U.S. Environmental Protection Agency
Polybrominated
Diphenyl Ethers
(PBDEs)
Project Plan
March 2006
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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).
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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
BDE-28
BDE-47
BDE-85
BDE-99
BDE-100
BDE-153
BDE-154
BDE-183
BDE-197
BDE-206
BDE-209
Number of
Bromine Atoms
3
4
5
5
5
6
6
7
8
9
10
Chemical Name
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-heptabromodiphenyI 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
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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.
UsesofPBDEs
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
pentaBDE
(DE-71)
octaBDE
(DE-79)
decaBDE
(DE-83R)
(Saytex
102E)
Composition of
Commercial
Mixtures'
24-38% tetraBDEs
50-62% pentaBDEs
4-12%hexaBDEs
0-l%triBDEs
0.5% pentaBDEs
12% hexaBDEs
45% heptaBDEs
33% octaBDEs
10% nonaBDEs
0.7% decaBDE
0.3 - 3% nonaBDEs
97-99% decaBDE
Uses
Flame retardant in
flexible polyurethane
foam for furniture,
mattresses and carpet
padding
Flame retardant in
aery Ion itrile-
butadiene-styrene
plastics used in
computer casings
Flame retardant in
high impact
polystyrene (HIPS)
television set cabinet
backs and commercial
upholstery fabric
2001 Demand
in Americas2
(metric tons)
7,100
1,500
24,500
Percentage
of World
Demand in
Americas2
95%
40%
44%
'Source of composition data is (Environ 2003) for pentaBDE, (ECB 2003) for octaBDE,
and (WHO 1994) for decaBDE.
2Bromine 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.
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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 BFR-
related 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.
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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.
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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/proiects/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.
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Objective 2: Assess and Evaluate Decabromodipbenyl 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 lower-
brominated 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
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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
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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.
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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.
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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-of-
life 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 dose-
response, and/or full risk assessments of certain flame retardant chemicals.
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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.
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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 BDE-
209. Findings of BDE-209 in arctic biota suggest the possibility of long-range
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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 inter-
individual variability is great, most notably for BDE-47.
Most of the breast milk biomon Storing 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
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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 PBDE-
containing 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 Toxiciry Profiles of PBDEs in Mammals
PHARMACOKINETICS
The available data indicate that the tetra congener BDE-47 and the penta congener BDE-
99 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
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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; Morris et al. 1973; Morris 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; Morris 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 CYP1 A. 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).
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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 ug/kg
and 300 jig/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 Ta (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.
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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
jig/kg. Daily sperm production and spermatid counts were significantly decreased
(Kuriyama et a!. 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 two-
year 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
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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 denominated in the intestinal
tract of the common carp. In a long term feeding study in which 13 tri- through deca-
PBDE 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).
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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 21 days 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
ug/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 (CYP1 A) 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 (Tjarniund 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 to 120 days via the diet.
DecaBDE had no effect on transketolase, ethoxyresorufin-0-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 three-
spined stickleback fed doses of a commercial pentaBDE mixture corresponding to
concentrations of 861 and 1630 mg/kg of fat tissue (Holmetal. 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
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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.
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and phase partitioning of perfluoroalkyl sulfonamides and polybrominated diphenyl ethers.
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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.htin. 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/ineetings/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/ineetings/poprc/meeting docs/reports/default.htm.
Organization for Economic Cooperation and Development (PECD). 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.
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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.
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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 non-
Amish 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
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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 ftirans in combustor
emission samples.
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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-lnduced 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).
Toxicitv and Estrogenic Activity of Polybrominatcd 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 Thvroid 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.
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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 wilt 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.
Bioavailabilitv 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 Retardancv 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 (MST). 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 fish-
eating 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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