TSCA Work Plan Chemical

Problem Formulation and Initial Assessment

Tetrabromobisphenol A and Related Chemicals Cluster

Flame Retardants

CASRN NAME

79-94-7 Phenol, 4,4'-(1-methylethylidene)bis[2,6-

dibromo

21850-44-2 Benzene, 1,1'-(1-methylethylidene)bis[3,5-

dibromo-4-(2,3-dibromopropoxy)-

25327-89-3 Benzene, 1,1'-(1-methylethylidene)bis[3,5-

dibromo-4-(2-propen-1-yloxy)-

37853-61-5 Benzene, 1,1'-(1-methylethylidene)bis[3,5-

dibromo-4-methoxyAugust 2015

United States

Environmental Protection Agency

EPA-HQ-OPPT-2014-0730-0004

August 2015 

Office of Chemical Safety and 

Pollution Prevention
Page 2 of 135

Table of Contents

List of Tables.....................................................................................................................................4

List of Figures....................................................................................................................................4

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

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

EXECUTIVE SUMMARY ......................................................................................................................9

1 INTRODUCTION........................................................................................................................12

1.1 SCOPE OF THE ASSESSMENT ............................................................................................................................................13

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

1.2.1 Federal..................................................................................................................................................................14

1.2.2 State .....................................................................................................................................................................14

1.2.3 International.........................................................................................................................................................15

1.2.3.1 European Union ............................................................................................................................................15

1.2.3.1 Canada...........................................................................................................................................................16

2 PROBLEM FORMULATION ........................................................................................................18

2.1 PHYSICAL AND CHEMICAL PROPERTIES...............................................................................................................................19

2.2 PRODUCTION VOLUME AND USES.....................................................................................................................................20

2.2.1.1 Production.....................................................................................................................................................20

2.2.1.2 Uses...............................................................................................................................................................22

2.2.1.3 Summary of Production and Use ..................................................................................................................26

2.3 FATE AND TRANSPORT....................................................................................................................................................26

2.4 EXPOSURES ..................................................................................................................................................................27

2.4.1 Releases to the Environment................................................................................................................................27

2.4.1.1 Chemical Manufacturing ...............................................................................................................................27

2.4.1.2 Processing .....................................................................................................................................................27

2.4.1.3 Recycling .......................................................................................................................................................27

2.4.1.4 Disposal .........................................................................................................................................................28

2.4.2 Presence in the Environment and Biomonitoring Data........................................................................................29

2.4.3 Occupational Exposures .......................................................................................................................................30

2.4.4 General Population Exposures .............................................................................................................................30

2.4.5 Consumer Exposures............................................................................................................................................31

2.5 HAZARD ENDPOINTS ......................................................................................................................................................31

2.5.1 Ecological Hazard..................................................................................................................................................31

2.5.2 Human Health Hazard ..........................................................................................................................................32

2.6 RESULTS OF PROBLEM FORMULATION ...............................................................................................................................32

2.6.1 Conceptual Models...............................................................................................................................................32

2.6.2 Analysis Plan .........................................................................................................................................................40

2.6.2.1 Environmental Assessment near Manufacturing Facilities...........................................................................40

2.6.2.2 Human Health Risk Assessment....................................................................................................................41

2.6.3 Sources and Pathways Excluded from Further Assessment.................................................................................42

2.6.3.1 Chemical Manufacturing ...............................................................................................................................42

2.6.3.2 Processing .....................................................................................................................................................43

2.6.3.3 Recycling .......................................................................................................................................................43

2.6.3.4 Disposal .........................................................................................................................................................44

2.6.3.5 Other Excluded Pathways .............................................................................................................................45

2.6.4 Uncertainties and Data Gaps................................................................................................................................46

2.6.4.1 Environmental Fate Data ..............................................................................................................................46

2.6.4.2 Release Data..................................................................................................................................................46

2.6.4.3 Exposure Information....................................................................................................................................46

2.6.4.4 Ecological Hazard Data..................................................................................................................................47

2.6.4.5 Human Health Hazard Data...........................................................................................................................47

References......................................................................................................................................49
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Data Available for TBBPA-bis(dibromopropyl ether), TBBPA-bis(allyl ether) and TBBPAbis(methyl ether) ............................................................................................................................71

A-1 EXCLUSION FROM FURTHER ASSESSMENT.........................................................................................................................73

A-2 CHEMICAL STRUCTURES ................................................................................................................................................74

A-3 PHYSICAL-CHEMICAL PROPERTIES ...................................................................................................................................75

A-4 PRODUCTION VOLUMES................................................................................................................................................76

A-5 USES .........................................................................................................................................................................77

A-6 FATE PROPERTIES ........................................................................................................................................................80

A-7 EXPOSURE ..................................................................................................................................................................81

A-8 ECOLOGICAL HAZARD ...................................................................................................................................................83

A-9 HUMAN HEALTH HAZARD .............................................................................................................................................84

Literature Searches and Data Quality .........................................................................86

B-1 LITERATURE AVAILABLE FOR THE CLUSTER MEMBERS..........................................................................................................86

B-2 DATA ADEQUACY.........................................................................................................................................................87

Fate and Transport.....................................................................................................88

C-1 FATE IN ENVIRONMENTAL MEDIA ...................................................................................................................................89

C-2 PERSISTENCE...............................................................................................................................................................90

C-3 BIOACCUMULATION/BIOCONCENTRATION........................................................................................................................91

C-4 EXCLUSION OF DEGRADATION PRODUCTS FROM FURTHER ASSESSMENT.................................................................................91

Toxics Release Inventory Emissions............................................................................93

D-1 TRI RELEASES FROM MANUFACTURERS............................................................................................................................93

TBBPA and other Dust Particle Concentrations in Occupational Settings .....................97

E-1 PROCESSING ...............................................................................................................................................................98

Ecological Hazard Study Summaries............................................................................99

F-1 TOXICITY TO AQUATIC ORGANISMS .................................................................................................................................99

F-2 TOXICITY TO TERRESTRIAL ORGANISMS ..........................................................................................................................105

F-3 TOXICITY TO AMPHIBIANS............................................................................................................................................107

F-4 SUMMARY OF ENVIRONMENTAL HAZARD .......................................................................................................................108

Appendix G Human Health Hazard Study Summaries..................................................................109

G-1 EPIDEMIOLOGY..........................................................................................................................................................109

G-2 TOXICOKINETICS ........................................................................................................................................................109

G-3 ACUTE TOXICITY ........................................................................................................................................................110

G-4 REPEATED-DOSE TOXICITY...........................................................................................................................................110

G-5 REPRODUCTIVE AND DEVELOPMENTAL TOXICITY ..............................................................................................................112

G-6 IRRITATION AND SENSITIZATION....................................................................................................................................115

G-7 GENOTOXICITY AND CARCINOGENICITY...........................................................................................................................115

G-8 STUDIES PROPOSED FOR RISK ASSESSMENT.....................................................................................................................122

G-9 UNCERTAINTIES.........................................................................................................................................................123

Parameters Needed for Estimating Fish Ingestion.....................................................124

Draft Approach for Estimating Exposure from Mouthing of TBBPA.............................126

I-1 TBBPA CONCENTRATIONS IN PRODUCTS AND PRODUCT SURFACES.....................................................................................126

I-2 MIGRATION RATES INTO SALIVA ...................................................................................................................................127

I-3 CHILDREN’S ACTIVITY PATTERNS...................................................................................................................................127

I-4 OTHER PARAMETERS BEING CONSIDERED.......................................................................................................................128

I-5 METHOD TO COMBINE EXPOSURE DATA ........................................................................................................................128

I-6 CONFIDENCE AND UNCERTAINTY IN THE AVAILABLE DATA..................................................................................................128

Dose-Response Assessment for Cancer Endpoints .....................................................129

J-1 CHOICE OF MODEL, POINTS OF DEPARTURE AND ORAL SLOPE FACTORS...............................................................................129

J-2 CALCULATION OF TARGET RISK LEVELS ...........................................................................................................................130

J-3 KEY SOURCES OF UNCERTAINTY....................................................................................................................................131
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EU and Canada Risk Assessments: Specific Evaluations Consulted for Current 

Assessment 133

K-1 EU CALCULATIONS OF TBBPA UPTAKE FROM SOIL NEAR MANUFACTURING AND PROCESSING SITES.........................................133

K-2 EU ENVIRONMENTAL ASSESSMENT AT PROCESSING SITES .................................................................................................133

List of Tables

Table 1-1: Chemical Names and Structures...............................................................................................................................13

Table 2-1: Data Required for Risk Assessment ..........................................................................................................................19

Table 2-2: Physical-Chemical Properties....................................................................................................................................20

Table 2-3: CDR Production Volume Data...................................................................................................................................21

Table 2-4: Industrial and Consumer Use Data for TBBPA from the CDR ...................................................................................23

Table 2-5: Availability of Exposure Data for TBBPA ...................................................................................................................29

Table 2-6: Environmental Exposure Scenarios Considered for Assessment..............................................................................35

Table 2-7: Human Health Exposure Scenarios Considered for Assessment ..............................................................................38

Table_Apx A-1: Data Availability and Read Across for Cluster Members..................................................................................71

Table_Apx A-2: Physical-Chemical Properties ...........................................................................................................................76

Table_Apx A-3: 2012 CDR Production Volume Data (Pounds/Year) for TBBPA-bis(dibromopropyl ether), TBBPA-bis(allyl 

ether) and TBBPA-bis(methyl ether) ................................................................................................................................77

Table_Apx A-4: Industrial and Consumer Use Data for TBBPA-bis(dibromopropyl ether), TBBPA-bis(allyl ether) and TBBPAbis(methyl ether)..............................................................................................................................................................79

Table_Apx A-5: Environmental Fate Endpoints for Three Cluster Members.............................................................................80

Table_Apx A-6: Availability of Exposure Data for Three Cluster Members...............................................................................82

Table_Apx C-1: Environmental Fate ..........................................................................................................................................88

Table_Apx D-1: Disposal and Releases of TBBPA by Industry as Reported in the 2012 TRI ......................................................93

Table_Apx D-2: Disposal and Releases of TBBPA by Industry as reported in the 2012 TRI .......................................................94

Table_Apx D-3: Disposal and Releases of TBBPA by Manufacturing Facility as Reported in the 2012 TRI ...............................95

Table_Apx D-4: TBBPA TRI Release Trends from 2001 to 2012.................................................................................................95

Table_Apx D-5: Air Emissions for Facilities Modeled in the Current Assessment .....................................................................96

Table_Apx E-1: Potential Occupational Exposures from Manufacture of TBBPA*....................................................................97

Table_Apx E-2: Potential exposures from processing of TBBPA*..............................................................................................98

Table_Apx F-1: Toxicity from TBBPA to Aquatic Organisms....................................................................................................102

Table_Apx F-2: Soil Invertebrate Toxicity Data for TBBPA (mg/kg) .........................................................................................106

Table_Apx F-3: Ecotoxicity Concentrations of Concern...........................................................................................................108

Table_Apx I-1: Plan for Evaluating Risk to Children from Ingestion of TBBPA from Products in the Home............................126

Table_Apx J-1: Parameters Used in Dose-Response Equations...............................................................................................130

Table_Apx J-2: Doses (in mg/kg-bw/day) Associated with Three Target Risk Levels ..............................................................131

List of Figures

Figure 1-1: General Structure for TBBPA and Related Chemicals..............................................................................................13

Figure 2-1: Conceptual Model for the TBBPA Environmental Assessment ...............................................................................34

Figure 2-2: Conceptual Model for the TBBPA Human Health Assessment................................................................................37
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AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS 

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

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

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

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

endorsement by EPA.

EPA Assessment Team

Lead: Amy Benson, OPPT/Risk Assessment Division (RAD)

Team Members:

Charles Bevington, OPPT/RAD

Pamela Buster, OPPT/Environmental Assistance Division (EAD)

Rehan Choudhary, OPPT/RAD

Ana Corado, OPPT/EAD 

Conrad Flessner, OPPT/RAD

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

Jeff Gallagher, OPPT/RAD

Kirsten Hesla, OPPT/Chemical Control Division (CCD)

David Lai, OPPT/RAD

David Lynch, OPPT/RAD

Tim Lehman, OPPT/CESSD

Larry Newsome, OPPT/RAD

Eva Wong, OPPT/RAD

Yintak Woo, OPPT/RAD

Management Leads:

Stan Barone, OPPT/RAD

Mark Townsend, OPPT/RAD

Acknowledgements

The following individuals contributed to portions of this document:

Vivian Hart, OPPT/RAD

Ruth Hummel, OPPT/RAD

Emma Lavoie, OPPT/CESSD

Yvette Selby-Mohamadu, OPPT/RAD

Portions of this document were developed with support from Abt Associates, ICF International, Versar 

and SRC, Inc.

Docket

Please visit the public docket (Docket: EPA-HQ-OPPT-2014-0730) to view supporting information.
Page 6 of 135

ABBREVIATIONS 

ABS Acrylonitrile butadiene styrene

ADEQ Arkansas Department of Environmental Quality

AERMIC AMS/EPA Regulatory Model Improvement Committee

AERMOD AERMIC AMS/EPA Regulatory Model

AMS American Meteorological Society

ASTM American Society for Testing and Materials

B1, 2 or 3 Bioaccumulation level 1, 2 or 3

B6C3F1 Mouse strain

B6C3F1/N Mouse strain

BA-59P Trade name for TBBPA

BAEP Brainstem auditory evoked potential

BAF Bioaccumulation factor 

BCF Bioconcentration factor 

BPA Bisphenol A

BSEF Brominated Science and Environmental Forum

CASRN Chemical Abstract Service Registry Number 

CBI Confidential business information

CFR Code of Federal Regulations

CDR Chemical data reporting

COC Concentration of concern 

DL Detection limit

Doverguard 59 Trade name for TBBPA

Doverguard 68 Trade name for TBBPA-bis(dibromopropyl ether) 

dw Dry weight 

EC European Commission

ECB European Chemicals Bureau

EC/HC Environment Canada and Health Canada

ECHA European Chemicals Agency 

ECOTOX EPA database of ecotoxicity studies

EPA United States Environmental Protection Agency 

EPI Estimation Programs Interface 

ER Estrogen receptor

EU European Union

e-waste electronic waste

F0 Parental generation

F1 First generation of offspring 

F344/NTac Rat strain

FR-720 Trade name for TBBPA-bis(dibromopropyl ether)

FR-1524 Trade name for TBBPA

GLCC Great Lakes Chemical Corporation

GLP Good laboratory practice 
Page 7 of 135

HPV High production volume 

ICL-IP ICL Industrial Products America, Inc.

ISO/DIS International Organization for Standardization/Draft International Standard

IUR Inventory update reporting

kg Kilogram 

lb Pound 

LC50 Lethal concentration at which 50% of test organisms die

LD50 Lethal dose at which 50% of test organisms die

LOAEL Lowest-observed-adverse-effect level 

LOEC Lowest-observed-effect concentration

LOQ Limit of quantitation

Log KOC Logarithmic soil organic carbon partition coefficient 

Log KOW Logarithmic octanol-water partition coefficient 

lw Lipid weight 

MATC Maximum acceptable toxicant concentration

mg/kg-bw/day Milligrams (of a chemical) per kilogram of body weight per day

MITI Ministry of International Trade and Industry (Japan)

MOA Mode of action

MOE Margin of exposure

MOS Margin of safety 

MSW Municipal solid waste

NAICS North American Industry Classification System 

NMRI Mouse strain

NOAEL No-observed-adverse-effect level 

NOEC No-observed-effect concentration 

NTP National Toxicology Program

OCSPP Office of Chemical Safety and Pollution Prevention 

OECD Organisation for Economic Co-operation and Development 

OPPT Office of Pollution Prevention and Toxics

P1, 2 or 3 Persistence level 1, 2 or 3

PAHs Polyaromatic hydrocarbons

PBDDs Polybrominated dibenzodioxins

PBDFs Polybrominated dibenzofurans

PND Postnatal day

QSAR Quantitative structure activity relationship

RCRA Resource Conservation and Recovery Act

REACH Registration, Evaluation, Authorisation and Restriction of Chemicals 

SAYTEX® CP-2000 Trade name for TBBPA

T3 Triiodothyronine

T4 Thyroxine

TBBPA Tetrabromobisphenol A

TOC Total organic carbon

Tp53 Gene for tumor suppressor p53 protein

TRI Toxics Release Inventory

TSCA Toxic Substances Control Act 
Page 8 of 135

TSH Thyroid stimulating hormone

TTR Transthyretin

UL Underwriters Laboratories

US United States

ww Wet weight 

WWTP Wastewater treatment plant 

yr Year
Page 9 of 135

EXECUTIVE SUMMARY 

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

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

Control Act (TSCA) in March 2012. Chemical risk assessments will be conducted if, as a result of scoping 

and problem formulation, there are exposures of concern, identified hazards and sufficient data for 

quantitative analysis. If an assessment identifies unreasonable risks to humans or the environment, 

EPA will pursue risk reduction. This document presents the problem formulation for TBBPA and related 

chemicals as part of the TSCA Work Plan.

EPA/OPPT included TBBPA-bis(dibromopropyl ether) (CASRN 21850-44-2) and TBBPA-bis(allyl ether) 

(CASRN 25327-89-3) in the TBBPA cluster as a result of an initial prioritization exercise because these 

compounds have additive flame retardant uses; EPA/OPPT assumes that additive uses will lead to 

higher potential for exposure. EPA/OPPT included a fourth chemical, TBBPA-bis(methyl ether) (CASRN 

37853-61-5), because monitoring studies have routinely found this substance in the environment. Its 

presence is likely to be a result of microbial transformation of TBBPA. 

Conclusions

As a conclusion of this problem formulation and initial assessment, EPA/OPPT will further assess the 

following risks to:

Environment

• Aquatic, sediment-dwelling or soil-dwelling organisms resulting from two manufacturing 

facilities that emitted the vast majority of TBBPA to air during a 13-year period (2000-2012) as 

indicated from Toxics Release Inventory (TRI) data.

Human Health

• Workers at manufacturing and processing facilities who may ingest TBBPA in dust from the air

after further developing assessment methods.

• Aggregate oral exposure from the following oral exposure pathways:

o Incidental ingestion of TBBPA in dust from outdoor sources

o Incidental ingestion of TBBPA in dust from indoor sources 

o Incidental ingestion of TBBPA from mouthing of consumer products

o Consumption of TBBPA in fish (recreational and subsistence fishers)

These aggregate exposures will be assessed and compared for the following: 1) those who live near 

two manufacturing facilities, and 2) those who do not live near such facilities. 
Page 10 of 135

EPA/OPPT will not specifically assess the following risks:

• To the general population near processing sites, due to smaller releases from processors than 

from manufacturers. 

• To the environment and human health from recycling plants given limited information 

regarding recycling of electronic products in the United States. 

• From product disposal, due to required controls, limited data or low concerns.

• From drinking water due to lack of information as well as a likelihood of low risk concerns.

• From eating food other than fish because this is considered the purview of other agencies.

• For adults exposed directly (through mouthing) to consumer products, based on low concerns.

Exclusion of Three Cluster Members and Degradation Products

Some limited information is available for the cluster members other than TBBPA. However, EPA/OPPT 

concluded that no quantitative risk assessment is needed for these other cluster members for one or 

more of the following reasons: limited information, inability to use the more robust data for TBBPA to 

read across to other cluster members, low toxicity or likely low risk concerns. 

EPA/OPPT also investigated the possibility of evaluating risks for degradation and combustion products 

of TBBPA. However, information is too limited on rates of degradation and the specificity of identified 

combustion products to incineration of TBBPA. Therefore, EPA/OPPT will not assess risks from 

exposure to these products in the proposed assessment.

TBBPA Data Evaluated During Problem Formulation 

TBBPA (CASRN 79-94-7) is used as a flame retardant, is persistent and has been detected in the 

environment, in humans and in biota. Of the brominated flame retardants, TBBPA has the highest US 

and global production volume with a reported 2011 US volume of 120 million pounds. It is used as both 

an additive and reactive flame retardant1 and is reacted to produce more than 70 compounds. It is 

used primarily in electronics but may be found in a variety of other products. 

In 2012, reports to TRI indicated that 52 manufacturing and processing facilities released or disposed 

approximately 127,845 pounds of TBBPA. The compound may undergo direct photolysis and indirect 

photo-oxidation, but the amount of vapor in air is expected to be low. It is expected to be persistent in 

water, soil and sediment and has a low bioaccumulation potential.

TBBPA has been found in humans (blood, breast milk and adipose tissue) and in biota (aquatic and 

terrestrial animals and plants and in birds). Several studies have also found TBBPA in a variety of 

environmental media that includes sediment, soil, landfill leachates, sewage sludge, surface water, 

wastewater and indoor and outdoor air.

 1 A reactive use is one in which TBBPA is covalently bound with the substrate matrix. An additive use means that TBBPA is 

not reacted with the substrate.
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Ecological toxicity studies include acute and chronic data for aquatic organisms (including sedimentdwelling organisms), terrestrial plants, soil invertebrates, birds and amphibians. Epidemiological 

studies and toxicity studies to inform human health hazard are also available. These include acute, 

repeated-dose, reproductive, developmental, carcinogenicity, genotoxicity, irritation and sensitization 

studies. Some information is also available on toxicokinetics.

EPA/OPPT followed Agency guidance during problem formulation and reviewed previous assessments, 

such as those by the EU and Canada, to help inform the proposed assessment for TBBPA (and TBBPAbis(allyl ether)). Other published and unpublished data sources were also reviewed. During problem 

formulation, EPA/OPPT identified available fate, exposure and hazard data, and characterized potential 

exposures, receptors and effects. 

To assist in targeting sources and exposure pathways of most concern, high-end exposure values from 

existing risk assessments or more recent data were compared with toxicity values. For the 

environmental scenarios, EPA/OPPT developed concentrations of concern (COCs) by applying 

routinely-used uncertainty factors. For human health scenarios, EPA/OPPT calculated a healthconservative toxicity value for developing uterine tumors using a recent carcinogenesis bioassay from 

the National Toxicology Program.

Results of Problem Formulation

The results of this problem formulation are illustrated in the conceptual models and described by the 

analysis plan that seeks to answer several assessment questions.

In summary, EPA/OPPT will conduct additional risk analysis of potential exposure to organisms 

surrounding manufacturing facilities using concentrations of concern to determine risk quotients. 

EPA/OPPT will also investigate potential exposure for workers and the general population/consumers

under the TSCA Existing Chemicals Program using existing data and methods. 

Occupational risks will focus on workers within manufacturing and various processing facilities. For the 

general population (with some exposure from consumer products), risks will be aggregated for 

multiple oral pathways (direct oral ingestion or indirect ingestion from inhaled dust) and will focus on 

individuals near manufacturing facilities and those farther away from such facilities. EPA/OPPT will 

compare these exposure estimates to cancer and developmental effects benchmark values to evaluate 

risk.
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1 INTRODUCTION

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

chemicals, in March 2012 EPA identified a work plan of chemicals for further assessment under the 

Toxic Substances Control Act (TSCA)2. After gathering input from stakeholders, EPA developed criteria 

used for identifying chemicals for further assessment3. The criteria focused on chemicals that meet 

one or more of the following factors: (1) potentially of concern to children’s health (for example, 

because of reproductive or developmental effects); (2) neurotoxic effects; (3) persistent, 

bioaccumulative, and toxic (PBT); (3) probable or known carcinogens; (4) used in children’s products; or 

(5) detected in biomonitoring programs. Using this methodology, EPA/OPPT identified a TSCA Work 

Plan of chemicals as candidates for risk assessment in the next several years. In the prioritization 

process, tetrabromobisphenol A (TBBPA) was identified for assessment based on its use as a flame 

retardant in epoxy resin circuit boards and in electronic enclosures in consumer uses, acute aquatic 

toxicity and environmental persistence. Other chemicals were added to the cluster during this initial 

prioritization based on considerations described in Section 1.1.

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

unacceptable risks to humans or the environment, EPA/OPPT will pursue risk reduction. The target 

audience for this risk assessment is primarily EPA risk managers; however, it may also be of interest to 

the broader risk assessment community as well as US stakeholders interested in TBBPA and related 

chemicals. The information presented in the risk assessment may be of assistance to other federal, 

state and local agencies as well as to members of the general public who are interested in the risks of

TBBPA and related chemicals.

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

prioritization exercise, includes scoping and problem formulation. During these steps EPA/OPPT 

reviews currently available data and information, including but not limited to, assessments conducted 

by others (e.g., authorities in other countries), published or readily available reports and published 

scientific literature. During scoping and problem formulation the more robust review of the factors 

influencing initial prioritization may result in refinement – either addition/expansion or 

removal/contraction – of specific hazard or exposure concerns previously identified in the prioritization 

methodology.

This document includes the results of scoping and problem formulation for TBBPA and related 

chemicals. In the initial prioritization and scoping stages EPA/OPPT determined which chemical(s) 

would be included and what uses would be considered in the assessment. During problem formulation, 

EPA/OPPT identified available exposure and hazard data, and characterized potential exposures, 

receptors and effects. EPA/OPPT developed two conceptual models, Figure 2-1 and Figure 2-2, and an 

analysis plan (Section 2.6.2) as a result of problem formulation.

 2 http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html 3 http://www.epa.gov/oppt/existingchemicals/pubs/wpmethods.pdf
Page 13 of 135

1.1 Scope of the Assessment

The four chemicals in the TBBPA and related chemicals assessment have the following general 

structure: 

Figure 1-1: General Structure for TBBPA and Related Chemicals

Table 1-1 identifies the chemical names, Chemical Abstract Service Registry Numbers (CASRNs) and

definitions of R groups that are shown in the above structure.

Table 1-1: Chemical Names and Structures

Chemical Name CASRN CAS Name R =

TBBPA 79-94-7 Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo H

TBBPAbis(dibromopropyl ether)21850-

44-2

Benzene, 1,1'-(1-methylethylidene)bis[3,5-dibromo4-(2,3-dibromopropoxy)- CH2(CHBr)2H

TBBPA-bis(allyl ether) 25327-

89-3

Benzene, 1,1'-(1-methylethylidene)bis[3,5-dibromo4-(2-propen-1-yloxy)-CH2CH=

CH2

TBBPA-bis (methyl ether) 37853-

61-5

Benzene, 1,1'-(1-methylethylidene)bis[3,5-dibromo4-methoxy- -CH3

Of all brominated flame retardants, TBBPA has the highest US and global production volume (BSEF, 

2014; EPA, 2014b). It is used as both an additive and reactive flame retardant4 and it is reacted to 

produce more than 70 compounds (EPA, 2015). 

In the initial prioritization process, EPA/OPPT considered structurally similar non-polymeric compounds 

that could be assessed along with TBBPA. Two of the compounds, TBBPA-bis(dibromopropyl ether) and 

TBBPA-bis(allyl ether), have additive flame retardant uses in addition to reactive uses. EPA/OPPT chose 

these two compounds based on the assumption that additive uses lead to higher potential for 

exposure than compounds with only reactive uses. EPA/OPPT included a fourth chemical, TBBPAbis(methyl ether), in the cluster based on studies that show it has routinely been found in the 

environment. Its presence is likely to be a result of microbial transformation of TBBPA (George and 

Haggblom, 2008). 

 4 A reactive use is one in which TBBPA is covalently bound with the substrate matrix. An additive use means that TBBPA is 

not reacted with the substrate.
Page 14 of 135

1.2 Regulatory and Assessment History

The United States government, individual states and foreign governments have regulated TBBPA or 

taken other actions with respect to TBBPA and some of the other cluster members. Primary risk 

assessments are the European Union’s environmental and human health assessments (EC, 2006, 2008)

and Canada’s recent environmental and human health assessment (EC/HC, 2013).

1.2.1 Federal

At the federal level, companies report production volume and chemical use information for TBBPA, 

TBBPA-bis(dibromopropyl ether) and TBBPA-bis(allyl ether) under the Chemical Data Reporting rule 

(EPA, 2014b). TBBPA and TBBPA-bis(dibromopropyl ether) are produced in volumes greater than 1 

million pounds per year and are thus considered high production volume (HPV) chemicals as defined by 

EPA and industry prepared a test plan that was submitted to EPA under the HPV Chemicals Challenge 

Program. TBBPA emissions are reported yearly to the Toxics Release Inventory (TRI) (EPA, 2012e).

1.2.2 State

The Oregon Department of Environmental Quality classifies TBBPA as a priority persistent pollutant as 

part of its water quality program based on concerns related to persistence and chronic toxicity to fish

(Oregon_DEQ, 2010a, 2010c). Oregon also provides data on use, exposure pathways and releases for 

TBBPA under this program (Oregon_DEQ, 2010b).

Washington lists TBBPA as a chemical of high concern based on human health effects5 and presence in 

humans and accordingly provides some toxicity and exposure information under the Children’s Safe 

Products Act (WSDE, 2011, 2014b). Washington also lists information regarding the amount of TBBPA 

contained in children’s products, as reported to the Washington State Department of Ecology (WSDE, 

2014a). 

California lists TBBPA and TBBPA-bis(dibromopropyl ether) as priority chemicals for biomonitoring

identified by a scientific guidance panel (SGP) from a list of designated chemicals compiled using 

Centers for Disease Control National Biomonitoring Program and other SGP recommendations

(California_Biomonitoring, 2014b, 2014c). No information is available regarding when biomonitoring 

might begin However, California is not yet biomonitoring for these chemicals

(California_Biomonitoring, 2013, 2014a). In addition, TBBPA and TBBPA-bis(dibromopropyl ether) are 

listed as candidate chemicals under the state’s Safer Consumer Products regulations. Presence on this 

list indicates that the chemical meets criteria for the initial priority products list specified in 

regulations. TBBPA is listed based on bioaccumulation, endocrine toxicity, environmental persistence, 

neurotoxicity, reproductive toxicity and other (undefined) toxicity. TBBPA would only be named as a 

chemical of concern if it was part of a product-chemical combination that is listed as a priority product 

(CalEPA, 2013). 

 5 However, it should be noted that a primary reference is for a formulated product called Saytex 111, not for TBBPA as a 

monomer.
Page 15 of 135

Maine uses a tiered system to classify chemicals (Maine_DEP, 2013c). The first level includes roughly 

1400 chemicals of concern including both TBBPA and TBBPA-bis(dibromopropyl ether) (Maine_DEP, 

2013c). This list uses tools such as the Washington state list and EPA TRI information (Maine_DEP, 

2013a). The second tier is comprised of 49 chemicals of high concern; TBBPA is the only chemical from 

the TBBPA and Related Chemicals Cluster on this list (Maine_DEP, 2013b). 

Minnesota lists TBBPA and TBBPA-bis(dibromopropyl ether) as chemicals of high concern based on 

persistence, bioaccumulation and toxicity and references other authoritative lists (MDH, 2013a, 

2013b). Among these authoritative sources, Minnesota refers to Washington state and EPA’s TRI

information.

States do not appear to regulate or provide information on either TBBPA-bis(allyl ether) or TBBPA 

bis(methyl ether).

1.2.3 International

1.2.3.1 European Union

In the European Union (EU), TBBPA and TBBPA-bis(dibromopropyl ether) are registered chemicals 

under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. This 

means that companies (registrants) provided the European Chemicals Agency with information on the 

uses, properties, hazards and potential risks for these substances (ECHA, 2015b). The EU has also 

conducted human health and environmental risk assessments of TBBPA (EC, 2006, 2008).

The other two cluster members are pre-registered in the EU, which means companies will be providing 

information on the properties and uses of these substances to the European Chemicals Agency by the 

extended registration deadline of May 2018. These two substances are pre-registered because the 

substances are manufactured or imported at 1 to 100 metric tons per year (ECHA, 2014). 

On October, 2014, ECHA proposed to update the Community Rolling Action Plan (CoRAP) and identified 

TBBPA as a proposed substance for evaluation in 2015. Member states evaluate substances included in 

the CoRAP to determine if the measures in place are enough to manage the risks. If not, an evaluation 

of whether there is a need for further action is conducted. Such action could include restrictions, 

identification of substances of very high concern or other actions outside the scope of REACH. The final 

decision regarding the substances to be evaluated in 2015 will be adopted by ECHA at the end of 

March 2015 (ECHA, 2015a).
Page 16 of 135

1.2.3.1.1 European Union Risk Assessment

Environmental Assessment

In their environmental risk assessment (EC, 2008), the European Union concluded that there is a need 

to limit risks to surface water, sediment and terrestrial organisms when TBBPA is used as an additive 

flame retardant in formulation (compounding) of acrylonitrile butadiene styrene (ABS). Risks for the 

terrestrial compartment were also identified at ABS conversion sites (which conduct final processing of 

semi-finished products with TBBPA as an additive flame retardant); the risks were found only when 

sewage sludge is applied to agricultural land. Risks to terrestrial organisms were also identified at sites 

where TBBPA is reacted into epoxy/polycarbonate resins. In addition, the European Union concluded 

there may be risks to organisms in the marine environment (EC, 2008). 

The EU environmental assessment indicated TBBPA may degrade to bisphenol A (BPA) in anaerobic 

sediments (EC, 2008). Formation of BPA from TBBPA was assessed in the updated risk assessment of 

BPA; after testing in snails was conducted, no risks were reported for all environmental organisms 

evaluated (United_Kingdom, 2008). 

Human Health Assessment

The human health assessment of TBBPA (EC, 2006) identified no health hazards of potential concern to 

adults. Therefore, no risk characterization was performed for workers. Also, because no health effects 

were identified for adults and because consumer exposures were found to be negligible, the European 

Union did not identify concerns for consumers. Similar conclusions were reached by the European 

Union when evaluating risks to humans via the environment (through food, air and drinking water). 

For infants, non-cancer health hazards were identified and two exposure scenarios were analyzed. One 

exposure scenario was based on the environmental scenario used for adults (described above) and the 

second scenario was based on exposure of infants via breast milk. The European Union concluded that 

risks were low and that risk reduction measures were not needed (EC, 2006). 

1.2.3.1 Canada

Pursuant to section 74 of the Canadian Environmental Protection Act, 1999, the Canadian government 

identified TBBPA and TBBPA-bis(dibromopropyl ether) in the categorization of the Domestic 

Substances List (DSL) as priorities for screening assessment because they met the criteria for 

persistence and inherent toxicity to non-human organisms. TBBPA was determined to present an 

intermediate potential for exposure of individuals in Canada.

On November 30, 2013, Canada published their final screening assessment of TBBPA and TBBPAbis(allyl ether) along with another substance, TBBPA bis(2-hydroxyethyl ether) (CASR RN 4162-45-2), 

which is not included in the EPA cluster (EC/HC, 2013)Environment and Health Canada conducted both 

environmental and human health assessments for TBBPA and TBBPA-bis(allyl ether) (EC/HC, 2013). For 

environmental organisms, Canada concluded the quantity of TBBPA and TBBPA-bis(allyl ether) that 

may be released to the environment is below the level expected to cause harm to organisms. 
Page 17 of 135

For humans, conservative estimates of exposure suggested that breast-fed infants may be exposed to 

more TBBPA than older Canadians. Yet, recent studies have shown that TBBPA was virtually 

undetected in breast milk and blood samples from pregnant women in North America. Therefore, 

Canada concluded that TBBPA is not harmful to human health at current levels of exposure. TBBPAbis(allyl ether) was also determined to not to be harmful for human health (EC/HC, 2013).
Page 18 of 135

2 PROBLEM FORMULATION 

The problem formulation stage is intended to determine the major factors to be considered in the 

assessment, including exposure pathways, receptors and health endpoints (EPA, 1998, 2014f). 

Accordingly, this problem formulation document summarizes the exposure pathways, receptors and 

health endpoints EPA/OPPT has recommended for inclusion in the risk assessment. To make this 

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

hazard data and determine its likely suitability for quantitative analysis. EPA/OPPT summarized the 

outcome of this evaluation in conceptual models that illustrate the exposure pathways, receptor 

populations and effects that will be considered in the risk assessment. EPA/OPPT also prepared an 

analysis plan to demonstrate the proposed approach to address remaining defined assessment 

questions that are possible based upon TSCA uses and best available data, tools and models.

TBBPA

Previous risk assessments identified several human health and some environmental scenarios that 

resulted in low risks for TBBPA. Some environmental scenarios evaluated in these previous 

assessments resulted in risks. Although EPA/OPPT referred to these previous risk assessments as much 

as possible to inform the current problem formulation process, there are several updates that were 

considered during the current effort that differ from the outcome of previous assessments. 

Unlike Canada and the European Union, TBBPA is manufactured in the United States. Therefore 

EPT/OPPT identified exposure near manufacturers for further evaluation. Also, a recent cancer 

bioassay has been published (NTP, 2014a) and has been used to determine which human health 

scenarios to evaluate further. Finally, new information regarding the presence of TBBPA in children’s 

products prompted EPA/OPPT to consider evaluating risks to children of certain ages as a result of 

exposure to consumer products. 

To assist in determining pathways that may be of particular concern, EPA/OPPT calculated very 

preliminary estimates by comparing high-end exposure values from existing risk assessments or recent 

published and unpublished data with provisional toxicity values. For the environmental scenarios, 

EPA/OPPT developed preliminary concentrations of concern (COCs) by applying routinely-used 

uncertainty factors (EPA, 2012d, 2013b) to results of selected ecotoxicity studies. For human health 

scenarios, EPA/OPPT calculated a provisional health-conservative toxicity value for developing uterine 

tumors using the recent carcinogenesis bioassay from the National Toxicology Program (NTP, 2014a). 

Scenarios specific to young children were also compared with a no observed adverse effect level 

(NOAEL) from a developmental toxicity study (Fukuda et al., 2004). These preliminary calculations 

allowed EPA/OPPT to understand which pathways might be of highest concern for TBBPA.
Page 19 of 135

Other Cluster Members

EPA/OPPT concluded that no quantitative risk assessment is needed for cluster members other than 

TBBPA for one or more of the following reasons: limited information, inability to use the more robust 

data for TBBPA to read across to other cluster members, low toxicity or likely low risk concerns. More 

information on these decisions and data for these chemicals are presented in Appendix A.

Appendix B presents information on literature searching and data adequacy, and Table 2-1 lists the 

type of information needed for each scenario, population and type of hazard. The literature search will 

be updated before conducting the risk assessment.

Table 2-1: Data Required for Risk Assessment

Workers General 

Population

Consumers Ecological 

Receptors

Exposure 

Scenarios

Manufacture and 

processing

Releases to the 

environment 

from 

manufacturing

Consumer 

product uses 

resulting in 

direct 

exposures or 

releases to 

indoor 

environments.

Releases to the 

environment from 

manufacturing

Exposure Measured or modeled concentrations in relevant media may be used. A 

combination of these approaches may be considered depending on the 

receptor and exposure scenario of interest

Hazard/Toxicity Hazard data, low dose extrapolation to obtain a 

cancer slope, bioavailability

Acute and chronic 

effects data

2.1 Physical and Chemical Properties

Table 2-2 identifies the physical-chemical properties for TBBPA, the only cluster member considered 

for further evaluation. Estimation program values (EPA, 2013a) for vapor pressure and water solubility 

were unrealistically low and log KOW values were unrealistically high. Therefore, estimated values are 

not reported in Table 2-2.
Page 20 of 135

Table 2-2: Physical-Chemical Properties

Chemical Name CASRN Melting

Point (°C) Boiling Point (°C)

Vapor 

Pressure

(mm Hg

@ 25°C)

Water 

Solubility 

(mg/L)

Octanol-Water 

Partition 

Coefficient 

(log KOW)

TBBPA 79-94-7 178 (a) > 200°C (a)

(decomposes)

< 1 x 10-6

(a)

4.16 

@ 25°C(b,c) 5.90 (a)

ND: no measured data

(a) EC (2006)

(b) Morf et al. (2003)

(c) Highest measured value (at neutral pH) from available literature

2.2 Production Volume and Uses

This section describes production and use information that informs EPA/OPPT’s discussions on sources, 

pathways and receptors to be evaluated for TBBPA.

2.2.1.1 Production

The 2011 national production volume of TBBPA as reported to the CDR was approximately 120 million 

pounds (EPA, 2014b)6. Production volume data for TBBPA is presented in Error! Reference source not 

found.. Production volume by company is not available in the publically available CDR because either 

no data were reported or companies filed confidential business information (CBI) claims (as noted in 

Error! Reference source not found.). There is little or no public information on the production or 

import volumes of final products treated with TBBPA-based flame retardants.

According to the Brominated Science and Environmental Forum (BSEF), TBBPA has the highest global 

production volume of all brominated flame retardants (BSEF, 2014).

2.2.1.1.1 Manufacturers

The CDR data (EPA, 2014b) identifies five companies that manufacture and/or import TBBPA: 

• Albemarle Corporation 

• ICL Industrial Products (ICL-IP) America, Inc. 

• LG Chemical America

• Sabic Innovative Plastics US, LLC 

• A company that was claimed as CBI

 6 The 2012 release of the CDR database contains domestic manufacturing volumes, import volumes, export volumes, and 

industrial and consumer use data for reporting sites during the year 2011. In addition, it reports past production volume, 

which includes domestic manufacturing volumes (including imports) for the year 2010. 
Page 21 of 135

Table 2-3: CDR Production Volume Data

Company Site

Domestic 

Manufacturing

Imported 

(lbs)

Exported 

(lbs)

Used 

on 

Site 

(lbs)a

2010 Past 

Production 

(Import/

Manufacture)

2011

National 

Production 

(lbs/yr)

Albemarle Corp South Plant

2270 Highway 79 South

Magnolia, AR 71753-9129

CBI ND CBI CBI CBI 119,837,559

ICL-IP America, Inc.

622 Emerson Road, Suite 500

St. Louis, MO 63141-6742

ND CBI CBI N/A CBI

LG Chemical America

910 Sylvan Avenue

Englewood Cliffs, NJ 07632

ND 485,159 0 N/A 454,941

Sabic Innovative Plastics US, LLC

State Route 892

Washington, WV 26181-0068

ND CBI 0 N/A CBI

CBI CBI ND 0 0 CBI

a The total volume (domestically manufactured and imported) of the chemical used at the reporting site. This number represents the 

volume of the chemical that did not leave the manufacturing site. 

CBI = Confidential business information

ND = No Data; the company did not provide the requested information.

N/A = Not Applicable; the imported chemical was never physically at the site

2.2.1.1.2 Trade Names

Albemarle Corporation and ICL-IP sell TBBPA as SAYTEX® CP-2000 and FR-1524, respectively

(Albemarle, 1999; ICL-IP, 2013b). Trade literature does not indicate the trade name of Sabic Innovative 

Plastics US, LLC’s or LG Chemical America’s TBBPA products. Additionally, although not listed in the 

2012 public CDR, company websites state that Chemtura7 sells TBBPA as BA-59P and Dover Chemical 

Corporation sells the chemical as Doverguard 59 (Dover_Chemical, 2012; ICL-IP, 2013b). Chemtura 

reported manufacturing TBBPA to the 2006 Inventory Update Rule (IUR), but Dover Chemical 

Corporation did not (EPA, 2014h). For more detailed information on manufacturers of TBBPA who 

reported for the CDR collection period that reported the 2011 production volume data, see Error! 

Reference source not found.. 

2.2.1.1.3 Import and Export 

CDR data indicate that TBBPA is imported but do not indicate whether TBBPA is exported (EPA, 2014b). 

According to the CDR, LG Chemical America imported 485,159 pounds of TBBPA in 2011, while other 

companies either did not report import and export volumes or claimed them as CBI.

 7 The division of Chemtura that produces bromine-based products (including TBBPA) is called Great Lakes Solutions 

(Chemtura, 2014).
Page 22 of 135

2.2.1.2 Uses

The CDR provides data on the industrial and consumer uses of TBBPA (EPA, 2014b). This data is 

summarized in Table 2-4.

For the purposes of the CDR, “industrial use” means use at a site where one or more chemical 

substances or mixtures are manufactured (including imported) or processed. “Consumer use” means 

the use of a chemical substance or a mixture containing a chemical substance (including as part of an 

article) when sold to or made available to consumers for their use.

2.2.1.2.1 Past Use as a Plasticizer

Additionally, TBBPA has been used as a plasticizer (NIEHS, 2002). However, this use has not been 

documented in more recent years (EC, 2006; EC/HC, 2013; EPA, 2014b, 2014h). 
Page 23 of 135

Table 2-4: Industrial and Consumer Use Data for TBBPA from the CDR

Company Site Type of 

Processing

Industrial Use Data Consumer Use Data

Sector Industrial Use

Percent of 

Production 

Volume

Consumer Use 

Product 

Category

Commercial or 

Consumer Use

Percent of 

Production 

Volume

Albemarle Corp South Plant

2270 Highway 79 South

Magnolia, AR 71753-9129

Processingincorporation into 

formulation, 

mixture or reaction 

product

Plastics Material 

and Resin 

Manufacturing

Flame 

retardants

26 Electrical and 

Electronic 

Products

Commercial 26

Not Known or 

Reasonably 

Ascertainable

Not Known or 

Reasonably 

Ascertainable

Not Known or 

Reasonably 

Ascertainable

71 Not Known or 

Reasonably 

Ascertainable

Not Known or 

Reasonably 

Ascertainable

71

ICL-IP America, Inc.

622 Emerson Road, Suite 

500

St. Louis, MO 63141-6742

Processingincorporation into 

formulation, 

mixture or reaction 

product

Computer and 

Electronic Product 

Manufacturing

Flame 

retardants

100 Electrical and 

Electronic 

Products

Both 100

LG Chemical America

910 Sylvan Avenue

Englewood Cliffs, NJ 07532

Processingincorporation into 

formulation, 

mixture or reaction 

product

Plastics Material 

and Resin 

Manufacturing

Flame 

retardants

100 Plastic and 

Rubber Products 

not covered 

elsewhere

Commercial 100

Sabic Innovative Plastics US, 

LLC

State Route 892

Washington, WV 26181-

0068

ND ND ND ND ND ND ND

CBI Processing as a 

reactant

All Other Basic 

Organic Chemical 

Manufacturing

Flame 

retardants

100 ND ND ND

ND = No Data; the company did not provide the requested information.

Source: EPA (2014b)
Page 24 of 135

2.2.1.2.2 Flame Retardant and Other Uses

TBBPA is one of the most widely used brominated flame retardants and is used as both an additive and 

reactive flame retardant (EPA, 2008a). Additive flame retardants are incorporated into polymers via 

physical mixing and are not chemically bound to the polymer. Reactive flame retardants are 

incorporated into polymers via chemical reactions at an early stage of manufacturing. Because

manufacturers can incorporate additive flame retardants into the product up until the final stages of 

manufacturing, it is usually easier for them to use additive rather than reactive flame retardants.

Reactive flame retardants have a greater effect on the chemical and physical properties of the polymer 

into which they are incorporated than do additive flame retardants (EPA, 2008a).

TBBPA has also been used as a chemical intermediate in the synthesis of other brominated flame 

retardants (NIEHS, 2002). 

As stated in Table 2-4, TBBPA’s main consumer use categories as a flame retardant are 1) electrical and 

electronic products and 2) plastic and rubber products not covered elsewhere. The category “plastic 

and rubber products not covered elsewhere” means that products are not covered under any other 

plastic or rubber product categories within the CDR. In electrical and electronic products, TBBPA is 

primarily used in printed circuit boards in the following products: telecommunications equipment, 

computers, industrial controls, remote controls, video recorders and electronics (EC, 2006; Qu et al., 

2013). TBBPA is incorporated into epoxy resins for printed circuit boards as a reactive flame retardant

at 15 to 17% by weight (EC, 2006).

Epoxy resins are also used to encapsulate electronic components (Morose, 2006). Electronic 

component encapsulates, which incorporate TBBPA at 2% by weight, are used to protect products from 

hazardous environmental conditions, such as moisture and dust. These products include plastic and 

paper capacitors, microprocessors, bipolar power transistors and other components of electrical 

equipment (EC, 2006; Morose, 2006).

With respect to TBBPA’s use in plastics and rubber products, it is likely the majority of this use is in 

electrical and electronic products. For example, a primary application of TBBPA is its use as an additive 

flame retardant in acrylonitrile butadiene styrene (ABS) resins (a type of plastic). These ABS resins are 

used in the enclosures or casings around electronics such as TV or computer monitor casings or

components in printers, fax machines, photocopiers, vacuum cleaners, coffee machines and

plugs/sockets. TBBPA is used in ABS and other plastics at 14 to 22% by weight, often in combination 

with antimony trioxide (EC, 2006). 

In addition to the CDR another dataset, which contains information on types of products that may use 

TBBPA is Washington State’s Children’s Safe Product Act (CSPA) database8. Under CSPA, 

manufacturers, importers or whole sale distributors of children’s products sold in Washington are 

required to report if their products contain a Chemical of High Concern to Children – one of which is 

TBBPA (Washington_State_DEC, 2014). As of September 6, 2014, TBBPA has been reported for use as a 

 8 https://fortress.wa.gov/ecy/cspareporting
Page 25 of 135

surface coating flame retardant in artists’ accessories9. It has also been reported to be present as 

synthetic polymer flame retardant in powered “viewing toys10”, “toy/games variety packs11” and in 

powered toy vehicles. Additionally, it is reported to be used as a flame retardant in textiles in baby 

car/booster seats; baby carriers; baby play pens/dens and baby swings. The concentrations of TBBPA in 

these products were reported as ranging from < 0.05 to > 1% (Washington State Department of 

Ecology, 2014b). It is not clear from the database whether these products were manufactured in the 

United States or imported as articles. The use of TBBPA in textiles is not reported in the publically 

available CDR. 

Non-flame retardant applications of TBBPA reported in Washington’s database of children’s products

include the chemical’s use as an adhesive in jewelry craft supplies, as a pigment in powered non-ride 

toy vehicles, as a stabilizer in clothing accessories and as a component of plastic resin or polymers in 

toys. The concentrations of TBBPA in these products were reported as ranging from < 0.01 to > 1% 

(WSDE, 2014a). 

TBBPA has also been reported as a contaminant with no function in children’s footwear, clothing, 

personal accessories, arts and crafts, baby feeding products (i.e., baby bibs, according to a single 

report) and bedding in the CSPA database. All contaminant concentrations were reported as less than 

0.05%, with about half reported as less than 0.01% (WSDE, 2014a).

SAYTEX® CP-2000 (Albemarle’s TBBPA product) is used as a reactive or additive flame retardant and is 

usually used in combination with other additives, such as antimony trioxide (Albemarle, 1999; EC, 

2006). Additionally, ICL-IP’s FR-1524 is used in epoxy, polycarbonate and phenolic resins (ICL-IP, 

2013b). 

ICL-IP’s Web site also states that TBBPA is “an important intermediate in the preparation of more 

sophisticated flame retardants” (ICL-IP, 2013b). Chemtura and Dover Chemical Corporation state that 

their TBBPA products, BA-59PTM and Doverguard 59, respectively, are intended for use in 

“thermoplastic and thermoset resin systems.” These resin systems include epoxy resins, 

polycarbonates, ABS and high impact polystyrene (Chemtura, 2013; Dover_Chemical, 2012, 2013).

 9 The product categories used by Washington State are defined by GS1 Global Product Classification Standards (WSDE, 

2013). Artists’ accessories are defined as any products that can be described/observed as an item designed to aid the 

artistic painting process (GS1, 2015). 10 Includes any products that can be described/observed as a powered educational toy designed to entertain and encourage 

learning by viewing changing scenes or patterns (GS1, 2015) 11 Includes any products that can be described/observed as two or more distinct Toys/Games products sold together which 

exist within the schema but belong to different classes, that is two or more products contained within the same pack which 

cross classes within the Toys/Games family.
Page 26 of 135

2.2.1.2.3 Regulatory Status and Future Trends Regarding Uses

No current state or federal legislation restricts the use of TBBPA (BSEF, 2013). The European Union’s 

REACH regulations require manufacturers and importers to report the properties and uses of 

substances that they manufacture or import at or above one metric ton per year, including TBBPA 

REACH does not, however, restrict the use of TBBPA or similar substances (ECHA, 2015b).

Although not a formal regulation, Underwriters Laboratories (UL) 94 is a predominant standard for the 

level of flame retardancy within products that can influence the specific flame retardant or the amount 

of a flame retardant that is used in electronic products. Compliance with the standard is not required 

nationally. However, individual companies, trade associations or local governments may choose to 

require electronic products under their jurisdiction to meet a UL 94 rating (UL_IDES, n.d.). 

2.2.1.3 Summary of Production and Use

TBBPA has the highest production volume of the brominated flame retardants. Five companies 

reported a total of 120 million pounds manufactured or imported in 2011, according to CDR data. It is 

used primarily as a reactive flame retardant, with uses as an additive flame retardant as well. Its use as 

a flame retardant is primarily for electrical or electronic products, where it may be present at levels up 

to 22%. A vast majority of printed circuit boards that meet stringent flame retardancy standards use 

TBBPA to achieve these ratings. TBBPA may also be used as an intermediate in the production of other 

flame retardants.

2.3 Fate and Transport

In air, TBBPA may undergo direct photolysis and indirect photo-oxidation, although low vapor pressure 

limits the amount of TBBPA vapor in air. In water TBBPA does not hydrolyze but may undergo 

photolysis. TBBPA is expected to have low volatility and low mobility in soil. Under anaerobic 

conditions, TBBPA may biodegrade to BPA. It may also undergo microbial O-methylation to form 

TBBPA-bis(methyl ether). Based on available data, TBBPA is considered moderately to highly persistent 

in water, soil and sediment and has a low bioaccumulation potential. Limited and uncertain data 

preclude assessment of risks from TBBPA’s degradation products as part of the proposed risk 

assessment for TBBPA. 

Appendix C includes details related to the fate and transport of TBBPA in air, water, soil and sediment 

as well as information on degradation products.
Page 27 of 135

2.4 Exposures

2.4.1 Releases to the Environment

TBBPA is a solid, is manufactured in plants in Arkansas and is then incorporated into polymer matrices 

either additively or reactively as noted in Section 2.2.1.2.2. Products in which TBBPA is used as a flame 

retardant are largely electronics; TBBPA can be used reactively in printed circuit boards and also 

incorporated into the acrylonitrile butadiene styrene (ABS) resins used in plastic housing of electronic 

products. TBBPA may be released at various stages of the life cycle: manufacture, processing, disposal, 

recycling and use. Toxics Release Inventory (TRI) data are available for manufacturers and processors. 

Information on releases is described in Appendix D.

2.4.1.1 Chemical Manufacturing

Based on North American Industry Classification System (NAICS) codes reported by facilities to TRI 

(EPA, 2012e) as well as production volume and use data reported to EPA under CDR (2011 reporting 

year) (EPA, 2014b) and IUR (2005 reporting year) (EPA, 2014h), three facilities are likely to manufacture 

all of the TBBPA that is produced domestically.

Of the years of available TRI reporting (2000 to 2012), two of these manufacturers were in operation 

from 2000 to 2011. In 2012, one of these manufacturing sites did not report TBPPA releases, and a 

different manufacturer reported emissions instead. 

According to TRI reports (EPA, 2012e), manufacturers and processors reported stack emissions to air. 

TBBPA is likely to be emitted as dust rather than vapor based on its low vapor pressure. Companies 

also released TBBPA to landfills.

2.4.1.2 Processing

Several facilities process TBBPA in the United States. The following processing sectors have reported 

TBBPA releases to TRI: chemicals, textiles, hazardous waste/solvent recovery, transportation 

equipment, plastics and rubber, paper and computers and electronic products (EPA, 2012e). For the 

years 2000-2012, processors emitted approximately 0.24 to 6.2% of the air releases reported by the 

manufacturing site with the highest release for these years (EPA, 2012e).

2.4.1.3 Recycling

EPA’s Office of Resource Conservation and Recovery (ORCR) estimated that approximately 25% of 

electronic waste (e-waste) was collected for recycling in 2009 (EPA, 2013d). After collection, electronic 

products that contain TBBPA might be reused, refurbished or recovered for their materials (EPA, 

2011a). Plastics can be recovered by chemical, mechanical or thermal processes (Kang and Schoenung, 

2005). Kang and Schoenung (2005) state that plastics recovered from electronics in the United States 

are used primarily in plastic lumber, outdoor furniture and road materials. However, it is not clear 
Page 28 of 135

whether this statement refers to plastic housing that contains flame retardants because the presence 

of additives (such as flame retardants) in plastics can act as an obstacle to recycling (Kang and 

Schoenung, 2005). 

Generally, circuit boards with epoxy resins that contain TBBPA are shredded because they cannot be 

re-melted to be used again. However, some boards are smelted as part of the recycling process to 

recover precious metals (EC, 2006; Kang and Schoenung, 2005). 

In the European Union, computer recycling companies often incinerate plastic housing from electronics 

(EC, 2006). If US recyclers operate in a similar manner, plastics that contain TBBPA may be incinerated 

with the potential for emissions. 

Products collected for recycling can also be exported. Yet estimates of such exports can range widely. 

Some estimates include 7% of the total monetary value of collected e-waste (ITC, 2013) to 50% of 

amounts generated in the western United States (BAN/SVTC, 2002). Due to these and other 

uncertainties, EPA/ORCR has not developed a method to estimate the total amount of e-waste that is 

collected in the United States and subsequently managed and processed domestically or exported 

(EPA, 2013d). 

2.4.1.4 Disposal

2.4.1.4.1 Disposal from Manufacturing, Processing and Recycling Facilities

Manufacturers dispose of TBBPA in onsite and offsite landfills. The offsite landfills were primarily RCRA 

Subtitle C hazardous waste landfills. One manufacturing facility also reported disposal of TBBPA in the 

category of “other off-site landfills” for 2002. “Other landfills” are non-hazardous waste landfills that 

may be regulated under a variety of other federal, state and local programs. Processors also reported 

disposal to RCRA Subtitle C and other landfills (EPA, 2012e). Finally, computer recycling companies 

usually landfill (or incinerate) plastic housing from electronics in the European Union (EC, 2006); these 

practices might be applicable to the United States.

2.4.1.4.2 Disposal of Consumer Products Containing TBBPA

Products that contain TBBPA can be disposed in various ways. In 2009, electronic waste (TVs, 

computers, peripherals, mice, keyboards and cell phones) totaled approximately 2.37 million short 

tons, as estimated by EPA/ORCR. The amount of this waste that contains TBBPA is unknown. This 

amount of electronic waste (also called e-waste) is about 1-2 percent of the total municipal waste 

stream (EPA, 2013d). Approximately 75% of e-waste was disposed in landfills and by other methods 

compared with 25% that was collected for recycling. 

Electronic waste after use is typically sent to landfills (EPA, 2011a). Electronic waste can also be sent to 

waste-to-energy incinerators (EPA, 2011a). Products that contain TBBPA can also be sent to municipal 

incinerators (Borgnes and Rikheim, 2004). Furthermore, ash generated from incineration can also be 

sent to landfills. 
Page 29 of 135

General household waste and landfill leachates can be sent to WWTPs, which can discharge effluents 

to water. Contaminants in the effluents can either remain in surface water or partition to sediments. 

WWTPs also generate sewage sludge, which can be processed to yield nutrient-rich organic materials 

called biosolids that can be applied to agricultural land as fertilizer (EPA, 2014j).

2.4.2 Presence in the Environment and Biomonitoring Data

Table 2-5 outlines the type of data available regarding presence in the indoor and outdoor 

environment as well as biomonitoring data available for TBBPA. Other sections in this Chapter describe

results of individual monitoring studies likely to be most representative of individual exposure 

pathways. Details regarding individual studies are described in detail in Supplemental Files 1

(Biomonitoring), 2 (Environmental and Wildlife Monitoring) and 3 (Residential Monitoring).

Table 2-5: Availability of Exposure Data for TBBPA

BIOMONITORING (HUMAN)

Blood 

Breast Milk 

Adipose Tissue 

Placenta

Urine

HUMAN EXPOSURE

Dust ingestion 

USGS NWIS DATA

Water

Suspended sediment

Solids

Biota

AIR

Ambient Air 

Indoor Air 

SOIL 

INDOOR DUST 

SEDIMENT

Freshwater 

Marine 

SLUDGE

amended soil

biosolids

landfill 

sewage 
Page 30 of 135

Table 2-5: Availability of Exposure Data for TBBPA

WATER

drinking water

groundwater

leachate 

precipitation 

surface water 

wastewater 

AIR AND WATER

deposition

BIOTA

avian 

fish 

aquatic animals (including shellfish) 

terrestrial animals 

vegetation 

 = some data available, US or international

2.4.3 Occupational Exposures

TBBPA is manufactured primarily at three plants in the United States. TBBPA is also processed at other 

sites and electronic and other consumer products can be recycled. Thus, there is a potential for 

exposure to workers in all of these sectors. 

EPA/OPPT considers inhalation of dust to be the most important TBBPA exposure pathway for workers. 

In particular, the inhalation of air-suspended dust (particulate matter) that is subsequently trapped in 

mucous and moved from the respiratory system to the gastrointestinal tract (EPA, 2011b) may 

contribute to exposures. This will be referenced in the current document as incidental ingestion of 

inhaled dust. Dermal exposure is also possible but available data indicates that absorption is limited.

Information on concentrations of TBBPA and particles not otherwise regulated within workplaces 

relevant to TBBPA is described in Appendix E.

2.4.4 General Population Exposures

The general population may be exposed to TBBPA due to its widespread detection in the indoor and 

outdoor environment. TBBPA has also been detected in several human and fish biomonitoring studies. 

The general population may be exposed to TBBPA through oral, inhalation or dermal exposure, 

although aggregate oral exposure is the focus of this assessment. Data summaries and references are 

available in Supplementary Files 1 through 3. 
Page 31 of 135

2.4.5 Consumer Exposures

TBBPA is used as a flame retardant, primarily in electronic products (such as TVs and computers). 

TBBPA has also been found in a variety of other products such as small plastic toys, jewelry and other 

children’s products as identified in recent studies (Di Napoli-Davis and Owens, 2013; Gallen et al., 

2014; Keller et al., 2014; van Bergen and Stone, 2014). 

Direct contact with products may lead to exposures depending on the conditions of use, such as 

frequency and duration of contact with the skin and subsequent hand to mouth or object to mouth 

contact. These products may also contribute to variable levels within indoor dust and air depending on 

the diversity of products present within a given building. A number of published studies have reported 

levels of TBBPA in indoor air and dust (see summaries of these studies in Supplementary File z). 

Note that although exposure from contact with consumer products is proposed for assessment in

Section 2.6, the types of exposures are primarily are not from contact of using the product directly 

(e.g., using a keyboard for a computer). Thus, they are discussed in the context of the general 

population (or of individuals living near manufacturing facilities).

2.5 Hazard Endpoints

2.5.1 Ecological Hazard

Ecotoxicity tests of aquatic and some terrestrial organisms exposed to TBBPA have evaluated a variety 

of effects including survival, immobilization, growth rate/biomass/yield, reproduction, emergence, 

growth and shell deposition. Depending on the type of organism, both acute and chronic studies are 

available. Based on results from some of these studies, TBBPA can be considered to be hazardous to 

the environment. 

In aquatic studies, a range of values and effects have been identified. The most sensitive species and 

effects from acute and chronic studies are reported here. TBBPA exposure by the marine diatom 

Skeletonema costatum resulted in a 72-hr EC50 of 0.09 mg/L, based on decreased growth (Walsh et al., 

1987). One of the lowest ecotoxicity endpoint values for a water-column species is the 96-hr EC50 of 

0.098 mg/L based on shell deposition in the Eastern oyster, a marine invertebrate species (SLS, 1989a). 

In a 70-day study using the blue mussel, a MATC of 0.023 mg/L was calculated based on growth rate 

and shell length (ACC, 2005). In fish, acute LC50 values are all at or less than 1 mg/L, with the lowest 

value reported as 0.4 mg/L in rainbow trout (GLCC, 1978b). A MATC of 0.22 mg/L was determined for 

fathead minnows in a 35-day test (SLS, 1989c). 

In sediment, several 28-day studies using worms, emergent flies or amphipods have been conducted, 

with the lowest MATC reported as 117 mg/L, based on effects on reproduction of a freshwater 

blackworm (Krueger, 2002a).

A range of terrestrial plants that include corn, cucumber, onion, ryegrass and tomato have been tested 

in 21-day studies, with the lowest MATC of 32 mg/kg dry soil (ACC-BFRIP, 2002). One 21-day and two 
Page 32 of 135

56-day studies have been conducted using terrestrial earthworms. The lowest MATC was 0.44 mg/kg 

dry weight in soil in one of the 56-day studies (ACC-BFRIP, 2005a).

Avian studies are limited, and reproductive and endocrine effects were not observed in the adult quail 

after in ovo exposure via injection of TBBPA into yolks (Berg et al., 2001; Halldin et al., 2001). In 

tadpoles, endocrine-related effects were not seen up to 500 ug/L (Garber et al., 2001) but thyroid 

hormone mediated gene expression was affected at 5.4 and 54 ug/L (Veldhoen et al., 2006). 

See Appendix F for details related to these ecotoxicological studies. 

2.5.2 Human Health Hazard

Available toxicokinetics data in rodents indicate that TBBPA is absorbed by the gastrointestinal tract, 

metabolized and excreted in the feces with limited tissue retention, with a half-life in humans of 2 

days. There is limited transfer of TBBPA to the fetus. The acute hazard concern is low via the oral, 

dermal and inhalation routes. Also, many repeated-dose, reproductive and developmental toxicity 

studies in rodents found no effects, some at doses > 1000 mg/kg-bw/day. TBBPA has tested negative in 

genotoxicity studies. Yet, there is some concern for cancer of the uterus as well as hemangiosarcomas 

and hemangiomas in all organs as observed in a cancer bioassay (NTP, 2014a). There is also a possible 

concern for developmental effects at 200 mg/kg-bw/day based on slight kidney lesions in newborn rats 

exposed to TBBPA. The lesions persisted after cessation of exposure, possibly due to immature 

metabolic capability or kidneys of these rats (Fukuda et al., 2004). Another study found very slight 

hepatocyte necrosis at 140.5 mg/kg-bw/day in offspring of female mice exposed to TBBPA during 

gestation through weaning of the offspring (Tada et al., 2006). 

Neurotoxicity and neurobehavioral effects have not been confirmed. One study found some potential 

for hearing loss when dams and newborns were dosed (Lilienthal et al., 2008) but there are questions 

about methods and uncertainty about which are the most relevant doses (e.g., both newborns and 

dams were exposed to TBBPA). An acute study resulted in some neurobehavioral effects but didn’t 

show a dose-response (Nakajima et al., 2009). No consistent neurobehavioral changes were seen in 

adolescents exposed to TBBPA (Kicinski et al., 2012). 

Appendix G presents a more detailed discussion of human health endpoints considered for the 

proposed assessment.

2.6 Results of Problem Formulation

2.6.1 Conceptual Models

During problem formulation, two conceptual models were developed to identify important sources, 

pathways, receptors and effects. See Figure 2-1 and Figure 2-2 respectively, for the proposed 

environmental and human health assessments. The scenarios that EPA/OPPT proposes to quantify for 

TBBPA are identified using solid arrows. Dotted lines are used for scenarios that cannot be evaluated 
Page 33 of 135

quantitatively due to lack of applicable or adequate data or information. Table 2-6 and Table 2-7

outline the scenarios that are being assessed and those that will not be assessed for TBBPA.
Page 34 of 135

Figure 2-1: Conceptual Model for the TBBPA Environmental Assessment

1. Chemical 

Manufacturing

Biosolids

SOURCES

Birds

EXPOSURE PATHWAYS ECOLOGICAL RECEPTORS EFFECTS

4. Disposal:

• From Above 

Sources

• Of Final Products

Water

Acute Toxicity

LEGEND 

 Solid lines = Pathway can be quantified

 Dashed lines = Pathway not significant, uncertain, or not quantifiable

 Shaded boxes/ovals = Pathway proposed for risk assessment; exposure 

and toxicity can be quantified

Fish,

Invertebrates, 

Algae

2. Processing

Toxicity

Chronic Toxicity

Soil-Dwelling 

Organisms

Dust Soil

3. Recycling

Sediment SedimentDwelling 

Organisms

Landfills

Incinerators

WWTPs
Page 35 of 135

Table 2-6: Environmental Exposure Scenarios Considered for Assessment

# Sources/Exposure Pathways Ecological 

Receptors

Included in 

Assessment?

Rationale, Limitations and Uncertainties

1 Chemical 

manufacturing Air – Particulates Birds NO Adequate toxicity data not available for avian species using inhalation as the exposure route

Soil Soil-dwelling 

organisms YES

Preliminary evaluation using data from 1977 for an Arkansas site and 

preliminary concentrations of concern from key ecotoxicity studies 

suggests there is a potential risk.

Water

Fish, 

Invertebrates, 

Algae

YES

Although physical properties limit TBBPA concentrations in surface 

water, TBBPA deposition from manufacturing facilities might be of 

concern.

Sediment

Sedimentdwelling 

organisms

YES

Preliminary evaluation using data from 1977 for an Arkansas site and 

preliminary concentrations of concern from key ecotoxicity studies 

suggests there is a potential risk

2 Processing Air – Particulates Birds

NO

Air emissions from processing plants are much smaller than those from 

manufacturing plants 

Soil Soil-dwelling 

organisms

Water

Fish, 

Invertebrates, 

Algae

Sediment

Sedimentdwelling 

organisms

3 Recycling Air – Particulates Birds NO Several factors result in significant uncertainty regarding use of existing 

data from other countries to evaluate the risks from recycling: 

• differences in environmental monitoring results among 

countries 

• Potential differences in recycling practices among countries

• unknown amount of e-waste exported from the United States; 

and 

• no current methods to assess the recycling process identified 

by EPA/ORCR

Soil Soil-dwelling 

organisms NO

Water

Fish, 

Invertebrates, 

Algae

NO

Sediment

Sedimentdwelling 

organisms

NO
Page 36 of 135

Table 2-6: Environmental Exposure Scenarios Considered for Assessment

# Sources/Exposure Pathways Ecological 

Receptors

Included in 

Assessment?

Rationale, Limitations and Uncertainties

4 Disposal Incinerators:

Air-particulates Multiple NO Limited data are available and destruction of TBBPA is likely when incinerated

WWTPs:

Biosolids and 

water

Multiple NO

Preliminary calculations using conservative assumptions regarding 

application of biosolids to agricultural land and high-end exposure 

values in water near a sewage treatment plant suggests low concerns

Landfills Multiple NO

Hazardous waste landfills (Title C): The majority of TRI releases are to 

hazardous waste landfills; controls are in place to limit exposure (e.g., 

sites are covered).

Other landfills: It is expected that only a small amount of TBBPA would 

be available and mobility in soil is limited given physical-chemical 

properties. (Note that some leachate analyses have shown TBBPA 

concentrations associated with particulate matter.)
Page 37 of 135

Figure 2-2: Conceptual Model for the TBBPA Human Health Assessment

LEGEND 

• Solid lines = Pathway can be quantified

• Dashed lines = Pathway uncertain or not quantifiable

• Shaded boxes/ovals = Pathway proposed for risk assessment; 

exposure and toxicity can be quantified 

SOURCES EXPOSURE PATHWAYS HUMAN RECEPTORS EFFECTS

Cancer

Developmental 

Toxicity 

(newborns, young 

children)

1. Chemical 

Manufacturing

3. Recycling

Consumers, 

General 

Population

Dust

Oral

Landfills

Soil, Plants,

Livestock

Surface 

Water, 

[Fish, 

Sediment]

Oral

4. Disposal:

• From Above 

Sources 

• Of Consumer 

Products

Incinerators

WWTPs

Oral

Water/

Soil

Dust

5. Use of Consumer 

Products:

• Homes

• Offices

• Daycare Facilities, 

Etc.

Workers

2. Processing 

[workers only]

Products
Page 38 of 135

Table 2-7: Human Health Exposure Scenarios Considered for Assessmenta

# Sources/Exposure Pathwaysb Human 

Receptors

Included in 

Assessment?

Rationale, Limitations and Uncertainties

1 Chemical 

manufacturing 

Dust

[unintended 

exposure from 

incidental ingestion 

of inhaled 

particles/dust]

Workers YES

Information on TBBPA and non-specific dust concentrations in air of 

manufacturing sites suggests potential concerns.

General 

population 

near facilities

YES

TRI reports that manufacturers emit TBBPA to air; there is potential 

concern for individuals who live near manufacturing facilities

Soil/plants/livestock

– dietary NO Data on plant uptake from soil are limited and no data are available for 

bioaccumulation into livestock

Surface water –

fish ingestion YES

Although physical properties limit TBBPA concentrations in surface 

water, TBBPA deposition from manufacturing facilities might be of 

concern; EPA/OPPT will estimate bioaccumulation of TBBPA into fish 

from the water column [but bioaccumulation from sediment-dwelling 

organisms to fish is not available].

2 Processing Dust

[unintended 

ingestion]

Workers YES

Information on TBBPA and non-specific dust concentrations in air of 

processing sites suggests potential concerns.

General 

population 

near facilities NO

Air emissions from processing plants are much smaller than those from 

manufacturing plants. Therefore, these emissions will not be modeled.

Soil/plants/livestock

Surface water –

Fish ingestion

3 Recycling Dust

[unintended 

ingestion]

Workers

NO

Several factors result in significant uncertainty regarding use of existing 

data from other countries to evaluate the risks from recycling: 

• differences in environmental monitoring results among 

countries 

• Potential differences in recycling practices among countries

• unknown amount of e-waste exported from the United States; 

and 

• no current methods to assess the recycling process identified 

by EPA/ORCR

General 

population 

near facilities

Soil/plants/livestock

- dietary

Surface water –

fish ingestion
Page 39 of 135

Table 2-7: Human Health Exposure Scenarios Considered for Assessmenta

# Sources/Exposure Pathwaysb Human 

Receptors

Included in 

Assessment?

Rationale, Limitations and Uncertainties

4 Disposal Incinerators:

Dust/[unintended 

ingestion]

General 

population NO

Limited data are available and destruction of TBBPA is likely when 

incinerated

WWTPs:

Water/soil

Preliminary calculations using conservative assumptions regarding highend exposure values in water near a sewage treatment plant and 

application of biosolids to agricultural land and suggests low concerns

Landfills:

Surface water –

fish ingestion

Hazardous waste landfills (Title C): The majority of TRI releases are to 

hazardous waste landfills; controls are in place to limit exposure (e.g., 

sites are covered).

Other landfills: It is expected that only a small amount of TBBPA would 

be available and mobility in soil is limited given physical-chemical 

properties. (Note that some leachate analyses have shown TBBPA 

concentrations associated with particulate matter.)

5 Consumer 

Product Use Products Children YES

Data available on TBBPA concentrations and surface loadings in 

products, including children’s products, suggests some potential for 

concern

Indoor dust

General 

population 

[adults and 

children]

YES

Preliminary calculations suggest that risks from this pathway alone are 

low, yet this pathway is included to assess aggregate exposure

a

Some pathways in this table are not being formally assessed. However, when conducting aggregate risk assessments, there may be contribution from 

one or more of these ‘unassessed’ pathways because EPA/OPPT will use data, such as TBBPA concentrations in outdoor dust levels or in fish eaten by the 

general population, that do not have identified TBBPA sources; this table simply indicates the pathways that are not being assessed as major sources of 

TBBPA exposure. 

b

Exposure pathways that depend on either inhalation of vapor or dermal uptake are not included in this table or in the conceptual models. TBBPA has a 

very low vapor pressure and therefore, exposure to vapor is negligible. Available information also suggests limited dermal uptake. c

Drinking water from different sources/pathways could contain TBBPA; however, data are not available for TBBPA in drinking water. d

Food other than fish is not assessed because it is the purview of other agencies.
Page 40 of 135

2.6.2 Analysis Plan

EPA/OPPT proposes assessing both environmental and human health risks for the scenarios outlined 

below based on available data and modeling of exposure. In the final risk assessment, EPA/OPPT will 

characterize the assumptions, limitations and uncertainties of the assessment that is generated.

Qualitative levels of confidence in the information used for the risk assessment will be discussed for 

transparency.

2.6.2.1 Environmental Assessment near Manufacturing Facilities

EPA/OPPT proposes to conduct an environmental assessment that focuses on the following key 

question:

1. Are air releases from two manufacturing facilities occurring at levels that would result in risk 

to aquatic, sediment-dwelling or soil-dwelling organisms?

During problem formulation, EPA/OPPT identified high-end concentrations of TBBPA in environmental 

media surrounding two US TBBPA manufacturing facilities (Pellizzari et al., 1978; Zweidinger, Cooper, 

Erickson, et al., 1979; Zweidinger, Cooper, and Pellizzari, 1979). EPA/OPPT also considered other data 

near brominated flame retardant manufacturers in China (Yang et al., 2012) when choosing exposure 

scenarios of concern. Although the US data are from 1977, sediment concentrations ranged from 

undetected to 330 mg TBBPA per kg sediment (Pellizzari et al., 1978; Zweidinger, Cooper, and 

Pellizzari, 1979). In soil, concentrations ranged from undetected to 150 mg/kg in 1977 (Pellizzari et al., 

1978). One very high-end surface water concentration of 4.87 μg/L was measured in a lake in China 

(Yang et al., 2012), which is located near several brominated flame retardant producers. 

From preliminary comparison of these high-end environmental concentrations with provisional COCs, 

EPA/OPPT determined that there might be current risk concerns for ecological receptors surrounding 

manufacturers of TBBPA given the likelihood that TBBPA persists in the environment.

EPA/OPPT plans to use estimated stack air release data (see Appendix D) for the two manufacturers 

that reported the highest releases over 13 years of TRI reporting (EPA, 2012e) as inputs to the 

AERMOD air deposition model (EPA, 2014i). Using facility air releases and site-specific inputs (e.g., 

meteorology, terrain), EPA/OPPT can calculate high-end estimates of the yearly TBBPA depositions 

onto water, sediment and soil for each year of TRI release data (from 2000 to 2012). 

For the environmental risk assessment, the environmental concentrations estimated from TRI releases 

can be compared with COCs to determine environmental risks for aquatic, sediment-dwelling and soildwelling organisms, expressed as risk quotients (RQs). A review of available ecological toxicity data and 

recommended COC values are presented in Appendix F.

EPA/OPPT may consider estimates from all years of TRI reporting and their associated environmental 

concentrations to estimate risks, and could accomplish this in different ways. EPA/OPPT could add
Page 41 of 135

exposures over multiple years of TRI reports, could focus on high-end exposures for a given year or 

could evaluate both. EPA/OPPT will assume no degradation of TBBPA in the proposed assessment. 

2.6.2.2 Human Health Risk Assessment

EPA/OPPT proposes to conduct human health risk assessments that focuses on the following two key 

questions:

1. Are there risks to workers from exposure to TBBPA through ingestion of suspended 

particulates/dust during manufacturing and processing activities?

As noted previously, workers may be exposed primarily by ingesting TBBPA dust from the air at work 

sites. During bagging or loading operations, dust may be generated within facilities that manufacture 

TBBPA and workers may be exposed by ingesting particles that are inhaled from the air. Also, during 

loading and unloading operations, dust may be generated within facilities that process or compound 

TBBPA. Dust generated from unloading operations is expected to be pure TBBPA. However, dust 

generated from compounding and loading operations is not expected to be pure TBBPPA. These two 

types of dust (pure vs. mixture) may have differences in bioavailability.

EPA/OPPT will evaluate risks from occupational exposure at manufacturing and processing plants.

Methods to quantify incidental ingestion of inhaled dust that consider issues such as bioavailability

must be developed. 

2. Are there risks from aggregate exposures for the general population based on ingestion of 

suspended particles/dust from outdoor air; dust ingestion from indoor environments; fish 

ingestion; and/or mouthing of objects containing TBBPA? 

Based on past TBBPA concentrations in environmental media at manufacturing facilities and more 

recent information on TBBPA emissions from manufacturers, there is potential concern for individuals 

living near such facilities. EPA/OPPT will investigate exposure for these individuals. In addition, 

EPA/OPPT will aggregate the relevant facility-specific exposures with other known exposures to TBBPA 

that focus on the oral route, including incidental ingestion of particles/dust from air. Although some of 

the additional exposures considered for aggregation are expected to be minor, EPA/OPPT is 

nonetheless interested in how such aggregation will affect risk estimates. These exposure estimates 

will be developed for adults and children as appropriate. Risks near facilities can then be compared 

with risks estimates calculated for individuals living farther away from manufacturing facilities.

Suspended particles/dust in outdoor air. As noted in Section 2.6.2.1, EPA/OPPT plans to estimate 

TBBPA air concentrations as a result of air releases at TBBPA manufacturing plants to the external 

environment. EPA/OPPT will estimate risks as incidental ingestion of inhaled dust after emissions from 

manufacturers, and EPA/OPPT will further consider methods to quantify such incidental ingestion.

There are also several studies in various countries that measured TBBPA concentrations in ambient air 

in different types of environments (e.g., rural, urban) that may represent exposures away from 

facilities (see Supplemental File 2 for studies of TBBPA concentrations in outdoor air).
Page 42 of 135

Dust from indoor environments. A wide range of studies have reported TBBPA in dust in a variety of 

indoor environments that can be ingestion directly from the air or from hand-to-mouth transfer of 

settled dust. EPA will review these studies and combine this information with age-specific activity 

patterns and exposure factors to estimate this type of exposure.

Fish ingestion. EPA/OPPT also plans to estimate exposure from fish ingestion. As described in Section 

2.6.2.1, air emissions deposited to water can be combined with estimates of TBBPA bioconcentration 

into fish and fish ingestion rates for families of recreational anglers living near the manufacturing 

facilities. There are also data available on concentrations of TBBPA in fish in various environments that 

may be appropriate to assess risks for individuals who live farther away from manufacturing facilities 

(see Supplemental File 2 for information on TBBPA concentrations in fish). More details on parameters 

that can be used for evaluation of fish ingestion are located in Appendix H.

Mouthing of products by children. Young children are likely to exhibit higher exposure than older 

children and adults due to their more prevalent object-to-mouth behavior. Therefore, EPA/OPPT will 

assess ingestion of TBBPA by children from direct contact with objects and hands that have touched 

such objects.

EPA/OPPT has found some data on both the concentrations and surface loadings of TBBPA in consumer 

products to which routine contact is possible. This information can be combined with information from 

Agency models and age-specific activity patterns and exposure factors to estimate exposure. More 

details about the proposed assessment approach are described in Appendix I.

For both key questions, the exposure estimates will be compared against relevant toxicity benchmarks. 

A cancer benchmark (uterine tumors for females; hemangiomas/hemangiosarcomas for males) 

developed using a linear low-dose model and a developmental toxicity benchmark will be used as 

appropriate for each exposure pathway (see Appendix J for the dose-response modeling of tumor data; 

and Appendix G for hazard information).

2.6.3 Sources and Pathways Excluded from Further Assessment

Several sources and pathways were excluded from further assessment for lack of data or expected low 

risks and are indicated in the conceptual models using dotted arrows.

2.6.3.1 Chemical Manufacturing

Environment. Exposure via directly inhaling TBBPA will not be assessed because no information is 

available on the toxicity of tetrabromobisphenol A to plants and other wildlife organisms (e.g., birds) 

exposed via the air. 

Human Health. EPA/OPPT is not proposing to assess the potential for dietary intake from eating crops 

and livestock around manufacturers for several reasons. Although the EU Risk Assessment (EC, 2008)

used KOW instead of measured bioconcentration or bioaccumulation factors and Koc values were used 

to determine uptake to plants and then livestock, more recent data of the uptake of TBBPA by cabbage 

and radishes from soil showed that a large amount of TBBPA was adsorbed to soil and not available for 
Page 43 of 135

transfer to plants (Li et al., 2011). Second, no data were found regarding the bioaccumulation of TBBPA 

into livestock. Third, the evaluation of exposures from food other than fish is the purview of agencies 

other than EPA. Appendix K presents details of the EU scenarios that resulted in risks to the 

environment.

2.6.3.2 Processing

The EU risk assessment for the environment found risks surrounding both acrylonitrile butadiene 

styrene (ABS) compounding sites and ABS conversion/epoxy resin manufacturing facilities from 

disposal to waste water and subsequent application to agricultural land or from air releases (EC, 2008). 

However, in the category of US plastics and rubber processors reporting to TRI, very minimal releases 

to wastewater and air were reported, with none reported as being used for treatment on agricultural 

land (EPA, 2012e). 

US processing sites in sectors other than the plastics and rubber sector have reported higher stack air 

releases to TRI (EPA, 2012e) than for the plastics/rubber sector. However, EPA/OPPT does not propose 

evaluating these releases either because they are only a small proportion of the air emissions from 

manufacturing sites.

Appendix K presents details of the EU scenarios that resulted in risks to the environment.

2.6.3.3 Recycling

Environment. TBBPA has been found in areas surrounding electronics recycling facilities in China, in 

soil, sediment and nearby waterways (Xu et al., 2012; Feng et al., 2012; He et al., 2010). In contrast, 

Schlabach et al. (2011) did not find TBBPA in sludge near car demolishing, waste recycling and 

municipal recycling/landfills in Norway. See Supplemental File 2 for details on TBBPA concentrations 

near recycling facilities.

There is significant uncertainty in evaluating the risks from recycling: consumption of TBBPA is 

expected to be higher in Asia than in the United States (He et al., 2010) whereas TBBPA was not 

detected in sediment and sludge in Norway; regulations for handling e-waste may differ between 

countries; a significant (yet unknown) amount of e-waste may be exported from the United States; and 

methods to assess other aspects of the recycling process have not been identified by EPA/ORCR. 

Because of these uncertainties, EPA/OPPT will not evaluate risks from TBBPA present in environmental 

media surrounding recycling facilities.

Human Health. Workers at recycling plants may be exposed to TBBPA particulates. Based on an 

assessment of computer and plastic recycling operations, the European Union estimated typical and 

reasonable worst case exposures as 0.02 and 4 mg/m3, respectively. The highest exposure potential 

was associated with plastic recycling (EC, 2006). Also, TBBPA concentrations were found in 

environmental media near e-waste recyclers as noted in the previous section, and these 

concentrations could affect the general population living near such facilities. 

EPA/OPPT is not planning to evaluate risks for workers or the general population given significant 

uncertainties regarding the recycling process in the United States as defined by EPA/ORCR.
Page 44 of 135

2.6.3.4 Disposal

2.6.3.4.1 Landfills

Some waste that contains TBBPA may be classified as hazardous and must be sent to RCRA Subtitle C 

hazardous waste landfills. EPA regulations at such landfills would significantly limit any exposure from 

these off-site disposals. Controls include double liners, double leachate collection and removal 

systems, a leak detection system, along with additional measures (EPA, 2013c). When non-hazardous 

waste is disposed in properly-managed municipal solid waste landfills (which also must comply with 

regulations to limit exposure), e-waste is not expected to threaten human health or the environment 

according to EPA/ORCR (EPA, 2013d). 

Furthermore, only limited leaching of TBBPA from landfills is likely because TBBPA is expected to 

adsorb to soil particles (based on its log KOC of 5.4). In their assessment, Canada noted the limited 

potential for TBBPA to reach groundwater (EC/HC, 2013). TBBPA has been measured in leachates from 

landfills in the Netherlands, Finland and Japan (de Boer et al., 2002; Osako et al., 2004; Peltola, 2002; 

Suzuki and Hasegawa, 2006). Most often TBBPA concentrations are quite low. Prior to treatment, 

however, TBBPA may be found at higher concentrations (up to 320 μg/kg dry weight), as seen in the 

Netherlands (de Boer et al., 2002); data on pre- and post-treatment suggests that concentrations could 

decrease by > 88 to 98% after treatment (Osako et al., 2004). Supplemental File 2 presents data on 

measured TBBPA levels in leachates and other environmental monitoring studies.

For the above reasons, EPA/OPPT will not evaluate risks from disposal of final products after use for 

the environment or humans.

Landfills that are no longer in operation or that are out of compliance with regulations limiting releases 

may result in the potential for exposure. However, an evaluation of these situations is beyond the 

scope of the proposed assessment.

2.6.3.4.2 Incinerators 

EPA/OPPT found only one study measured TBBPA emissions (0.008 ng/L to air) from a mixed 

household and commercial waste incinerator in Japan (Borgnes and Rikheim, 2004). Also, EC/HC 

(2013) assumed that control devices on incinerators would limit releases of TBBPA to air. Therefore, 

due to limited data and likely destruction of TBBPA during incineration, EPA/OPPT will not calculate 

risks from incineration of TBBPA-containing products for the environment or humans. 

2.6.3.4.3 Wastewater Treatment Plants (WWTPs)

Facility waste and final consumer products that contain TBBPA may be sent to WWTPs. Exposure to 

TBBPA could occur after discharge of effluents from WWTPs to water, where it could remain in surface 

water or partition to sediments or from generation of sludge that is then applied to agricultural land.
Page 45 of 135

Environment - Water. TBBPA has been found in WWTP effluents, waterbodies, sediment and sewage 

sludge/biosolids (see Supplemental File 2 for individual study data). Comparing a high-end surface 

value of 0.02 μg/L downstream from a sewage treatment plant in Germany (Kuch et al., 2001) with a 

chronic COC of 1 μg/L suggests low concern. Also, previous assessments have not identified risks from 

disposal of consumer products (EC, 2008; EC/HC, 2013).

Environment - Sludge Applied to Land. EPA/OPPT conducted a preliminary calculation to estimate 

potential TBBPA concentrations in soil after application of sewage sludge to land using conservative 

assumptions (no degradation and ten years of application) and a high-end TBBPA concentration in 

sludge (1329 μg/kg) from Spain (Guerra et al., 2010). The resulting TBBPA concentration after soil 

mixing is below the COC determined for earthworms (= 44 μg/kg), suggesting low concern. North 

American levels in sludge (Quade, 2003), although older by a few years, are all lower than Guerra et al. 

(2010).

Human Health -Water. It is possible that individuals may eat fish or obtain drinking water in areas near 

WWTPs. Data on TBBPA concentrations in fish were not located for areas specifically located near 

WWTPs.

12 Also, data on TBBPA concentrations in treated drinking water is not available. Therefore, 

EPA/OPPT will not assess these pathways in the current assessment.

However, as a preliminary exercise to determine whether there are possible concerns for people in the 

vicinity of WWPTs, EPA/OPPT used an exposure estimate from the Canadian assessment (EC/HC, 2013)

based on a high-end surface water TBBPA concentration of 0.02 μg/L from Kuch et al. (2001) obtained 

near a WWTP; the highest exposure estimate from EC/HC (2013) was 1.0 x 10-6 mg/kg-bw/day, for ages 

0.5 to 11 years. EPA/OPPT multiplied this exposure value by the most health-conservative slope factor 

from the NTP (2014a) bioassay.

13 The preliminary risk of 3.3 x 10-9 is approximately 300 times lower 

than the target risk level of 1 x 10-6.

14

Note that other surface water values in non-manufacturing areas were lower than the values in Kuch 

et al. (2001). Therefore, based on information from current published studies on TBBPA in surface 

waters, risk from TBBPA in drinking water is likely to be of low concern for non-industrial areas.

Although sewage sludge can be applied to agricultural land, risks resulting from this possible scenario 

are not being considered for lack of information on uptake from soil, as described in Section 2.6.3.1.

2.6.3.5 Other Excluded Pathways

 12 Fish ingestion for the general population not specific to this exposure pathway will be included in the risk assessment as a 

part of the aggregate risk assessment. 

13 Value is 0.00329/[mg/kg-bw/day] for development of uterine tumors 14 The age group of 0.5 to 11 years combines two ranges (0.5-4 years; 5-11 years) from EC/HC (2013) and was used because 

several years of exposure are most appropriate (e.g., roughly 1/10th of the human life span) when comparing with the 

cancer benchmark. The resulting estimated risk is calculated as 0.00329/[mg-kw/bw/day] * 0.000052 mg/kg-bw/day = 1.7 x 

10-7 and is lower than the target risk level of 1.0 x 10-6

.
Page 46 of 135

Mouthing Products with TBBPA for Adults. Although children may place products that contain TBBBPA 

in their mouths frequently, this is not considered a pathway of concern for adults, given the low 

likelihood of such behavior for this population.

Drinking Water. As noted in Section 2.6.3.4.3, intake of TBBPA from drinking water is not being 

assessed as part of the aggregate exposure estimates because data on TBBPA concentrations in treated 

drinking water are not available. Yet, a preliminary calculation of specific to WWTPs suggests this 

pathway may be of low concern.

Food. Because the presence of TBBPA in food is the purview of other agencies, it will not be evaluated 

in the proposed TBBPA risk assessment, except that the ingestion of fish by the general population will 

be used as a comparison to fish intake for individuals who live near manufacturing facilities.

2.6.4 Uncertainties and Data Gaps

2.6.4.1 Environmental Fate Data

Biodegradation data are lacking for organisms that have not already been acclimated to TBBPA. In 

addition, for biodegradation and photolysis endpoints, data on rates of transformation and identity of 

degradation products are limited.

2.6.4.2 Release Data

The TRI database is a comprehensive source of environmental release data for the United States. 

However, there are certain limitations and uncertainties when using the data for a risk assessment. 

For example, TRI information is self-reported and limited to those facilities that meet certain criteria 

(EPA, 2012e). A facility must report to TRI if it:

1. is in a specific industry; 

2. employs 10 or more full-time equivalent employees; and

3. manufactures or processes more than 25,000 pounds of a TRI-listed chemical or 

otherwise uses more than 10,000 pounds of a TRI-listed chemical in a given year.

In addition, facilities can use various methods to estimate the releases they report to TRI (EPA, 2012e). 

These methods can include continuous monitoring, periodic monitoring, and use of emission factors, 

best engineering judgment and other methods. 

Over the past 13 years, the two facilities considered for quantitative risk assessment – Great Lakes 

Chemical Solutions (with Chemtura as the parent company) and Albemarle – have used engineering 

calculations, published emission factors or site specific emission factors as a basis for reporting their air

emissions to TRI.

2.6.4.3 Exposure Information
Page 47 of 135

Several exposure parameters to be included in any modeling for TBBPA are variable and limited data 

exist. Therefore, there is uncertainty in evaluating risks for children exposed through contact with 

consumer products and subsequent ingestion of TBBPA. Furthermore, there is a lack of current 

measured TBBPA concentrations in environmental media. There is a lack of measured TBBPA 

concentrations in sediment in a variety of areas in the United States. Finally, very limited data are 

available on TBBPA concentrations in the workplaces specific to manufacture and use of TBBPA.

2.6.4.4 Ecological Hazard Data

Uncertainties and limitations of the hazard data may result from the lack of robust data for aquatic, 

sediment, terrestrial and avian species. Most importantly, exposure to TBBPA will likely occur primarily 

in sediments and soil. Yet, few acceptable sediment and soil toxicity experiments have been conducted 

on TBBPA.

Uncertainties also exist in the assessment factors typically used with toxicity values to determine 

concentrations of concern. Actual variability may differ from the values of 4 or 5 for acute studies and 

10 for chronic studies typically used by EPA/OPPT for TSCA-related activities. 

2.6.4.5 Human Health Hazard Data

NTP concluded that for hepatoblastomas in male mice, there is some evidence of carcinogenic activity 

that can be attributed to TBBPA. However, the data did not provide a good fit using the cancer 

multistage model (Hummel, 2013b), and none of the other models available in the benchmark dose 

response modeling software resulted in goodness of fit p-values at acceptable levels of > 0.1 when 

considering the full shape of the dose-response curve (Hummel, 2013a). Thus, this tumor type cannot 

be considered in a quantitative risk assessment of TBBPA.

The CARC noted that according to the IPCS MOA framework (IPCS, 2007), data are not adequate to 

draw conclusions about the mode(s) of action for the tumor incidence associated with TBBPA. 

Therefore, as recommended by EPA (2005), linear low dose extrapolation was used as the default 

option for modeling tumor data. Yet, because mode of action data are not conclusive, it is possible that 

a non-linear mode of action could explain the relationship between TBBPA and tumor incidence. 

Cancer multistage models were chosen for modeling the cancer bioassay data based on adequate fits 

for two tumor types and biological considerations even though other models also resulted in adequate 

fits of the data.

NTP (2014a) administered TBBPA to rodents via oral gavage throughout their lifetime at doses from 

250 to 1000 mg/kg-bw/day. Thus, there is uncertainty as to whether less than lifetime or even lifetime 

exposure by humans exposed to lower doses of TBBPA associated with dust particles or as other forms 

for less than a lifetime or even a full lifetime. Data are not available to determine quantitative TBBPA 

disposition for time periods longer than those evaluated in available toxicokinetics studies.

The studies evaluating reproductive and developmental toxicity show a wide variety of results from no 

effects up to very high doses to subclinical effects at low doses when using TBBPA as the test 
Page 48 of 135

substance. Thus, there is uncertainty in choosing any developmental toxicity study for evaluation in a 

quantitative risk assessment of TBBPA.

Only few inhalation and dermal studies are available and therefore, there is uncertainty as to effects 

specifically from these routes. There are also only limited studies in humans.
Page 49 of 135

References

Abbott, L., L. Altringer, A. F. Kingery, and D. A. Mayhew. 1981. Acute Dermal LD50 Toxicity Study in 

Albino Rabbits, Acute Eye Irritation Study in Albino Rabbits, Acute Oral LD50 Toxicity Study in 

Albino Rats, Primary Skin Irritation Study in Albino Rabbits with BE-51. WIL-81225. WIL Research 

Laboratories, Inc. for Great Lakes Chemical Corporation. (as cited in IPCS, 1995).

ACC-BFRIP (American Chemistry Council Brominated Flame Retardant Industry Panel). 2002. 

Tetrabromobisphenol A: A Toxicity Test to Determine the Effects of the Test Substance on 

Seedling Emergence of Six Species of Plants. Study conducted by, Wildlife International Ltd., 

(March 5, 2002). Project No 439-102 (as cited in ACC, 2006).

ACC-BFRIP (American Chemistry Council - Brominated Flame Retardants Industry Panel). 2003. Effect of 

Tetrabromobisphenol A on the Survival and Reproduction of the Earthworm, Eisenia fetida. 

Study conducted by Aufterhiede, J., T. Kendall , and W. Nixon, ABC Laboratories, Inc. and 

Wildlife International, Ltd., (February 12, 2003), Columbia, MO and Easton, MD. ABC Study No. 

47014 and Wildlife International Project No. 439C-131.

ACC-BFRIP (American Chemistry Council-Brominated Flame Retardants Industry Panel). 2005a. Effect of 

Tetrabromobisphenol A on the Reproduction of the Earthworm, Eisenia fetida. ABC Study No. 

49264/Wildlife International, Ltd. Project No. 439C-145. ABC Laboratories Inc. and Wildlife 

International, Ltd. (as cited in EC/HC, 2013).

ACC-BFRIP (American Chemistry Council - Brominated Flame Retardants Industry Panel). 2005b. 

Tetrabromobisphenol-A (TBBPA): A 28-Day Sediment Toxicity Test with Chironomus riparius 

Using Spiked Sediment. Project Number 439A-130. Easton, MD. (as cited in EC/HC, 2013).

ACC-BFRIP (American Chemistry Council - Brominated Flame Retardants Industry Panel). 2006. 

Tetrabromobisphenol-A (TBBPA): A Prolonged Sediment Toxicity Test with Hyalella azteca Using 

Spiked Sediment. Study conducted by Krueger, H., S. T. Thomas , and T. Z. Kendall, Wildlife 

International, Ltd., Easton, MD.

ACC (American Chemistry Council). 2000. Brominated Flame Retardant End-User Survey - Phase 1. 

Study conducted by Breysse, P. , and J. Kacergis, Johns Hopkins School of Hygiene and Public 

Health, (May 19, 2000), Baltimore, MD. Doc ID 84010000001.

ACC (American Chemistry Council). 2003. Tetrabromobisphenol A: A 96-Hour Flow-through Acute 

Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss). Final Report. Study conducted by 

Blankenship, A., R. Van Hoven , and H. Krueger, Wildlife International, Ltd., (July 8, 2003), 

Easton, MD. FYI-1103-01472.

ACC (American Chemistry Council). 2005. Determination of Effects on the Growth of the Common 

Mussel Mytilus edulis. Study conducted by Brown, R., D. Smyth , and S. Kent, Brixham 
Page 50 of 135

Environmental Laboratory and Wildlife International, Ltd., (April 2005), Brixham, UK and 

Arlington, VA. FYI-0705-01497.

ACC. 2006. HPV Data Summary and Test Plan for Phenol, 4,4'-Isopropylidenbis[2,6-Dibromo-

(Tetrabromobisphenol a, TBBPA). Test plan revision/updates, revised test plan. Robust 

summaries & test plans: Phenol, 4,4'-isopropylidenbis[2,6-dibromo-. 

http://www.epa.gov/chemrtk/pubs/summaries/phenolis/c13460rt3.pdf.

ACS (American Cancer Society). 2015. What Are the Key Statistics About Endometrial Cancer?

http://www.cancer.org/cancer/endometrialcancer/detailedguide/endometrial-uterine-cancerkey-statistics (accessed on March 20, 2015).

Ahlers, J., C. Riedhammer, M. Vogliano, R. Ebert, R. Kühne, and G. Schüürmann. 2008. Acute to Chronic 

Ratios in Aquatic Toxicity – Variation across Trophic Levels and Relationship with Chemical 

Structure. Environmental Toxicology and Chemistry, 25(11), 2937-2945.

Albemarle. 1999. Saytex® Cp-2000 Flame Retardant. Baton Rouge, Louisiana. 

http://albemarle.com/Products-and-Markets/Polymer-Solutions/Fire-Safety-Solutions/SAYTEXCP-2000-169C183.html (accessed on October 24, 2013).

Alison, R. H., C. C. Capen, and D. E. Prentice. 1994. Neoplastic Lesions of Questionable Significance to 

Humans. Toxicologic Pathology, 22(2), 179-186.

Allard, A. S., M. Remberger, and A. H. Neilson. 1987. Bacterial O-Methylation of Halogen-Substituted 

Phenols. Applied and Environmental Microbiology, 53(4), 839-845.

Arbeli, Z., and Z. Ronen. 2003. Enrichment of a Microbial Culture Capable of Reductive Debromination 

of the Flame Retardant Tetrabromobisphenol a, and Identification of the Intermediate 

Metabolites Produced in the Process. Biodegradation, 14(6), 385-395.

Babich, M. 2014. Report to the US CPSC: Appendix E2 - Children's Oral Exposure to Phthalate 

Alternatives from Mouthing Soft Plastic Children's Articles. Chronic Hazard Advisory Panel on 

Phthalates and Phthalate Alternatives, Bethesda, MD.

Balch, G. C., and C. D. Metcalfe. 2001. In Vivo Toxicity Testing of PBDEs Using Early Life Stages of the 

Japanese Medaka and the Xenopus Tail Resorption Model. 3rd Annual Workshop on 

Brominated Flame Retardants in the Environment. Canada Centre for Inland Waters, August 23-

24, pp. 59-60. (as cited in EC, 2006 and ACC, 2006).

BAN/SVTC (The Basel Action Network and Silicon Valley Toxics Coalition). 2002. Exporting Harm: The 

High-Tech Trashing of Asia. (as cited in Kang and Schoenung, 2005).

Banasik, M., M. Hardy, R. D. Harbison, C. H. Hsu, and T. Stedeford. 2009. Letter to the Editor: 

Tetrabromobisphenol A and Model-Derived Risks for Reproductive Toxicity. Toxicology, 260,

150-152.
Page 51 of 135

Bansal, N., V. Yendluri, and R. M. Wenham. 2009. The Molecular Biology of Endometrial Cancers and 

Their Implications for Pathogenesis, Classification, and Targeted Therapies. Cancer Control, 16, 

8-13.

Berg, C., K. Halldin, and B. Brunstrom. 2001. Effects of Bisphenol a and Tetrabromobisphenol a on Sex 

Organ Development in Quail and Chicken Embryos. Environmental Toxicology and Chemistry, 

20(12), 2836-2840.

Blagosklonny, M. V. 2000. p53 from Complexity to Simplicity: Mutant p53 Stabilization, Gain-ofFunction, and Dominant-Negative Effect. The FASEB Journal, 14, 1901-1907.

Borgnes, D., and B. Rikheim. 2004. Decomposition of BFRs and Emission of Dioxins from Co-Incineration 

of MSW and Electrical and Electronic Plastics Waste. Organohalogen Compounds, 66, 890-898.

Brown, D. D., Z. Wang, J. D. Furlow, A. Kanamori, R. A. Schawartzman, B. F. FRemo, and A. Pinder. 1996. 

The Thyroid Hormone-Induced Tail Resorption Program During Xenopus laevis Metamorphosis. 

Developmental Biology, 93, 1924-1929.

Brusick, D. 1977. Mutagenicity Evaluation of Compound 279-117-2: Final Report. Litton Biometrics, Inc. 

to Great Lakes Chemical Corporation. (as cited in IPCS, 1995).

BSEF (Bromine Science Environmental Forum). 2013. TBBPA Factsheet: Tetrabromobisphenol A for 

Printed Circuit Boards and ABS Plastics. Brussels, Belgium.

BSEF (Bromine Science and Environmental Forum). 2014. About Tetrabromobisphenol A (TBBPA). 

Brussels, Belgium. http://www.bsef.com/about-tbbpa/ (accessed on May 19, 2014).

CalEPA (California Environmental Protection Agency). 2013. Safer Consumer Product Regulations -

Informational "Initial" List of Candidate Chemicals and Chemical Groups, October 18, 2013. 

California Department of Toxic Substances Control, Sacramento, California. 

https://dtsc.ca.gov/SCP/upload/Informational_Initial_Candidate-Chemicals-List_10-18-13.pdf 

(accessed on June 19, 2014).

California_Biomonitoring (California Contaminant Biomonitoring Program). 2013. Priority Chemicals, 

May 2013. California Department of Public Health, Department of Toxic Substances Control, 

and Office of Environmental Health Hazard Assessment, Sacramento, California. 

http://www.biomonitoring.ca.gov/chemicals/priority-chemicals (accessed on June 19, 2014).

California_Biomonitoring (California Contaminant Biomonitoring Program). 2014a. Designated 

Chemicals, February 2014. California Department of Public Health, Department of Toxic 

Substances Control, and Office of Environmental Health Hazard Assessment, Sacramento, 

California. http://www.biomonitoring.ca.gov/chemicals/designated-chemicals (accessed on 

June 19, 2014).
Page 52 of 135

California_Biomonitoring (California Contaminant Biomonitoring Program). 2014b. Designated 

Chemicals, October 2014. California Department of Public Health, Department of Toxic 

Substances Control, and Office of Environmental Health Hazard Assessment, Sacramento, CA. 

http://www.biomonitoring.ca.gov/sites/default/files/downloads/DesignatedChemicalList_Octo

ber2014.pdf (accessed on March 16, 2015).

California_Biomonitoring (California Contaminant Biomonitoring Program). 2014c. Priority Chemicals, 

June 2014. California Department of Public Health, Department of Toxic Substances Control, 

and Office of Environmental Health Hazard Assessment, Sacramento, CA. 

http://biomonitoring.ca.gov/sites/default/files/downloads/PriorityChemicalsList_June2014.pdf

(accessed March 16, 2015).

Canton, R. F., J. T. Sanderson, S. Nijmeijer, A. Bergman, R. J. Letcher, and M. van den Berg. 2006. In 

Vitro Effects of Brominated Flame Retardants and Metabolites on CYP17 Catalytic Activity: A 

Novel Mechanism of Action? Toxicology and Applied Pharmacology, 216, 274-281.

CARC (Cancer Assessment Review Committee). Cancer Assessment Document: Evaluation of the 

Carcinogenic Potential of Tetrabromobisphenol A (TBBPA). memorandum to Lai, D. (Office of 

Pollution Prevention and Toxics, US Environmental Protection Agency), September 17, 2014.

Chemtura. 2013. Flame Retardants - Products - BA-59PTM. Great Lakes Solutions, West Lafayette, 

Indiana. http://www.greatlakes.com/Flame_Retardants/Products/BA-59P (accessed on October 

24, 2013).

Chemtura. 2014. About Chemtura. 

http://www.chemtura.com/corporatev2/v/index.jsp?vgnextoid=6a6238f220d6d210VgnVCM10

00000753810aRCRD&vgnextchannel=6a6238f220d6d210VgnVCM1000000753810aRCRD&vgne

xtfmt=default (accessed on May 19, 2014).

Chen, J. Q., T. R. Brown, and J. D. Yager. 2008. Mechanisms of Hormone Carcinogenesis: Evolution of 

Views, Role of Mitochondria. Advances in Experimental Medicine and Biology, 630, 1-18.

Chen, S.-J., Y.-J. Ma, J. Wang, D. Chen, X.-J. Luo, and B.-X. Mi. 2009. Brominated Flame Retardants in 

Children's Toys: Concentration, Composition and Children's Exposure and Risk Assessment. 

Environmental Science and Technology, 43(11), 4200-4206.

Chow, W. S., W. K. L. Chan, and K. M. Chan. 2013. Toxicity Assessment and Vitellogenin Expression in 

Zebrafish (Danio rerio) Embryos and Larvae Acutely Exposed to Bisphenol a, Endosulfan, 

Heptachlor, Methoxychlor and Tetrabromobisphenol A. Journal of Applied Toxicology, 33(7), 

670-678.

Conova, S. 2003. Estrogen's Role in Cancer. In Vivo, 2(10), 

http://www.cumc.columbia.edu/publications/in-vivo/Vol2_Iss10_may26_03/.
Page 53 of 135

de Boer, J., C. Allchin, B. Zegers, J. P. Boon, S. H. Brandsma, S. Morris, A. W. Kruijt, I. van der Veen, J. M. 

van Hesselingen, and J. J. H. Haftka. 2002. HBCD and TBBPA in Sewage Sludge, Sediments and 

Biota, Including Interlaboratory Study. RIVO report number CO33/02. RIVO - the Netherlands 

Institute for Fisheries Research, Ymuiden and Yerseke, Netherlands.

de Winter-Sorkina, R., M. I. Bakker, G. van Donkersgoed, and J. D. van Klaveren (RIVM – Netherlands 

Institute of Public Health and the Environment). 2003. Dietary Intake of Brominated Flame 

Retardants by the Dutch Population.

Di Napoli-Davis, G., and J. E. Owens. 2013. Quantitation of Tetrabromobisphenol-a from Dust Sampled 

on Consumer Electronics by Dispersed Liquid-Liquid Microextraction. Environmental Pollution, 

180, 274-280.

Dover_Chemical. 2012. Doverguard 59: Tetrabromobisphenol A. Dover, Ohio. 

http://www.doverchem.com/Portals/0/DG59.pdf (accessed on October 24, 2013).

Dover_Chemical. 2013. Doverguard® Brominated Flame Retardants. Dover, Ohio. 

http://www.doverchem.com/Products/DoverguardBrominatedFlameRetardants.aspx (accessed 

on October 24, 2013).

Dow_Chemical. 1975. Results of a 90-Day Toxicological Study in Rats Given Tetrabromobishphenol a in 

the Diet. Study conducted by Quast, J. F., C. G. Humiston , and B. A. Schwetz, Toxicology 

Research Laboratory, Health and Environmental Research, The Dow Chemical Company, (July 

11, 1975), Midland, MI. OTS#0206824. Doc ID 878216066.

Driffield, M., N. Harmer, E. Bradley, A. R. Fernandes, M. Rose, D. Mortimer, and P. Dicks. 2008. 

Determination of Brominated Flame Retardants in Food by LC-MS/MS: Diastereoisomer-Specific 

Hexabromocyclododecane and Tetrabromobisphenol A. Food Additives and Contaminants. Part 

A: Chemistry, Analysis, Control, Exposure and Risk Assessment, 25(7), 895-903.

EC (European Commission). 2000. Iuclid Dataset: Existing Chemical Substance Id 79-94-7. European 

Chemicals Bureau, Joint Research Centre, Institute for Health and Consumer Protection, 

European Chemical Substances Information System. 

http://esis.jrc.ec.europa.eu/index.php?PGM=hpv.

EC (European Commission). 2006. European Union Risk Assessment Report for 2,2’,6,6’-Tetrabromo4,4’-Isopropylidenediphenol (Tetrabromobispheonl-a or TBBP-A) Part II – Human Health, CAS 

No. 79-94-7, EINECS No. 201-236-9. 4th Priority List, Volume: 63, EUR22161 EN. Institute for 

Health and Consumer Protection, Joint Research Centre, Luxembourg. 

http://esis.jrc.ec.europa.eu/doc/risk_assessment/REPORT/tbbpaHHreport402.pdf.

EC (European Commission). 2008. Risk Assessment of 2,2',6,6-Tetrabromo-4,4'-Isopropylidene Diphenol 

(Tetrabromobisphenol-A): CAS Number: 79-94-7; EINECS Number: 201-236-9; Final 

Environmental Rar of February 2008. R402_0802_env. Rapporteur: United Kingdom. 

http://echa.europa.eu/documents/10162/17c7379e-f47b-4a76-aa43-060da5830c07.
Page 54 of 135

EC/HC (Environment and Health Canada). 2013. Screening Assessment Report: Phenol, 4,4'-(1-

Methylethylidene)Bis[2,6-Dibromo- (CASRN 79-94-7); Ethanol, 2,2'-[(1-

Methylethylidene)Bis[(2,6-Dibromo-4,1-Phenylene)Oxy]]Bis (CASRN 4162-45-2); Benzene, 1,1'-

(1-Methylethylidene)Bis[3,5-Dibromo-4-(2-Propenyloxy)- (CASRN 25327-89-3). Government of 

Canada. http://www.ec.gc.ca/ese-ees/default.asp?lang=En&n=BEE093E4-1.

ECHA (European Chemicals Agency). 2013. Registered Substances - Search Page. European 

Commission, Helsinki, Finland. http://echa.europa.eu/information-on-chemicals/registeredsubstances (accessed on November 4, 2013).

ECHA (European Chemicals Agency). 2014. Pre-Registered Substances - Search Page. European 

Commission, Helsinki, Finland. http://echa.europa.eu/information-on-chemicals/preregistered-substances (accessed on June 19, 2014).

ECHA (European Chemicals Agency). 2015a. Substance Evaluation. Agency of the European Union, 

Helsinki, Finland. http://echa.europa.eu/regulations/reach/evaluation/substance-evaluation

(accessed on Februrary 10, 2015).

ECHA (European Chemicals Agency). 2015b. Understanding Reach. Agency of the European Union, 

Helsinki, Finland. http://echa.europa.eu/web/guest/regulations/reach/understanding-reach

(accessed on February 5, 2015).

EFSA. 2011. Scientific Opinion on Tetrabromobisphenol A (TBBPA) and Its Derivatives in Food. EFSA 

Journal, 9(12), 2477 +.

EPA (US Environmental Protection Agency). 1998. Guidelines for Ecological Risk Assessment. 

EPA/630/R-95/002F. Risk Assessment Forum, Washington, DC. http://www.epa.gov/raf.

EPA (US Environmental Protection Agency). 1999a. Category for Persistent, Bioaccumulative, and Toxic 

New Chemical Substances. 64 US Government Printing Office, Washington, DC 213 (November 

4, 1999), pp. 60194-60204.

EPA (US Environmental Protection Agency). 1999b. Determining the Adequacy of Existing Data - Draft. 

Office of Pollution Prevention and Toxics, Washington, DC. 

http://www.epa.gov/hpv/pubs/general/datadfin.htm.

EPA (US Environmental Protection Agency). 2005. Guidelines for Carcinogen Risk Assessment. 

EPA/630/P-03/001F. Risk Assessment Forum, Washington, DC. 

http://epa.gov/cancerguidelines/.

EPA (US Environmental Protection Agency). 2008a. Partnership to Evaluate Flame Retardants in Printed 

Circuit Boards: Draft Report. Design for the Environment, Office of Pollution Prevention and 

Toxics, Washington, DC. 
Page 55 of 135

http://www.epa.gov/dfe/pubs/projects/pcb/full_report_pcb_flame_retardants_report_draft_1

1_10_08_to_e.pdf.

EPA (US Environmental Protection Agency). 2008b. Stochastic Human Exposure and Dose Simulation 

Model for Multimedia, Multipathway Chemicals: SHEDS-Multimedia Model Version 3 Technical 

Manual. 600/R-08/118. Office of Research and Development, USEPA and with help from Alion 

Science and Technology, Inc., Washington, DC.

EPA (US Environmental Protection Agency). 2011a. Electronics Waste Management in the United States 

through 2009. EPA 530-R-11-002. Office of Resource Conservation and Recovery, Washington, 

D. C. . http://www.epa.gov/osw/conserve/materials/ecycling/docs/fullbaselinereport2011.pdf.

EPA (US Environmental Protection Agency). 2011b. Exposure Factors Handbook. EPA/600/R-09/052F. 

National Center for Environmental Assessmet, Office of Research and Development, 

Washington, DC. http://www.epa.gov/ncea/efh/pdfs/efh-complete.pdf.

EPA (US Environmental Protection Agency). 2011c. Integrated Risk Information System (IRIS) Glossary. 

National Center for Environmental Assessment, Office of Research and Development, 

Washington, DC. 

http://ofmpub.epa.gov/sor_internet/registry/termreg/searchandretrieve/glossariesandkeywor

dlists/search.do?details=&glossaryName=IRIS%20Glossary (accessed on September 24, 2014).

EPA (US Environmental Protection Agency). 2012a. Benchmark Dose Technical Guidance. EPA/100/R12/001. Risk Assessment Forum, Washington, DC. 

http://www.epa.gov/raf/publications/pdfs/benchmark_dose_guidance.pdf.

EPA (US Environmental Protection Agency). 2012b. Estimation Programs Interface SuiteTM for 

Microsoft® Windows, V 4.11. Washington, DC. 

http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.

EPA (US Environmental Protection Agency). 2012c. Standard Operating Procedures for Residential 

Pesticide Exposure Assessment. Health Effects Division, Office of Pesticide Programs, Office of 

Chemical Safety and Pollution Prevention, Washington, DC. 

http://www.epa.gov/opp00001/science/USEPA-OPP-HED_Residential%20SOPs_Oct2012.pdf.

EPA (US Environmental Protection Agency). 2012d. Sustainable Futures and P2 Framework Manual. 

EPA/748/B-12/001. Office of Chemical Safety and Pollution Prevention, Washington, DC. 

http://www.epa.gov/oppt/sf/pubs/sf-p2-manual.html.

EPA (US Environmental Protection Agency). 2012e. Toxics Release Inventory (TRI) Program. 

Washington, DC. http://www.epa.gov/tri/index.htm (accessed on June 9 and 19, 2014).

EPA (US Environmental Protection Agency). 2013a. Estimation Programs Interface SuiteTM for 

Microsoft® Windows, V4.10. Washington, DC. 
Page 56 of 135

http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm (accessed on September 18, 

2013).

EPA (US Environmental Protection Agency). 2013b. Interpretive Assistance Document for Assessment of 

Discrete Organic Chemicals - Sustainable Futures Summary Assessment. Washington, DC. 

http://www.epa.gov/oppt/sf/pubs/iad_discretes_june2013.pdf.

EPA (US Environmental Protection Agency). 2013c. Wastes - Hazardous Waste - Treatment and 

Disposal: Hazardous Waste Land Disposal Units (LDUs). Office of Resource Conservation and 

Recovery, Washington, DC. http://www.epa.gov/epawaste/hazard/tsd/td/index.htm (accessed 

on November 22, 2013).

EPA (US Environmental Protection Agency). 2013d. Wastes - Resource Conservation - Common Wastes 

and Materials - Ecycling: Frequent Questions. Office of Resource Conservation and Recovery, 

Washington, DC. http://www.epa.gov/epawaste/conserve/materials/ecycling/faq.htm

(accessed on November 25, 2013).

EPA (US Environmental Protection Agency). 2014a. An Alternatives Assessment for the Flame Retardant 

Decabromodiphenyl Ether (Decabde): Final Report. Design for the Environment, Office of 

Pollution Prevention and Toxics, Washington, DC. 

http://www.epa.gov/oppt/dfe/pubs/projects/decaBDE/deca-report-complete.pdf.

EPA (US Environmental Protection Agency). 2014b. Chemical Data Reporting. Office of Pollution 

Prevention and Toxics, Washington, DC. http://www.epa.gov/oppt/cdr/ (accessed on June 19, 

2014).

EPA (US Environmental Protection Agency). 2014c. ECOTOX Database. Mid-Continent Ecology Division, 

Duluth, MN. http://cfpub.epa.gov/ecotox/.

EPA (US Environmental Protection Agency). 2014d. Estimated Fish Consumption Rates for the U.S. 

Population and Selected Subpopulations (NHANES 2003-2010). EPA-820-R-14-002. Washington, 

DC. http://water.epa.gov/scitech/swguidance/fishshellfish/fishadvisories/upload/EstimatedFish-Consumption-Rates-for-the-U-S-Population-and-Selected-Subpopulations-NHANES-2003-

2010.pdf.

EPA (US Environmental Protection Agency). 2014e. Flame Retardants in Printed Circuit Boards: 

Updated Draft Report. Design for the Environment, Washington, DC. 

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

EPA (US Environmental Protection Agency). 2014f. Framework for Human Health Risk Assessment to 

Inform Decision Making. EPA/100/R-14/001. Office of the Science Advisor, Risk Assessment 

Forum, Washington, DC. http://www.epa.gov/raf.

EPA (US Environmental Protection Agency). 2014g. Harmonized Test Guidelines. Office of Chemical 

Safety and Pollution Prevention. http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm.
Page 57 of 135

EPA (US Environmental Protection Agency). 2014h. Non-Confidential 2006 IUR Company/Chemical 

Records. Office of Pollution Prevention and Toxics, Washington, DC. 

http://cfpub.epa.gov/iursearch/ (June 20, 2014).

EPA (US Environmental Protection Agency). 2014i. Technology Transfer Network - Support Center for 

Regulatory Atomospheric Modeling: Preferred/Recommended Models. Office of Air and 

Radiation, Office of Air Quality Planning and Standards, Research Triangle Park, NC. 

http://www.epa.gov/scram001/dispersion_prefrec.htm (accessed on February 11, 2015).

EPA (US Environmental Protection Agency). 2014j. Water: Sewage Sludge (Biosolids). Office of Water, 

Washington, DC. http://water.epa.gov/polwaste/wastewater/treatment/biosolids/ (October 

14, 2014).

EPA (US Environmental Protection Agency). 2015. Substance Registry Services. Washington, DC. 

http://ofmpub.epa.gov/sor_internet/registry/substreg/home/overview/home.do (accessed on 

March 9, 2015).

Eriksson, J., S. Rahm, N. Green, A. Bergman, and E. Jakobsson. 2004. Photochemical Transformations of 

Tetrabromobisphenol a and Related Phenols in Water. Chemosphere, 54, 117-126.

Eriksson, P., E. Jakobsson, and A. Frederiksson. 2001. Brominated Flame Retardants: A Novel Class of 

Developmental Neurotoxicants in Our Environment? Environmental Health Perspectives, 109, 

903-908.

Eriksson, P., E. Jakobsson, and A. Fredriksson. 1998. Developmental Neurotoxicity of Brominated Flame 

Retardants, Polybrominated Diphenyl Ethers, and Tetrabromobisphenol A. Organohalogen 

Compounds, 35, 375-377.

Fackler, P. 1989. Tetrabromobisphenol A. Determination of Biodegradability in a Sediment/Water 

Microbial System. SLS Report 89-8-3070. Springborn Life Sciences, Inc., Wareham, MA. 

http://www.epa.gov/chemrtk/pubs/summaries/phenolis/c13460rr3.pdf. (as cited in ACC, 

2006).

FSAI (Food Safety Authority of Ireland). 2010. Investigation into Levels of Chlorinated and Brominated 

Organic Pollutants in Carcass Fat, Offal, Eggs and Milk Produced in Ireland, Monitoring and 

Surveillance Series. http://www.fsai.ie/searchresults.html?searchString=offal%20chlorinated%20brominated.

Fukuda, N., Y. Ito, M. Yamaguchi, K. Mitumori, M. Koizumi, R. Hasegawa, E. Kamata, and M. Ema. 2004. 

Unexpected Nephrotoxicity Induced by Tetrabromobisphenol a in Newborn Rats. Toxicology 

Letters, 150, 145-155.

Gallen, C., A. Banks, S. H. Brandsma, C. Baduel, P. Thai, G. Eaglesham, A. Heffernan, P. Leonards, P. 

Bainton, and J. F. Mueller. 2014. Towards Development of a Rapid and Effective Non-Destructive 
Page 58 of 135

Testing Strategy to Identify Brominated Flame Retardants in the Plastics of Consumer Products. 

Science of the Total Environment, 491-492, 255-265.

Garber, E. A. E., G. L. Larsen, H. Hakk, and A. Bergman. 2001. Frog Embryo Teratogenic Assay: Xenopus 

(FETAX) Analysis of the Biological Activity of Tetrabromobisphenol a (TBBPA). Poster 

presentation at Second International Workshop on Brominated Flame

Retardants, May 14-16, Stockholm University, Sweden.

George, K. W., and M. M. Haggblom. 2008. Microbial O-Methylation of the Flame Retardant 

Tetrabromobisphenol-A. Environmental Science and Technology, 42(15), 5555-5561.

GLCC (Great Lakes Chemical Corporation). 1967. Acute Inhalation Toxicity Study of 

Tetrabromobisphenol A to Rats. Sponsored by the Brominated Flame Retardants Industry Panel 

(Unpublished), St. Louis, MO. (as cited in EC/HC, 2013).

GLCC (Great Lakes Chemical Corporation). 1978a. The Acute Toxicity of FMBP4A (Tetrabromobisphenol 

a) to the Bluegill Sunfish, Lepomis macrochirus Rafinesque. Study conducted by Calmbacher, C. 

W., A. G. Vilkas , and C. Hutchinson, Union Carbide Environmental Services, prepared for 

Velsicol Chemical Corporation, Tarrytown, NY. OTS# 0206828. Doc ID 878216107.

GLCC (Great Lakes Chemical Corporation). 1978b. The Acute Toxicity of FMBP4A (Tetrabromobisphenol 

a) to the Rainbow Trout, Salmo gairdneri Richardson. Study conducted by Calmbacher, C. W., A. 

G. Vilkas , and C. Hutchinson, Union Carbide Environmental Services, prepared for Velsicol 

Chemical Corporation, (March 30, 1978), Chicago, IL. OTS0206828. Doc ID 878216108.

GLCC (Great Lakes Chemical Corporation). 1978c. Acute Toxicity of FMBP4A (Tetrabromobisphenol a) to 

the Water Flea Daphnia magna Straus. Study conducted by Morrissey, A. E., A. G. Vilkas , and C. 

Hutchinson, Union Carbide Environmental Services, prepared for Velsicol Chemical Corporation, 

(May 8, 1978), Tarrytown, NY. OTS# 0206828. Doc ID 878216112.

GLCC (Great Lakes Chemical Corporation). 1982. Ames/Salmonella Plate Assay Report on Bis(2,3-

Dibromopropyl)Ether of Tetrabromobisphenol a with Attachments. Study conducted by. 

0503680. 8888200436.

GLCC (Great Lakes Chemical Corporation). 1988a. Acute Toxicity of Tetrabromobisphenol a to Fathead 

Minnow (Pimephales promelas) under Flow-through Conditions. Study conducted by, Springorn 

Life Sciences, (November 16, 1988), Wareham, MA. OTS# 0525512. Doc ID 40-8898095.

GLCC (Great Lakes Chemical Corporation). 1988b. Toxicity of Tetrabromobisphenol a to the Freshwater 

Green Alga Selenastrum capricornutum. Study conducted by, Springborn Life Sciences, Inc., 

(November 16, 1988), Wareham, MA. OTS# 0525512. Doc ID 40-8898095.

GLCC (Great Lakes Chemical Corporation). 1989a. Bioconcentration and Elimination of 14C-Residues by 

Fathead Minnows (Pimephales promelas) Exposed to Tetrabromobisphenol-A. Report No. 89-3-

2952. Springborn Life Sciences, Inc., Wareham, MA.
Page 59 of 135

GLCC (Great Lakes Chemical Corporation). 1989b. Bioconcentration and Elimination of C-Residues by 

Eastern Oysters (Crassostrea virginica) Exposed to Tetrabromobisphenol a (Final Report) with 

Attached Studies and Cover Letter 081889. Study conducted by Fackler, P. H. , and P. D. Royal, 

Springborn Life Sciences, Inc., (August 16, 1989), Wareham, MA. OTS# 0525518. Doc ID 40-

8998118.

GLCC (Great Lakes Chemical Corporation). 1989c. Determination of the Biodegradability of 

Tetrabromobisphenol A in Soil under Aerobic Conditions. Final Report. Study conducted by, 

Springborn Life Sciences, Inc., (January 20, 1989), Wareham, MA. OTS# 0525513. Doc ID 42083 

G3-2.

GLCC (Great Lakes Chemical Corporation). 1989d. Determination of the Biodegradability of 

Tetrabromobisphenol A in Soil under Anaerobic Conditions (Final Report) with Attachments and 

Cover Letter Dated 013189. Study conducted by, Springborn Life Sciences, Inc., (January 19, 

1989), Wareham, MA. OTS# 0525513. Doc ID 42083 G3-2.

GLCC (Great Lakes Chemical Corporation). 1989e. The Subchronic Toxicity of Sediment-Sorbed 

Tetrabromobisphenol a to Chironomus tentans under Flow-through Conditions (Final Report) 

with Cover Sheet and Letter Dated 101689. Study conducted by Breteler, R. J., J. R. Hoberg, N. 

Garvey, S. R. Connor, D. A. Hartley, S. P. Shepherd, P. H. Fackler , and P. D. Royal, Springborn 

Laboratories, Inc., Wareham, MA. OTS# 0525507. Doc ID 40-8998109.

Goodman, L., G. Cripe, P. Moody, and D. Halsell. 1988. Acute Toxicity of Malathion, 

Tetrabromobisphenol a and Tributyltin Chloride to Mysids (Mysidopses bahia) of Three Ages. 

Bulletin of Environmental Contamination and Toxicology, 41, 746-753.

Gorman, N. 2012. The Relationship between Inadvertent Ingestion and Dermal Expousre Pathways: A 

New Integrated Conceptual Model and a Database of Dermal and Oral Transfer Efficiences. 

Annals of Occupational Hygiene, 56(9), 1000-1012.

Gosavi, R. A., G. A. Knudsen, L. S. Birnbaum, and L. C. Pedersen. 2013. Mimicking of Estradiol Binding by 

Flame Retardants and Their Metabolites: A Crystallographic Analysis. Environmental Health 

Perspectives, 121(10), 1194-1199.

GS1. 2015. GPC Browser. http://www.gs1.org/1/productssolutions/gdsn/gpc/browser/ (accessed on 

March 9, 2015).

Guerra, P., E. Eljarrat, and D. Barcelo. 2010. Simultaneous Determination of Hexabromocyclododecane, 

Tetrabromobisphenol a, and Related Compounds in Sewage Sludge and Sediment Samples from 

Ebro River Basin (Spain). Analytical and Bioanalytical Chemistry, 397, 2817-2824.

Gustafsson, K., and M. Wallen. 1988. Status Report on Tetrabromobisphenol A (CAS No. 79-94-7) -

Unpublished Report. Clearing House Sweden, National Chemicals Inspectorate, Solna, Sweden. 

(as cited in EC/HC, 2013).
Page 60 of 135

Hagmar, L., A. Sjodin, P. Hoglund, K. Thuresson, L. Rylander, and A. Bergman. 2000. Biological Half-Lives 

of Polybrominated Diphenyl Ethers and Tetrabromobisphenol a in Exposed Workers. 

Organohalogen Compounds, 47, 198-201.

Hakk, H., G. Larsen, A. Bergman, and U. Orn. 2000. Metabolism, Excretion, and Distribution of the 

Flame Retardant Tetrabromobisphenol-a in Conventional and Bile-Duct Cannulated Rats. 

Xenobiotica, 30(9), 881-890.

Halldin, K., C. Berg, A. Bergman, I. Brandt, and B. Brunstrom. 2001. Distribution of Bisphenol a and 

Tetrabromobisphenol a in Quail Eggs, Embryos and Laying Birds and Studies on Reproduction 

Variables in Adults Following in Ovo Exposure. Archives of Toxicology, 75, 597-603.

Hamers, T., J. H. Kamstra, E. Sonneveld, A. J. Murk, M. H. A. Kester, P. L. Andersson, J. Legler, and A. 

Brouwer. 2006. In Vitro Profiling of the Endocrine-Disrupting Potency of Brominated Flame 

Retardants. Toxicological Sciences, 92(1), 157-173.

Hanada, H., K. Katsu, T. Kanno, E. F. Sato, A. Kashiwagi, J. Sasaki, M. Inoue, and K. Utsumi. 2003. 

Cyclosporin a Inhibits Thyroid Hormone-Induced Shortening of the Tadpole Tail through 

Membrane Permeability Transition. Comparative Biochemistry and Physiology. Part B, 135, 473-

483.

He, M. J., X. J. Luo, L. H. Yu, J. Liu, X. L. Zhang, S. J. Chen, D. Chen, and B. X. Mai. 2010. 

Tetrabromobisphenol-A and Hexabromocyclododecane in Birds from an E-Waste Region in 

South China: Influence of Diet on Diastereoisomer- and Enantiomer-Specific Distribution and 

Trophodynamics. Environmental Science and Technology, 44(15), 5748-5754.

Herr, D. (US EPA, Office of Research and Development, National Health and Environmental Effects 

Research Laboratory). Review of Lilienthal et al., 2008 Regarding Brainstem Auditory Evoked 

Potentials and Tetrabromobisphenol A. Memorandum to: Benson, A. (US Environmental 

Protection Agency, Office of Pollution Prevention and Toxics), September 3, 2013.

HTRI (Hill Top Research, Inc.). 1966. Acute Toxicity and Irritation Studies of [Sic] Tetrabromobisphenol A 

(Unpublished). (as cited in EC, 2006).

Hummel, R. (US Environmental Protection Agency). Liver Hepatoblastoma Stats. Personal 

communication with: Benson, A. (US Environmental Protection Agency), November 13, 2013.

Hummel, R. (US Environmental Protection Agency). Results of Dose Response Modeling of NTP 2013 

Cancer Data. Personal communication with: Benson, A. (US Environmental Protection Agency), 

November 14, 2013.

Hummel, R. 2014. BMDS Wizard Output Report - Hemangiosarcomas and 

Hemangiomas/Hemangiosarcomas (Combined). Office of Pollution Prevention and Toxics, US 

Environmental Protection Agency, Washington, DC.
Page 61 of 135

IBRI (International Bio-Research, Inc.). 1967. Acute Oral Toxicity of Tetrabromobisphenol a to Rats 

(Unpublished). (as cited in EC, 2006).

ICL-IP (ICL Industrial Products). 2013a. FR-720. http://icl-ip.com/?products=fr-720 (accessed on 

October 24, 2013).

ICL-IP (ICL Industrial Products). 2013b. FR-1524. http://icl-ip.com/?post_type=products&p=3062

(accessed on October 24, 2013).

IPCS (International Programme on Chemical Safety). 1995. Tetrabromobisphenol A and Derivatives. 

Environmental Health Criteria 172. United Nations Environment Programme, the International 

Labor Organisation and the World Health Organization, Geneva, Switzerland. 

http://www.inchem.org/documents/ehc/ehc/ehc172.htm.

IPCS (International Programme on Chemical Safety). 1997. Flame Retardants: A General Introduction. 

Environmental Health Criteria 192. United Nations Environment Programme, the International 

Labor Organisation and the World Health Organization, Geneva, Switzerland. 

http://www.inchem.org/documents/ehc/ehc/ehc192.htm.

IPCS (International Programme on Chemical Safety). 2007. IPCS Framework for Analysing the Relevance 

of a Cancer Mode of Action for Humans and Case Studies (Part 1). Harmonization Proejct 

Document No. 4. World Health Organization, the International Labour Organization, and the 

United Nations Environment Programme. 

http://www.who.int/ipcs/methods/harmonization/areas/cancer_mode.pdf.

IRDC (International Research and Development Corporation). 1975. Fourteen-Day Inhalation Toxicity 

Study in Rats (Unpublished). (as cited in EC, 2006).

IRDC (International Research and Development Corporation). 1979. Three Week Dermal Toxicity Study 

in Rabbits (Unpublished). (as cited in EC, 2006).

ITC (United States International Trade Commission). 2013. Used Electronic Products: An Examination of 

U.S. Exports. Investigation No. 332-528; USITC Publication 4379. Washington, DC.

Kang, H.-Y., and J. M. Schoenung. 2005. Electronic Waste Recycling: A Review of U.S. Infrastructure and 

Technology Options. Resources, Conservation and Recycling, 45, 368-400.

Kashiwagi, A., H. Hanada, M. Yabuki, T. Kanno, R. Ishisaka, J. Sasaki, M. Inoue, and K. Utsumi. 1999. 

Thyroxine Enhancement and the Role of Reactive Oxygen Species in Tadpole Tail Apoptosis. Free 

Radical Biology and Medicine, 26(7/8), 1001-1009.

Keller, A. S., P. N. Raju, T. F. Webster, and H. M. Stapleton. 2014. Flame Retardant Applications in 

Camping Tents and Potential Exposure. Envionmental Science and Technology Letters, 1, 152-

155.
Page 62 of 135

Kicinski, M., M. K. Viaene, E. D. Hond, G. Schoeters, A. Covaci, A. C. Dirtu, V. Nelen, L. Bruckers, K. 

Croes, I. Sioen, W. Baeyens, N. Van Larebeke, and T. S. Nawrot. 2012. Neurobehavioral Function 

and Low-Level Exposure to Brominated Flame Retardants in Adolescents: A Cross-Sectional 

Study. Environmental Health, 11, 1-12.

Knudsen, G. A., L. M. Jacobs, R. K. Kuester, and I. G. Sipes. 2007. Absorption, Distribution, Metabolism 

and Excretion of Intravenously and Orally Administered Tetrabromobisphenol a [2,3-

Dibromopropyl Ether] in Male Fischer-344 Rats. Toxicology, 237, 158-167.

Krueger, H. e. a. (Wildlife International, Ltd. ). 2002a. Tetrabromobisphenol A: A Prolonged Sediment 

Toxicity Test with Lumbriculus Variegatus Using Spiked Sediment with 2% Total Organic Carbon. 

Project Number: 439a-115. Easton, MD. (as cited in ACC, 2006).

Krueger, H. e. a. 2002b. Tetrabromobisphenol A: A Prolonged Sediment Toxicity Test with Lumbriculus 

variegatus Using Spiked Sediment with 5% Total Organic Carbon Project Number: 439A-116. 

Wildlife International, Ltd., Easton, MD. (as cited in ACC, 2006 ).

Kuch, B., W. Korner, and H. Hagenmaier. 2001. [Monitoring Von Bromierten Flammschutzmitteln in 

Fliessgewassern, Abwassern Und Klarschlammen in Baden-Wurttemberg].

Kuester, R. K., A. M. Solyom, V. P. Rodriguez, and I. G. Sipes. 2007. The Effects of Dose, Route, and 

Repeated Dosing on the Disposition and Kinetics of Tetrabromobisphenol a in Male F-344 Rats. 

Toxicological Sciences, 96(2), 237-245.

Kuiper, R. V., E. J. van den Brandhof, P. E. Leonards, L. T. van der Ven, P. W. Wester, and J. G. Vos. 2007. 

Toxicity of Tetrabromobisphenol a (TBBPA) in Zebrafish (Danio rerio) in a Partial Life-Cycle Test. 

Archives of Toxicology, 81(1), 1-9.

Larsen, G., F. Casey, A. Bergman, and H. Hakk. 2001. Mobility, Sorption and Fate of 

Tetrabromobisphenol a (TBBPA) in Loam Soil and Sand. Abstracts of the 2nd International 

Workshop on Brominated Flame Retardants. Part 2 - Analysis and Fate, Products, Standards and 

Uses, Stockholm, Sweden. 

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&frm=1&source=web&cd=5&ved=0CD0QFj

AE&url=http%3A%2F%2Fwww.researchgate.net%2Fprofile%2FTom_Harner%2Fpublication%2F

244465065_Measurements_of_OctanolAir_Partition_Coefficients_(_K_OA_)_for_Polybrominat

ed_Diphenyl_Ethers_(PBDEs)_Predicting_Partitioning_in_the_Environment%2Ffile%2F9c96052

6a70f0039a2.pdf&ei=8hu8U5i5OYqqsQTUzYDwBA&usg=AFQjCNFUYNoYed3Nj0yEkmhBFMIPTf

pSSg&sig2=t_o5cht8FU1t6qL4JfvgGw&bvm=bv.70138588,d.ZGU.

Lax, S. F. 2004. Molecular Genetic Pathways in Various Types of Endometrial Carcinoma: From a 

Phenotypical to a Molecular-Based Classification. Virchows Archiv: European Journal of 

Pathology, 444, 213-223.
Page 63 of 135

Li, Y., Q. Zhou, Y. Wang, and X. Xie. 2011. Fate of Tetrabromobisphenol a and 

Hexabromocyclododecane Brominated Flame Retardants in Soil and Uptake by Plants. 

Chemosphere, 82(2), 204-209.

Lilienthal, H., C. M. Verwer, L. T. van der Ven, A. H. Piersma, and J. G. Vos. 2008. Exposure to 

Tetrabromobisphenol a (TBBPA) in Wistar Rats: Neurobehavioral Effects in Offspring from a 

One-Generation Reproduction Study. Toxicology, 246(1), 45-54.

Lipnick, R. L. 1995. Structure-Activity Relationships. In Rand, G. R., Fundamentals of Aquatic Toxicology

(2nd ed., Chapter 20, pp. 609-655). Taylor and Francis, London, England.

Maine_DEP (Department of Environmental Protection). 2013a. Chemicals of Concern. 

http://www.maine.gov/dep/safechem/concern/documents/ChemicalsofConcernList12_2011.p

df (accessed on Februrary 3, 2015).

Maine_DEP (Department of Environmental Protection). 2013b. Chemicals of High Concern. 

http://www.maine.gov/dep/safechem/highconcern/ (accessed on February 3, 2015).

Maine_DEP (Department of Environmental Protection). 2013c. Safer Chemicals in Children's Products. 

http://www.maine.gov/dep/safechem/index.html (accessed on February 3, 2015).

Mariussen, E., and F. Fonnum. 2003. The Effect of Brominated Flame Retardants on Neurotransmitter 

Uptake into Rat Brain Synaptosomes and Vesicles. Neurochem. Int., 43, 533-542. (as cited in 

NTP, 2013).

MDH (Minnesota Department of Health). 2013a. Chemicals of High Concern List. 

http://www.health.state.mn.us/divs/eh/hazardous/topics/toxfreekids/chclist/mdhchc2013.pdf

(accessed on July 2, 2014).

MDH (Minnesota Department of Health). 2013b. Toxic Free Kids Act: Chemicals of High Concern, July 

2013. 

http://www.health.state.mn.us/divs/eh/hazardous/topics/toxfreekids/highconcern.html#list

(accessed on February 3. 2015).

Meerts, I. A. T. M., Y. Assink, P. H. Cenijin, B. M. Weijers, and H. H. J. van den Berg. 1999. Distribution of 

the Flame Retardant Tetrabromobisphenol a in Pregnant and Fetal Rats and Effect on Thyroid 

Hormone Homeostasis. Oganohalogen Compounds, 40, 375-378. (as cited in EC, 2006).

Morf, L., R. Taverna, H. Daxbeck, and R. Smutny. 2003. Selected Polybrominated Flame Retardants: 

PBDEs and TBBPA; Substance Flow Analysis. Environmental Series No. 338. Swiss Agency for the 

Environment, Forests and Landscape, Berne, Switzerland.

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

Hexabromocyclododecane (HBCD). Lowell Center For Sustainable Production, University of 
Page 64 of 135

Massachusetts, Lowell, Massachusetts. 

http://www.chemicalspolicy.org/downloads/AternativestoTBBPAandHBCD.pdf.

MPI_Research. 2001. Final Report - an Oral Prenatal Developmental Toxicity Study with 

Tatrabromobisphenol-a in Rats (Unpublished).

MPI_Research. 2002a. A 90-Day Oral Toxicity Study of Tetrabromobisphenol-a in Rats with a Recovery

Group (Unpublished). (as cited in EC, 2006).

MPI_Research. 2002b. An Oral Two Generation Reproductive, Fertility and Developmental 

Neurobehavioral Study of Tetrabromobisphenol-a in Rats (Unpublished). (as cited in EC, 2006).

MPI_Research. 2003. Amendment to the Final Report. An Oral Two Generation Reproductive, Fertility 

and Developmental Neurobehavioural Study of Tetrabromobisphenol-a in Rats (Unpublished 

Report). (as cited in EC, 2006).

Muller, P. A. J., and K. H. Vousden. 2013. p53 Mutations in Cancer. Nature: Cell Biology, 15(1), 2-8.

Nakajima, A., D. Saigusa, N. Tetsu, T. Yamakuni, Y. Tomioka, and T. Hishinuma. 2009. Neurobehavioral 

Effects of Tetrabromobisphenol a, a Brominated Flame Retardant, in Mice. Toxicology Letters, 

189(1), 78-83.

Neumann, F. 1991. Early Indicators for Carcinogenesis in Sex-Hormone-Sensitive Organs. Mutation 

Research, 248, 341-356.

NIEHS (National Institute of Environmental Health Sciences). 2002. Tetrabromobisphenol A [79-94-7]: 

Review of Toxicological Literature. Prepared for Scott Masten, Ph.D. by Karen E. Haneke, M.S., 

Integrated Laboratory Systems. 

http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/tetrabromobisphenola_508

.pdf.

NIEHS (National Institute of Enviornmental Health Sciences). 2015. Review of the EPA Hazard 

Identification and Dose Response for Tetrabromobisphenol A. National Institutes of Health. 

(January 7, 2015).

NITE (National Institute of Technology and Evaluation). 2010a. #28: Biodegradation in Water: Screening 

Tests for CASRN 21850-44-2. Japan Chemicals Collaborative Knowledge Database, Ministry of 

Economy, Trade and Industry and Ministry of the Environment, Japan. 

http://www.safe.nite.go.jp/jcheck/template.action?ano=8003&mno=4-212&cno=21850-44-

2&request_locale=en (accessed on February 11, 2014).

NITE (National Institute of Technology and Evaluation). 2010b. #32: Bioaccumulation: 

Aquatic/Sediment for TBBPA (CASRN 79-94-7). Japan Chemicals Collaborative Knowledge 

Database, Ministry of Economy, Trade and Industry and Ministry of the Environment, Japan. 
Page 65 of 135

http://www.safe.nite.go.jp/jcheck/template.action?ano=849&mno=4-0205&cno=79-94-

7&request_locale=en (accessed on November 14, 2014).

NLM (National Library of Medicine). 2009. Hazardous Substance Database Entry for 2-Bromophenol 

(CASRN 95-56-7). http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~TtZAHq:3 (accessed 

on October 4, 2014).

Noda, T., S. Morita, S. Ohgaki, and M. Shimizu. 1985. Safety Evaluation of Chemicals for Use in 

Household Products (VII) Teratological Studies on Tetrabromobisphenol-A in Rats. Annual 

Report of the Osaka Institute of Public Health and Environmental Sciences, 48, 106-112. (as 

cited in EC, 2006).

NTP (National Toxicology Program). 2014a. NTP Technical Report on the Toxicology Studies of 

Tetrabromobisphenol A (CAS No. 79-94-7) in F344/NTac Rats and B6C3F1/N Mice and 

Toxicology and Carcinogenesis Studies of Tetrabromobisphenol A in Wistar Han [Crl:WI(Han)] 

Rats and B6C3F1/N Mice (Gavage Studies). NTP TR 587. National Institutes of Helath, Public 

Health Service, US Department of Health and Human Services, Research Triangle Park, NC. 

http://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr587_508.pdf.

NTP (National Toxicology Program). 2014b. Report on Carcinogens, Thirteenth Edition, Estrogens, 

Steroidal. US Department of Health and Human Services. 

http://ntp.niehs.nih.gov/pubhealth/roc/roc13/index.html.

Nyholm, J. R., C. Lundberg, and P. L. Andersson. 2010. Biodegradation Kinetics of Selected Brominated 

Flame Retardants in Aerobic and Anaerobic Soil. Environmental Pollution, 158(6), 2235-2240.

OECD (Organisation for Economic Cooperation and Development). 2003. Guidance Document on 

Reporting Summary Information on Environmental, Occupational and Consumer Exposure. 

ENV/JM/MONO(2003)16. Environment Directorate, Joint Meeting of the Chemicals Committee 

and the Working Party on Chemicals, Pesticides and Biotechnology, Paris, France. 

http://www.oecd-ilibrary.org/environment/guidance-document-on-reporting-summaryinformation-on-environmental-occupational-and-consumer-exposure_9789264079113-en.

OECD (Organisation for Economic Cooperation and Development). 2015. OECD Guidelines for the 

Testing of Chemicals. Paris, France. 

http://www.oecd.org/chemicalsafety/testing/oecdguidelinesforthetestingofchemicals.htm

(accessed on March 9, 2015).

Ohta, R., A. Takagi, H. Ohmukai, H. Marumo, A. Ono, Y. Matsushima, T. Inoue, H. Ono, and J. Kanno. 

2012. Ovariectomized Mouse Uterotrophic Assay of 36 Chemicals. The Journal of Toxicological 

Sciences, 37(5), 879-889.

Oregon_DEQ (Department of Environmental Quality). 2010a. Attachment 2. Priority Persistent 

Pollutant List (P3 List). http://www.deq.state.or.us/wq/SB737/ (accessed on June 19, 2014).
Page 66 of 135

Oregon_DEQ (Department of Environmental Quality). 2010b. Attachment 4. Pollutant Profiles. 

http://www.deq.state.or.us/wq/SB737/docs/LegRpAtt420100601.pdf (accessed on June 19, 

2014).

Oregon_DEQ (Department of Environmental Quality). 2010c. Water Quality: Senate Bill 737 

Implementation: Addressing Priority Persistent Pollutants in Oregon's Water. 

http://www.deq.state.or.us/wq/SB737/#TLR (accessed on February 2, 2015).

Osako, M., Y.-J. Kim, and S. Sakai. 2004. Leaching of Brominated Flame Retardants in Leachate from 

Landfills in Japan. Chemosphere, 57, 1571-1579.

OSHA (Occupational Safety and Health Administration). 2015. Chemical Exposure Health Data. United 

States Department of Labor, Washington, DC. 

https://www.osha.gov/opengov/healthsamples.html (accessed on February 6, 2015).

Ozkaynak, H., J. Xue, V. G. Zartarian, G. Glen, and L. Smith. 2011. Modeled Estimates of Soil and Dust 

Ingestion Rates for Children. Risk Analysis, 31(4), 592-608.

Pellizzari, E. D., R. A. Zweidinger, and M. D. Erickson. 1978. Environmental Monitoring near Industrial 

Sites: Brominated Chemicals. Part I and II. Contract Number 68-01-1978. Research Triangle 

Institute, for Office of Toxic Substances, U.S. Environmental Protection Agency, Washington, 

D.C.

Peltola, J. 2002. An Environmental Screening of Four Brominated Flame Retardants in Finland. to be 

published in Chemosphere. (as cited in EC, 2008).

Qu, G., A. Liu, T. Wang, C. Zhang, J. Fu, M. Yu, J. Sun, N. Zhu, Z. Li, G. Wei, Y. Du, J. Shi, S. Liu, and G. 

Jiang. 2013. Identification of Tetrabromobisphenol a Allyl Ether and Tetrabromobisphenol a 2,3-

Dibromopropyl Ether in the Ambient Environment near a Manufacturing Site and in Mollusks at 

a Coastal Region. Environmental Science and Technology, 47(9), 4760-4767.

Qu, G., J. Shi, T. Wang, J. Fu, Z. Li, P. Wang, T. Ruan, and G. Jiang. 2011. Identification of 

Tetrabromobisphenol A Diallyl Ether as an Emerging Neurotoxicant in Environmental Samples 

by Bioassay-Directed Fractionation and HPLC-APCI-MS/MS. Environmental Science and 

Technology, 45, 5009-5016.

Quade, S. C. 2003. Determination of Tetrabromobisphenol a in Sediment and Sludge. (M.S. 

dissertation), University of Guelph, Ottawa, Canada.

Raftogianis, R., C. Creveling, R. Weinshilboum, and J. Weisz. 2000. Chapter 6: Estrogen Metabolism by 

Conjugation. Journal of the National Cancer Institute Monographs, 27.

Russo, J., and I. H. Russo. 2004. Genotoxicity of Steroidal Estrogens. Trends in Endocrinolology and 

Metabolism, 15(5), 211-214.
Page 67 of 135

Saegusa, Y., H. Fujimoto, G. H. Woo, K. Inoue, M. Takahashi, K. Mitsumori, A. Nishikawa, and M. 

Shibatani. 2009. 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. Reproductive Toxicology, 28, 456-467.

Saegusa, Y., H. Fujimoto, G. H. Woo, T. Ohishi, L. Wang, K. Mitsumori, A. Nishikawa, and M. Shibutani. 

2012. Transient Aberration of Neuronal Development in the Hippocampal Dentate Gyrus after 

Developmental Exposure to Brominated Flame Retardants in Rats. Archives of Toxicology, 86(9), 

1431-1442.

Samsonek, J., and F. Puype. 2013. Occurrence of Brominated Flame Retardants in Black Thermo Cups 

and Selected Kitchen Utensils Purchased on the European Market. Food Additives and 

Contaminants, Part A, 30(11), 1976-1986.

Schauer, U. M. D., W. Volkel, and W. Dekant. 2006. Toxicokinetics of Tetrabromobisphenol a in Humans 

and Rats after Oral Administration. Toxicological Sciences, 91, 49-58.

Schlabach, M., M. Remberger, E. Brorstrom-Lunden, K. Norstrom, L. Kaj, H. Andersson, D. Herzke, A. 

Borgen, and M. Harju. 2011. Brominated Flame Retardants (BFR) in the Nordic Environment. 

TemaNord 2011:528. Nordic Council of Ministers, Copenhagen, Denmark. 

http://www.norden.org/en/publications/publikationer/2011-528.

Shi, Z., Y. Wu, J. Li, Y. Zhao, and J. Feng. 2009. Dietary Exposure Assessment of Chinese Adults and 

Nursing Infants to Tetrabromobisphenol a and Hexabromocyclododecanes: Occurrence 

Measurements in Foods and Human Milk. Environmental Science and Technology, 43, 4314-

4319.

Sidhu, S., A. Morgan, M. Kahandawala, K. Muddasani, B. Gullet, and D. Tabor. 2013. Use of Cone 

Calorimeter to Identify Selected Polyhalogenated Dibenzo-P-Dioxins/Furans and Polyaromatic 

Hydrocarbon Emissions from the Combustion of Ciruit Board Laminates: Final Report. October 

22. University of Dayton Research Institute and the U.S. Environmental Protection Agency, 

Dayton, Ohio and Research Triangle Park, North Carolina.

Sjodin, A., D. Patterson, and A. Bergman. 2003. A Review on Human Exposure to Brominated Flame 

Retardants – Particularly Polybrominated Diphenyl Ethers. Environment International, 29, 829-

839.

SLS (Springborn Life Sciences, Inc.). 1989a. Acute Toxicity of Tetrabromobisphenol a to Eastern Oysters 

(Crassostrea virginica) under Flow-through Conditions. 89-1-2898. Wareham, MA. (EC, 2008).

SLS (Springborn Life Sciences, Inc.). 1989b. The Chronic Toxicity of Tetrabromobsiphenol a (TBBPA) to 

Daphnia magna under Flow-through Conditions. SLS Study No. 89-01-2925. Wareham, 

Massachusettes. (as cited in ACC, 2006).
Page 68 of 135

SLS (Springborn Life Sciences). 1989c. The Toxicity of Tetrabromobisphenol a (TBBPA) to Fathead 

Minnow (Pimephales promelas) Embryos and Larvae. SLS Study No. 89-2-2937. Wareham, MA. 

(as cited in ACC, 2006).

Stoner_Laboratories. 1978. The Bioaccumulation of Tetrabromobisphenol A in the Bluegill Sunfish. 

Project 780241. Santa Clara, CA. (as cited in EC, 2008).

Strain, G. M., M. Banasik, M. Hardy, and T. Stedeford. 2009. Tetrabromobisphenol A (TBBPA) and 

Model-Derived Risks for Neurobehavioral Effects in Offspring from a One-Generation 

Reproduction Study. Toxicology, 260(1-3), 155-157.

Suzuki, S., and A. Hasegawa. 2006. Determination of Hexabromocyclododecane Diastereoisomers and 

Tetrabromobisphenol A in Water and Sediment by Liquid Chromatography/Mass Spectrometry. 

Analytical Sciences, 22(March), 469-474.

Sverdrup, L. E., T. Hartnik, E. Mariussen, and J. Jensen. 2006. Toxicity of Three Halogenated Flame 

Retardants to Nitrifying Bacteria, Red Clover (Trifolium pratense), and a Soil Invertebrate 

(Enchyraeus crypticus). Chemosphere, 64, 96-103.

Tada, Y., T. Fujitani, N. Yano, H. Takahashi, K. Yuzawa, H. Ando, Y. Kubo, A. Nagasawa, A. Ogata, and H. 

Kamimura. 2006. Effects of Tetrabromobisphenol a, a Brominated Flame Retardant, in ICR Mice 

after Prenatal and Postnatal Exposure. Food and Chemical Toxicology, 44(8), 1408-1413.

Thomas, R. G. 1982a. Volatilization from Soil. In Lyman, W. J., Handbook of Chemical Property 

Estimation Methods (Chapter 16, pp. 16.11-16.39). McGraw-Hill Book Company, New York, NY.

Thomas, R. G. 1982b. Volatilization from Water. In Lyman, W. J., Handbook of Chemical Property 

Estimation Methods (Chapter 15, pp. 15.11-15.33). McGraw-Hill Book Company, New York, NY.

Tobe, M., Y. Kurokawa, Y. Nakaji, H. Yoshimoto, A. Takagi, Y. Aida, J. Monna, K. Naito, and M. Saito. 

1986. Subchronic Toxicity Study of Tetrabromobisphenyl-A: Report to the Ministry of Health and 

Welfare. (as cited in IPCS, 1995).

UL_IDES (Underwriter Laboratories IDES). n.d. UL 94 Flame Rating. 

http://www.ides.com/property_descriptions/UL94.asp (accessed on June 23, 2014).

United_Kingdom. 2008. Annex Xv Restriction Report - November 30 2008. 

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&frm=1&source=web&cd=1&ved=0CB0QFj

AA&url=http%3A%2F%2Fecha.europa.eu%2Fdocuments%2F10162%2F13630%2Ftrd_uk_bisphe

nol_a_en.rtf&ei=tiqU8ODMcuysQTG54CwAw&usg=AFQjCNEIbrGxxYSbZhuaErjWBvEKeHffDw&sig2=cj6NndGPjwC

9LVWwaLCR6A&bvm=bv.69620078,d.cWc.
Page 69 of 135

van Bergen, S., and A. Stone. 2014. Flame Retardants in General Consumer and Children's Products. 14-

04-021. Department of Ecology, State of Washington, Olympia, WA. 

https://fortress.wa.gov/ecy/publications/SummaryPages/1404021.html.

Van der Ven, L. T., T. Van de Kuil, A. Verhoef, C. M. Verwer, H. Lilienthal, P. E. Leonards, U. M. Schauer, 

R. F. Canton, S. Litens, J. F. H. De, T. J. Visser, W. Dekant, N. Stern, H. Hakansson, W. Slob, d. B. 

M. Van, J. G. Vos, and A. H. Piersma. 2008. Endocrine Effects of Tetrabromobisphenol-a (TBBPA) 

in Wistar Rats as Tested in a One-Generation Reproduction Study and a Subacute Toxicity Study. 

Toxicology, 245(1-2), 76-89.

VCC (Velsicol Chemical Corporation). 1978a. Acute Toxicity of Tetrabromobisphenol A (Unpublished). 

8EHQ-0678-0185. (as cited in EC/HC, 2013).

VCC (Velsicol Chemical Corporation). 1978b. Pilot Teratology Study in Rats with Tetrabromobisphenol a 

with Cover Letter Dated 04/17/78. Study conducted by. 0200479.

Veldhoen, N., A. Boggs, K. Walzak, and C. C. Helbing. 2006. Exosure to Tetrabromobisphenol-a Alters 

Th-Associated Gene Expression and Tadpole Metamorphosis in the Pacific Tree Frog Pseudacris 

regilla. Aquatic Toxicology, 78, 292-302.

Viberg, H., and P. Eriksson. 2011. Differences in Neonatal Neurotoxicity of Brominated Flame 

Retardants, PBDE 99 and TBBPA, in Mice. Toxicology, 289(1), 59-65.

Waaijers, S. L., J. Hartmann, A. M. Soeter, R. Helmus, S. A. E. Kools, P. de Voogt, W. Admiraal, J. R. 

Parsons, and M. H. S. Kraak. 2013. Toxicity of New Generation Flame Retardants to Daphnia 

magna. Science of the Total Environment, 463, 1042-1048.

Walsh, G. E., M. J. Yoder, L. L. McLaughlin, and E. M. Lores. 1987. Responses of Marine Unicellular 

Algae to Brominated Organic Compounds in Six Growth Media. Ecotoxicology and 

Environmental Safety, 14, 215-222.

Washington_State_DEC (Washington State Department of Ecology). 2014. Overview of the Law. 

http://www.ecy.wa.gov/programs/swfa/cspa/ (accessed on September 18, 2014).

Wichmann, H., F. T. Dettmer, and M. Bahadir. 2002. Thermal Formation of PBDD/F from 

Tetrabromobisphenol A - a Comparison of Polymer Linked TBBPA with Its Additive Incorporation 

in Thermoplastics. Chemosphere, 47, 349-355.

Wollenberger, L., L. Dinan, and M. Breitholtz. 2002. Effects of Brominated Flame Retardants on Two 

Marine Copepod Species, Acartia tonsa and Nitocra spinipes, and on the Ecdysteroid-Responsive 

Drosophila melanogaster BII-Cell-Line. Organohalogen Compounds, 57, 451-454.

WSDE (Washington State Department of Ecology). 2011. Rationale for Reporting List of Chemicals of 

High Concern to Children. http://www.ecy.wa.gov/programs/swfa/cspa/pdf/79947.pdf

(accessed on June 19, 2014).
Page 70 of 135

WSDE (Washington State Department of Ecology). 2013. Reporting Guidance - Product Categories and 

Scope. http://www.ecy.wa.gov/programs/swfa/cspa/pdf/cspaguide_category.pdf (accessed on 

March 9, 2015).

WSDE (Washington State Department of Ecology). 2014a. Children's Safe Product Act Reports. 

https://fortress.wa.gov/ecy/cspareporting/Reports/ReportViewer.aspx?ReportName=Chemical

ReportByCASNumber (accessed on June 19, 2014).

WSDE (Washington State Department of Ecology). 2014b. The Reporting List of Chemicals of High 

Concern to Children (CHCC). http://www.ecy.wa.gov/programs/swfa/cspa/chcc.html (accessed 

on February 2, 2015).

Yager, J. D. 2014. Mechanisms of Estrogen Carcinogenesis: The Role of E2/E1-Quinone Metabolites 

Suggests New Approaches to Preventive Intervention - a Review. Steroids, August 24, 2014; 

Epub ahead of print.

Yang, S., S. Wang, F. Wu, Z. Yan, and H. Liu. 2012. Tetrabromobisphenol A: Tissue Distribution in Fish, 

and Seasonal Variation in Water and Sediment of Lake Chaohu, China. Environmental Science 

and Pollution Research, 19, 4090-4096.

Zalko, D., D. Prouillac, A. Rui, E. Perdu, L. Dolo, I. Jouanin, C. Canlet, L. Debaruwer, and J.-P. Cravedi. 

2006. Biotransformation of the Flame Retardant Tetrabromobisphenol a by Human and Rat 

Sub-Cellular Liver Fractions. Chemosphere, 64, 318-327.

Zatecka, E., L. Ded, F. Elzeinova, A. Kubatova, A. Dorosh, H. Margaryan, P. Dostalova, and J. Peknicova. 

2013. Effect of Tetrabrombisphenol a on Induction of Apoptosis in the Testes and Changes in 

Expression of Selected Testicular Genes in CD1 Mice. Reproductive Toxicology, 35, 32-39.

Zweidinger, R. A., S. D. Cooper, M. D. Erickson, L. C. Michael, and E. D. Pellizzari. 1979. Sampling and 

Analysis for Semivolatile Brominated Organics in Ambient Air. In Schuetzle, D., Monitoring Toxic 

Substances (ACS Symposium Series 94 ed., Chapter 13, pp. 217-231). American Chemical 

Society, Washington, DC.

Zweidinger, R. A., S. D. Cooper, and E. D. Pellizzari. 1979. Identification and Quantitation of Brominated 

Fire Retardants. In Hall, C. E. V., Measurement of Organic Pollutants in Water and Wastewater, 

ASTM STP 686 (pp. 234-250). American Society for Testing and Materials, Philadelphia, PA.
Page 71 of 135

Data Available for TBBPA-bis(dibromopropyl ether), 

TBBPA-bis(allyl ether) and TBBPA-bis(methyl ether) 

Although EPA decided not to conduct assessments for the three cluster members other than TBBPA, 

there are some data available for these compounds. Table_Apx A-1 presents an overview of the data 

available for all cluster members, to show the comparison of the other cluster members with the index 

chemical TBBPA. The ability to use TBBPA data to characterize these other chemicals (i.e. the ability to 

read-across) is also discussed for environmental and human health endpoints.

Table_Apx A-1: Data Availability and Read Across for Cluster Members

Endpoint

Chemical

TBBPA TBBPA-bis(dibromo 

propyl ether)

TBBPAbis(allyl ether)TBBPAbis(methyl ether)

Production Volume and Uses

Production Volume

(2010 or 2011) X X X ND

Industrial Uses X X ND ND

Consumer Uses X X ND ND

Physical-Chemical Properties

Melting Point X X X X

Boiling Point X X X X

Vapor Pressure X X X X

Water Solubility X ND ND ND

Octanol-Water 

Partition Coefficient X ND ND X

Fate Properties

Biodegradation X X ND ND

Experimental 

Bioconcentration 

Data

X ND ND ND

Exposure (Monitoring Data)

Environmental 

media X X X X

Biota X X X X

Environmental Effects

Acute fish X X ND ND

Chronic fish X ND ND ND

Acute invertebrate X X ND ND

Chronic 

invertebrates X ND ND ND

Algae X X ND ND

Sediment toxicity X ND ND ND

Earthworms X X ND ND
Page 72 of 135

Table_Apx A-1: Data Availability and Read Across for Cluster Members

Endpoint

Chemical

TBBPA TBBPA-bis(dibromo 

propyl ether)

TBBPAbis(allyl ether)TBBPAbis(methyl ether)

Potential for read 

across from TBBPA? NA

No; 

Physical-chemical 

properties differ

No; 

Physical-chemical 

properties differ

No; 

Physical-chemical 

properties differ

Human Health

Acute Oral X X X ND

Acute Dermal X X X ND

Acute Inhalation X X ND ND

Repeated-Dose

X

[oral and limited 

dermal/inhalation]

X

[oral] ND ND

Developmental X ND ND ND

Reproductive X ND ND ND

Genetic Toxicity

X

[gene mutations, 

chromosomal 

aberrations, other]

X

[gene mutations, 

chromosomal 

aberrations, other]

X

[gene mutations] ND

Neurotoxicity/

neurobehavioral X ND* ND ND

Skin Irritation X X ND ND

Eye Irritation X X ND ND

Sensitization X X ND ND

Carcinogenicity X ND ND ND

Potential for read 

across from TBBPA? NA

No;

This compound has 

alkylating potential

[high mw, low 

solubility limit 

toxicity]

No;

This compound has 

alkylating/epoxide 

forming potential

[high mw, low 

solubility limit toxicity]

Yes;

Structurally and 

mechanistically 

similar to TBBPA

NA = not applicable; X = data available; ND = no data available

*in vitro only

The data for each of these endpoints are described in the following sections: 

A-1. Exclusion from Further Assessment

A-2. Chemical Structures

A-3. Physical-Chemical Properties

A-4. Production Volumes 

A-5. Uses 

A-6. Fate Properties

A-7. Exposure 

A-8. Ecological Hazard

A-9. Human Health Hazard
Page 73 of 135

A-1 Exclusion from Further Assessment

EPA/OPPT does not propose to conduct risk assessments for the three cluster members other than 

TBBPA for reasons detailed below. 

A-1-1 TBBPA-bis(dibromopropyl ether)

Regarding ecological toxicity, the only adequate data for this compound are for earthworms, and the 

results indicate low toxicity (ECHA, 2013). The toxicity estimation program EcoSAR v. 1.11 (EPA, 2012b)

is not well suited for use with this compound to fill additional endpoints because log KOW values are 

expected to be higher than those used to develop the algorithms used within EcoSAR. Yet, TBBPAbis(dibromopropyl ether) is likely to have low water solubility and a high octanol-water partition 

coefficient and no toxic effects are expected in aquatic and other organisms when considering 

quantitative structure activity relationships (QSARs) (Lipnick, 1995). 

For human health, a toxicokinetics study in rats shows low absorption by TBBPA-bis(dibromopropyl 

ether) (Knudsen et al., 2007), which limits its ability to reach target cells. Lack of absorption is expected 

given the compound’s high molecular weight and log KOW and low water solubility. Low toxicity has 

been indicated in available studies and is likely to be due to its limited absorption (ECHA, 2013; GLCC, 

1982; IPCS, 1995).

Due to differences in physical-chemical properties compared with TBBPA and its potential to act as an 

alkylating agent, EPA/OPPT has determined that TBBPA toxicity studies should not be used as 

surrogate data for this compound for either ecological or human health toxicity endpoints. Therefore, 

EPA/OPPT will not assess risks to this compound for these reasons as well as the limited toxicity data 

available. The expected low toxicity of the compound also suggests that gathering additional data on 

this compound is not a high priority.

A-1-2 TBBPA-bis(allyl ether)

No adequate ecological toxicity data were found for TBBPA-bis(allyl ether) and it is not expected to 

exhibit effects in aquatic and other organisms due to physical-chemical properties and QSARs (Lipnick, 

1995).

Regarding the potential to result in human health effects, absorption is likely to be limited as is the 

ability to reach target cells. Limited toxicity information suggests low toxicity (Abbott et al., 1981; 

Brusick, 1977; EC/HC, 2013; Qu et al., 2011). 

Similar to the dibromoether, differences in physical-chemical properties and reactivity due to TBBPAbis(allyl ether)’s alkylating potential preclude using TBBPA toxicity data to read across to this 

compound. EPA/OPPT does not propose to assess risks from this compound due to these differences 

and the limited toxicity information. Again, the expected low toxicity indicates that this compound is 

not a high priority for obtaining data in order to conduct a risk assessment.
Page 74 of 135

A-1-3 TBBPA-bis(methyl ether)

No adequate ecological toxicity data were found for this compound, and like the other two cluster 

members, it is not expected to exhibit effects in aquatic and other organisms due to physical-chemical 

properties and QSARs (Lipnick, 1995). Also, differences in physical-chemical properties compared with 

TBBPA suggest that TBBPA cannot be used as a surrogate for ecological toxicity.

No human health toxicity data were found for TBBPA-bis(methyl ether). Unlike the ecological toxicity 

endpoints, TBBPA could be used as a surrogate compound for TBBPA-bis(methyl ether) to estimate 

human health hazards based on enough similarity in the chemicals’ structures. However, TBBPAbis(methyl ether) is found only as a transformation byproduct of TBBPA; EC (2008) indicates that it may 

be a minor degradation product. In addition, its concentrations in the environment are usually lower 

than TBBPA concentrations (see Supplemental File 2 for environmental concentrations). Furthermore, 

scenarios of concern for TBBPA are not relevant for TBBPA-bis(methyl ether) because it is not 

manufactured or found in consumer products. Therefore, EPA/OPPT does not propose conducting a 

risk assessment on this compound.

A-2 Chemical Structures

Individual compound structures for the three cluster members are given in the sections below.

A-2-1 TBBPA-bis(dibromopropyl ether)

A-2-2 TBBPA-bis(allyl ether)

O O

Br

Br

Br

Br

H3C

CH3

Br

Br Br

Br
Page 75 of 135

A-2-3 TBBPA-bis(methyl ether)

A-3 Physical-Chemical Properties

TBBPA-bis(methyl ether), TBBPA-bis(allyl ether) and TBBPA-bis(dibromopropyl ether) are solids with 

low vapor pressure and low water solubility. Table_Apx A-2 identifies the physical-chemical properties, 

which are only available for some cluster members. Estimation program values (EPA, 2013a) for vapor 

pressure and water solubility were unrealistically low and log KOW values were unrealistically high. 

Therefore, estimated values are not reported in Table_Apx A-2. However, compared with TBBPA, the 

other cluster members are expected to have lower water solubility and vapor pressures and higher 

octanol-water partition coefficients (log KOWs) given their larger size and higher molecular weights.

O O

H2C

Br

Br

CH3

H3C

Br

Br CH2

O O

H3C

Br

Br

CH3

H3C

Br

Br

CH3
Page 76 of 135

Table_Apx A-2: Physical-Chemical Properties 

Chemical Name CASRN Melting 

Point (°C) Boiling Point (°C)

Vapor 

Pressure

(mm Hg

@ 25°C)

Water 

Solubility 

(mg/L)

Octanol-Water 

Partition 

Coefficient 

(log KOW)

TBBPAbis(dibromopropyl 

ether)

21850-

44-2 95 > 200°C (dec) < 1x 10-6 ND ND

TBBPA-bis(allyl 

ether)

25327-

89-3 120 > 200°C (dec) < 1 x 10-6 ND ND

TBBPA-bis (methyl 

ether)

37853-

61-5 ND > 200°C (dec) < 1 x 10-6 ND > 6.4

ND: no measured data

Source: IPCS (1995)

A-4 Production Volumes

A-4-1 TBBPA-bis(dibromopropyl ether)

According to the 2012 CDR, the production volume of TBBPA-bis(dibromopropyl ether) is between 1 

and 10 million pounds per year, as shown in

Table_Apx A-3. The CDR database identifies ICL-IP America, Inc., ICC Chemical Corporation and one 

company that claimed CBI as manufacturers/importers of TBBPA-bis(dibromopropyl ether) (EPA, 

2014b). 

Trade names for TBBPA-bis(dibromopropyl ether) include ICL-IP’s FR-720 and Dover Chemical 

Corporation’s (a subsidiary of ICC Industries, Inc.) Doverguard 68 (Dover_Chemical, 2013; ICL-IP, 

2013a).

CDR data do not indicate whether this chemical is imported (EPA, 2014b). All companies listed in the 

2012 CDR database exported 0 pounds and did not report import volumes or claimed the data as CBI.

A-4-2 TBBPA-bis(allyl ether)

CDR data identifies ICC Chemical Corporation as a manufacturer/importer of TBBPA-bis(allyl ether). 

The national production volume for TBBPA bis(allyl ether) is withheld from the 2012 CDR to protect CBI 

claims. However, one of the two ICC sites reported a past production volume (for the year 2010) of 

124,575 pounds (EPA, 2014b), as shown in

Table_Apx A-3.
Page 77 of 135

CDR data do not indicate whether this chemical is imported (EPA, 2014b). All companies listed in the 

2012 CDR database exported 0 pounds and did not report import volumes or claimed the data as CBI.

A-4-3 TBBPA-bis(methyl ether)

There are no reports for TBBPA-bis(methyl ether) in the 2012 CDR database (EPA, 2014b). 

Table_Apx A-3: 2012 CDR Production Volume Data (Pounds/Year) for TBBPA-bis(dibromopropyl 

ether), TBBPA-bis(allyl ether) and TBBPA-bis(methyl ether)

A-5 Uses

Chemical 

Name

Company Site 2012 

Domestic 

Manufacturin

g

2012 

Importe

d

2012 

Exporte

d 

201

2 

Use

d on 

Site1

2010 Past 

Production 

(import and 

manufactur

e)

2011 

National 

Productio

n 

TBBPAbis(dibrom

o-propyl 

ether)

ICL-IP America, Inc.

622 Emerson Road, 

Suite 500

St. Louis, MO 63141

ND CBI 0 N/A 426,480 1 million to 

10 million

ICC Chemical 

Corporation

460 Park Avenue

New York, NY 10022

ND CBI 0 N/A CBI

CBI ND CBI 0 N/A CBI

TBBPAbis(allyl 

ether)

ICC Chemical 

Corporation

460 Park Avenue

New York, NY 10022

ND CBI 0 N/A CBI Withheld

ICC Chemical 

Corporation

3676 Davis Rd NW

Dover, OH 44622

79,640 ND 0 0 124,575 Withheld

TBBPAbis(methyl 

ether)

NR NR NR NR NR NR NR

1The total volume (domestically manufactured and imported) of the chemical used at the reporting site without leaving the site. 

ND = No Data; the company did not provide the requested information.

NR = No Reports; “No Reports” in the CDR public database indicates that production volume was not reported for the IUR/CDR for a 

given year. This does not necessarily indicate that a chemical was not manufactured in the United States, but rather indicates that a 

chemical, if manufactured, had a production volume below the reporting threshold.

N/A = Not Applicable; the imported chemical was never physically at the site.

“Withheld” in the CDR public database indicates that the national production volume of a chemical was unable to be aggregated in 

order to protect to CBI claims.

Source: EPA (2014b)
Page 78 of 135

The 2012 CDR data are minimal for industrial and consumer uses of TBBPA-bis(dibromopropyl ether)

and TBBPA bis(allyl ether), as shown in Table_Apx A-4.

The CDR database does not contain records for TBBPA-bis(methyl ether) (EPA, 2014b). In 1995 the IPCS 

Environmental Health Criteria for TBBPA and derivatives stated that as of 1994 TBBPA-bis(methyl 

ether) was not used for commercial purposes based on the personal communications from a Great 

Lakes Chemicals representative (IPCS, 1995). Instead, it was noted that this compound was a product 

of environmental biotransformation. 

The Environmental Health Criteria for flame retardants (IPCS, 1997) listed TBBPA-bis(methyl ether) as 

a flame retardant for expandable polystyrene, but no references were provided. Furthermore, under 

EPA’s Design for the Environment Program, companies that produce polystyrene foam did not report 

using any TBBPA-based products, including TBBPA-bis(methylether), in flame retardant applications.

Although there is one report of TBBPA-bis(methyl ether)’s use as a flame retardant, multiple other 

sources indicate that it is not used in products. Thus, for purposes of this assessment it is assumed that 

TBBPA-bis(methyl ether) appears in the environment solely as a transformation product of TBBPA.
Page 79 of 135

Table_Apx A-4: Industrial and Consumer Use Data for TBBPA-bis(dibromopropyl ether), TBBPA-bis(allyl ether) and TBBPA-bis(methyl ether)

Chemical 

Name

Manufacturing Site Type of 

Processing

Industrial Use Data Consumer Use Data

Sector Industrial 

Use

Percent of 

Production 

Volume

Consumer Use 

Product 

Category

Commercial 

or Consumer 

Use

Percent of 

Production 

Volume

TBBPAbis(dibromo 

propyl ether)

ICL-IP America, Inc.

622 Emerson Road, Suite 500

St. Louis, MO 63141-6742

Processingincorporation into 

formulation, 

mixture or reaction 

product

Plastics Product 

Manufacturing

Flame 

retardants

100 Plastic and 

Rubber Products 

not covered 

elsewhere

Commercial 100

ICC Chemical Corporation

460 Park Avenue

New York, NY 10022-1906

ND ND ND ND ND ND ND

CBI Processingincorporation into 

article

Plastics Material 

and Resin 

Manufacturing

Flame 

retardants

100 Plastic and 

Rubber Products 

not covered 

elsewhere

Commercial 100

TBBPA-bis(allyl 

ether)

ICC Chemical Corporation

460 Park Avenue

New York, NY 10022-1906

ND ND ND ND ND ND ND

Dover Chemical Corp

3676 Davis Road North West

Dover, OH 44622-9771

ND ND ND ND ND ND ND

TBBPAbis(methyl 

ether)

NR NR NR NR NR NR NR NR

ND = No Data; the company did not provide the requested information.

NR = No Reports; “No Reports” in the CDR public database indicates that production volume was not reported for the IUR/CDR for a given year. This does not necessarily indicate that a chemical was 

not manufactured in the United States, but rather indicates that a chemical, if manufactured, had a production volume below the reporting threshold.

Source: EPA (2014b)
Page 80 of 135

A-6 Fate Properties

If released to air, degradation of these substances by sunlight and reactants in the atmosphere to less 

brominated simpler substances is expected to be slow. If released to water, sediment or soil, the fate 

of these cluster members may be influenced by partitioning to suspended solids, soil and sediment, 

respectively. Microbial biodegradation to less brominated substances can occur in the absence of 

oxygen (anaerobic conditions). The biodegradation of these substances in the environment is 

dependent on a number of factors including the presence of acclimated microorganisms capable of 

biodegrading the chemicals in those media and oxygen levels in the media (anaerobic conditions 

promote reductive debromination). A range of degradation rates is possible (from minutes to years). 

TBBPA-bis(methyl ether), TBBPA-bis(allyl ether) and TBBPA-bis(dibromopropyl ether) have high 

estimated bioaccumulation factors.

Table_Apx A-5 lists fate endpoints that are available for the three cluster members and information is 

discussed in subsequent sections.

Table_Apx A-5: Environmental Fate Endpoints for Three Cluster Members

Endpoint TBBPA-bis

(dibromopropyl ether)

TBBPA-bis(allyl ether) TBBPA-bis(methyl ether)

Photodegradation 

Half-life

1 day (estimated, 1.5×106 

hydroxyl radicals per cm3; 

12-hour day)a

1.9 hours (estimated, 

1.5×106 hydroxyl radicals 

per cm3

; 

12-hour day)a

2.2 days (estimated, 

1.5×106 hydroxyl radicals 

per cm3

; 12-hour day)a

Hydrolysis 

Half-life

Stable Stable Stable

Biodegradation1% after 28 days (not readily 

biodegradable, OECD 301C)b

No data No data

Bioconcentration BAF = 1.2×104 (estimated)a BAF = 3.9×105

(estimated)a

BAF = 8.6×106

(estimated)a

Log KOC 6.8 (estimated)a 5.8 (estimated)a 4.8 (estimated)a

Fugacitya

(Level III 

Model)

Air (%)

Water (%)

Soil (%)

Sediment (%)

<0.1

4.9

94.8

0.2

<0.1

5.9

93.0

1.1

<0.1

4.4

92.3

3.2

Persistencec P3 (high) P3 (high) P3 (high)

BioaccumulationcB3 (high) B3 (high) B3 (high)

a EPA (2013a)

b NITE (2010a)

c Criteria specified in: EPA (1999a)
Page 81 of 135

A-6-1 Fate in Environmental Media

A-6-1-1 Air 

TBBPA-bis(methyl ether) and TBBPA-bis(dibromopropyl ether) are expected to undergo relatively slow

atmospheric hydroxy radical oxidation with estimated atmospheric half-lives of a few days. TBBPAbis(allyl ether) is expected to have a much shorter half-life (approximately 2 hours) (EPA, 2013a). 

However, the relatively low vapor pressures of these substances suggest that they will not exist in the 

vapor phase under environmental conditions so atmospheric photo-oxidation is likely to be a slow 

process. 

A-6-1-2 Fate in Water 

Hydrolysis is expected to be relatively unimportant based on the chemical structures of these 

compounds. TBBPA-bis(dibromopropyl ether) is not readily biodegradable (NITE, 2010a). Volatilization 

from water surfaces will be a relatively unimportant fate process for these compounds based upon an 

estimated Henry's law constant of <1.0 × 10-10 atm-m3/mole (EPA, 2013a). 

A-6-1-3 Fate in Soil, Sediment and Groundwater 

These cluster members are expected to have low mobility in soil based on estimated log KOC values 

ranging from 4.8 – 6.8 (EPA, 2013a). 

A-6-2 Bioconcentration/Bioaccumulation and Persistence

Persistence and bioconcentration potential are qualitatively characterized according to the criteria set 

forth in EPA/OPPT’s New Chemicals Program (EPA, 1999a). These cluster members lack experimental 

bioconcentration and bioaccumulation data. However, based on the estimated BCF and BAF values for 

the substances they are expected to have high bioconcentration potential. 

A-7 Exposure

There are a variety of monitoring data for the three cluster members. For the current assessment, 

EPA/OPPT consulted data adequacy guidance available for the High Production Volume (HPV) Program 

and specific guidance on using exposure data developed by the Organisation for Economic Cooperation 

and Development (OECD) (OECD, 2003). Table_Apx A-6 presents a summary table of available 

monitoring data, and more detailed information is in Supplemental Files 2 and 3.
Page 82 of 135

Table_Apx A-6: Availability of Exposure Data for Three Cluster Members

CAS NUMBER 21850-44-2 25327-89-3 37853-61-5

CHEMICAL NAME

TBBPAbis(dibromo 

propyl ether)

TBBPAbis(allyl ether)TBBPAbis(methyl ether)

BIOMONITORING (HUMAN)

Blood

Breast Milk

Adipose Tissue

Placenta

Urine

HUMAN EXPOSURE

Dust ingestion

USGS NWIS DATA

Water

Suspended sediment

Solids

Biota

AIR

Ambient Air 

Indoor Air

SOIL  

INDOOR DUST 

SEDIMENT

Freshwater   

Marine  

SLUDGE

amended soil

biosolids

landfill 

sewage   

WATER

drinking water

groundwater

leachate   

precipitation

surface water 

wastewater   
Page 83 of 135

Table_Apx A-6: Availability of Exposure Data for Three Cluster Members

CAS NUMBER 21850-44-2 25327-89-3 37853-61-5

CHEMICAL NAME

TBBPAbis(dibromo 

propyl ether)

TBBPAbis(allyl ether)TBBPAbis(methyl ether)

AIR AND WATER

deposition

BIOTA

avian  

fish    

aquatic animals (including 

shellfish)    

terrestrial animals  

vegetation 

 = some data available, US or international

A-8 Ecological Hazard

A-8-1 TBBPA-bis(dibromopropyl ether)

There are a few studies for TBBPA-bis(dibromopropyl ether). Algae, fish and aquatic invertebrates were 

exposed to TBBPA-bis(dibromopropyl ether) in different water accommodation fraction (WAF) toxicity 

studies (ECHA, 2013). However, the compound was tested at 100 mg/L or higher, which is significantly 

above its water solubility (ECHA, 2013). In addition to testing above the water solubility, the 

researchers did not measure the test concentrations. As a result, these studies were not acceptable 

and were not included in this review.

A 56-day reproduction study is available for the earthworm Eisenia fetida. The study was conducted 

using OECD test guideline 207. A chronic value of 724 mg/kg was determined (ECHA, 2013).

No chronic aquatic toxicity studies using fish or aquatic invertebrates (either water column or 

sediment) were found for TBBPA-bis(dibromopropyl ether).

A-8-2 TBBPA-bis(allyl ether)

EPA/OPPT did not locate standard ecotoxicity studies that evaluated the effects of TBBPA-bis(allyl 

ether) on organisms in the environment. 
Page 84 of 135

A-8-3 TBBPA-bis(methyl ether)

EPA/OPPT did not locate standard ecotoxicity studies that evaluated the effects of TBBPA-bis(methyl 

ether) on organisms in the environment. 

A-9 Human Health Hazard

A-9-1 TBBPA-bis(dibromopropyl ether)

EPA/OPPT estimates that TBBPA-bis-(dibromopropyl ether) would not be absorbed through the skin as 

a neat material, would have poor skin absorption when in solution and would have poor absorption via 

the lungs and gastrointestinal tract. 

Following single or repeated (5 or 10 days) oral administrations of 20 mg/kg [14C]-TBBPAbis(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. Distribution to the 

tissues accounted for <1% of the dose at 96 hours. Ninety-five percent of the dose was excreted in the 

feces within 36 hours of administration after conjugation via glucuronidation and/or sulfation. 

Elimination in the urine accounted for <0.1% of the administered dose and 1% of the dose was 

excreted in the bile after 24 hours (ECHA, 2013; Knudsen et al., 2007). 

Based on oral and dermal LD50 values >2, 000 mg/kg and an inhalation LC50 value >20 mg/L in rats, the 

acute mammalian toxicity of TBBPA-bis(dibromopropyl ether) is considered low (ECHA, 2013). Oral and 

dermal LD50 values were >20,000 mg/kg in mice (IPCS, 1995). These data indicate that this compound 

has low acute toxicity. 

Mice administered TBBPA-bis(dibromopropyl ether) in their diet at 200 or 2,000 mg/kg-bw/day for 90 

days showed no mortality or abnormal symptoms upon gross pathological examination. The NOAEL 

was determined to be 2,000 mg/kg-bw/day (highest dose tested) (ECHA, 2013; IPCS, 1995).

TBBPA-bis(dibromopropyl ether) is not an eye or skin irritant in rabbits. The compound was not a skin 

sensitizer in a guinea pig maximization test (ECHA, 2013).

Although the compound was reported to be mutagenic to Salmonella typhimurium strains TA100 and 

TA1535 in one assay, it was negative in two other bacterial reverse mutation assays. In the assay that 

was positive for genotoxicity, the compound was slightly less pure (95.1 vs. 99.8%) than the batch used 

in one of the negative assays that used a very similar method. The test substance purity was not stated 

in the third bacterial assay. In an assay using mouse lymphoma cells, the compound was also negative 

for mutagenicity (ECHA, 2013; GLCC, 1982). TBBPA-bis(dibromopropyl ether) did not cause 

chromosomal aberrations or sister chromatid exchanges in Chinese hamster ovary (CHO) cells, was 
Page 85 of 135

negative in an in vivo micronucleus assay in mice and did not produce unscheduled DNA synthesis in 

rats (IPCS, 1995). 

The dibromopropyl groups in TBBPA-bis-(dibromopropyl ether) have alkylating potential. However, it is 

unlikely that this compound can act as an alkylating agent due to its large molecular weight, low water 

solubility and high log KOW. These properties all reduce the bioavailability of the compound. This is 

supported by the genotoxicity data of TBBPA-bis(dibromopropyl ether), which are predominantly 

negative. TBBPA-bis(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 progestrogenic pathways 

(Canton et al., 2006). TBBPA-bis(dibromopropyl ether) competed with thyroid hormone precursor 

thyroxine (T4) for binding to human transthyretin (TTR), but did not exhibit thyroid hormone (T3) 

mimicking activity (Hamers et al., 2006).

A-9-2 TBBPA-bis(allyl ether)

TBBPA-bis(allyl ether) has low acute oral and dermal toxicity. The oral LD50 in rats was > 5000 mg/kg 

bw, and the dermal LD50 in rabbits was > 2000 mg/kg (Abbott et al., 1981; EC/HC, 2013). 

TBBPA-bis(allyl ether) was negative in Salmonella and Saccharomyces when tested with and without 

metabolic activation (Brusick, 1977; EC/HC, 2013). 

Environmental fractions of TBBPA-bis(allyl ether) induced high cytotoxicity in neuronal cells of primary 

cultured cerebellar granule cells. However, the cytotoxic effect was not confirmed by studies in human 

liver carcinoma Hep G2, human breast cancer MCF-7 and mouse leukemic monocyte macrophage RAW 

264.7 cell lines (EC/HC, 2013; Qu et al., 2011).

A-9-3 TBBPA-bis(methyl ether)

No toxicity data were found for TBBPA-bis(methyl ether). Replacement of the hydrogen atom of the 

two hydroxy groups in TBBPA by methyl groups slightly increases the size of the compound. There are 

no structural alerts for genotoxicity and carcinogenicity of TBBPA-bis(methyl ether). The overall toxicity 

of TBBPA-bis(methyl ether) is not expected to be higher than TBBPA based on structure-activity 

relationship analysis.
Page 86 of 135

Literature Searches and Data Quality 

B-1 Literature Available for the Cluster Members

During background, scoping and problem formulation, EPA/OPPT reviewed other recently performed 

assessments and searched published and unpublished literature. The literature review included the 

cluster members’ chemistry, uses, sources (including industrial releases), fate, exposure and hazard to 

humans and ecological receptors. 

First, EPA/OPPT reviewed previous risk assessments to determine whether various scenarios could 

result in risks within the United States. The primary sources of information were human health and 

environmental risk assessments for TBBPA conducted by the EU (EC, 2006, 2008) and health and 

environmental risk assessments conducted by Canada for TBBPA and TBBPA-bis(allyl ether) (EC/HC, 

2013). Other assessments included several predictions of the intake of TBBPA from its presence in food 

(de Winter-Sorkina et al., 2003; Driffield et al., 2008; EFSA, 2011; FSAI, 2010; Shi et al., 2009). 

In addition, EPA/OPPT reviewed hazard profiles prepared under EPA’s Design for the Environment 

Program for two members of the TBBPA cluster. The hazard profile for TBBPA is contained within 

Flame Retardants in Printed Circuit Boards: Updated Draft Report (EPA, 2014e). A recent profile is 

available for TBBPA-bis(2,3-dibromopropyl ether) in the final document An Alternatives Assessment for 

the Flame Retardant Decabromodiphenyl Ether (DecaBDE) (EPA, 2014a) and was consulted for the 

current TBBPA cluster assessment.

Another source of hazard and exposure information along with physical-chemical and fate properties 

for both TBBPA and TBBPA-bis(dibromopropyl ether) is the public data available for chemicals 

submitted to the European Chemicals Agency under REACH (ECHA, 2014).

In addition to reviewing these sources, EPA/OPPT conducted a review of toxicology and exposure 

studies published through June 2013. EPA/OPPT searched Toxline and Pubmed from the US National 

Library of Medicine for toxicology, biomedical and health literature. EPA/OPPT also searched the 

Chemical Abstracts Service from the American Chemical Society for chemical information. Other 

sources of information reviewed were the publicly available databases such as EPA’s Chemical Data 

Reporting (CDR) and Inventory Update Reporting (IUR) databases.

EPA/OPPT also searched for additional exposure information in other databases for the time period of 

2007 through August 2013. The Web of Science includes multidisciplinary science information from 

Thomson Reuters; the BIOSIS Citation Index contains life sciences information and is also from 

Thomson Reuters; CAB Abstracts contains life sciences literature from CABI; and Medline contains 

biomedical literature from the US National Library of Medicine. Search terms included the chemical 

CAS number and chemical abbreviation as well as concentration, environmental, monitoring, human, 

exposure, urine, blood, air, water, soil and sediment. 

EPA/OPPT’s summary of the environmental hazard of TBBPA is based in part on experimental studies 

previously summarized in the 2013 Canadian Assessment (EC/HC, 2013) and the final European Risk 
Page 87 of 135

Assessment Report (EC, 2008), study reports from EPA’s TSCATS database, public literature searches 

and confidential sources. Although all data identified in confidential sources were evaluated, only 

information already made public (either in published risk assessments or journal articles) is included in 

this risk assessment. In addition, EPA/OPPT searched the ECOTOX database to identify peer-reviewed 

articles (EPA, 2014c). Source articles from these searches were retrieved and reviewed.

In some cases (e.g., when a significant pathway was identified), more recent literature (after August or 

June 2013) was also consulted.

B-2 Data Adequacy

Data was acceptable if it met standard quality criteria, which varies according to the type of 

information reviewed. Most toxicity or exposure monitoring studies referenced in previous risk 

assessments, such as those conducted by the European Union (EU) or Canada, were considered to be 

adequate if the previous assessment indicated that the studies were valid. However, EPA/OPPT 

reviewed selected studies referenced in such assessments when either the interpretation and 

description of results or the adequacy of the study was not clearly stated. 

For the studies described in previous assessments that EPA/OPPT evaluated further and for recently 

published studies, EPA/OPPT followed data adequacy guidance developed for the High Production 

Volume (HPV) Chemicals Program (EPA, 1999b). The guidance generally suggests that EPA use studies 

conducted according to accepted testing guidelines such as EPA harmonized guidelines for pesticides 

and industrial chemicals or Organisation for Economic Cooperation and Development (OECD) test 

guidelines. Scientific quality criteria established for the HPV Program include: a clear description of the 

endpoints, inclusion of appropriate controls, identification of test substance and test organism, stated 

exposure duration and administration route, transparent reporting of effect concentrations and 

adherence to recommended tests strategies (EPA, 1999b). These criteria are based on guidelines 

developed and used by EPA’s Office of Chemical Safety and Pollution Prevention and OECD (EPA, 

2014g; OECD, 2015). The guidance also allows EPA/OPPT to use data that don’t strictly follow such 

guidelines, primarily when less acceptable data can support the conclusions from a larger body of 

studies for a particular endpoint using a weight–of–evidence approach.

EPA/OPPT also used study reliability criteria presented in a 2003 OECD Guidance Document on 

Reporting Summary Information on Environmental, Occupational and Consumer Exposure (OECD, 2003)

to evaluate studies that reported environmental and residential (indoor dust, etc.) monitoring data and 

biomonitoring studies. 

Finally, EPA/OPPT used scientific judgment based on an understanding of TBBPA’s unique 

physicochemical and fate characteristics to judge data quality and whether a particular study can 

contribute to TBBPA’s overall hazard identification. This scientific evaluation allowed EPA/OPPT to 

consider whether any identified study deficiencies would detract from the results or would be minor 

enough so that EPA/OPPT could still rely on the study conclusions for hazard identification.
Page 88 of 135

Fate and Transport

The environmental transport and transformation of TBBPA is strongly influenced by its low volatility, 

low water solubility and its slow degradation by biotic and abiotic processes in the environment. 

Where particulate TBBPA is released to air its oxidation by OH radicals is expected to be slow. TBBPA 

may be subject to photolysis in air but the rates and products are unknown. Ultimately air releases of 

TBBPA would be expected to undergo deposition to terrestrial and aquatic environments. TBBPA tends 

to partition to soil and sediment where it can undergo microbial O-methylation to form TBBPAbis(methyl ether). It can also undergo debromination under anaerobic conditions to form bisphenol A 

(BPA). Although these transformations have been observed, the overall environmental persistence of 

TBBPA is expected to be moderate to high. Measured bioconcentration factors indicate that TBBPA has 

a low potential for bioconcentration. 

The rate of loss of the substance, typically due to degradation, may be less than its rate of entry to the 

environment. Therefore, levels of the compound in the environment may increase over time, leading 

to greater potential for exposure. EPA/OPPT will assume that loss is slow and that levels will increase 

over time when estimating exposure in the proposed assessment. 

Table_Apx C-1 summarizes environmental fate data for TBBPA. 

Table_Apx C-1: Environmental Fate

Endpoint Results

Photodegradation 

half-life

3.6 days (estimated, 1.5×106 hydroxyl radicals per cm3; 12-hour day)a

Hydrolysis Half-life Stable

Biodegradation 18.1 – 25.7% after 64 days (Massachusetts sandy loam, aerobic conditions)b;

59.9 – 64.1% after 64 days (Arkansas silty loam, aerobic conditions)b;

56.8 – 58.9% after 64 days (California clay loam, aerobic conditions)b

;

43 – 56.3% after 64 days (Massachusetts sandy loam, anaerobic conditions)c

;

35 – 46.6% after 64 days (Arkansas silty loam, anaerobic conditions)c

;

9.4 – 10.5% after 64 days (California clay loam, anaerobic conditions)c

;

0% after 14 days (not readily biodegradable, OECD 301C)d

Bioconcentration BCF = 720 (measured in eastern oysters)e

BCF = 1,200-1,300 (measured in fathead minnows)h;

BCF = 30 – 341 (measured in carp based on a water concentration of 0.08 

mg/L)d

;

BCF = 52 – 485 (measured in carp based on a water concentration of 0.008 

mg/L)d

;

BCF = 20 – 170 (measured in bluegill for water concentrations of 0.0098 –

0.0014 mg/L)f

 

BAF = 717.5 (estimated)a

Log KOC 5.4 (estimated)a 

4.8 (measured)g

6.0 (measured)g

5.2 (measured)g

5.0 (measured)g
Page 89 of 135

Table_Apx C-1: Environmental Fate

Endpoint Results

Fugacitya

(Level III Model)

Air (%)

Water (%)

Soil (%)

Sediment (%)

<0.1

1.8

69.1

29.1

a EPA (2013a); b GLCC (1989c); c GLCC (1989d); d

NITE (2010b); e GLCC (1989b); f Stoner_Laboratories (1978); 

g GLCC (1989e); h GLCC (1989a)

C-1 Fate in Environmental Media

C-1-1 Fate in Air

TBBPA is expected to undergo relatively slow atmospheric hydroxy radical oxidation. Estimated 

atmospheric half-lives of a few days were predicted using Version 4.10 of EPISuite (EPA, 

2013a). However, the relatively low vapor pressure of TBBPA suggests that it will not exist in the vapor 

phase under environmental conditions. Therefore, atmospheric photo-oxidation is likely to be a slow 

process. TBBPA has been shown to undergo direct photolysis in water when irradiated with UV light in 

the environmental spectrum (300 – 390 nm) and may be subject to photolysis in the atmosphere 

(Eriksson et al., 2004). 

C-1-2 Fate in Water 

TBBPA released to water will sorb to suspended solids and sediments due to its low water solubility 

and high log KOC value. Hydrolysis of TBBPA is expected to be relatively unimportant due to the 

absence of structural components that hydrolyze under environmental conditions. Volatilization from 

water surfaces will be a relatively unimportant fate process based upon an estimated Henry's law 

constant of <1.0 × 10-10 atm-m3

/mole (Thomas, 1982b).

In studies of photolysis, TBBPA was irradiated in water with the range of solar UV wavelengths that are 

encountered in the environment. Photolysis half-lives ranged from 16 minutes at pH 10 to 350 minutes 

at pH 5.5. TBBPA was shown to photodegrade via cleavage between the tertiary carbon and one of the 

benzene rings. The main decomposition products were 4-(2- hydroxyisopropyl)-2,6-dibromophenol; 4-

isopropylene-2,6-dibromophenol; and 2,6-dibromo-4-isopropylene (Eriksson et al., 2004).

TBBPA is not readily biodegradable. It achieved 0% of its theoretical oxygen demand over a 14-day 

incubation period using an activated sludge inoculum and the modified MITI (OECD 301C) test (NITE, 

2010b). In an aerobic river water and sediment biodegradation study TBBPA degraded with half lives in 

the range of 48-84 days (Fackler, 1989). 
Page 90 of 135

C-1-3 Fate in Soil and Sediment 

TBBPA is expected to have low mobility in soil based on both estimated and measured log KOC values.

Larsen et al. (2001) investigated the leaching potential of TBBPA applied to soil and sand columns and 

found no TBBPA leached from the bottom of the soil column with much of it retained in the upper 1 cm 

of the soil. The adsorption of TBBPA to sediment was determined during a toxicity study on sedimentdwelling midge larvae (GLCC, 1989e). The solid-phase concentrations were not measured during the 

study and are based on the nominal amount of substance added. The mean value for the organic 

carbon-water partition coefficient (KOC) that was estimated from the data was 68,753 l/kg (log KOC 4.8). 

In addition, as part of the 14-day toxicity study, sediment-solids and sediment pore water 

concentrations were measured allowing estimates of the value of Koc to be made. The mean values of 

KOC obtained were 1,008,730, 141,980 and 94,830 l/kg (log KOC 6.0, 5.2 and 5.0) for sediments with 

organic carbon contents of 0.25, 2.7 and 6.8% respectively. 

Hydrolysis of TBBPA in soil and sediments is expected to be relatively unimportant due to the absence 

of structural components that hydrolyze under environmental conditions. Volatilization of TBBPA from 

moist soil surfaces is not expected to be an important fate process given its low Henry's law constant 

(<1.0 × 10-10 atm-m3/mole) (Thomas, 1982a). TBBPA is not expected to volatilize from dry soil surfaces 

based upon its low vapor pressure. 

The biodegradation potential of TBBPA under aerobic and anaerobic conditions in a 64-day test was 

investigated using three soils. Under aerobic conditions, TBBPA was degraded 18– 64% (GLCC, 1989c). 

Under anaerobic conditions, the degradation range was 9 – 56 % (GLCC, 1989d). Two main 

biodegradation products were noticed in each soil. However, these were not positively identified and 

did not appear to be the dimethyl derivative TBBPA-bis(methyl ether) or the diethyl derivative (GLCC, 

1989c, 1989d). In another study, biodegradation half-lives of 65 days, 93 days and 430 days were 

reported for TBPPA in an aerobic activated sludge, aerobic digested sludge and anaerobic activated 

sludge, respectively (Nyholm et al., 2010).

TBBPA has been shown to degrade to BPA under anaerobic conditions and form the intermediates 

tribromobisphenol A (Tri BBPA), dibromobisphenol A (DiBBPA) and monobromobisphenol A, which 

were rapidly consumed (Arbeli and Ronen, 2003). TBBPA has also been demonstrated to undergo 

microbial O-methylation by bacterial isolates and sediments to form the TBBPA derivative, TBBPAbis(methyl ether) (Allard et al., 1987). Conversions to the methylated derivative of approximately 60% 

in 24 hours were observed with pure culture bacterial isolates. In sediments, conversion rates ranged 

from 10% in 60 days to 50% in 80 days (George and Haggblom, 2008).

C-2 Persistence

Biotic and abiotic degradation studies have shown TBBPA to degrade very slowly under most 

environmental conditions with half-lives greater than 2 months in water, soil and sediment (Fackler, 

1989; GLCC, 1989c, 1989d; NITE, 2010b). 

The persistence of TBBPA is influenced by a number of factors. These include the environmental media 

to which the substance partitions; the presence of acclimated microorganisms capable of biodegrading 
Page 91 of 135

the chemical in those media; oxygen levels in the media (anaerobic conditions promote degradation of 

TBBPA by reductive debromination) and prolonged direct exposure to sunlight leading to photolysis of 

the molecule. When microorganisms are not acclimated, oxygen levels are high and direct exposure to 

sunlight is limited, TBBPA has been shown to be resistant to environmental degradation processes.

C-3 Bioaccumulation/Bioconcentration

The majority of bioconcentration studies in fish and mollusks indicate that TBBPA has a low 

bioconcentration potential. However, a single study using fathead minnows reported a BCF value of 

1200-1300 (GLCC, 1989a). In this study that used 14C-TBBPA, radioactivity was eliminated from the 

tissues with a half life of less than 24 hours. In further analysis of the data, as discussed in EC (2008), 

the BCF was calculated in terms of a ratio of parent TBBPA to the total body burden of radioactivity, 

resulting in a BCF of approximately 160 for just TBBPA and not its degradates. This recalculated value is 

consistent with the results of other fish bioconcentration studies. 

Based upon the experimental evidence and expert opinion, TBBPA is expected to have low 

bioaccumulation potential.

C-4 Exclusion of Degradation Products from Further Assessment

For a full consideration of possible risks from the manufacture, use and disposal of TBBPA, EPA/OPPT 

identified the most likely compounds that could result from combustion, biodegradation or photolysis 

of TBBPA. Based on data available for these compounds, EPA/OPPT determined whether the 

compounds might result in risks to human health or the environment and whether it would be feasible 

to assess risks from these compounds in the current assessment. As a result of this scoping analysis, 

EPA/OPPT concluded that data on degradation are limited, uncertain or both. Therefore, EPA/OPPT will 

not assess risks from TBBPA’s degradation products in a risk assessment. 

C-4-1 Combustion Products 

Incineration of TBBPA can result in polybrominated dibenzo-p-dioxins (PBDDs) and polybrominated 

dibenzofurans (PBDFs) as well as polyaromatic hydrocarbons (PAHs). 

A recent study found that PBDDs, PBDFs and PAHs were emitted from incineration of TBBPA epoxy 

laminates. PAHs were emitted at higher levels from this laminate than from non-flame retardant 

laminates (Sidhu et al., 2013). In another study, Wichmann et al. (2002) found that PBDDs and PBDFs 

were emitted at similar magnitudes when comparing emissions from TBBPA used in reactive 

applications to those in additive flame retardant applications with PBDFs released in higher amounts 

that PBDDs. 

An accurate estimate of the amount of TBBPA within electronic waste is not available. Furthermore, 

EPA/OPPT doesn’t have robust information on the amount of electronic waste that is incinerated in the 
Page 92 of 135

United States. Finally, compounds other than TBBPA can result in similar combustion products when 

incinerated. Therefore, the contribution of TBBPA to combustion byproducts is not possible to 

determine with enough accuracy to include in EPA/OPPT’s proposed risk assessment.

C-4-2 Biodegradation Products 

Bisphenol A (BPA; CAS 80-05-7) is a possible product of reductive debromination of TBBPA, primarily 

under anaerobic conditions. Thus TBBPA could be a source of BPA in the environment (EC, 2008). 

Overall, biodegradation data are considered to be too limited to predict, with confidence, the rate at 

which TBBPA degrades to BPA in the environment. This is because the majority of the studies use 

microorganisms that have been collected from environments contaminated with TBBPA, exposed to 

TBBPA over extended periods to induce adaptation to degrade the substance and are conducted under 

laboratory conditions that are not necessarily representative of the environment.

C-4-3 Photodegradation Products

TBBPA may photodegrade to form a range of bromophenols and dibromoisopropylphenol derivatives. 

Overall there appears to be limited to no human health toxicity data for dibromophenols. Some 

ecotoxicity data are available for 2-bromophenol (CAS 95-56-7) (NLM, 2009). Due to uncertainties in 

extrapolation from laboratory to the field, it is not certain how much of these products would be 

formed in the environment (Eriksson et al., 2004).
Page 93 of 135

Toxics Release Inventory Emissions

This appendix describes EPA/OPPT’s approach to assessing exposure surrounding manufacturing 

facilities. For both the environment and human health, EPA/OPPT modeled the impact of TBBPA 

deposition from TRI-reported air releases from two manufacturing facilities that emitted the highest 

amounts of TBBPA.

D-1 TRI Releases from Manufacturers

In this assessment, EPA/OPPT used data from the Toxics Release Inventory (TRI) to characterize 

environmental releases of TBBPA. The TRI is a database that contains detailed information on releases 

and transfers of certain listed toxic chemicals from industrial facilities. The database is maintained by 

the Agency and is updated annually (EPA, 2012e).

In 2012, a total of 52 facilities across 7 industries reported releases of TBBPA to TRI (EPA, 2012e). This 

information is reported in Table_Apx D-1. See Table_Apx D-2 for a more detailed account of these 

disposals and releases. 

Based on data from the 2012 TRI, the chemicals industry accounted for ~97% of all reported TBBPA 

disposal and releases. Two facilities from the chemicals industry accounted for ~94% of these disposal 

and releases. Of the total disposal and releases, 94.5% were to land and 4.5% to air. 

Table_Apx D-1: Disposal and Releases of TBBPA by Industry as Reported in the 2012 TRI

Industry NAICSa

Code

Number 

of 

Facilities

Disposal and Releases (pounds per year)

On-site Off-site Total Percent of 

Total

Chemicals 325 23 75,786 48,174 123,960 97.0%

Textiles 313/314 5 143 1,557 1,700 1.3%

Hazardous 

Waste/Solvent 

Recovery

562 4 662 762 1,425 1.1%

Transportation 

Equipment 336 8 8 560 567 0.4%

Plastics and Rubber 326 6 33 154 187 0.1%

Paper 322 1 5 0 5 <0.1%

Computers/Electronics 

Products 334 5 1 1 2 <0.1%

Total 52 76,637 51,208 127,845 100%

a – North American Industry Classification System (NAICS)

Source: EPA (2012e)
Table_Apx D-2: Disposal and Releases of TBBPA by Industry as reported in the 2012 TRI 

Industry NAICS 

Code

Total On-site Disposal and Releases Total Off-site Disposal and 

Releases Total Onand Off-site 

Disposal and 

Releases

Underground 

Injection 

Class I 

Wells

RCRA 

Subtitle C 

Landfills

Other 

On-Site 

Landfills

Fugitive 

Air 

Emissions

Stack Air 

Emissions

Surface 

Water 

Discharges

RCRA 

Subtitle C 

Landfills

Other 

Landfills

Other 

Land 

Disposal

Chemicals 325 100 0 70,182 44 5,453 6 44,205 3,969 0 123,960

Textiles 313/314 0 0 0 141 2 0 0 1,557 0 1,700

Hazardous 

Waste/Solvent 

Recovery

562 0 656 0 0 7 0 0 762 0 1,425

Transportation 

Equipment 336 0 0 0 1 6 0 0 29 531 567

Plastics and 

Rubber 326 0 0 0 33 0 0 0 154 0 187

Paper 322 0 0 0 5 0 0 0 0 0 5

Computers / 

Electronics 

Products

334 0 0 0 0 1 0 0 1 0 2

Total 100 656 70,182 224 5,469 6 44,205 6,471 531 127,845

Source: EPA (2012e)
Page 95 of 135

The two top-releasing facilities in the 2012 TRI are shown in Table_Apx D-3. In 2012, the Dow Chemical 

facility in Freeport, Texas was one of the two highest emitters. However, historical emissions have 

been highest from Great Lakes Chemical (El Dorado, Arkansas) and Albemarle (Magnolia, Arkansas), as 

indicated in Table_Apx D-4.

Table_Apx D-3: Disposal and Releases of TBBPA by Manufacturing Facility as Reported in the 2012 

TRI

Facility NAICS 

Code

Disposal and Releases (pounds per year)

On-site Off-site Total Percent of Total

Dow Chemical

(Freeport, TX) 325 68,882 0 68,882 53.9%

Albemarle

(Magnolia, AR) 325 6,410 44,176 50,586 39.6%

Remaining 50 facilities N/A 1,345 7,032 8,377 6.6%

Total 76,637 51,208 127,845 100%

Source: EPA (2012e)

Over the past 13 years, disposal and releases of TBBPA, as reported in TRI, have decreased by ~84%. 

During this time, two facilities from the chemicals industry were, on average, responsible for ~90% of 

all TBBPA disposal and releases (see Table_Apx D-4). These disposal and releases were primarily to land 

or air.

Table_Apx D-4: TBBPA TRI Release Trends from 2001 to 2012

Year

Disposal and Releases from All Facilities

(pounds per year)

Disposal and Releases 

from Great Lakes 

Chemical and Albemarle

On-site Off-site Total Percent of Total

2000 257,134 537,846 794,981 94%

2001 250,689 625,651 876,340 96%

2002 190,326 863,971 1,054,297 98%

2003 145,766 497,653 643,419 98%

2004 113,779 466,078 579,857 98%

2005 106,737 253,070 359,807 98%

2006 114,902 210,464 325,367 92%

2007 83,124 261,016 344,139 98%

2008 48,962 153,536 202,497 95%

2009 46,906 113,089 159,995 95%

2010 64,801 180,459 245,260 96%

2011 58,837 157,583 216,420 88%

2012 76,637 51,208 127,845 40%

 Source: EPA (2012e)
Page 96 of 135

The stack air emissions data for the two facilities modeled in this assessment are outlined in Table_Apx 

D-5. On average, from 2000 to 2012, these two manufacturing plants have accounted for 97% of all 

TBBPA emitted to air in the United States. The Great Lakes facility produced the majority of these

emissions from 2000 to 2011. In 2012, this facility reported no emissions to air (EPA, 2012e).

Table_Apx D-5: Air Emissions for Facilities Modeled in the Current Assessment

Year

Stack Air Emissions 

(pounds per year)

Great Lakes Chemical Albemarle

2000 41,824 15,403

2001 40,455 11,000

2002 45,030 6,000

2003 61,724 6,000

2004 59,989 6,042

2005 52,933 5,982

2006 55,900 4,938

2007 49,156 5,557

2008 38,724 1,684

2009 40,821 1,689

2010 48,692 1,590

2011 32,987 1,590

2012 0 5,000

Source: EPA (2012e)
Page 97 of 135

TBBPA and other Dust Particle Concentrations in 

Occupational Settings 

Workers may be exposed primarily by ingesting TBBPA dust from the air at work sites. Limited data are 

available for TBBPA at manufacturing and processing sites. These data are described below along with 

data for particles not otherwise regulates (PNOR) at the same types of facilities that would 

manufacture and process TBBPA. EPA/OPPT will consider all of these data to estimate risks to workers.

Manufacturing

During bagging or loading operations, dust may be generated within facilities that manufacture TBBPA 

and workers may be exposed by ingesting particles that are inhaled from the air. To consider potential 

workplace exposures within facilities, EPA/OPPT examined Chemical Exposure Health Data (CEHD) 

from the Occupational Safety and Health Administration (OSHA, 2015). Because TBBPA is not 

specifically listed in OSHA’s database, data for particulates not otherwise regulated (PNOR) were used 

to develop estimates of TBBPA exposures. This exposure data represents the NAICS codes listed below, 

which were reported in the 2012 TRI and are judged to be representative of facilities that accounted 

for approximately 97% of TBBPA releases reported in the 2012 TRI:

• 3251 Basic Chemical Manufacturing

• 3252 Resin, Synthetic Rubber and Artificial Synthetic Fibers and Filaments Manufacturing

• 3255 Paint, Coating and Adhesive Manufacturing

• 3259 Other Chemical Product and Preparation Manufacturing

Potential dust exposures related to TBBPA manufacturing (NAICS Code 3251) are summarized in 

Table_Apx E-1. EPA/OPPT will evaluate risks of ingesting dust after inhalation by workers inside these 

types of facilities. 

Table_Apx E-1: Potential Occupational Exposures from Manufacture of TBBPA*

Exposure Type Potential Dust Exposures

(mg/m3)**

Comments

PNOR

(Total Dust)

Range: 0.47 to 195  30 data points; personal samples; ten years of 

data (2002 to 2011); not specific to TBBPA

 OSHA PEL for PNOR (Total Dust): TimeWeighted Average (TWA) 15 mg/m3

 NAICS Code: 3251

PNOR

(Respirable 

Fraction)***

Range: 0.07 to 19  21 data points; personal samples; ten years of 

data (2002 to 2011); not specific to TBBPA

 OSHA PEL for PNOR (Respirable 

Fraction): TWA 5 mg/m3

 NAICS Code: 3251

Source: OSHA (2015)

* Dust concentrations are used as surrogates for TBBPA from similar industry sectors as TBBPA sectors.

**These exposure estimates are not TWA values; thus they cannot be compared directly to the OSHA PELs.

*** < 10 μm based on particle sampling methods (see: 

https://www.osha.gov/dsg/topics/silicacrystalline/dust/chapter_1.html)
Page 98 of 135

E-1 Processing

During loading and unloading operations, dust may be generated within facilities that process or 

compound TBBPA. Dust generated from unloading operations is expected to be pure TBBPA. However, 

dust generated from compounding and loading operations is not expected to be pure TBBPPA. These 

two types of dust (pure vs. mixture) may have different bioavailabilities. Potential exposures from 

processing TBBPA are summarized in Table_Apx E-2. EPA/OPPT will evaluate occupational risk from 

exposure in processing plants to TBBPA as/in dust after ingestion from air.

Table_Apx E-2: Potential exposures from processing of TBBPA*

Data Source Potential TBBPA Exposures

(mg/m3)

Comments

EU TBBPA RA

(EC, 2006)

0.2 to 12

2 to 50

 Personal Samples (n=13)

 Model estimates based on EASE 

(Estimation and Assessment of Substance 

Exposure)

 Monitoring data is for 

compounding operations; 

represents unloading of 

powder; specific to TBBPA.

ACC BFR End 

User Survey

(ACC, 2000)

0.1 to 15

0.1 to 2

0.0007 to 79

 Total dust, personal samples (n=52)

 Total dust, personal samples (n=11); BFR 

identified as TBBPA

 Bromine content; personal samples (n=34)

 Monitoring data represents 

BFR end user sites.

 Most measurements are for 

total dust samples (not TBBPA 

specific).*

OSHA CEHD**

(OSHA, 2015)

0.02 to 268

0.05 to 169

 Total dust; Personal Samples (n=146)

 Respirable dust; Personal Samples (n=63)

 Ten years of data (2002 to 

2011)

 Targeted to represent 

processing facilities (NAICS 

Codes: 3252, 3255, 3259)

 Data is not specific to TBBPA.*

* Data are for dust concentrations that could be used as a surrogate for TBBPA concentrations based on similarities in 

industry sectors where the dust is generated.

**These exposure estimates are not TWA values; thus they cannot be compared directly to the OSHA PELs.
Page 99 of 135

Ecological Hazard Study Summaries

The following sections describe standard toxicity studies that were considered for use in the proposed 

TBBPA risk assessment for environmental organisms.

The test species, test conditions and toxicity endpoints were summarized and evaluated for data 

quality. Data quality inclusion criteria included: use of appropriate analytical and test controls, 

identification of test substance and test organism, stated exposure duration, a clear description of the 

effect endpoints and transparent reporting of effect concentrations. Guideline studies as well as 

studies using other protocols were included if they met data quality criteria. 

Available toxicity information on representative test species are used to denote toxicity to a wider 

group of organisms within individual taxa or species groups such as aquatic plants, aquatic 

invertebrates (both water column and sediment), fish and soil invertebrates.

Because only limited experimental data are available to characterize toxicity to these species and taxa, 

acute and chronic uncertainty factors that account for both differences in species sensitivities and 

variability among laboratories that conducted the studies can be applied to toxicity values to calculate 

lower bound levels on the concentration associated with toxicity to organisms in the species or taxa 

described above. These lower bound values are referred to as concentrations of concern (COCs). 

The uncertainty factors are based on established EPA/OPPT methods (EPA, 2012d, 2013b) These 

factors are dependent upon the availability of datasets that can be used to characterize relative 

sensitivities across multiple species within a given taxa or species group, but are often standardized in 

risk assessments conducted under TSCA because the data available for most industrial chemicals is 

limited (Ahlers et al., 2008). 

F-1 Toxicity to Aquatic Organisms

Studies considered to be of sufficient quality are summarized in Table_Apx F-1. Some effects were 

observed in other acute aquatic studies, but those values were considerably above the reported water 

solubility for TBBPA. EPA found a few acceptable studies to characterize chronic toxicity to aquatic 

organisms.

F-1-1 Aquatic Plant Toxicity

Toxicity was observed, with 72-hr EC50 values ranging from 0.09 to >5.6 mg/L, when algae were 

exposed to TBBPA (GLCC, 1988b; Walsh et al., 1987).
Page 100 of 135

F-1-2 Aquatic Invertebrate Toxicity

F-1-2-1 Water Column

Acute exposure to TBBPA by freshwater aquatic invertebrates (Daphnia magna) resulted in 48-hour 

EC50 values15 of 0.60 and 0.96 mg/L (GLCC, 1978c; Waaijers et al., 2013). In addition, TBBPA was toxic 

to several marine invertebrates at low concentrations. The Eastern oyster (Crassostrea virginica) 

exhibited a 96-hour EC50 value of 0.098 mg/L based on shell deposition (GLCC, 1989b). In an acute 

mysid shrimp (Mysidopsis bahia) marine ecotoxicity study, adverse effects from TBBPA were observed 

with 96-hour EC50 values ranging from 0.86 to 1.2 mg/L (Goodman et al., 1988). A TBBPA concentration 

of 0.40 mg/L caused lethality in the marine invertebrate species Acartia tonsa under static conditions 

(Wollenberger et al., 2002). In addition, Chironomus tentans were exposed to TBBPA in a 14-day 

toxicity study (GLCC, 1989e). Adverse effects (lethality) were observed at 0.13 mg/L (14-day LC50). 

Adverse effects from TBBPA have been observed in chronic invertebrate studies at concentrations of 

less than 1 mg/L. Chronic exposure of aquatic invertebrates to TBBPA resulted in a 21-day MATC of 

0.540 mg/L based on reproductive effects (SLS, 1989b). In addition, shell length reduction in the 

common mussel (Mytilus edulis) was observed in a 70-day GLP study, with a MATC of 0.023 mg/L (ACC, 

2005).

F-1-2-2 Sediment

The available sediment toxicity studies for sediment-dwelling worms, emergent insects and amphipods 

indicate that observed effects exhibited sediment toxicity in the range of 117 - 500 mg/kg for the 

species tested. 

Wildlife International (Krueger, 2002a, 2002b) studied survival and reproduction in a repeated 28-day 

study using the blackworm Lumbriculus variegates, exposed to TBBPA. For total organic carbon (TOC) 

contents of 2 and 5%, the MATCs were 117 and 329 mg/kg sediment dry weight, respectively. 

In another 28-day study using the midge Chironomus riparius exposed to TBBPA, a MATC for 

emergence was determined to be 177 mg/kg. In this same study, a 28-day EC50 of 235 mg/kg dry 

weight was derived based on midge emergence (ACC-BFRIP, 2005b). In another sediment toxicity test, 

amphipods (Hyalella azteca) were exposed to TBBPA, resulting in a 28-day NOEC and LOEC of 250 and 

500 mg/kg dry weight, respectively, based on the survival endpoint (ACC-BFRIP, 2006). The MATC for 

H. azteca was 354 mg/kg dry weight.

 15 Similar to the LC50, the EC50 is the effect concentration at which 50% of the test organisms show a specific effect other 

than lethality. The value is calculated using the % of organisms affected at the concentrations used in the toxicity study.
Page 101 of 135

F-1-3 Fish Toxicity

For a variety of fish species, acute toxicity studies resulted in 96-hour LC50 values16 ranging from 0. 40 

to 1.1 mg/L under static and flow-through conditions with measured and nominal concentrations 

(GLCC, 1978b, 1988a).

Adverse effects from TBBPA have been observed in chronic fish studies at concentrations of less than 1 

mg/L. A 35-day fish maximum acceptable toxicity concentration (MATC) 17 for Pimephales promelas

was 0.22 mg/L for hatching (SLS, 1989c). A zebrafish embryo toxicity test was conducted with TBBPA, 

but considered unacceptable for the purposes of this hazard assessment due to a lack of replicates and 

difficulties with study interpretation (only body burden concentrations presented) (Kuiper et al., 2007). 

Chronic exposure of aquatic invertebrates to TBBPA resulted in a 21-day MATC of 0.540 mg/L (SLS, 

1989b). In addition, shell length reduction in the common mussel (Mytilus edulis) was observed in a 70-

day GLP study, with a MATC of 0.023 mg/L (ACC, 2005).

F-1-4 Concentrations of Concern

The most sensitive species is expected to be protective of a wider variety of species that are not 

specifically represented by the available experimental data. These were used for both water column 

and sediment species, with application of uncertainty factors, to calculate acute and chronic COCs.

F-1-4-1 Water Column

Considering data from acute studies of fish, aquatic invertebrates and algae, the C. virginica 96-hour 

EC50 of 0.098 mg/L resulted in the lowest value and EPA/OPPT divided this 96-hour EC50 value by an 

uncertainty factor (UF) of 5 for acute tests using invertebrates, as per established EPA/OPPT methods 

(EPA, 2012d, 2013b) to give an acute COC of 0.02 mg/L (or 20 μg/L). 

Although a value of 0.090 mg/L using Skeletonema costatum is the single most sensitive acute toxicity 

value, the resulting value (0.0225 mg/L) is not the most sensitive COC when divided by the standard 

aquatic plant uncertainty factor of 4.

For chronic concerns, the Mytilus edulis 70-day chronic value of 0.023 mg/L based on growth rate is the 

most sensitive value. When divided by an uncertainty factor (UF) of 10 for chronic effects, as per 

established EPA/OPPT methods (EPA, 2012d, 2013b), the resulting chronic COC is 0.002 mg/L (or 2 

μg/L).

F-1-4-2 Sediment

The L. variegates 28-day MATC of 117 mg/L, based on reproduction, was divided by an uncertainty 

factor (UF) of 10 for chronic effects, as per established EPA/OPPT methods (EPA, 2012d, 2013b), to give 

a chronic COC of 11.7 mg/L (or 11,700 μg/L).

 16 LC50 is the lethal concentration at which 50% of the test organisms die. It is calculated using the % of organisms that die at 

the concentrations in the toxicity study and is not necessarily a concentration that was used in the study.

17 The MATC is calculated as the geometric mean of the NOEC and LOEC from the study.
Page 102 of 135

Table_Apx F-1: Toxicity from TBBPA to Aquatic Organisms

Test Organism Fresh/

Salt 

Water

Test Guideline/

Study Type

Duration Endpoint Concentration 

(mg/L)

Chemical 

Analysis

Effects Reference

Aquatic Plants

Green algae

Pseudokirchneriella

subcapitata

Fresh USEPA 40 CFR 

797.1050

72-hr EC50 >5.6 Measured 

Static

Biomass GLCC (1988b)

Green algae

Chlorella sp.

Salt USEPA 40 CFR 

797.1050

96-hr EC50 >1.5 Measured 

Static

Growth Walsh et al. 

(1987)

Diatom

Skeletonema 

costatum

Salt USEPA 40 CFR 

797.1050

72-hr EC50 0.09 Measured 

Static

Growth Walsh et al. 

(1987)

Diatom

Thalassiosira 

pseudonana

Salt USEPA 40 CFR 

797.1050

72-hr EC50 0.13 Measured 

Static

Growth Walsh et al. 

(1987)

Aquatic Invertebrates: Water Column

Water flea

Daphnia magna

Fresh OECD TG 202 48-hr LC50 0.96 Nominal 

Static

Mortality GLCC (1978c)

Water flea

Daphnia magna

Fresh OECD TG 202, 

2004

48-hr LC50 0.60 Nominal 

Static

Mortality Waaijers et al. 

(2013)

Eastern oyster

Crassostrea 

virginica

Salt USEPA CFR 40 TG 

797.1800

96-hr EC50 0.098 Measured

Flow- through

Shell deposition SLS (1989a)

Mysid shrimp

Mysidopsis bahia

Salt _a 96-hr LC50 0.86 Measured 

Flow-through

Mortality Goodman et al. 

(1988)

Marine copepod

Acartia tonsa

Salt Draft ISO/DIS 

14669

48-hr LC50 0.40 Nominal 

Semi-static

Mortality Wollenberger et 

al. (2002)

Midge

Chironomus 

tentans

Fresh ASTM, 1987 

E1706-05

14-day LC50 0.13 Measured

Flow-through

Mortality GLCC (1989e)
Page 103 of 135

Table_Apx F-1: Toxicity from TBBPA to Aquatic Organisms

Test Organism Fresh/

Salt 

Water

Test Guideline/

Study Type

Duration Endpoint Concentration 

(mg/L)

Chemical 

Analysis

Effects Reference

Water flea

Daphnia magna Fresh USEPA CFR 40 797.1330 21-day

LOEC 0.98 Flow-through 

Measured NOEC 0.30 Reproduction SLS (1989b)

MATC 0.54

Blue mussel

Mytilus edulis Salt _a 70-day

LOEC 0.032 Flow-through 

Measured

Growth rate, 

shell length NOEC 0.017 ACC (2005)

MATC 0.023

Aquatic Invertebrates: Sediment

Blackworm

Lumbriculus 

variegatus

Fresh USEPA OPPTS 

850.1735, ASTM 

E1706/95b

28-day 

Tested in 2.5% 

OC content

LOEC 151

NOEC 90 Measured Reproduction Krueger (2002a)

MATC 117

Blackworm

Lumbriculus 

variegatus

Fresh

USEPA OPPTS 

850.1735, ASTM 

E1706/95b

28-day

Tested in 5.9% 

OC content

LOEC 426

NOEC 254 Measured Reproduction Krueger (2002b)

MATC 329

Harlequin fly

Chironomus 

riparius 

Fresh OECD TG 218 28-day

LOEC 250

Nominal Emergence 

development NOEC 125 ACC-BFRIP (2005b)

MATC 177

Amphipod 

crustacean

Hyalella azteca

Fresh USEPA OPPTS 

850.1735

28-day LOEC 500

NOEC 250 Nominal Survival ACC-BFRIP (2006)

MATC 354

Fish

Rainbow trout

Oncorhynchus 

mykiss

Fresh OECD TG 203, 

1984

96-hr LC50 0.40 Nominal Mortality GLCC (1978b)

Bluegill sunfish

Lepomis 

macrochirus

Fresh OECD TG 203, 

ASTM, 1975

96-hr LC50 0.51 Nominal Mortality GLCC (1978a)

Fathead minnow

Pimephales 

promelas

Fresh OECD TG 203, 

1984 

96-hr LC50 0.54 Measured 

Flow-through

Mortality GLCC (1988a)
Page 104 of 135

Table_Apx F-1: Toxicity from TBBPA to Aquatic Organisms

Test Organism Fresh/

Salt 

Water

Test Guideline/

Study Type

Duration Endpoint Concentration 

(mg/L)

Chemical 

Analysis

Effects Reference

Rainbow trout

Oncorhynchus 

mykiss

Fresh OECD TG 203 96-hr LC50 1.1 Measured 

Flow-through

Mortality ACC (2003)

Zebra fish

Danio rerio

Fresh OECD TG 202 96-hr LC50 1.1 Nominal 

Static

Mortality Chow et al. (2013)

Fathead 

minnow

Pimephales 

promelas

Fresh USEPA CFR 40 

797.1600 35-day

LOEC 0.31

Flow-through

Measured

Early Life Stage 

Survival,

Hatching

NOEC SLS (1989c) 0.16

MATC 0.22

Note: The shaded rows indicate the principal study used for assessing acute / chronic risks to aquatic organisms. a Test guideline/type not reported

LOEC = Lowest Observed Effect Concentration

NOEC = No Observed Effect Concentration

MATC = Maximum Acceptable Toxicant Concentration

OC = Organic Carbon
Page 105 of 135

F-2 Toxicity to Terrestrial Organisms

F-2-1 Terrestrial Plant Toxicity

The effect of tetrabromobisphenol-A (purity: 99%) on 21-day emergence and growth of six species of 

plants (ACC-BFRIP, 2002) was determined using OECD Guideline 208 (proposed version), US EPA OPPTS 

850.4100 (1996) and US EPA OPPTS 850.4225 (1996).

The following six plant species were tested: Monocots - corn (Zea mays), onion (Allium cepa), ryegrass 

(Lolium perenne); Dicots - cucumber (Cucumis sativa), soybean (Glycine max) and tomato (Lycopersicon 

esculentum). Overall, treatment-related effects on seedling growth were seen in five out of the six 

species tested (soybean was the exception). In contrast, no treatment-related effects were seen on 

seedling emergence or condition of seedling in any of the species tested. The MATCs for corn, 

cucumber, onion, ryegrass and tomato are 518, 32, 518, 127 and 518 mg/kg dry soil, respectively (ACCBFRIP, 2002). 

Terrestrial plants were not considered for the proposed TBBPA risk assessment. For perspective, TBBPA 

is two to three orders of magnitude less toxic to terrestrial plants than to soil-dwelling organisms.

F-2-2 Soil Invertebrate Toxicity

EPA considered three studies evaluating potential toxicity to soil-dwelling organisms to be of sufficient 

quality to support hazard characterization of TBBPA. These studies are summarized in Table_Apx F-2.

In 2003, earthworms (Eisenia fetida) were exposed to TBBPA in a 56-day reproductive study (ACCBFRIP, 2003). The experimentally-derived and analytically-measured 56-day NOEC, LOEC and MATC

values were 2.1, 4.5 and 3.1 mg/kg soil (dry weight), respectively. In 2005, results from a 56-day 

reproductive study with soil-dwelling worms (E. fetida) indicated that adverse effects from TBBPA were 

observed at nominal concentrations as low as 0.63 mg/kg (LOEC) (ACC-BFRIP, 2005a). The reported 

nominal NOEC is 0.31 mg/kg dry weight soil and the MATC was determined to be 0.44 mg/kg dry 

weight soil. Furthermore, an additional earthworm study was conducted in 2006 using reproduction as 

the endpoint of concern (Sverdrup et al., 2006). Sverdrup et al. (2006) exposed Enchytraeus crypticus

to TBBPA for 21 days. Based on reproduction, the experimentally-derived and analytically-measured 

21-day NOEC, LOEC and MATC values were 3, 10 and 5.5 mg/kg soil (dry weight), respectively. 
Page 106 of 135

Table_Apx F-2: Soil Invertebrate Toxicity Data for TBBPA (mg/kg)

Test Organism Test Guideline/

Study Type

Duration 

(day) Endpoint Value (mg/kg)

Test 

Analysis Effect Reference

Terrestrial Organisms

Earthworm

(Enchytraeus 

crypticus)

ISO, 2002 21-day 

LOEC 10

Measured Reproduction Sverdrup et al. 

(2006) NOEC 3

MATC 5.5

Earthworm 

(Eisenia fetida)

USEPA OPPTS 850.6200, 

OECD TG 207 56-day

LOEC 4.5

Measured Reproduction ACC-BFRIP 

(2003)

NOEC 2.1

MATC 3.1

Earthworm 

(Eisenia fetida)

USEPA OPPTS 850.6200, 

OECD TG 207/222 56-day

EC50 0.91

Nominal Reproduction ACC-BFRIP, 

2005a

LOEC 0.63

NOEC 0.31

MATC 0.44

Note: The shaded row indicates the principal study used for assessing acute risks to aquatic organisms.

LOEC = Lowest Observed Effect Concentration

NOEC = No Observed Effect Concentration

MATC = Maximum Acceptable Toxicant Concentration

The most sensitive species is expected to be protective of a wider variety of species that are not 

specifically represented by the available experimental data. The E. fetida 56-day MATC of 0.44 mg/kg, 

based on reproduction, was the lowest endpoint, and it was divided by an uncertainty factor (UF) of 10 

for chronic effects, as per established EPA/OPPT methods (EPA, 2012d, 2013b), to give a chronic COC 

of 0.044 mg/kg or 44 μg/kg.

F-2-3 Avian Toxicity

Under EPA’s High Production Volume (HPV) Chemical Challenge program, data on birds have been 

submitted for TBBPA (ACC, 2006) and are described below. 

Several experiments have been conducted on distribution and effects of TBBPA in birds. 14C-TBBPA 

was injected into quail eggs (1.9 μg/g egg) on day 3 of incubation, and uptake and distribution of 14CTBBPA was studied in 6- and 9- day-old quail embryos. TBBPA was also administered to adult females 

(single oral or intravenous doses, 250 μg/bird) to investigate its distribution. In addition, the potential 

for certain reproductive and endocrine effects were evaluated in adult birds after embryonic exposure 

(15 μg/g egg). The embryonic uptake of TBBPA was low (< 1% of the radiolabel) after yolk injection on 

day 3 and was distributed in the yolk, although metabolism was detected based on labeling in the liver, 

bile and allantoic fluid. Thus, TBBPA’s transfer to the embryo from the yolk was low with rapid 

metabolism and excretion (Halldin et al., 2001).

In laying quail, TBBPA was rapidly eliminated via bile and excreted in feces, and transfer to egg yolks 

was low. This effect was seen after oral and intravenous administration. In ovo exposure to TBBPA (15 

μg/g egg) did not cause estrogen-like effects in the adult quail. Egg-laying was not affected in female 
Page 107 of 135

birds, and no effect in male quail on sexual behavior, testis weight or plasma testosterone was 

detected (Halldin et al., 2001). 

A previous study by the same group of investigators after 45 μg TBBPA /g was injected in quail eggs 

also did not find estrogenic-like effects (Berg et al., 2001).

Given the lack of effects observed in these studies and method of exposure (egg injection) for some 

studies, EPA/OPPT doesn’t plan to evaluate these effects in the proposed risk assessment.

F-3 Toxicity to Amphibians

Data on amphibians have also been submitted to EPA for TBBPA (ACC, 2006) and have been evaluated 

by EC/HC (2013). 

In the frog embryo teratogenesis assay: Xenopus (FETAX) bioassay, TBBPA was evaluated for potential 

hormonal activity in the tadpole (Xenopus) embryo during the first 96 hours of development. Mortality, 

malformation rate and growth inhibition/acceleration were evaluated by measuring changes in embryo 

length and the presence of features indicative of earlier/later life stages. At 0.1, 1, 10 100 or 500 μg/L, 

TBBPA had no effect on Xenopus development when using either standard or minimal levels of sodium 

and potassium (Garber et al., 2001). 

TBBPA was also evaluated in the tadpole (Xenopus) tail regression assay to determine possible effects 

on thyroid hormones. At developmental stage 5818, TBBPA was microinjected into tadpoles at doses up 

to 60 μg/tadpole. Although positive controls showed delayed tail resorption, TBBPA showed no effects 

on tail resorption (Balch and Metcalfe, 2001).

TBBPA was found to decrease functioning of the thyroid hormone, triiodothyronine (T3), which is

critical to the triggering and control of metamorphosis in amphibians(Brown et al., 1996; Hanada et al., 

2003; Kashiwagi et al., 1999). Veldhoen et al. (2006) studied pre-metamorphic tadpoles of the Pacific tree

frog (Pseudacris regilla) and found that normal thyroid hormone-mediated gene expression profiles

were significantly altered at both TBBPA concentrations (5.4 μg/L and 54 μg/L) evaluated. The results

show changes in endocrine-regulated gene expression at a sensitive life stage of the frog can occur 

within hours of exposure to low concentrations (EC/HC, 2013). 

The possible adverse effects of tetrabromobisphenol A exposure on the endocrine system in 

amphibians have shown mixed results. Furthermore, the effect of changes in gene expression is 

not clear. For these reasons, EPA/OPPT has not considered these results further for inclusion 

in a risk assessment of TBBPA.

 18 Normal growth at this stage would be the following: hind limbs emerged and forelimbs formed but not emerged.
Page 108 of 135

F-4 Summary of Environmental Hazard

Ecotoxicity studies for TBBPA have been conducted in aquatic plants, aquatic invertebrates (water 

column and sediment), fish, terrestrial plant species, soil invertebrates and birds. Four COCs were 

derived for the assessment, as summarized in Table_Apx F-3. The first COC in the table was 

determined by dividing the acute effect level by an uncertainty factor of 5; the three chronic COCs 

were calculated using a chronic uncertainty factor of 10. 

Table_Apx F-3: Ecotoxicity Concentrations of Concern

Environmental Toxicity Concentration of Concern 

(COC)

Species and Effect Reference

Acute toxicity, aquatic water 

column organisms 

0.02 mg/L Eastern oyster; 

shell deposition

SLS (1989a)

Chronic toxicity, aquatic 

water column organisms

0.002 mg/L Blue mussel;

Growth rate, 

shell length

ACC (2005)

Chronic toxicity, 

aquatic/sediment-dwelling 

organisms

11.7 mg/kg Blackworm;

reproduction

Krueger (2002a)

Chronic toxicity, terrestrial 

organisms

0.044 mg/kg Earthworm;

reproduction

ACC-BFRIP (2005)
Page 109 of 135

Appendix G Human Health Hazard Study Summaries

The toxicological effects of TBBPA have been extensively reviewed and evaluated by the European 

Union (EC, 2006) and Health Canada (EC/HC, 2013). EPA/OPPT’s Design for the Environment and the 

National Toxicology Program (EPA, 2014e; NTP, 2014a) have also provided toxicity reviews. Therefore, 

most of the sections below that describe available toxicokinetics and toxicodynamics studies as well as 

mode of action data rely heavily on previous assessments. The reader is referred to these previous 

reviews and original articles for more detailed information. A more recent study, the NTP (2014a)

cancer bioassay, is described in more detail.

Most studies using TBBPA have been rodent studies, primarily conducted via the oral route. In a recent 

NTP cancer bioassay, TBBPA was associated with more than one tumor type in rodents. Also, some 

developmental/newborn rodent studies resulted in effects. However, many of the subchronic, 

reproductive and developmental toxicity studies conducted in rodents found no effects at the highest 

doses tested.

G-1 Epidemiology 

In a cross-sectional study on 515 high school students in Belgium, TBBPA measured in serum was not 

consistently associated with changes in neurobehavioral function in these adolescents, as assessed by 

several types of tests (Kicinski et al., 2012). 

G-2 Toxicokinetics

There are no in vivo toxicokinetics data via the dermal route for TBBPA. However, in vitro data show 

that TBBPA applied as 2 mg/cm2 to human skin for 24 hours results in limited absorption (< 1%) (ECHA, 

2013). This information, combined with TBBPA’s low water solubility, high molecular weight and high 

log KOW suggest that the compound will have limited absorption through the skin (EC, 2006). 

Data are also lacking on TBBPA’s toxicokinetics after inhalation. TBBPA has a median particle size of 

approximately 31.81 to 52.20 μm. Approximately 4% of the particles are <15 μm in diameter (EC, 

2006). The particle size distribution indicates that only a small amount of TBBPA is expected to be 

respirable (< 10 μm) and an even smaller amount of this respirable fraction is expected to deposit in 

the alveolar region of the lungs after inhalation. Another amount will deposit in the nasopharyngeal 

region and be either exhaled or swallowed/absorbed through the GI tract. The EU assumed that 

approximately 75% of inhaled particles will be absorbed; 70% of this was assumed to be from 

swallowing/GI tract absorption and 5% from absorption through the lung (EC, 2006).

Several oral toxicokinetics studies have been conducted in rodents. An oral study of Sprague Dawley 

rats shows that considerable amounts (e.g., > 70%) of TBBPA can be absorbed by the gastrointestinal 

tract (Hakk et al., 2000). TBBPA can undergo Phase II metabolism directly, primarily conjugation via 

glucuronidation and/or sulfation. The conjugated forms are then excreted primarily via the feces after 

oral exposure (Hakk et al., 2000; Kuester et al., 2007; Schauer et al., 2006).
Page 110 of 135

Approximately 95% of TBBPA or its metabolites were excreted in the feces within 72 hours after a 

single oral administration and only about 1% was excreted in the urine (Hakk et al., 2000). There was 

limited retention of TBBPA or metabolites in the blood and tissues (liver: 0.4%, muscle: 0.12%, skin: 

0.12%, fat: 0.7%, blood: 0.01%). Rapid elimination and low tissue retention of TBBPA were also 

reported in Fischer 344 rats following oral or intravenous routes of exposure. Rates of elimination and 

tissue retention were comparable for single doses or for repeated daily doses of 20 mg/kg-bw for 5 or 

10 consecutive days (Kuester et al., 2007). One study in pregnant rats found limited transfer of TBBPA 

or its metabolites to the fetus; tissues in the pregnant rats and fetuses contained about 1.2% and 

0.34%, respectively, of radioactivity 48 hours after exposure to 14C ring-labeled TBBPA (Meerts et al., 

1999). 

Similar to results of rat studies, TBBPA-glucuronide and TBBPA-sulfate were identified as the major 

metabolites in humans after oral administration of TBBPA (Schauer et al., 2006; Zalko et al., 2006). The 

half-life of TBBPA in humans has been estimated to be about 2 days (Hagmar et al., 2000; Sjodin et al., 

2003).

 

G-3 Acute Toxicity

Acute oral, dermal and inhalation studies have been performed with TBBPA. These studies show that 

TBBPA has low acute toxicity by all routes of exposure. The oral LD50s are > 50,000 mg/kg-bw in rats 

and 3200 mg/kg-bw in mice; the dermal LD50 is > 10,000 mg/kg-bw in rabbits; and inhalation LC50s are 

> 10.92 mg/L in rats and > 50 mg/L in mice (GLCC, 1967; Gustafsson and Wallen, 1988; HTRI, 1966; 

IBRI, 1967; VCC, 1978a).

Nakajima et al. (2009) evaluated neurobehavioral changes in an open-field test 3 hours after gavage 

exposure using 0.1, 5 or 250 mg/kg-bw/day TBBPA. Some behavioral effects were seen at 0.1 and 5.0 

but not at 250 mg/kg-bw/day. TBBPA was found in the striatum at the two lowest doses and showed 

non-specific accumulation in the brain at 250 mg/kg-bw/day. Given the lack of a dose response, it is 

difficult to make a conclusion regarding acute neurobehavioral effects from this study. 

G-4 Repeated-Dose Toxicity

The chronic and subchronic toxicity of TBBPA was investigated in an inhalation study, a dermal study 

and several oral repeated-dose studies. The inhalation and dermal studies are discussed. Oral studies 

of 90 days or longer are also summarized. 

G-4-1 Inhalation

In a 14-day inhalation study in rats (IRDC, 1975), the EU concluded that no adverse systemic effects 

were reported at 2, 6 and 18 mg/L, with the exception of signs of mechanical irritation in all treatment 

groups due to the high dust levels (EC, 2006).
Page 111 of 135

G-4-2 Dermal

In a 21-day dermal study, TBBPA was administered to rabbits at doses up to 2,500 mg/kg-bw/day for 6 

hours/day, 5 days/week. No toxicologically significant effects were identified (IRDC, 1979).

G-4-3 Oral – Gavage

In a 90-day oral gavage study, rats were administered TBBPA at doses of 0, 100, 300 or 1,000 mg/kgbw/day (MPI_Research, 2002a). No neurobehavioral effects were observed during the weekly 

functional observational battery evaluations. Slight changes in hematological evaluations and clinical 

chemistry were reported; however, the EU concluded that these effects were not toxicologically 

significant. Statistically significant decreases in serum T4 were reported in males and females, but no 

accompanying change in serum T3, thyroid stimulating hormone (TSH) or histopathology of the liver, 

thyroid, parathyroid or pituitary was reported. The EU again concluded that the decreases in serum T4

were not adverse. Absolute spleen weight was decreased in males in the top two dose groups; no 

histopathological findings were noted. An increase in relative epididymis weight was reported in the 

middle dose group; however, no changes in relative epididymis weight or histopathology were 

identified in the high dose group. Again, the EU concluded that these findings were of no toxicological 

significance (EC, 2006). 

In a recent subchronic toxicity study, groups of 10 male and 10 female F344/NTac rats and B6C3F1 

mice were administered 0, 10, 50, 100, 500 or 1,000 mg/kg-bw/day TBBPA in corn oil by gavage, 5 days 

per week for up to 14 weeks (NTP, 2014a). In the rats, dose-related decreases in serum T4 levels 

occurred on day 4 and at week 14 in 500 and 1,000 mg/kg-bw/day males and females. These effects 

occurred less consistently at 100 mg/kg-bw/day. Significant increases occurred in liver weights of 500 

and 1,000 mg/kg-bw/day rats (males and females) and significant decreases occurred in spleen weights 

of 500 and 1,000 mg/kg-bw/day males. No treatment-related histopathologic lesions were observed.

In the mice, liver weights of 500 mg/kg-bw/day males and 1,000 mg/kg-bw/day males and females 

were significantly greater than those of the vehicle controls. Kidney weights were significantly 

decreased and spleen weights were significantly increased in 1,000 mg/kg-bw/day males. At 500 and 

1000 mg/kg-bw/day, males exhibited increased incidences of renal tubule cytoplasmic alterations. No 

additional treatment-related histopathologic lesions were observed in mice in this 14-week study (NTP, 

2014a). 

Administration of TBBPA in corn oil to Wistar Han rats at 0, 250, 500 or 1,000 mg/kg-bw/day 5 days per 

week by gavage for up to 105 weeks resulted in decreased body weight (by at least 10% lower than 

vehicle controls after week 25) at 500 and 1,000 mg/kg-bw/day. At three months, thymus weights in 

the 1,000 mg/kg-bw/day dose group were significantly lower and liver weights were higher than 

vehicle controls. Females at all doses exhibited increased incidences of nonneoplastic lesions of the 

uterus (NTP, 2014a). 

B6C3F1 mice (50/sex/dose) were also administered TBBPA via gavage in corn oil at 0, 250, 500 or 1,000 

mg/kg-bw/day for 5 days/week for up to 105 weeks. Mice at 1,000 showed decreased body weights 
Page 112 of 135

(by more than 10% after week 25) and decreased survival compared with vehicle controls. In male 

mice, nonneoplastic lesions were seen in the liver and kidney at 250 and 500 mg/kg-bw/day. Male 

mice at 500 mg/kg-day and female mice at 250 and 500 mg/kg-bw/day exhibited forestomach lesions 

(NTP, 2014a).

G-4-4 Oral – Dietary

Rats were fed a diet for 3 months that included approximately 0, 0.3, 3, 30 or 100 mg/kg-bw/day 

TBBPA. No changes were observed in clinical signs, body weights, hematology, clinical chemistry, 

urinalysis, organ weights, gross or microscopic pathology (Dow_Chemical, 1975).

TBBPA was given to B6C3F1 mice at 0, 500, 4900, 15,600 or 50,000 ppm (approximately 0, 71, 700, 

2,200 or 7,100 mg/kg-bw/day) for 3 months. All mice at 7,100 mg/kg-bw/day died but no mice died at 

lower doses. Body weight gains were decreased at 2,200 and 7,100 mg/kg-bw/day and red blood cells, 

hemoglobin, hematocrit, serum triglycerides and total serum proteins were decreased at 2,200 mg/kgbw/day. Increased spleen weights were also observed (Tobe et al., 1986).

G-5 Reproductive and Developmental Toxicity

G-5-1 Multigenerational Studies

No effects on reproduction, fertility or developmental toxicity including neurobehavioral abnormalities 

(e.g., motor activity, learning and memory, auditory response) were observed in an OECD compliant 

two-generation study in Sprague-Dawley rats using gavage doses of 0, 10, 100 or 1,000 mg/kg-bw/day 

(MPI_Research, 2002b, 2003). In this study, there were significant decreases in serum thyroxine (T4) 

levels in F0 and F1 offspring at 100 and 1,000 mg/kg-bw/day. Mean serum T3 levels were also 

significantly lower in F0 males at the highest dose (1,000 mg/kg-bw/day), but no changes were found in 

the F0 females or in the male or female F1 offspring. There were also no effects on TSH levels or 

microscopic changes in the liver or pituitary gland; the thyroid was not examined histopathologically. 

There was no dose-response relationship in T4 levels; following the 30-day recovery period, the levels 

were similar to controls. The European Union concluded that the thyroxine effects were not 

toxicologically significant (EC, 2006). 

Van der Ven et al. (2008)reported the results of a one-generation reproduction dietary study in Wistar 

rats using TBBPA doses of ~ 0, 3, 10, 30, 100, 300, 1,000 or 3,000 mg/kg-bw/day. In this study, 

exposure lasted 11 weeks (males) and 2 weeks (females) prior to mating and during mating (both 

sexes). For females, dosing continued throughout gestation and lactation. After weaning, dosing of 

offspring were 10 weeks old. Dams exhibited decreased body weight at the highest dose along with 

reduced food consumption. However, benchmark doses calculated at the lower 95% confidence limit 

for an associated 10% decrease in body weight were close to the highest dose and sometimes higher 

than 3000 mg/kg-bw/day. There were no effects on the reproduction parameters examined, including 

sperm count or morphology.
Page 113 of 135

In offspring, decreased plasma T4 levels were associated with lower bounds on benchmark doses 

(BMDL10s) of 30.8 and 16.1 mg/kg-bw/day in males and females, respectively. Modeling of the 

increased T3 levels in female offspring resulted in a BMDL10 of 2.3 mg/kg-bw/day; this effect was not 

seen in males. The authors also report BMDL10s of 0.5 and 0.6 mg/kg-bw/day, respectively, for 

increased testicular and pituitary gland weights in male offspring. The testes, pituitary gland and 

thyroid gland did not exhibit histopathological changes to accompany the increased organ weights or 

hormone changes. Other effects in offspring (decreased anogenital distance in females at day 7 but not 

day 4 or 21; number of days to vaginal opening) were observed. However, BMDLs for these effects 

were calculated as 2736 and 2745 mg/kg-bw/day, respectively (Van der Ven et al., 2008). Review of 

data by dose level as presented in this publication didn’t always reveal clear dose-response

relationships.

The possible neurobehavioral effects in offspring from the above one-generation reproduction study 

were investigated from PND 50 to 140 after being exposed in utero and after direct dosing of TBBPA. 

The authors examined auditory responses by measuring brainstem auditory evoked potentials (BAEPs), 

which are electrophysiologic responses elicited by auditory stimuli and recorded from the scalp or 

brain surface as waveform with a series of positive and negative peaks (Lilienthal et al., 2008). 

The authors reported that BAEP thresholds and wave IV latency were increased in exposed female 

offspring in the low sound frequency range. In the males, absolute latency of wave IV and interpeak 

latencies II-IV were also increased at low frequencies of sound. The authors reported a BMDL10 of 8 

mg/kg-bw/day for wave IV latency. BMDLs for increased BAEP thresholds in females ranged from 1 to 

40 mg/kg-bw depending on the sound frequency at which they were measured (Lilienthal et al., 2008). 

Both of the above studies have been criticized for various reasons. Banasik et al. (2009) expressed 

concerns about Van der Ven et al. (2008) regarding the use of modeling software, methodology and 

conduct of the study. Also, the effects identified by Van der Ven et al. (2008) were not considered 

critical endpoints by Health Canada (EC/HC, 2013). Some of the methods and statistical analyses of the 

findings presented by Lilienthal et al. (2008) were also called into question by Strain et al. (2009).

Other limitations or deficiencies of Lilienthal et al. (2008) were identified by comparing the study with 

EPA’s Office of Chemical Safety and Pollution Prevention (OCSPP) Test Guidelines on Neurophysiology: 

Sensory Evoked Potentials (870.6855, August 1998). According to these EPA test guidelines, a 

pigmented strain of rat is the preferred animal species to be tested because albino strains of animals 

have known abnormalities of the visual and auditory systems. Furthermore, at least 10 nulliparous and 

nonpregnant rats per group should be used, and positive control groups exhibiting functional changes 

in the sensory systems to be tested are recommended. Instead, the study of Lilienthal et al. (2008)

used groups of 5-6 pregnant Wistar rats (which are albino rats) and did not include positive controls.

In a separate review of Lilienthal et al. (2008) by an EPA neurotoxicologist, it was noted that although 

the criticisms by Strain et al. (2009) have some merit, they are not sufficient to completely dismiss the 

findings (Herr, 2013). EPA/OPPT believes that this study suggests the potential for auditory effects but 

will not use this study in a quantitative risk assessment given some concerns (one being the use of 

albino rats) and the difficulty determining what exposures may lead to the effects (e.g., whether

exposure by the dams/parents or direct exposure to the offspring experiencing the effects is most 

relevant). 
Page 114 of 135

Zatecka et al. (2013) conducted a 2-generation drinking water study in CD1 outbred mice. In the 

parental generation, TBBPA was administered only to pregnant dams during gestation (at 0 or 0.035 

mg/kg-bw/day) and not to fathers. F1 offspring were then dosed during pre-pubescence, pubescence 

and up to adulthood and evaluated at 70 days of age. In the F1 offspring, there was an increased 

incidence of apoptotic cells in testes and increased expression of genes encoding proteins important 

during spermatogenesis. The F1 generation was then bred in a cross-over fashion using four patterns 

(both parents exposed; neither exposed; mother exposed; father exposed). The F2 offspring were then 

evaluated at 70 days of age; it is not clear from the study description whether the F2 rats had access to 

TBBPA in the drinking water or from dam’s milk or both. In the F2 offspring with both parents exposed 

to TBBPA, testicular weights were reduced (p < 0.01), prostate weights were increased (p < 0.05) and 

seminal vesicle weights were increased (p < 0.01). The F2 generation with only fathers exposed showed 

increased epididymis weights (p < 0.01). No visible abnormalities or pathological changes in 

seminiferous tubule morphology were seen. The significance in these effects is unclear because only 

one dose was used and histopathological, sperm and other reproductive effects were not observed. 

G-5-2 Prenatal and Postnatal Developmental Toxicity Studies

There were no significant dose-related effects on T4, T3 or TSH in offspring at PND 20 or postnatal week 

11 after pregnant Sprague-Dawley rats were fed TBBPA at dietary levels of 0, 100, 1,000 or 10,000 ppm 

(~ 17, 149 or 1472 mg/kg-bw/day) from gestation day (GD) 10 to PND 20. However, offspring exhibited 

slight decreases in T3 on PND 20 that were not dose-related. TBBPA did not alter brain development or 

other reproductive parameters. The study did not state whether offspring had direct access to TBBPA 

in the food (Saegusa et al., 2009). 

In a pilot range-finding study (VCC, 1978b), no developmental effects were observed in offspring of 

dams administered TBBPA up to 10,000 mg/kg-bw/day from GD 6-15. In a standard developmental 

toxicity study (Noda et al., 1985), pregnant Wistar rats were administered TBBPA via gavage from GD 0 

to 20 at doses up to 2,500 mg/kg-bw/day. No effects were seen in dams or in offspring evaluated up to 

PND 21. In another developmental toxicity study (MPI_Research, 2001), pregnant rats were 

administered TBBPA via gavage up to 1,000 mg/kg-bw/day from GD 0 to 19 and again, no effects were 

observed in dams or offspring.

No differences in various neurobehavioral measures in a study of NMRI mice administered 0.75 and 

11.5 mg TBBPA/kg-bw orally on PND 10 (Eriksson et al., 2001; Eriksson et al., 1998). 

Viberg and Eriksson (2011) report biochemical changes related to cholinergic effects in neonatal NMRI 

mice treated with 11.5 mg TBBPA/kg-day. Radioactivity from TBBPA dosing was highest (at 3.7%) in the 

brain at 3 hours, decreased to 0.9% at 24 hours and was 0.3% by 7 days after dosing. It is not entirely 

clear whether the study controlled for possible litter effects. Although some evaluations were done 

with equal numbers of animals per litter, methods of litter culling were less clear for other assessments 

(Viberg and Eriksson, 2011). 

In a study in which TBBPA was administered at 0%, 0.01%, 0.1% or 1% in the diet to pregnant ICR mice 

(6/dose) from the first day of gestation to weaning at postnatal day 27, no effects on average litter 

size, litter weight, total number of offspring, average male or female offspring weights or dam weights 
Page 115 of 135

were reported (Tada et al., 2006). The offspring drank the dam’s milk while the dams were being 

treated. Also, offspring had access to dam’s food from PND 22 to 27; it is not known how much was 

ingested. Changes in total cholesterol, triglycerides and organ weights (liver, brain, spleen) were seen 

primarily at the highest dose (p < 0.05) in the dams. Female offspring exhibited an increased incidence 

of renal tubule atrophy at the highest dose. Based on enlargement of hepatocytes and very slight focal 

necrosis of hepatocytes in female offspring, Health Canada considered the LOAEL to be 0.1% (~140.5 

mg/kg-bw/day during gestation), with a NOAEL of 0.01% (~15.7 mg/kg-bw/day during gestation).19

Littermates were used as independent variables for the experimental and statistical analyses. Thus, the 

tendency of littermates to respond more similarly to one another than non-litter mates was not fully 

taken into account. However, the authors chose the same number (4 offspring of each sex) randomly 

from each litter to partially account for such effects (Tada et al., 2006).

In a dietary developmental toxicity study, Saegusa et al. (2012) administered TBBPA to Sprague Dawley 

rats from GD 10 through PND 12. The highest concentration (10,000 ppm or ~ 800 mg/kg-bw/day) 

resulted in increased interneurons in the dentate hilus-expressing reelin; this effect suggests 

alterations in neuronal migration. It is not clear from this study whether offspring had direct access to 

TBBPA in the diet of the dams after birth.

In a study of newborn rats directly dosed by gavage from days 4 to 21 after birth, an effect on the 

kidneys (polycystic lesions associated with the dilation of tubules) was noted at 200 and 600 mg/kgbw/day but not at 40 mg/kg-bw/day. Effects at 600 mg/kg-bw/day were considered moderate in 

females and severe in males whereas the lesions seen in the two males that exhibited effects at 200 

mg/kg-bw/day were of slight severity. At 85 days of age, nephrotoxic lesions were still seen at 200 and 

600 mg/kg-bw/day. There were no neurobehavioral effects as assessed by testing reflexes on PND 21 

(Fukuda et al., 2004). Based on the slight effects in the kidney at 200 mg/k-bw/day, the LOAEL is 

considered to be 200 and the NOAEL 40 mg/kg-bw/day.

In comparison, no similar effect was found in 5-week old rats dosed via gavage with 2,000 or 6,000 

mg/kg-bw/day for 18 days (Fukuda et al., 2004). The EU suggested that the kidney effects observed in 

the newborn rats are likely due to the immature metabolic capability and/or immature kidneys (EC, 

2006).

G-6 Irritation and Sensitization

The European Union and Canada concluded that TBBPA is not a skin, eye or respiratory irritant and is 

not considered to be a skin or respiratory sensitizer in animals or humans (EC, 2006; EC/HC, 2013; 

GLCC, 1967; Gustafsson and Wallen, 1988; HTRI, 1966; IBRI, 1967; VCC, 1978a). 

G-7 Genotoxicity and Carcinogenicity

The following sections present the finding of the NTP (2014a) cancer bioassay and discuss conclusions 

from the Office of Pesticide Program’s (OPP’s) Cancer Assessment Review Committee (CARC) about 

 19 The LOAEL and NOAEL during lactation are associated with doses of 379.9 and 42.1 mg/kg-bw/day, respectively.
Page 116 of 135

TBBPA-related tumors and human relevance. Mode of action is also discussed along with EPA/OPPT’s 

overall classification regarding human relevance.

G-7-1 Genotoxicity

Both in vitro and in vivo assays discussed in available reviews have found that TBBPA is not genotoxic. 

These studies include multiple bacterial reverse mutation assays with and without metabolic 

activation, an in vitro test for intragenic recombination in mammalian cells, an in vitro mammalian 

chromosomal aberration test using human peripheral blood lymphocytes (with and without metabolic 

activation) and a mouse micronucleus study(EC, 2006; NTP, 2014a).

G-7-2 NTP Carcinogenesis Bioassays

NTP recently published a report of the results of carcinogenesis studies of TBBPA in rats and mice (NTP, 

2014a). Groups of Wistar Han rats and B6C3F1 mice were administered 0, 250, 500 or 1,000 mg/kgbw/day TBBPA in corn oil by gavage, 5 days per week for up to 105 weeks. At 0 and 1,000 mg/kgbw/day, 60 rats/sex/dose were used and at 250 and 500 mg/kg-bw/day, 50 rats/sex/dose were used. 

Fifty mice/sex/dose were used for all doses. 

G-7-2-1 Findings in Rats

Males

In males, mean body weights were at least 10% lower than controls after week 25. There were no 

clinical findings and survival did not differ between dosed groups and controls. At three months, there 

were no treatment-related lesions. After two years, the incidences of interstitial cell adenoma of the 

testis were slightly increased at 500 (1/50) and 1,000 mg/kg-bw/day (3/50) compared to controls 

(0/50) (p < 0.05 for the trend test). Pairwise comparisons were not statistically significant.

Females

Body weights were similar in all groups, including controls. There were no clinical findings and survival 

was similar among all groups. No treatment-related lesions were seen at the three-month evaluation.

For the uterus only (not other tissues), NTP first evaluated the tissues transversely and later evaluated 

them longitudinally. According to the original transverse evaluation, there were increases in both 

neoplastic and non-neoplastic lesions of epithelial origin. Cystic endometrial hyperplasia of the 

endometrium was increased at 1,000 mg/kg-bw/day (p < 0.05 by the Poly-3 test). NTP found positive 

dose-response trends in the incidences of 1) adenoma (p = 0.001) and 2) adenocarcinoma (epithelial 

origin) (p < 0.05; Poly-3 test). When tumors were combined, the incidences of adenoma, 

adenocarcinoma or malignant mixed Müllerian tumors of the uterus showed a positive trend (p < 0.05 

by the Poly-3 test). By pairwise comparison, the incidences were significantly increased in the 500 and 

1,000 mg/kg-bw/day groups (p < 0.05 and < 0.01 by the Poly-3 test). The combined incidences of these 

three tumor types in control, low-, mid- and high-dose groups were: 3/50, 7/50, 11/50 and 13/50, 

respectively. 
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More nonneoplastic and neoplastic lesions of epithelial origin were identified after longitudinal 

evaluation of residual uterine tissue. When the original and residual evaluations were combined, 

atypical endometrial hyperplasia was significantly higher than controls at all doses (p < 0.01; Poly-3 

test). However, cystic endometrial hyperplasias were no longer significantly higher than controls. There 

were positive trends (Poly-3 test) in the incidences of 1) adenocarcinoma alone (p < 0.01) and 2) the 

combined incidences of adenoma, adenocarcinoma or malignant mixed Müllerian tumor (p < 0.001) for 

the combination of original and residual sections. For both adenocarcinomas alone and for the 

combined tumor types, pairwise comparisons showed that incidences were increased in the 500 and 

1,000 mg/kg-bw/day groups (p <0.01; Poly-3 test). The combined incidences of the three tumor types 

in the control, low-, mid- and high-dose groups were: 6/50, 11/50, 16/50 and 19/50, respectively. 

In the ovaries, incidences of rete ovarii cysts were significantly greater at 500 and 1,000 mg/kg-bw/day 

compared with controls (p < 0.05; Poly-3 test).

G-7-2-2 Findings in Mice

Both Sexes – Decreased Survival

Survival of mice at 1,000 mg/kg-bw/day (577 days for males; 413 days for females) was lower than 

controls (687 days for males; 711 days for females) (p < 0.001). Decreased survival was seen as early as 

6 months. Although (NTP, 2014a) reports numbers of 1,000 mg/kg-bw/day mice that had neoplasms, 

the incidence is lower than the 500 mg/kg-bw/day group and the decreased survival at 1,000 mg/kgbw/day was not attributed to the tumors. Instead, decreased survival was associated with decreased 

body weight gain and may have been due to gastrointestinal toxicity. Because of the decreased 

survival at the highest dose, NTP (2014a) evaluated tumors only for the 0, 250 and 500 mg/kg-bw/day 

dose groups. 

Males

Several non-neoplastic lesions were observed in the kidney and forestomach. Renal tubule cytoplasmic 

alterations were observed at 250 and 500 mg/kg-bw/day (< 0.01; Poly-3 test) and increased in severity 

by dose. In the forestomach, the 500 mg/kg-bw/day males exhibited ulcers, mononuclear cell 

infiltration, inflammation and epithelium hyperplasia (p < 0.05 or < 0.01).

Both nonneoplastic and neoplastic lesions were observed in the liver. Compared with the control 

group, the number of male mice with clear cell foci was increased at 500 mg/kg-bw/day; eosinophilic 

foci were significantly increased at 250 and 500 mg/kg-bw/day (p < 0.01 for all). The incidence of 

multiple hepatocellular adenoma was significantly increased at 500 mg/kg-bw/day compared with 

controls (p < 0.05; Poly-3 test). In addition, the incidences of hepatoblastoma (11/50) and the 

combined incidence of hepatocellular carcinoma or hepatoblastoma (24/50) in 250 mg/kg-bw/day 

males (11/50) were significantly greater than those in the vehicle controls(2/50 or 12/50, respectively) 

(p < 0.01; Poly-3 test). Differences were not statistically significant at 500 mg/kg-bw/day or by trend 

tests. 
Page 118 of 135

Other increased incidences of tumors were observed in the intestines or in all organs. The combined 

incidences (0/50, 0/50 and 3/50 at 0, 250 and 500 mg/kg-bw/day) of adenoma or carcinoma of the 

large intestine (cecum or colon) occurred with a significant positive trend (< 0.05 by the Poly-3 test). 

The incidences of 1) hemangiosarcomas or 2) combined hemangiomas/hemangiosarcomas (3/50, 5/50 

and 9/50 at 0, 250 and 500 mg/kg-bw/day) when summing tumors for all organs occurred with 

significant positive trends (p < 0.05 by the Poly-3 test). By pairwise comparison, hemangiosarcomas 

were higher than controls at 1,000 mg/kg-bw/day (p < 0.05; Poly-3 test).

Females

Females exhibited ulcers, mononuclear cell infiltration, inflammation and epithelium hyperplasia in the 

forestomach at 250 and 500 mg/kg-bw/day (females). No increased incidences of tumors were found 

in female mice. 

G-7-2-3 NTP Conclusions Regarding Tumors Related to TBBPA Treatment

Under the condition of these studies, NTP concluded that there was clear evidence of carcinogenic 

activity of TBBPA in female Wistar Han rats based on increased incidences of uterine epithelial tumors, 

which primarily included uterine adenocarcinomas. There was some evidence of carcinogenic activity 

of TBBPA in male B6C3F1/N mice based on the increased incidences of hepatoblastoma. NTP 

concluded that there was equivocal evidence of carcinogenic activity of TBBPA in male Wistar Han rats 

based on slightly increased incidences of testicular adenoma. The large intestine neoplasms and 

hemangiosarcoma (all organs) are considered equivocal findings. There was no evidence of 

carcinogenic activity of TBBPA in female B6C3F1/N mice (NTP, 2014a). 

G-7-3 CARC Conclusions Regarding Weight of Evidence for 

TBBPA-Related Tumors

The results of independent reviews of cancer bioassays/carcinogenicity, often of pesticides, are often 

subsequently peer-reviewed by EPA’s Cancer Assessment Review Committee (CARC), which reviews 

data and recommends a cancer classification. This classification will then determine how the Agency 

regulates pesticides or other reviewed compounds. The committee also recommends methods to 

quantify human health risk (http://www.epa.gov/pesticides/health/cancerfs.htm). During the problem 

formulation of TBBPA, EPA’s OPPT asked the CARC to provide an independent review of the newly 

available NTP study to help inform the cancer assessment. 

The CARC conclusions are based on whether clear statistically significant dose-response trends and 

pairwise statistical comparisons can be seen, whether precursor lesions were observed and whether 

tumors are clearly within historical control ranges.

Similar to the NTP conclusions, the CARC considered uterine tumors in rats to be clearly related to 

TBBPA treatment. However, in contrast to NTP’s conclusions, the CARC made the following 

conclusions: 
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• TBBPA treatment is not associated with testicular tumors in male rats and intestinal tumors 

(other than the hemangiosarcomas

• TBBPA is associated with hemangiomas and hemangiosarcomas in male mice 

• TBBPA is not related to hepatoblastomas in male mice based on the lack of either statistical 

significance or a dose trend. Despite statistical significance at the highest dose, the liver 

adenomas in male mice are not of concern from TBBPA exposure because incidences were 

within the historical control range and there were no precursor lesions. 

The CARC’s conclusions for each tumor type is further delineated in Supplemental File 4 (CARC, 2014). 

The CARC concluded that there is not enough evidence regarding the mode of action (MOA) to meet 

the International Programme on Chemical Safety (IPCS) 2007 Human Relevance Framework. This lack 

of clear MOA and unknown human relevance resulted in CARC deferring to the default science position 

of the 2005 EPA Cancer Guidelines (EPA, 2005) that tumors are relevant to humans. More information 

on the CARC’s overall weight of evidence specifically regarding relevance to humans is discussed in

Section 2.6.4.5G-7-5.

G-7-4 Mode of Action Considerations for Cancer

TBBPA’s possible MOAs for induction of tumors are not clearly understood. Although not an evaluation 

of all available data, some considerations as to TBBPA’s possible cancer MOAs are discussed here, with 

an emphasis on MOAs related to uterine tumors. 

Based on the toxicokinetics data, it is possible that liver effects (i.e., enlargement of hepatocytes, 

increased liver weight and slight focal necrosis of hepatocytes) observed in adult rats and/or mice after 

exposures to high doses of TBBPA for extended periods could be due to saturated metabolic capability 

and diminished elimination/excretion of the compound.

Negative genotoxicity studies suggest that a direct genotoxic MOA is not considered likely for 

tumorigenesis. The CARC also concluded that there is no likely concern for mutagenicity for TBBPA 

(CARC, 2014).

Uterine tumors can arise in response to endogenous estrogen overstimulation in aged rats, which can 

be exacerbated by administration of exogenous chemicals through direct and indirect pathways (Alison 

et al., 1994; Lax, 2004). After binding directly to estrogen receptors (ERs) in a cell, endogenous 

estrogen and estrogen agonists can activate hormone-responsive genes that promote DNA synthesis 

and cell proliferation. Therefore, estrogen and estrogen agonists can act as tumor promoters by 

inducing proliferation of cells with pre-existing mutations and eventually lead to tumor formation. 

Estrogen (as a result of excessive exposure) has been recognized as a known human carcinogen (IARC 

group 1 carcinogen) (NTP, 2014b).

The ER binding activity of TBBPA has been investigated in a number of in vitro screening assays. Review 

of the overall weight-of-evidence from in vitro assays has indicated that there is no significant 

estrogenic potential for TBBPA. A recent study in mice has shown that TBBPA was negative for 

estrogenic responses by both subcutaneous injection and oral routes of exposure up to 1,000 mg/kg-
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bw/day (Ohta et al., 2012). Because in vitro and in vivo studies showed that TBBPA has no significant 

estrogenic potential, TBBPA is unlikely to operate directly by the ER-mediated pathway for the 

induction of uterine tumors.

Conjugations (glucuronidation and sulfation) are the major biotransformation pathways for excretion 

of TBBPA in rats, and these pathways are shared by estrogen (Raftogianis et al., 2000). Competition for 

glucuronosyl-transferases and/or sulfotransferases by TBBPA could indirectly result in higher levels of 

estrogen and increased formation of estrogen-derived reactive radicals following exposure to high 

concentrations of TBBPA (NTP, 2014a). 

In addition to competing with enzymes that metabolize estrogen, a recent crystallographic analysis of 

TBBPA and a related brominated compound suggests that TBBPA, in addition to being a weak agonist, 

may bind to and actually inhibit sulfotransferases (e.g., SULT1E1) that metabolize estrogen (Gosavi et 

al., 2013) thereby causing possible buildup of estrogen. 

Besides the promotional and indirect genotoxic effects, estradiol (and its interconvertible metabolite 

estrone) can also exert genotoxic effects after being metabolized to catechols and then to reactive 

quinones that can form DNA adducts and contribute to oxidative DNA damage by reactive oxygen 

species (Bansal et al., 2009; Chen et al., 2008; Russo and Russo, 2004; Yager, 2014). If unrepaired, 

these mutations may lead to tumor formation. There are data that suggest that both estrogen activity 

and oxidative stress are required to induce cancer (Conova, 2003).

The Tp53 tumor suppressor gene is responsible for cell cycle checkpoint maintenance and genomic 

stability, and loss of cell cycle checkpoint control due to Tp53 mutations can result in the development 

of various tumor types in rodents and humans (Blagosklonny, 2000; Muller and Vousden, 2013). In the 

NTP bioassays (NTP, 2014a), a statistically significant increase in the incidence of mutations of the Tp53

tumor suppressor gene was noted in uterine adenocarcinomas from TBBPA treated rats (60%) 

compared to the incidences in mutations associated with spontaneous tumors from control rats (20%). 

It is possible that increased incidence of Tp53 mutations may be caused by the reactive oxygen radicals 

or metabolites produced after metabolism of the high levels of circulating estrogens due to 

competitive binding/inhibition of high doses of TBBPA to sulfotransferases or glucuronosyltransferases. However, with the exception of multiple mutations in uterine tumors of two rats treated 

with TBBPA, there was no difference between the mutation spectra of spontaneous tumors and those 

from TBBPA-treated rats. Therefore, it may be more likely that increased estrogen levels due to 

competitive inhibition of estrogen conjugations by high doses of TBBPA may cause uterine tumors by 

promoting pre-existing Tp53 mutations in the uterus by turning on hormone-responsive genes that 

promote DNA synthesis and cell proliferation. 

Uterine/endometrial cancer is one of the most common cancers in women with over 54,000 new cases 

estimated for 2015 (ACS, 2015).There are two types of uterine carcinoma with respect to histology, 

MOA and molecular genetic pathways. Type I carcinoma (the most common type), is associated with 

expression of ER, estrogen overstimulation, endometrial hyperplasia and Tp53 mutations in only about 

10-20 % of the carcinoma. Type II carcinoma is unrelated to estrogen and frequent lack of estrogen 

receptor activities. It is associated with atrophic endometrium, and Tp53 mutations (90%) are the most 

frequent genetic alterations (Lax, 2004). In light of the high incidence of Tp53 mutations in the uterine 
Page 121 of 135

adenocarcinomas, weak ER binding potential and the lack of increased levels of circulating estrogen in 

TBBPA-treated rats, it is likely that TBBPA induced type II carcinoma in the rats (rather than type I 

carcinoma). This notion is supported by the findings that there was no increase in endometrial 

hyperplasia (which is associated with type I carcinoma) in all dosed groups of female rats in the NTP 

bioassays when the original and residual tissues evaluations were combined; instead a new atypical 

hyperplasia was identified (NTP, 2014a). The two types of uterine/endometrial carcinomas seen in the 

rat study are similar to those observed in humans (e.g, Bansal et al., 2009) suggesting that the rat 

model is relevant to humans. 

Another possible MOA for TBBPA’s association with uterine tumors deserves consideration. An in vitro

study investigating the effects of TBBPA on the uptake of neurotransmitters into isolated rat brain 

synaptosomes showed a mixed concentration-dependent competitive/non-competitive mode of 

inhibiting dopamine uptake (Mariussen and Fonnum, 2003). Uterine tumors can be induced by 

dopamine receptor agonists in the rat through such an indirect estrogen pathway. Dopamine serves as 

a key regulator of serum prolactin by activating dopamine receptors on the pituitary to inhibit the 

secretion of prolactin. Chronic administration of dopamine receptor agonists to rats can result in 

decreased serum prolactin levels after competitively binding to the dopamine receptors on the 

pituitary, leading to estrogen dominance. Such dominance is due to increased estrogen synthesis after 

luteolysis of the persistent corpora lutea and the formation of new follicles. This estrogen dominance 

then leads to estrogen activity (i.e., expression of hormone-responsive genes that promote cell 

proliferation) and oxidative stress, which may induce hyperplasia and tumors of the uterus. This 

carcinogenic effect has not been demonstrated in other species including humans because prolactin is 

the luteotrophic hormone in rodents but not in primates (Alison et al., 1994; Neumann, 1991). 

Although the data above demonstrate TBBPA antagonism of dopamine uptake, it is unknown if TBBPA 

can also act as a dopamine agonist. 

NTP is now conducting additional studies that evaluate treatment-related molecular changes in the 

uterus (NIEHS, 2015).

As noted in Section G-7-3, the CARC concluded that available mode of action data were not adequate 

to meet the International Programme on Chemical Safety (IPCS) Human Relevance Framework (IPCS, 

2007). The CARC did not discuss the specific information that was lacking to establish an MOA. 

However, there are several important considerations identified by the Human Relevance Framework in 

determining an MOA for any compound. The Framework specifies that the postulated key events 

critical to the induction of tumors should be measured consistently. Concordance of dose-response 

relationships between the key events and tumors is also needed, with consideration of Bradford Hill 

criteria and whether differences in biological response (such as dose transitions) may occur at different 

sections of the dose-response curve. Temporally, postulated key events for a mode of action should be 

observed before the tumors are seen. There should be enough information to suggest some strength, 

consistency and specificity when associating key events with tumor incidence. Biological plausibility is 

important, as is the consideration of whether alternate modes of action occur (IPCS, 2007). 
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G-7-5 Classification of Carcinogenic Potential for Humans

The weight of evidence for whether TBBPA is associated with tumors in rodents was presented in 

2.6.4.5G-7-3. This section (G-7-5) specifically discusses conclusions regarding the relevance of these 

data to humans. 

The CARC classified TBBPA as likely to be carcinogenic to humans according to criteria described in 

EPA’s 2005 Cancer Guidelines. Some criteria that can influence a classification decision include the 

presence of: 1) tumors in more than one species and sex, 2) more than one tumor type, 3) uncommon 

tumors, 4) dose-response relationships, 5) tumors known to occur in humans and 6) the presence of 

non-neoplastic lesions.

The CARC based their conclusion on the presence of uterine epithelial tumors (combined adenoma, 

adenocarcinoma or malignant mixed Müllerian tumors) in female Wistar Han rats and hemangiomas 

and hemangiosarcomas in male B6C3F1 mice. 

In separate comments, the NTP also agreed with the CARC that TBBPA is likely to be carcinogenic to 

humans (NIEHS, 2015). 

G-8 Studies Proposed for Risk Assessment

Data on tumor incidences are available from the NTP cancer bioassay (NTP, 2014a). Based on EPA’s 

CARC and the NTP conclusions that TBBPA is likely to be carcinogenic to humans and because MOA 

information is limited, EPA/OPPT will evaluate risks using data on uterine tumors (females) and 

hemangiomas and hemangiosarcomas (males) from this study Appendix J describes the method used 

to determine slope factors from a linear low-dose extrapolation. EPA/OPPT will use these slope factors 

in a risk assessment of TBBPA.

EPA/OPPT will also use a study of developmental effects to assess risk for children in scenarios 

discussed in Chapter 0. Although EPA/OPPT may consider other studies further, the study by Fukuda et 

al. (2004) is likely to be the most appropriate study for several reasons. The study directly dosed young 

animals so that matching results with exposure data is easier than studies that dosed both dams and 

offspring. It is possible that TBBPA causes adverse effects primarily as a result of exposure to TBBPA by

young rodents. This is a plausible conclusion based on the breadth of studies that appear to suggest 

effects are more likely when young animals are dosed directly. The European Union suggested that the 

kidney effects observed in the newborn rats could be due to immature metabolic capability and/or the 

immature kidneys of such young animals (EC, 2006).
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G-9 Uncertainties

G-9-1 Carcinogenesis Bioassay Methods

NTP (2014a) administered TBBPA to rodents via oral gavage throughout their lifetime. It is not known 

whether similar adverse effects would result if humans are exposed to TBBPA associated with dust 

particles or as other forms for less than a lifetime (or even a full lifetime). 

The doses used in NTP (2014a) ranged from 250 to 1000 mg/kg-bw/day. It is possible that at lower 

exposures likely to be experienced by humans, TBBPA would be excreted before it could exert adverse 

effects. Yet, the available toxicokinetics data are limited in their ability to answer this question. Lowerdose toxicokinetics studies show similar rates of excretion as higher doses via the oral route and the 

longest toxicokinetics studies are 10 days (Kuester et al., 2007). Therefore, TBBPA’s toxicokinetic 

behavior after longer exposure durations, lower concentrations and exposure via dust (vs. gavage) is 

not known.

G-9-2 Developmental Toxicity Data

The studies evaluating reproductive and developmental toxicity show a wide variety of results from no 

effects up to very high doses to some subclinical effects at low doses. Also, it is not clear whether 

dosing dams and offspring or just dosing offspring results in effects of TBBPA treatment. Thus, there is 

uncertainty in choosing any developmental toxicity study for evaluation in a quantitative risk 

assessment of TBBPA.
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Parameters Needed for Estimating Fish Ingestion

Bioconcentration factors and fish ingestion rates are needed to estimate risks from TBBPA intake 

through eating fish from one water body identified near one of the Arkansas manufacturing facilities. 

Chapter 0 presents bioconcentration factors (BCFs) that can be used to estimate the concentration of 

TBBPA in fish from the predicted water concentrations. For this assessment, EPA/OPPT will consider 

using 720 L/kg, measured using eastern oysters (GLCC, 1989b). The values of 1200-1300 L/kg from 

GLCC (1989a) are higher, but they are based on measuring total radioactivity and reflect measurement 

of the parent compound and metabolites rather than the parent compound only; thus, this value is not 

being considered. The lowest measured BCF is 20 L/kg (EC, 2000).

For this assessment, EPA/OPPT plans to use a fish consumption rate of 22 g/day for the recreational 

fishers who may fish from this water body and the adult members of their family. This value is the 

default fish consumption rate for adults recommended for the protection of human health in EPA’s 

Office of Water (OW) 2014 draft ambient water quality criteria (AWQC). This value represents the 90th

percentile consumption rate of freshwater and estuarine finfish and shellfish for the US adult 

population 21 years and older as summarized in Table 9a of EPA (2014d). The estimate is based on data 

from the 2003-2004 National Health and Nutrition Evaluation Survey (NHANES). Statewide studies of 

freshwater recreational fish intake are summarized in the Exposure Factors Handbook (EPA, 2011b) for 

a number of states. However, there is no study available from Arkansas. Mean intake from statewide 

surveys, as reported in EPA (2011b), range from 5 to 51 g/day and 95th percentile values range from 

14-61 g/day. 

For children, EPA/OPPT is considering using 90th percentile consumption rates of freshwater and 

estuarine finfish and shellfish, also using NHANES data, for specific age groups as detailed in Table 20a 

of EPA (2014d). For children age 1 to <3 years the value is 4.7 g/day; for children 3 to <6 year the value 

is 5.8 g/day; and for children age 6 to <11 year the value is 7.7 g/day.

Children < 11 is the age range most relevant for considering effects of developing cancer given that this 

is a bit more than one tenth of the human life span (EPA, 2005). A shorter age range, from one < three 

years, could be an appropriate age range for developmental effects based on toxicity studies 

suggesting effects in newborns vs. a lack of effects in somewhat older rodents (Fukuda et al., 2004). 

The body weight used in estimating intake of TBBPA via fish ingestion will correspond to the receptor 

and toxicological endpoint of interest. For estimating risks of developing uterine tumors, EPA/OPPT

proposes to use the body weight of 74.8 kilograms, which is the average weight of female adults aged

30 to <40 years old as presented in the Exposure Factors Handbook (EPA, 2011b). For estimating risks 

of developing hemangiomas or hemangiosarcomas, EPA proposes using a value of 87.0, the average 

weight for males aged 30 to <40 (EPA, 2011b). For children aged 1 to <2 years the recommended mean 

body weight is 11.4 kg; for 2 to <3 year the weight is 13.8 kg; for 3 to <6 years the weight is 18.6 kg; 

and for 6 to <11 years the weight is 31.8 kg (EPA, 2011b). 
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Exposure can be estimated using these parameters in the following equation:

X = (WC * BCF * FC)/(1000 * BW)

Where:

X = Intake of TBBPA via fish ingestion, μg/kg-bw/day

WC = TBBPA water concentration, μg/L

BCF = Bioconcentration factor, L/kg

FC = Fish consumption, g/day

1000 = Conversion factor for fish weight, g/kg

BW = Body weight of human receptors being assessed, kg
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Draft Approach for Estimating Exposure from 

Mouthing of TBBPA

TBBPA flame retardants in this cluster are either additive or reactive components used in plastic 

articles and may or may not be chemically bonded to the polymers. Thus, TBBPA may migrate from 

the polymer matrix to the surface of the article and have the potential for exposures through direct 

contact. The presence of TBBPA in a variety of products indicates the potential for consumer exposure 

via object to mouth contact and hand to mouth contact with articles. EPA/OPPT will consider the 

methods and parameters discussed below to estimate mouthing exposures.

Table_Apx I-1: Plan for Evaluating Risk to Children from Ingestion of TBBPA from Products in the 

Home

Exposure Scenario Rationale Assessment Approach

Mouthing of products 

(object-to-mouth) as well 

as hand-to-mouth 

transfer by young 

children in the home

Exposures are expected to be 

highest in children; younger 

children are expected to have 

longer duration of mouthing 

activity when compared to older 

children and adults.

Sufficient data to quantify 

exposure and toxicity

Concentrations of TBBPA in products and surface 

loadings will be combined with age-specific 

activity patterns and exposure factors to 

estimate an exposure in mg/kg-bw/day for 

children. Measured or estimated migration 

rates in saliva can also be considered if available. 

To estimate developmental risk, exposure for 1-

year olds will be compared with a toxicity value 

from a developmental study in a margin of 

exposure (MOE) evaluation. 

For cancer risk, exposure for children in a wider 

age range (0 to 7) will be multiplied by cancer 

slope factors to estimate cancer risk.

EPA/OPPT will consult with CPSC and conduct 

additional literature searches to identify 

whether migration data specific to TBBPA are 

available. 

Data from published and unpublished literature 

as well as previous assessments will be 

considered. 

I-1 TBBPA Concentrations in Products and Product Surfaces

Recent studies have shown that TBBPA is present in many different types of consumer products and 

articles as well as on the surfaces of many products. These products include electronic appliances, 

electronic devices, plastic toys, plastic jewelry and tents (Di Napoli-Davis and Owens, 2013; Gallen et 

al., 2014; Keller et al., 2014; Samsonek and Puype, 2013; van Bergen and Stone, 2014). Gallen et al. 

(2014) evaluated the TBBPA content of many different products using X-ray fluorescence, wipe 
Page 127 of 135

sampling and destructive methods to estimate concentrations. Di Napoli-Davis and Owens (2013) used 

wipe sampling on the surface of electronic products. van Bergen and Stone (2014) used destructive 

methods (cryogenic milling and gas chromatography/mass spectrometry) to estimate concentrations 

for a wide range of products and product components. Within the Washington State database (WSDE, 

2014a), TBBPA concentrations within products are reported as ranges; in the proposed TBBPA risk 

assessment, EPA/OPPT could use the mid-point of these ranges with conversion factors to estimate 

loading on the surface of various products. Keller et al. (2014) used wipe sampling to estimate TBBPA 

loading on the surface of a tent. Samsonek and Puype (2013) measured TBBPA on the surface of black 

coffee mugs. The results of these studies show that the range of TBBPA concentrations and surface 

loadings in and on a variety of products span several orders of magnitude.

EPA/OPPT may use these data to estimate a range of TBBPA surface loadings (TBBPA/cm2) potentially 

available for transfer to hands and into saliva. 

I-2 Migration Rates into Saliva

The migration from the surface of a product into human saliva can be measured through in vivo or in 

vitro testing. Results of these tests are expressed as the mass of a chemical per surface area per unit 

time. For example, values could be expressed as pg, μg or mg per either cm2 or 10 cm2 per minute. 

In an in vivo study, central tendency migration rates for polybrominated diphenyl ethers (PBDEs) 

ranged from 0.000003 to 0.0026 to μg/10 cm2-minute and high-end migration rates ranged from 

0.00004 to 0.03 μg/10 cm2-minute (Chen et al., 2009). Babich (2014) summarized available in vitro

testing of phthalates; central tendency migration rates ranged from 1.1 μg/10 cm2-mintue to 4.4 μg/10 

cm2-minute while high-end migration rates ranged from 1.9 μg/10cm2-minute to 11.4 μg/10 cm2-

minute (Babich, 2014).

In vitro and in vivo estimates can vary over several orders of magnitude for a given chemical and 

product combination. PBDEs have very low water solubility (and lower migration rates) while 

phthalates have moderate water solubility. While many other physical-chemical properties may 

influence migration potential into saliva, water solubility is likely to be one of the most important 

factors. Thus, because TBBPA’s water solubility is between the values reported for PBDEs and 

phthalates, it is possible that the migration rate of TBBPA into saliva could be between the ranges 

reported in Babich (2014) and Chen et al. (2009).

I-3 Children’s Activity Patterns

Based on the type of product sampled in the above studies, an object may be handled routinely by a 

child, resulting in TBBPA transfer from the object to the child’s hand and then subsequently to his or 

her mouth. An article could also be directly placed in a child’s mouth. Thus, EPA/OPPT will assign these 

objects as having the potential for either “hand to mouth” transfer or “object to mouth” transfer. 

Because children have higher hand–to-mouth and object-to-mouth activity than adults and adult 

exposure is expected to be minimal, EPA/OPPT will evaluate exposure for only for children. 
Page 128 of 135

Furthermore, mouthing behaviors are typically more prevalent among the youngest children. Thus, to 

estimate developmental toxicity risks, EPA/OPPT will evaluate exposure for 1-year olds, which is the 

age with the highest exposure potential as a result of mouthing behavior. 

However, to estimate cancer risk, a wider age range is recommended because a longer exposure 

duration is thought to be required before tumors develop. EPA/OPPT proposes evaluating exposures 

for children from age 0 through 7 years old to estimate cancer risks.

EPA will use data on the frequency and duration of touching objects and placing them in mouths; this 

information will be adapted from the Exposure Factors Handbook (EPA, 2011b).

I-4 Other Parameters Being Considered

Additional default parameters used in EPA’s Standard Operating Procedures for Residential Pesticide 

Exposure Assessment (EPA, 2012c), EPA’s SHEDS model (EPA, 2008b), or contained within the Transfer 

Efficiency Database (Gorman, 2012) could also be considered. Measured data is preferred over 

defaults.

I-5 Method to Combine Exposure Data

The variables used to estimate exposures could be considered in a deterministic way, assigning a fixed 

variable representative of high-end or central-tendency exposures (EPA, 2012c). These variables could 

also be considered in a probabilistic manner by sampling from distributions (EPA, 2008b; Ozkaynak et 

al., 2011).

I-6 Confidence and Uncertainty in the Available Data

A variety of the parameters to be included in any modeling are highly variable and some may be data 

poor. 

The potential for exposure may increase under the following circumstances: (1) if routine contact and 

close proximity with the product is expected; (2) if the product contacts liquid; (3) if the product is 

often warm or hot; or (4) if very young children use or are frequently near such products (Gallen et al., 

2014).
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Dose-Response Assessment for Cancer Endpoints

The data from NTP (2014a) described in Appendix G were used to develop a dose-response 

relationship using linear low-dose extrapolation.

J-1 Choice of Model, Points of Departure and Oral Slope Factors

The CARC recommended a model that uses low dose linear extrapolation20 for quantification of human 

risk from TBBPA (CARC, 2014). EPA/OPPT agrees that using a linear low-dose model is most 

appropriate because there are limitations that preclude a clear understanding of TBBPA’s MOA in 

relation to the observed tumors. If TBBPA acts via a non-linear/threshold mechanism, the use of linear 

low dose extrapolation will over-predict cancer risk.

EPA/OPPT modeled the dose response for uterine tumors and for hemangiomas and 

hemangiosarcomas using a cancer multistage model (EPA, 2012a), with linear extrapolation at low 

doses as recommended by EPA (2005) to determine the point of departure — the 90% lower bound 

benchmark dose (BMDL). Using the BMDL, two slope factors were calculated for females using the 

following data: 1) combined incidence of all uterine tumors of epithelial origin (adenocarcinomas, 

adenomas and malignant mixed Müllerian tumors); and 2) uterine adenocarcinomas only. Likewise, 

two slope factors were calculated for males: 1) the combined incidence of hemangiomas or 

hemangiosarcomas; and 2) hemangiosarcomas only (Hummel, 2013b, 2014). Table_Apx J-1 lists BMDs,

BMDLs and slope factors.

Based on recommendations from EPA (2005) and EPA (2012a), EPA/OPPT used the dose associated 

with a 10% extra cancer risk as the point of departure to model the TBBPA tumor data. 

The oral slope factor, which approximates a 95% confidence limit, is the upper bound on increased 

cancer risk from a lifetime of oral exposure to a chemical and is usually expressed as a proportion of 

the population affected per mg of the chemical per kg-bw/day (EPA, 2011c). The oral slope factor can 

also be used to determine the extra lifetime risk that an individual may develop cancer. In the TBBPA 

assessment, EPA/OPPT will use the slope factor to calculate individual risk.

The slope factor for the risk of developing tumors was calculated using the following equation:

Equation 1 SF(human, daily) = 0.1/(BMDL(animal, 10% extra risk) * DAF * 5/7)

Where:

SF(human, daily) = slope factor expressing the extra lifetime risk (mg TBBPA/kg-bw/day)-1

0.1 = benchmark response level (10%)

BMDL = lower 90% confidence bound on the benchmark dose

DAF = dosimetric adjustment factor = (BWanimal/BWhuman)

(1/4) = 0.24

 20 The CARC recommended the Q1* for modeling (CARC, 2014), but EPA/OPPT used a multistage model according to more 

recent EPA recommendations (EPA, 2012a).
Page 130 of 135

5/7 = conversion from NTP (2014a) dosing of 5 days/week to 7 days/week exposure 

(this factor is used only for the general population exposures)

Table_Apx J-1: Parameters Used in Dose-Response Equations

BMDL(animal, 10% extra risk)

mg/kg-bw/day

BMDL(10HED)a

mg/kg-bw/day

SF(human, daily)

(mg/k-bw/day)-1

Tumors in Females

Uterine tumors 

(combined) 177 42.6 0.00329

Uterine 

adenocarcinomas 191 45.9 0.00305

Tumors in Males

Hemangiosarcomas 

and hemangiomas 216 51.8 0.00270

Hemangiosarcomas 200 48.0 0.00292

Sources: Hummel (2013b); Hummel (2014)

BMDL(10HED) = BMDL(animal, 10% extra risk) * DAF

Further work will be needed to determine factors to account for the amount of inhaled particulates 

that might be swallowed/absorbed. The European Union suggested that 70% of inhaled particulates 

might be swallowed (EC, 2006). EPA/OPPT has not yet determined a value for the proposed 

assessment. 

J-2 Calculation of Target Risk Levels

The slope factor can be used to calculate a TBBPA dose associated with three target risk levels:

Equation 2 SF(human,daily)

(1 mmmm TTTTTTTTTT pppppp kk pppppp bbbb pppppp dddddd) = RRRR

xx

Where:

SF(human, daily) = extra lifetime risk per 1 mg TBBPA/kg-bw/day from Eq. 1

RL = target risk level (1/10,000; 1/100,000; or 1/1,000,000)

 x = the daily dose associated with the chosen target risk level (mg/kg-bw/day)

The relationship can be rearranged to solve for x for any target risk level:

x = 

RRRR∗1 mmmm TTTTTTTTTT pppppp kk pppppp bbbb

SF(human,daily)

Resulting doses associated with the three risk levels are listed in Table_Apx J-2.
Page 131 of 135

Table_Apx J-2: Doses (in mg/kg-bw/day) Associated with Three Target Risk Levels

Target Risk Level

1 x 10-6 1 x 10-5 1 x 10-4

Uterine tumors 

(combined) 0.000304 0.00304 0.0304

Uterine 

adenocarcinomas 0.000328 0.00328 0.0328

Hemangiosarcomas 

and hemangiomas 0.000370 0.00370 0.0370

Hemangiosarcomas 0.000343 0.00343 0.0343

J-3 Key Sources of Uncertainty

J-3-1 Tumors Modeled

NTP concluded that for hepatoblastomas in male mice, there is some evidence of carcinogenic activity 

that can be attributed to TBBPA. Thus, EPA/OPPT investigated possible dose-response relationships 

using the cancer multistage model and other models. The effects at 250 and 500 mg/kg-bw/day were 

statistically significantly different from controls using pairwise comparisons (p < 0.05). Furthermore, 

the data showed a statistically significant dose-related trend using the one-sided Cochran-Armitage 

trend test (p < 0.05). However, the data did not provide a good fit using the cancer multistage model 

(Hummel, 2013b), and none of the other models available in the benchmark dose response modeling 

software resulted in goodness of fit p-values at acceptable levels of > 0.1 when considering the full 

shape of the dose-response curve (Hummel, 2013a). Thus, this tumor type cannot be considered in a 

quantitative risk assessment of TBBPA.

J-3-2 Use of Linear Low-Dose Extrapolation

The CARC noted that according to the IPCS MOA framework (IPCS, 2007), data are not adequate to 

draw conclusions about the mode(s) of action for the tumor incidence associated with TBBPA. 

Therefore, as recommended by EPA (2005), linear low dose extrapolation was used as the default 

option for modeling tumor data.

There are several reasons that a non-linear mode of action could explain the relationship between 

TBBPA and tumor incidence. EPA/OPPT and the CARC determined that a direct genotoxic MOA for 

tumorigenesis is unlikely. In addition, uterine tumors might be a result of TBBPA’s competitive binding 

of enzymes involved in the conjugation of endogenous estrogens or TBBPA’s enzyme inhibition; any 

resulting higher estrogen levels might lead to tumors only after a threshold dose of TBBPA is achieved. 

Furthermore, if damage to DNA occurs from the generation of reactive oxygen species (e.g., as a result 

of metabolism of TBBPA), such damage may also lead to tumor formation via a non-linear MOA. 
Page 132 of 135

J-3-3 Choice of Dose-Response Model

Cancer multistage models were chosen for modeling based on adequate fits for two tumor types and 

biological considerations even though other models also resulted in adequate fits of the data.
Page 133 of 135

EU and Canada Risk Assessments: Specific 

Evaluations Consulted for Current Assessment

Some of the more detailed evaluations of the EU and Canadian risk assessments that were considered 

during problem formulation are described below.

K-1 EU Calculations of TBBPA Uptake from Soil Near 

Manufacturing and Processing Sites

The European Union (EU) human health risk assessment of TBBPA (EC, 2006) estimated risks used a log 

KOW of 5.9 and a KOC of 49,726 L/kg to calculate uptake of TBBPA from soil to plants and livestock for 

several manufacturing (and processing) scenarios. Resulting estimates of dietary intake ranged from 

1.7 x 10-5 to 2.92 mg/kg-bw/day, with the highest value estimated at sites where TBBPA is used as an 

intermediate in the production of TBBPA derivatives. The next highest estimate was 2.33 mg/kgbw/day for individuals living near manufacturing facilities.21 EPA/OPPT does not plan to use log Kow or 

Koc values based on the potential for predict uptake that is higher than actual uptake to 

plants/livestock.

K-2 EU Environmental Assessment at Processing Sites

The EU risk assessment for the environment evaluated processing sites and a discussion of their 

analysis and applicability to the current TBBPA assessment is described below.

K-2-1 Acrylonitrile Butadiene Styrene (ABS) Compounding 

Sites

Although the EU found risks at processing sites, the generic scenarios used in the EU risk assessment 

for ABS compounding facilities would not readily apply to United States facilities that process TBBPA

because reported release information from TRI differs from the release assumptions used by the EU.

Using two approaches, the EU concluded that environmental risks are possible at ABS (plastic) 

compounding sites that use TBBPA as an additive flame retardant (EC, 2008):

• a generic scenario evaluation based on flame retardant use in polymers with some TBBPAspecific data using certain worst-case assumptions and

• a site-specific evaluation using monitored emissions data from a single site. 

For the generic approach, the EU used default release estimates and several worst-case assumptions. 

The largest releases were TBBPA dust losses from raw materials handling and other particulate 

releases, which eventually went to wastewater. 

 21These two highest values reported in the EU risk assessment were used only as examples because the EU doesn’t produce 

TBBPA or its derivatives (EC, 2006). 
Page 134 of 135

In addition to these more generic scenarios, the EU monitored TBBPA emissions from one ABS

compounding site and identified risks for aquatic, sediment- and soil-dwelling organisms. The EU 

specifically stated that air emissions led to risks for soil-dwelling organisms. The site-specific 

monitoring information is confidential, however. Therefore, the amount of TBBPA emitted and the 

types of emissions (i.e. whether there were also releases to land and water in addition to air releases) 

are not known (EC, 2008). 

For all years of TBBPA reporting to TRI, the largest amount transferred to WWTPs occurred in 2003, 

when 152 pounds (all facilities) were released to wastewater. In nine of the reporting years (2000-

2002; 2007-2012), 10 or fewer pounds of TBBPA were sent to wastewater treatment plants (WWTPs). 

Facilities reported minimal direct releases to surface water. The highest value was 71 pounds in 2003 

(EPA, 2012e). Thus, assumptions related to releases differ significantly between the European Union 

and the United States.

In the United States during 2012, six facilities were identified in the category of plastics and rubber 

facilities (NAICS code 326), the category that would include ABS compounding sites. One of these 

facilities reported 33 pounds as fugitive air emissions. Four of the facilities disposed a total of 154 

pounds of TBBPA to “other landfills.” No other releases (including stack air releases) were reported for 

these facilities. Similar emissions were reported for facilities within this industry category in previous 

years. Between 2000 and 2012, the highest fugitive air emissions for a single facility was 37 pounds, in 

2010 (EPA, 2012e). Thus, for similar types of processing plants as those evaluated by the EU, only 

limited emissions have been reported to TRI for US facilities.

Overall, both the types and amounts of emissions reported for these facilities differ between the EU 

and the United States. Unlike the releases reported in the EU analysis for the ABS compounding sites, 

releases reported by US plastics and rubber facilities to TRI are not expected to result in environmental 

risks.

K-2-2 ABS Conversion Sites and Epoxy Resin Manufacturing 

Facilities

The EU risk assessment also found risks for soil-dwelling organisms surrounding facilities that 

manufacture epoxy and/or polycarbonate resins and at ABS conversion sites. However, these risks 

were found for situations where sludge is generated/applied to agricultural land. The EU notes that 

when these activities were taken into account, risks were not identified for these generic scenarios. 

Furthermore, the EU did not identify environmental risks when using actual site-specific data at eight 

epoxy resin manufacturers and at two sites using TBBPA in reactive flame retardant applications (EC, 

2008).

US facilities have reported minimal TBBPA releases to surface water and WWTPs as stated above. Also, 

no releases were reported to land treatment (EPA, 2012e). 
Page 135 of 135

K-2-3 EPA’s Conclusion for Processing Sites

When considering ABS compounding sites (reactive uses), TRI reporting shows that plastics and rubber 

facilities reported minimal air emissions and no other releases of note. 

Other processing sites in the United States have reported higher stack air releases. However, given that 

these are a small proportion of the air emissions from the top manufacturing site, EPA/OPPT did not 

further evaluate these releases.

For manufacturing epoxy and polycarbonate resins and ABS conversion sites, measured data for the 

ten surveyed sites in the EU risk assessment showed low risks. Although some risks were identified in 

generic scenarios in the EU risk assessment, TRI data indicate minimal or no releases from such 

processing sites in the United States.

K-2-4 Canada’s Fugacity-Based Model of Sludge Applied to Land

The Canadian government (EC/HC, 2013) ran a fugacity-based model to estimate risks from TBBPA in 

sludge applied to land. Using different assumptions from those used in EPA/OPPT’s preliminary

calculation (but similarly using a high-end TBBPA sludge concentration), risks to soil organisms were 

determined to be low (EC/HC, 2013). Although EPA/OPPT doesn’t use these fugacity-based models 

when estimating exposure, these results support EPA/OPPT’s preliminary calculation for this pathway.