reported in a secondary source.
Guideline study. Performed according
to current EPA, OECD guidelines,
and GLP.
No data located.
Reported in a secondary source. Non-
guideline study. Not a standard test
used by regulatory agencies to assess
genotoxicity. Reliability and
predictive ability is unknown.
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
Reproductive Effects
DATA
REFERENCE DATA QUALITY
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 FI
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 (Fi males); and
14.3, 138 and 1,363 mg/kg-day (Fj
females)
Delayed eye opening and surface righting
reflex response (Fj 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)
inF] 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
Fi animals
NOAEL =14.3 mg/kg-day
LOAEL =138 mg/kg-day (based on
reduced number of primordial ovarian
follicles in F ] 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% treatment-
related 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
2 8-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. Non-
guideline 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/kg-
day) 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 (BMD0s = 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 BMDLSDi 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 Ft 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/kg-
day)
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/kg-
day, (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
Saegusa et al., 2009 (continued)
DATA QUALITY
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/kg-
day)
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 (F] males); and
14.3, 138 and 1,363 mg/kg-day (Fj
females)
No effect on spontaneous locomotor
activity (10 min intervals for a total of 60
min; FI pups). No difference between
controls and treated Fj 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 (F] 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 FI 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 haloperidol-
induced cataleptic behavior in 110-day
old female rats in the 30 and 100 mg/kg-
day 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)
BMD 05 = 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 treatment-
related 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. Non-
guideline 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 non-
guideline 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)
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
In vitro plasma membrane uptake study in
removed brains of male Wister rats
Doses: 2-20
Inhibition of neurotransmitter uptake into
synaptosomes, dopamine uptake into
synaptic vesicles and glutamate uptake at
low concentrations
EPA, 2011
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.
Mariussen and Fonnum, 2003 (as
cited in EINECS, 2008;
NICNAS, 2012)
Estimated based on structural alert for
cyclic halogenated aliphatic
hydrocarbons.
Study reported in a secondary source.
4-57
-------
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 haloperidol-
induced cataleptic behavior in 110-day
old female rats in the 30 and 100 mg/kg-
day 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)
BMD 05 = 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
Repeated Dose Effects
DATA
REFERENCE
DATA QUALITY
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/kg-
day)
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 (F] males); and
14.3, 138 and 1,363 mg/kg-day (Fj
females)
Increased serum TSH (F0 females at
150 ppm and FI 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
j 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)
4^60
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.
-------
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/kg-
day)
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 article-
related 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)
4^62
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 a
isomer (6.3%), (3 isomer (9.1%) and y
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.
-------
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
2 8-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 dose-
dependent 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
2 8-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 2 8-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) 4-65
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.
-------
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
DATA
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
1 8 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
REFERENCE
Kurokawa et al., 1984 (as cited in
EINECS, 2008; EPA, 2005;
NICNAS, 2012)
DATA QUALITY
Reported in a secondary source.
Study was not conducted according to
OECD guidelines.
LOW: Based on negative results for skin Sensitization in human volunteers and guinea pigs.
Negative, patch test with 10% HBCD in
volunteers
Negative, guinea pigs
Negative, mice:
Local lymph node assay with 2, 20 or
50% w/v HBCD in DMF
EPA, 2005
EPA, 2005; NICNAS, 2012
EPA, 2005; NICNAS, 2012
Reported in a secondary source.
Guideline study.
Reported in a secondary source.
Guideline study. Performed according
to current EPA, OECD guidelines and
GLP.
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
Respiratory Sensitization
Respiratory
Sensitization
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
DATA
Positive, guinea pigs
Intra-dermal injection and topical
application
REFERENCE
EINECS, 2008; EPA, 2005;
NICNAS, 2012
DATA QUALITY
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.
No data located.
No data located.
VERY LOW: HBCD is not an eye irritant in rabbits.
Non-irritant, rabbits
EPA, 2005; NICNAS, 2012
Reported in a secondary source with
limited study details.
VERY LOW: HBCD is not a dermal irritant in rabbits or guinea pigs.
Non-irritant, rabbits
Non-irritant, guinea pigs
EPA, 2005; NICNAS, 2012
EINECS, 2008
Reported in a secondary source with
limited study details.
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 FI females (1,363 mg/kg-day) exposed to HBCD in a two-
generation 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 Ft 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 Y-HBCD-exposed Oncorhynchus mykiss. Fish fed a a-HBCD-
enriched diet exhibited altered glucuronyltransferase activity and thyroid epithelial cell heights, and fish fed
P-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 (a-, P- and y-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, y-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).
a-HBCD and y-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
2 8-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/kg-
day)
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 (Fl males); and
14.3, 138 and 1,363 mg/kg-day (Fj
females)
Increased TSH (FO females at >150 ppm
and FI females at >15,000 ppm);
decreased serum FSH levels in F0 males
and increased in F0 females at
15,000 ppm; increased DHT in F] 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/kg-
day)
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/kg-
day)
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 a-, (3- and y-diastereomers,
respectively; maximum concentration
was 446 ug HBCD/g lipid weight (Iw)
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 a-, (3- or y-HBCD for
56 days
Test concentrations were 0.47 and
0.84 ng/g (a- and y-HBCD, respectively)
Disruption of thyroid axis most evident in
y-HBCD-exposed group (lower circular
FT4 and higher FT3; increase in thyroid
epithelial cell height)
Fish fed the a-HBCD-enriched diet also
exhibited altered glucuronyltransferase
activity and thyroid epithelial cell heights
and the (3-HBCD group had altered FT4
and FT3 and glucuronyltransferase
activity
Palace et al., 2008
Guideline study. The (3-isomer was
below the detection limit.
4-74
-------
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. Non-
guideline 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 disrupter
Doses (test for T3 potentiating effect):
10-12.5 uM (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 uM (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% a, 8.7% (3, and 81.0% y-
HBCD.
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% a, 8.7% (3, and 81.0% y-
HBCD.
4-76
-------
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
in the presence or absence of T3 hormone
for 96 hours
Moderate AR and PR antagonistic
activity was reported for y-HBCD. Very
low or no antagonistic activation was
detected for the other two receptors, AhR
and ER. a-HBCD and y-HBCD showed
T3-enhanced activity at 1 uM 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.
4-77
-------
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
a-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-a and liver fatty acid-binding
protein
Results indicate that xenobiotic-
metabolizing 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
2 8-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.
4-78
-------
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)
Lepomis macrochirus 96-hour LC5
>100 mg/L (nominal)
Leuciscus idus 96-hour LC50
> 10,000 mg/L (nominal)
Fish 96-hour LC50 = 0.30 mg/L
(Estimated)
ECOSAR class: Neutral organics
EPA, 2005; NICNAS, 2012
EPA, 2005
EPA, 2005
ECOSAR vl. 10
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.
Reported in a secondary source with
limited study details. Value exceeds
water solubility.
Reported in a secondary source with
limited study details. Value exceeds
water solubility.
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.
4-79
-------
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
l.Omg/L.
Exposure to HBCD results in oxidative
stress and may induce apoptosis through
involvement of caspases
NOEC = 0.05 mg/L
LOEC = 0.1mg/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 magnet 4 8-hour EC50
>0.0068 mg/L (nominal) or
>0.0032 mg/L (mean measured)
EPA, 2005; NICNAS, 2012
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. No toxicity at HBCD's limit of
water solubility; NES.
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
ECOSARvl.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 ug 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.
4-81
-------
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6
PROPERTY/ENDPOINT
DATA
S. costatum 96-hour EC50 >0.0025 mg/L
S. costatum 72-hour EC50 >0.0406 mg/L
(40.6 ug HBCD/L)
NOEC >0.0406 mg/L (only concentration
tested)
LOEC = Not identified
Thalassiosira pseudonana 72-hour EC50
>0.05-0.37 mg/L
Scenedesmus subspicatus 96-hour EC50
>500 mg/L
No effect on growth inhibition
REFERENCE
ECHA, 2008
Desjardins et al., 2004 (as cited in
ECHA, 2008; NICNAS, 2012)
Walsh et al., 1987 (as cited in
EPA, 2005; NICNAS)
Siebel-Sauer and Bias, 1987 (as
cited in EINECS, 2008)
DATA QUALITY
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%
a-, 8. 5% (3- and 79.1%
y-diastereomers; total HBCD was
93.6% of test substance. There were
no effects at the highest concentration
tested.
Reported in a secondary source with
limited study details; LOECs were
not identified. One test concentration
at the limit of water solubility; NES.
Reported in a secondary source with
limited study details. No toxicity at
HBCD's limit of water solubility.
Reported in a secondary source.
Guideline study performed according
to current EPA, OECD guidelines and
GLP. Value exceeds water solubility.
4-82
-------
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
ECOSARv. 1.10
The estimated effect exceeds the
water solubility of 0.66 mg/L, but not
by lOx 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 y-HBCD
in Daphnia magna.
Fish ChV
Oncorhynchus mykiss 88-day NOEC
>0.0037 mg/L (y-HBCD).
27-Day hatching period; 61 days post-
hatch showed no effects on hatching
success, time to swim-up, larval survival,
fry survival or growth
Fish ChV = 0.043 mg/L (Estimated)
ECOSAR class: Neutral organics
Drotter et al., 2001; EPA, 2005
ECOSAR v. 1.10
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
y-HBCD's water solubility). HBCD
was not chronically toxic to rainbow
trout at concentrations at or above its
limit of solubility.
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 TEARS)
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. magnet 21-day life cycle toxicity test.
Nominal test concentrations were 0.85,
1.7, 3.4 and 13.6 (ig/L; measured test
concentrations were 0.87, 1.6, 3.1,
5.6 and 11 (ig/L.
LOEC = 0.0056 mg/L ([0.0042 mg/L
geometric mean]; reduced mean lengths)
NOEC = 0.0031 mg/L (y-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% a-, 8.5% (3- and
79.1% y-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
ECOSARv. 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.
4-85
-------
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
ECOSARv. 1.10
The effect level exceeds the water
solubility of 0.66 mg/L, but not by
lOx 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.
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 = 3.2mg/kgdwt
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 urn) 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.
4-86
-------
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 bw-
day). 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: a-, 27%; (3-
, 30%; y-,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
OO ?
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.
4-87
-------
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6
PROPERTY/ENDPOINT
DATA
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
REFERENCE
Fernie et al., 2009
DATA QUALITY
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
Henry's Law Constant -
HLC (atm-m3/mole)
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.
4.6xlO"5 at 25°C (Calculated from
Measured values)
6.0xlO-6 at 25°C (Estimated)
a-HBCD: 4.8xlO'9
(3-HBCD: l.SxlO'8
y-HBCD: S.SxlO'10
(Calculated from Measured values)
EPI/Physprop database for
CASRN 3 194-5 5 -6
EPI
Kuramochi et al., 2010
Derived from measured vapor
pressure (4.7xlO~7 mm Hg) and water
solubility (8.6xlO~3 mg/L) values.
Value was obtained from the
measured vapor pressure and water
solubility.
Value was obtained from the
measured vapor pressure (a-HBCD
7.9x10-"; (3-HBCD 4.4X10'11;
y-HBCD 6.3 x 10'13) and water
solubility.
4-88
-------
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Sediment/Soil
Adsorption/Desorption
Coefficient - Koc
9. IxlO4 (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 30ID
Approximately 22% degradation after 56
days; aerobic sludge inherent
biodegradation study (Measured)
OECD Test Guideline 302B
EINECS, 2008; NICNAS, 2012
Values reported in a secondary
source. Guideline studies performed
according to current EPA, OECD
guidelines and GLP.
EINECS, 2008; NICNAS, 2012
4-89
-------
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 y-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 y-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.
4-90
-------
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
a-HBCD: 113 days
(3-HBCD: 68 days
y-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.
4-91
-------
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6
PROPERTY/ENDPOINT
Air
Reactivity
Atmospheric Half-life
Photolysis
DATA
Aerobic sediment half-life: 1 1 days;
32 days
Anaerobic sediment half-life: 2 days
(y-HBCD) (Measured)
OECD Test Guideline 308
Degraded by abiotic and biotic processes
in soil and aquatic sediment with reported
half-lives of 2 days to 2 months
(Measured)
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)
1.7 days (Estimated)
Not a significant fate process (Estimated)
REFERENCE
ECHA, 2008; NICNAS, 2012
Davis et al., 2005, 2006; EPA,
2010
ECHA, 2008
EPI
Mill, 2000; Professional
judgment
DATA QUALITY
Value reported in a secondary source.
Guideline study. The test
concentration was too low to allow
for the quantification of a- and
(3-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
y-HBCD.
Provides supporting information
about HBCD degradation.
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.
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 a,
(3 and y HBCD diastereomers using time
dependent-density functional theory
(TD-DFT).
Zhao etal., 2010
Hydrolysis
No degradation after 39 days (Measured)
EINECS, 2008
Half-life at pH 8:
Half-life at pH 7:
(Estimated)
1.2xl0lu years
1.2x10" years
EPI
Professional judgment
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.
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.
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.
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
Fish BAF
BCF = 8,974 (Measured)
Oncorhynchus mykiss (whole fish) at a
nominal concentration of 3.4 (ig HBCD/L
for 70 days long (25-day uptake, 35-day
depuration); nominal concentrations
based on y-isomer
The three stereoisomers of HBCD were
present in O. mykiss in rough
approximation to that of the commercial
product used as test article
BCF= 18,100 (Measured)
(steady-state, log BCF 4.26) in
Pimephales promelas at a mean water
concentration of 6.2 ug HBCD/L for
32 days
4,100 (Estimated for 3194-55-6)
350,000 (Estimated for 25637-99-4)
Drottar and Kruger, 2000;
EINECS, 2008; EPA, 2005;
NICNAS, 2012
Guideline study performed according
to current EPA, OECD guidelines and
GLP.
EINECS, 2008; Veith et al., 1979
EPI
Non-guideline study that was
conducted before the implementation
of standardized test procedures for
BCF.
These estimated results are from the
BCFBAF vS.Ol Arnot-Gobas
method, reporting the upper trophic
value with an entered measured Log
QW value of 5.6.
4-94
-------
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Mammalian BAF
Earthworm BAF
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
a-HBCD: 9.2
(3-HBCD: 4.3
y-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.
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 a-HBCD: 99
Relative BAF (3-HBCD: 11
Relative BAF y-HBCD: 1
EINECS, 2008
Values were obtained from a
secondary source provide supporting
information concerning the isomer
profile of HBCD bioaccumulation.
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 a-HBCD: 0.3-0.8 dwt/wwt
BAF (3-HBCD: 0.01-0.04 dwt/wwt
BAF y-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.
4-95
-------
Hexabromocyclododecane (HBCD) CASRN 25637-99-4; 3194-55-6
PROPERTY/ENDPOINT
Metabolism in Fish
DATA
Metabolite formation was studied in
juvenile rainbow trout (O. mykiss) liver
and muscle
Bioisomerization:
Fish exposed to the (3-isomer resulted in
a-isomer and y-isomer
Fish exposed to the a-isomer resulted in
no (3-isomer and a small amount of
y-isomer
Fish exposed to the y-isomer resulted in a
linear increase in the a-isomer over the
first 14 days of depuration and this
isomer was still found after 112 days
depuration; no (3-isomer was found after
112 days depuration
REFERENCE
NICNAS, 2012
DATA QUALITY
Values were obtained from a
secondary source and provide
species-specific isomer profile
information.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
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, 201 Ib; NICNAS,
2012; La Guardia et al., 2012).
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).
Detected in breast milk, blood plasma and adipose tissue. This chemical was not included in the NHANES
biomonitoring report (CDC, 201 1; ECHA, 2008; HSDB, 201 Ib; Marvin et al., 201 1; 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
/7-valuea
Variance
/7-valueb
Means
chi-square
/7-valueb
Scaled
residuals of
interest0
AIC
BMDRDio-/.
(mg/kg-
day)
BMDLRDio-/.
(mg/kg-day)
All doses included
Constant variance
Exponential
Hill6
Lineard
Polynomial (2-degree)d
Polynomial (3-degree)d
Power6
NA
0.06
0.06
0.06
0.06
0.06
0.77
0.77
0.77
0.77
0.77
NA
0.02
0.02
0.02
0.02
0.000000188 /
-0.28
0.20 /HD
0.20 /HD
0.20 /HD
0.20 /HD
-178.58
-174.60
-174.60
-174.60
-174.60
18.67
2376.16
2376.16
2376.16
2376.16
7.11
1189.99
1189.99
1189.99
1189.99
Highest dose dropped
Constant variance
Exponential (model 2)
Exponential (model 3)
Exponential (model 4)
Hill"
Lineard
Polynomial (2-degree)d
Power6
0.05
0.05
0.05
0.57
0.57
0.57
0.38
0.38
NA
-0.65 / 0.07
-0.65/0.07
4.38E -08 /
2.22E-08
-134.64
-134.64
-133.42
119.68
119.68
39.57
73.53
73.53
9.73
NA
0.05
0.05
0.05
0.57
0.57
0.57
0.37
0.37
0.37
-0.66/0.07
-0.66/0.07
-0.66 / 0.07
-134.63
-134.63
-134.63
120.98
120.98
120.98
75.95
75.95
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
aValues >0.05 fail to meet conventional goodness-of-fit criteria.
Values <0.10 fail to meet conventional goodness-of-fit criteria.
°Scaled residuals at doses immediately below and immediately above the benchmark dose.
Coefficients restricted to be negative.
ePower 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.
4-97
-------
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
Exponential Model 2 with 0.96 Confidence Level
o
s
s.
§
0.98
0.96
0.94
0.92
0.9
0.88
0.86
0.84
Exponential
BMDL
BMD
20
40
60 80
dose
100
120
140
11:3808/232012
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
/7-valuea
Variance
/7-valueb
Means
chi-square
/7-valueb
Scaled
residuals of
interest0
AIC
EMBRYO"/.
(mg/kg-
day)
BMDLRDjoy.
(mg/kg-day)
Constant variance
Exponential (model 2)
Exponential (model 3)
Exponential (model 4)
Exponential (model 5)
Hille
Lineard
Polynomial (2-degree)d
Polynomial (3-degree)d
Power6
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.48
0.48
0.48
0.48
0.48
0.48
0.48
0.48
0.48
0.03
0.03
0.23
0.23
0.29
0.03
0.03
0.03
0.03
-0.12/HD
-0.12/HD
-0.00004 /
0.00014
-0.00004 /
0.00014
0. 16 / -0.80
-0.12/HD
-0.12/HD
-0.12/HD
-0.12/HD
32.47
32.47
28.89
28.89
28.57
32.42
32.42
32.42
32.42
1518.54
1518.54
14.01
14.01
15.85
1505.30
1505.30
1505.30
1505.30
960.56
960.56
0.03
0.04
0.00005
913.61
913.61
913.61
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
aValues >0.05 fail to meet conventional goodness-of-fit criteria.
bValues <0.10 fail to meet conventional goodness-of-fit criteria.
°Scaled residuals at doses immediately below and immediately above the benchmark dose.
dCoefficients restricted to be positive.
ePower 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
-------
I
o
s
s.
§
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
HB Model with 0.96 Confidence Level
6.5
5.5
4.5
B UDL
BMD
200 400 600 800 1000 1200 1400
dose
13:0208032012
4-100
-------
Barontini, F.; Cozzani, V.; Cussola, A.; Petarca, L. Investigation of hexabromocyclododecane
thermal degradation pathways by gas chromatography/mass spectrometry. Rapid Commun. Mass
Spectrom. 2001, 15 (9), 690-698.
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 December 19,
2011).
Chengelis, C. An oral (gavage) 90-day toxicity study of HBCD in rats. Study No. WIL-186012.
WIL Research Laboratories, Inc. Ashland, Ohio. 2001.
Chengelis, C.P. A 28-day repeated dose oral toxicity study of HBCD in rats. WIL Research
Laboratories Inc., Ashland, Ohio, p. 925. 1997.
Crump, D.; Chiu, S.; Egloff, C.; Kennedy, SW. Effects of hexabromocyclododecane and
polybrominated diphenyl ethers on mRNA expression in chicken (Gallus domesticus)
hepatocytes. ToxicolSci. 2008, 106 (2), 479-87.
Davis, J.W.; Gonsior, S.; Marty, G.; Ariano, J. The transformation of hexabromocyclododecane
in aerobic and anaerobic soils and aquatic sediments. Water Res. 2005, 39, 1075-1084.
Davis, J.W.; Gonsior, S.J.; Markham, D.A.; Friederich, U.R.S.; Hunziker, R.W.; Ariano, J.M.
Biodegradation and product identification of [14C]hexabromocyclododecane in wastewater
sludge and freshwater sediment. Environ. Sci. Technol. 2006, 40, 5395-5401.
Deng, J.; Yu, L.; Liu, C.; Yu, K.; Shi, X.; Yeung, L.W.Y.; Lam, P.K.S.; Wu, R.S.S.; Zhou, B.
Hexabromocyclododecane-Induced Developmental Toxicity and Apoptosis in Zebrafish
Embryos. Aquatic Toxicol. 2009, 93 (1), 29-36.
Desjardins, D.; MacGregor, J.; Krueger, H. Final report: hexabromocyclododecane (HBCD): a
72-hour toxicity test with the marine diatom (Skeletomema costatum). Wildlife International
Project Number: 439A-125. 2004.
Desjardins, D.; MacGregor, J.; Krueger, H. Final report. Chapter 2, Hexabromocyclododencane
(HBCD): A 72-hour toxicity test with the marine diatom (Skeletonema costatum) using a co-
solvent. 2005.
Drottar, K.R.; Krueger, H.O. Hexabromocyclododecane (HBCD): A flow-through life-cycle
toxicity test with the cladoceran (Daphnia magnd). Final report. 1998. 439A-108, pp 78 pp.
Wildlife International Ltd, Easton, Maryland, USA.
Drottar, K.R.; Krueger, H.O. Hexabromocyclododecane (HBCD): A flow-through
bioconcentration test with the rainbow trout (Oncorhynchus mykiss). Final report. 2000. 439A-
111, pp 1-137. Wildlife International Ltd, Easton, Maryland, USA.
4-101
-------
Drottar, K.R.; MacGregor, J.A.; Krueger, H.O. Hexabromocyclododecane (HBCD): An early
life-stage toxicity test with the rainbow trout (Onchorhynchus mykiss). Project No.: 439A-112.
Wildlife International, Ltd. Easton, MD. 2001.
ECHA (European Chemicals Agency). SVHC support document. Substance name:
Hexabromocyclododecane and all major diastereoisomers identified.
2008. http://echa.europa.eu/documents/10162/13638/svhc_supdoc_hbccd_publication_en.pdf
(accessed on June 1, 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/.
EINECS (European Inventory of Existing Commercial Chemical Substances).
Hexabromocyclododecane. Risk assessment report. 2008. Luxembourg: Office for Official
Publications of the European Communities.
Ema, M.; Fujii, S.; Hirata-Koizumi, M.; Matsumoto, M. Two-generation reproductive toxicity
study of the flame retardant hexabromocyclododecane in rats. Reprod Toxicol. 2008, 25, 335-
351.
Environment Canada. Screening assessment report on hexabromocyclododecane Chemical
Abstracts Service Registry Number 3194-55-6. Health Canada. 2011. http://www.ec.gc.ca/ese-
ees/7882C148-8AE4-4BA4-8555-668C49F91500/HBCD%20-%20FSAR%20-%20EN.pdf
(accessed on July 1, 2012)
EPA (U.S. Environmental Protection Agency). High Production Volume (HPV) data summary
and test plan for hexabromocyclododecane (HBCD) CAS No. 3194-55-6. 2005. Prepared by the
American Chemistry Council's Brominated Flame Retardant Industry Panel (BFRIP), Arlington,
VA. http://www.epa.gov/oppt/chemrtk/pubs/summaries/cvclodod/cl3459tc.htm (accessed on
August 13, 2012).
EPA (U.S. Environmental Protection Agency). Initial risk-based prioritization of high production
volume chemicals. Chemical/category: Hexabromocyclododecane (HBCD). U.S. Environmental
Protection Agency Risk-Based Prioritization Document.
2008. http://www.epa.gOv/hpvis/rbp/HBCD.3194556.Web.RBP.31308.pdf (accessed on August
13,2012).
EPA (U.S. Environmental Protection Agency). Hexabromocyclododecane (HBCD) action plan
summary. 2010. Office of Pollution Prevention and
Toxics. http://www.epa.gov/oppt/existingchemicals/pubs/actionplans/RIN2070-
AZ10 HBCD%20action%20plan Final 2010-08-09.pdf (accessed December, 20, 2011).
4-102
-------
EPA (U.S. Environmental Protection Agency). Sustainable futures. Usingnoncancer screening
within the SF Initiative. Environmental Protection Agency: Washington DC.
2011. http://www.epa.gov/opptintr/sf/pubs/noncan-screen.htmtfsystemic (accessed on December
14,2011).
EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.1. U.S.
Environmental Protection Agency: Washington D.C. http://www.epa.gov/opptintr/exposure/.
Eriksson, P.; Fischer, C.; Wallin, M.; Jakobsson, E.; Fredriksson, A. Impaired behaviour,
learning and memory, in adult mice neonatally exposed to hexabromocyclododecane (HBCDD).
Environ. Toxicol. Pharmacol. 2006, 21 (3), 317-322.
Fernie, K.J.; Shutt, J.L.; Letcher, R.J.; Ritchie, I.J.; Bird, D.M. Environmentally relevant
concentrations of DE-71 and HBCD alter eggshell thickness and reproductive success of
American kestrels. Environ. Sci. Technol. 2009, 43, 2124-30.
Fery, Y.; Buschauer, I; Salzig, C.; Lang, P.; Schrenk, D. Technical pentabromodiphenyl ether
and hexabromocyclododecane as activators of the pregnane-X-receptor (PXR). Toxicology.
2009.264,45-51.
Gentes, M.L; Letcher, R.J.; Caron-Beaudoin, E.; Verreault, J. Novel flame retardants in urban-
feeding ring-billed gulls from the St. Lawrence River, Canada. Environ. Sci. Technol. 2012, 46,
9735-9744.
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.
HSDB (Hazardous Substances Data Bank). 1,2,5,6,9,10-Hexabromocyclododecane. CAS No.
3194-55-6. 2011a. Database of the National Library of Medicine's TOXNET
system, http://toxnet.nlm.nih.gov/ (accessed on December 20, 2011).
HSDB (Hazardous Substances Data Bank). Hexabromocyclododecane. CAS No. 25637-99-4.
201 Ib. Database of the National Library of Medicine's TOXNET
system, http://toxnet.nlm.nih.gov/ (accessed on December 20, 2011).
IUCLID. Hexabromocyclododecane. Substance ID: 25637-99-4. European Commission.
2000. http://esis.irc.ec.europa.eu/doc/IUCLID/data sheets/25637994.pdf (accessed June 1, 2012)
Kuiper, R. V.; Canton, R. F.; Leonards, P. E.; Jenssen, B. M.; Dubbeldam, M.; Wester, P. W.;
van den Berg, M.; Vos, J. G.; Vethaak, A. D., Long-term exposure of European flounder
(Platichthys flesus) to the flame-retardants tetrabromobisphenol A (TBBPA) and
hexabromocyclododecane (HBCD). Ecotoxicol. Environ. Saf. 2007, 67 (3), 349-360.
Kuramochi, H.; Suzuki, H.; Kawamoto, K.; Osako, M.; Sakai, S. Measurements of water
solubility and 1-octanol/water partition coefficient of three hexabromocyclododecane
4-103
-------
diastereoisomers. Brominated Flame Retardants International Symposium Abstracts: Risk
Assessment, 2007.
Kuramochi, H.; Sakai, S. Measurement of vapor pressures of some PBDEs and HBCD
diastereoisomers. Brominated Flame Retardants International Symposium Abstracts: Risk
Assessment, 2010.
Kurokawa, Y.; Inoue, T.; Uchida, Y.; et al. Carcinogenesis test of flame retarder
hexabromocyclododecane in mice. Hardy, M.; Albemarle Corporation, personal communication,
Department of Toxicology, National Public Health Research Institute, Biological Safety Test
Research Center. 1984. Unpublished, translated from Japanese.
La Guardia, M.; Hale, R.; Harvey, E.; Mainor, T.; Ciparis, S. In situ accumulation of HBCD,
PBDEs, and several alternative flame-retardants in the bivalve (Corbiculafluminea) and
gastropod (Elimiaproximo). Environ. Sci. Technol. 2012, 46 (11), 5798-5805.
Law, K.; Palace, V.P.; Halldorson, T.; Danell, R.; Wautier, K.; Evans, B.; Alaee, M.; Marvin, C.;
Tomy, G.T. Dietary accumulation of hexabromocyclododecane diastereoisomers in juvenile
rainbow trout (Oncorhynchus mykiss) I: bioaccumulation parameters and evidence of
bioisomerization. Environ. Toxicol. Chem. 2006, 25 (7), 1757-1761.
Lilienthal, H.; Van der Ben, L.; Roth-Haerer A; Hack, A.; Piersma, A.; Vos, J. Neurobehavioral
toxicity of brominated flame retardants: Differential effects of PBDE-99, TBBPA and HBCD
and endocrine relation. Dioxin Conference 2006. Oslo. Organohalogen Compounds. 2006. 68,
128-130. (Abstract).
Lilienthal, H, van der Ven, L.T.; Piersma, A.H.; Vos, J.G. Effects of the brominated flame
retardant hexabromocyclododecane (HBCD) on dopamine-dependent behavior and brainstem
auditory evoked potentials in a one-generation reproduction study in Wistar rats. Toxicol. Lett.
2009, 185, 63-72.
Mariussen, E.; Fonnum, F. The effect of brominated flame retardants on neurotransmitter uptake
into rat brain synaptosomes and vesicles. Neurochem. Int. 2003, 43, 533-542.
Marvin, C.H.; Tommy, G.T.; Armitage, J.A., Arnot, J.A.; McCarthy, L.; Covaci, A.; Palace, V.
Hexabromocyclododecane: Current understanding of chemistry, environmental fate and
toxicology and implications for global management. Environ. Sci. Technol. 2011, 44, 8613-8623.
Mill, T. (2000) Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of
Property Estimation Methods for Chemicals, Environmental Health Sciences (355-382). Boca
Raton: Lewis Publishers.
Ministry of the Environment, Japan (MOEJ); 6-Week Administration Study of 1,2,5,6,9,10-
Hexabromocyclododecane for Avian Reproduction Toxicity under Long-day Conditions using
Japanese Quail. Report. Research Institute for Animal Science in Biochemistry & Toxicology,
2009
4-104
-------
Murai, T.; Kawasaki, H.; Kanoh, S. Studies on the toxicity of insecticides and food additives in
pregnant rats-fetal toxicity of hexabromocyclododecane. Pharmacometrics (Japan). 1985, 29
(6), 981-986.
NAS (National Academy of Sciences). Toxicological risks of selected flame-retardant chemicals.
2000. Subcommittee on Flame-Retardant Chemicals, National Research Council, Washington,
D.C. http://www.nap.edu/catalog.php?record_id=9841 (accessed December 19, 2011).
NICNAS (National Industrial Chemicals Notification and Assessment Scheme).
Hexabromocyclododecane. Priority Existing Chemical Assessment Report. 2012.
Commonwealth of Australia.
NOHSC (National Occupational Health and Safety Commission) Approved criteria for
classifying hazardous substances. 2004. NOHSC: 1008, 3rd ed. National Occupational Health and
Safety
Commission, http://www.safeworkaustralia.gov.au/sites/SWA/AboutSafeWorkAustralia/WhatW
eDo/Publications/Documents/258/ApprovedCriteria_Classifying_Hazardous_Substances_NOHS
C1008-2004 PDF.pdf (accessed on August 14, 2012).
Oetken, M.; Ludwichowski, K.-U.; Nagel, R. Validation of the preliminary EU-concept of
assessing the impact of chemicals to organisms in sediment by using selected substances. 2001.
UBA-FB 299 67 411, Institute of Hydrobiology, Dresden University of Technology, Dresden,
Germany.
OECD (Organization for Economic Co-Operation and Development).
Hexabromocyclododecane. Screening Information Dataset Initial Assessment Profile (SIAP).
2007. http://webnet.oecd.org/Hpv/UI/handler.axd?id=ea58acll-e090-4b24-b281-200ae351686c.
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-nonabrominated 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 rams) 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 = Moderate hazard = 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
|y
o
H
u
^
|y
o
g
a
C«
U
£.
'B
o
1
0)
s
1
sS
"a
S
0
0)
p
13
'Si
o
2
§
z
0)
0
p
•a
S
0)
1
0
-*^
sS
.a
%
=
c/^
a
•jj
C/5
c-1
o "5
"S
!• >rt
II
a
-*^
t,
HH
0)
0
"3
•H
hH
sS
S
0)
p
Aquatic
Toxicity
u
y
a
1
U
Environmental
Fate
0)
u
-*^
1
a
1
3
3
u
3
0
M
Butadiene styrene brominated copolymer | 1195978-93-8
4-107
-------
Butadiene styrene brominated copolymer
Representative structure
CASRN: 1195978-93-8
MW: 60,000-160,000;
<0.1%<1,000;
<0.1%<500
MF: (C8H9)x(C4H6Br2)y(C4H6Br2)2
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 Innovation™ 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)
Boiling Point (°C)
Vapor Pressure (mm Hg)
Water Solubility (mg/L)
>300 (Estimated)
<10'8 (Estimated)
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)
<10"3 (Estimated)
Professional judgment
Professional judgment; Boethling
andNabholz, 1997
Dow, 2005c
Professional judgment; Boethling
andNabholz, 1997
No data located.
Cutoff value used for large, high MW
solid.
Cutoff value for large, high MW
polymers according to polymer
assessment literature.
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.
Cutoff value for large, high MW non-
ionic polymers according to polymer
assessment literature.
4-110
-------
Butadiene styrene brominated copolymer CASRN 1195978-93-8
PROPERTY/ENDPOINT
Log Kow
Flammability (Flash Point)
Explosivity
Pyrolysis
DATA
Approximately 2 (Measured)
According to Guideline OECD 117;
calculated for residual solvent from an
acute invertebrate toxicity study water
accommodated fraction (WAF) sample.
Nonflammable (Estimated)
Not expected to form explosive mixtures
with air (Estimated)
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)
REFERENCE
Dow, 2007a; Dow, 2012
Professional judgment
Professional judgment
Professional judgment
DATA QUALITY
No data located; polymers with a
MW > 1,000 are outside the domain
of the available estimation methods.
Inadequate, the log K0w 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 1 17
"Partition Coefficient (N-
octanol/water), High Performance
Liquid Chromatography (FIPLC)
Method".
Separate analysis of WAF identified
the impurities to be solvent present in
the sample (i.e. 1,2-dichloroethane).
No experimental data located; based
on its use as a flame retardant.
No experimental data located; based
on its use as a flame retardant.
Based on analysis of the chemical
structure.
4-111
-------
Butadiene styrene brominated copolymer CASRN 1195978-93-8
PROPERTY/ENDPOINT
pH
pKa
DATA
Not applicable
Not applicable
REFERENCE
Professional judgment
Professional judgment
DATA QUALITY
Does not contain functional groups
that are expected to ionize under
environmental conditions.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
HUMAN HEALTH EFFECTS
Toxicokinetics
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or
Inhaled
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
Carcinogenicity
OncoLogic Results
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.
No absorption expected for any route of
exposure (Estimated)
Professional judgment
No data located.
Estimated based on professional
judgment.
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.
Oral, rat LD50 >2,000 mg/kg in Up and
Down Procedure.
Oral, mouse LD50 >5,000 mg/kg
Oral, rat LD50 >2,000 mg/kg in Up and
Down Procedure.
Limited bioavailability expected
(Estimated)
Dow, 2007e
Dow, 2005a
Dow, 2007e
Professional judgment; Boethling
andNabholz, 1997
Sufficient study details provided.
Sufficient study details provided.
Sufficient study details provided.
Based on polymer assessment
literature.
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.
No data located.
4-112
-------
Butadiene styrene brominated copolymer CASRN 1195978-93-8
PROPERTY/ENDPOINT
Carcinogenicity (Rat
and Mouse)
Combined Chronic
Toxicity/Carcinogenici
ty
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal
Aberrations in vitro
Chromosomal
Aberrations in vivo
DNA Damage and
Repair
Other
Reproductive Effects
DATA
Limited bioavailability expected
(Estimated)
REFERENCE
Professional judgment; Boethling
andNabholz, 1997
DATA QUALITY
Based on polymer assessment
literature.
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.
Negative in Ames assay in S. typhimurium
TA98, TA100, TA1535, TA1537, and in
E. coll WP2uvrA in the presence of
metabolic activation
Limited bioavailability expected
(Estimated)
Negative in rat lymphocyte chromosomal
aberration test (RLCAT)
Limited bioavailability expected
(Estimated)
Dow, 2005b
Professional judgment; Boethling
andNabholz, 1997
Dow, 2006
Professional judgment; Boethling
andNabholz, 1997
Sufficient study details and
supporting data provided.
Based on polymer assessment
literature.
Sufficient study details and
supporting data provided.
Based on polymer assessment
literature.
No data located.
No data located.
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.
4-113
-------
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
Reproduction and
Fertility Effects
Limited bioavailability expected
(Estimated)
Professional judgment; Boethling
andNabholz, 1997
Based on polymer assessment
literature.
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/kg-
day (highest dose tested)
Combined Repeated
Dose with
Reproduction/
Developmental
Toxicity Screen
Limited bioavailability expected
(Estimated)
Prenatal Development
Postnatal Development
Dow, 2007f
Professional judgment; Boethling
andNabholz, 1997
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.
Based on polymer assessment
literature.
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)
There were no neurological effects
observed in a combined repeated dose
toxicity study (2 8-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)
Professional judgment; Boethling
andNabholz, 1997
Dow, 2007f
Based on polymer assessment
literature.
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)
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)
Professional judgment; Boethling
andNabholz, 1997
Dow, 2007f
Based on polymer assessment
literature.
Sufficient study details and
supporting data provided; conducted
according to OECD guidelines.
4-116
-------
Butadiene styrene brominated copolymer CASRN 1195978-93-8
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
Respiratory
Sensitization
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
Endocrine Activity
Immunotoxicity
DATA
REFERENCE
DATA QUALITY
LOW: This polymer did not cause skin Sensitization in a guideline study.
Does not cause skin Sensitization in guinea
pig by Buehlertest
Dow, 2007b
Sufficient study details and
supporting data provided. Conducted
according to OECD Test Guideline
406
No data located.
No data located.
MODERATE: This polymer is mildly irritating to rabbit eyes, with effects clearing within 72 hours post
instillation.
Non-irritating (species not specified)
Mildly irritating, rabbits
Single instillation of 20 mg of the test
substance caused iritis and conjunctivitis,
clearing within 72 hours.
Dow, 2011
Dow, 2007c
Limited study details and no
supporting data provided.
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.
LOW: This polymer is slightly irritating to the skin of rabbits.
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.
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
andNabholz, 1997
Based on polymer assessment
literature.
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
Immune System
Effects
DATA
Limited bioavailability expected
(Estimated)
REFERENCE
Professional judgment; Boethling
andNabholz, 1997
DATA QUALITY
Based on polymer assessment
literature.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
Not applicable
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.
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
NES
Professional judgment
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
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
Fish ChV
Daphnid ChV
Green Algae ChV
DATA
NES
NES
NES
REFERENCE
Professional judgment
Professional judgment
Professional judgment
DATA QUALITY
The large MW, limited
bioavailability and low water
solubility suggest that there will be
NES.
The large MW, limited
bioavailability and low water
solubility suggest that there will be
NES.
The large MW, limited
bioavailability and low water
solubility suggest that there will be
NES.
ENVIRONMENTAL FATE
Transport
Henry's Law Constant
(atm-m3/mole)
Sediment/Soil
Adsorption/Desorption
Coefficient - Koc
Level III Fugacity
Model
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.
<10"8 (Estimated)
>30,000 (Estimated)
Professional judgment; Boethling
andNabholz, 1997
Professional judgment; Boethling
andNabholz, 1997
High MW polymers are expected to
have low vapor pressure and are not
expected to undergo volatilization
according to polymer assessment
literature.
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.
No data located.
4-120
-------
Butadiene styrene brominated copolymer CASRN 1195978-93-8
PROPERTY/ENDPOINT
Persistence
Water
Soil
Air
Aerobic
Biodegradation
Volatilization Half-life
for Model River
Volatilization Half-life
for Model Lake
Aerobic
Biodegradation
Anaerobic
Biodegradation
Soil Biodegradation
with Product
Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
DATA
REFERENCE
DATA QUALITY
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.
Recalcitrant (Estimated)
>1 year (Estimated)
>1 year (Estimated)
Anaerobic Biodegradation OECD 311
study exhibited no biodegradation after 62
days (Measured)
Professional judgment; Boethling
andNabholz, 1997
Professional judgment
Professional judgment
Dow, 2009a
High MW synthetic polymers are
expected to be non-biodegradable
according to polymer assessment
literature.
Based on the magnitude of the
estimated Henry's Law constant.
Based on the magnitude of the
estimated Henry's Law constant.
No data located.
Guideline study.
No data located.
No data located.
No data located.
4-121
-------
Butadiene styrene brominated copolymer CASRN 1195978-93-8
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Reactivity
Photolysis
Hydrolysis
Other
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
Not susceptible to hydrolysis according to
OECD 111 based on average DOC values
of:
1.76±0.51mg/LatpH1.2;
0.81±0.30mg/LatpH4;
1.25±0.35mg/LatpH7;
1.33±0.40mg/LatpH9
obtained from 914 ± 112 mg/L of sample
at 49.9 °C for 5 days (Measured)
Dow, 2007g
This polymer is stable in PEG400 for 21
days; 2.5-250 mg/mL samples analyzed by
HPLC/RI (Measured)
Dow, 2007i
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.
Guideline study.
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.
4-122
-------
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)
BAF
Metabolism in Fish
Professional judgment; Boethling
andNabholz, 1997
Cutoff value for large, high MW,
insoluble polymers according to
polymer assessment literature.
No data located.
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 PI0-0476. 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 PI0-0476. 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 PI0-0476. 2006.
Dow. The Dow Chemical Company. Marino, T; Hales, C; Najar J. An acute toxicity study with the daphnid, Daphnia magna. PMN
number PI0-0476. 2007a.
Dow. The Dow Chemical Company. Dermal sensitization study in guinea pigs (Buehler method). PMN number PI0-0476. 2007b.
Dow. The Dow Chemical Company. Primary eye irritation study in rabbits. PMN number PI0-0476. 2007c.
Dow. The Dow Chemical Company. Primary skin irritation study in rabbits. PMN number PI0-0476. 2007d.
Dow. The Dow Chemical Company. Acute oral toxicity up and down procedure in rats. PMN number PI0-0476. 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 PI0-0476. 2007f.
Dow. The Dow Chemical Company. Determination of Hydrolysis Rate Following OECD 111 Guidelines. PMN number PI 0-0476.
2007g.
Dow. The Dow Chemical Company. Evaluation of biodegradability in Anaerobic Digester Sludge According to OECD Guideline 311.
PMN number PI0-0476. 2009a.
Dow. The Dow Chemical Company. Evaluation of biodegradability in Anaerobic Digester Sludge According to OECD Guideline 311.
PMN number PI0-0476. 2009b.
Dow. The Dow Chemical Company. Exposure of Polymer Samples to Artificial Sunlight Irradiation. PMN number PI0-0476. 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 PI0-0476. 2009c.
Dow. The Dow Chemical Company. Solution/Extraction behavior in Water following the OECD 120 Guideline. PMN number PI0-
0476. 2005c.
Dow. The Dow Chemical Company. Stability study. PMN number PI0-0476. 20071.
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/fdsvs/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 VI = Moderate hazard = 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
JO
H
"3
3
^
'0
'3
M
O
8
sS
U
&
.y
o
o
OJ
o
0)
o
•a
o
8.
0)
B
0
3
0)
a
13
u
S~~
3
0)
o
a
•a
0)
"S3
0)
8.
0
1
0)
C/5
a
C/5
r*> S
o -g
2 -S
ft'g
(2 c^
a
sS
0)
*%
0
*C
HH
13
§
0)
Q
Aquatic
Toxicity
"3
3
u
'3
S
u
Environmental
Fate
Oj
o
a
S
'S
0)
0.
a
o
"3
3
sS
M
TBBPA-bis brominated ether
derivative*
97416-84-7
z.§
tf
tf
tf
tf
L
tf
L*
Z,
L
Z,
L
H
H
4-126
-------
TBBPA-bis brominated ether derivative
Br^f
°wBr <
B^} J
Vx^;
3r Br — v
k/O<^
JC
/^Sr
CASRN: 97416-84-7
MW: 971.68
MF: C23H24Br8O2
Physical Forms:
Neat: Solid
Use: Flame retardant
SMILES : BrCC(Br)(C)COc 1 c(Br)cc(C(C)(C)c2cc(Br)c(OCC(Br)(C)CBr)c(Br)c2)cc 1 Br
Synonyms: Benzene, l,l'-(l-rnethylethylidene)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); l,l'-Propane-2,2-diylbis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene]; 1
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
dibromophenyl] propane.
Trade Names: PYROGUARD SR-130; SR-130
3-
,5-
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.
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:
,Br
Br Br Br [
jAxQyk rAv/°\^\Br
Br BAAXABr
Tetrabromobisphenol A bis(2,3-dibromopropyl) ether (CASRN 21850-44-2)
Structural Alerts: Polyhalogenated aromatic hydrocarbons, Immunotoxicity (EPA, 201 la)
Risk Phrases: Not classified by Annex VI Regulation (EC) No. 1272/2008 (ESIS, 201 1)
Hazard and Risk Assessments: None identified
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)
Approximately 110 (Measured)
Eurosarm MSDS, 2010
DKS, 2012
Reported for PYROGUARD SR-130,
containing approximately 100%
CASRN 97416-84-7.
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
260 decomposes (Measured)
DKS, 2012
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.
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)
<3.3xlO-° 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)
<4.2xlO"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
Log Kow
Flamm ability (Flash Point)
Explosivity
Pyrolysis
pH
pKa
DATA
90.4%
purity of TBBPA-bis brominated
ether derivative CASRN 97416-84-
7); no study details provided.
Estimated value is greater than the
cutoff value, >10, according to
methodology based on HPV
assessment guidance.
No experimental data located; based
on its use as a flame retardant.
No experimental data located; based
on its use as a flame retardant.
Based on analysis of the chemical
structure.
Does not contain functional groups
that are expected to ionize under
environmental conditions.
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
Dermal Absorption in vitro
Absorption,
Distribution,
Metabolism &
Excretion
Oral, Dermal or
Inhaled
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.
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
No data located.
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
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
DATA
Following single or repeated (5 or
10 days) oral administration of 20 mg/kg
[14C]-TBBPAbis(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 (ig/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)
REFERENCE
Knudsen et al., 2007; Professional
judgment
DATA QUALITY
Estimated based on data for the
analog TBBPA
bis(2,3-dibromopropyl) ether; study
details reported in primary source.
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.
Mouse LD50 >20,000 mg/kg
(Estimated by analogy)
Mouse LD50 >20,000 mg/kg
(Estimated by analogy)
IPCS, 1995; Professional
judgment
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.
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
Inhalation
Carcinogenicity
OncoLogic Results
Carcinogenicity (Rat
and Mouse)
Combined Chronic
Toxicity/
Carcinogenicity
DATA
Mouse LC50 >87,000 mg/m3 (87 mg/L)
(Estimated by analogy)
REFERENCE
Great Lakes Chemical
Corporation, 1982b; Professional
judgment
DATA QUALITY
Estimated based on data for the
analog TBBPA
bis(2,3-dibromopropyl) ether; limited
study details reported in a secondary
source.
MODERATE: No data located. Estimated to have potential for Carcinogenicity based on the potential for
alkylation and professional judgment.
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
No data located.
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.
No data located.
4-133
-------
TBBPA-bis brominated ether derivative CASRN 97416-84-7
PROPERTY/ENDPOINT
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
Chromosomal
Aberrations in vitro
Chromosomal
Aberrations in vivo
DNA Damage and
Repair
Other (Mitotic Gene
Conversion)
DATA
REFERENCE
DATA QUALITY
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.
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)
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)
Negative for micronucleated
polychromatic erythrocytes in B6C3F1
mice
(Estimated by analogy)
Negative for unscheduled DNA synthesis
assay in Sprague-Dawley rats at 10, 50,
100, 500 and 1,000 (ig/mL
(Estimated by analogy)
Great Lakes Chemical
Corporation, 1982a; Professional
judgment
IPCS, 1995; Professional
judgment
NTP, 2011; Professional
judgment
IPCS, 1995; Professional
judgment
Estimated based on data for the
analog TBBPA
bis(2,3-dibromopropyl) ether.
No data located.
Estimated based on data for the
analog TBBPA
bis(2,3-dibromopropyl) ether.
Estimated based on data for the
analog TBBPA
bis(2,3-dibromopropyl) ether.
Estimated based on data for the
analog TBBPA
bis(2,3-dibromopropyl) ether.
No data located.
4-134
-------
TBBPA-bis brominated ether derivative CASRN 97416-84-7
PROPERTY/ENDPOINT
Reproductive Effects
Reproduction/
Developmental
Toxicity Screen
Combined Repeated
Dose with
Reproduction/
Developmental
Toxicity Screen
Reproduction and
Fertility Effects
Developmental Effects
Reproduction/
Developmental
Toxicity Screen
Combined Repeated
Dose with
Reproduction/
Developmental
Toxicity Screen
Prenatal Development
Postnatal Development
DATA
REFERENCE
DATA QUALITY
MODERATE: Estimated based on a mechanistic consideration of its potential to act as an alkylating agent
using professional judgment.
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.
No data located.
No data located.
MODERATE: Estimated based on a mechanistic consideration of its potential to act as an alkylating agent
using professional judgment.
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.
No data located.
No data located.
No data located.
4-135
-------
TBBPA-bis brominated ether derivative CASRN 97416-84-7
PROPERTY/ENDPOINT
Neurotoxicity
Neurotoxicity
Screening Battery
(Adult)
Repeated Dose Effects
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
Respiratory
Sensitization
Eye Irritation
DATA
REFERENCE
DATA QUALITY
LOW: Low potential for neurotoxicity estimated based on expert judgment. No data located.
Low potential for neurotoxicity
(Estimated)
Expert judgment
Estimated based on expert judgment.
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)
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)
Professional judgment
IPCS, 1995; Professional
judgment
Based on a closely related
confidential analog with similar
structure and functional groups.
Based on the analog TBBPA
bis(2,3-dibromopropyl) ether; limited
study details reported in a secondary
source.
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.
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)
Not sensitizing, guinea pigs
(Estimated by analogy)
Professional judgment
Submitted Confidential Study
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.
Estimated by analogy to a closely
related confidential analog. Reported
in a submitted confidential study;
Study conducted according to GLP.
No data located.
No data located.
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
Eye Irritation
Dermal Irritation
Dermal Irritation
Endocrine Activity
DATA
Low potential for eye irritation
(Estimated)
REFERENCE
Expert j udgment
DATA QUALITY
Estimated based on expert judgment.
LOW: Estimated not to cause dermal irritation based on expert judgment. No experimental located.
Low potential for dermal irritation
(Estimated)
Expert j udgment
Estimated based on expert judgment.
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)
Positive for estradiol sulfotransferase
(E2SULT)-enzyme inhibition in E2SULT
assay
(Estimated by analogy)
Negative for agonistic and antagonistic
interactions with AhR, androgen,
progesterone and estrogen receptors in
series of CALUX assays
(Estimated by analogy)
Positive for displacement of thyroid
hormone precursor T4 from plasma
transport protein in TTR binding assay
(Estimated by analogy)
Negative for potentiating and antagonistic
activity with T3 -mediated cell
proliferation in T-screen
(Estimated by analogy)
Canton et al., 2006; Professional
judgment
Hamers et al., 2006; Professional
judgment
Hamers et al., 2006; Professional
judgment
Hamers et al., 2006; Professional
judgment
Hamers et al., 2006; Professional
judgment
Based on the analog TBBPA
bis(2,3-dibromopropyl) ether; data
taken from primary study.
Based on the analog TBBPA
bis(2,3-dibromopropyl) ether; data
taken from primary study.
Based on the analog TBBPA
bis(2,3-dibromopropyl) ether; data
taken from primary study.
Based on the analog TBBPA
bis(2,3-dibromopropyl) ether; data
taken from primary study.
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
Immunotoxicity
Immune System
Effects
DATA
REFERENCE
DATA QUALITY
Potential for immunotoxicity based on the presence of the polyhalogenated aromatic hydrocarbons
structural alert and professional judgment.
Potential for immunotoxicity based on the
presence of the polyhalogenated aromatic
hydrocarbons structural alert
EPA, 201 la; Professional
judgment
Estimated based on the presence of a
structural alert.
ECOTOXICITY
ECOSAR Class
Acute Aquatic Toxicity
Fish LC50
Halo Ethers
LOW: Based on estimated acute toxicity values for fish, Daphnid, and green algae that suggest no effects at
saturation (NES).
Fish 96-hour LC50 = S.OlxlO'6 mg/L
ECOSAR class: Halo ethers
Fish 96-hour LC50 = 3.47xlO'7 mg/L
ECOSAR class: Neutral organics
ECOSAR v. 1.10
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.
NES: The log Kow of 12.4 for this
chemical exceeds the SAR limitation
for the log Kow of 8.O.; NES are
)redicted 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
Daphnid LC50
Green Algae EC50
Chronic Aquatic Toxicity
Fish ChV
DATA
Daphnid 48-hour LC50 = 1.33xlO"6 mg/L
ECOSAR class: Neutral organics
Green Algae 96-hour = l.SlxlO"6 mg/L
ECOSAR class: Neutral organics
REFERENCE
ECOSAR v. 1.10
ECOSAR v. 1.10
DATA QUALITY
NES: The log Kow of 12.4 for this
chemical exceeds the SAR limitation
for the log Kow of 8.0; NES are
)redicted for these endpoints.
Narcosis classes (neutral organics) are
)rovided for comparative purposes;
3fE assessment methodology will use
the lowest estimated toxicity value
)rovided by ECOSAR classes that
lave a more specific mode of action
relative to narcosis.
NES: The log Kow of 12.4 for this
chemical exceeds the SAR limitation
for the log Kow of 8.0; NES are
)redicted for these endpoints.
Narcosis classes (neutral organics) are
provided for comparative purposes;
3fE assessment methodology will use
the lowest estimated toxicity value
)rovided by ECOSAR classes that
lave a more specific mode of action
relative to narcosis.
LOW: Based on estimated chronic toxicity values for fish, Daphnid, and green algae that suggest NES.
Fish ChV =1.68xlQ-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
FishChV=1.06xlO-7mg/L
ECOSAR class: Neutral organics
ECOSARv. 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
he lowest estimated toxicity value
provided by ECOSAR classes that
have a more specific mode of action
•elative to narcosis.
Daphnid ChV
Daphnid ChV = 7.33xlO'7 mg/L
ECOSAR class: Neutral organics
ECOSARv. 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
he lowest estimated toxicity value
provided by ECOSAR classes that
have a more specific mode of action
•elative to narcosis.
Green Algae ChV
Green Algae ChV = 4.59x10"' mg/L
ECOSAR class: Neutral organics
ECOSARv. 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
he lowest estimated toxicity value
provided by ECOSAR classes that
have a more specific mode of action
•elative to narcosis.
ENVIRONMENTAL FATE
4-140
-------
TBBPA-bis brominated ether derivative CASRN 97416-84-7
PROPERTY/ENDPOINT
Transport
Henry's Law Constant
(atm-m3/mole)
Sediment/Soil
Adsorption/Desorption
Coefficient - Koc
Level III Fugacity
Model
Persistence
Water
Soil
Aerobic
Biodegradation
Volatilization Half-life
for Model River
Volatilization Half-life
for Model Lake
Aerobic
Biodegradation
DATA
REFERENCE
DATA QUALITY
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.
<10"8 (Estimated)
>3 0,000 (Estimated)
Air = <1% (Estimated)
Water = 5%
Soil = 95%
Sediment = 1 year (Estimated)
>1 year (Estimated)
EPI
EPI
EPI
Not expected to be an important fate
process.
Based on the magnitude of the
estimated Henry's Law constant.
Based on the magnitude of the
estimated Henry's Law constant.
No data located.
4-141
-------
TBBPA-bis brominated ether derivative CASRN 97416-84-7
PROPERTY/ENDPOINT
Air
Reactivity
Anaerobic
Biodegradation
Soil Biodegradation w/
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
Environmental Half-life
DATA
Probable (Anaerobic-methanogenic
biodegradation probability model)
8.3 hours (Estimated)
Not a significant fate process (Estimated)
> 180 days (Estimated)
REFERENCE
EPI
EPI
Mill, 2000; Professional judgment
PBT Profiler; EPI
DATA QUALITY
Not expected to be an important fate
process.
No data located.
No data located.
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.
No data located.
The substance does not contain
functional groups that would be
expected to hydrolyze readily under
environmental conditions.
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
Bioaccumulation
Fish BCF
BAF
Metabolism in Fish
DATA
REFERENCE
DATA QUALITY
HIGH: High potential for bioaccumulation based on an estimated BAF of 1,600.
<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)
1,600 (Estimated)
DKS, 2012
EPI
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).
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
No data located.
No data located.
This chemical was not included in the NHANES biomonitoring report (CDC, 201 1).
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).
Canon, 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/datadfm.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.htmtfsystemic (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.irc.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/ehc 172.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 VI = Moderate hazard = 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
JO
"5
3
^
'0
'3
O
'8
sS
U
&
o
"o
OJ
o
0)
u
s
1
(2
0)
8.
_0
"3
0)
Q
13
u
o
B
s
0)
o
Q
•a
-------
TBBPA bis(2,3-dibromopropyl) ether
,Br
Br Br Br [
1 1
^^°^^ ^Y°^^Br
^ Br^^J^XBr
CASRN: 21850-44-2
MW: 943.62
MF: C21H20Br8O2
Physical Forms:
Neat: Solid
Use: Flame retardant
SMILES: O(clc(cc(cclBr)C(clcc(c(OCC(Br)CBr)c(cl)Br)Br)(C)C)Br)CC(Br)CBr
Synonyms: Benzene, !,!'-(l-methylethylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)-; l,l'-(l-Methylethylidene)bis(3,5-dibromo-4-(2,3-
dibromopropoxy))benzene; !,!'-(l-Methylethylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)]benzene; l,l'-(Isopropylidene)bis(3,5-dibromo-4-(2,3-
dibromopropoxy)benzene); l,l'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)benzene]; l,l'-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-l-(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).
4-147
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
PHYSICAL/CHEMICAL PROPERTIES
Melting Point (°C)
Boiling Point (°C)
Vapor Pressure (mm Hg)
117 (Measured)
114 (Measured)
90-100 (Measured)
95 (Measured)
107.3 (Measured)
Reported as a range 104. 3-1 16. 6 using
Optical melting determination
113.39 (Measured)
Differential scanning calorimeter
Decomposition at >270 (Measured)
2.2 ±0.15 x 1Q-4 at20°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)
<10'8 (Estimated)
Tokyo Chemical Industry Co.,
2010; ChemSpider, 2011
NICNAS, 2001
IPCS, 1995; Great Lakes
Chemical Corporation, 1982a
Mack, 2004
ECHA, 2013
ECHA, 2013
IPCS, 1995
ECHA, 2013
EPI; EPA, 1999
Selected value for assessment.
Sufficient details were not available
to assess the quality of this study;
value reported in a secondary source.
These reported values may be for a
commercial mixture.
Nonguideline, non-good laboratory
practice (GLP) study reported in a
secondary source.
Nonguideline, non-GLP study
reported in a secondary source.
Decomposition is expected before the
boiling point is reached.
Guideline study reported for FR-720
in a secondary source.
Cutoff value for nonvolatile
compounds according to HPV
assessment guidance.
4-148
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Water Solubility (mg/L)
Log Kow
Flammability (Flash Point)
Explosivity
Pyrolysis
pH
DATA
<10"3 (Estimated)
IxlO3 (Measured)
99%.
12 (Estimated)
Autoignition: 740°C (Measured)
Ignition produced orange flame; according
to IEC 61241-2-1 Method B Minimum
ignition; GLP study
Autoignition: >500 mJ (Measured)
No ignition was observed; according to
IEC 61241-2-3 Minimum ignition energy;
GLP study
Not expected to form explosive mixtures
with air (Estimated)
Not applicable
REFERENCE
EPI; EPA, 1999
IPCS, 1995
NICNAS, 2001
ECHA, 2013
EPI; EPA, 1999
ECHA, 2013
ECHA, 2013
Professional judgment
Professional judgment
DATA QUALITY
Cutoff value for non-soluble
compounds according to HPV
assessment guidance.
Inadequate; these values are not
consistent with a nonpolar, highly
brominated material with a MW near
1,000.
Cutoff value from a guideline study
reported in a secondary source.
Estimated value is greater than the
cutoff value, >10, according to
methodology based on HPV
assessment guidance.
Nonguideline study; purity of test
substance TDBPE 720 not stated.
Reported in a secondary source.
Nonguideline; purity of test substance
TDBPE 720 not stated. Reported in a
secondary source.
No experimental data located; based
on its use as a flame retardant.
No data located.
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]-TBBPAbis(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 (ig/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.
4-150
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Other
Acute Mammalian Toxicity
Acute Lethality
Oral
Dermal
Inhalation
Carcinogenicity
OncoLogic Results
DATA
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: tmb'- 24. 8h; CLb: O.lmL/min.
Systemic bioavailability was 2.2%. Liver
was the major site of disposition.
REFERENCE
ECHA, 2013
DATA QUALITY
Well conducted study. Not
performed according to GLP and
standard testing guidelines.
LOW: Based on oral and dermal LD50 values >2, 000 mg/kg and an inhalation LC50 value >20 mg/L.
Mouse LD50 >20,000 mg/kg
Rat oral LD50 > 2,000 mg/kg
Mouse LD50 >20,000 mg/kg
Rat dermal LD50 > 2,000 mg/kg
Mouse LC50 >87,000 mg/m3 (87 mg/L)
Rat 1 hr-inhalation LC50 >24.4 mg/L;
Whole-body exposure to dust.
IPCS, 1995
ECHA, 2013
IPCS, 1995
ECHA, 2013
Great Lakes Chemical
Corporation, 1982b
ECHA, 2013
Limited study details reported in a
secondary source.
Sufficient study details reported in a
secondary source. GLP study
conducted using OECD guidelines.
Limited study details reported in a
secondary source.
Sufficient study details reported in a
secondary source. GLP study
conducted using OECD guidelines.
Limited study details reported in a
secondary source.
Sufficient study details reported in a
secondary source.
MODERATE: No data located. Estimated to have potential for carcinogenicity based on the potential for
alkylation and professional judgment.
No data located.
4-151
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Carcinogenicity (Rat
and Mouse)
Combined Chronic
Toxicity/
Carcinogenicity
Genotoxicity
Gene Mutation in vitro
Gene Mutation in vivo
DATA
There is potential for Carcinogenicity
effects based on a mechanistic
consideration of the potential for
alkylation (Estimated)
REFERENCE
Professional judgment
DATA QUALITY
Based on mechanistic
considerations.
No data located.
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.
There is potential for mutagenicity based
on a mechanistic consideration of the
potential for alkylation. (Estimated)
Positive, Ames assay (standard plate) in
Salmonella typhimurium strains TA1535
and TA100 with and without metabolic
activation and TA98 without metabolic
activation.
Negative, Salmonella typhimurium
strains TA1535, TA1537, TA100 and
TA98 and Escherichia coli Wp2uvrA
with and without metabolic activation.
Negative, mouse lymphoma L5 178Y
cells with and without metabolic
activation.
Professional judgment
Great Lakes Chemical
Corporation, 1982a; ECHA,
2013
Submitted confidential study;
ECHA, 2013
Submitted confidential study;
ECHA, 2013
Based on closely related
confidential analogs with similar
structures and functional groups.
Sufficient study details reported.
Reported in a submitted confidential
study; Study conducted according to
GLP
Reported in a submitted confidential
study; Study conducted according to
GLP
No data located.
4-152
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Chromosomal
Aberrations in vitro
Chromosomal
Aberrations in vivo
DNA Damage and
Repair
Other (Mitotic Gene
Conversion)
Reproductive Effects
Reproduction/
Developmental Toxicity
Screen
Combined Repeated
Dose with
Reproduction/
Developmental Toxicity
Screen
Reproduction and
Fertility Effects
DATA
Negative chromosomal aberrations in
Chinese hamster ovary (CHO)
cytogenetic assay with and without
metabolic activation (precipitation was
observed at the highest concentration).
Negative, sister chromatid exchanges in
Chinese hamster ovary (CHO) cells with
and without metabolic activation.
Negative for micronucleated
polychromatic erythrocytes in B6C3F1
mice.
Negative for unscheduled DNA synthesis
assay in Sprague Dawley rats at 10, 50,
100, 500 or 1,000 ng/mL.
Negative, unscheduled DNA synthesis,
rathepatocytes.
REFERENCE
IPCS, 1995
Submitted confidential study
NTP, 2011; ECHA, 2013
IPCS, 1995
Submitted confidential study
DATA QUALITY
Reported in a secondary source.
Reported in a submitted confidential
study; Study conducted according to
GLP
Reported in a secondary source.
Reported in a secondary source.
Reported in a submitted confidential
study; Study conducted according to
GLP
MODERATE: Estimated to have potential for reproductive effects based on the potential for alkylation and
professional judgment.
There is potential for reproductive
effects based on a mechanistic
consideration of the potential for
alkylation (Estimated)
Professional judgment
Based on mechanistic
considerations.
No data located.
No data located.
4-153
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Developmental Effects
Reproduction/
Developmental Toxicity
Screen
Combined Repeated
Dose with
Reproduction/
Developmental Toxicity
Screen
Prenatal Development
Postnatal Development
Neurotoxicity
Neurotoxicity Screening
Battery (Adult)
Repeated Dose Effects
DATA
REFERENCE
DATA QUALITY
MODERATE: Estimated to have potential for developmental effects based on the potential for alkylation
and professional judgment.
There is potential for developmental
effects based on a mechanistic
consideration of the potential for
alkylation (Estimated)
Professional judgment
Based on mechanistic
considerations.
No data located.
No data located.
No data located.
LOW: Estimated not to have potential for neurotoxicity based on expert judgment; no data located.
Low potential for neurotoxicity.
(Estimated)
Expert j udgment
Estimated based on expert
judgment.
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)
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)
Potential for immunotoxicity based on
polyhalogenated aromatic hydrocarbons
structure.
Professional judgment
IPCS, 1 995 ;ECHA, 2013
EPA, 2011; Professional
judgment
Based on closely related
confidential analogs with similar
structures and functional groups.
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.
Estimated based on the presence of
a structural alert.
4-154
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Skin Sensitization
Skin Sensitization
Respiratory Sensitization
Respiratory
Sensitization
Eye Irritation
Eye Irritation
Dermal Irritation
Dermal Irritation
DATA
REFERENCE
DATA QUALITY
LOW: Not a skin sensitizer in guinea pigs. There is potential for skin Sensitization based on the potential for
alkylation.
There is potential for skin Sensitization
based on a mechanistic consideration of
the potential for alkylation.
Not sensitizing, guinea pigs
Professional judgment
Submitted confidential study;
ECHA, 2013
Based on mechanistic
considerations.
Reported in a submitted confidential
study; Study conducted according to
GLP
No data located.
No data located.
LOW: Minimal eye irritation in rabbits clearing within 48 hours.
Low potential for eye irritation.
(Estimated)
Workers report development of eye
irritation following exposure to a
complex mixture of airborne
contaminants that included TBBPA
bis(2,3-dibromopropyl) ether.
Minimal irritation, rabbits; irritation was
reversed within 24-48 hours.
Expert judgment
Great Lakes Chemical
Corporation, 1999
Submitted confidential study;
ECHA, 2013
Estimated based on expert
judgment.
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.
Reported in a submitted confidential
study; Study conducted according to
GLP and OECD guidelines.
LOW: Not a skin irritant in rabbits.
Low potential for dermal irritation.
(Estimated)
Negative, rabbits
Expert j udgment
Submitted confidential study;
ECHA, 2013
Estimated based on expert
judgment.
Reported in a submitted confidential
study; Study conducted according to
GLP and OECD guidelines.
4-155
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Endocrine Activity
DATA
Workers report development of dermal
irritation following exposure to a
complex mixture of airborne
contaminants that included TBBPA
bis(2,3-dibromopropyl) ether.
REFERENCE
Great Lakes Chemical
Corporation, 1999
DATA QUALITY
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.
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.
Positive for estradiol sulfotransferase
(E2SULT)-enzyme inhibition in
E2SULT assay.
Negative for agonistic and antagonistic
interactions with aryl hydrocarbon
(AhR), androgen (AR), progesterone
(PR), and estrogen (ER) receptors in
series of CALUX assays.
Positive for displacement of thyroid
hormone precursor thyroxine (T4) from
plasma transport protein in TTR binding
assay.
Negative for potentiating and
antagonistic activity with T3 -mediated
cell proliferation in T-screen.
Canton et al., 2006
Hamers et al., 2006
Hamers et al., 2006
Hamers et al., 2006
Hamers et al., 2006
Data taken from primary study.
Data taken from primary study.
Data taken from primary study.
Data taken from primary study.
Data taken from primary study.
4-156
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Immunotoxicity
Immune System Effects
DATA
REFERENCE
DATA QUALITY
Potential for immunotoxicity based on the presence of polyhalogenated aromatic hydrocarbon structure
and professional judgment.
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
Acute Aquatic Toxicity
Fish LC50
Halo ethers
LOW: Based on experimental and estimated acute toxicity values for fish, daphnid, and algae that suggest
no effects at saturation (NES).
Fish 96-hour LC50 = 1.5xlO"5 mg/L
(Estimated)
ECOSAR: Halo ethers
Fish 96-hour LC50 = 2.2xlQ-6 mg/L
(Estimated)
ECOSAR: Neutral organics
Fish (Oryzias latipes) 96-hour LC50 >
500 mg/L;
Semi -static conditions.
ECOSAR version 1.11
ECOSAR version 1.11
ECHA, 2013
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.
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.
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.
4-157
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
DATA
REFERENCE
DATA QUALITY
Fish (Oncorhynchus mykiss) 96-hour
LC50> lOOmg/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"° mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR version 1.11
Daphnia magna 48-hour EC50 > 100
mg/L;
Water accommodated fraction (WAF)
nominal concentration.
ECHA, 2013
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.
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.
4-158
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Chronic Aquatic Toxicity
Fish ChV
Daphnid ChV
DATA
Green algae (Pseudokirchneriella
subcapitatd) 48 and 72-hour EC50
(growth rate/biomass) >100mg/L;
WAF nominal concentration.
REFERENCE
ECHA, 2013
DATA QUALITY
Sufficient study details reported in a
secondary source. GLP study
conducted using OECD guidelines.
The value exceeds the estimated
water solubility; NES are predicted.
LOW: Based on estimated chronic toxicity values for fish, daphnid and green algae that suggest NES.
Fish ChV = 8.78xl(r7mg/L
(Estimated)
ECOSAR: Halo ethers
Fish ChV = 6.6xl(r7mg/L
(Estimated)
ECOSAR: Neutral organics
Daphnid ChV = S.SSxlO'6 mg/L
(Estimated)
ECOSAR: Neutral organics
ECOSAR version 1.11
ECOSAR version 1.11
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.
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.
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.
4-159
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Green Algae ChV
DATA
Green Algae ChV = 0.00016 mg/L
(Estimated)
ECOSAR: Neutral organics
REFERENCE
ECOSAR version 1.11
DATA QUALITY
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
Henry's Law Constant
(atm-m3/mole)
Sediment/Soil
Adsorption/Desorption
Coefficient - Koc
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.
<10'8 (Estimated)
>3 0,000 (Estimated)
>3 0,000 (Measured)
Reported as log Koc »5.63at 25°C;
OECD TG 121: Estimation of Adsorption
Coefficient on Soil and Sewage Sludge
(HPLC); GLP-study
EPI; Professional judgment
EPI; EPA, 2005
ECHA, 2013
Cutoff value for nonvolatile
compounds.
Cutoff value for nonmobile
compounds.
Guideline study reported in a
secondary source, although the
experimental values were outside the
scope of the protocol (log K0c 1.5-
5.0); radiochemical purity of test
substance (TBBPA-bis(2,3-
dibromopropyl ether)) >99%.
4-160
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Level III Fugacity Model
Persistence
Water
Aerobic Biodegradation
Volatilization Half-life for
Model River
Volatilization Half-life for
Model Lake
DATA
>3 0,000 (Measured)
Reported as log K0c 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
Air: <1% (Estimated)
Water = 5%
Soil = 95%
Sediment: <1%
REFERENCE
ECHA, 2013
EPI
DATA QUALITY
Guideline study reported in a
secondary source, although the
experimental values were outside the
scope of the protocol (log K0c 1.5-
5.0); purity of test substance (FR-720)
not stated.
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.
1% after 4 weeks
OECD 30 1C; test concentration of
100 mg/L and concentration of activated
sludge inoculum of 30 mg/L (Measured)
Passes Ready Test: No
Test method: OECD TG 301B: CO2
Evolution Test
1% degradation after 29 days using an
activated sludge inoculum. (Measured)
>1 year (Estimated)
>1 year (Estimated)
MITI, 2007
ECHA, 2013
EPI
EPI
Adequate, guideline study.
Adequate, guideline study reported in
a secondary source; purity of test
substance FR-720 is 95%.
4-161
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Soil
Air
Reactivity
Aerobic Biodegradation
Anaerobic
Biodegradation
Soil Biodegradation w/
Product Identification
Sediment/Water
Biodegradation
Atmospheric Half-life
Photolysis
Hydrolysis
Environmental Half-life
DATA
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; GLP-
study (Measured)
0% degradation after 100 days in natural
sediment; OECD TG 308: Aerobic and
Anaerobic Transformation in Aquatic
Sediment Systems; GLP-study (Measured)
12 hours (Estimated)
50%/>1 year at 50°C and pH 4, 7, and 9
OECD TG 111: Hydrolysis as a function
of pHand OPPTS 835.21 10: Hydrolysis
as a function of pH; GLP study
> 180 days (Estimated)
REFERENCE
ECHA, 2013
ECHA, 2013
EPI
PBT Profiler; EPI
DATA QUALITY
Adequate guideline study reported in
a secondary source with 14C-TBBPA-
DBPE. No transformation products
were observed; degradation assessed
with 4 different soil types.
Adequate, guideline study reported in
a secondary source with 14C-TBBPA-
DBPE.Degradation results assessed
with 2 sediment types, material mass
balance was reported for both types:
1 .98% in water and 84.48% in
sediment.
No data located.
No data located.
No data located.
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.
Half-life estimated for the
predominant compartment (soil), as
determined by EPI and the PBT
Profiler methodology.
4-162
-------
TBBPA bis(2,3-dibromopropyl) ether CASRN 21850-44-2
PROPERTY/ENDPOINT
Bioaccumulation
Fish BCF
BAF
Metabolism in Fish
DATA
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)
REFERENCE
de Jourdan, et al., 2013
DATA QUALITY
Nonguideline field study providing
supporting data about the partitioning
and fate/persistence of this compound
under environmental conditions.
HIGH: Based on an estimated BAF of 12,000 and its detection in Great Lakes Herring gull eggs, potential for
bioaccumulation is high.
3.4 to 43 (15 |o,g/L concentration)
<17to 130(1. 5 |o,g/L concentration)
(Measured)
12,000 (Estimated)
MITI, 2007
EPI
Adequate, guideline study.
No data located.
ENVIRONMENTAL MONITORING AND BIOMONITORING
Environmental Monitoring
Ecological Biomonitoring
Human Biomonitoring
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., 201 1).
Detected in Great Lakes Herring gull eggs (Letcher and Chu, 2010).
This chemical was not included in the National Health and Nutrition Examination Survey biomonitoring report
(CDC, 2011).
4-163
-------
Canton, 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). l,r-(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 SFInitiative. U.S. Environmental Protection Agency: Washington
D.C. http://www.epa.gov/opptintr/sf/pubs/noncan-screen.htmtfsystemic (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/datadfm.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/.
4-164
-------
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/publikasioner/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/ehc 172.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.
Mack, A.G. Flame Retardants, Halogenated. Kirk-Othmer Encyclopedia of Chemical Technology. Wiley-Interscience. Posted online:
September 17, 2004.
MITI (Japanese Ministry of International Trade and Industry). Biodegradation and bioaccumulation data of existing chemicals based
on the CSCL Japan. Compiled under the supervision of Chemical Products Safety Division, Basic Industries Bureau, Ministry of
4-165
-------
International Trade & Industry, Japan; Chemicals Inspection & Testing Institute, Japan. Ed.; Japan Chemical Industry Ecology-
Toxicology & 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/Existing-
Chemical s/Reviewon_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).
4-166
-------
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 (!) 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 201 la) 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 offish, 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 TBBPA-
bis 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-to-
mouth 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?querv=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 life-
cycle 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
-------
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 (Sail 2010). While coatings face several technical and economic hurdles, separate non-
adhered 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 (COWI2011). 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
201 Ib).
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 (COWI2011). The
performance requirements for perlite insulation are specified in ASTM C728 which lists its R-
value 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
201 Ob). 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; COWI2011). 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 (COWI2011; 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
201 Ic). 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 201 Ib). EPA has also developed
an informational website addressing concerns for SPF
use: http://www.epa.gov/dfe/pubs/projects/spf/sprav_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 R-
value 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 below-
grade. 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,
Hudacketal. 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 R-
value 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
90 91
materials provided by the U.S. Department of Energy , Environmental Building News , The
Pharos Project22, GreenSpec23, manufacturer websites, and the respective trade association
websites, as well as the references cited above.
20 http://www.energysavers.gov/vour home/insulation airsealing/index.cfm?mytopic=l 1510
21 http ://www.buildinggreen. coin/news/index, cfm
22 http://www.pharosproject.net/
23 http://www.greenspec.co.uk/insulation-introduction.php
5-13
-------
References
"Foam-in-Place Polyurethane Insulation" (2008). Environmental Building News.
AirKrete Inc. (2009). "AirKrete." Retrieved June 14, 2011, from http://www.airkrete.com/.
Arctic Monitoring and Assessment Program (2009). AMAP Assessment 2009: Human Health in
the Arctic. Oslo, Norway.
Arnot, J., L. McCarty, et al. (2009). An evaluation of hexabromocyclododecane (HBCD) for
Persistent Organic Pollutant (POP) properties and the potential for adverse effects in the
environment. Submitted to European Brominated Flame Retardant Industry Panel
(EBFRIP).
Bell, M. L. and K. Ebisu (2012). "Environmental Inequality in Exposures to Airborne Particulate
Matter Components in the United States." Environ Health Perspect 120(12): 1699-1704.
BioBased Insulation. (2012). "Supporting Our Claims." Retrieved October 5, 2012,
from http://www.biobased.net/resources/index.htmltfsealant.
Covaci, A., A. C. Gerecke, et al. (2006). "Hexabromocyclododecanes (HBCDs) in the
Environment and Humans: A Review." Environ Sci Technol 40: 3679-3688.
COWI (2011). Alternatives to the Use of Flame Retarded EPS in Buildings, Norwegian Ministry
on the Environment: Climate and Pollution Agency.
Davis, J. W., S. J. Gonsior, et al. (2006). "Biodegradation and Product Identification of
[14C]Hexabromocyclododecane in Wastewater Sludge and Freshwater Aquatic
Sediment." Environ Sci Technol 40(17): 5395-5401.
Ehrlich, B. (2009). "Mineral Wool Residential and Commercial Insulation." Environmental
Building News.
Ehrlich, B. (2010). "CertainTeed Introduces a Formaldehyde-Free Batt
Insulation." Environmental Building News.
Graham, M. (2010). "Revised R Values." Professional RoofmgfDecember, 2010).
Greenspec. (2010). "Insulation Materials." Retrieved July 20, 2011,
from http://www.greenspec.co.uk/insulation-introduction.php.
Haneke, K. E. (2002). Tetrabromobisphenol Abis(2,3-dibromopropyl ether) [21850-44-2]:
Review of Toxicological Literature. November 2002. Prepared for National Institute of
Environmental Health.
Harju, M., E. S. Heimstad, et al. (2009). Current state of knowledge and monitoring
requirements: Emerging "new" brominated flame retardants in flame retarded products
and the environment (TA-2462/2008), Norwegian Pollution Control Authority.
5-14
-------
Healthy Building Network. (2011). "Pharos." Retrieved June 9, 2011,
from http://www.pharosproject.net.
ICA Fittings. (2011). "Mineral Wool 1200° - MSDS." Retrieved December 29, 2011,
from http://www.icainsulation.com/msdsmwl200.html.
Landrigan, P. J., B. Sonawane, et al. (2002). "Chemical contaminants in breast milk and their
impacts on children's health: an overview." Environmental Health Perspectives 110(6):
a313-a315.
Letcher, R. J. and S. Chu (2010). "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 44(22): 8615-8621.
Madonik, A. (2011). Should Green Buildings Contain Fire Retardants? Design for the
Environment Kick-Off Meeting, Crystal City, VA.
Meijer, L., J. Weiss, et al. (2008). "Serum concentrations of neutral and phenolic organohalogens
in pregnant women and some of their infants in The Netherlands." Environ Sci Technol
42(9): 3428-3433.
Minnesota Sustainable Housing Initiative. (2007). "Components: Insulation." Retrieved June 2,
2011, from http://www.greenhousing.umn.edu/comp insulation.html.
Myren, M., T. Mose, et al. (2006). "The human placenta - an alternative for studying foetal
exposure." Toxicology in Vitro 21(7): 1332-1340.
National Academy of Sciences (2008). Science and Decisions: Advancing Risk Assessment.
Washington D.C.
National Toxicology Program (NTP). (2013a). "Testing Status: Tetrabromobisphenol A-bis(2,3-
dibromopropyl ether)." Retrieved May 3, 2013,
from http://ntp.niehs.nih.gov/?obiectid=BD48F894-123F-7908-7B7E35D7CFAA5298.
National Toxicology Program (NTP). (2013b). "TR-587: Technical Report Pathology Tables and
Curves. Pathology Tables, Survival and Growth Curves from NTP Long-Term Studies.
TR-587: Tetrabromobisphenol A (TBBPA)." Retrieved May 3, 2013,
from http://ntp.niehs.nih.gov/?obiectid=lAF3931A-FF57-C2F8-3948D37883F3B052.
Persistent Organic Pollutants Review Committee (2012). Report of the Persistent Organic
Pollutants Review Committee on the work of its eighth meeting: Addendum to the risk
management evaluation on hexabromocyclododecane. Geneva, United Nations
Environment Programme.
Polyisocyanurate Insulation Manufacturers Association. (2011). "About Polyiso Insulation."
Retrieved June 9, 2011,
5-15
-------
from http://www.pima.org/contentpage/ContentPage.aspx?ModuleID=5&SubModuleID=
45.
Qu, G., J. Shi, et al. (2011). "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 45(11): 5009-5016.
Sail, L. (2010). Exploration of Management Options for Hexabromocyclododencane (HBCD):
Paper for the 8th Meeting of the UNECE CLRTAP Task Force on Persistent Organic
Pollutants, Montreal 18-20, Climate and Pollution Agency in Norway.
Schroer, D., M. Hudack, et al. (2012). Rigid Polymeric Foam Boardstock Technical Assessment.
Shi, T., S. J. Chen, et al. (2009). "Occurrence of brominated flame retardants other than
polybrominated diphenyl ethers in environmental and biota samples from southern
China." Chemosphere 74(7): 910-916.
Smith, T. L., J. D. Carlson, et al. (1993). Steel Deck Corrosion Associated with Phenolic Roof
Insulation: Problem Causes, Prevention, Damage Assessment and Corrective
Action. 10th Conference on Roofing Technology. Gaithersburg, MD.
Stillerman, K. P. (2008). "Environmental Exposures and Adverse Pregnancy Outcomes: A
Review of the Science." Reproductive Sciences 15(7): 631-650.
Sustainable Sources. (2011). "Insulation." Retrieved June 8, 2011,
from http://insulation.sustainablesources.com/.
The Dow Chemical Company (2013). TUFF-R™ and Super TUFF-R™ Polyisocyanurate
Insulation.
The Dow Chemical Company (n.d.). THERMAX™ Sheathing.
U.S. Department of Energy (2008). Insulation Fact Sheet.
U.S. Department of Energy. (2011). "Types of Insulation." Retrieved June 9, 2011,
from http://www.energysavers.gov/your_home/insulation_airsealing/index.cfm?mytopic
=11510.
U.S. Department of Energy. (2012). "Energy Saver: Types of Insulation." Retrieved March 1,
2013, from http://www.doe.gov/energvsaver/articles/types-insulation.
U.S. EPA (2008). Partnership to Evaluate Flame Retardants in Printed Circuit Boards. Review
Draft.
U.S. EPA (201 la). 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
5-16
-------
U.S. EPA (201 Ib). Methylene Diphenyl Diisocyanate (MDI) And Related Compounds Action
Plan.
U.S. EPA. (201 Ic). "Spray Polyurethane Foam (SPF) " Retrieved August 29, 2011,
from http ://www. epa. gov/dfe/pub s/proj ects/spf/sprav_polyurethane foam. html.
U.S. EPA. (2012a). "Health Concerns, Spray Polyurethane Foam (SPF)." Retrieved October 5,
2012,
from http://www.epa.gov/dfe/pubs/projects/spf/health_concerns_associated_with_chemic
als in sprav_polyurethane foam_products.html.
U.S. EPA (2012b). Interpretive Assistance Document for Assessment of Polymers. Sustainable
Futures Summary Assessment. Washington, D.C.
U.S. EPA (2013). Significant New Use Rules on Certain Chemical Substances. 78 FR 38210-
38223.
Wilson, A. (1993). "Cellulose Insulation: An In-Depth Look at the Pros and
Cons." Environmental Building News.
Wilson, A. (1995). "Insulation Materials: Environmental Comparisons." Environmental
Building News.
Wilson, A. (2005). "Insulation: Thermal Performance is Just the Beginning." Environmental
Building News.
Wilson, A. (2010a). "Avoiding the Global Warming Impact of Insulation." Environmental
Building News 19(6).
Wilson, A. (201 Ob). "Foam-In-Place Insulation." Retrieved June 8, 2011,
from http://www.greenbuildingadvisor.com/blogs/dept/energy-solutions/foam-place-
insulation.
Wilson, A. (2010c). "Foamglas Insulation: A Great Option for Below-Grade." Environmental
Building News.
Wilson, A. (2011). "Greensulate - A fungus-based insulation material that's grown rather than
manufactured." Retrieved February 11,2013,
from http://greenspec.buildinggreen.com/blogs/greensulate-fungus-based-insulation-
material-thats-grown-rather-manufactured.
Xue, J., V. Zartarian, et al. (2007). "A Meta-Analysis of Children's Hand-to-Mouth Frequency
Data for Estimating Nondietary Ingestion Exposure." Risk Anal. 27(2): 411-420.
5-17
------- |