### ________________________________ _____________________________ U.S. Environm ental Protection Agency



# Polybrominated Diphenyl Ethers (PBDEs) Project Plan

March 2006U.S. Environmental Protection Agency Polybromin ated Diphenyl Ethers (PBDEs) Pr oject P l an March 2006

A. INT R ODUCTION Polybrom inated diphenyl ethers (P BDEs) are a group of brom inated flam e retardant chem icals of increasing interest to scientis ts, governm e nt agencies, and the public. These chem icals have been used in a variety of m anufactured product s, including foa m cushioning used in furniture and plastics used in televisions and com puters. In the event of a fire inv o lving th ese products, P B DEs slowignition and rate of fire growth, allowing more tim e for people to extingu ish o r escap e th e fire. However, fi ndings that PBDEs are widely distributed in the environm ent and are p r es ent at increasing lev e ls in people hav e raised concerns about the pot ential risks of PBDE exposur e to hum an health and the environm ent. This Project Plan provides a brief summaryof relevant inform ation on PBDEs, and outlin es the U.S. Environm ental Pro t ection Age n cy’s ac tiv ities reg ard in g PBDEs and related che m icals. In c onsider ing a c tiv ities re lated to f l am e retardant ch em icals, EPA will work with all interes t ed partie s to ensure th at f i re saf e ty, environm ental conce rns and public he alth concerns ar e all tak e n into acc ount. EPA will post this Project Plan and other m a terials related to PBDEs on i t s web site at www.epa.gov/oppt/pbde

. The website will be perio d ically updated to report progress on the activities described in this Pro j ect Plan. EPA will use a variety of communicati ons tools, in clu d ing periodic updates to the website, to inform stakeholders and the public regarding prog ress on the activities described in this Project Plan.

B. BACKGROUND I N FORMATI O N ON PB DEs PBDE Congeners and Commercia l Mix t ures PBDEs are a fam ily of chem icals with a common structure of a brom inated diphenyl ether m o lecule which may have anywhere from one to ten brom ine atoms attached (Figure 1). Each individual PBDE variant, distinguished fr om others by both the number of brom ine atom s and the placem ent of those atoms, is referred to as a cong ener. For exam ple, there are 42 tetrabrom odiphenyl ethe r congeners, each with four brom ine atom s in different configurations. In theory, there could be as m any as 209 PBDE congeners, but a m u ch sm aller num ber of congeners ar e commonly found in the comm e rcial PBDE products and in m easurem ents of PBDEs in hu mans and the environm ent (see Table 1).

1Figure 1. Generaliz ed Structure o f Poly brominated Diphenyl Ethers where (m+ n) = 1 to 10 bromines

There are three typ e s of commercial PBDE products, which are referred to as pentabrom odiphenyl ether (pentaBDE), oc tabromodiphenyl ether (octaBDE), and decabrom odiphenyl ether (decaBDE). Each of these comm er cial p r oducts, however, actually contains a m i xture of various PBDE congeners (see Table 2). T h e leading commercial pentaBDE m i xture, known as DE- 71, is prim arily com p rised of tetraBDEs (especially BDE-47) and pentaBDEs (esp ecially BDE-99 and BDE-100) – congeners with 4 or 5 brom ine atoms – along with sm aller quantities of hexaBDEs (BDE-153 and BDE-154, with 6 brom ine atom s). The comm erc i al octaBDE m i xture is prim arily com p rised of heptaBDEs and octaB D Es (congene rs with 7 or 8 brom ine atom s) and also contains hexaBDEs and nonaBDEs (with 6 or 9 brom ine atoms) along with sm all quantities of decaBDE (10 brom ine atom s). The commercial decaBDE product is com p rised alm o st entirely of the single fully-brom i nated congener, known as BDE-209, which has the m a xi m u m 10 brom ine atom s. Dec a BDE contains sm all quantities of nonaBDEs (congeners w ith 9 brom ine atom s) as well.

TABLE 1. Selected PBDE Congeners Congener Num b er of B r om ine A t om s Chem ical Nam e 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’-tetrabrom odiphenyl ether 2,2’,3,4,4’-pentabrom odiphenyl ether 2,2’,4,4’,5-pentabrom odiphenyl ether 2,2’,4,4’,6-pentabrom odiphenyl 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’-oct abrom odiphenyl ether 2,2’,3,3’,4,4’,5,5’,6-nonabrom odiphenyl ether 2,2’,3,3’,4,4 ’,5,5’,6,6’-d ecabrom odiphenyl eth e r

2A s m all number of the PBDE congeners are f ound m o st frequently, and in the greatest concentrations, in hum a nand environm ental sam p les. BDE-47 tends to be found m o re frequently than other congeners in m easure m ents from humans, fi sh and other biota, followed by BDEs 99, 100, 153 and 154. In m e a s urem ents of house dust, sedim e nts, and indoor air, B D E-209 (decaBDE) seem s to be dom i nant.

Uses of PBDEs PBDEs and other flam e retardant chem icals are used in certai n products to reduce the risk of fire, particularly in item s that are sus ceptible to igniting in f i re s ituation s , like furniture, or in which fires m ay start, like electrical devices. T h e comm ercial pent aBDE product is used alm o st entirely in flexible polyurethane foam i nfurniture, m a ttresses, carpet padding, and automobile seats. The commercial octaBDE product is used in acrylonitrile-butadie ne-s tyrene (ABS) plas tic that is used in certain electric and electro n ic devices. Commercial decaBDE is used prim arily in high-im pact polystyrene (HIPS) plastic that is frequently used to m a ke the back part of television sets , and is also u s ed in certain typ e s of f

l am e-retardant textiles. In recent years, alm o st all pentaBDE use has taken place in the Am ericas, while s o m e what le s s than half of worldwide use of octaBDE and decaBDE has been in the Am ericas (see Tab l e 2).

Concerns about PBDEs In recent years, scientists have m easured PBDEs in hum an a d ipose tissues, serum and breast m ilk, fish, birds, m arine m a mm als, sediments, sludge, house dust, indoor and outdoor air, and superm arket foods. The m echa n ism s or pathways by which the PB DEs move into and through the environm ent and humans are not known, but are likely to include releases from manufacturing of th e chemicals, m anufacturing of products like plastics or textiles, aging and wear of produc ts like sofas and electr onics, and releases at the end of product life (disposal , recycling). In general, le vels of PBDEs in hum ans and the environm ent are higher in NorthAm erica th an in other regions of the world, a finding that is of ten attributed to the gre a te r use of pentaBDE in North Am erica. Studies have also been conducte d in laboratory anim als to gaina better understanding of the potentia l health risk s of PBDEs. Studies of various comm e rcial m i xtures and individual congeners have suggested potenti al concerns about liver toxicity, thyroid toxicity, developm ental toxicity, and devel opm ental neurotoxicity. These findings raise particular concerns about poten tial risks to children. In addition, the pres en ce of PBDEs in house dust and breast m ilk indicates that ther e are likely to be pa thways of exposure to PBDEs that are of particular relev an ce for child r e n. However, ther e rem a ins m u ch to learn about both exposure to PBDEs and the potential health eff ects; and there are different concerns for the different P B DEs.
A m o re detailed summ ary of th e current scientific understand ing of PBDEs is presented in Appendix A.

3TABLE 2. Commercial PBDE Products
Comm ercial PBDE Product Com positio n of Comm ercial Mixtures 1 Uses 2001 De m a nd in Am ericas 2 (m etric tons ) Percentage of W o rld De m and in Am ericas 2 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% octaB D Es 10% nonaBDEs 0.7% decaB DE 0.3 – 3% nonaBDEs 97–99% decaBDE Flam e retard ant in flexible polyurethane foa m for furni ture, m a ttresses and carpet padding
Flam e retard ant inacrylonitrilebutadiene-styrene plastics used in com puter casings

Flam e retard ant in high im pact polystyrene (HIPS) telev i sion se t cabin et backs and comm ercial upholstery fabric 7,100

1,500

24,500 95%

40%

44%

1 Source of com position data is (Environ 2003) for pentaBDE, (ECB 2003) for octaBDE, and (WHO 1994) for decaBDE. 2 Brom ine Sc ience and E nvironm ent Foundation estim ates from www.bs ef.com

. In 2005, values for pentaBDE and octaBDE in the Am ericas were expected to go to zero.

Actions Regarding PBDE Product i on and Use Increasing inform ation on PBDEs i nthe e nvironm ent has drawn the attention of policym akers at the international, national, state and local levels. In 2002, the European Parliam e nt adopted a ban on m arketing a nd use of pentaBDE and octaBDE throughout the European Union (EU). The ban went into ef fect in August 2004. In July 2003, the State of California adopted a ban on the m anufacture or distribution in commerce of any product containing pentaBDE or octaBDE. These restrictions are scheduled to take effect in 2006. Hawaii, Illino i s , New York, Maine, Maryland, Michigan and Oregon have adopted laws sim ila r to California’s, and several other states are considering sim ilar actions.

4Great Lakes Che m ical Corporation, the sole U.S. producer of the comm er cial pentaB DE and octaBDE m i xtures, disconti nued production of these two pr oducts in the U.S. at the end of 2004. In general, d ecaBDE is not subject to the restrictions that h a v e been adopted for pentaBDE and octaBDE. There is anEU re gulation thatwill prohibit the use of certa in chem icals in electric and electronic equi pm ent as of July 2006. DecaBDE had been included on the list of ch em icals that w ould be prohibited, but the EU granted an exem ption for this chemical in October 2005. Other international ac tivities concerning PBDEs include an A r ctic Council brom inated flam e retardants (BFRs) project and ongoi ng work by the BFRs Clearinghouse of the Organization for Econom ic Cooper a tion and De velopm ent (OECD). The Arctic Council is an inter-governm e ntal forum addressing Ar ctic issues whose m e m b ers include Canada, Denm ark, Finland, Iceland, Norway, the Ru ssian Federation, Sweden and the United States. EPA has been involved in the initia l developm ent of the Arctic C ouncil’s BFRrelated activities, intends to continue involvem e nt in their further developm ent, im ple m entation and tracking, and will provide technical expertise and other resources, where possible and as appropriate. The OECD i s a forum where th e governm ents of 30 m arket de mocracies work together to addr ess the econom ic, social, environm ental and governance challenges of the world econom y. The OECD’s BFR Clearinghouse has developed h azard /risk in form ation fact sheets on the PBDEs, intends to u pdate th e fact sheets ev ery2-3 years, and will work to im prove cooperation between pro ducers and users of BFRs in order to reduce em issions to the environm ent. More inf o r

m ation on internationa l a c tiv ities is presented in Appendix B.

PBDE-Related Activities in the U. S. Federal Governmen t The U.S. federal governm ent is playing a subs tantia l role in resear ch and assessm ent of PBDEs, and in taking appropriate m anagem e nt actions to respond to both scientific developm ents and developm ents in the m arket for PBDEs. A selection of federal governm e nt activities includes:

• EPA has proposed a Significant New Us e Rule (SNUR) that would require prior notification to EPA by any ma nufacturer or im porter intending to reintroduce pentaBDE or octaBDE in the U.S. The proposed rule would also provide EP A with authority to review the intended production or im port of pentaBDE or octaBDE before it begins and to take actions to control potential risks as needed.

• EPA is leading a Furniture Flam e Retardan cy Partnersh i p to evaluate alte rnatives to PBDEs in f urniture ap plications. The partnership includes furniture and fabric m anufactur ers, chem ical m anufacturers and environm ental organizations. Its focus ha s been assessm ent of alternativ es to pentaBDE to inf o rm decisions on ad option of substitutes.

5• PentaBDE, octaBDE and decaBDE are being ev aluated under EPA’s Voluntary C h ildren’s Chem ical Ev aluation Program (VCCEP). Under VCCEP, PBDE m anufacturers collect a nd develop exposure and health effects inform ation on their chem icals, integ r ate that inf o rm ation in a risk as sessm ent, and prepare a “data n eed s assessm ent.” EPA has com p leted its Data Need s Decisions for the PBDEs and has requ ested that the PBDEs m anufacturers develop add ition a l data f o r asses s ing risks to children’s he alth.

• As part of its National Lake Fish Ti ssue Study, EPA is m easuring PBDEs in about 340 fish sam p les collected fr om 166 lakes and reservoirs. The statistical design of the s tudy will allow EPA to de velop th e first national estim ates of m ean concentrations an d distributions of PBDEs in fish.

• EPA is reviewing the available toxico logy data and preparing toxicological profiles for tetraBDE, pentaBDE, hexa BDE and decaBDE congeners und er its Integrated R i sk Inform ation System (IRIS) program.

• EPA is conducting and sponsoring a num b er 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 Exam ination Survey (NHANE S). PBDEs are being m easured for the first tim e in this ongoing program , with survey data for 2003-2004 expected to be released in 2006.

• The U.S. De partm e nt of Agriculture is conducting studies of the absorption and m e tabolism of PBDEs in anim als, and has also conducted m easurements of PBDEs in m eat and poultry.

• The U.S. Food and Drug Adm i nistration is conducting studies on m e thods for the analysis of PBDEs in different f ood and feed m a trices, and has m easured PBDEs in select fish samples.

• The National Toxicology Program (NTP ) is conducting a subchronic toxicity study of the commercial pentaBDE m i xtur e in laboratory anim als, along with pharm acokinetic studies of three PBDE congeners.

• The National Institute of Standards and Technology is conducting studies on the em issions of PBDEs from plastics us ed in item s such as com puters an d telev i sion s.

• The U.S. Ge ological Survey is conduc ting studies on the presence of PBDEs in indoor environm ents and the m i gr ation of PBDEs from pl astics in com puters. More inform ation on fe deral governm ent resear ch and assessm e nt of PBDEs is presented in Appendices C and D.

6EPA’s Project Plan for PBDEs The cessation of pentaBDE and octaBDE m anufacture in the U. S. is an important action that EPA believes will result in reduced am ounts of these chem icals in the environm ent. However, the need for investigating exposur es to and effects of PBDEs and related chem icals continues. In addition to change s in the m arket status of pentaBDE and octaBDE, f o rthcom ing changes in f urniture f l amm ability req u irem ents (b eing cons ide r ed by the federal Consum er Product Safety Comm is sion and the State of California) m ay incre a se de m and for safer flam e retardant ch em i cals and alternative m eans of achieving flam e retardancy in products. This P r oject Pl an identifies four key areas in which EPA is pursuing activities addressing concerns regard ing PBDEs and other flam e retardants. Many of these activities involve partnership and coordination with other federal agencies, industry and nongovernm e ntal organizations. EPA’s four objectives are: Objective 1: Assess Substitutes for Pentabromodiphenyl Ether and Octabromodiphenyl Ether. As U.S. m anufacturers ev a l uate alte rnatives to pentaBDE and octaBDE, EPA is providi ng guidance on the potential hazards of alternative flam e retardants. EPA is c onducting a num ber of activ ities to identify, and to encourage developm ent of, envir onm entally-preferab le flam e retardant chem icals and inherent ly flam e retardant m a terials. Objective 2: Assess an d Evaluate Decabromodiphenyl Ether. EPA is pursuing a num b er of activities to help better understand the p o tential f o r hum an health and ecological risks from e xposure to decaBDE and any breakdown products. Objective 3 : Assess Risks o f Penta b romodiphenyl Ether and Octabromodiphenyl Ether. Although U.S. production of pentaBDE and octaBDE has been discontinued, the release of and exposure to these chem icals is likely to continue for an extended peri od of tim e, given their environm ental persistence and the stocks of pentaB DE and octaBDE contained in existing furniture, electronic component s and other products. EP A is therefore continuing to pursue an im proved understanding of exposure to these chem icals and the associated h azards. Objective 4 : Track Developments Concerning Other Bro m inated Flame Retardants of Interest. In addition to the PB DEs, there are m any other brom inated f l am e retardants cur r ently in use. EPA will tr ack scientif ic developm ents regarding environm ental levels, hum an exposure, and potential hazards.

7C. KEY ACTIVITI E S Objective 1: Assess Substitutes for Pentabromodiphenyl Ether and Octabromodiphenyl Ether The sole U.S. m anufacturer of pentaBDE and oc taBDE phased out production of these products at the end of 2004. Users of pentaB DE and octaBDE are currently evaluating and sele ctin g alte rnative f l am e retardants to replace thes e chem icals. For the flame-retarded polyurethane foa m m arket, where pentaBDE has been a dom inant product for m any years, evaluation and selection of alternative flam e retardants is a major undertak ing. Foa m and furniture m anufacturer s need to cons ider m u ltiple factors in selecting flam e retardants, including: com p liance with flammability standards, cost of the flam e retardant, compatibility with existing production equipm ent, costs of any necessary capital investm e nts, ease of foa mproduction, effect on im portant foam characteristics (such as d ura bility, softness/firmne ss, and co lor), and possible health and environm ental risks. The foa m m anufacturers are best situated to evaluate the cost and perform ance-related factors, with assistance from the chem ical m anufacturers who sup p ly the flam e retardants and the furniture m anuf acturers and other custom ers for the foam

. However, the foa m and furniture m anufactur ers are looking to sc ientif ic e xperts, including those at EPA, to provide guidance on the potential risks of alternative flam e retardants. There are sim ilar issues related to id entifying replacem ents for octaBDE in plas tics. However, the trans i tion to alte rnative s f o r octaBDE is expected to be less challenging than that for pentaBDE, because the volum e of use of octaBDE is sm aller and altern ative f l am e retardants f o r use in sim ilar ap plications are available. Specific Activities
1.1 EPA has form ed a Furniture Flam e Retard ancy P artnership w ith several industry associations and other stak eholders. The Partnership has conducted a screening level h azard assessm ent of flam e retard ant ch em i cals that m ay be suitable substitutes for pentaBDE. For each alternative chem ical , the available s c ientific studies have been reviewed and summ arized, data gaps identified, and environm ental and hum an health effect e ndpoints characterized. This screening assessm ent was com p leted in September 2005 and is available at http://www.epa.gov/opptintr/dfe/ pubs/projects/flam eret/index.htm

. The inf o rm ation in this repo rt will he lp f urniture m anuf acturer s in corporat e he alth and environm ental cons iderations into their selection of replacem en ts for pentaBDE.
1.2 EPA will work with th e Furniture Flam e Retardancy Partners hip to review additional d a ta on flam e retardant ch em i cals used in furniture as appropriate.
1.3 EPA will monitor d e velopm ents in th e m arket for replacing o c taBDE and will assess oc taB D E substitutes if warrant ed.

8Objective 2: Assess an d Evaluate Decabromodiphenyl Ether EPA will continue to ev aluate two b r oad risk ass e ssm ent issues for decaB DE. The first issue is the potential for hum an health and eco lo gical risk s from exposure to decaBD E itself. The second issue is the potential fo r breakdown or transform a tion of decaBDE in the environm ent, in organism s or from com bustion of decaBDE containing products. Inform ation regarding this i ssu e is ne cessary f o r d e term ining the relativ e importance o f the breakdo wn or transf orm a tion products inthe overall risk of decaBDE.
Specific Activities
2.1 EPA is conducting a review of the availab l e tox i cology data f o r decaBDE, and will update the decaBDE assessm ent in EPA’ s IRIS databas e
. Com p letion of this assessm ent is projected f o r 2006.
2.2 EPA will monitor ongo ing and planned rese archon the tox i city of decaB D E and its m e tabolites. Of particular interest are a developm ental neurotoxicity study of decaBDE that is b e ing sponsored bythe European Union , and studies conducted by the FIRE project (Flam e retardants Integ r ated Risk assess m e nt for Endocrine effects; see www.riv m .n l/fire ) in Europe. FIRE is conducting 28-day toxicity study in rats , and m ay follow this w i th othe r an imal stud ies. E P A will coordinate with the EU and the FIRE projec t to ensure that all relevant inform ation regarding decaBDE toxicology is shared in a tim e ly m anne r. 2.3 EPA will further investig ate th e environm ental fate and m e tabolism of dec a BDE, including the potential f o r form ati on of lower-brom i nated congeners by debrom ination of decaBDE in the envi ronm ent. Through its VCCEP program , EPA has determ ined that additional data are need ed to addres s the potential of decaBDE to degrade to o ther subs tan ces inthe environm ent. EPA will work with the industry sponsors of the decaBDE V CCEP assessm ent to address th is d a ta need.
2.4 EPA will prepare a white paper that re views th e available inform ation on the environm ental fate of decaBDE. The pur pose of this paper is to assess the potential for debrom ination of decaBDE through various natural m e chanism s (e.g. exposure to light, breakdown via m e t abolism in living organism s), the rate, extent and conditions under which debrom ination m ay occur, and whether debrom ination of decaBDE is likely to be a s i gnificant source of lowerbrom inated PBDEs in hum ans and wildlif e. Th e white pape r will also id entif y additional studies that w ould be helpful to developing a better understanding of the environm ental fate of decaBDE. Em erging inform ation currently un der developm ent and anticipated over the com i ng year will be an im portant part of this evaluation, includ ing data needs identified thr ough VCCEP. This effort will be initiated in 2006, and the white paper will be peer reviewed in accordance with

9EPA’s Peer Review Handbook and the Office of Managem e nt and Budget’s Final Information Quality Bulletin for Peer Review

. 2.5 EPA will conduct an interim review of all available scient ific inform ation concern i ng decaBDE in 2006/2007. The inform a tion to b e co nsidered in this review will include CDC NHANES dataon 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 environm ental fate of decaBDE, inform ation develope d under VCCEP, and other studies that m ay becom e available concerning decaBDE toxicology and environm ental fate (including studies conducted or funded by EPA and other agencies listed in Appendices C and D). Based on this inte rim review, EPA wil l consider whether the inf o rm ation warrant s pursuing ad dition a l r e se arch, r i sk as sessm ent or regulation using existing legal authorities.
2.6 EPA is preparing to propose a SNUR under the Toxic Substances Control Act (TSCA) f o r f l am e retardants id entif ie d as cand i d a tes for use to m eet the resident ial u pholstered furniture flammability standards und er consid eration by the State of California and the U.S. Consum er Product Safety Comm ission (CPSC). Sixteen chem ical subs tances/cat egories, including decaBDE, are being considered for inclusion in the SNUR. The SNUR would require persons who intend to m a nufacture, import, or process any of these chem i cal substances, or articles containing them , for use as a fl am e retardant in residential upholstered f urniture to notif y EPA at le ast 90 d ays before comm encing such activity

. The required notice would provide EPA with th e opportunity to evaluate the intended use, and if necessary, to prohibit or lim it such activity before it occurs.
2.7 EPA' s Furniture Flam e Retardancy Partne rship is coordinating with the CPSC and will dis c uss whether to undertak e a p r ojec t to ev a l uate enviro nm entally p r ef erable fabric flam e retardant ch em icals, barrier techno lo gies, inh e rently flam e retardant m a terials and other fire safety approaches.
Objective 3 : Assess Risks o f Penta b ro modiphenyl Ether and Octabromodiphenyl Ether Production of pentaBDE and octaB D E in the U.S. was discontinued at the end of 2004. EPA has proposed a rule under TSCA that will pr ovide it with the authority to review any new plans to m anufacture or im port pentaBDE and octaBDE. However, the release of and exposure to these chem icals is likely to continue for an extended period of tim e, given the stocks of pentaBDE and oc taBDE c ontained in existing fu rniture, electron ic com ponents, and other products, and the pers istence of these com pounds. Debrom ination of decaBDE m ay also co ntribute to f u ture expos ures. In add ition, it is po ssible that pentaBDE or octaBDE could be present in so m e products (furniture foam and plastics) im ported into the U.S. EPA intends to investigate this issue further and seek further inform ation on the presence of pentaBDE and oc taBDE in imported articles. More

10inform ation on pathways of exposure to pentaBD E and octaB D E will help identify the types of activities that might be m o st effectiv e in reducing exposure, if su ch activities are deem ed necessary. Specific Activities
3.1 In Decem be r 2004, EPA proposed a TSCA SN UR that would require prior notice to EPA from any entity planning to begi n m anufa c ture or im port of pentaBDE or octaBDE, or any of the PBDE conge ners that comprise these m i xtures, for any use, after January 1, 2005. EPA plans to prom ulgate the SNUR in 2006. The SNUR will enable EPA to rev i ew any intended f u ture m anufactur e or im port of pentaBDE and octaBDE. Based on health or environm ental concerns that m ay be identified during such a review, EPA coul d tak e a c tions to pro h ibit o r lim it the production, processing, distribut ion in comm erc e , use, and disposal of these chem icals.
3.2 EPA will prepare a white paper that reviews and synthesizes the available inform ation on exposure pathways for PBDEs. The purpose of this paper is to address: first, the relativ e im portance of different pathways of exposure (i.e. food vs. house dust vs. indoor air); and sec ond, inform ation on how PBDEs get into various exposure m e dia (e.g., particular foods including fish, house dust, indoor air, sedim e nts), including m i gration of PBDEs fr om products in use and releases from disposal or incineration of produc ts. Inform ation on current disposal and recycling practices for end- of-life products cont aining PBDEs will be collected. The white p aper will als o identif yaddition a l s tud ies th at would be helpf u l to developing a better understan ding of exposure pathways for PBDEs. Thi s 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 Managem e nt and Budget’s Final In for m ation Quality Bulletin for Peer Review

. 3.3 EPA is conducting a review of the availabl e toxicology data f o r tetra-, penta- and hexaBDE congeners under its IRIS program

. Completion of these assessm e nts is projected for 2006.
3.4 Through its VCCEP program , EPA has iden tified additional toxi city inform ation as a data need for both pentaBDE and octaBDE. Specifically, EPA has determ ined that the prim ary data needs are two generation reproductive toxicity studies for b o th pentaBD E and octaB D E. EPA will work with the indus try sponsor of the pentaBDE and octaB D E VC CEP assessm ents to address these data needs. EPA will a l so se ek f urther re s earch on th e toxic ity of pentaBDE and octaBDE. Through thes e efforts, EPA will identify and prioritize p r oposed additional toxicology studies of indi vidual PBDE congeners and/or PBDE m i xtures common in hum an sa m p le s. EPA will consider d e v e loping a p r oposal for NTP to conduct a set of tests to bette r characterize the toxicology of several individual P B DE conge ners.

113.5 EPA will conduct an interim review of all available scie ntific inform ation concerning pentaBDE and octaBDE in 2006/200 7. The inform ation in this review will in clude CDC data on PBDE body burde ns in the U.S. population, data from EPA’s National Lake Fish Tissue Study, NTP studies of pentaBDE toxicology, and other studies that may becom e available concerning toxicology and environm ental fate of PBDEs (includi ng studies conducted or funded by EPA and other ag encies lis ted in Appendices C and D). Based on th is inte rim review, EPA will cons ide r whether th e inf o rm ation warrants p ursuing add i tiona l activities, which could include:

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

• conducting a risk assessm e nt of pe nt aBDE, octaBDE, or selected congeners. A risk assessm e nt of th e s e chem icals would include a review of the hazards, a dose-response evaluation, an exposure assessm ent, and a risk characterization.

• activities to reduce pote ntial exposures to lower-brom inated PBDE congeners.
Objective 4 : Track Developments Concern ing Other Bro m inated Flame Retard ants of Interest PBDEs are just one group of fla m e retardant ch em icals currently in us e in the U.S. The various flam e retardants in use have different chem ical and biological properties; therefore, each m u st be evaluated independe ntly. In addition to PBDEs, there are two other brom inated flam e retardants in part icular that have be en m easured in the environm ent and are the subject of continui ng inte rest: te trab r o m obisphenol A (TBBPA) and hexabro m ocyclododecane (HBCD). A nother chem ical of interest is decabrom odiphenyl ethane, which has been used as a substitute for decaB D E in Europe and has been m easured in environm ental sam p les

. Specific Activities
4.1 Any new fla m e retardants not alreadyin comm erc e in the U.S. m u st be subm itted to EPA for a prem anufac ture review under TSCA. During the review period, EPA m ay take action to prohibit or li m it the production, processing, distribution in comm erc e , use, and disposal of new ch e m ical substances that raise health or environm ental conce rns. EPA will continue to sc rutin ize newf l am e retardants proposed for m anufacture and im port into th e U.S. m arket and, where appropriate, will se ek co ntrol m easur es and/or d e velopm ent of additiona l data on such chem icals by their m anufacturers un de r TSCA Section 5 authorities.

124.2 EPA will monitor the developing s c ie nce on bro m inated flam e retardants, including TBBPA and HBCD. Among the im portant activities underway are studies of T BBPA and HBCD as part of the European Comm ission FIRE project. EPA will als o m onitor in f o rm ation on disposal and recyc ling practices f o r end-of

life consumer products contain i ng flam e re tardant chem icals

. EPA will review the available inform ation on other brom inated flam e retardants in 2006/2007. Based on this review, EP A will consider whethe r the inf o rm ation warrant s pursuing ad dition a l ac tivities, whichcould inc l u d e initiating additional s t udies of environm ental fate, exposure pathways , and/or toxicology of certain flame retardant chem icals, and conducting IR IS assessm e nts of haz ard and doseresponse, and/or full risk assessm ents of certain flam e retardant chem icals.

13D. CONCL U SION This Project Plan identifies a num ber of activities that EPA is conducting regarding PBDEs, as well as a c tiv ities it inten d s to initia te or conside r within the next two years. Many of the activities are focused on iden tifying and prioritizing data needs and generating new inform ation to help unde rstand risks of PBDEs and other flam e retardants. As the activities outlined in the Pro j e c t Pl an proceed, EPA may identify and initiate additional a c tiv ities that have not be en def i ned atthis tim e. EPA will evaluate use of additional voluntary approaches and its existing legal authorities, when necessary, to obtain additional information on potential rel eases, exposures, effects and risks of PBDEs and other flam e retardants and to take actio ns to reduce potential risks, if deem ed appropriate. EPA will als o continue to track activ ities and in itiatives atthe state and lo cal level, a s well as internationally, and w ill exch ange techn i cal inform ation with other governm e nt agencies. In addition, EPA will m a i n tain updated inform ation on its PBDEs activities on its web site at www.epa.gov/oppt/pbde.

REFE RE NCES ECB (2003). European Union Risk Assessm ent Report: diphenyl ether, octabrom o derivative. E uropean Chem icals Bureau. Ispra, Italy. Environ (2003). Tier 1 Assessm ent of the Pote ntial Hea lth Risks to Child r e n Associate d with Exposure to Commercial Pentabrom odiphenyl Ether P r oduct. Environ Intern ational Corporation

. Em eryville , Calif ornia. WHO (1994). Brom inated Diphe nyl Ethers. Environm ental Health Criteria 162. W o rld Health Organization, International P r ogr amm e on Che m ical Safety. Geneva, Switzer land.

14APPE NDI X A. CURRENT SCI E NTIFIC UNDERS T ANDI NG OF PBDEs The scientif ic literature o nPBDEs is growing at a rapid rate. This appendix presents a summary of the science on PBDEs a s of early 2005. It is not m eant to represent an exhaustive r e view and e v aluation of the PBDEs lite rature. A detailed eva l uation of studies or lim itations of the available inform ation is beyond the scope of this docum ent, and this summ ary should not be tak e n to repres ent an assessm e nt of the hazards o r risks of PBDEs. EPA is currently conducting de tailed assessm ents of the toxicological inform ation for several PBDE conge ners as part of its Integrated Risk Inf o rm ation System (IRIS) program

. Wh en com p leted, these assessm ents will prov ide a thorough review of th e toxico logical literature for tetra-, p e nta- , h e xa- and decaBDE congeners.

PBDEs in t h e Environment and PBDE Exposures
PBDEs wer e first detected in the envir onm ent in 1979 (Alaee and W e nning 2002) and in biota in the 1980s (Jansson et al. 198 7). R ecent PBDE monitoring efforts suggest that several PBDE congeners are ubi quitous in the environm ent (N TP 2001) and that levels of PBDEs in sedim e nt, air, wildlife, and hum a n tissues are increasi ng. Measurem ents of PBDE congeners in hum ans, fish and other biota detect BDE-47 m o re frequently than other congeners. However, m onitoring efforts have not analyzed collected sam p les for all possible PBDE congeners. Therefore, pot ential contributions of other congeners m ay have been overlooked.
SEDIMENT , SLUDGE AND E FFL UENT PBDEs have been found in sedim e nt sam p les, sewage effluent, and sewage sludge with differing congener profiles. Detailed analyses of sedim e nt cores from Lake Superior detected decaBDE (BDE-209) in m u ch gr eater concentrations than other PBDE congeners (Song et al. 2004). PBDEs found insewage sludge and effluent m ay be a contributor to the PBDEs insedim e nt. TetraBDE, pentaBDE, and decaBDE conge ners represent the m a jority of PB DEs found in a sam p les of Gr eat Lakes sew a ge sludge (Hale et al. 2003) and in San Francisco Bay area se wage effluent and sludge (North 2004). The congener profiles in both studies indicate the largest portion of the to tal PBDE present in the sludge sam p les to be BDE-99. BDE-47 and BDE-209 are also dom inant congeners in both studies. No explanation is available for the difference in congener profiles in sludge, effluent, and sed i m e nt. Potential re g i onal differences in PBDE deposition and varying rates of congener breakdown in the environm ent m ay contribute to the differing congener profiles in these three m e dia.
AIR AND INDOOR E NVIRONM ENTS PBDEs have been detected in am bient air and indoor environm ents (Harrad et al. 2004; Jaward et al. 2004; Lee et al. 2004; Shoeib etal. 2004; W ilford et al . 2004). Due to its low volatility and strong sorption to part iculates, the deca con g ener BDE-209 is not thought to be a likely candidate for airborne transport (Hale et al. 2003); however, the m a jority of studies conducted to date have not analyzed outdoor air sam p les for BDE209. Findings of BDE-209 in arctic biota suggest the possibility of long-range

15distribution (Ikonom ou et al. 2002 ; Wolkers et al. 2004). In door air samples contain a variety of tetraBDE, pentaBDE, and hexaBD E congeners (Harrad et al. 2004). The decaBDE congener, BDE-209, has b een m easured in outdoor and indoor window surfaces (Butt et al. 2004 ). In additio n, te traBDE, pentaBDE and decaBDE congeners are present in North Am erican house dust (R udel et al. 2003; Stap leton et al. 2005).
W I LDLIFE Num e rous ecological studies provide convincing evidence that som e PBDEs bioaccum u late (Hites et al. 2004; NTP 2001). Studies exam ining 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. (Ikonom ou et al. 2002; Lebeuf et al. 2004; Norstrom et al. 2002; Zhu and Hites 2004)

. Studies of Baltic Sea biota in dicate that PBDE conc entrations increase with the trophic level, s uggesting biom agnification of PBDEs in aquatic ecosystem s (Haglund et al . 1997; NTP 2001). New evidence suggests the breakdown of higher brom inated congene rs in fish and m a mmalian tissues, which m ay contribute to the accum u lation of lower brom inated congeners (Morck et al. 2003; Stapleton et al. 2004a; S t aplet on et al. 2004b; Tomy et al. 20 04). Bioaccum ulation in a whale of m e thoxylated P B DEs, including m e thoxylated BDE-47, has been shown to be of natural origin and not from industrial sources. Several m e thoxylated-P BDEs are known natural products, and have been observe d in dolphins and other m arine m a mmals, sponges, algae, and acorn worm s (Teuten et al. 2005). PBDE congener profiles in wildlif e tiss ues are like l y de pendent on a com b ination of direct uptake from the environm ent, natural synthesis, debrom inati on of higher brom inated congeners to lower brom inated congeners and differential bi om agnification over trophic levels.
FOOD Regional analyses have detected PBDEs in fish, m eat, 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 dom inate the PBDE congene r profile (Hites 2004; Ohta et al. 2002; Schecter et al. 2004) while BDE-99 is the dom inant congener in m eat (Huwe et al. 2002; Schecter et al. 2004). Detectab le levels of BDE-209 are also found in m any food sa m p les (Schecter et al. 2004). In dairy sam p les, conge ner profiles indicate a wider variation than either fish or m eat (Schecter et al. 2004). It should be noted, howev er, th at the analys es of food ite ms are currently lim ited to sm all num b ers of sam p l e s from a lim ited num b er of locations.
HUMAN TISSUES PBDEs have been found in hum an breast m il k, adipose tissue, and blood sam p les (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 lim ited at this tim e
. BDE-47 appears to be the dom inant congener in hum an tissues in the U.S.; however, the sam p le sizes have been very sm all and the interindividual variability is gr eat, m o st notably for BDE-47. Most of the breast m ilk biom onitoring data have been generated in Sweden, although there are very lim ited data available f o r the U.S. and Canada. The largest breast m ilk study to date in the U.S. (Schecter et al. 2003) analyzed 47 individual breast m ilk sam p l e s

16from nursing m o thers in Texas. The levels in these volunteer wom e n we re m arkedly 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; Strandm an et al. 2000). In the U.S., lim ited data are ava ilab l e f o r PBDE l e vels in blood serum

. However, com p ared to blood m onitoring data from Sw eden, Japan, and Norway, the m o st recent blood serum levels in U. S. populatio ns are high er and quite v ariab le. A recent retrospective tim e trend study of PBDEs in verysm all sam p l e s of blood serum in the U.S. has shown that m e dian levels of the indivi dual congeners as well as total PBDEs have increased in the U.S. from 1985 to 2002 (Sjodi n et al. 2004). Data on PBDE blood serum levels in 12 m a ternal and fetal pairs from I ndiana indicated that 6 PBDE congeners w e re m easured in blood serum sam p les and that the predom inant congener was BDE-47 (Mazdai et al. 2003). The range of total PBDE s in the m a ternal and fetal sam p les were very sim ilar; however, the variability between the pairs wa s great, especially for BDE-47.
EXPOSURE PATHWAYS As described above, PBDEs are present in m any critical exposure m e dia, including various foods, indoor air and house dust. However, the m eans by which hum ans and wildlife are exposed to P B DEs are not well understood. PBDEs m ay enter the environm ent in a variety of ways: release from manufacture of the PBDEs or of PBDEcontaining products; release of PBDEs from pr oducts while they are in use; and release from products when disposed of or recycle d. There are m any uncerta inties regarding the pathway of PBDEs from releas e to their presence in critical environm ents and exposure m e dia. It is likely that the presence of PBDEs in indoor environm ents (house dust, indoor air, and indoor window surfaces) is in la rg e part du e to m i gration o f PBDEs from products, including furniture and carpet foam an d plastics in televisi ons and com puters. Little is known about how PBDEs enter aqua tic environm ents, and how they enter the food chain. The biom onitoring data described above indica te that there is hum an exposure to PBDEs; but the rela tive contributions of differe nt exposure routes (such as inhalation, f ood ingestion, dust ingestion or dermal absorption) have not been characterized. The relative im portance of these types of exposure m ay be different for infants, young children, olde r children, and adults.
Pharmacokinetic and Toxicity Profiles of PBDEs in Mammals
PHARM A C OKINETIC S The available data indicate that the tetr a congener BDE-47 and the penta congener BDE99 are well absorbed and highly distributed to fatty tissu es, such as adip ose, adren a l glands, gastrointestinal tract, skin and liver (Hakk et al. 2002; Orn and Klasson-W e hler 1998; Staskal et al. 2005). Te tra- and pentaBDEs are slow ly m e tabolized and slowly elim inated in rats (Hakk et al. 2002; Hakk and Letcher 2003). In m i ce BDE-47 (a tetraBDE) is also well absorbed and distribute d, b u t it is ef f ective l y elim inated, with u p to 81% of th e dose excreted with in 5 days (Stask al et al. 2005). DecaBDE is poorly

17absorbed by rats, with more than 90% of the dose excreted w ithin 2 days (Morck et al. 2003).
HEPATIC E FFECTS Studies conducted in rodents have dem onstrat ed hepatotoxic potential with exposure to PBDE m i xtures. The spectrum of he patic e ffects observed in studies of various PBDE congeners and m i xtures includes m i crosom al enzym e induction, liver enlargem ent, and degenerative histopathologic alterations. In rodents, dietary expos ure to 5-10 m g /kg/day (IRDC 1976; IRDC 1977; Norris et al. 1973; Norris et al. 1975; Zhou et al. 2001; Zhou et al. 2002) and 56 m g /kg/day (Carlson 1980) of PBDEs typically caused liver enlargem ent with or without degenerative changes, and the in cidence and severity of effects were generally dose-related an d m o re frequent and pronounced in m a les than fem a les. Effects are generally m o re severe with comm e rcial m i xtures of octaBDE and pe ntaBDE than decaBDE (Carlson 1980 ; IRDC 1976; IRDC 1977; Norris et al. 1973; No rris et al. 19 75; NTP 1986; W I L Research Laboratories 1984; Z hou et al. 2001; Zhou et al. 2002). S o m e of the studies indicating thyr oid effects of decaB DE were conducted on older commercial m i xtures that contained more im purities th at the products curren tly m anufactured. When scientists began studying PBDEs, there was som e expe ctation that the PBDEs m i ght have som e toxicological si m ilarities to dio x ins, due to th e structur al sim ilarities of these chem i cals. To test this hypothesis, sc ientists conducted studies of hepatic enzym e activity. Induction of the cytochrom e P450 enzym e CYP1A is a well-established characteristic of chem ica l s that bind to the aryl hydrocarbon re ceptor (AhR), m o st notably dioxins, furans and co-planar P CBs (also known collectively as "dioxin-like com pounds" )

. By bindin g to the Ah R a chem ical m ay initiate a num ber of other effects that characterize "dio xin-like" toxicity in addition to inducing CYP1A. He nce CYP1A induction is considered an indicator that a chem ical can bind to the AhR and has the potential to cause toxicity si m ilar to dioxin. Initial studie s w e re conducted in comm er cial PBDE m i xtures and have been reported to induce CYP1A at doses of 18 – 60 m g /kg (Hallgren et al 2001; Stoker et al. 2004). However, the tetra congener B D E-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 co mm er cial PBDE m i xtures, but not for individual P B DE conge ners. Given that there is no indi cation of CYP1A induction by PBDE congeners, th is s uggests th at there is a co nstitu ent of the comm erc i al m i xtures, i.e. a contam inant other than the PBDE congene rs, that is responsible for the enzym e induction. It appears that PBDEs them selv es do not have dioxin-like activity.
IMMUNOL OGICAL E FFECTS Disruption o f norm a l immune function m ay result in an inab ility of the an im al to resp ond to and re cov e r from further stresso rs such as illness and disease. Short term (14-day) exposure to 18-72 m g /kg/day of commercial pe ntaBDE m i xtures in m i ce resulted in suppressed antibody response, decreased thym us weight (Fowles et al. 1994) and decreased IgG i m m unogl obulin production (T huvander and Darnerud 1999). Short-term exposure of m i ce to 18 mg/kg/day of BDE-47 caused significantly reduced num b ers of total lym phocytes and splenocytes (T huvander and Darnerud 1999). Ch ronic ingestion of decaBDE at 2240 m g /kg/day for 103 weeks caused splenic lesions in rats (NTP 1986).

18No inhibition of the immune response system was observed in a study of the effect of BDE 85 (Fe rnlof et al. 1997). Currently available inform ation is insufficient to adequately characterize the imm unot oxic potential of PBDEs

. DEVEL O P M ENTAL AND NEUROBE H AVIORAL AL TERATIONS Gestational exposure to 1000 m g /kg/day of d ecaBDE for 19 days resu lted in increased early reso rptions in r a ts ; the autho r s c oncluded th at the s e wer e of lim ited signif i can ce based on comparison to historical co ntrol data (Hardy et al. 2002). Developm ental neurotoxic effects have been found in rodent studies of exposure to individual P B DE conge ners. In neonatal m i ce, postnatal day 10 was determ ined to be a critical window of sensitivity to PBDE exposure. Ani m als treated with 0.6 and 6 mg/kg/day of BDE-99 for 15 days (B ranchi et al. 2002) and single 0.4 m g /kg doses of BDEs 47, 99, 153, or 209 (Birnbaum and Staska l 2004; Branchi et al. 2003; Eriksson et al. 2001; Viberg et al. 2002; Viberg et al. 2003a; Vi berg et al. 2003b) showed neurobehavioral alterations , hyperact ivity extending into adulthood, and a nonhabituating behavior profile. In m a le offspring of da m s treated with single 60 μg/kg and 300 μg/kg doses of BDE-99, developm ental reproductive and neurobehavioral landm arks were significantly delayed (Kuriyam a et al. 2005). Developm ental reproductive effects have also been observ ed following 31 days of exposure to 30 mg/kg/day and 60 m g /kg/day of the comm ercial pentaBDE m i xture (S toker et al. 2004).
ENDOCRI NE DISR UPTING EFF E CTS Evidence from experimental anim al studies for certain PBDE congeners and comm e r cial m i xtures has indicated the potential f o r eff ects on the thyroid system . Thyroid effects include reduced serum levels of the thyroid horm one T 4 (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 hyperpla sia, which is a sign of disrupted thyroid function, was observed in m a le m i ce orally exposed to 3200 mg/kg/day or m o re of decaBDE (NTP 1986). Disruption s in m a ternal and fetal thyr oid hom eostasis can result in neurologic im pairm e nt, including developm en tal delays and decrea sed IQ in children of

m o thers with sm all r e duction s in T 4 (Haddow et al. 1999; Pop et al. 1999; Pop et al. 2003). Hydroxylated BDEs, which are m e tabolites of PBDEs, have been shown to inhibit estrogen sulfotransferase, leading to an appare nt estrogenic effect (Kester et al. 2002). A study of the estrogenic potential of se veral PBDE congeners and hydroxylated m e tabolites found 11 PBDE congeners and 2 hyd roxylated metabolites with estrogenic activity (Meerts et al. 2001)

. Stoker and co-workers found endocrine effects and developm ental delays with exposures to th e comm e rcial pentaBDE m i xture of 30 and 60 mg/kg/day for 31 days , indicating inhibition of endogenous androgen activity (Stoker et al. 2004). A n ti-androgenic and es trogenic activity ar e of concern as they m ay lead to a disruption of norm a l endocrine function and pot entially result in reproductive failure and estrogen

- related can cers
.

19REPRODUCTIVE EFF E CTS Male and fem a le rats exposed to the co mmercial pentaBDE m i xt ure DE-71 exhibited delayed pubertal develo pm ent with dosing at 30 and 60 m g / kg/day for 5, 21 or 31 days (Stoker et al. 2004). Of the androgen-depende nt tissues in exposed m a le rats, sem i nal vesicle and ventral prostate weights were reduced, while te stes and epididym al weights were not affected. Preputial separation and age of vaginal opening were significantly delayed in exposed fe m a le rats. Kuriyam aand co-workers evaluated m a le reproductive health in the rat offspring of da m s e xpos ed to BDE-99 in single doses of 60 and 300 μg/kg. Daily sperm production and sperm a tid counts were significantly decreased (Kuriyam a et al. 2005). EPA’s Voluntary Children’s Chem ical Evaluation Program (VCCEP) ha s concluded that the lim ited repr oductive toxicity data for pentaBDE and octaBDE constitutes an important data need f o r th ese chem icals.
CANCER There is so m e evidence that decaBDE is car cinogenic in rats and m i ce froman NTP twoyear cancer bioassay (NTP 1986). Statistically significant incr eases in the incidence of hepatic neoplastic nodules were seen in m a le rats at 1120 and 2240 m g /kg/day, and in fe m a le rats at 2550 m g /kg/day. Increased incidence of hepatoce llular adenom as or carcinom as (com bined) were seen in m a le m i ce at 3200 m g /kg/day; increases relative to controls were seen in m a le m i ce dosed at 6650 mg/kg/day and in fem a le m i ce dosed at 3760 and 7780 m g /kg/day but were not statistically significant. Based on these results, EPA has classified decaBDE as a possible hum an carcinogen (U.S. EPA 1995). As part of the IRIS assessm ent of decaBDE, EPA is currently updating its assessm e nt of the carcinogenic potential of decaBDE to reflect the A g ency’s revised Guidelin es for Carcinogen Risk Assessment (U.S. EPA 2005). Studies of the carcinogenic potential of pentaBDE and octaBDE have not been conducted.
Pharmacokinetic and Toxicity Profile s o f PBDEs in Ecological Recep tors Effects of PBDEs in ecologica l receptors are currently lim ite d. To date, a variety of endpoints have been assessed in a very lim ite d number of species, pr im arily invertebrates and fish commonly used in aquatic toxicitytesting. Detailed reviews of studies conducted through 1999 can be found in the Eur opean Union risk assessm e nts for the PBDEs (ECB 2001; ECB 2002; ECB 2003). No pub lished reports of PBDE toxicity in birds or m a mmalian wildlife were lo cated. Ho wever, recent prelim inary reports ind i cate studies to investigate effect s of PBDEs on a variety of s ublethal endpoints in avian and m a mmalian wildlife are underway (S ETAC 2004).
PHARM A C OKINETIC S In a study of uptake, accum u lation and ex cretion of BDE-47, -99, and -153 by blue mussels, the uptake rate for BDE-47 and BDE-99 was approxim ately 10 tim es higher than for BDE-153, but that depuration rates we re sim ilar for all three PB DEs (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 estim at ed to be quite low (0.02-0.13%) (Kierkegaard

20et al. 1999a). Sim ilarly, incarp exposed via the diet for 100 days, BDE-209 did not accum u late (Stapleton et al. 2004a). BDE-47 wa s distributed in liv er, gall bladder, kidneys, brain, chorion of the eye and perivisc eral adipo s e tissue in pik e (Burreau an d Brom an 1998; Burreau et al. 2000). Recent stud ies suggest m e tabolic deb r om ination of higher brom inated co ngeners occurs in fish. Stapleton and co-workers (S tapleton et al. 2004a; Stapleton et al. 2004b) found that BDE-99, -183 and -209 adm i nistered via th e diet are debrom inated in the intestinal tract of the comm on carp. In a long term feeding study in which 13 tri- through decaPBDE congeners (pur itygreater th an 96%) were fed to juvenile lake trout, Tomyet al. report the detection of increasing concentra tions of lower brom inated congeners and occurrence of three penta- and hexa- congeners that were not pres ent in the technical product used to dose the fish, in the f ood theywere fed or in control fish, supporting the hypothesis that higher brom inated congeners are debrom inated to lower brom inated congeners (Tomy et al. 2004). Hydroxylated and/or m e thoxylated P B DE c onge ners have b e en found in Baltic salm on, herring, ringed seal, and gray seal (A splund et al. 1997; Asplund etal. 1999; Haglund et al. 1997; Kierkegaard et al. 1999b).
PLANT S The commercial pentaB DE m i xture was esse ntially 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 e ffects on the g r o w th of three species of m arine algae at concentrations up to 1 m i crogram per liter (Walsh et al. 1987).
INVERTE B RATES 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). Wh ile som e effects were reported for pentaBDE, the si gnificance of the results is confounded by the fact that the test concentrations often exceeded th e solubili ty lim its of some of the m i xture (ECB 2001). Daphnid repro duction was not affected in this test. PentaBDE did not cause toxic effects to earthworm s in a 14-day study (ECB 2001). Chronic exposure of sedim e nt organism s (e.g., Hyalella azteca, Chironomus riparius and L u mbriculus variega t us ) to pentaBDE produced no-observable- ef f ect-con centr ation s (NOECs) in the low m illig ram per kilogram range forpentaB DE (ECB 2001) and no adverse effects were seen with octaBDE (ECB 2003). Effects of specific PBDE congeners o ntwo cr ustacean species have been d e m onstrated

. Full life-cycle studies in dicate BDE-47, BDE-99 and BDE-100, at low m i crogram per liter concentrations affect la rval developm ent and population growth rate in the copepod Nitocra sp in ipes (Breitholtz and W o llenberger 2 003). BDE-28, BDE-47, BDE-99 and BDE-100 were found to inhibit larv al developm ent in the copepod Acartia tonsa in th e low m i crogram per liter concentratio n range (W ollenberger et al. 2005).

21FISH A variety of PBDE m i xtures have been found to have very low or no acute toxicity in fish. Commercial m i xtures of pentaBDE, octaBDE, and decaBDE had low or no acute toxicity to Japanese m e daka and rainbow trout at the solubility lim it, even when a carrier solvent was used to increase wa ter solubility (ECB 2001; Hardy 2002). In an early life stage toxicity study conduc ted with rainbow trout, no effects were observed on hatching, swim up or larval and fry survival following 21days waterborne exposure to a pentaBDE m i xture. At 60 days post-hatch, statistica lly signif i cant effects on juvenile fish length and weight were observed at the highest concentration tested (16 μ g/L) (ECB 2001). Hornung et al. assessed th e toxicity of single congeners, BDE-47, BDE-85, and BDE-99, using an egg injection bioassay developed to assess the toxicity of dioxin- like c h em icals in early lif e stages of rainbow trout. W h ile this b i o a ssay has g r eat sensitivity for detecting dioxi n-like toxicity, none of the PBDE congeners tested caused sim ilar early life st age toxicity (Hor nung et al. 1996). As noted above, structural sim ilarities of PBDE s and dioxins led scient ists to suspec t that PBDEs have toxicological properties sim ilar to dioxins. The potential for PBDEs to possess dioxin-like activity ha s been explored by m easuri ng induction of the hepatic enzym e cytochrom e P450 (CYP1A) because th is is a well-es t ablish e d char acteristic of chem icals th at bind to th e AhR, inclu d ing dioxins. Hepatic C Y P1A activity was weakly induced (only 2-3 fold) in rainbow trout larvae injected with a commercial pentaBDE m i xture (Norrgren et al. 1993). Likewise, CYP1A activity wa s induced in three-spined stickleback f e d chironom ids contam i n ated w ith the sam e PBDE m i xture (Holm et al. 1993). In contrast, in rainbow trout fe d food containing BDE-47 and BDE-99, CYP1A activ ity was inhibited (T jarnlund 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 adm i nistered to juvenile lak e trout to assess bio accum u latio n and biotransform ation (Tomy et al. 2004). In this study, no increase in C Y P1A activity was observed at concentrations of the PBDE congeners above those observed in the environm ent. The finding that commercial PB DE m i xtures affected CYP1A activity b u t that individual congeners di d not is consistent with th e m a mmalian literature, and sim ilarly suggests that the enzym e inducti on is due to som e contam inant in the commercial m i xtures rather than the PBDE congeners th em selves. A variety of other biochem i cal endpoints have been assessed in fish exposed to PBDEs. DecaBDE increas ed liv er weight and plasm a lactate lev e ls and decreased the num ber of lym phocytes in rainbow trout dosed with 10 m g decaBDE for up to120 d ays via the d i et. DecaBDE had no effect on transketo l ase , ethoxyresorufin- O -deethylase, or ethoxycoumarin- O -deethylase activity in the same ra inbow trout (Kierkegaard et al. 1999a). Fat accum u latio n in liv er an d reduced sp awning success was observed in threespined stick l eback fed doses of a comm er cial pentaBDE m i xture corresponding to concentrations of 861 and 1630 m g /kg of fa t tissue (Holm et al. 1993). R e duced glutathione reductase activity, hem a tocrit and blood glucose levels were observed in rainbow trout fed a total dose of 21 mg/kg of BDE-47 or 19.5 m g /kg BDE-99 via their

22diet over 22 days (Tjarnlund et al. 1998). However, in the sam e study, no effects on condition factor, liver and spleen som a tic indi ces, white blood cell counts or hem oglobin were observed. Wh ether these biochem i cal changes significantly affect health of individual fish or fish populati ons is currently not established.

REFE RE NCES
Alaee M and Wenning RJ ( 2002). The si gnificance of brom inated fl am e r e tardant s in the

environm ent: current under s tanding, issu es and challenges. Chemosphere 46:57 9

- 82. Asplund L, A thanasiadou M, Eriksson U, Sjodin A, Borjeson H and Bergm an A (1997). Ma ss

spectro m e tric screening for organohalogen substances (OHs) in blood plasm a fro m Baltic sal m on ( Salmo salar). Organoh alogen Compd 33: 35 5-9. Asplund L, A thanasiadou M, Sjodi n A, Berg m an A and Borjeson H (1999). Or ganohalogen

substances in m u scle, egg and bl ood fr om healthy Baltic sal m on ( Salmo salar) and Baltic salm on affected b y the M 7 4 syndrom e. Ambio 28: 67- 76. Birnbaum LS and Staskal DF (2004). B r om in ated flame retardants : cause for concern? Environ Health Perspect 112:9-1 7

. Branchi I, Alleva E and Costa LG (2002 ). Effects of Perinatal Expo sure to a Pol ybrom inated

Dipheny l Eth e r (PBDE 99) on Mo use Neurobehavioural Develop m ent. NeuroToxicology 23:37 5-38 4. Branchi I, Capone F, Allev aE and Costa LG (2003). P o l y brom inated dip h eny l ethers:

neurobehavio r al effects following devel opm ental exp o sure. Neurotoxicology24: 449-6 2

. Breitholtz M and Wollenbe rger L (200 3). Effect s of three PBDEs on developm ent, reprod uction and pop ulatio n growth rate of the harpacticoid copepo d Nitocra spinipes

. Aquat Toxicol 64:8 5

­ 96. Burreau S, Axelm an J, Broman D and Ja kobsson E ( 1 997). Dietar y uptake in pi k e (Esox lucius ) of some pol ychlorinated bi pheny ls, p o l y chlori nated n a phthalenes and p o l y br om inated dipheny l ethers ad m i ni stered in natural diet. Environ Toxicol Chem 16:250 8- 2513

. Burreau S and Brom an D (1998). Uptak e of PBDEs in pike ( Esox lu cius ) from food. Organohalogen Compd 39 :39-42

. Burreau S, Broman D and Orn U (2000) . Tissue distributionof 2 , 2' ,4,4'

- tetrabrom o [ 14C] d ipheny l

ether ([ 14C]

- PBDE 47) in pike (Esox lu cius ) after dietary exposure--a ti m e series study using whole body autoradiograp hy
. Chemosphere 40:977- 85. Butt CM, Diam ond ML, Truong J, Ikon o m ou MG andter Schure AF (200 4). Spatial distributi on

of pol ybrom inated dipheny l ethers in so uthe rn Ontario as m e asured in in door an d out door window organic films. Environ Sci Technol 38 :7 24 -31

. Carlson GP (1980). Ind u ction of xenobi otic metabolism in rats by short-term ad ministration of brom inated dipheny l ethers. Toxicol Lett 5:19-2 5

.

23ECB (2001). European Uni on Risk Assessment Re port: dipheny l ether, pentabro m o derivative. European Che m ic als Bure au. Ispra, Italy. ECB (2002). European Uni on Risk Assessment Re port: bis(pentabr o m opheny l) e ther. European

Che m ic als B u reau. Ispra, Italy

. ECB (2003). European Uni on Risk Assessment Report: dipheny l ether, octabromo derivative.

European Che m ic als Bure au. Ispra, Italy. Environ (2003). Tier 1 Assess ment of the Poten tial Health Risks to Children Associated with

Exposure to Co mmercial Pentabrom o d i pheny l Ether Product. E n v i ron Internati onal Corporat ion. E m ery v ille, California. Eriksson P, J akobsson E and Fredriksson A (2001) . B r om inat ed flame ret ardants: a novel class of

developm ental neurotoxic ants in our environm ent? Environ Health Perspect 109:903-8

. Fernlof G, Gadhasson I, Po dra K, Darnerud PO and T huvander A ( 1997). Lack o f effects of so me indivi dual po lybrom inated dipheny l ether (P BDE) and pol y c hl orinat ed bipheny l ( P CB) congeners on hum an ly m phocy t e functio ns in vitro

. Toxicol Lett 90 :189-9 7

. Fowles JR, F a irbrother A, Baecher -Steppan L and Kerkvliet NI (1994). Imm unologic and endocrine effects of the flame-retardant pentab rom odipheny l ether ( D E-71) in C5 7BL/6J m i ce. Toxicology86 :4 9

- 61

. Gustaffson K , Bjork M, Burreau S and Gilek M (1999). Bioaccu mulation kinetics of brom ina t ed

fla m e r e tarda n ts (polybrominated dipheny l ethers) in blue m u ssel s ( Mytilus ed ulis ). Environ Toxicol Chem 18:1 218- 24. Haddow JE, Palo m aki GE, Allan WC, William s JR , Knight GJ, Gagnon J, O' Heir CE, Mitchell

ML, Herm os RJ, Waisbren SE, Faix JD and Kl ein RZ (1999) . Maternal thy r oi d d e ficiency during pregnancy an d subs equent neuro p sy ch ological developm ent of the child. N Engl J M e d 341:5 49-5 5

. Haglund PS, Zook DR, Bu ser H and Hu J (1997). I d en tification and quantificationof

pol y b r o m i nat e d diphenyl ethers and met hoxy

- pol ybr ominated dipheny l ethers in baltic biota. Environ Sci T echnol 31: 32 81-87. Hakk H, Larsen G and Klasson-Wehler E (2002) . Ti s s ue disposition, excre tion and m e tabolism of 2,2' ,4,4' , 5-pentabrom odipheny l ether ( B DE -99) in th e male Sprague-Dawley rat. Xenobiotic a 32:36 9-82

. Hakk H and Letcher RJ (2 003). Metabo lism in the to xicokinetics and fate of bro m inated flame retardants--a review. Environ Int 29:8 0 1

- 28. Hale RC, Alaee M, Manchester-Neesvig JB, Stapleton HM and Ik onom ou MG (2003).

Pol y brom inated dipheny l ether flam e retardan ts in the North Ameri can environment. Environ Int 29:77 1-9. Hardy ML (2 002). T h e tox i colog y of the three co mmercial pol y b ro minated diph eny l oxi de (ether)

flam e r e tardants. Chemosphere 46:757- 77.

24Hardy ML, S c hroeder R, Biesemeier J and Manor O ( 2002). Prenatal oral (gavage) developm ent a l toxicity study of decabrom odipheny l oxide in rats. Int J Toxicol 21 :8 3

- 91

. Harrad S, Wijeseker a R, Hunter S, Halliwell C and Baker R (2004) . Preli m inary assessment of

U.K. human dietary and inhalation expo sure to pol ybr om inated dip h eny l ethers. Environ Sci Technol 38: 2 345-5 0

. Hites RA (20 04). Pol ybro m inated diph eny l ethe rs in the environm ent and in people: a metaanaly s is of concentrations. Environ Sci T echnol 38: 94 5-56. Hites RA, Fo ran JA, Schwager SJ, Knuth BA , Ham ilton MC and C arpenter DO (2004). Global

asse ss ment of polybrom ina t ed diphenyl ethers in farm ed and wild s a l m on. Environ Sci Technol 38:49 45-9

. Holm G, Norrgren L, And e rsson T and Thuren A (19 93). Effects of exposure to food contam inatedwith PBDE, PCN or PCB on reprod uction, liver m o rpholo g y an d cy tochr o m e P450 activity in the three-spined stickleb ack, Gasteros t eus aculeatus

. Aquat T oxicol 27:3 3 -50. Hornung M W , Zabel EW and Peterson RE (1996). T oxic equivale ncy factors of pol ybrom inated dibenzo-p-di oxin, dibenzofuran, bipheny l , and pol yhalogenated di pheny l ether congeners based on rainbow trout early life stage m o rtalit y. Toxicol Appl Pharmacol 140: 227- 34. Huwe JK, Lo rentzsen M, Thuresson K and Bergm an A (2002). Analy s is of m ono- to decabrom inated dipheny l ethers in chicke ns at the part per billion level. Chemosphere 46:6 35-4 0

. Ikonom ou MG, Ray n e S and Addison RF (2002). Exponential incr eases of the brom inat ed flame

retardants, polybrom inated dipheny l ethers, in the Canadian Arctic from 1981 to 2000

. Environ Sci Technol 3 6 :188 6-92

. IRDC (1976). Decabro m o d i pheny l ether and octa bromodiphenyl ether. A twenty

- e ight day toxicity study in rats. International Research and Development Corporation. S ubmitted to U.S. EPA under T S CA Section 8D, Fiche no. OTS0523 32 2. IRDC (1977). Octabro m odipheny l ether. Thirteen week feeding stu dy in rats. Int e rnational

Research and Developmen t Corporation. Subm itte d to U.S. EPA under TSCA Section 8D, Fi che no. OTS05 2 2 297. Jansson B, Asplund L an d Olsson M (19 87). Br om inated flam e retardants--ubiqu itous

environm ental pollutants ? Chemosphere 16:2 343- 49. Jaward FM, Meijer SN, Steinnes E, Tho m as GO and Jones KC (2004). Further studies on th e

latitudinal an d tem poral trends of persistent organic p o llutants in N o rwegian and U.K. backgroun d air. Environ Sc i Technol 38 : 2523- 30. Kester MH, Bulduk S , van Toor H, Ti b boel D, Meinl W, Glatt H, Falany CN, C oughtrie MW ,

Schuur AG, Brouwer A and Visser TJ (2002). Potentinhibi tion of estrogen sulfotransferase by hy dro x y lated metabolites o f pol yhalogen a ted ar o m atic hy drocarbons reveals alt e rn ative mechanis m f o r estrogenic activity of endocrine disrupters. J Clin Endocrinol M e tab 87: 114 2- 50.

25Kierkegaard A, Balk L, Tjarnlund U, de Wit C and Jansson B (199 9a). Dietary u p take and effects of decabrom o dipheny l ether in the rainbow trout ( Oncorhynchus mykiss ). Enviro n Sci Technol 33:16 13-1 7

. Kierkegaard A, Sellstro m U, Bignert A, Olss on M, Asplund L, Jansson B and d e Wit C (199 9b).

Tem poral trends of a pol yb rom i nated dipheny l ether (PBDE), a m e t hoxy l ated PBDE and hexabrom ocy c lododecane (HBCD) in S w edish biota. Organohalogen Compd 40 :367-3 70. Kuriy am aSN, Talsness CE , Grote K and Chahoud I ( 2 005). Developmental Exposure to Low

Dose PBDE 99: 1--Effects on Male Fertility and Neur obehavior i n Rat Offspring. Environ Health Perspect 113:14 9-5 4

. Lebeuf M, Gouteux B, Me asures L and Trottier S (2004). Levels and tem poral trends (1988­ 1999) of p o l ybrom inated dipheny l ethers in bel uga wh ales (Delphinapterus leucas) fro m the St. Lawrence Estu ary , Canada. Environ Sci Technol 38: 2 971-7. Lee RG, Thomas GO and Jones KC (2004). PBDEs in the atm o sp here of three locations in

western Europe. Environ S c i Technol 38 :699-7 06. Mazdai A, Dodder NG, Abernath y MP, Hites RA and Bigsb y RM (2003) . Pol ybrom inated

dipheny l ethers in maternal and fetal blo od sam ples. Environ Health Perspect 111:1249- 52. Meerts IA, Letcher RJ, Ho ving S, Marsh G, Berg m a n A, Lemmen JG, van der Burg B and

Brouwer A (2001). I nvitr o estrogenicity of pol ybrom inated dipheny l ethers, hy dr ox y l ated PDBEs, and pol y b r o m i nated bisphenol A co m pound s. Environ Health Perspect 109:3 99-4 07. Meirony t e D, Noren K and Berg m an A (1999). Anal ysis of pol y b r o minated diph eny l ethers in

Swedish human m ilk. A ti me-rel ated trend study, 1 9 7 2 -199 7. J Tox i col Environ Health A 58:32 9-41

. Meirony t e Guvenius D an d Noren K (2 001). P o l y br o m inated Dipheny l Ethers inSwedish Human

Milk. The F o llow-up study
. Second Inter n ati onal Wor k shop on Bro m inated Flame Retardants, Stockholm , Sweden, World Health Organization, Th e Swedish Ministry of the Environm ent, and the Roy a l Swedish Acade my of Sciences.
Meirony t e Guvenius D, Aronsson A, E kman-Or deberg G, Berg m a n A and Noren K (200 3).

Hu m an prenatal and postnat al exposure to pol ybrom inated dipheny l ethers, pol y c hlorinated bipheny ls, po ly chl o robi phe ny lols, and pe ntachlorophe nol. Environ Health Perspect 111:12 35­ 41. Morck A, Hakk H, Orn U and Klasson Wehler E (2003). Decabrom odipheny l e ther in the rat:

absorption, di stribution, m e tabolism , andexcretion. Drug M e tab Dispos 31: 900- 7. Norris JM, Ehrmantraut JW, Gibbons CL, Kociba R, Schwetz B, Rose J, Hu m i ston C, Jewett G,

Cru mmett W, Gehring P, T i rsell J and Brosier J (1973) . Toxicolo gical and enviro nmental facto r s involved in th e selection of decabro m odipheny l oxide as a fire ret ar d ant chem i cal

. Appl P o lym Symp 22:19 5- 219. Norris JM, Ehrmantraut JW, Kociba RJ, Schwetz B A , Rose JQ, Hu m i ston CG, Jew ett GL ,

Cru mmet WB, Gehring PJ, Tirsell JB and Bros ier JS (1975) . Eval uation of decabrom odipheny l oxide as a flame-ret ardant che m ic al. Chem Hum H e alth Environ 1 : 100-1 16.

26Norstro m RJ, Sim on M, Moisey J, Wake ford B and Weseloh DV (2 002). Geogra phical distributio n ( 2000) an d te m poral trends (1981- 200 0) of brom inated dip h eny l ethers in Great Lakes herring gull eggs. E n viron Sci Technol 36:4 783 -9. North KD (2004). Trackin g pol ybrom inated dipheny l ether releases in a wastewater treatment

plant effluent , Palo Alto, C a lifornia. Environ Sci Technol 3 8 :44 84- 8. NTP (1986). Technical Report o nthe T oxicolog yan d Carcinogenesis Studies of

Decabro m odi pheny l Oxi d e (CAS NO. 1163-19-5) in F344/N Rats and B6C3F1 Mice (Feed Studies). National Toxicology Progra m
. Rese arch Tria ngle Park, NC. NTP (2001). Technical Pentabrom odipheny l Ether, Technical Octabrom odipheny l Ether,

Tetrabro m odipheny l Ether, Pentabrom odipheny l Ether, Hexabrom o d ipheny l Ethe r: Review of Toxicological Literature. National Toxic o logy Program
. Research Triangle Park, NC. Ohta S, Ishizuka D, Nishim ur a H, Nak a o T, Ao zasa O, Shim idzu Y, Ochiai F, Kida T, Nishi M and Mi y a ta H (2002) . Comparison of p o l ybrom inat ed dipheny l ethers in fish, veg e tables, and meats and levels in hum an milk of nursi ng wom e n in Japan. Chem osphere 46:6 89-96. Orn U and Klasson-Wehler E (199 8). M e tabolism of 2,2' ,4,4'

- tetrabrom odipheny l ether in rat and m ouse. Xenobiotica 2 8 :19 9 -211. Petreas M, S h e J, Brown FR, Winkler J, Windham G, Rogers E, Zhao G, Bhatia R and Charles

MJ (2003). H i gh b o dy bur dens of 2,2' ,4 ,4'

- tetr abro modipheny l eth e r (BDE-47) in California wo m e n. Environ Health Perspect 111:1175-9. Pop VJ, Kuij pens JL, van Baar AL, Verkerk G, van S on MM, de Vijlder JJ, Vulsma T, Wiersi nga

WM, Drexhage HA and Vader HL (1999). Low m a te rnal free thy r oxine concentr ations durin g early pregnancy are associa t ed with im pa ir ed psy c homotor development in infancy

. Clin Endocrinol ( O

xf) 50:149- 55. Pop VJ, Brouwers EP, Vad e r HL, Vulsma T, van Baar AL and de Vijlder JJ (2003). Maternal

hy pothy ro xin a em ia during early pregnan c y and s ubsequent child d e velopment: a 3-y ear foll o w up study. Clin Endocrinol (Oxf) 59:282- 8. Rudel RA, Cam ann DE, Spengler JD, Korn LR and Brody JG (2003). Phthalates, alky lphenols,

pesticides, polybrom inated dipheny l ethers, and other endocrine-disrupting com p ounds i nind o o r air and dust. Environ Sci T echnol 37: 45 43-53. Schecter A, Pavuk M, Pap k e O, Ry an JJ , Birnbaum L and Rosen R (2003) . Pol ybrom inated dipheny l ethers (PBDEs) in U.S. m o thers' milk. Environ Health Perspect 111:1723-9. Schecter A, Papke O, Tung KC, Staskal D and Birnbaum L (2004). Pol y brom inated dipheny l ethers contamination of Un ited States food. Environ S c i Technol 38 :5306- 11. SETAC (2004). FourthSE TAC World Congress, 25th Annual Me eting in North America - Abstracts. So ciety of Environm ental Toxicology and Che m istry

.

27She J, Petreas M, Winkler J , Visita P, McKinney M an d Kopec D (2002). PBDEs in the San Francisco Bay Area: m e asurem ents in harbor seal blubber and human breast adipose tissue. Chemosphere 46:6 97-7 07. Shoeib M, H arner T, Ikon om ou M and Kannan K (2004). I ndo or and out door a i r concentrations

and phase partitioning of perfluoroalky l sulf onam i des and polybrom inated dipheny l ethers. Environ Sci T echnol 38: 13 13-20. Sjodin A, Jones RS, Focant JF, Lapeza C , Wang RY, McGahe e EE, 3rd, Zhang Y, Turner WE,

Slazy k B, Ne edham LL and Patterson DG, Jr. (2004). Retrospective tim e -trend study of pol y b r o m i nated dipheny l ether and pol yb rom i nate d and p o l y chlori nated bipheny l levels in hum an se ru m from the Uni t ed States. Environ Health Perspect 112:654-8. Song W, For dJC, Li A, Mills WJ, Buckley DR and R o ckne KJ (2004). Pol ybrominated dipheny l

ethers in the sedi m ents of the Great Lak es. 1. Lake Superior. Environ Sci Technol 38: 328 6-9 3

. Stapleton HM, Alaee M, Letcher RJ an d Baker JE (2004a). Debromination of th e flam e ret ar d ant

decabro m odipheny l ether by juvenile carp ( Cyprinus carpio ) follo wing dietar y exposure. Environ Sci T echnol 38: 11 2-9. Stapleton HM, Letcher RJ and Baker JE (2004 b). D e brom ination of pol ybrom inated dipheny l

ether congeners BDE 99 and BDE 183 i nthe intestinal tract of the common carp ( Cyprinus carpio ). Environ Sci Technol 38: 105 4-6 1

. Stapleton HM, Dodder NG, Offenberg JH, Scha ntz MM and Wise SA (2005). Pol y brom inated dipheny l ethers in house d u st and clothe s dry e r li nt. E n v Sci Technol 39: 925- 31. Staskal DF, Diliberto JJ, DeVito MJ and Bir nbaum LS (2005). T oxicokinetics of BDE 47 in fem a le m i ce: effect of dose, route of exp o sure, and ti me. Toxicol Sci83:21 5-23. Stoker TE, L aws SC, Crofton KM, Hedge JM, Ferrell JM and Coo p er RL (2004 ). Assessment of DE-71, a commercial pol y b rom i nated dip h eny l ether ( P BDE) m i xture, in the EDSP male and fem a le pubertal protocols. Toxicol Sci7 8 :144- 55. Strandman T, Koistinen J and Vartiainen T (200 0). Po lybrom inated dipheny l ethers (PBDEs) in placenta and hum an m ilk. Organohalogen Compd 47 :61-64

. Teuten EL, Xu L and Reddy CM (2005). Two abundant bioaccum u lated halogenated co m pounds are natural products. Scien c e 307:91 7-2 0

. Thuvander A and Darnerud PO (1999). E ffects of pol ybrom inated dipheny l ether ( P BDE) and pol y c hlori n ated bipheny l ( P CB) on some imm unologi cal parameters after oral exposure in rat s and m i ce. Toxicological and Environm ental Chemistry 79:229-4 2

. Tjarnlund U, Ericson G, Orn U, de Wit C and Balk L ( 1998). Effects of two pol yb rom i nated

dipheny l ethers on rainbowtrout ( Oncor h

ynchus mykiss ) exposed via food. Mar Environ Res 46:10 7-12

. Tomy GT, Palace VP, H a ll dorson T, Bra e kevelt E, Da nell R, Wautier K, Evans B, Brinkworth L

and Fisk AT (2004). Bioaccu m u lation, biotransformat ion, and bioc hem i cal ef fects of brom inated dipheny l ethers in juvenile lake trout ( Sa lvelinus nama ycush ). Environ Sci Technol 38: 149 6-5 04.

28U.S. EPA (1995). Integrate dRisk Infor m ation Sy ste m
. Decabrom odipheny l e ther (DBDPE) (CASRN 1163-19-5). US Environm ental Protection Agency , Offi ce of Research and Develop m ent

. U.S. EPA (2005). Guidelines for Carcin ogen Ri sk Assess ment. U. S. Environm e n tal Protection

Agency , Risk Asse ss ment Forum

. Viberg H, Fredriksson A an d Eriksson P (2002)

. Neonatal exposure to the brom inated flam e

retardant 2,2' ,4,4' , 5-pentabrom odiphenyl ether causes altered suscept i bilit y in the c holinergic transm itter sy stem in the adult m ouse. Toxicol Sci67:1 04-7. Viberg H, Fredriksson A an d Eriksson P (2003a). Neo n atal exposure to pol ybro m inated diph eny l

ether (PBDE 153) disrupts spontaneous behaviour, im pairs learning and m e mory , and decreases hippocam pal cholinergic receptors in adult m i c e
. Toxicol Appl Pharmacol 192:9 5 -106. Viberg H, Fredriksson A, Jakobsson E, Or n U and Eriksson P (20 0 3b). Neurobe havioral derangem e nts in adult m i ce receiving decabro m i nateddiphenyl ether (PBDE 209) during a defined perio dof neo n atal brain develop m ent. Toxicol Sci76:1 12-2 0

. Walsh G, Yoder M, McLaughlin L and Lores E (1987). Responses of m arine un icellular alga e to

brom inated organic co m pounds in sixgr owth m e dia. Ecotox Environ S a fety14: 215-2 2

. WHO (1994). Brom inated Dipheny l Eth e rs. Environm ental Health Criteria 162 . World Health

Organization, International Programme on Chem ical Safety . Geneva, Switzerland. WIL Research Laboratories (1984). 90- day dietary study i nrats with pentabrom odipheny l o x i d e

(DE-71) (Final Report). Subm itted to U. S. EPA under TSCA Section 8D, Fiche no. OTS05243 36

. Wilford BH, Harner T, Zhu J, Shoeib M and Jones KC (2004). Passive sam p ling survey of pol y b r o m i nated dipheny l ether flam e retardants in ind oor and outd o o r air in Ottawa, Canada: i m plications for sources and exposure. E n viron Sci Technol 38 :5 312 -8

. Wolkers H, van Bavel B, Derocher AE, Wiig O, Kovacs KM, Ly dersen C and Lindstrom G (2004). Congener-specifi c accu m u lation and food chain transfer of pol y b r o m i nat e d diphenyl ethers in two arctic food chains. Environ Sci Technol 3 8 :166 7-74

. Wollenberger L, Dinan L and Breitholtz M (2005) . Brom inated flame reta rdants: activities in a crustace an developm ent tes t and in an ec dy steroid screening assay

. Environ Toxicol Chem 24:40 0-7. Zhou T, Ross DG, DeVito MJ and Crofton KM (20 0 1 ) . Effects of short-term in vivo exp o sure to pol y b r o m i nated dipheny l ethers on thy r o i d horm on es and hepatic enzy m e activit ies in weanling rats. Toxicol Sci61:7 6 -82. Zhou T, Tay l or MM, DeVito MJ and Cr ofton KM (2 0 02). Develop m ental exposure to brom inated

dipheny l ethers results in thy r oid horm one disruptio n. Toxicol Sci6 6 :105- 16. Zhu LY and Hites RA (20 04). Tem poral trends and s p atial distributions of br ominated flam e retardants in archived fi shes fro m the G r eat Lakes. Environ Sci Technol 38 :2 779 -8 4

.
29APPENDIX B. Selected Intern ational Activities on PBDEs European Union (EU)

. The use of both pentaB DE and octaBDE in the EU was banned as of August 2004. In 2004, the EU reached an agreem ent with th e European chem ical industry for the industry to conduct a voluntary prog ram to re duce em issions of decaBDE, and to con duct a program to m onitor decaBDE in the environm ent. In add itio n, the EU announced it will sponso r a study of developm ental neuro t oxicity in laboratory anim als for decaBDE. The EU’s Restriction on Hazardous Substances (RoHS) directive wi ll pro h ibit the use of certain chem icals in electrical and electr onic equipm ent as of July 2006. DecaBDE had been on the list of chem icals to be prohibi ted, but the EU granted an exem ption for decaBDE in October 200 5. The EU is also funding the FIRE project (Flam e retardants Integrated Risk assessm ent for Endocrine effects). The objective of the FIRE project is to conduct toxicological studies and exposure assessm ents to characterize th e possible em erging health risk for hum ans and wildlife of PBDEs, tetrabrom obi sphenol A and hexabromocyclododecane by endocrin e related m echanism s
. FIRE is being conducted bya partn e rsh i p of m u ltiple resear ch centers a c ross E urope; se e www.riv m .nl/fire for m o re inform ation.
Intern ational Agreem ents on Pers is tentOrganic Po llutants (POPs)

. PentaB DE has been proposed by Norway for listing under two inte rnational agreem ents: the United Nations Econom ic Comm ission for Europe (UNECE ) Convention on Long-range Transboundary Air Pollution (LRTAP) Protocol on POPs, and the United Nations Environm ent Program (UNEP) Stockholm Convention on P O Ps. EPA, with other interested U.S. federal agencies, is actively involved in the consider ation of the proposals inaccordance with the treaties’ respective review pro cesses and the participatory st atus of the U.S. under these agreem ents. For m o re inform ation on the LRTAP POPs protocol and the proposal by Norway, see http://www.unece.org/env/lrtap/welcom e.ht m l , 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/welcom e .23.ht m l

. For inform a tion on the Stockholm Convention and Norway’s proposal, see http://www.pops.int/default.htm , http://www.pops.int/docum ents/m eeti ngs/cop_1/chem listing/Default.htm , and the Report of

the First m eeting of the Persis tent Organic Pollutants Review Comm ittee at http://www.pops.int/docum ents/m eetings/ poprc/m eeting_docs/reports/default.htm

. Organization for Econom ic Cooper a tion and Developm ent (OECD). The Brom inated Flam e Retardant (BFR) Clearinghouse of the OECD has developed hazard/risk inform ation fact sheets o nthe PBDEs, as well as HBCD and TBBPA, and has identified critical data gaps. OECD intends to fo llow the developm ent of new inform ation on BFRs, update the fact sheets every 2-3 years, and work to im prove cooperation between producers and users of BFRs in order to reduce em issions to the environm ent.

30Arctic Council

. The Arctic Council is an inter-governm ental forum addressing Arctic issues whose m e mbers include Canada, Denm ark, Finland, Iceland, Norway, Sweden, the Russian Federation and the United States. Th e objectives of the Council’s Brom inated Flam e Retardants Project are to: red u ce or e lim inate sources and releases of BFRs that are found in the Arctic environm ent; identi fy and develop saf e waste-handling and recycling practices for products containing br ominated flam e retardants; and identify alternative flam e retardant chem icals and t echnologies and prom ot e saf e alte rnatives.

31APPENDI X C. PBDE Research and Assessm ent Activities Conducted by or Funded by EPA

Levels in th e Environment and Biota
Breast M ilk Measurem ents in Calif o rnia Under a grant from EPA, the California Envi ronm ental Prote c tion Agenc yis collec tin g breast m ilk sam p les and analyzing th em for the presence of PBDEs. Analysis of PBDEs in Br east Milk and House Dust EPA plans to issue a co operative ag reem ent to m easure PBDEs and hexabrom ocyclododecan e (HBCD) in breast m i lk; assess whether levels in dust correlate with body burdens of PBDEs and HBCD; expl ore whether body burdens of PBDEs are decreased in the subjects via lactation; and explore possibl e biological differences am ong wom e n that m i ght explain va riability in body burdens. Pilot Study on Concentrations of PBDEs in Human Milk EPA has funded a study by Pennsylvania State U n iversity and the Centers for Disease Control and Prevention (CDC) to m e asure conc e n trations of PBDEs in hum an m ilk breast m ilk in two very different populatio ns of 20 wom e n each: Am ish women, and nonAm ish woman living in more traditional suburba n settings in Pennsylvania. The purpose of the study is to assess whethe r lifestyle factors, dem ographi cs, or other determ inants of exposures appear to be correlated with levels of these chem i c als. Methods Advancem ent in Milk Analysis As part of the Methods Advancem e n t in Mi lk A n alysis (MA M A) study, in support of the National Children’s Study, scientists in EPA’s National Health and Environm ental Effects Research Laboratory (NHEERL) are working in collaboration with the CDC to m easure and identify PBDEs present in the m ilk and serum of wom e n in North Carolina. The research will ass e ss diet, lifesty le, occ upatio n, stage of lactation, sam p le collectio n and storage m e thods as significant variables. PDBEs in Lake Superior W a tershed EPA has funded a study by the Minnesota Poll ution Control Agency (MPCA) to assess the prev alen ce, potential for local so urces and accum u lation trends of PBDEs in the St. Louis River and western Lake Superior watershed. This project will estimate the prevalence o f PBDEs in surficial sed i m e nts and fish. Trends in PBDE accum u lation in am bient and industrially -im p acted lo cation s will be exam ined by analyzin g sedim e nt cores from a rem o te lake and the Duluth-Superior Harbor. Levels of PBDEs in Eggs of W i sconsin Corm or ants EPA has funded a W i sconsin Departm e nt of Natural Resources project to investigate the presence and levels of PBDEs in double crested corm orant eggs taken from Lake Michigan and the Bay of Green Bay. Corm orant eggs to be analyzed for PBDEs include

32archived eggs collected by the U.S. Fishand W i ldlife Servic e during the 1970s, 1980s and 1990s (between 25 and 40 eggs). PBDEs in Cord Blood, Great Lakes Sedim e nts and Fish Under an EPA STAR (Science to Achieve Results) grant to Indiana University, researchers will m easure PBDE concentration s in um bilical cord blood from 50 newborn U.S. infants and sam p les of their m o thers’ blood collected at delivery to assess fetal exposure to PBDEs. The researchers will al so measure PBDEs in Great Lakes sedim e nt cores and fish to assess long term trends of PBDEs in environm ent. PBDEs at the Calum e t W a ter Reclam ation Plant (Chicago) This project will characteri ze levels of 14 PBDE conge ners in aqueous and sludge sam p les at various s t age s in the tre a tm en t f acility , includ ing the inf l uent, ef f l uent, digestion sludge, and final sludge product. The project is a screening level analysis of the fate (including transform a tions and degradati ons ) of PBDEs within th e water rec l am ation plant. This is a collaborative effort among U. S. EPA, the U.S. Departm e nt of Agriculture (USDA), the U.S. Geological Survey, and th e Metropolitan W a ter Reclamation District of Greater C h icago. Samples will b e collect ed in 2005 and early 2006, with a final report expected in the summ er of 2006.
POTW Measurem ents of PBDEs A scientist in EPA Regi on 10 m easured levels of PBDEs in sam p les of effluents and biosolids collected from five public ly -owned tre a tm ent works (POTW s ) in the state of Washington in 2002.
End-of-Life/Disposal Leaching of Hazardous Che m icals fr om Discard e d Electronic Devices EPA has provided funding to the Universi ty of Florida to evaluate potential environm ental im pact of flam e retardants in p l as tics in electro ni c devices, including potential for leach ing of flam e retardants from the plas tics. Debrom ination and Biotransform ation of PBDEs in sedim e nts Under an EPA STAR grant to Purdue Un iversity, resear che r s will ass e ss whether decaBDE undergoes red u ctive d e bro m ination and, if so, will quantify th e products of this biotransform ation.
Com bustion-derived PBDEs and PBDD/Fs: El ectronics recycling and municipal w a ste EPA’s National Risk Managem e nt Laboratory has been studying the incineration of m a terials th at m ay contain PBDEs. Resear chers have m easured brom inated organic com pounds in m unicipal waste com b ustor flue gas; exam ined incineration of recycled phone boards, m o therboards and keyboards; and taken sam p les from a municipal waste com bustor and to analyze for presence of br om inated organic com pounds. They are now developing m e thods to m easure PBDEs and brom inated dioxins and furans in com bustor em ission samples.

33PBDEs Toxicology and Health Risk Assessmen t Data for Calculating a pentaBDE Margin of Exposure EPA has issued a contract to analyze leve ls of PBDEs in blood sam p les from pregnant rats, fetuses and offspring exposed to the co mm er cial pentaB DE m i xture, DE-71. These data will allow com p arison of blood or adipos e tissue concentrations in hum ans to those found in rats for what appear to be the cr itical endpoints in rodent studies. This inform ation should allow for a screening level analysis of the m argin-of-exposure for this class of chem icals. Neurological Consequences of PBDE-Induced Decreases in Thyroid Horm ones During Developm ent EPA’s NHEERL is conducting animal studie s of the relationship between thyroid horm one de creases caused by PBDEs duri ng developm ent and alterations in neurobehavioral outcomes. Research is currently focused on the comm er cial p e ntaB DE m i xture, DE-71. Low Dose Effects of Thyroid Toxicants on Neurodevelopm ent Under an EPA STAR grant, research ers at th e University of Massachusetts are exam ining the effects o f several thyr oid tox i cants , including PBDEs, on neurodevelopm ental endpoints in rats. The s t udy will characterize dos e-respon se relationship s between PBDE levels, thyroid horm one levels, and neurodevelopm ental endpoints. Studies of Potential Endocrine Disruption by pentaBDE Researchers in EPA’s NHEERL use d the co mmercial pentaBDE product and individual PBDE congeners contained in that m i xture to te st the sensitivity of different test rat study protocols for identifying thyroid active chem icals, and to identify potential endocrine disrupting ef fects. This work has beenpublished by T.E. Stoker and colleagues in Toxicolog i cal Scien ces (2004) and Toxicology and Applied Pharmacology(2005). Toxicity and Estrogenic Ac tivity of Polybrom inated Diphenyl Ethers (P BDEs) Under a grant from EPA, the W i sconsin Departm e nt of Natural Resources is conducting resear ch to : 1) dete rm ine estrog enic activ ity of BDE-47 and BDE-99 using the E-screen assay; 2) determ ine the acute and chronic toxi city of BDE-47 to the aquatic invertebrate, Ceriodaphnia dubia ; 3) determ ine th e concentration of PBDEs in sedim e nts of the Sheboygan River basin; and 4) determ ine th e concentration of PBDEs in wastewater treatm ent plant and industrial efflue nts in the Sheboygan River basin. PBDEs/PCBs and Thyroid Outcom es An EPA STAR grant is funding research by the W i sconsin Departm e nt of Health to characterize exposure to PBDEs from consum p tion of Lake Michigan sport fish and to determ ine mechanism s by which PBDEs in Gr eat Lakes fish m ay act separately or synergistically with PCB exposur e to im pair thyroid function.

34Pharm acokinetics of PBDEs in Mice Scientists in EPA’s NHEERL are inv e stig ati ng the absorption, distr i bution , m e tabolis m, and excretion of the tetraBDE conge ner BDE- 47 in adult m i ce and during developm ent. A physiologically based pharm acokinetic m odel is being developed to predict the behavior un der m u ltiple scenarios. T h e tissu e dis tribution, m e tabolism , and elim ination of pentaBDE congeners BDE-99 and -100, and hexaBDE congener BDE-153 are also being investigated in m i ce. Articles re porting on this work by D.F. Staskal and colleagues have been published in T oxicolog i cal Sciences (2005). Fetal Exposure Modeling An EPA STAR grant to Research Triangle In stitute is supporting work to develop a physiologically-based pharm acokinetic (PBP K) model for BDE-47 and BDE-99 in an anim al m o del system (rats) that can be used to estim ate fetal exposures to PBDEs in hum ans. Necessary p art itioning and m e tabo lic param e ters will b e m easured using in- v ivo and in-v itro experim e nts

. The developed PBPK model will b e useful for studying dif f e rent asp ects of expo sure, inc l uding the im pact of chronic and inte rm ittent expo sur e s on tim e-sens itiv e, develo pm ental events. The exp o sures of a g r oup of m o thers and th eir newborn children to the target congeners will be determ ined. Mode of Action for Developm en tal Neurotoxicity of PBDEs Scientists in EPA’s NHEERL ar e conducting research to eval uate intracel lular signaling as a potential m ode of ac tion for the devel opm ental neurotoxicity of PBDEs. Both in vitro and in vivo app r oac h es will b e utilized to ad dress th is iss u e in PBDE m i xtures and selected individual congeners. The in vitro ef f ects will b e co mpared with in vivo stud ies in term s of t h e effects an d the concentrations at which effects are observed. In addition, the results from PBDE mixtur es and individual congeners will be com p ared with other structurally related chem icals. This research will aid in understand ing a comm on mode of developm ental neurotoxicity for th es e persistentchem icals. Developm ental Neurotoxic ity of Comm ercial pentaBDE and BDE-47 in Mice Scientists in EPA’s NHEERL ar e conducting research to repe at the studies of Eriksson and co-workers that have found developm enta l neurotoxic effects of PBDEs in m i ce. These stud ies will also conduct long -term dos ing of the dam as well as the pup and the body burden s will be d e term ined both experim e ntally and by pharm acokinetic m odeling approaches. Bioavailability of PBDEs from Hous e Dust Scientists in EPA’s NHEERL are collaborat ing with scientists at USDA and Duke University to investigate the bioav a ilability of PBDEs from dust in rats. Standardized sam p les of house dust will be used and over 20 PBDE conge ners m easured.
VCCE P Chem icals o f potential concern to ch ildren’s health are the subject of evaluation in the pilot Volunt ary Child ren ’ s Chem ical Ev aluation Program (VCCEP). VCCEP was developed to ensure that ther e are ad equate pub licly availab l e data to asse ss the im pact that industrial chem icals m ay have on children. PentaBDE, octaBDE and decaBDE are

35am ong the chem icals being assessed in the VCCE P pilot. Further in formation regarding VCCEP is availab l e at http://www.epa.gov/chemrtk/vccep

. IRIS Assessm e nts for PBDEs EPA is conducting reviews of the available to xicology data f or tetra-, penta-, hexa- and decaBDE congeners und er its Integrated Risk Inf o rm ation System (IRIS) program

. Com p letion of these assessm en ts is projected for 2006.
Alternatives Analysis Furniture Flam e Retardancy Partners hip The Furniture Flam e Retardancy Partnership is a joint venture of th e furniture industry, chem ical m a nufacturers, environm ental groups and EPA to better understand fire safety options for the furniture industry. T h rough th e F urniture Flam e Retardancy Partnership, EPA and its partners hope to identify and m ove toward environm entally friendly approaches to m eeting fire safety standards. The partnership initially focused on providing up-to-date toxicolo gical and environm ental inform ation on fl am e retardants used in furniture foam , a s alternatives to pentaBDE, so that furn iture m anufacturers and suppliers are able to m a ke inform ed decisions about which chem icals to use. The Partnership also plans to develop a process fo r identifying and developing data needed to assess po tential risks fro mfla m e retardan t ch em i cals used in furniture. More inf o rm ation is ava ilab l e at http://www.epa.gov/opptintr/dfe/pub s/projects/flam eret/index.htm

. Market Analysis of PBDEs In 2003, an EPA contractor prep ared a review of m arket data on PBDEs. The report included a review of PBDEs suppliers, usage data, and a review of inform ation available at thattim e on alte rnativ es to pent aB DE in flexible polyurethane foam

. Regulatory Activities SNUR for pentaBDE and octaBDE EPA has proposed a Significant New Use Ru le (SNUR) under section 5(a)(2) of the Toxic Substances Control Act (TSCA) that would require m anufacturers and im porters to notify EPA at least 90 days before commencing the m anufacture or im port of pentaBDE or octaBDE. The required notice would provide EPA with the opportunity to evaluate each chem ical substance’s u s e, and if necessary, to prohibit or lim it such activity before it occurs. EPA expects to finalize the SNUR in 2006. Residential Furnitur e SNUR EPA is preparing to propose a SNUR under sect ion 5(a)(2) of TSCA for flam e retardants identified as candidates for use to m eet the residential upholster ed furniture (RUF) flammability standard s under consideration by the State of California and the U.S. Consum er Product Safety Comm ission (CPSC). Sixteen chem ical substances/categories,

36including decaBDE, are being c onsidered for inclusion in the SNUR. The SNUR wou l d require persons who intend to m anufacture, im port, or process any of these chem ical substances, or articles contai n i ng th em , for use as a flam e re tardant (FR) in RUF to notif y EPA at least 90 days before comm encing such activity. The required notice would provide EP A with the opportunity to evaluate each chem ical substance’s use as a F R in RUF, and if necessary, to prohibit or lim it such a c tiv ity bef o r e it oc curs. Monitoring of Drinking Water EPA proposed its Unregulated Contam inant Monitoring Regulation (UCMR 2) under the Safe Drinking W a ter Act in the Federa l Register on August 22, 2005 (70 FR 49093). Under UCMR 2, EPA is proposing to require 3,910 public water system s to m onitor for 26 unregulated chem icals, including BD E conge ners 47, 99, 100 and 153. EPA expects to publish the final regulation in 2006 and m onitoring is expected to occur during the 2007 to 2010 tim efra m e
. The data collected thro ugh the UCMR program will be us ed to assess the level of these chem icals in finish ed drinking water and assist the Agency in deciding whether a drinking wa ter regulation is needed.

37APPE NDI X D. PB DE s Research and Assessm ent Activ i ties a t Other U.S. Federal Agencies Centers for Disease Control and Prevention (CDC)

. As part of the Natio nal Health and Nutrition Exam ination Survey (NHANES), CDC is analyzing blood sam p les collected in 2003-2004 for levels of 10 PBDE congeners. Re sults of this nati onally-representative statistical sample are expect ed in 2006, for two age groups (ages 12- 19 years, and age 20 and older) as well as gender and race/ethnici ty sub-groups. The survey is continuous, and additional re sults will be available in f u ture years to allow evaluation of any trends. C D C is also conducting several additional studies of P B DEs ai m e d at determ ining body burdens in segm ents of t h e population that m ay be m o re highly exposed and identifying which routes of exposure are of m a in im portance for the hum an population. Food and Drug Adm i nistration (FDA)

. FDA has been working with the food and feed industries to understand sources of PBDEs and other persistent contam inants. FDA is conducting studies on m e thods for the analysis of PBDEs in different food and feed m a trices, an d has m easured PBDEs in select fish sam p les. In 2006, FDA will in clude appropriate food and feed in a sam p ling program to asses s PBDE levels, and will us e this inform ation to assess dietary PBDE exposures to determ ine appropriate risk m anage ment options. National Ins titute of Standards and Technology (NIST)

. NIST is conducting research to exam ine the rates by which PBDEs are em itted f r o m plastic s over tim e due to natural weathering, increased temperat ures and irradiant exposures

. NIST is also conducting studies to measure PBDEs in house dust, Ca lifornia sea lions, and rainbow trout. National Oceanic and Atmos pheric Ad m i nistration (NOAA)

. NOAA has m e asured levels of PBDEs in m u ssel tissue and sedim e nt s near the W o rld Trade Center site, and in sedim e nts in the Chesapeake Bay. National Toxicology Program (NTP)

. NTP is currently conduc ting a subchronic toxicity study of commercial pentaBDE (DE-71) in rats and m i ce. NTP is also planning to do a chronic s tud y to look for cancer po tential, butplans for this s t udy will not be finalized until after th e subchronic study is co mpleted. In addition, NTP is conducting studies o f gene expression and tissue distribution for BDE congeners 47, 99, and 153.
U.S. Departm e nt of Agr i culture (USDA)

. USDA is conducting research on the absorption, disposition, m e tabolism , and excr etion (ADME) of PBDEs. Studies of ADME in rats have been conducted o ncommercial pentaBDE, octaBDE and decaBDE m i xtures. Rodent ADME studies have also been conducted on BDE congeners 47, 99, 100, 154 and 209. Studies in rats are planned for BDEs 153 a nd 183, along with further study of BDE-209. ADME studies of the pent aBDE m i xture and BDE-47 are also being conducted in chickens. USDA has also c onducted som e m e asurem ents of PBDE levels in m eats and poultry, and will be ex tending th es e analyses to addition a l food sam p les.

38U.S. Geological Survey (USGS)

. The USGS is conducting studies to: measure indoor air levels of PBDEs in hom es and offices; m easure levels of PBDEs in fi sh and fisheating birds; evaluate the environm ental fate of P B DEs; and determ ine the potential for weathered recycled computer equ i p m ent to contam inate nearby soil and sedim e nts.

39