_____________________________________________________________ 

U.S. Environmental Protection Agency 

Polybrominated 

Diphenyl Ethers 

(PBDEs) 

Project Plan 

March 2006 
U.S. Environmental Protection Agency 

Polybrominated Diphenyl Ethers (PBDEs) Project Plan 

March 2006 

A. INTRODUCTION 

Polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardant 

chemicals of increasing interest to scientists, government agencies, and the public. These 

chemicals have been used in a variety of manufactured products, including foam 

cushioning used in furniture and plastics used in televisions and computers. In the event 

of a fire involving these products, PBDEs slow ignition and rate of fire growth, allowing 

more time for people to extinguish or escape the fire. However, findings that PBDEs are 

widely distributed in the environment and are present at increasing levels in people have 

raised concerns about the potential risks of PBDE exposure to human health and the 

environment. 

This Project Plan provides a brief summary of relevant information on PBDEs, and 

outlines the U.S. Environmental Protection Agency’s activities regarding PBDEs and 

related chemicals. In considering activities related to flame retardant chemicals, EPA 

will work with all interested parties to ensure that fire safety, environmental concerns and 

public health concerns are all taken into account. EPA will post this Project Plan and 

other materials related to PBDEs on its web site at www.epa.gov/oppt/pbde. The website 

will be periodically updated to report progress on the activities described in this Project 

Plan. EPA will use a variety of communications tools, including periodic updates to the 

website, to inform stakeholders and the public regarding progress on the activities 

described in this Project Plan. 

B. BACKGROUND INFORMATION ON PBDEs 

PBDE Congeners and Commercial Mixtures 

PBDEs are a family of chemicals with a common structure of a brominated diphenyl 

ether molecule which may have anywhere from one to ten bromine atoms attached 

(Figure 1). Each individual PBDE variant, distinguished from others by both the number 

of bromine atoms and the placement of those atoms, is referred to as a congener. For 

example, there are 42 tetrabromodiphenyl ether congeners, each with four bromine atoms 

in different configurations. In theory, there could be as many as 209 PBDE congeners, 

but a much smaller number of congeners are commonly found in the commercial PBDE 

products and in measurements of PBDEs in humans and the environment (see Table 1). 

1 
Figure 1. Generalized Structure of Polybrominated Diphenyl Ethers where (m+n) = 

1 to 10 bromines 

There are three types of commercial PBDE products, which are referred to as 

pentabromodiphenyl ether (pentaBDE), octabromodiphenyl ether (octaBDE), and 

decabromodiphenyl ether (decaBDE). Each of these commercial products, however, 

actually contains a mixture of various PBDE congeners (see Table 2). The leading 

commercial pentaBDE mixture, known as DE-71, is primarily comprised of tetraBDEs 

(especially BDE-47) and pentaBDEs (especially BDE-99 and BDE-100) – congeners 

with 4 or 5 bromine atoms – along with smaller quantities of hexaBDEs (BDE-153 and 

BDE-154, with 6 bromine atoms). The commercial octaBDE mixture is primarily 

comprised of heptaBDEs and octaBDEs (congeners with 7 or 8 bromine atoms) and also 

contains hexaBDEs and nonaBDEs (with 6 or 9 bromine atoms) along with small 

quantities of decaBDE (10 bromine atoms). The commercial decaBDE product is 

comprised almost entirely of the single fully-brominated congener, known as BDE-209, 

which has the maximum 10 bromine atoms. DecaBDE contains small quantities of 

nonaBDEs (congeners with 9 bromine atoms) as well. 

TABLE 1. Selected PBDE Congeners 

Congener Number of 

Bromine Atoms 

Chemical Name 

BDE-28 

BDE-47 

BDE-85 

BDE-99 

BDE-100 

BDE-153 

BDE-154 

BDE-183 

BDE-197 

BDE-206 

BDE-209 

3 

4 

5 

5 

5 

6 

6 

7 

8 

9 

10 

2,4,4’-tribromodiphenyl ether 

2,2’,4,4’-tetrabromodiphenyl ether 

2,2’,3,4,4’-pentabromodiphenyl ether 

2,2’,4,4’,5-pentabromodiphenyl ether 

2,2’,4,4’,6-pentabromodiphenyl ether 

2,2’,4,4’,5,5’-hexabromodiphenyl ether 

2,2’,4,4’,5,6’-hexabromodiphenyl ether 

2,2’,3,4,4’,5’,6-heptabromodiphenyl ether 

2,2’,3,3’,4,4’,6,6’-octabromodiphenyl ether 

2,2’,3,3’,4,4’,5,5’,6-nonabromodiphenyl ether 

2,2’,3,3’,4,4’,5,5’,6,6’-decabromodiphenyl ether 

2 
A small number of the PBDE congeners are found most frequently, and in the greatest 

concentrations, in human and environmental samples. BDE-47 tends to be found more 

frequently than other congeners in measurements from humans, fish and other biota, 

followed by BDEs 99, 100, 153 and 154. In measurements of house dust, sediments, and 

indoor air, BDE-209 (decaBDE) seems to be dominant. 

Uses of PBDEs 

PBDEs and other flame retardant chemicals are used in certain products to reduce the risk 

of fire, particularly in items that are susceptible to igniting in fire situations, like 

furniture, or in which fires may start, like electrical devices. The commercial pentaBDE 

product is used almost entirely in flexible polyurethane foam in furniture, mattresses, 

carpet padding, and automobile seats. The commercial octaBDE product is used in 

acrylonitrile-butadiene-styrene (ABS) plastic that is used in certain electric and electronic 

devices. Commercial decaBDE is used primarily in high-impact polystyrene (HIPS) 

plastic that is frequently used to make the back part of television sets, and is also used in 

certain types of flame-retardant textiles. In recent years, almost all pentaBDE use has 

taken place in the Americas, while somewhat less than half of worldwide use of octaBDE 

and decaBDE has been in the Americas (see Table 2). 

Concerns about PBDEs 

In recent years, scientists have measured PBDEs in human adipose tissues, serum and 

breast milk, fish, birds, marine mammals, sediments, sludge, house dust, indoor and 

outdoor air, and supermarket foods. The mechanisms or pathways by which the PBDEs 

move into and through the environment and humans are not known, but are likely to 

include releases from manufacturing of the chemicals, manufacturing of products like 

plastics or textiles, aging and wear of products like sofas and electronics, and releases at 

the end of product life (disposal, recycling). In general, levels of PBDEs in humans and 

the environment are higher in North America than in other regions of the world, a finding 

that is often attributed to the greater use of pentaBDE in North America. 

Studies have also been conducted in laboratory animals to gain a better understanding of 

the potential health risks of PBDEs. Studies of various commercial mixtures and 

individual congeners have suggested potential concerns about liver toxicity, thyroid 

toxicity, developmental toxicity, and developmental neurotoxicity. These findings raise 

particular concerns about potential risks to children. In addition, the presence of PBDEs 

in house dust and breast milk indicates that there are likely to be pathways of exposure to 

PBDEs that are of particular relevance for children. However, there remains much to 

learn about both exposure to PBDEs and the potential health effects; and there are 

different concerns for the different PBDEs. 

A more detailed summary of the current scientific understanding of PBDEs is presented 

in Appendix A. 

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TABLE 2. Commercial PBDE Products 

Commercial 

PBDE 

Product 

Composition of 

Commercial 

Mixtures1 

Uses 2001 Demand 

in Americas2 

(metric tons) 

Percentage 

of World 

Demand in 

Americas2 

pentaBDE 

(DE-71) 

octaBDE 

(DE-79) 

decaBDE 

(DE-83R) 

(Saytex 

102E) 

24-38% tetraBDEs 

50-62% pentaBDEs 

4-12% hexaBDEs 

0-1% triBDEs 

0.5% pentaBDEs 

12% hexaBDEs 

45% heptaBDEs 

33% octaBDEs 

10% nonaBDEs 

0.7% decaBDE 

0.3 – 3% nonaBDEs 

97–99% decaBDE 

Flame retardant in 

flexible polyurethane 

foam for furniture, 

mattresses and carpet 

padding 

Flame retardant in 

acrylonitrilebutadiene-styrene 

plastics used in 

computer casings 

Flame retardant in 

high impact 

polystyrene (HIPS) 

television set cabinet 

backs and commercial 

upholstery fabric 

7,100 

1,500 

24,500 

95% 

40% 

44% 

1

Source of composition data is (Environ 2003) for pentaBDE, (ECB 2003) for octaBDE, 

and (WHO 1994) for decaBDE.

2

Bromine Science and Environment Foundation estimates from www.bsef.com. In 2005, 

values for pentaBDE and octaBDE in the Americas were expected to go to zero. 

Actions Regarding PBDE Production and Use 

Increasing information on PBDEs in the environment has drawn the attention of 

policymakers at the international, national, state and local levels. In 2002, the European 

Parliament adopted a ban on marketing and use of pentaBDE and octaBDE throughout 

the European Union (EU). The ban went into effect in August 2004. 

In July 2003, the State of California adopted a ban on the manufacture or distribution in 

commerce of any product containing pentaBDE or octaBDE. These restrictions are 

scheduled to take effect in 2006. Hawaii, Illinois, New York, Maine, Maryland, 

Michigan and Oregon have adopted laws similar to California’s, and several other states 

are considering similar actions. 

4 
Great Lakes Chemical Corporation, the sole U.S. producer of the commercial pentaBDE 

and octaBDE mixtures, discontinued production of these two products in the U.S. at the 

end of 2004. 

In general, decaBDE is not subject to the restrictions that have been adopted for 

pentaBDE and octaBDE. There is an EU regulation that will prohibit the use of certain 

chemicals in electric and electronic equipment as of July 2006. DecaBDE had been 

included on the list of chemicals that would be prohibited, but the EU granted an 

exemption for this chemical in October 2005. 

Other international activities concerning PBDEs include an Arctic Council brominated 

flame retardants (BFRs) project and ongoing work by the BFRs Clearinghouse of the 

Organization for Economic Cooperation and Development (OECD). The Arctic Council 

is an inter-governmental forum addressing Arctic issues whose members include Canada, 

Denmark, Finland, Iceland, Norway, the Russian Federation, Sweden and the United 

States. EPA has been involved in the initial development of the Arctic Council’s BFRrelated activities, intends to continue involvement in their further development, 

implementation and tracking, and will provide technical expertise and other resources, 

where possible and as appropriate. The OECD is a forum where the governments of 30 

market democracies work together to address the economic, social, environmental and 

governance challenges of the world economy. The OECD’s BFR Clearinghouse has 

developed hazard/risk information fact sheets on the PBDEs, intends to update the fact 

sheets every 2-3 years, and will work to improve cooperation between producers and 

users of BFRs in order to reduce emissions to the environment. 

More information on international activities is presented in Appendix B. 

PBDE-Related Activities in the U.S. Federal Government 

The U.S. federal government is playing a substantial role in research and assessment of 

PBDEs, and in taking appropriate management actions to respond to both scientific 

developments and developments in the market for PBDEs. A selection of federal 

government activities includes: 

• EPA has proposed a Significant New Use Rule (SNUR) that would require 

prior notification to EPA by any manufacturer or importer intending to 

reintroduce pentaBDE or octaBDE in the U.S. The proposed rule would also 

provide EPA with authority to review the intended production or import of 

pentaBDE or octaBDE before it begins and to take actions to control potential 

risks as needed. 

• EPA is leading a Furniture Flame Retardancy Partnership to evaluate 

alternatives to PBDEs in furniture applications. The partnership includes 

furniture and fabric manufacturers, chemical manufacturers and 

environmental organizations. Its focus has been assessment of alternatives to 

pentaBDE to inform decisions on adoption of substitutes. 

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• PentaBDE, octaBDE and decaBDE are being evaluated under EPA’s 

Voluntary Children’s Chemical Evaluation Program (VCCEP). Under 

VCCEP, PBDE manufacturers collect and develop exposure and health effects 

information on their chemicals, integrate that information in a risk assessment, 

and prepare a “data needs assessment.” EPA has completed its Data Needs 

Decisions for the PBDEs and has requested that the PBDEs manufacturers 

develop additional data for assessing risks to children’s health. 

• As part of its National Lake Fish Tissue Study, EPA is measuring PBDEs in 

about 340 fish samples collected from 166 lakes and reservoirs. The 

statistical design of the study will allow EPA to develop the first national 

estimates of mean concentrations and distributions of PBDEs in fish. 

• EPA is reviewing the available toxicology data and preparing toxicological 

profiles for tetraBDE, pentaBDE, hexaBDE and decaBDE congeners under its 

Integrated Risk Information System (IRIS) program. 

• EPA is conducting and sponsoring a number of research activities to help 

develop a better understanding of releases, exposure and effects of PBDEs. 

• A national survey of PBDEs body burdens in the U.S. population is being 

conducted by the Centers for Disease Control and Prevention (CDC), as part 

of the National Health and Nutrition Examination Survey (NHANES). 

PBDEs are being measured for the first time in this ongoing program, with 

survey data for 2003-2004 expected to be released in 2006. 

• The U.S. Department of Agriculture is conducting studies of the absorption 

and metabolism of PBDEs in animals, and has also conducted measurements 

of PBDEs in meat and poultry. 

• The U.S. Food and Drug Administration is conducting studies on methods for 

the analysis of PBDEs in different food and feed matrices, and has measured 

PBDEs in select fish samples. 

• The National Toxicology Program (NTP) is conducting a subchronic toxicity 

study of the commercial pentaBDE mixture in laboratory animals, along with 

pharmacokinetic studies of three PBDE congeners. 

• The National Institute of Standards and Technology is conducting studies on 

the emissions of PBDEs from plastics used in items such as computers and 

televisions. 

• The U.S. Geological Survey is conducting studies on the presence of PBDEs 

in indoor environments and the migration of PBDEs from plastics in 

computers. 

More information on federal government research and assessment of PBDEs is presented 

in Appendices C and D. 

6 
EPA’s Project Plan for PBDEs 

The cessation of pentaBDE and octaBDE manufacture in the U.S. is an important action 

that EPA believes will result in reduced amounts of these chemicals in the environment. 

However, the need for investigating exposures to and effects of PBDEs and related 

chemicals continues. In addition to changes in the market status of pentaBDE and 

octaBDE, forthcoming changes in furniture flammability requirements (being considered 

by the federal Consumer Product Safety Commission and the State of California) may 

increase demand for safer flame retardant chemicals and alternative means of achieving 

flame retardancy in products. This Project Plan identifies four key areas in which EPA is 

pursuing activities addressing concerns regarding PBDEs and other flame retardants. 

Many of these activities involve partnership and coordination with other federal agencies, 

industry and nongovernmental organizations. 

EPA’s four objectives are: 

Objective 1: Assess Substitutes for Pentabromodiphenyl Ether and 

Octabromodiphenyl Ether. As U.S. manufacturers evaluate alternatives to 

pentaBDE and octaBDE, EPA is providing guidance on the potential hazards of 

alternative flame retardants. EPA is conducting a number of activities to identify, 

and to encourage development of, environmentally-preferable flame retardant 

chemicals and inherently flame retardant materials. 

Objective 2: Assess and Evaluate Decabromodiphenyl Ether. EPA is 

pursuing a number of activities to help better understand the potential for human 

health and ecological risks from exposure to decaBDE and any breakdown 

products. 

Objective 3: Assess Risks of Pentabromodiphenyl Ether and 

Octabromodiphenyl Ether. Although U.S. production of pentaBDE and 

octaBDE has been discontinued, the release of and exposure to these chemicals is 

likely to continue for an extended period of time, given their environmental 

persistence and the stocks of pentaBDE and octaBDE contained in existing 

furniture, electronic components and other products. EPA is therefore continuing 

to pursue an improved understanding of exposure to these chemicals and the 

associated hazards. 

Objective 4: Track Developments Concerning Other Brominated Flame 

Retardants of Interest. In addition to the PBDEs, there are many other 

brominated flame retardants currently in use. EPA will track scientific 

developments regarding environmental levels, human exposure, and potential 

hazards. 

7 
C. KEY ACTIVITIES 

Objective 1: Assess Substitutes for Pentabromodiphenyl Ether and 

Octabromodiphenyl Ether 

The sole U.S. manufacturer of pentaBDE and octaBDE phased out production of these 

products at the end of 2004. Users of pentaBDE and octaBDE are currently evaluating 

and selecting alternative flame retardants to replace these chemicals. 

For the flame-retarded polyurethane foam market, where pentaBDE has been a dominant 

product for many years, evaluation and selection of alternative flame retardants is a major 

undertaking. Foam and furniture manufacturers need to consider multiple factors in 

selecting flame retardants, including: compliance with flammability standards, cost of 

the flame retardant, compatibility with existing production equipment, costs of any 

necessary capital investments, ease of foam production, effect on important foam 

characteristics (such as durability, softness/firmness, and color), and possible health and 

environmental risks. The foam manufacturers are best situated to evaluate the cost and 

performance-related factors, with assistance from the chemical manufacturers who supply 

the flame retardants and the furniture manufacturers and other customers for the foam. 

However, the foam and furniture manufacturers are looking to scientific experts, 

including those at EPA, to provide guidance on the potential risks of alternative flame 

retardants. 

There are similar issues related to identifying replacements for octaBDE in plastics. 

However, the transition to alternatives for octaBDE is expected to be less challenging 

than that for pentaBDE, because the volume of use of octaBDE is smaller and alternative 

flame retardants for use in similar applications are available. 

Specific Activities 

1.1 EPA has formed a Furniture Flame Retardancy Partnership with several industry 

associations and other stakeholders. The Partnership has conducted a screening 

level hazard assessment of flame retardant chemicals that may be suitable 

substitutes for pentaBDE. For each alternative chemical, the available scientific 

studies have been reviewed and summarized, data gaps identified, and 

environmental and human health effect endpoints characterized. This screening 

assessment was completed in September 2005 and is available at 

http://www.epa.gov/opptintr/dfe/pubs/projects/flameret/index.htm. The 

information in this report will help furniture manufacturers incorporate health and 

environmental considerations into their selection of replacements for pentaBDE. 

1.2 EPA will work with the Furniture Flame Retardancy Partnership to review 

additional data on flame retardant chemicals used in furniture as appropriate. 

1.3 EPA will monitor developments in the market for replacing octaBDE and will 

assess octaBDE substitutes if warranted. 

8 
Objective 2: Assess and Evaluate Decabromodiphenyl Ether 

EPA will continue to evaluate two broad risk assessment issues for decaBDE. The first 

issue is the potential for human health and ecological risks from exposure to decaBDE 

itself. The second issue is the potential for breakdown or transformation of decaBDE in 

the environment, in organisms or from combustion of decaBDE containing products. 

Information regarding this issue is necessary for determining the relative importance of 

the breakdown or transformation products in the overall risk of decaBDE. 

Specific Activities 

2.1 EPA is conducting a review of the available toxicology data for decaBDE, and 

will update the decaBDE assessment in EPA’s IRIS database. Completion of this 

assessment is projected for 2006. 

2.2 EPA will monitor ongoing and planned research on the toxicity of decaBDE and 

its metabolites. Of particular interest are a developmental neurotoxicity study of 

decaBDE that is being sponsored by the European Union, and studies conducted 

by the FIRE project (Flame retardants Integrated Risk assessment for Endocrine 

effects; see www.rivm.nl/fire) in Europe. FIRE is conducting 28-day toxicity 

study in rats, and may follow this with other animal studies. EPA will coordinate 

with the EU and the FIRE project to ensure that all relevant information regarding 

decaBDE toxicology is shared in a timely manner. 

2.3 EPA will further investigate the environmental fate and metabolism of decaBDE, 

including the potential for formation of lower-brominated congeners by 

debromination of decaBDE in the environment. Through its VCCEP program, 

EPA has determined that additional data are needed to address the potential of 

decaBDE to degrade to other substances in the environment. EPA will work with 

the industry sponsors of the decaBDE VCCEP assessment to address this data 

need. 

2.4 EPA will prepare a white paper that reviews the available information on the 

environmental fate of decaBDE. The purpose of this paper is to assess the 

potential for debromination of decaBDE through various natural mechanisms (e.g. 

exposure to light, breakdown via metabolism in living organisms), the rate, extent 

and conditions under which debromination may occur, and whether 

debromination of decaBDE is likely to be a significant source of lowerbrominated PBDEs in humans and wildlife. The white paper will also identify 

additional studies that would be helpful to developing a better understanding of 

the environmental fate of decaBDE. Emerging information currently under 

development and anticipated over the coming year will be an important part of 

this evaluation, including data needs identified through VCCEP. This effort will 

be initiated in 2006, and the white paper will be peer reviewed in accordance with 

9 
EPA’s Peer Review Handbook and the Office of Management and Budget’s Final 

Information Quality Bulletin for Peer Review. 

2.5 EPA will conduct an interim review of all available scientific information 

concerning decaBDE in 2006/2007. The information to be considered in this 

review will include CDC NHANES data on decaBDE body burdens in the U.S. 

population, other studies reporting decaBDE body burdens in the U.S., data from 

EPA’s National Lake Fish Tissue Study, the EPA White Paper on environmental 

fate of decaBDE, information developed under VCCEP, and other studies that 

may become available concerning decaBDE toxicology and environmental fate 

(including studies conducted or funded by EPA and other agencies listed in 

Appendices C and D). Based on this interim review, EPA will consider whether 

the information warrants pursuing additional research, risk assessment or 

regulation using existing legal authorities. 

2.6 EPA is preparing to propose a SNUR under the Toxic Substances Control Act 

(TSCA) for flame retardants identified as candidates for use to meet the 

residential upholstered furniture flammability standards under consideration by 

the State of California and the U.S. Consumer Product Safety Commission 

(CPSC). Sixteen chemical substances/categories, including decaBDE, are being 

considered for inclusion in the SNUR. The SNUR would require persons who 

intend to manufacture, import, or process any of these chemical substances, or 

articles containing them, for use as a flame retardant in residential upholstered 

furniture to notify EPA at least 90 days before commencing such activity. The 

required notice would provide EPA with the opportunity to evaluate the intended 

use, and if necessary, to prohibit or limit such activity before it occurs. 

2.7 EPA's Furniture Flame Retardancy Partnership is coordinating with the CPSC and 

will discuss whether to undertake a project to evaluate environmentally preferable 

fabric flame retardant chemicals, barrier technologies, inherently flame retardant 

materials and other fire safety approaches. 

Objective 3: Assess Risks of Pentabromodiphenyl Ether and Octabromodiphenyl 

Ether 

Production of pentaBDE and octaBDE in the U.S. was discontinued at the end of 2004. 

EPA has proposed a rule under TSCA that will provide it with the authority to review any 

new plans to manufacture or import pentaBDE and octaBDE. However, the release of 

and exposure to these chemicals is likely to continue for an extended period of time, 

given the stocks of pentaBDE and octaBDE contained in existing furniture, electronic 

components, and other products, and the persistence of these compounds. Debromination 

of decaBDE may also contribute to future exposures. In addition, it is possible that 

pentaBDE or octaBDE could be present in some products (furniture foam and plastics) 

imported into the U.S. EPA intends to investigate this issue further and seek further 

information on the presence of pentaBDE and octaBDE in imported articles. More 

10 
information on pathways of exposure to pentaBDE and octaBDE will help identify the 

types of activities that might be most effective in reducing exposure, if such activities are 

deemed necessary. 

Specific Activities 

3.1 In December 2004, EPA proposed a TSCA SNUR that would require prior notice 

to EPA from any entity planning to begin manufacture or import of pentaBDE or 

octaBDE, or any of the PBDE congeners that comprise these mixtures, for any 

use, after January 1, 2005. EPA plans to promulgate the SNUR in 2006. The 

SNUR will enable EPA to review any intended future manufacture or import of 

pentaBDE and octaBDE. Based on health or environmental concerns that may be 

identified during such a review, EPA could take actions to prohibit or limit the 

production, processing, distribution in commerce, use, and disposal of these 

chemicals. 

3.2 EPA will prepare a white paper that reviews and synthesizes the available 

information on exposure pathways for PBDEs. The purpose of this paper is to 

address: first, the relative importance of different pathways of exposure (i.e. food 

vs. house dust vs. indoor air); and second, information on how PBDEs get into 

various exposure media (e.g., particular foods including fish, house dust, indoor 

air, sediments), including migration of PBDEs from products in use and releases 

from disposal or incineration of products. Information on current disposal and 

recycling practices for end-of-life products containing PBDEs will be collected. 

The white paper will also identify additional studies that would be helpful to 

developing a better understanding of exposure pathways for PBDEs. This effort 

will be initiated in 2006, and the white paper will be peer reviewed in accordance 

with EPA’s Peer Review Handbook and the Office of Management and Budget’s 

Final Information Quality Bulletin for Peer Review. 

3.3 EPA is conducting a review of the available toxicology data for tetra-, penta- and 

hexaBDE congeners under its IRIS program. Completion of these assessments is 

projected for 2006. 

3.4 Through its VCCEP program, EPA has identified additional toxicity information 

as a data need for both pentaBDE and octaBDE. Specifically, EPA has 

determined that the primary data needs are two generation reproductive toxicity 

studies for both pentaBDE and octaBDE. EPA will work with the industry 

sponsor of the pentaBDE and octaBDE VCCEP assessments to address these data 

needs. EPA will also seek further research on the toxicity of pentaBDE and 

octaBDE. Through these efforts, EPA will identify and prioritize proposed 

additional toxicology studies of individual PBDE congeners and/or PBDE 

mixtures common in human samples. EPA will consider developing a proposal 

for NTP to conduct a set of tests to better characterize the toxicology of several 

individual PBDE congeners. 

11 
3.5 EPA will conduct an interim review of all available scientific information 

concerning pentaBDE and octaBDE in 2006/2007. The information in this review 

will include CDC data on PBDE body burdens in the U.S. population, data from 

EPA’s National Lake Fish Tissue Study, NTP studies of pentaBDE toxicology, 

and other studies that may become available concerning toxicology and 

environmental fate of PBDEs (including studies conducted or funded by EPA and 

other agencies listed in Appendices C and D). Based on this interim review, EPA 

will consider whether the information warrants pursuing additional activities, 

which could include: 

• initiating further studies of exposure levels, exposure pathways, and/or 

toxicology of PBDEs. 

• conducting a risk assessment of pentaBDE, octaBDE, or selected 

congeners. A risk assessment of these chemicals would include a review 

of the hazards, a dose-response evaluation, an exposure assessment, and a 

risk characterization. 

• activities to reduce potential exposures to lower-brominated PBDE 

congeners. 

Objective 4: Track Developments Concerning Other Brominated Flame Retardants 

of Interest 

PBDEs are just one group of flame retardant chemicals currently in use in the U.S. The 

various flame retardants in use have different chemical and biological properties; 

therefore, each must be evaluated independently. In addition to PBDEs, there are two 

other brominated flame retardants in particular that have been measured in the 

environment and are the subject of continuing interest: tetrabromobisphenol A (TBBPA) 

and hexabromocyclododecane (HBCD). Another chemical of interest is 

decabromodiphenyl ethane, which has been used as a substitute for decaBDE in Europe 

and has been measured in environmental samples. 

Specific Activities 

4.1 Any new flame retardants not already in commerce in the U.S. must be submitted 

to EPA for a premanufacture review under TSCA. During the review period, 

EPA may take action to prohibit or limit the production, processing, distribution 

in commerce, use, and disposal of new chemical substances that raise health or 

environmental concerns. EPA will continue to scrutinize new flame retardants 

proposed for manufacture and import into the U.S. market and, where appropriate, 

will seek control measures and/or development of additional data on such 

chemicals by their manufacturers under TSCA Section 5 authorities. 

12 
4.2 EPA will monitor the developing science on brominated flame retardants, 

including TBBPA and HBCD. Among the important activities underway are 

studies of TBBPA and HBCD as part of the European Commission FIRE project. 

EPA will also monitor information on disposal and recycling practices for end-oflife consumer products containing flame retardant chemicals. EPA will review 

the available information on other brominated flame retardants in 2006/2007. 

Based on this review, EPA will consider whether the information warrants 

pursuing additional activities, which could include initiating additional studies of 

environmental fate, exposure pathways, and/or toxicology of certain flame 

retardant chemicals, and conducting IRIS assessments of hazard and doseresponse, and/or full risk assessments of certain flame retardant chemicals. 

13 
D. CONCLUSION 

This Project Plan identifies a number of activities that EPA is conducting regarding 

PBDEs, as well as activities it intends to initiate or consider within the next two years. 

Many of the activities are focused on identifying and prioritizing data needs and 

generating new information to help understand risks of PBDEs and other flame 

retardants. 

As the activities outlined in the Project Plan proceed, EPA may identify and initiate 

additional activities that have not been defined at this time. EPA will evaluate use of 

additional voluntary approaches and its existing legal authorities, when necessary, to 

obtain additional information on potential releases, exposures, effects and risks of PBDEs 

and other flame retardants and to take actions to reduce potential risks, if deemed 

appropriate. 

EPA will also continue to track activities and initiatives at the state and local level, as 

well as internationally, and will exchange technical information with other government 

agencies. In addition, EPA will maintain updated information on its PBDEs activities on 

its web site at www.epa.gov/oppt/pbde. 

REFERENCES 

ECB (2003). European Union Risk Assessment Report: diphenyl ether, octabromo 

derivative. European Chemicals Bureau. Ispra, Italy. 

Environ (2003). Tier 1 Assessment of the Potential Health Risks to Children Associated 

with Exposure to Commercial Pentabromodiphenyl Ether Product. Environ 

International Corporation. Emeryville, California. 

WHO (1994). Brominated Diphenyl Ethers. Environmental Health Criteria 162. World 

Health Organization, International Programme on Chemical Safety. Geneva, 

Switzerland. 

14 
APPENDIX A. CURRENT SCIENTIFIC UNDERSTANDING OF PBDEs 

The scientific literature on PBDEs is growing at a rapid rate. This appendix presents a 

summary of the science on PBDEs as of early 2005. It is not meant to represent an 

exhaustive review and evaluation of the PBDEs literature. A detailed evaluation of 

studies or limitations of the available information is beyond the scope of this document, 

and this summary should not be taken to represent an assessment of the hazards or risks 

of PBDEs. EPA is currently conducting detailed assessments of the toxicological 

information for several PBDE congeners as part of its Integrated Risk Information 

System (IRIS) program. When completed, these assessments will provide a thorough 

review of the toxicological literature for tetra-, penta-, hexa- and decaBDE congeners. 

PBDEs in the Environment and PBDE Exposures 

PBDEs were first detected in the environment in 1979 (Alaee and Wenning 2002) and in 

biota in the 1980s (Jansson et al. 1987). Recent PBDE monitoring efforts suggest that 

several PBDE congeners are ubiquitous in the environment (NTP 2001) and that levels of 

PBDEs in sediment, air, wildlife, and human tissues are increasing. Measurements of 

PBDE congeners in humans, fish and other biota detect BDE-47 more frequently than 

other congeners. However, monitoring efforts have not analyzed collected samples for 

all possible PBDE congeners. Therefore, potential contributions of other congeners may 

have been overlooked. 

SEDIMENT, SLUDGE AND EFFLUENT 

PBDEs have been found in sediment samples, sewage effluent, and sewage sludge with 

differing congener profiles. Detailed analyses of sediment cores from Lake Superior 

detected decaBDE (BDE-209) in much greater concentrations than other PBDE 

congeners (Song et al. 2004). PBDEs found in sewage sludge and effluent may be a 

contributor to the PBDEs in sediment. TetraBDE, pentaBDE, and decaBDE congeners 

represent the majority of PBDEs found in a samples of Great Lakes sewage sludge (Hale 

et al. 2003) and in San Francisco Bay area sewage effluent and sludge (North 2004). The 

congener profiles in both studies indicate the largest portion of the total PBDE present in 

the sludge samples to be BDE-99. BDE-47 and BDE-209 are also dominant congeners in 

both studies. No explanation is available for the difference in congener profiles in 

sludge, effluent, and sediment. Potential regional differences in PBDE deposition and 

varying rates of congener breakdown in the environment may contribute to the differing 

congener profiles in these three media. 

AIR AND INDOOR ENVIRONMENTS 

PBDEs have been detected in ambient air and indoor environments (Harrad et al. 2004; 

Jaward et al. 2004; Lee et al. 2004; Shoeib et al. 2004; Wilford et al. 2004). Due to its 

low volatility and strong sorption to particulates, the deca congener BDE-209 is not 

thought to be a likely candidate for airborne transport (Hale et al. 2003); however, the 

majority of studies conducted to date have not analyzed outdoor air samples for BDE209. Findings of BDE-209 in arctic biota suggest the possibility of long-range 

15 
distribution (Ikonomou et al. 2002; Wolkers et al. 2004). Indoor air samples contain a 

variety of tetraBDE, pentaBDE, and hexaBDE congeners (Harrad et al. 2004). The 

decaBDE congener, BDE-209, has been measured in outdoor and indoor window 

surfaces (Butt et al. 2004). In addition, tetraBDE, pentaBDE and decaBDE congeners are 

present in North American house dust (Rudel et al. 2003; Stapleton et al. 2005). 

WILDLIFE 

Numerous ecological studies provide convincing evidence that some PBDEs 

bioaccumulate (Hites et al. 2004; NTP 2001). Studies examining trends of PBDE levels 

in North American wildlife have found sharp increases over periods of 10-20 years, with 

PBDE levels doubling every 3-5 years. (Ikonomou et al. 2002; Lebeuf et al. 2004; 

Norstrom et al. 2002; Zhu and Hites 2004). Studies of Baltic Sea biota indicate that

PBDE concentrations increase with the trophic level, suggesting biomagnification of 

PBDEs in aquatic ecosystems (Haglund et al. 1997; NTP 2001). New evidence suggests 

the breakdown of higher brominated congeners in fish and mammalian tissues, which 

may contribute to the accumulation of lower brominated congeners (Morck et al. 2003; 

Stapleton et al. 2004a; Stapleton et al. 2004b; Tomy et al. 2004). Bioaccumulation in a 

whale of methoxylated PBDEs, including methoxylated BDE-47, has been shown to be 

of natural origin and not from industrial sources. Several methoxylated-PBDEs are 

known natural products, and have been observed in dolphins and other marine mammals, 

sponges, algae, and acorn worms (Teuten et al. 2005). PBDE congener profiles in 

wildlife tissues are likely dependent on a combination of direct uptake from the 

environment, natural synthesis, debromination of higher brominated congeners to lower 

brominated congeners and differential biomagnification over trophic levels. 

FOOD 

Regional analyses have detected PBDEs in fish, meat, and dairy products (Hites 2004; 

Huwe et al. 2002; Ohta et al. 2002; Schecter et al. 2004). In fish and dairy products, 

BDE-47 appears to dominate the PBDE congener profile (Hites 2004; Ohta et al. 2002; 

Schecter et al. 2004) while BDE-99 is the dominant congener in meat (Huwe et al. 2002; 

Schecter et al. 2004). Detectable levels of BDE-209 are also found in many food samples 

(Schecter et al. 2004). In dairy samples, congener profiles indicate a wider variation than 

either fish or meat (Schecter et al. 2004). It should be noted, however, that the analyses 

of food items are currently limited to small numbers of samples from a limited number of 

locations. 

HUMAN TISSUES 

PBDEs have been found in human breast milk, adipose tissue, and blood samples (Hites 

2004; Mazdai et al. 2003; Petreas et al. 2003; Schecter et al. 2003; She et al. 2002). Data 

for the U.S. are very limited at this time. BDE-47 appears to be the dominant congener in 

human tissues in the U.S.; however, the sample sizes have been very small and the interindividual variability is great, most notably for BDE-47. 

Most of the breast milk biomonitoring data have been generated in Sweden, although 

there are very limited data available for the U.S. and Canada. The largest breast milk 

study to date in the U.S. (Schecter et al. 2003) analyzed 47 individual breast milk samples 

16 
from nursing mothers in Texas. The levels in these volunteer women were markedly 

higher for all congeners than those that have been reported in Sweden and Finland 

(Meironyte et al. 1999; Meironyte Guvenius and Noren 2001; Meironyte Guvenius et al. 

2003; Strandman et al. 2000). 

In the U.S., limited data are available for PBDE levels in blood serum. However, 

compared to blood monitoring data from Sweden, Japan, and Norway, the most recent 

blood serum levels in U.S. populations are higher and quite variable. A recent 

retrospective time trend study of PBDEs in very small samples of blood serum in the U.S. 

has shown that median levels of the individual congeners as well as total PBDEs have 

increased in the U.S. from 1985 to 2002 (Sjodin et al. 2004). Data on PBDE blood serum 

levels in 12 maternal and fetal pairs from Indiana indicated that 6 PBDE congeners were 

measured in blood serum samples and that the predominant congener was BDE-47 

(Mazdai et al. 2003). The range of total PBDEs in the maternal and fetal samples were 

very similar; however, the variability between the pairs was great, especially for BDE-47. 

EXPOSURE PATHWAYS 

As described above, PBDEs are present in many critical exposure media, including 

various foods, indoor air and house dust. However, the means by which humans and 

wildlife are exposed to PBDEs are not well understood. PBDEs may enter the 

environment in a variety of ways: release from manufacture of the PBDEs or of PBDEcontaining products; release of PBDEs from products while they are in use; and release 

from products when disposed of or recycled. There are many uncertainties regarding the 

pathway of PBDEs from release to their presence in critical environments and exposure 

media. It is likely that the presence of PBDEs in indoor environments (house dust, 

indoor air, and indoor window surfaces) is in large part due to migration of PBDEs from 

products, including furniture and carpet foam and plastics in televisions and computers. 

Little is known about how PBDEs enter aquatic environments, and how they enter the 

food chain. The biomonitoring data described above indicate that there is human 

exposure to PBDEs; but the relative contributions of different exposure routes (such as 

inhalation, food ingestion, dust ingestion or dermal absorption) have not been 

characterized. The relative importance of these types of exposure may be different for 

infants, young children, older children, and adults. 

Pharmacokinetic and Toxicity Profiles of PBDEs in Mammals 

PHARMACOKINETICS 

The available data indicate that the tetra congener BDE-47 and the penta congener BDE99 are well absorbed and highly distributed to fatty tissues, such as adipose, adrenal 

glands, gastrointestinal tract, skin and liver (Hakk et al. 2002; Orn and Klasson-Wehler 

1998; Staskal et al. 2005). Tetra- and pentaBDEs are slowly metabolized and slowly 

eliminated in rats (Hakk et al. 2002; Hakk and Letcher 2003). In mice BDE-47 (a 

tetraBDE) is also well absorbed and distributed, but it is effectively eliminated, with up 

to 81% of the dose excreted within 5 days (Staskal et al. 2005). DecaBDE is poorly 

17 
absorbed by rats, with more than 90% of the dose excreted within 2 days (Morck et al. 

2003). 

HEPATIC EFFECTS 

Studies conducted in rodents have demonstrated hepatotoxic potential with exposure to 

PBDE mixtures. The spectrum of hepatic effects observed in studies of various PBDE 

congeners and mixtures includes microsomal enzyme induction, liver enlargement, and 

degenerative histopathologic alterations. In rodents, dietary exposure to 5-10 mg/kg/day 

(IRDC 1976; IRDC 1977; Norris et al. 1973; Norris et al. 1975; Zhou et al. 2001; Zhou et 

al. 2002) and 56 mg/kg/day (Carlson 1980) of PBDEs typically caused liver enlargement 

with or without degenerative changes, and the incidence and severity of effects were 

generally dose-related and more frequent and pronounced in males than females. Effects 

are generally more severe with commercial mixtures of octaBDE and pentaBDE than 

decaBDE (Carlson 1980; IRDC 1976; IRDC 1977; Norris et al. 1973; Norris et al. 1975; 

NTP 1986; WIL Research Laboratories 1984; Zhou et al. 2001; Zhou et al. 2002). Some 

of the studies indicating thyroid effects of decaBDE were conducted on older commercial 

mixtures that contained more impurities that the products currently manufactured. 

When scientists began studying PBDEs, there was some expectation that the PBDEs 

might have some toxicological similarities to dioxins, due to the structural similarities of 

these chemicals. To test this hypothesis, scientists conducted studies of hepatic enzyme 

activity. Induction of the cytochrome P450 enzyme CYP1A is a well-established 

characteristic of chemicals that bind to the aryl hydrocarbon receptor (AhR), most 

notably dioxins, furans and co-planar PCBs (also known collectively as "dioxin-like 

compounds"). By binding to the AhR a chemical may initiate a number of other effects 

that characterize "dioxin-like" toxicity in addition to inducing CYP1A. Hence CYP1A 

induction is considered an indicator that a chemical can bind to the AhR and has the 

potential to cause toxicity similar to dioxin. Initial studies were conducted in commercial 

PBDE mixtures and have been reported to induce CYP1A at doses of 18 – 60 mg/kg 

(Hallgren et al 2001; Stoker et al. 2004). However, the tetra congener BDE-47 did not 

induce CYP1A at doses up to 100 mg/kg (Staskal et al. 2005). Studies in fish (see below) 

have also found CYP1A induction from commercial PBDE mixtures, but not for 

individual PBDE congeners. Given that there is no indication of CYP1A induction by 

PBDE congeners, this suggests that there is a constituent of the commercial mixtures, i.e. 

a contaminant other than the PBDE congeners, that is responsible for the enzyme 

induction. It appears that PBDEs themselves do not have dioxin-like activity. 

IMMUNOLOGICAL EFFECTS 

Disruption of normal immune function may result in an inability of the animal to respond 

to and recover from further stressors such as illness and disease. Short term (14-day) 

exposure to 18-72 mg/kg/day of commercial pentaBDE mixtures in mice resulted in 

suppressed antibody response, decreased thymus weight (Fowles et al. 1994) and 

decreased IgG immunoglobulin production (Thuvander and Darnerud 1999). Short-term 

exposure of mice to 18 mg/kg/day of BDE-47 caused significantly reduced numbers of 

total lymphocytes and splenocytes (Thuvander and Darnerud 1999). Chronic ingestion of 

decaBDE at 2240 mg/kg/day for 103 weeks caused splenic lesions in rats (NTP 1986). 

18 
No inhibition of the immune response system was observed in a study of the effect of 

BDE 85 (Fernlof et al. 1997). Currently available information is insufficient to 

adequately characterize the immunotoxic potential of PBDEs. 

DEVELOPMENTAL AND NEUROBEHAVIORAL ALTERATIONS 

Gestational exposure to 1000 mg/kg/day of decaBDE for 19 days resulted in increased 

early resorptions in rats; the authors concluded that these were of limited significance 

based on comparison to historical control data (Hardy et al. 2002). 

Developmental neurotoxic effects have been found in rodent studies of exposure to 

individual PBDE congeners. In neonatal mice, postnatal day 10 was determined to be a 

critical window of sensitivity to PBDE exposure. Animals treated with 0.6 and 6 

mg/kg/day of BDE-99 for 15 days (Branchi et al. 2002) and single 0.4 mg/kg doses of 

BDEs 47, 99, 153, or 209 (Birnbaum and Staskal 2004; Branchi et al. 2003; Eriksson et 

al. 2001; Viberg et al. 2002; Viberg et al. 2003a; Viberg et al. 2003b) showed 

neurobehavioral alterations , hyperactivity extending into adulthood, and a 

nonhabituating behavior profile. In male offspring of dams treated with single 60 μg/kg 

and 300 μg/kg doses of BDE-99, developmental reproductive and neurobehavioral 

landmarks were significantly delayed (Kuriyama et al. 2005). Developmental 

reproductive effects have also been observed following 31 days of exposure to 30 

mg/kg/day and 60 mg/kg/day of the commercial pentaBDE mixture (Stoker et al. 2004). 

ENDOCRINE DISRUPTING EFFECTS 

Evidence from experimental animal studies for certain PBDE congeners and commercial 

mixtures has indicated the potential for effects on the thyroid system. Thyroid effects 

include reduced serum levels of the thyroid hormone T4 (thyroxine) with exposure to 

commercial pentaBDE at doses of 3 mg/kg/day (Stoker et al. 2004), 10 mg/kg/day (Zhou 

et al. 2001; Zhou et al. 2002), and single acute doses of 0.8 mg/kg and greater (Fowles et 

al. 1994). In addition, follicular cell hyperplasia, which is a sign of disrupted thyroid 

function, was observed in male mice orally exposed to 3200 mg/kg/day or more of 

decaBDE (NTP 1986). Disruptions in maternal and fetal thyroid homeostasis can result 

in neurologic impairment, including developmental delays and decreased IQ in children 

of mothers with small reductions in T4 (Haddow et al. 1999; Pop et al. 1999; Pop et al. 

2003). 

Hydroxylated BDEs, which are metabolites of PBDEs, have been shown to inhibit 

estrogen sulfotransferase, leading to an apparent estrogenic effect (Kester et al. 2002). A 

study of the estrogenic potential of several PBDE congeners and hydroxylated 

metabolites found 11 PBDE congeners and 2 hydroxylated metabolites with estrogenic 

activity (Meerts et al. 2001). Stoker and co-workers found endocrine effects and 

developmental delays with exposures to the commercial pentaBDE mixture of 30 and 60 

mg/kg/day for 31 days , indicating inhibition of endogenous androgen activity (Stoker et 

al. 2004). Anti-androgenic and estrogenic activity are of concern as they may lead to a 

disruption of normal endocrine function and potentially result in reproductive failure and 

estrogen-related cancers. 

19 
REPRODUCTIVE EFFECTS 

Male and female rats exposed to the commercial pentaBDE mixture DE-71 exhibited 

delayed pubertal development with dosing at 30 and 60 mg/kg/day for 5, 21 or 31 days 

(Stoker et al. 2004). Of the androgen-dependent tissues in exposed male rats, seminal 

vesicle and ventral prostate weights were reduced, while testes and epididymal weights 

were not affected. Preputial separation and age of vaginal opening were significantly 

delayed in exposed female rats. Kuriyama and co-workers evaluated male reproductive 

health in the rat offspring of dams exposed to BDE-99 in single doses of 60 and 300 

μg/kg. Daily sperm production and spermatid counts were significantly decreased 

(Kuriyama et al. 2005). EPA’s Voluntary Children’s Chemical Evaluation Program 

(VCCEP) has concluded that the limited reproductive toxicity data for pentaBDE and 

octaBDE constitutes an important data need for these chemicals. 

CANCER 

There is some evidence that decaBDE is carcinogenic in rats and mice from an NTP twoyear cancer bioassay (NTP 1986). Statistically significant increases in the incidence of 

hepatic neoplastic nodules were seen in male rats at 1120 and 2240 mg/kg/day, and in 

female rats at 2550 mg/kg/day. Increased incidence of hepatocellular adenomas or 

carcinomas (combined) were seen in male mice at 3200 mg/kg/day; increases relative to 

controls were seen in male mice dosed at 6650 mg/kg/day and in female mice dosed at 

3760 and 7780 mg/kg/day but were not statistically significant. Based on these results, 

EPA has classified decaBDE as a possible human carcinogen (U.S. EPA 1995). As part 

of the IRIS assessment of decaBDE, EPA is currently updating its assessment of the 

carcinogenic potential of decaBDE to reflect the Agency’s revised Guidelines for 

Carcinogen Risk Assessment (U.S. EPA 2005). Studies of the carcinogenic potential of 

pentaBDE and octaBDE have not been conducted. 

Pharmacokinetic and Toxicity Profiles of PBDEs in Ecological Receptors 

Effects of PBDEs in ecological receptors are currently limited. To date, a variety of 

endpoints have been assessed in a very limited number of species, primarily invertebrates 

and fish commonly used in aquatic toxicity testing. Detailed reviews of studies 

conducted through 1999 can be found in the European Union risk assessments for the 

PBDEs (ECB 2001; ECB 2002; ECB 2003). No published reports of PBDE toxicity in 

birds or mammalian wildlife were located. However, recent preliminary reports indicate 

studies to investigate effects of PBDEs on a variety of sublethal endpoints in avian and 

mammalian wildlife are underway (SETAC 2004). 

PHARMACOKINETICS 

In a study of uptake, accumulation and excretion of BDE-47, -99, and -153 by blue 

mussels, the uptake rate for BDE-47 and BDE-99 was approximately 10 times higher 

than for BDE-153, but that depuration rates were similar for all three PBDEs (Gustaffson 

et al. 1999). Uptake efficiencies of BDE-47, BDE-99 and BDE-153 by pike fed trout 

injected with the congeners were 90%, 62% and 40%, respectively (Burreau et al. 1997). 

In contrast, uptake of decaBDE is estimated to be quite low (0.02-0.13%) (Kierkegaard 

20 
et al. 1999a). Similarly, in carp exposed via the diet for 100 days, BDE-209 did not 

accumulate (Stapleton et al. 2004a). BDE-47 was distributed in liver, gall bladder, 

kidneys, brain, chorion of the eye and perivisceral adipose tissue in pike (Burreau and 

Broman 1998; Burreau et al. 2000). 

Recent studies suggest metabolic debromination of higher brominated congeners occurs 

in fish. Stapleton and co-workers (Stapleton et al. 2004a; Stapleton et al. 2004b) found 

that BDE-99, -183 and -209 administered via the diet are debrominated in the intestinal 

tract of the common carp. In a long term feeding study in which 13 tri- through decaPBDE congeners (purity greater than 96%) were fed to juvenile lake trout, Tomy et al. 

report the detection of increasing concentrations of lower brominated congeners and 

occurrence of three penta- and hexa- congeners that were not present in the technical 

product used to dose the fish, in the food they were fed or in control fish, supporting the 

hypothesis that higher brominated congeners are debrominated to lower brominated 

congeners (Tomy et al. 2004). 

Hydroxylated and/or methoxylated PBDE congeners have been found in Baltic salmon, 

herring, ringed seal, and gray seal (Asplund et al. 1997; Asplund et al. 1999; Haglund et 

al. 1997; Kierkegaard et al. 1999b). 

PLANTS 

The commercial pentaBDE mixture was essentially non-toxic to a freshwater alga 

exposed to concentrations ranging from 1.7 ug/L to 26 ug/L in a standard 96-hour 

toxicity test (ECB 2001). DecaBDE had no effects on the growth of three species of 

marine algae at concentrations up to 1 microgram per liter (Walsh et al. 1987). 

INVERTEBRATES 

PentaBDE and octaBDE have been tested for effects on Daphnia magna. In 21-day life 

cycle studies, OctaBDE did not affect survival, reproduction or growth of Daphnia 

magna at concentrations ranging from 0.123 ug/L to 1.96 ug/L (ECB 2003). While some 

effects were reported for pentaBDE, the significance of the results is confounded by the 

fact that the test concentrations often exceeded the solubility limits of some of the 

mixture (ECB 2001). Daphnid reproduction was not affected in this test. PentaBDE did 

not cause toxic effects to earthworms in a 14-day study (ECB 2001). Chronic exposure 

of sediment organisms (e.g., Hyalella azteca, Chironomus riparius and Lumbriculus 

variegatus) to pentaBDE produced no-observable-effect-concentrations (NOECs) in the 

low milligram per kilogram range for pentaBDE (ECB 2001) and no adverse effects were 

seen with octaBDE (ECB 2003). 

Effects of specific PBDE congeners on two crustacean species have been demonstrated. 

Full life-cycle studies indicate BDE-47, BDE-99 and BDE-100, at low microgram per 

liter concentrations affect larval development and population growth rate in the copepod 

Nitocra spinipes (Breitholtz and Wollenberger 2003). BDE-28, BDE-47, BDE-99 and 

BDE-100 were found to inhibit larval development in the copepod Acartia tonsa in the 

low microgram per liter concentration range (Wollenberger et al. 2005). 

21 
FISH 

A variety of PBDE mixtures have been found to have very low or no acute toxicity in 

fish. Commercial mixtures of pentaBDE, octaBDE, and decaBDE had low or no acute 

toxicity to Japanese medaka and rainbow trout at the solubility limit, even when a carrier 

solvent was used to increase water solubility (ECB 2001; Hardy 2002). 

In an early life stage toxicity study conducted with rainbow trout, no effects were 

observed on hatching, swim up or larval and fry survival following 21days waterborne 

exposure to a pentaBDE mixture. At 60 days post-hatch, statistically significant effects 

on juvenile fish length and weight were observed at the highest concentration tested (16 

μg/L) (ECB 2001). Hornung et al. assessed the toxicity of single congeners, BDE-47, 

BDE-85, and BDE-99, using an egg injection bioassay developed to assess the toxicity of 

dioxin-like chemicals in early life stages of rainbow trout. While this bioassay has great 

sensitivity for detecting dioxin-like toxicity, none of the PBDE congeners tested caused 

similar early life stage toxicity (Hornung et al. 1996). 

As noted above, structural similarities of PBDEs and dioxins led scientists to suspect that 

PBDEs have toxicological properties similar to dioxins. The potential for PBDEs to 

possess dioxin-like activity has been explored by measuring induction of the hepatic 

enzyme cytochrome P450 (CYP1A) because this is a well-established characteristic of 

chemicals that bind to the AhR, including dioxins. Hepatic CYP1A activity was weakly 

induced (only 2-3 fold) in rainbow trout larvae injected with a commercial pentaBDE 

mixture (Norrgren et al. 1993). Likewise, CYP1A activity was induced in three-spined 

stickleback fed chironomids contaminated with the same PBDE mixture (Holm et al. 

1993). In contrast, in rainbow trout fed food containing BDE-47 and BDE-99, CYP1A 

activity was inhibited (Tjarnlund et al. 1998). DecaBDE had no effect on CYP1A 

activity in rainbow trout exposed for 120 days via the diet (Kierkegaard et al. 1999a). 

Thirteen different PBDE congeners (28, 47, 66, 77, 85, 99, 100, 138, 153, 154, 183, 190, 

and 209) were administered to juvenile lake trout to assess bioaccumulation and 

biotransformation (Tomy et al. 2004). In this study, no increase in CYP1A activity was 

observed at concentrations of the PBDE congeners above those observed in the 

environment. The finding that commercial PBDE mixtures affected CYP1A activity but 

that individual congeners did not is consistent with the mammalian literature, and 

similarly suggests that the enzyme induction is due to some contaminant in the 

commercial mixtures rather than the PBDE congeners themselves. 

A variety of other biochemical endpoints have been assessed in fish exposed to PBDEs. 

DecaBDE increased liver weight and plasma lactate levels and decreased the number of 

lymphocytes in rainbow trout dosed with 10 mg decaBDE for up to120 days via the diet. 

DecaBDE had no effect on transketolase , ethoxyresorufin-O-deethylase, or 

ethoxycoumarin-O-deethylase activity in the same rainbow trout (Kierkegaard et al. 

1999a). Fat accumulation in liver and reduced spawning success was observed in threespined stickleback fed doses of a commercial pentaBDE mixture corresponding to 

concentrations of 861 and 1630 mg/kg of fat tissue (Holm et al. 1993). Reduced 

glutathione reductase activity, hematocrit and blood glucose levels were observed in 

rainbow trout fed a total dose of 21 mg/kg of BDE-47 or 19.5 mg/kg BDE-99 via their 

22 
diet over 22 days (Tjarnlund et al. 1998). However, in the same study, no effects on 

condition factor, liver and spleen somatic indices, white blood cell counts or hemoglobin 

were observed. Whether these biochemical changes significantly affect health of 

individual fish or fish populations is currently not established. 

REFERENCES 

Alaee M and Wenning RJ (2002). The significance of brominated flame retardants in the 

environment: current understanding, issues and challenges. Chemosphere 46:579-82. 

Asplund L, Athanasiadou M, Eriksson U, Sjodin A, Borjeson H and Bergman A (1997). Mass 

spectrometric screening for organohalogen substances (OHs) in blood plasma from Baltic 

salmon (Salmo salar). Organohalogen Compd 33:355-9. 

Asplund L, Athanasiadou M, Sjodin A, Bergman A and Borjeson H (1999). Organohalogen 

substances in muscle, egg and blood from healthy Baltic salmon (Salmo salar) and Baltic 

salmon affected by the M74 syndrome. Ambio 28:67-76. 

Birnbaum LS and Staskal DF (2004). Brominated flame retardants: cause for concern? Environ 

Health Perspect 112:9-17. 

Branchi I, Alleva E and Costa LG (2002). Effects of Perinatal Exposure to a Polybrominated 

Diphenyl Ether (PBDE 99) on Mouse Neurobehavioural Development. NeuroToxicology 

23:375-384. 

Branchi I, Capone F, Alleva E and Costa LG (2003). Polybrominated diphenyl ethers: 

neurobehavioral effects following developmental exposure. Neurotoxicology 24:449-62. 

Breitholtz M and Wollenberger L (2003). Effects of three PBDEs on development, reproduction 

and population growth rate of the harpacticoid copepod Nitocra spinipes. Aquat Toxicol 64:85­

96. 

Burreau S, Axelman J, Broman D and Jakobsson E (1997). Dietary uptake in pike (Esox lucius) 

of some polychlorinated biphenyls, polychlorinated naphthalenes and polybrominated diphenyl 

ethers administered in natural diet. Environ Toxicol Chem 16:2508-2513. 

Burreau S and Broman D (1998). Uptake of PBDEs in pike (Esox lucius) from food. 

Organohalogen Compd 39:39-42. 

Burreau S, Broman D and Orn U (2000). Tissue distribution of 2,2',4,4'-tetrabromo[14C]diphenyl 

ether ([14C]-PBDE 47) in pike (Esox lucius) after dietary exposure--a time series study using 

whole body autoradiography. Chemosphere 40:977-85. 

Butt CM, Diamond ML, Truong J, Ikonomou MG and ter Schure AF (2004). Spatial distribution 

of polybrominated diphenyl ethers in southern Ontario as measured in indoor and outdoor 

window organic films. Environ Sci Technol 38:724-31. 

Carlson GP (1980). Induction of xenobiotic metabolism in rats by short-term administration of 

brominated diphenyl ethers. Toxicol Lett 5:19-25. 

23 
ECB (2001). European Union Risk Assessment Report: diphenyl ether, pentabromo derivative. 

European Chemicals Bureau. Ispra, Italy. 

ECB (2002). European Union Risk Assessment Report: bis(pentabromophenyl) ether. European 

Chemicals Bureau. Ispra, Italy. 

ECB (2003). European Union Risk Assessment Report: diphenyl ether, octabromo derivative. 

European Chemicals Bureau. Ispra, Italy. 

Environ (2003). Tier 1 Assessment of the Potential Health Risks to Children Associated with 

Exposure to Commercial Pentabromodiphenyl Ether Product. Environ International Corporation. 

Emeryville, California. 

Eriksson P, Jakobsson E and Fredriksson A (2001). Brominated flame retardants: a novel class of 

developmental neurotoxicants in our environment? Environ Health Perspect 109:903-8. 

Fernlof G, Gadhasson I, Podra K, Darnerud PO and Thuvander A (1997). Lack of effects of some 

individual polybrominated diphenyl ether (PBDE) and polychlorinated biphenyl (PCB) 

congeners on human lymphocyte functions in vitro. Toxicol Lett 90:189-97. 

Fowles JR, Fairbrother A, Baecher-Steppan L and Kerkvliet NI (1994). Immunologic and 

endocrine effects of the flame-retardant pentabromodiphenyl ether (DE-71) in C57BL/6J mice. 

Toxicology 86:49-61. 

Gustaffson K, Bjork M, Burreau S and Gilek M (1999). Bioaccumulation kinetics of brominated 

flame retardants (polybrominated diphenyl ethers) in blue mussels (Mytilus edulis). Environ 

Toxicol Chem 18:1218-24. 

Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, O'Heir CE, Mitchell 

ML, Hermos RJ, Waisbren SE, Faix JD and Klein RZ (1999). Maternal thyroid deficiency 

during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 

341:549-55. 

Haglund PS, Zook DR, Buser H and Hu J (1997). Identification and quantification of 

polybrominated diphenyl ethers and methoxy-polybrominated diphenyl ethers in baltic biota. 

Environ Sci Technol 31:3281-87. 

Hakk H, Larsen G and Klasson-Wehler E (2002). Tissue disposition, excretion and metabolism of 

2,2',4,4',5-pentabromodiphenyl ether (BDE-99) in the male Sprague-Dawley rat. Xenobiotica 

32:369-82. 

Hakk H and Letcher RJ (2003). Metabolism in the toxicokinetics and fate of brominated flame 

retardants--a review. Environ Int 29:801-28. 

Hale RC, Alaee M, Manchester-Neesvig JB, Stapleton HM and Ikonomou MG (2003). 

Polybrominated diphenyl ether flame retardants in the North American environment. Environ Int 

29:771-9. 

Hardy ML (2002). The toxicology of the three commercial polybrominated diphenyl oxide (ether) 

flame retardants. Chemosphere 46:757-77. 

24 
Hardy ML, Schroeder R, Biesemeier J and Manor O (2002). Prenatal oral (gavage) 

developmental toxicity study of decabromodiphenyl oxide in rats. Int J Toxicol 21:83-91. 

Harrad S, Wijesekera R, Hunter S, Halliwell C and Baker R (2004). Preliminary assessment of 

U.K. human dietary and inhalation exposure to polybrominated diphenyl ethers. Environ Sci 

Technol 38:2345-50. 

Hites RA (2004). Polybrominated diphenyl ethers in the environment and in people: a metaanalysis of concentrations. Environ Sci Technol 38:945-56. 

Hites RA, Foran JA, Schwager SJ, Knuth BA, Hamilton MC and Carpenter DO (2004). Global 

assessment of polybrominated diphenyl ethers in farmed and wild salmon. Environ Sci Technol 

38:4945-9. 

Holm G, Norrgren L, Andersson T and Thuren A (1993). Effects of exposure to food 

contaminated with PBDE, PCN or PCB on reproduction, liver morphology and cytochrome 

P450 activity in the three-spined stickleback, Gasterosteus aculeatus. Aquat Toxicol 27:33-50. 

Hornung MW, Zabel EW and Peterson RE (1996). Toxic equivalency factors of polybrominated 

dibenzo-p-dioxin, dibenzofuran, biphenyl, and polyhalogenated diphenyl ether congeners based 

on rainbow trout early life stage mortality. Toxicol Appl Pharmacol 140:227-34. 

Huwe JK, Lorentzsen M, Thuresson K and Bergman A (2002). Analysis of mono- to decabrominated diphenyl ethers in chickens at the part per billion level. Chemosphere 46:635-40. 

Ikonomou MG, Rayne S and Addison RF (2002). Exponential increases of the brominated flame 

retardants, polybrominated diphenyl ethers, in the Canadian Arctic from 1981 to 2000. Environ 

Sci Technol 36:1886-92. 

IRDC (1976). Decabromodiphenyl ether and octabromodiphenyl ether. A twenty-eight day 

toxicity study in rats. International Research and Development Corporation. Submitted to U.S. 

EPA under TSCA Section 8D, Fiche no. OTS0523322. 

IRDC (1977). Octabromodiphenyl ether. Thirteen week feeding study in rats. International 

Research and Development Corporation. Submitted to U.S. EPA under TSCA Section 8D, Fiche 

no. OTS0522297. 

Jansson B, Asplund L and Olsson M (1987). Brominated flame retardants--ubiquitous 

environmental pollutants? Chemosphere 16:2343-49. 

Jaward FM, Meijer SN, Steinnes E, Thomas GO and Jones KC (2004). Further studies on the 

latitudinal and temporal trends of persistent organic pollutants in Norwegian and U.K. 

background air. Environ Sci Technol 38:2523-30. 

Kester MH, Bulduk S, van Toor H, Tibboel D, Meinl W, Glatt H, Falany CN, Coughtrie MW, 

Schuur AG, Brouwer A and Visser TJ (2002). Potent inhibition of estrogen sulfotransferase by 

hydroxylated metabolites of polyhalogenated aromatic hydrocarbons reveals alternative 

mechanism for estrogenic activity of endocrine disrupters. J Clin Endocrinol Metab 87:1142-50. 

25 
Kierkegaard A, Balk L, Tjarnlund U, de Wit C and Jansson B (1999a). Dietary uptake and effects 

of decabromodiphenyl ether in the rainbow trout (Oncorhynchus mykiss). Environ Sci Technol 

33:1613-17. 

Kierkegaard A, Sellstrom U, Bignert A, Olsson M, Asplund L, Jansson B and de Wit C (1999b). 

Temporal trends of a polybrominated diphenyl ether (PBDE), a methoxylated PBDE and 

hexabromocyclododecane (HBCD) in Swedish biota. Organohalogen Compd 40:367-370. 

Kuriyama SN, Talsness CE, Grote K and Chahoud I (2005). Developmental Exposure to Low 

Dose PBDE 99: 1--Effects on Male Fertility and Neurobehavior in Rat Offspring. Environ 

Health Perspect 113:149-54. 

Lebeuf M, Gouteux B, Measures L and Trottier S (2004). Levels and temporal trends (1988­

1999) of polybrominated diphenyl ethers in beluga whales (Delphinapterus leucas) from the St. 

Lawrence Estuary, Canada. Environ Sci Technol 38:2971-7. 

Lee RG, Thomas GO and Jones KC (2004). PBDEs in the atmosphere of three locations in 

western Europe. Environ Sci Technol 38:699-706. 

Mazdai A, Dodder NG, Abernathy MP, Hites RA and Bigsby RM (2003). Polybrominated 

diphenyl ethers in maternal and fetal blood samples. Environ Health Perspect 111:1249-52. 

Meerts IA, Letcher RJ, Hoving S, Marsh G, Bergman A, Lemmen JG, van der Burg B and 

Brouwer A (2001). In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated 

PDBEs, and polybrominated bisphenol A compounds. Environ Health Perspect 109:399-407. 

Meironyte D, Noren K and Bergman A (1999). Analysis of polybrominated diphenyl ethers in 

Swedish human milk. A time-related trend study, 1972-1997. J Toxicol Environ Health A 

58:329-41. 

Meironyte Guvenius D and Noren K (2001). Polybrominated Diphenyl Ethers in Swedish Human 

Milk. The Follow-up study. Second International Workshop on Brominated Flame Retardants, 

Stockholm, Sweden, World Health Organization, The Swedish Ministry of the Environment, and 

the Royal Swedish Academy of Sciences. 

Meironyte Guvenius D, Aronsson A, Ekman-Ordeberg G, Bergman A and Noren K (2003). 

Human prenatal and postnatal exposure to polybrominated diphenyl ethers, polychlorinated 

biphenyls, polychlorobiphenylols, and pentachlorophenol. Environ Health Perspect 111:1235­

41. 

Morck A, Hakk H, Orn U and Klasson Wehler E (2003). Decabromodiphenyl ether in the rat: 

absorption, distribution, metabolism, and excretion. Drug Metab Dispos 31:900-7. 

Norris JM, Ehrmantraut JW, Gibbons CL, Kociba R, Schwetz B, Rose J, Humiston C, Jewett G, 

Crummett W, Gehring P, Tirsell J and Brosier J (1973). Toxicological and environmental factors 

involved in the selection of decabromodiphenyl oxide as a fire retardant chemical. Appl Polym 

Symp 22:195-219. 

Norris JM, Ehrmantraut JW, Kociba RJ, Schwetz BA, Rose JQ, Humiston CG, Jewett GL, 

Crummet WB, Gehring PJ, Tirsell JB and Brosier JS (1975). Evaluation of decabromodiphenyl 

oxide as a flame-retardant chemical. Chem Hum Health Environ 1:100-116. 

26 
Norstrom RJ, Simon M, Moisey J, Wakeford B and Weseloh DV (2002). Geographical 

distribution (2000) and temporal trends (1981-2000) of brominated diphenyl ethers in Great 

Lakes herring gull eggs. Environ Sci Technol 36:4783-9. 

North KD (2004). Tracking polybrominated diphenyl ether releases in a wastewater treatment 

plant effluent, Palo Alto, California. Environ Sci Technol 38:4484-8. 

NTP (1986). Technical Report on the Toxicology and Carcinogenesis Studies of 

Decabromodiphenyl Oxide (CAS NO. 1163-19-5) in F344/N Rats and B6C3F1 Mice (Feed 

Studies). National Toxicology Program. Research Triangle Park, NC. 

NTP (2001). Technical Pentabromodiphenyl Ether, Technical Octabromodiphenyl Ether, 

Tetrabromodiphenyl Ether, Pentabromodiphenyl Ether, Hexabromodiphenyl Ether: Review of 

Toxicological Literature. National Toxicology Program. Research Triangle Park, NC. 

Ohta S, Ishizuka D, Nishimura H, Nakao T, Aozasa O, Shimidzu Y, Ochiai F, Kida T, Nishi M 

and Miyata H (2002). Comparison of polybrominated diphenyl ethers in fish, vegetables, and 

meats and levels in human milk of nursing women in Japan. Chemosphere 46:689-96. 

Orn U and Klasson-Wehler E (1998). Metabolism of 2,2',4,4'-tetrabromodiphenyl ether in rat and 

mouse. Xenobiotica 28:199-211. 

Petreas M, She J, Brown FR, Winkler J, Windham G, Rogers E, Zhao G, Bhatia R and Charles 

MJ (2003). High body burdens of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in California 

women. Environ Health Perspect 111:1175-9. 

Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, Vulsma T, Wiersinga 

WM, Drexhage HA and Vader HL (1999). Low maternal free thyroxine concentrations during 

early pregnancy are associated with impaired psychomotor development in infancy. Clin 

Endocrinol (Oxf) 50:149-55. 

Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL and de Vijlder JJ (2003). Maternal 

hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year followup study. Clin Endocrinol (Oxf) 59:282-8. 

Rudel RA, Camann DE, Spengler JD, Korn LR and Brody JG (2003). Phthalates, alkylphenols, 

pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor 

air and dust. Environ Sci Technol 37:4543-53. 

Schecter A, Pavuk M, Papke O, Ryan JJ, Birnbaum L and Rosen R (2003). Polybrominated 

diphenyl ethers (PBDEs) in U.S. mothers' milk. Environ Health Perspect 111:1723-9. 

Schecter A, Papke O, Tung KC, Staskal D and Birnbaum L (2004). Polybrominated diphenyl 

ethers contamination of United States food. Environ Sci Technol 38:5306-11. 

SETAC (2004). Fourth SETAC World Congress, 25th Annual Meeting in North America - 

Abstracts. Society of Environmental Toxicology and Chemistry. 

27 
She J, Petreas M, Winkler J, Visita P, McKinney M and Kopec D (2002). PBDEs in the San 

Francisco Bay Area: measurements in harbor seal blubber and human breast adipose tissue. 

Chemosphere 46:697-707. 

Shoeib M, Harner T, Ikonomou M and Kannan K (2004). Indoor and outdoor air concentrations 

and phase partitioning of perfluoroalkyl sulfonamides and polybrominated diphenyl ethers. 

Environ Sci Technol 38:1313-20. 

Sjodin A, Jones RS, Focant JF, Lapeza C, Wang RY, McGahee EE, 3rd, Zhang Y, Turner WE, 

Slazyk B, Needham LL and Patterson DG, Jr. (2004). Retrospective time-trend study of 

polybrominated diphenyl ether and polybrominated and polychlorinated biphenyl levels in 

human serum from the United States. Environ Health Perspect 112:654-8. 

Song W, Ford JC, Li A, Mills WJ, Buckley DR and Rockne KJ (2004). Polybrominated diphenyl 

ethers in the sediments of the Great Lakes. 1. Lake Superior. Environ Sci Technol 38:3286-93. 

Stapleton HM, Alaee M, Letcher RJ and Baker JE (2004a). Debromination of the flame retardant 

decabromodiphenyl ether by juvenile carp (Cyprinus carpio) following dietary exposure. 

Environ Sci Technol 38:112-9. 

Stapleton HM, Letcher RJ and Baker JE (2004b). Debromination of polybrominated diphenyl 

ether congeners BDE 99 and BDE 183 in the intestinal tract of the common carp (Cyprinus 

carpio). Environ Sci Technol 38:1054-61. 

Stapleton HM, Dodder NG, Offenberg JH, Schantz MM and Wise SA (2005). Polybrominated 

diphenyl ethers in house dust and clothes dryer lint. Env Sci Technol 39:925-31. 

Staskal DF, Diliberto JJ, DeVito MJ and Birnbaum LS (2005). Toxicokinetics of BDE 47 in 

female mice: effect of dose, route of exposure, and time. Toxicol Sci 83:215-23. 

Stoker TE, Laws SC, Crofton KM, Hedge JM, Ferrell JM and Cooper RL (2004). Assessment of 

DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture, in the EDSP male and 

female pubertal protocols. Toxicol Sci 78:144-55. 

Strandman T, Koistinen J and Vartiainen T (2000). Polybrominated diphenyl ethers (PBDEs) in 

placenta and human milk. Organohalogen Compd 47:61-64. 

Teuten EL, Xu L and Reddy CM (2005). Two abundant bioaccumulated halogenated compounds 

are natural products. Science 307:917-20. 

Thuvander A and Darnerud PO (1999). Effects of polybrominated diphenyl ether (PBDE) and 

polychlorinated biphenyl (PCB) on some immunological parameters after oral exposure in rats 

and mice. Toxicological and Environmental Chemistry 79:229-42. 

Tjarnlund U, Ericson G, Orn U, de Wit C and Balk L (1998). Effects of two polybrominated 

diphenyl ethers on rainbow trout (Oncorhynchus mykiss) exposed via food. Mar Environ Res 

46:107-12. 

Tomy GT, Palace VP, Halldorson T, Braekevelt E, Danell R, Wautier K, Evans B, Brinkworth L 

and Fisk AT (2004). Bioaccumulation, biotransformation, and biochemical effects of brominated 

diphenyl ethers in juvenile lake trout (Salvelinus namaycush). Environ Sci Technol 38:1496-504. 

28 
U.S. EPA (1995). Integrated Risk Information System. Decabromodiphenyl ether (DBDPE) 

(CASRN 1163-19-5). US Environmental Protection Agency, Office of Research and 

Development. 

U.S. EPA (2005). Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection 

Agency, Risk Assessment Forum. 

Viberg H, Fredriksson A and Eriksson P (2002). Neonatal exposure to the brominated flame 

retardant 2,2',4,4',5-pentabromodiphenyl ether causes altered susceptibility in the cholinergic 

transmitter system in the adult mouse. Toxicol Sci 67:104-7. 

Viberg H, Fredriksson A and Eriksson P (2003a). Neonatal exposure to polybrominated diphenyl 

ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases 

hippocampal cholinergic receptors in adult mice. Toxicol Appl Pharmacol 192:95-106. 

Viberg H, Fredriksson A, Jakobsson E, Orn U and Eriksson P (2003b). Neurobehavioral 

derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a 

defined period of neonatal brain development. Toxicol Sci 76:112-20. 

Walsh G, Yoder M, McLaughlin L and Lores E (1987). Responses of marine unicellular algae to 

brominated organic compounds in six growth media. Ecotox Environ Safety 14:215-22. 

WHO (1994). Brominated Diphenyl Ethers. Environmental Health Criteria 162. World Health 

Organization, International Programme on Chemical Safety. Geneva, Switzerland. 

WIL Research Laboratories (1984). 90-day dietary study in rats with pentabromodiphenyl oxide 

(DE-71) (Final Report). Submitted to U.S. EPA under TSCA Section 8D, Fiche no. 

OTS0524336. 

Wilford BH, Harner T, Zhu J, Shoeib M and Jones KC (2004). Passive sampling survey of 

polybrominated diphenyl ether flame retardants in indoor and outdoor air in Ottawa, Canada: 

implications for sources and exposure. Environ Sci Technol 38:5312-8. 

Wolkers H, van Bavel B, Derocher AE, Wiig O, Kovacs KM, Lydersen C and Lindstrom G 

(2004). Congener-specific accumulation and food chain transfer of polybrominated diphenyl 

ethers in two arctic food chains. Environ Sci Technol 38:1667-74. 

Wollenberger L, Dinan L and Breitholtz M (2005). Brominated flame retardants: activities in a 

crustacean development test and in an ecdysteroid screening assay. Environ Toxicol Chem 

24:400-7. 

Zhou T, Ross DG, DeVito MJ and Crofton KM (2001). Effects of short-term in vivo exposure to 

polybrominated diphenyl ethers on thyroid hormones and hepatic enzyme activities in weanling 

rats. Toxicol Sci 61:76-82. 

Zhou T, Taylor MM, DeVito MJ and Crofton KM (2002). Developmental exposure to brominated 

diphenyl ethers results in thyroid hormone disruption. Toxicol Sci 66:105-16. 

Zhu LY and Hites RA (2004). Temporal trends and spatial distributions of brominated flame 

retardants in archived fishes from the Great Lakes. Environ Sci Technol 38:2779-84. 

29 
APPENDIX B. Selected International Activities on PBDEs 

European Union (EU). The use of both pentaBDE and octaBDE in the EU was banned 

as of August 2004. 

In 2004, the EU reached an agreement with the European chemical industry for the 

industry to conduct a voluntary program to reduce emissions of decaBDE, and to conduct 

a program to monitor decaBDE in the environment. In addition, the EU announced it 

will sponsor a study of developmental neurotoxicity in laboratory animals for decaBDE. 

The EU’s Restriction on Hazardous Substances (RoHS) directive will prohibit the use of 

certain chemicals in electrical and electronic equipment as of July 2006. DecaBDE had 

been on the list of chemicals to be prohibited, but the EU granted an exemption for 

decaBDE in October 2005. 

The EU is also funding the FIRE project (Flame retardants Integrated Risk assessment for 

Endocrine effects). The objective of the FIRE project is to conduct toxicological studies 

and exposure assessments to characterize the possible emerging health risk for humans 

and wildlife of PBDEs, tetrabromobisphenol A and hexabromocyclododecane by 

endocrine related mechanisms. FIRE is being conducted by a partnership of multiple 

research centers across Europe; see www.rivm.nl/fire for more information. 

International Agreements on Persistent Organic Pollutants (POPs). PentaBDE has been 

proposed by Norway for listing under two international agreements: the United Nations 

Economic Commission for Europe (UNECE) Convention on Long-range Transboundary 

Air Pollution (LRTAP) Protocol on POPs, and the United Nations Environment Program 

(UNEP) Stockholm Convention on POPs. EPA, with other interested U.S. federal 

agencies, is actively involved in the consideration of the proposals in accordance with the 

treaties’ respective review processes and the participatory status of the U.S. under these 

agreements. For more information on the LRTAP POPs protocol and the proposal by 

Norway, see http://www.unece.org/env/lrtap/welcome.html, 

http://www.unece.org/env/popsxg/proposals%20for%20NEW%20pops.htm, and the 

Report of the 23rd Session of the Executive Body at 

http://www.unece.org/env/eb/welcome.23.html. For information on the Stockholm 

Convention and Norway’s proposal, see http://www.pops.int/default.htm, 

http://www.pops.int/documents/meetings/cop_1/chemlisting/Default.htm, and the Report 

of the First meeting of the Persistent Organic Pollutants Review Committee at 

http://www.pops.int/documents/meetings/poprc/meeting_docs/reports/default.htm. 

Organization for Economic Cooperation and Development (OECD). The Brominated 

Flame Retardant (BFR) Clearinghouse of the OECD has developed hazard/risk 

information fact sheets on the PBDEs, as well as HBCD and TBBPA, and has identified 

critical data gaps. OECD intends to follow the development of new information on 

BFRs, update the fact sheets every 2-3 years, and work to improve cooperation between 

producers and users of BFRs in order to reduce emissions to the environment. 

30 
Arctic Council. The Arctic Council is an inter-governmental forum addressing Arctic 

issues whose members include Canada, Denmark, Finland, Iceland, Norway, Sweden, the 

Russian Federation and the United States. The objectives of the Council’s Brominated 

Flame Retardants Project are to: reduce or eliminate sources and releases of BFRs that 

are found in the Arctic environment; identify and develop safe waste-handling and 

recycling practices for products containing brominated flame retardants; and identify 

alternative flame retardant chemicals and technologies and promote safe alternatives. 

31 
APPENDIX C. PBDE Research and Assessment Activities Conducted by or Funded 

by EPA 

Levels in the Environment and Biota 

Breast Milk Measurements in California 

Under a grant from EPA, the California Environmental Protection Agency is collecting 

breast milk samples and analyzing them for the presence of PBDEs. 

Analysis of PBDEs in Breast Milk and House Dust 

EPA plans to issue a cooperative agreement to measure PBDEs and 

hexabromocyclododecane (HBCD) in breast milk; assess whether levels in dust correlate 

with body burdens of PBDEs and HBCD; explore whether body burdens of PBDEs are 

decreased in the subjects via lactation; and explore possible biological differences among 

women that might explain variability in body burdens. 

Pilot Study on Concentrations of PBDEs in Human Milk 

EPA has funded a study by Pennsylvania State University and the Centers for Disease 

Control and Prevention (CDC) to measure concentrations of PBDEs in human milk breast 

milk in two very different populations of 20 women each: Amish women, and nonAmish woman living in more traditional suburban settings in Pennsylvania. The purpose 

of the study is to assess whether lifestyle factors, demographics, or other determinants of 

exposures appear to be correlated with levels of these chemicals. 

Methods Advancement in Milk Analysis 

As part of the Methods Advancement in Milk Analysis (MAMA) study, in support of the 

National Children’s Study, scientists in EPA’s National Health and Environmental 

Effects Research Laboratory (NHEERL) are working in collaboration with the CDC to 

measure and identify PBDEs present in the milk and serum of women in North Carolina. 

The research will assess diet, lifestyle, occupation, stage of lactation, sample collection 

and storage methods as significant variables. 

PDBEs in Lake Superior Watershed 

EPA has funded a study by the Minnesota Pollution Control Agency (MPCA) to assess 

the prevalence, potential for local sources and accumulation trends of PBDEs in the St. 

Louis River and western Lake Superior watershed. This project will estimate the 

prevalence of PBDEs in surficial sediments and fish. Trends in PBDE accumulation in 

ambient and industrially-impacted locations will be examined by analyzing sediment 

cores from a remote lake and the Duluth-Superior Harbor. 

Levels of PBDEs in Eggs of Wisconsin Cormorants 

EPA has funded a Wisconsin Department of Natural Resources project to investigate the 

presence and levels of PBDEs in double crested cormorant eggs taken from Lake 

Michigan and the Bay of Green Bay. Cormorant eggs to be analyzed for PBDEs include 

32 
archived eggs collected by the U.S. Fish and Wildlife Service during the 1970s, 1980s 

and 1990s (between 25 and 40 eggs). 

PBDEs in Cord Blood, Great Lakes Sediments and Fish 

Under an EPA STAR (Science to Achieve Results) grant to Indiana University, 

researchers will measure PBDE concentrations in umbilical cord blood from 50 newborn 

U.S. infants and samples of their mothers’ blood collected at delivery to assess fetal 

exposure to PBDEs. The researchers will also measure PBDEs in Great Lakes sediment 

cores and fish to assess long term trends of PBDEs in environment. 

PBDEs at the Calumet Water Reclamation Plant (Chicago) 

This project will characterize levels of 14 PBDE congeners in aqueous and sludge 

samples at various stages in the treatment facility, including the influent, effluent, 

digestion sludge, and final sludge product. The project is a screening level analysis of the 

fate (including transformations and degradations) of PBDEs within the water reclamation 

plant. This is a collaborative effort among U.S. EPA, the U.S. Department of Agriculture 

(USDA), the U.S. Geological Survey, and the Metropolitan Water Reclamation District 

of Greater Chicago. Samples will be collected in 2005 and early 2006, with a final report 

expected in the summer of 2006. 

POTW Measurements of PBDEs 

A scientist in EPA Region 10 measured levels of PBDEs in samples of effluents and 

biosolids collected from five publicly-owned treatment works (POTWs) in the state of 

Washington in 2002. 

End-of-Life/Disposal 

Leaching of Hazardous Chemicals from Discarded Electronic Devices 

EPA has provided funding to the University of Florida to evaluate potential 

environmental impact of flame retardants in plastics in electronic devices, including 

potential for leaching of flame retardants from the plastics. 

Debromination and Biotransformation of PBDEs in sediments 

Under an EPA STAR grant to Purdue University, researchers will assess whether 

decaBDE undergoes reductive debromination and, if so, will quantify the products of this 

biotransformation. 

Combustion-derived PBDEs and PBDD/Fs: Electronics recycling and municipal waste 

EPA’s National Risk Management Laboratory has been studying the incineration of 

materials that may contain PBDEs. Researchers have measured brominated organic 

compounds in municipal waste combustor flue gas; examined incineration of recycled 

phone boards, motherboards and keyboards; and taken samples from a municipal waste 

combustor and to analyze for presence of brominated organic compounds. They are now 

developing methods to measure PBDEs and brominated dioxins and furans in combustor 

emission samples. 

33 
PBDEs Toxicology and Health Risk Assessment 

Data for Calculating a pentaBDE Margin of Exposure 

EPA has issued a contract to analyze levels of PBDEs in blood samples from pregnant 

rats, fetuses and offspring exposed to the commercial pentaBDE mixture, DE-71. These 

data will allow comparison of blood or adipose tissue concentrations in humans to those 

found in rats for what appear to be the critical endpoints in rodent studies. This 

information should allow for a screening level analysis of the margin-of-exposure for this 

class of chemicals. 

Neurological Consequences of PBDE-Induced Decreases in Thyroid Hormones During 

Development 

EPA’s NHEERL is conducting animal studies of the relationship between thyroid 

hormone decreases caused by PBDEs during development and alterations in 

neurobehavioral outcomes. Research is currently focused on the commercial pentaBDE 

mixture, DE-71. 

Low Dose Effects of Thyroid Toxicants on Neurodevelopment 

Under an EPA STAR grant, researchers at the University of Massachusetts are examining 

the effects of several thyroid toxicants, including PBDEs, on neurodevelopmental 

endpoints in rats. The study will characterize dose-response relationships between PBDE 

levels, thyroid hormone levels, and neurodevelopmental endpoints. 

Studies of Potential Endocrine Disruption by pentaBDE 

Researchers in EPA’s NHEERL used the commercial pentaBDE product and individual 

PBDE congeners contained in that mixture to test the sensitivity of different test rat study 

protocols for identifying thyroid active chemicals, and to identify potential endocrine 

disrupting effects. This work has been published by T.E. Stoker and colleagues in 

Toxicological Sciences (2004) and Toxicology and Applied Pharmacology (2005). 

Toxicity and Estrogenic Activity of Polybrominated Diphenyl Ethers (PBDEs) 

Under a grant from EPA, the Wisconsin Department of Natural Resources is conducting 

research to: 1) determine estrogenic activity of BDE-47 and BDE-99 using the E-screen 

assay; 2) determine the acute and chronic toxicity of BDE-47 to the aquatic invertebrate, 

Ceriodaphnia dubia; 3) determine the concentration of PBDEs in sediments of the 

Sheboygan River basin; and 4) determine the concentration of PBDEs in wastewater 

treatment plant and industrial effluents in the Sheboygan River basin. 

PBDEs/PCBs and Thyroid Outcomes 

An EPA STAR grant is funding research by the Wisconsin Department of Health to 

characterize exposure to PBDEs from consumption of Lake Michigan sport fish and to 

determine mechanisms by which PBDEs in Great Lakes fish may act separately or 

synergistically with PCB exposure to impair thyroid function. 

34 
Pharmacokinetics of PBDEs in Mice 

Scientists in EPA’s NHEERL are investigating the absorption, distribution, metabolism, 

and excretion of the tetraBDE congener BDE-47 in adult mice and during development. 

A physiologically based pharmacokinetic model is being developed to predict the 

behavior under multiple scenarios. The tissue distribution, metabolism, and elimination 

of pentaBDE congeners BDE-99 and -100, and hexaBDE congener BDE-153 are also 

being investigated in mice. Articles reporting on this work by D.F. Staskal and 

colleagues have been published in Toxicological Sciences (2005). 

Fetal Exposure Modeling 

An EPA STAR grant to Research Triangle Institute is supporting work to develop a 

physiologically-based pharmacokinetic (PBPK) model for BDE-47 and BDE-99 in an 

animal model system (rats) that can be used to estimate fetal exposures to PBDEs in 

humans. Necessary partitioning and metabolic parameters will be measured using in-vivo 

and in-vitro experiments. The developed PBPK model will be useful for studying 

different aspects of exposure, including the impact of chronic and intermittent exposures 

on time-sensitive, developmental events. The exposures of a group of mothers and their 

newborn children to the target congeners will be determined. 

Mode of Action for Developmental Neurotoxicity of PBDEs 

Scientists in EPA’s NHEERL are conducting research to evaluate intracellular signaling 

as a potential mode of action for the developmental neurotoxicity of PBDEs. Both in 

vitro and in vivo approaches will be utilized to address this issue in PBDE mixtures and 

selected individual congeners. The in vitro effects will be compared with in vivo studies 

in terms of the effects and the concentrations at which effects are observed. In addition, 

the results from PBDE mixtures and individual congeners will be compared with other 

structurally related chemicals. This research will aid in understanding a common mode of 

developmental neurotoxicity for these persistent chemicals. 

Developmental Neurotoxicity of Commercial pentaBDE and BDE-47 in Mice 

Scientists in EPA’s NHEERL are conducting research to repeat the studies of Eriksson 

and co-workers that have found developmental neurotoxic effects of PBDEs in mice. 

These studies will also conduct long-term dosing of the dam as well as the pup and the 

body burdens will be determined both experimentally and by pharmacokinetic modeling 

approaches. 

Bioavailability of PBDEs from House Dust 

Scientists in EPA’s NHEERL are collaborating with scientists at USDA and Duke 

University to investigate the bioavailability of PBDEs from dust in rats. Standardized 

samples of house dust will be used and over 20 PBDE congeners measured. 

VCCEP 

Chemicals of potential concern to children’s health are the subject of evaluation in the 

pilot Voluntary Children’s Chemical Evaluation Program (VCCEP). VCCEP was 

developed to ensure that there are adequate publicly available data to assess the impact 

that industrial chemicals may have on children. PentaBDE, octaBDE and decaBDE are 

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among the chemicals being assessed in the VCCEP pilot. Further information regarding 

VCCEP is available at http://www.epa.gov/chemrtk/vccep. 

IRIS Assessments for PBDEs

EPA is conducting reviews of the available toxicology data for tetra-, penta-, hexa- and 

decaBDE congeners under its Integrated Risk Information System (IRIS) program. 

Completion of these assessments is projected for 2006. 

Alternatives Analysis 

Furniture Flame Retardancy Partnership 

The Furniture Flame Retardancy Partnership is a joint venture of the furniture industry, 

chemical manufacturers, environmental groups and EPA to better understand fire safety 

options for the furniture industry. Through the Furniture Flame Retardancy Partnership, 

EPA and its partners hope to identify and move toward environmentally friendly 

approaches to meeting fire safety standards. The partnership initially focused on 

providing up-to-date toxicological and environmental information on flame retardants 

used in furniture foam, as alternatives to pentaBDE, so that furniture manufacturers and 

suppliers are able to make informed decisions about which chemicals to use. The 

Partnership also plans to develop a process for identifying and developing data needed to 

assess potential risks from flame retardant chemicals used in furniture. More 

information is available at 

http://www.epa.gov/opptintr/dfe/pubs/projects/flameret/index.htm. 

Market Analysis of PBDEs 

In 2003, an EPA contractor prepared a review of market data on PBDEs. The report 

included a review of PBDEs suppliers, usage data, and a review of information available 

at that time on alternatives to pentaBDE in flexible polyurethane foam. 

Regulatory Activities 

SNUR for pentaBDE and octaBDE 

EPA has proposed a Significant New Use Rule (SNUR) under section 5(a)(2) of the 

Toxic Substances Control Act (TSCA) that would require manufacturers and importers 

to notify EPA at least 90 days before commencing the manufacture or import of 

pentaBDE or octaBDE. The required notice would provide EPA with the opportunity to 

evaluate each chemical substance’s use, and if necessary, to prohibit or limit such activity 

before it occurs. EPA expects to finalize the SNUR in 2006. 

Residential Furniture SNUR

EPA is preparing to propose a SNUR under section 5(a)(2) of TSCA for flame retardants 

identified as candidates for use to meet the residential upholstered furniture (RUF) 

flammability standards under consideration by the State of California and the U.S. 

Consumer Product Safety Commission (CPSC). Sixteen chemical substances/categories, 

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including decaBDE, are being considered for inclusion in the SNUR. The SNUR would 

require persons who intend to manufacture, import, or process any of these chemical 

substances, or articles containing them, for use as a flame retardant (FR) in RUF to notify 

EPA at least 90 days before commencing such activity. The required notice would 

provide EPA with the opportunity to evaluate each chemical substance’s use as a FR in 

RUF, and if necessary, to prohibit or limit such activity before it occurs. 

Monitoring of Drinking Water 

EPA proposed its Unregulated Contaminant Monitoring Regulation (UCMR 2) under the 

Safe Drinking Water Act in the Federal Register on August 22, 2005 (70 FR 49093). 

Under UCMR 2, EPA is proposing to require 3,910 public water systems to monitor for 

26 unregulated chemicals, including BDE congeners 47, 99, 100 and 153. EPA expects 

to publish the final regulation in 2006 and monitoring is expected to occur during the 

2007 to 2010 timeframe. The data collected through the UCMR program will be used to 

assess the level of these chemicals in finished drinking water and assist the Agency in 

deciding whether a drinking water regulation is needed. 

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APPENDIX D. PBDEs Research and Assessment Activities at Other U.S. Federal 

Agencies 

Centers for Disease Control and Prevention (CDC). As part of the National Health and 

Nutrition Examination Survey (NHANES), CDC is analyzing blood samples collected in 

2003-2004 for levels of 10 PBDE congeners. Results of this nationally-representative 

statistical sample are expected in 2006, for two age groups (ages 12- 19 years, and age 20 

and older) as well as gender and race/ethnicity sub-groups. The survey is continuous, and 

additional results will be available in future years to allow evaluation of any trends. CDC 

is also conducting several additional studies of PBDEs aimed at determining body 

burdens in segments of the population that may be more highly exposed and identifying 

which routes of exposure are of main importance for the human population. 

Food and Drug Administration (FDA). FDA has been working with the food and feed 

industries to understand sources of PBDEs and other persistent contaminants. FDA is 

conducting studies on methods for the analysis of PBDEs in different food and feed 

matrices, and has measured PBDEs in select fish samples. In 2006, FDA will include 

appropriate food and feed in a sampling program to assess PBDE levels, and will use this 

information to assess dietary PBDE exposures to determine appropriate risk management 

options. 

National Institute of Standards and Technology (NIST). NIST is conducting research to 

examine the rates by which PBDEs are emitted from plastics over time due to natural 

weathering, increased temperatures and irradiant exposures. NIST is also conducting 

studies to measure PBDEs in house dust, California sea lions, and rainbow trout. 

National Oceanic and Atmospheric Administration (NOAA). NOAA has measured 

levels of PBDEs in mussel tissue and sediments near the World Trade Center site, and in 

sediments in the Chesapeake Bay. 

National Toxicology Program (NTP). NTP is currently conducting a subchronic toxicity 

study of commercial pentaBDE (DE-71) in rats and mice. NTP is also planning to do a 

chronic study to look for cancer potential, but plans for this study will not be finalized 

until after the subchronic study is completed. In addition, NTP is conducting studies of 

gene expression and tissue distribution for BDE congeners 47, 99, and 153. 

U.S. Department of Agriculture (USDA). USDA is conducting research on the 

absorption, disposition, metabolism, and excretion (ADME) of PBDEs. Studies of 

ADME in rats have been conducted on commercial pentaBDE, octaBDE and decaBDE 

mixtures. Rodent ADME studies have also been conducted on BDE congeners 47, 99, 

100, 154 and 209. Studies in rats are planned for BDEs 153 and 183, along with further 

study of BDE-209. ADME studies of the pentaBDE mixture and BDE-47 are also being 

conducted in chickens. USDA has also conducted some measurements of PBDE levels 

in meats and poultry, and will be extending these analyses to additional food samples. 

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U.S. Geological Survey (USGS). The USGS is conducting studies to: measure indoor 

air levels of PBDEs in homes and offices; measure levels of PBDEs in fish and fisheating birds; evaluate the environmental fate of PBDEs; and determine the potential for 

weathered recycled computer equipment to contaminate nearby soil and sediments. 

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