Analytical and environmental aspects of the flame retardant tetrabromobisphenol-A and its derivatives

R

At

ASa

b

c

d

a

AA

KTTAEHRR

C

0d

Journal of Chromatography A, 1216 (2009) 346–363

Contents lists available at ScienceDirect

Journal of Chromatography A

journa l homepage: www.e lsev ier .com/ locate /chroma

eview

nalytical and environmental aspects of the flame retardantetrabromobisphenol-A and its derivatives

drian Covacia,∗, Stefan Voorspoelsb, Mohamed Abou-Elwafa Abdallahc, Tinne Geensa,tuart Harradc, Robin J. Lawd

Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumInstitute for Reference Materials and Measurements (IRMM), European Commission, Joint Research Centre, Retieseweg 111, B-2440 Geel, BelgiumDivision of Environmental Health and Risk Management, School of Geography, Earth and Environmental Sciences, University of Birmingham, Birmingham B15 2TT, UKThe Centre for Environment, Fisheries and Aquaculture Science, Cefas Burnham Laboratory, Remembrance Avenue, Burnham on Crouch, Essex CM0 8HA, UK

r t i c l e i n f o

rticle history:vailable online 14 August 2008

eywords:etrabromobisphenol-ABBPAnalytical methodsnvironmental levelsuman exposure

a b s t r a c t

The present article reviews the available literature on the analytical and environmental aspects oftetrabromobisphenol-A (TBBP-A), a currently intensively used brominated flame retardant (BFR). Ana-lytical methods, including sample preparation, chromatographic separation, detection techniques, andquality control are discussed. An important recent development in the analysis of TBBP-A is the grow-ing tendency for liquid chromatographic techniques. At the detection stage, mass-spectrometry is awell-established and reliable technology in the identification and quantification of TBBP-A. Althoughinterlaboratory exercises for BFRs have grown in popularity in the last 10 years, only a few participat-ing laboratories report concentrations for TBBP-A. Environmental levels of TBBP-A in abiotic and bioticmatrices are low, probably due to the major use of TBBP-A as reactive FR. As a consequence, the expected
egulatory aspects
eview human exposure is low. This is in agreement with the EU risk assessment that concluded that there is norisk for humans concerning TBBP-A exposure. Much less analytical and environmental information exists
for the various groups of TBBP-A derivatives which are largely used as additive flame retardants.
© 2008 Elsevier B.V. All rights reserved.

ontents

1. TBBP-A—general information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3471.1. Production and usage volumes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3471.2. Applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3471.3. Regulatory aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3481.4. Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3481.5. TBBP-A derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3501.6. Strategy of the review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351

2. Analytical methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3512.1. Physico-chemical properties of TBBP-A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3512.2. Extraction and clean-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351

2.2.1. Abiotic samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3512.2.2. Biological samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3532.2.3. Fractionation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354

2.3. GC–MS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.4. LC–MS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.5. Capillary electrophoresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.6. Quality assurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.7. Analytical methods for TBBP-A derivatives. . . . . . . . . . . . . . . . . . . . . . . . .

∗ Corresponding author. Tel.: +32 3 820 2704; fax: +32 3 820 2722.E-mail address: [email protected] (A. Covaci).

021-9673/$ – see front matter © 2008 Elsevier B.V. All rights reserved.oi:10.1016/j.chroma.2008.08.035

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357

http://www.sciencedirect.com/science/journal/00219673

http://www.elsevier.com/locate/chroma

mailto:[email protected]

dx.doi.org/10.1016/j.chroma.2008.08.035

A. Covaci et al. / J. Chromatogr. A 1216 (2009) 346–363 347

3. Environmental levels (TBBP-A and derivatives) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3573.1. Abiotic matrices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357

3.1.1. Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3573.1.2. Indoor dust . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3583.1.3. Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3593.1.4. Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3593.1.5. Sewage sludge and sediment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359

3.2. Biological matrices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3603.3. Food. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3603.4. Humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361

4. Concluding remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362

. . . . . .

1

1

Utihobd

wtrigttAa(1io

aEeAapu

fio4

1

FcatptFi

oloTTradsbfe

b

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. TBBP-A—general information

.1. Production and usage volumes

Tetrabromobisphenol-A (TBBP-A) is currently produced in theSA, Israel and Japan, but not in the EU [1,2]. The industrial produc-

ion process involves the bromination of bisphenol-A with brominen the presence of a solvent, such as methanol or a halocarbon, 50%ydrobromic acid or aqueous alkyl monoethers. Due to the naturef the process and the by-products (hydrobromic acid and methylromide) that can be formed, the production process is largely con-ucted in closed systems [3].

TBBP-A was reported as the brominated flame retardant (BFR)ith the highest production volume, covering around 60% of

he total BFR market [4,5]. Yet the most recent informationeleased by the Bromine Science and Environmental Forum (BSEF)s based upon the market demand figures for 2001 [5]. Thelobal consumption estimates of TBBP-A vary from 120,000 [6]o 150,000 tons/year, including TBBP-A derivatives [7]. At thatime (2001), Asia registered the highest consumption of TBBP-

(89,400 tons/year) followed by the Americas (18,000 tons/year)nd Europe (11,600 tons/year). The European BFR Industry PanelEBFRIP) reported the size of the global TBBP-A market to be70,000 tons in 2004 [8]. They also state that the market is increas-ng (Fig. 1) and that a shift in the consumption volume can bebserved towards Asia.

TBBP-A can be imported into a country in various forms, eithers a primary product or in finished or partially finished products.xamples include plastics, printed circuit boards and electronic
quipment. These imports may be an important source of TBBP-in the EU, but limited information is available. The TBBP-A risk
ssessment estimated the imported amount of TBBP-A in the EU asrimary product to be 13,800 tons/year, in partially finished prod-cts (e.g. polymers, epoxy resins) around 6000 tons/year and in

Fig. 1. TBBP-A market size in metric tons during 1995–2004 (as given in Ref. [8]).

rtafiriuTiet

fiAectlc

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362

nished products around 20,200 tons/year [1,2]. The total amountf TBBP-A imported into the EU was estimated to be around0,000 tons/year [1,2].

.2. Applications

BSEF [5] reported that 58% of TBBP-A is used as a reactiveR in epoxy, polycarbonate and phenolic resins in printed cir-uit boards, 18% is used for the production of TBBP-A derivativesnd oligomers, while 18% is used as additive FR in the manufac-ure of acrylonitrile–butadiene–styrene (ABS) resins or high impactolystyrene (HIPS). However, BFR industry spokespersons claimhat, since it was not effective, TBBP-A was never used as an additiveR in HIPS [1,2], while the European Flame Retardants Associationndicates that TBBP-A is “possibly” used in HIPS [9].

TBBP-A is used primarily as an intermediate in the manufacturef epoxy and polycarbonate resins, where it becomes bound cova-ently in the polymer and is thus an integral part of the product. Thenly potential for exposure that remains originates from un-reactedBBP-A, if an excess has been added during the production process.BBP-A is also used as a reactive FR in polycarbonate and unsatu-ated polyester resins. Polycarbonates are used in communicationnd electronics equipment, electronic appliances, transportationevices, sports and recreation equipment, lighting fixtures andigns. Unsaturated polyesters are used for making simulated mar-le floor tiles, bowling balls, furniture parts, coupling compoundsor sewer pipes, automotive patching compounds, buttons, and forncapsulating electrical devices.

Commercial FR epoxy resins contain up to approximately 20%romine. The main use of these resins is in the manufacturing ofigid epoxy laminated printed circuit boards. There are two mainypes of rigid or reinforced laminated printed circuit boards thatre commonly used [10]. These are usually either based on glassber reinforced epoxy resin (designated FR4) or cellulose papereinforced phenolic resin (designated FR2), but a range of types available. The FR4-type laminate is by far the most commonlysed laminate and is typically made by reaction of around 15–17%BBP-A in the epoxy resin [10]. The most commonly used laminates approximately 1.6-mm thick and the TBBP-A content has beenstimated at around 0.42 kg/m2 [10]. This type of laminate is usedypically in computers and telecommunications equipment.

As an additive FR, TBBP-A is generally used with antimony oxideor optimum performance [6]. Antimony oxide is not used generallyn conjunction with TBBP-A in reactive FR applications [1,2]. TBBP-

is considered an alternative additive FR to octabromodiphenyl
ther (OctaBDE) mixture in ABS. The use of OctaBDE in this appli-ation is no longer allowed in the EU [11]. It is therefore possiblehat the amount of TBBP-A used in this application in particu-ar could increase in the future. As additive FR, it does not reacthemically with the other components of the polymer, and there-

3 atogr.

fwoauncbTmtTwt

bm4pHd

1

AwwsteeeCoip

f2ourctfihra

cnrrafitPTsidrT

bu

ibsa[taturE

dbesa[dhewTp

cbuEA[taw

blha

dTedApuwe

1

Tate

48 A. Covaci et al. / J. Chrom

ore may leach out of the polymer matrix after incorporation,ith important implications for human exposure. Concentrations

f TBBP-A commonly found in these applications are between 10%nd 20% (by weight), depending on the polymer. ABS resins aresed in automotive parts, pipes and fittings, refrigerators, busi-ess machines, and telephones. HIPS resins are used in packaging,onsumer products, electrical and electronic equipment, furniture,uilding and construction materials [3]. The largest additive use ofBBP-A is found in television casings [1,2]. Other uses include: PConitor casings, components in printers, fax machines and pho-

ocopiers, vacuum cleaners, coffee machines and plugs/sockets.BBP-A is also used in the manufacture of derivatives, some ofhich are also used as flame retardants, generally in niche applica-

ions, see Section 1.5 [3].A large number of organobromine compounds, such as

romophenols, are naturally produced in the environment,any by marine organisms [12]. In particular bis(3,5-dibromo-

-hydroxyphenyl)methane, structurally similar to TBBP-A, isroduced by the segmented marine worm Thelepus setosus [12].owever, TBBP-A itself has not yet been identified as being pro-uced by natural sources.

.3. Regulatory aspects

Currently, there are no restrictions on the production of TBBP-or its derivatives. In 2003, an EU Directive on the handling ofaste electrical and electronic equipment (WEEE) [13] was adoptedhich contains the following elements: (i) the EU Member States

hall setup separate collection schemes and ensure the properreatment, recovery and disposal of WEEE; (ii) the treatment, recov-ry and disposal of WEEE shall be financed by producers to createconomic incentives to adapt the design of electrical and electronicquipment to the prerequisites of sound waste management; (iii)onsumers shall have the possibility to return their equipment freef charge and need to be informed about the possibilities of return-ng WEEE; (iv) The WEEE Directive requires selective treatment oflastics containing BFRs, including TBBP-A.

In Europe, TPPB-A is on the fourth list of priority chemicals [14]oreseen under European Council (EC) Regulation No. 793/93 of3 March 1993 regarding the evaluation and control of the risksf existing substances. REACH is a recently implemented EU reg-lation on chemicals and their safe use, which deals with theegistration, evaluation, authorization and restriction of chemi-al substances and entered into force on 1st June 2007 [15]. Inhe context of the REACH legislation, TBBP-A will be one of therst substances to go through the registration procedure due to itsigh production volume [5]. All the necessary studies for REACHegistration are already developed in the context of the EU riskssessment.

The EU risk assessment of TBBP-A on human health (Part II) con-luded that there was no human health hazards of concern ando risks were identified [2]. This preliminary report identified noisk for TBBP-A when used as a reactive BFR, such as in the epoxyesins of printed circuit boards. However, the EU environmental riskssessment for TBBP-A confirmed a risk in some scenarios for sur-ace water, sediment and soil when TBBP-A is used as an additiven ABS plastics [1]. BSEF indicates that risks from additive applica-ion are manageable through a Voluntary Emissions Control Actionrogram (VECAP), to which 89% of European customers who useBBP-A in an additive application have agreed to reduce their emis-
ions [8]. Many uncertainties remain regarding the risk assessment,n particular concerning the emission estimates and the biodegra-ation rates in the environment [16]. It should be noted that theisk assessment report also identified a risk if sludge containingBBP-A is applied to agricultural land (see next paragraph). Industry
piprt

A 1216 (2009) 346–363

elieves, however, that this does not happen and that sludge fromser sites is either sent for incineration or to controlled landfills [5].

The EU environmental risk assessment also concluded that theres a need for further information and/or testing [1]. It is possi-le that TBBP-A degrades to bisphenol-A during anaerobic sewageludge treatment processes (which could lead to bisphenol-A beingpplied to soil), or in anaerobic freshwater and marine sediments1,17]. The potential risks to sediment and soil have been assessed inhe updated risk assessment of bisphenol-A, for both reactive anddditive flame retardant uses [17]. Currently, TBBP-A is not listed inhe EU Water Framework Directive, which came into force in Jan-ary 2007 [18]. Hence, there are no European monitoring schemesunning currently to assess the presence of this chemical in theuropean water bodies.

Another possible metabolite/degradation product – TBBP-Aimethyl ether – may meet the screening criteria for a persistent,ioaccumulative and toxic (PBT) substance, albeit using mainlystimated data. Its presence has been investigated in some recenttudies of anaerobic transformation in freshwater aquatic sedimentnd sewage sludge, and anaerobic and aerobic soil transformation1]. Although inconclusive, the results suggest that it is a very minoregradation product. Given that a need for risk reduction measuresas already been identified for some uses (which should reduce thenvironmental burden of the parent compound), no further specificork is recommended to address this issue at the present time.

he risk characterization for the marine environment indicates aossible risk from some applications.

A similar reduction mandate was enacted in Japan in 2001 (Recy-ling of Specified Kinds of Home Appliances), and one is currentlyeing established in China for electronic and electrical waste (Reg-lations on Recycling and Disposal of Waste and Used Householdlectrical Appliances) [19]. The Ministry of Japan included TBBP-in their environmental surveillance program beginning in 2003

20]. China is currently preparing legislation on WEEE, similar tohe EU Directive concerning WEEE 2002/96/EC, which is timelys China is becoming a major recipient of electronic and electricalaste [21].

In North America the legislative focus is still firmly on the poly-rominated diphenyl ethers (PBDEs), while TBBP-A has received

ittle attention to date. Canada is in the process of assessing theuman and environmental risks of TBBP-A and its diglycidyl andllyl ether derivatives [22].

In June 2005, the Australian Ministry for Health and Ageingeclared TBBP-A as a “Priority Existing Chemical”. In the near future,BBP-A will therefore be subjected to an assessment of its potentialffects to human health and the environment, which will be con-ucted under the National Industrial Chemicals Notification andssessment Scheme. The Australian authorities are currently com-iling from importers and producers information on quantities andse of these substances as well as general scientific informationhich is already available. No regulatory actions are under consid-

ration elsewhere [5].

.4. Toxicity

Oral administration studies with rats and mice indicate thatBBP-A has a low acute toxicity, with LD50 >5 and >4 g/kg for ratsnd mice, respectively [3]. Due to the structural resemblance tohe thyroid hormone thyroxin (T4) and bisphenol A, a suspectedndocrine disruptor [17], the major concern regarding TBBP-A is its
otential as an endocrine disruptor. The thyroid hormonal activ-
ty of TBBP-A was examined by Kitamura et al. [23] using ratituitary GH3 cell lines, in which release of growth hormone is thy-oid hormone-dependent. In those experiments, TBBP-A stimulatedhe production of growth hormone and enhanced the prolifera-

A. Covaci et al. / J. Chromatogr. A 1216 (2009) 346–363 349

Fig. 2. Chemical structures of TBBP-A (a) and principal derivatives: TBBP-A dimethyl ether (b), TBBP-A bis(2,3-dibromopropyl ether) (c), TBBP-A bis(allyl ether) (d), TBBP-Abis(2-hydroxyethyl ether) (e), TBBP-A brominated epoxy oligomer end-capped with epoxy groups (f), TBBP-A brominated epoxy oligomer end-capped with tribromophenol(g), TBBP-A carbonate oligomer end-capped with phenyl groups (h) and TBBP-A carbonate oligomer end-capped with tribromophenol (i).

350 A. Covaci et al. / J. Chromatogr. A 1216 (2009) 346–363

Table 1Main uses of TBBP-A derivative flame retardants

Compound Use

Tetrabromobisphenol-A dimethyl ether Not produced commerciallyTetrabromobisphenol-A dibromopropyl ether Additive flame retardant in polyolefins and copolymers such as polyethylene, polypropylene

and polybutylenesTetrabromobisphenol-A bis(allyl ether) Reactive flame retardant in polystyrene foamsTetrabromobisphenol-A bis(2-hydroxyethyl ether) An additive flame retardant in engineering polymers, epoxy resins, polyesters, polyurethane,

laminates for electronic circuit boards and adhesives and coatingsT ve flam

thalatT ve flam

todhtwoemToties

iorrwtpn

bpwiasippr

1

mmeoddi

pdIp

jubebob

fo

ecl[d

AbobcBbHptaaT5

wtTta[tdb

da[t

etrabromobisphenol-A brominated epoxy oligomer Reactitereph

etrabromobisphenol-A carbonate oligomer Additi

ion of GH3 cells. TBBP-A similarly also enhanced proliferationf the rat pituitary MtT/E-2 cell lines, whose growth is estrogen-ependent. These results suggest that TBBP-A acts both as a thyroidormone and estrogen agonist [23]. These findings are similaro those of Ghisari [24] who observed a growth of GH3 cellshich could not be counteracted by the inhibiting growth effect

f the anti-estrogen fulvestrant. These data also indicate that theffect of TBBP-A is thyroid hormone-like and estrogen receptor-ediated [24]. In an in vitro study performed by Kester et al. [25],

BBP-A proved to be a rather potent inhibitor of the sulfationf estradiol by estrogen sulfotransferase, an important inactiva-ion pathway of estradiol. Inhibition of this enzyme may lead toncreased bioavailability of estradiol in vivo. The resulting weakstrogen-like properties have been confirmed by several othertudies [26–28].

While TBBP-A produced a thyreomimetic effect on the GH3 pitu-tary cell line (see above), an anti-thyroidal effect was observedn Chinese hamster ovary cells transiently transfected with T3eceptors, as well as an inhibition of the binding of triiodothy-onine (T3) to thyroid hormone receptors [29]. Moreover, TBBP-Aas shown to be a potent in vitro inhibitor for the binding of T4

o transthyretin, the thyroid hormone-binding transport protein inlasma. The binding of TBBP-A is 10 times stronger than that of theatural ligand T4 [30,31].

TBBP-A is also immunotoxic, as demonstrated by in vitro inhi-ition of the expression of CD25, a receptor essential for theroliferation of activated T-cells [32]. Further, TBBP-A neurotoxicityas determined by inhibition in vitro of neurotransmitter uptake

nto synaptosomes and dopamine uptake into synaptic vesicles [33]nd generation of free radicals [34]. Additionally, TBBP-A has beenhown to interfere with cellular signaling pathways [35]. Toxicolog-cal effects, such as severe disorientation, lethargy, decreased eggroduction and decreased reproductive success were observed in aartial life-cycle test with zebrafish (Danio rerio) exposed to envi-onmentally relevant water-borne concentrations of TBBP-A [36].

.5. TBBP-A derivatives

TBBP-A is also used in the manufacture of derivatives [1,2]. Theain derivatives (Fig. 2) produced from TBBP-A are TBBP-A dibro-opropyl ether, TBBP-A bis(allyl ether), TBBP-A bis(2-hydroxyethyl

ther), TBBP-A brominated epoxy oligomer, and TBBP-A carbonateligomers [3]. The main use of these derivatives is as flame retar-ants, usually in specialized (or niche) applications (Table 1). Theseerivatives may be used as either reactive or additive intermediates

n polymer manufacture.
TBBP-A bis(2,3-dibromopropyl ether) is used as an additive FR in
olyolefins and copolymers, such as high density polyethylene, lowensity polyethylene, polypropylene and polybutylenes [3,37,38].

n general, product loadings vary between 1 and 10% (by weight) inolypropylene [39]. Loadings can be reduced when used in con-

utwtp

e retardant in high-impact polystyrene, ABS, ABS/polycarbonate, polybutylenee-alloys, polybutylene terephthalate and thermosetting resinse retardant in ABS and engineering thermoplastics

unction with antimony oxide. Flame retarded polypropylene issed in building applications (mainly in pipes for water discharge,ut also film and sheet for roofing), textiles, and in electrical andlectronic applications such as wire nuts, lamp sockets, coil bob-ins, connectors, wire and cable, housings of electrical appliancesr TV yokes [40]. De Schryver et al. [41] reported that it could alsoe used in high impact polystyrene at 5% by weight.

TBBP-A bis(allyl ether) is used as a reactive FR in polystyreneoams (expandable polystyrene-EPS) [3,37,38]. There is a major lackf data for this derivative.

TBBP-A bis(2-hydroxyethyl ether) is used as an additive FR inngineering polymers (e.g. polybutylene terephthalate and poly-arbonate), epoxy resins, thermoplastic polyesters, polyurethane,aminates for electronic circuit boards, adhesives and coatings3,37,38]. Also for this derivative, there is a major lack ofata.

TBBP-A brominated epoxy oligomers are also known as TBBP-diglycidyl ethers. There are two chemically different types of

rominated epoxy oligomers. One has two epoxy groups at the endf the molecule, similar to epoxy resins used for printed circuitoards (EP-type). The other type, which is TBBP-A epoxy end-apped with tribromophenol (EC-type), has no reactive groups.oth types of oligomer are reactive FRs used in housings forusiness machinery and electrical/electronics parts based uponIPS, ABS, ABS/polycarbonate, polybutylene terephthalate-alloys,olybutylene terephthalate and thermosetting resins. The concen-rations of these FRs in ABS are around 20% (by weight). As wells fully tribromophenol end-capped oligomers, some products arevailable with around 50% end-capping with tribromophenol [42].he molecular weights of the products vary between 700 and0,000 g/mole, and differ depending on the application.

TBBP-A carbonate oligomers are produced by reaction of TBBP-Aith phosgene [37]. In this respect, they can be considered similar

o the reactive use of TBBP-A in polycarbonates described above.hese oligomers are used as additive FRs in ABS and engineeringhermoplastics such as poly(butyleneterephthalate), polycarbon-te, poly(ethyleneterephthalate) and phenol–formaldehyde resins3,37]. Both phenoxy-terminated TBBP-A carbonate oligomers andribromophenoxy-terminated TBBP-A carbonate oligomers are pro-uced [3]. A TBBP-A diglycidyl ether-carbonate oligomer has alsoeen reported.

TBBP-A dimethyl ether (diMe-TBBP-A) is not known to be pro-uced commercially and it is not certain whether it is used asflame retardant [3], but it has been found in the environment

43–45]. The occurrence in the environment can be explained byhe O-methylation of TBBP-A in certain biological processes [46].

Others: bis(hydroxyethyl) TBBP-A ethylene glycol can also be
sed to produce polyester fibers [37]. Ash and Ash [38] indicatedhat TBBP-A diacrylate could be used in automotive coatings andire and cable coatings. A TBBP-A bis(2-ethylether acrylate) deriva-
ive has also been reported. The commercial significance of theseroducts is unclear.

atogr.

1

tpctteTosafP

2

Pdmpatppear

2

taetdn(wawai(otib

2

2

s

(

A. Covaci et al. / J. Chrom

.6. Strategy of the review

All available literature on TBBP-A (analytical methods, levels inhe environment and humans), published until February 2008 ineer-reviewed scientific journals, conference proceedings or offi-ial reports found on the internet, was acquired and classified. Sincehis was not the primary scope of the review, information about theoxicology of TBBP-A was only briefly mentioned. Although sev-ral reviews are available for BFRs [47–49], specific information onBBP-A is often “lost” in the greater dataset available for PBDEsr hexabromocyclododecanes (HBCDs). Therefore, we identified atringent need for a comprehensive review on TBBP-A in which thevailable literature is critically discussed and recommendations forurther research are given. Similar reviews are already available forBDEs [50] and HBCDs [51].

. Analytical methods

Although the literature is abundant in analytical methods forBDEs and HBCDs, there are far fewer methods described for theetermination of TBBP-A. In fact, it seems that TBBP-A has been seenerely as a potential additional analyte and not as a target com-

ound itself, other than in a few cases. Determinations are usuallyccomplished using LC–MS techniques, where TBBP-A is measuredogether with HBCD or other phenolic (halogenated) organic com-ounds. Table 2 summarizes relevant data for selected analyticalrocedures used for the determination of TBBP-A in a wide vari-ty of abiotic and biotic samples. Further information on variousnalytical methods for BFRs, including TBBP-A, has recently beeneviewed [47,48].

.1. Physico-chemical properties of TBBP-A

Due to its distinct physico-chemical properties, the determina-ion of TBBP-A requires specific analytical approaches and thesere highlighted below. The pKa1 and pKa2 values of TBBP-A arestimated at 7.5 and 8.5, respectively [3], which means that in neu-ral environments, a substantial part of the TBBPA is present in itsissociated state. This causes losses in the clean-up steps when aeutral environment combined with polar solvent is maintainedthe polar solvent could just be a small amount of co-extractedater from the sample). Care should be taken to avoid these losses

nd a possible solution is to treat the raw extract with acidifiedater. This results in non-dissociated TBBP-A only, which is driven

lmost quantitatively towards the organic phase. Such behaviours similar to that of other phenolic organohalogenated compoundse.g. pentachlorophenol). These properties have a significant effectn the partitioning of TBBP-A in the environment and biota. Con-rarily to PBDEs and HBCDs, which are neutral compounds, TBBP-As not accumulating in fatty tissues, but it is primarily retained inlood through protein binding.

.2. Extraction and clean-up

.2.1. Abiotic samplesAbiotic matrices reviewed include (i) water, (ii) air, (iii) soil,

ediment and sewage sludge and (iv) polymers (Table 2).

(i) Water. Because of the low concentrations expected in water,
large volumes (up to 1000 mL) are typically required to ensurepositive detection of TBBP-A [52,71]. Suzuki and Hasegawa [52]used solid-phase extraction (SPE) on Abselut Nexus cartridgesas a fast and valuable technique allowing the simultaneousdetermination of TBBP-A (recovery 103 ± 16%) and other BFRs,
A 1216 (2009) 346–363 351

together with a significant reduction in the organic solvent con-sumption from 50 mL dichloromethane (DCM) to 5 mL acetone.

A restricted access media-molecularly imprinted polymer(RAM-MIP) was used for the selective on-line pre-treatmentand enrichment of TBBP-A in a river water sample, followedby separation and determination by LC–MS [54]. The between-day precision for the assay of TBBP-A at 25 pg/mL was 1.6%.Solid-phase micro-extraction (SPME) has been investigatedfor the determination of brominated phenols and TBBP-A inaqueous samples [72]. The extraction procedure involves an insitu acetylation followed by SPME extraction. The studied fac-tors were the type of fiber, extraction mode (direct immersionor headspace), exposure of the fiber directly into the sampleor into the headspace over the sample and extraction tem-perature. The polydimethylsiloxane fiber was found the mostsuitable for the extraction of TBBP-A from water and the high-est response was achieved in headspace mode at 100 ◦C. Theobtained limits of detection (LOD) were at the low pg/mL level.

(ii) Air. For air samples, filters (glass fiber and PUFs) were extractedby sonication and analyzed without further clean-up [55]. Sim-ilarly, Inoue et al. [56] have eluted the filters used for airsampling with methanol (MeOH) and analyzed the extractswithout further clean-up.

iii) Soil, sediment and sewage sludge. The sample preparation forBFR analysis, including TBBP-A, in sewage sludge and soil hasbeen reviewed by Eljarrat and Barcelo [49] and the most com-mon methods are given in Table 2. Soxhlet extraction, a robust,efficient and low-cost technique, is a primary option for thedetermination of BFRs in soils and sediments. In general, mix-tures of acetone and n-hexane in different proportions (1:1or 1:3, v/v) have been found to provide the best recoveriesfor TBBP-A [57]. Pressurized liquid extraction (PLE) has alsobeen evaluated for the analysis of TBBP-A in dried soil, sedi-ments and sewage sludge. Extraction with DCM at 100 ◦C hasbeen found to provide almost quantitative recoveries (∼80%)of TBBP-A [60], providing that several PLE cycles (e.g. 2 × 5 mincycle) instead of a single longer PLE cycle were carried out.

An alternative procedure based on matrix solid-phase dis-persion (MSPD) for sample preparation in the analysis ofhalogenated bisphenol derivatives in river and marine sedi-ment and urban sewage sludge has been developed by Blancoet al. [73]. Approximately 200 mg sewage sludge or sedimentwere acidified with HCl, dried with Na2SO4, followed by mixingwith 1 g C18-modified silica and 2 g Florisil. Acetonitrile (7 mL)delivered clean extracts combined with the highest recoveriesfor TBBP-A (63%).

A liquid–liquid extraction (LLE) followed by SPE has beendeveloped for the simultaneous determination of halogenatedbisphenol-A derivatives, including TBBP-A, in sediment andsludge samples [58]. Samples were extracted with methyltert-butyl ether and the analytes were partitioned using anaqueous solution of NaOH. The extract was subsequently acidi-fied, and enrichment and desalting were performed by passingthe extract over a C18 cartridge and a silica filled cartridge,respectively. After clean-up, the target compounds were deter-mined by LC–MS/MS. The method LOD for sediment and sludgefor TBBP-A was 0.05 ng/g dry weight (dw). Mean recovery ofTBBP-A from spiked samples was 102 ± 5%.

A stir bar coated with poly(dimethysiloxane)-�-cyclodextrinon one side has been prepared for the first time by a sol–gel
method and was coupled with ultrasonic assisted extractionfor the determination of TBBP-A in soil and dust samples byHPLC with diode array detection (DAD) [74]. Extraction time,desorption solvent, concentration of MeOH/acetone and NaClin the matrix, pH, temperature and stirring speed were opti-

352A

.Covacietal./J.Chrom

atogr.A1216

(2009)346–363

Table 2Overview of typical analytical procedures used for the determination of TBBP-A in selected matrices

Sample type Pre-treatment Extraction procedure Clean-up Instrumentalanalysis

Recovery (%) RSD (%) LOD (ng/mL,ng/g, ng/m3)

Reference

WaterLandfill leachate (1000 mL) Filtration Abselut Nexus SPE

(AcN, 5 mL)– LC–APCI-MS/MS 103 13 0.0002 [52]

Wastewater (50 mL) 1 mL of ascorbic acid(0.1M)—to avoid chlorinationduring storage

SPE-C18 cartridges(Bond Elut, 500 mg;Varian)

– LC–ESI-MS/MS >85% – 0.02 [53]

River water (2 mL) Filtration, isotope imprinting – – LC–ESI-MS >95% 1–4 0.01 [54]

AirAir samples (3 m3) 25 mm glass fiber filter and 2

PUF plugs pre-cleaned withMeOH, Acet and DCM

Sonication (2 × 5 mL,2 × 20 min, AcN)

Filtration LC–ESI-MS/MS 75–93 – – [55]

Air samples (10 m3) 47 mm glass fiberfilter + Empore disk (SDB-XD47 mm/0.5 mm)

Elution with 30 mLMeOH

– LC–ESI-MS 87–99.5 – 0.1 [56]

Soil, sediment and sewageMarine sediment (1 g) Air dry Sonication (AcN, 10

min)– LC–APCI-MS/MS 101 4 0.0002 [52]

Sediments and sewage sludge Mixed with Na2SO4 Soxhlet with Acet:Hex(3:1, 6 h or 1:1, 12 h)

LLE with H2SO4 + GPC + SiO2 LC–ESI-MS – – 0.5 [57]

Sediments and sewage sludge(10 g)

Mixed with Na2SO4 Soxhlet (MTBE, 12 h) SPE-C18 cartridges + SPE-Sicartridges (500 mg, 3 mL)

LC–ESI-MS/MS 102.2 5.1 0.05 [58]

Sediments and sewage sludge(0.1–1.8 g)

– Sonication(DCM:MeOH 1:9,1 h) + agitation (3 h)

SPE Supelclean ENVI-18cartridges (3 ml) + filtration.

LC–ITD/MS 94 15 0.5 [59]

Sediment (10 g) sewage sludge(1 g)

Freeze dry + homogenization PLE (DCM, 100 ◦C,12.7 MPa)

Derivatization(CH2N2) + SiO2 + deactSiO2 + SiO2–H2SO4 + SiO2–AgNO3

GC-HRMS >80 – – [60]

Soil (30 g) – Soxhlet (Acet:DCM 4:1,22 h)

SPE C18-cartridges (1.5 mL,100mg) + filtration

UPLC–ESI-MS/MS 30.8–92.5 – – [61]

Biological samplesHarbour porpoises Mixed with Na2SO4 Soxhlet (Acet:Hex 1:1,

4 h)GPC + LLE with H2SO4 LC–ESI-MS – – – [62]

Marine mammals, fish andmarine invertebrates

Mixed with Na2SO4 Soxhlet with Acet:Hex(3:1, 6 h) or homog. byUltra Turrax

LLE with H2SO4 + GPC + SiO2 LC–ESI-MS – – 0.5 [57]

Cod muscle (5 g) Na2SO4 Soxhlet (Acet:Hex, 1:1,4 h)

GPC + SiO2–H2SO4 + deact SiO2(1.5% H2O)

LC–ESI-MS 80–127 9–27 1–200 [63]

Fish (2–10 g) Mixed with Na2SO4 Soxhlet (Acet:Hex 1:1,7 h)

LLE with H2SO4 LC–ESI-MS/MS 79–93 6–7 0.1 [64]

Egg (10 g) Homogenization + Na2SO4(overnight)

Column extraction(Acet:cyclohexane,1:3, 1 h)

GPC + deact Florisil (0.5%H2O) + derivatization

LC–TOF-MS 56–94 8 20 [65]

GC–LRMS 14 10GC–HRMS – 1

Blood serum (10 mL) – -LLE (EtOAc,12 + 8 mL) + LLE (AcN,3 mL + Hex, 3 × 3 mL)

Hex layer (PBDEs): Oasis HLBSPE + SiO2 + SiO2–H2SO4

GC–HRMS (aftersylilation)

40 4–7 0.2–4 [66]

Adipose tissue (0.5 g) – -LLE (AcN, 3mL + Hex,3 × 3 mL)

AcN layer (HBCD + TBBP-A):enzymatic hydrolysis (50 ◦C,4 h) + Oasis HLB + silica SPE

Human milk (1 g) Freeze dry, homogenization SLE (Acet:DCM, 1:1,12 + 6 mL) + LLE (AcN,3 mL + Hex, 3 × 3 mL)

Human serum (5 mL) Formic acid Abselut Nexus SPE SiO2 LC–ESI-MS/MS 83–104 <8 0.004 (wetweight)

[67]

Tissues of humans, dolphinsand sharks (3, 20 g)

Mixed with Na2SO4 Soxhlet DCM:Hex (3:1;16 h)

GPC + LLE withH2SO4 + filtration

LC–ESI-MS/MS 93.2 6.3 0.0003 (wetweight)

[68]

A. Covaci et al. / J. Chromatogr.

Poly

mer

sW

EEE

pol

ymer

frac

tion

s(9

80)

THF

+D

CM

+m

ixed

wit

hsi

lica

gel+

dri

edPL

E(i

so-o

ctan

e,3

cycl

es)

Dil

uti

on+

filt

rati

onLC

-UV

-APC

I-M

S90

–135

–10

–10

0[6

9]

WEE

Ep

olym

erfr

acti

ons

(980

)D

isso

lved

inTH

F+

filt

rati

on–

GPC

LC-U

V10

5–12

2–

10–1

00/

50–1

00,

00

0[7

0]LC

-UV

-APC

I-M

S

WEE

Ep

olym

erfr

acti

ons

Pulv

eriz

edin

mil

lsU

ltra

son

icat

ion

(iso

-pro

pan

ol)

Filt

rati

onLC

-UV

––

790,

00

0[7

0]

Ace

t,ac

eton

e;A

cN,a

ceto

nit

rile

;H

ex,n

-hex

ane;

DC

M,d

ich

loro

met

han

e;Et

OA

c,et

hyla

ceta

te;

MTB

E,m

ethy

l-te

rt-b

uty

leth

er.S

olve

nt

mix

ture

s:p

rop

orti

ons

asv/

v.PU

F,p

olyu

reth

ane

foam

.Oth

erac

rony

ms,

asid

enti

fied

inth

ebo

dy

text

.

(

2

l(sefaITmo

A 1216 (2009) 346–363 353

mised. The following analytical parameters were determinedfor the optimised method: repeatability (5–9%), intermedi-ate precision (10%), recovery (56–71%) and detection limits(4.2 �g/L).

iv) Polymers. Altwaiq et al. [75] examined different proceduresfor the extraction of TBBP-A and its derivatives from variouspolymer materials. These procedures included supercriticalcarbon dioxide (CO2), modified supercritical CO2, solvent andSoxhlet extraction. The extraction efficiency varied accordingto the applied methods. The results proved the high capacityof solvents such as toluene, tetrahydrofuran and acetonitrilefor the extraction of several BFRs, whereas extraction using acombination of CO2 and organic solvents was more efficientthan by using supercritical CO2 alone. PLE [69] and ultrasonicsolvent extraction (USE) with 2-propanol [70] have also beendeveloped for the extraction and identification of BFRs in poly-mers used in electrical and electronic equipment (EEE), suchas TV and PC monitor housings.

For polymers containing high concentrations of TBBP-A, sim-pler analytical techniques have been proposed. Schlummer etal. [69] used LC–UV/MS to identify and quantify TBBP-A inpost-consumer plastics from e-waste. Quantification provedto be more reproducible by UV, which was probably due tothe co-extraction of polymer components that accumulate inthe atmospheric pressure chemical ionization (APCI) source.The authors therefore suggest using UV for the quantificationand MS for identification and validation purposes. A similarapproach based on a rapid method for the extraction of var-ious BFRs followed by LC–UV was developed by Pöhlein etal. [70]. The overall runtime required for extraction and chro-matographic analysis was less than 10 min. Kikuchi et al. [76]analyzed BFRs in matrix polymers by Raman spectroscopywithout any sample pre-treatment. The LOD was approxi-mately 100 �g/g and analysis was only 1 min. Based on thedistinctive bands, the DecaBDE technical mixture and TBBP-Acould be identified. Energy dispersive X-ray fluorescence anal-ysis, LC-UV, GC–MS and infrared spectroscopy techniques havealso been evaluated for the analysis of polymers after variousextraction procedures [75].

A TBBP-A analogue (tetrabromobisphenol-S-bis-(2,3-dibromopropyl ether)), which contains sulfur, has beenidentified in polypropylene used in the manufacture of TVcabinets [77]. Various chromatographic and spectroscopictechniques were used for the correct identification of thisTBBP-A derivative.

The feasibility of using radiofrequency glow dischargeplasma spectrometry coupled with optical emission spectrom-etry (rf-GD-OES) as a rapid and simple tool to directly analyzepolymers containing BFRs has recently been investigated [78].The best detection limit (0.044% Br) was achieved by measuringat 827.24 nm in a He discharge. The linearity range extended upto a bromine content of 27%.

.2.2. Biological samplesTable 2 summarizes relevant methods related to TBBP-A in bio-

ogical samples. The reviewed categories include (i) biological fluidsi.e. serum and plasma) and (ii) fatty foodstuffs and animal tis-ues. Usually, only drying and homogenization is carried out beforextraction of biological samples as with abiotic samples. Exceptor serum and plasma, (semi)liquid samples (e.g. eggs) are usu-
lly freeze-dried and then treated as any other solid biotic sample.n general, similar extraction techniques and solvents are used forBBP-A analysis in abiotic and fat-containing matrices, and theain differences between both sets of analytical protocols refer
nly to the subsequent clean-up steps.

3 atogr.

(

2

ommfcptssft(aaf[tD

2

moao

cmrbhaLo[

oa

(ottM1D

2

Bfatwav

dLidsmltltw

isoa

smiad

fmtti[ttd

oTppi


(i) Serum and plasma. Direct solvent shaking with ethyl acetate andacetonitrile has been demonstrated to provide relatively low,but reproducible recoveries for TBBP-A (40%), despite the highnumber of manipulation steps [66]. One of the main limita-tions of these LLE-based procedures is the long settling time orcentrifugation required for phase separation.

Alternative SPE-based methods [79,80] have also been pro-posed. These methods proved to be less laborious and allowedreduced solvent consumption and processing time, the pos-sibility of miniaturization, and parallel sample preparation,which increases sample throughput. Hayama et al. [67] havesetup a method for the determination of TBBP-A in humanserum using SPE and LC coupled to electrospray interface (ESI)MS/MS (Table 2). 13C-labelled TBBP-A was a suitable surro-gate standard for the reproducible determination of TBBP-A.Method limit of quantification (LOQ) was as low as 4 pg/gserum.

ii) Biological tissues and fatty foodstuffs. Similar extraction tech-niques as used for abiotic samples have been used fordetermination of TBBP-A in complex biological tissues andfatty foodstuffs. Binary solvent mixtures typically contain-ing acetone:n-hexane [45] or DCM:n-hexane [65] have beenpreferred for Soxhlet-based extractions. These techniqueshave a number of advantages, such as minimum sam-ple pre-treatment required, simplicity, and high recoveries(>80%) [57].

.2.3. FractionationFor specific applications, isolation of the target analytes from

ther organohalogen compounds present in the extract can beandatory so as to minimize interferences during the final deter-ination step. Deactivated silica gel has been successfully applied

or the quantitative separation of TBBP-A from PBDEs. In thisase, iso-octane was used for the elution of PBDEs, while a moreolar solvent, i.e. diethyl ether:iso-octane (15:85, v/v), was requiredo elute TBBP-A [57]. Florisil (activated at 450 ◦C for 12 h andubsequently deactivated with 0.5% H2O, w/w) has also beenuccessfully used to separate neutral organohalogen compoundsrom phenolic analytes, such as TBBP-A [65]. In this case, neu-ral compounds were first eluted with mixtures of DCM:n-hexane1:3, v/v), while polar mixtures of acetone:n-hexane (15:85, v/v)nd methanol:DCM (12:88, v/v) were needed to elute phenolicnalytes [65]. Sorbents, such as Oasis HLB®, have been reportedor the fast separation of TBBP-A from HBCD diasteroisomers66]. DCM:n-hexane (1:1, v/v) was used to elute HBCDs fromhe SPE cartridge, while TBBP-A was subsequently eluted withCM [66].

.3. GC–MS

Among the predominant BFRs, TBBP-A is the most polarolecule, and thus requires different and more complicated meth-

ds so that a proper determination can be carried out. Acidificationnd derivatization are compulsory before GC analysis can be carriedut [80].

A GC-HRMS method requiring derivatization with methyl-hloroformate was developed by Berger et al. [65]. However, thisethod suffered from a rather restricted linear range and low

ecoveries due to incomplete derivatization, which was explainedy the presence of bulky bromine substituents adjacent to the two
ydroxyl groups. Although the GC–MS method showed better sep-ration properties and was more sensitive for standard solutions,C–ESI-time-of-flight (TOF)-MS was superior for the quantificationf egg extracts, with a satisfactory LOQ of 3 pg TBBP-A on-column65]. This was explained by the high-resolution filtering potential
t

Tbt

A 1216 (2009) 346–363

f the TOF-MS, which minimizes the matrix background from thenalyte’s mass chromatograms.

Comprehensive two-dimensional gas chromatographyGC × GC) coupled with �ECD or TOF-MS, a technique thatffers excellent separation power, has also been evaluated forhe analysis of PBDEs and possible co-eluants [82]. It was foundhat the second dimension GC column improves the separation of

e-TBBP-A and TBBP-A from any co-eluting PBDE congeners (BDE54 and BDE 153, respectively, when the first dimension GC is aB-1 or DB-5 column).

.4. LC–MS

In a review of the available methods for the determination ofFRs, Covaci et al. [48] indicated that LC–MS could be applicable

or the simultaneous analysis of TBBP-A with HBCDs. LC has thedvantage that no derivatization step is required before determina-ion of TBBP-A, whereas this step is necessary for its determinationith GC. Derivatization has been reported to produce errors and/or

nalyte losses [81]. Table 3 summarizes the parameters used forarious determination methods for TBBP-A.

Frederiksen et al. [86] compared LC–MS/MS to GC–MS for theetermination of TBBP-A in biota samples and concluded thatC–MS/MS is the method of choice, not only because derivatizations not needed, but also because of its higher sensitivity and betteretection limits. Chu et al. [58] found that the efficiency of the LCeparation and MS sensitivity for TBBP-A are largely affected by theobile phase used. They reported a 30% increase in response fol-

owing replacement of acetonitrile with MeOH in the mobile phase,ogether with a more stable detector baseline, which resulted in aower LOQ. Further enhancement in response was observed uponhe addition of 1 mM ammonium acetate to the mobile phase,hich may be due to ionization enhancement.

Another advantage of the LC–MS/MS determination of TBBP-As that it enables the use of the 13C-labelled TBBP-A as surrogatetandard. This greatly enhances the quality of the analytical databtained by compensating for any matrix-related effects that canffect analyte ion intensity [48].

A typical chromatogram obtained by LC–MS/MS for standardolutions of native and 13C-labelled TBBP-A, together with a chro-atogram for the standard reference material SRM 2585 are given

n Fig. 3a and b. A single quadrupole full scan from m/z = 300 to 570nd the product ion scan for m/z = 540.8 are also given in Fig. 3c and, respectively (Abdallah, unpublished data).

Tollbäck et al. [55] reported that the most suitable LC–MS inter-ace for TBBP-A analysis is ESI operating in negative ionization

ode. ESI gave 30–40 times lower LODs compared to APCI. In addi-ion, it permits monitoring of the intact TBBP-A molecule throughhe soft ionization of ESI resulting in improved method selectiv-ty and accuracy. This finding agrees with results of Morris et al.57]. However, for the quantification of TBBP-A in polymer frac-ions from WEEE using HPLC-UV/MS, Schlummer et al. [69] usedhe APCI source in negative ion mode, since initial trials with ESIid not produce suitable mass fragments after UV exposure.

Ion-trap MS (ITD-MS) was also reported for the determinationf TBBP-A in sediment and sewage sludge after LC separation [59].he ITD scan range was set from m/z 145–543. Although ion sup-ression of the TBBP-A signal due to matrix components in the ESIrocess was not high, sewage sludge extracts suffered greatly from

on suppression and extensive clean-up was required to minimize
his effect.
Suzuki and Hasegawa [52] reported the analysis of HBCDs andBBP-A in leachate samples by LC–APCI-MS. In this case, ionizationy APCI yielded signal to noise (S/N) ratios two to five times higherhan those obtained by ESI for HBCDs, while for TBBP-A, the S/N

A.Covaciet

al./J.Chromatogr.A

1216(2009)

346–363355

Table 3Overview of LC–MS and GC–MS parameters used for in the analysis of TBBP-A

Compound Column Dimensions Mobile phase(gradient)

Flow (mL/min) Mobile phase modifiers Ionization Instrument Ion Sourcetemp (◦C)

Reference

LC–MSTBBP-A Develosil C30 (Nomura) 150 × 2 mm, 5 �m AcN:H2O (y) 0.2 – APCI Triple quadrupole MRM 542.7 → 445.8 250 [52]TBBP-A SunFire C18 (Waters) 150 × 2.1 mm, 3.5 �m MeOH:H2O (y) 0.2 – ESI Triple quadrupole MRM 543 → 444 280 [53]TBBP-A Cosmosil 5C18-MS-II 50 × 2 mm, 5 �m AcN:H2O (y) 0.2 – ESI Single quadrupole 542 100 [54]TBBP-A Xterra C18 (Waters) 150 × 2.1 mm, 3.5 �m MeOH:H2O (y) 0.2 10 mM ammonium

acetateESI Triple quadrupole MRM 542.7 → 417.8 135 [55]

TBBP-A Mightysil RP-18 (KantoChemicals)

150 × 4.6 mm, 5 �m AcN:H2O (y) 0.2 0.01% acetic acid ESI Single quadrupole SIM 542 – [56]

TBBP-A Luna C18 (Phenomenex) 150 × 2 mm, 5 �m AcN:H2O (y) 0.25 10 mM ammoniumacetate

ESI Single quadrupole 540.9 150 [57]

TBBP-A Genesis C18 120Acolumn

150 × 2.1 mm, 4 �m MeOH:H2O (y) 0.2 – ESI Triple quadrupole MRM 543 → 81 130 [58]

TBBP-A Discovery C18 column(Supelco) and SymmetryC8 column (Waters)

50 × 2.1 mm, 5 �m,150 × 4.6 mm,3.5 �m

MeOH:H2O (y)and MeOH:H2O(n)

0.3 – ESI Ion-trap Scan (145–543) – [59]

TBBP-A Hypersil GOLD C18 100 × 2.1 mm, 3 �m MeOH:H2O:AcN(y)

0.2 20 mMammoniumacetate and0.05 mM ammoniumchloride

ESI Single quadrupole – – [62]

TBBP-A Gemini-C18 200 × 2 mm, 3 �m MeOH:H2O (y) 0.2 0.01% acetic acid ESI Triple quadrupole MRM 541.7 → 419.8 120 [64]TBBP-A Ace 3 C18 (Advanced

ChromatographyTechnologies)

150 × 2.1 mm, 3 �m MeOH:H2O (y) 0.2 1 mM ammoniumacetate

ESI TOF Scan (230–550) 130 [65]

TBBP-A Mightysil (Kanto) 150 × 2 mm, 3 �m AcN:MeOH:H2O(y)

0.2 – ESI Triple quadrupole MRM (542.7 → 445.8) – [67]

TBBP-A Hypersil C18 100 × 2.1 mm, 5 �m MeOH:H2O (y) 0.25 10 mM ammoniumacetate

ESI Triple quadrupole MRM540.9 → 79/540.9 → 81

300 [68]

TBBP-A Nucleodur 100-C8(Interchim)

250 × 4 mm, 5 �m AcN:H2O (y) 1 0.1% acetic acid APPI QTrap scan n.a. [83]

TBBP-A Hypersil ODS C18(Thermo Electron)

250 × 4.6 mm, 5 �m MeOH:buffer(AmmoniumAcetate) (n)

1 – APCI Triple quadrupole Scan (150–1000) n.a. [69]

UPLC–MS/MSTBBP-A RP Waters Acquity BEH

C18

50 × 2.1 mm, 1.7 �m AcN:H2O (y) 0.45 – ESI Triple quadrupole MRM 542.7 → 445.8 120 [61]

TBBP-A Acquity BEH C18 150 × 2.1 mm, 1.7 �m MeOH:H2O (y) 0.5 – ESI Triple quadrupole MRM 542.60 → 419.70and 542.60 → 447.60

– [84]

HPLC–UVTBBP-A, PBDEs, HBCD Hypersil ODS C18

(Thermo Electron)250 × 4.6 mm, 5 �m(40 ◦C)

MeOH:buffer(ammoniumacetate) (n)

1 – – UV (203nm) n.a. [69]

TBBP-A, PBDEs, DBPE Luna 5 � Phenyl-Hexyl(Phenomenex)

150 × 4.6 mm, 5 �m(50 ◦C)

MeOH:2-aminoethanol:water(n)

2.5 – – UV (200–400 nm) – – [70]

TBBP-A-dbpe Zorbax XDB-C18(Agilent)

150 × 4.6 mm, 5 �m(40 ◦C)

AcN:H2O (y) 1 – – DAD – – [85]

TBBP-A SphereClone ODS 2(Phenomenex)

250 × 4.6 mm, 5 �m MeOH:THF:buffer(AmmoniumAcetate) (n)

1 – – UV (230, 254 nm) [69]

Compound Column Dimensions Injection mode Derivatization Ionization Instrument Ion Source temperature (◦C) Reference

GC–MSTBBP-A DB-5 ms (J&W Scientific) 30 m × 0.25 mm × 0.1 �m Splitless Methyl chloroformate EI HRMS 556.7608, 554.7629 275 [65]TBBP-A UB5-P (Interchim) 15 m × 0.25 mm × 0.25 �m Splitless MSTFA EI HRMS 682.8509, 684.8489 230 [66]

For acronyms, see Table 2 and text.


Fig. 3. LC–MS/MS chromatogram of (a) a standard solution containing 20 and 50 pg on column for 13C-labelled TBBP-A and native TBBP-A, respectively, (b) a standard referencem scan frc ethanol S3 C1

f 9 for

raa(

aterial (SRM 2585—organic contaminants in indoor dust), (c) a single quadrupoleonditions: gradient using a mobile phase of water/methanol (1:1, solvent 1) and minearly to 100% (solvent 2) over 6 min, held for 5 min. Column: Varian Pursuit XRollowing multiple-reaction monitoring (MRM) transitions were as follows: 540.8-7

atio using APCI was almost half that of ESI. Recently, Debrauwer etl. [83] have investigated the applicability of LC techniques for thenalysis of PBDEs. The use of atmospheric pressure photo ionizationAPPI) may facilitate the analysis of PBDEs and phenolic com-

pocf

om m/z = 300 to 570 and (d) the product ion scan for m/z = 540.8. Chromatographicl (solvent 2) at a flow rate of 150 �L/min, starting at 35% (solvent 2) then increased

8 reversed phase analytical column (150 mm × 2 mm i.d., 3 �m particle size). Thethe native TBBP-A and 552.8-79 for the 13C-labelled TBBP-A.

ounds, such as TBBP-A, in the same run. Without performing fullptimization, LODs were found to be in the range of 200–1500 pg onolumn. This methodology allows to use LC–MS/MS-based methodsor the identification of biotransformation products of BFRs [87].

atogr.

M[amae

2

syteapis1s1

2

wo[bucmrunptpo

bymheoHnare

2

laivttTtm

letbmZttf1

3

3

n(

3

ao

sc[tsmvhtiA3Tlp(T

uctavdCtf

aacs(Northeast Atlantic Ocean ranged from <0.04 to 0.17 pg/m3 [93]. The


Recently, ultra performance liquid chromatography (UPLC)–ESI-S/MS was reported for analysis of TBBP-A in soil and food samples

61,84]. This technique combines all the advantages of LC–MS/MS inddition to shorter residence time of the analyte on-column, thusinimizing the potential for losses on-column due to adsorption

nd degradation. The short analysis time (4 min) can double thefficiency of the analytical method.

.5. Capillary electrophoresis

Capillary electrophoresis (CE), an efficient technique for theeparation of charged species, was also found useful for the anal-sis of TBBP-A [73,88]. Blanco et al. [88] developed a method forhe determination of TBBP-A and other phenolic compounds innvironmental samples by non-aqueous CE coupled to a diode-rray detector (210 nm for TBBP-A), using MeOH as solvent. Somearameters affecting the electrophoretic separation were stud-

ed, such as salt concentration, electrolyte pH, and capillary andolution temperature. Calibration curves were linear from 0.5 to0 ng/�L. This technique was successfully applied for the analy-is of TBBP-A in water samples. Method LOQ was approximately2 pg/�L.

.6. Quality assurance

TBBP-A tends to adsorb to glass when using n-hexane as solvent,hile it remains in solution when using MeOH [89]. Additional rec-

mmendations regarding this issue can be found in Päpke et al.90] and de Boer and Wells [81]. Reported data for TBBP-A shoulde supported by appropriate QA/QC protocols, which can representp to 30% of the total analytical effort. At this moment, there are noertified reference materials available for TBBP-A, although severalaterials have already been certified for PBDEs [91]. Such mate-

ials are necessary to evaluate the accuracy of analytical methodssed for the determination of TBBP-A. Presently, the method true-ess and precision can only be tested through standard additionrocedures [90]. When possible, proper incubation and aging ofhe spiked samples should be conducted so that the spiked com-ounds mimic as closely as possible the behaviour of the naturallyccurring analytes.

Since 1999, several international interlaboratory studies haveeen organized with the aim of improving the quality of the anal-sis of BFRs [81]. A wide range of matrices, including fish andarine mammal tissue, fish oil, shellfish, sediments, sewage sludge,

uman milk and standard solutions, have been used during thesexercises and this has enabled researchers to validate their meth-ds and to implement reliable QC procedures. Besides PBDEs andBCDs, the analysis of TBBP-A was also suggested, but unfortu-ately, only very few laboratories have submitted results for TBBP-And/or diMe-TBBP-A. Therefore, the TBBP-A data presented in thiseview should presumably associated with an uncertain analyticalrror.

.7. Analytical methods for TBBP-A derivatives

Regarding TBBP-A derivatives, almost no data have been pub-ished to date. In a study on degradation products of TBBP-A formedfter UV-exposure, ESI-MS did not prove to be very useful, while theonization of TBBP-A degradation products by means of APPI wasery efficient [83]. A potential drawback of APPI is its susceptibility
owards the mobile phase composition. Higher signals were seenowards the end of the gradient elution, close to 100% acetonitrile.his particular feature could constitute a limitation for the quan-itative analysis of mixtures of BFRs, their degradation products or
etabolites [81].

ltoaA

A 1216 (2009) 346–363 357

Köppen et al. [85] analyzed TBBP-A bis(2,3-dibromopropy-ether) (TBBP-A-dbpe) in sediment and sewage sludge. Differentxtraction methods were compared; both fluidised bed extrac-ion and ASE were found suitable with the latter preferredased upon its speed and lower solvent consumption. Chro-atographic resolution of the extract was achieved using a

orbax XDB-C18 column (150 mm × 4.6 mm i.d., 5 �m). Detec-ion by ITD-MS using an APCI interface was evaluated, but thisechnique did not yield sufficient ionization, making it inadequateor quantitative analysis. Detection by DAD (220 nm) led to LODs of0 and 22 ng/g in sediment and sewage sludge, respectively [85].

. Environmental levels (TBBP-A and derivatives)

.1. Abiotic matrices

Despite its extensive use, TBBP-A data for abiotic matrices areot so abundant than data available for other BFRs, such as PBDEsTable 4).

.1.1. AirElevated indoor air concentrations (several orders of magnitude

bove those found in outdoor air) have been reported for specificccupational environments, such as electronics dismantling plants.

In Sweden, TBBP-A was detected (mean 29.7 ng/m3) in 12 airamples at a plant for the recycling of electronics (dismantling ofomputers, TV sets, etc.) and in offices equipped with computers92]. In four offices equipped with computers, the mean concentra-ion was 0.035 ng/m3. TBBP-A could not be detected in two outdooramples. In another Swedish study, Sjödin et al. [93] reported aean TBBP-A concentration of 0.036 ng/m3 in six office microen-

ironments containing computers, 0.093 ng/m3 from two teachingalls and 0.035 ng/m3 from two computer repair facilities. Concen-rations were below detection limits (unreported) in outdoor air,ndicating indoor sources of TBBP-A. They also reported high TBBP-

concentrations in air from an electronics recycling plant (mean0 ng/m3 in the dismantling hall and 140 ng/m3 in the shredder).he study found that TBBP-A was present primarily in the particu-ate phase rather than in the vapor phase [93]. This may suggest thatassive air sampling devices that sample primarily the vapor phasee.g. PUF disk samplers) may not be appropriate for monitoringBBP-A.

The importance of electronic goods as an emission source isnderlined by Tollbäck et al. [55], who reported that the TBBP-Aoncentration in air from a dismantling hall within a Swedish elec-ronics recycling plant was 13.8 ng/m3. Inoue et al. [56] reportedmean concentration of 0.2 ng/m3 in indoor air from 26 microen-ironments in Japan, where TBBP-A was found above the limit ofetection (0.1 ng/m3) in samples from 14 out of the 26 locations.oncentrations in the matched outdoor and indoor samples fromwo houses in Hokkaido, Japan, were 7.1 and 9 pg/m3, respectivelyor the first house, and 9.5 and 16 pg/m3 for the second [94].

Xie et al. [95] investigated the presence of TBBP-A in outdoorir from a rural site in northern Germany, over the Wadden Seand offshore in the Northeast Atlantic Ocean (Table 4). Comparableoncentrations of TBBP-A were found both at the northern Germanite (ranging from <0.04 to 0.85 pg/m3) and over the Wadden Searanging from 0.31 to 0.69 pg/m3). Concentrations of TBBP-A in the

atter higher concentration was present in a sample collected offhe West Norwegian coast, indicating an input source from land tocean. Interestingly, Alaee et al. [96] reported TBBP-A to be presentt 70 pg/m3 in the airborne particulates collected in 2000 in therctic (Dunai, Russia).


Table 4Mean and/or range of TBBP-A concentrations in abiotic matrices

Matrix Location TBBP-A concentration Ref.

AirRecycling plant Sweden 29.7 ng/m3 [92]Computer office Sweden 0.035 ng/m3 [92]Outdoor air Sweden <LOD [92]Computer office Sweden 0.036 ng/m3 [93]Teaching hall Sweden 0.093 ng/m3 [93]Computer repair facility Sweden 0.035 ng/m3 [93]Outdour air Sweden <LOD [93]Dismantling hall Sweden 30 ng/m3 [93]Shredder Sweden 140 ng/m3 [93]Dismantling hall electronics recycling plant Sweden 13.8 ng/m3 [55]Indoor air microenvironments Japan 0.2 ng/m3 [56]Outdoor air Japan 7.1–9.5 pg/m3 [94]Indoor air house Japan 9–16 pg/m3 [94]Outdoor air rural site Northern Germany <0.04–0.85 pg/m3 [95]Outdoor air Wadden Sea 0.31–0.69 pg/m3 [95]Outdoor air Northeast Atlantic <0.04–0.17 pg/m3 [95]Outdoor air Arctic, Russia 70 pg/m3 [96]

Indoor dustDomestic dust Hokkaido, Japan 490–520 ng/g [94]Pooled domestic dust UK 190–340 ng/g [99]Office dust EU offices 5–47 ng/g [100]Newly constructed building Michigan, USA 0.4–2 ng/g [101]Dust inside computers China 8.9–39.6 �g/g [74]

WaterLand leachate from industrial waste sites Japan 0.3–540 ng/L [52]Before treatment plant Japan 130 ng/L [52]After treatment plant Japan 7 ng/L [52]Raw leachate from landfill Japan <LOD −620 ng/L [102]Treated leachate from landfill Japan <LOD −11 ng/L [102]

SoilOutside production plant China 0.12 ng/g [61]Soil China 25.2 ± 2.7 ng/g [103]Near garbage discharge site China 1.4–1.8 �g/g [74]

SedimentSediment Neya River, Japan 20 ng/g dw [43]Sediment downstream plastic factory Sweden 270 ng/g (TBBP-A) [44]

1500 ng/g (diMe-TBBP-A)Sediment upstream plastic factory Sweden 34 ng/g (TBBP-A) [44]

24 ng/g (diMe-TBBP-A)Sediment close to BFR manufacturing site River Skerne, UK 9.8 �g/g dw [57]Sediment River Tees, UK 25 ng/g dw [57]Sediment Scheldt basin 0.1–67 ng/g dw [57]Sediment Western Scheldt 0.1–3.2 ng/g dw [57]Sediment Dutch rivers 0.1–6.9 ng/g dw [57]Sediment UK rivers 2–5 ng/g dw [57]Sediment Detroit River 0.6–1.84 ng/g dw [60]Sediment Lakes Mjøsa, Losna Norway 0.04–0.13 ng/g dw [104]Sediments Asia <0.2–1.6 ng/g [52]

Sewage sludgeSewage sludge (influent) The Netherlands <6.9 ng/g dw [57]Sewage sludge (effluent) The Netherlands 42 ng/g dw [57]Sewage sludge The Netherlands 79 ng/g dw [57]Sewage sludge (influent) UK 7.5 ng/g dw [57]Sewage sludge (effluent) UK <3.9 ng/g dw [57]Sewage sludge UK 57 ng/g dw [57]Treated sludge Cork, Ireland 192 ng/g dw [57]Sewage sludge Sweden <0.3–220 ng/g dw [105]Sewage sludge Sweden 32 ng/g dw [106]Compost and digestate Switzerland 510 ng/g dw [107]

OnMoCanSou

3

ibt

Sewage sludge from wastewater treatment and pollution control plantSewage sludge from wastewaterSewage sludge from sewage treatment plantsSewage sludge

.1.2. Indoor dustThe presence of additive BFRs, such as PBDEs and HBCDs,

n indoor dust and the consequences for human exposure haseen the subject of increasing recent interest. Information onhe presence of TBBP-A in indoor dust is far less extensive and

atftr

tario, Canada 2.1–28.3 ng/g dw [58]ntreal, Canada 300 ng/g dw [108]ada <1–46.2 ng/g dw [109]thern Ontario, Canada 14.3–43.8 ng/g dw [109]

ppears to constitute a research gap. The available data suggesthat concentrations of TBBP-A are at the low end of those foundor PBDEs and HBCDs [97,98]. This is consistent with the facthat TBBP-A is used primarily as a reactive FR and as such itselease from treated goods is likely to be less facile than for com-

atogr.

pF

5Srofcto4

TbcTosAs

bCwi

3

wiittAfmecs

3

oaGp(mddbAbs

3

gacIacw

([t

sTfmfvli(rcl

sdddsssd

tmwspesb

p5tect

TlOdsdInicw

Ccsams


ounds whose use pattern is largely or exclusively as additiveRs.

Takigami et al. [94] reported TBBP-A concentrations of 490 and20 ng/g in two samples of domestic dust from Hokkaido, Japan.imilar concentrations were detected by Santillo et al. [99], whoeported TBBP-A to be present above the detection limit in 4 outf 10 pooled samples of UK domestic dust. Concentrations in theseour samples ranged from 190 to 340 ng/g, exceeding substantiallyoncentrations reported in an earlier study of dust in offices fromhe European Parliament building, where concentrations in 9 outf 16 samples where TBBP-A was detectable were between 5 and7 ng/g [100].

More recently, Chernyak et al. [101] monitored the change inBBP-A concentrations in indoor dust from a newly constructeduilding in Michigan, USA, over the period following the building’sonstruction, furnishing, and occupation. A continuous increase inBBP-A concentration in dust from 0.4 to 2.0 ng/g was observedver 1 year, suggesting that the dust samples had not yet reachedaturation with TBBP-A over this period. The increase in the TBBP-concentration in the dust was less dramatic than for other BFRs,

uch as BDE 209.Yu and Hu [74] reported concentrations of TBBP-A ranging

etween 18.9 and 39.6 �g/g in dust samples from computers inhinese offices (n = 4). However, these results should be interpretedith care since the analysis was performed using HPLC-DAD, yield-

ng less specific detection than with MS detection.

.1.3. WaterSuzuki and Hasegawa [52] reported TBBP-A concentrations in

ater ranging from 0.3 to 540 ng/L in landfill leachates from fivendustrial waste sites in Japan, while concentrations of TBBP-A innfluent and effluent wastewater were 130 and 7.7 ng/L, respec-ively. In another study, TBBP-A was measured in leachate samplesaken from seven Japanese landfills [102]. Concentrations of TBBP-

were up to 620 ng/L for the raw leachate and up to 11 ng/Lor the treated leachate. Three sites that not only had crushed

aterial from bulk wastes, such as waste electric and electronicquipments, but also were under operation or within a year afterlosure, indicated a higher concentration of BFRs than the otherites.

.1.4. SoilTo date there appears to be very few reports on concentrations

f TBBP-A in soil. Jin et al. [61] reported TBBP-A at 0.12 ng/g insoil sample taken outside a TBBP-A production plant in China.iven its reported propensity for partitioning to the atmosphericarticulate phase [93] and its octanol–water partition coefficientlog Kow = 5.90), one would anticipate that soil would constitute a

ajor sink. However, this will be influenced by the rate of degra-ation in soil coupled to subsequent atmospheric transport andeposition. The concentration of TBBP-A in Chinese soil measuredy SPE followed by HPLC–ITD-MS was 25.2 ± 2.7 ng/g (n = 4) [103].nother Chinese study reports TBBP-A concentrations rangingetween 1.4 and 1.8 �g/g in soil collected near a garbage dischargeite [74].

.1.5. Sewage sludge and sedimentSimilar to soil, the physico-chemical properties of TBBP-A sug-

est that sewage sludge and sediment are important sinks. Thevailable data support this and reflect also the release to such matri-
es from industrial plants that either manufacture or use TBBP-A.n 1983, Watanabe et al. [43] reported (for the first time) TBBP-At 20 ng/g dw in sediment from the Neya River in Japan. The con-entrations of TBBP-A and its dimethylated derivative in sedimentere higher downstream (270 and 1500 ng/g dw) than upstream
oP

dm

A 1216 (2009) 346–363 359

34 and 24 ng/g dw) of a plastic factory using TBBP-A in Sweden44]. TBBP-A was also found in sewage sludge from the wastewaterreatment plant of the factory [44].

Morris et al. [57] determined TBBP-A in river and estuarineediment samples from Belgium, the Netherlands and the UK.he highest concentration of TBBP-A (9.8 �g/g dw) was found inreshwater sediments from the River Skerne (UK) close to a BFR

anufacturing site. The mean concentration in the River Tees,urther downstream, was 25 ng/g dw. The same study also pro-ided an indication of the expected range of concentrations inocations not influenced directly by industrial emissions, report-ng concentrations of TBBP-A in sediments from the Scheldt basin0.1–67 ng/g dw), the Western Scheldt (0.1–3.2 ng/g dw), Dutchivers (0.1–6.9 ng/g dw) and UK rivers (2–5 ng/g dw). Lower con-entrations of TBBP-A were found in sediments from Norwegianakes (0.04–0.13 ng/g dw) [104].

TBBP-A was also quantified in influents, effluents and sewageludge from the Netherlands (mean values of 42, <6.9, and 79 ng/gw, respectively) and the UK (mean values of 7.5, <3.9 and 57 ng/gw, respectively) [57]. A maximum concentration of 192 ng/gw was quantified in a secondary treated and dewatered sludgeample from Cork, Ireland [57]. These concentrations are con-istent with those reported in a survey of 57 Swedish sewageludge samples, where concentrations ranged from <0.3 to 220 ng/gw [105].

In 50 Swedish sewage treatment plants (STPs), TBBP-A concen-rations were below LOQ (not reported) in 12 samples, while the

ean concentration was 32 ng/g dw [106]. Higher concentrationsere found in a few sludge samples from STPs with known or

uspected point sources (textile industries, extruded polystyreneroduction), but in some cases, the source was unknown. How-ver, TBBP-A concentrations were significantly lower in digesterludge samples than in the raw sludge samples, indicating anaero-ic biodegradation of TBBP-A.

The first comprehensive study of BFRs in source-separated com-ost and digestate from Switzerland showed mean TBBP-A levels of10 ng/g dw [107]. The concentrations observed were at or abovehe levels found in background soils, which are the main recipi-nt of compost and digestate. Where actually applied, compost canontribute considerably to the total input of organic pollutants tohe soil.

In North America, Chu et al. [58] reported concentrations ofBBP-A ranging from 2.1 to 28.3 ng/g dw in sludge samples col-ected from wastewater treatment and pollution control plants inntario, Canada. In the same study, TBBP-A was detected above theetection limit of 0.05 ng/g dw in only 3 of 55 surface sedimentamples from Lake Erie and in only one sample could TBBP-A beetermined quantitatively, at a concentration of 0.51 ng/g dw [58].

mportantly, the authors found that TBBP-A can undergo debromi-ation, in agreement with the debromination of TBBP-A reported

n estuarine sediments [108]. TBBP-A was also detected at a con-entration of 300 ng/g dw in sewage sludge produced from theastewaters of the Montreal area [59].

TBBP-A has been reported at moderate concentrations inanadian sludges. Lee and Peart [109] have reported a medianoncentration of 12.4 ng/g (range <1–46.2 ng/g dw) in sewageludge from 34 Canadian sewage treatment plants. Quade etl. [60] have reported low concentrations of TBBP-A in sedi-ent from the Detroit river (range 0.60–1.84 ng/g dw). Sewage

ludge collected from Southern Ontario had the same range
f concentrations (14.3–43.8 ng/g dw) as reported by Lee andeart [109].
In Asia, low concentrations of TBBP-A (<0.2–1.6 ng/g) wereetermined in sediments sampled before treatment in water treat-ent plants in Japan [52].


Table 5Mean and range of TBBP-A concentrations (ng/g lipid weight) in biological matrices

Species Tissue Location TBBP-A concentration (ng/g lw) Refs.

InvertebratesCommon whelk Whole North Sea 5.0–96 [57]Sea star Whole Scheldt estuary <1–2 [57]Sea star Whole Tees estuary 205 [57]Hermit crab Whole North Sea <1–35 [57]Mysid Whole Scheldt estuary 0.8–0.9 [110]

FishWhiting Muscle North Sea <97 to 245 (mean 136) [57]Cod Liver North Sea <0.3–1.8 [57]Hake Liver Atlantic <0.2 [57]Eel Muscle Scheldt estuary <0.1–13 (mean 1.6) [57]Eel Muscle Dutch rivers <0.1–1.3 (mean 0.3) [57]Yellow eel Muscle Scheldt basin <0.1–2.1 [57]Yellow eel Muscle Dutch rivers <0.1–1.0 [57]Perch, pike, smelt, vendace, trout Muscle Norway 1.0–13.7 [104]Atlantic cod Muscle Norway 0.5 and 2.5 [111]Bull shark Muscle Florida, USA 9.5 ± 12.0 [68]Atlantic sharpnose shark Muscle Florida, USA 0.87 ± 0.50 [68]

BirdsCormorant Liver Wales and England 2.5–14 [57]Common tern Egg Western Scheldt <2.9 [57]Peregrine falcon, White-tailed sea eagle, Osprey, Golden eagle, Egg Norway <0.003–0.013a [112]Peregrine falcon Egg Norway nd (TBBP-A) [113]

<0.1–940 (diMe-TBBP-A)

Marine mammalsHarbour seal Blubber Wadden Sea <14 [57]Harbour porpoise Blubber North Sea <11 [57]Harbour porpoise Blubber North Sea 0.1–418 [57]Harbour porpoise Blubber Tyne/Tees 0.31 [57]Harbour porpoise Blubber UK 6–35a [62]Bottlenose dolphin Blubber Florida, USA 1.2 ± 3.0 [68]

HumansElectronics dismantling Serum Sweden 1.1–4.0 [114]Computer technicians Serum Sweden 0.55–1.84 [115]Electronics dismantling Serum Norway 0.64–1.8 (mean 1.3) [116]Circuit board producers Serum Norway <0.1–0.80 (mean 0.54) [116]Laboratory personnel Serum Norway <0.1–0.52 (mean 0.34) [116]General population Serum Norway 0.34–0.71 [79]

G issue

3

cisfeiwi[

pat

flwyofc

cc(asrw

aio<Iwtc[

General population Serumeneral population Adipose t

a Concentrations in ng/g wet weight.

.2. Biological matrices

Despite the extensive use of TBBP-A, data for biotic matri-es are scarce (Table 5). Herzke et al. [112] determined TBBP-An two eggs from each of four different Norwegian bird of preypecies (osprey, golden eagle, white-tailed sea eagle and peregrinealcon), which have different feeding habits and habitats. Theseggs were sampled between 1992 and 2002. TBBP-A was detectedn all eight samples in a concentration range of <3–13 pg/g wet

eight (ww), which indicates that TBBP-A is distributed widelyn a broad range of prey items of predatory birds in Norway112].

Law et al. [62] determined TBBP-A in the blubber of 68 por-oises (Phocoena phocoena) stranded in UK waters between 1994nd 2003. TBBP-A was detected in only 18 samples, with concen-rations between 6 and 35 ng/g ww.

Morris et al. [57] determined TBBP-A in a variety of aquatic biotarom the North Sea, including five cormorant (Phalacrocorax carbo)iver samples from England. Levels ranged from 2.5–14 ng/g lipid

eight (lw) [57]. TBBP-A was also detected in mysid shrimp (Neom-sis integer) from two sites in the Scheldt estuary at concentrationsf 0.8 and 0.9 ng/g lw [110]. In liver of Atlantic cod (Gadus morhua)rom the Norwegian Arctic collected in 1998 and 2002, TBBP-Aoncentrations ranged from 0.5 to 2.5 ng/g lw [111].

3

Td

Japan 1.35 [117]New York, USA 0.048 ± 0.102 [68]

Recently, Johnson-Restrepo et al. [68] have measured theoncentrations of TBBP-A in three marine top-predators fromoastal waters of Florida, USA. The overall mean concentrationsmean ± SD) of TBBP-A were 1.2 ± 3.0 ng/g lw, 9.5 ± 12.0 ng/g lw,nd 0.87 ± 0.50 ng/g lw in bottlenose dolphin blubber (n = 15), bullhark muscle (n = 13) and Atlantic sharpnose shark muscle (n = 3),espectively. The highest concentration of TBBP-A (35.6 ng/g lw)as measured in bull shark muscle.

Thirty-three peregrine falcon eggs from South Greenland werenalyzed by Vorkamp et al. [113]. TBBP-A could not be detectedn any of the eggs whereas diMe-TBBP-A was quantifiable in 29ut of 33 eggs. Concentrations of diMe-TBBP-A ranged between0.1 and 940 ng/g lw, with a mean concentration of 280 ng/g lw.n a preliminary recent screening study, TBBP-A and diMe-TBBP-Aere not detected in any of the samples of egg, liver and adipose

issue of marine biota from Greenland and the Faroe Islands, indi-ating limited or no transport of these compounds to remote areas86,118].

.3. Food

To the best of our knowledge, dedicated studies that focus onBBP-A and its derivatives in foodstuffs have not been reported toate. It is assumed that less-persistent BFRs, such as TBBP-A, do

atogr.

nifobsTl

is(iffiitCcrsid

sifd[cp(pPitr

3

fitvTao

itopimspwu

ttgtwe

aobsbr

p1sFpowttow

va

tU0lwfl

bbtSts

4

Tttrr

iarelHroeatfurther investigation. Moreover, future work should also focus on


ot biomagnify and hence will not be present at significant levelsn food of animal origin [119]. Saito et al. [120] developed a methodor the determination of TBBP-A in cattle adipose tissue and swinergans, but this was not applied to real samples. Only a limited num-er of studies have investigated the presence of TBBP-A in animalpecies (e.g. fish) that are suitable for human consumption [57,104].hese studies both reported that concentrations of TBBP-A wereow (Section 3.2 and Table 4).

Recently, 19 composite food group samples have been analyzedn the UK for a wide range of pollutants, including TBBP-A [121]. Thetudy did not detect any TBBP-A at concentrations above the LOD0.36 ng/g). The UK Food Standards Agency estimated the dietaryntake from fisheries products (composite samples of 48 species ofarmed and wild fish and shellfish, together with ten samples ofsh oil dietary supplements) through the analysis of BFRs, includ-

ng TBBP-A [122]. TBBP-A was not detected in any of the samplesested. Based on these results, the UK Committee on Toxicity ofhemicals in Food, Consumer Products and the Environment con-luded that the levels of TBBP-A detected in fish and shellfish do notaise toxicological concerns and that the estimated dietary expo-ure to TBBP-A (<1.6 ng/kg body weight/day) seems to have limitedmplications for health [123]. No data are available for TBBP-Aerivatives.

Despite the low levels of TBBP-A reported in food for human con-umption, the European Food Safety Authority [124] issued advicen 2006 concerning the routine measurements of BFRs in food andeed. A scientific committee concluded that, based on literatureata, TBBP-A should be included within the monitoring programs124]. This conclusion was reached after considering the followingriteria: (i) analytical feasibility to measure the chemical com-ounds routinely in accredited laboratories, (ii) production volume,iii) occurrence of the chemical compounds in food and feed, (iv)ersistence and (v) toxicity. In contrast to what was decided for theBDEs, HBCDs and PBBs, TBBP-A was not recommended directly fornclusion in the core group of analytes to be monitored. The scien-ific panel pointed out that it would be desirable to initiate a specificesearch program for reactive BFRs, such as TBBP-A.

.4. Humans

In general, reports of TBBP-A in human samples are scarce. Therst report of TBBP-A being present in human tissues dates backo 1979. In Arkansas, USA, TBBP-A was found in human hair in theicinity of TBBP-A manufacturing sites [44]. More recent reports ofBBP-A in human samples are also mainly focused on occupation-lly exposed workers [114–116], because of the greater likelihoodf exposure in occupational environments (Table 5).

Due to its limited presence in foodstuffs (as far as it has beennvestigated), direct exposure via inhalation might be consideredhe predominant route of human exposure [119]. In this respect,ccupationally exposed workers are at higher risk than the generalopulation. High concentrations of TBBP-A in the air (30 ng/m3)

nside an electronics dismantling area of a dismantling facility wereeasured [119]. In a follow-up study of the people working in the

ame electronics recycling facility, Hagmar et al. [114] revealed theresence of TBBP-A (range 1.1–4.0 ng/g lw) in the serum of theorkers engaged in the recycling process, which indicates systemicptake of this chemical.

Jakobsson et al. [115] investigated TBBP-A exposure in computerechnicians. TBBP-A could be found in 80% of the technicians, while
he compound could not be measured in the serum of a controlroup comprising office clerks and hospital cleaners. The concen-rations found in this study ranged between <0.55 and 1.84 ng/g lw,hich are comparable to the concentrations reported by Hagmar
t al. [114].

eocel

A 1216 (2009) 346–363 361

Thomsen et al. [116] analyzed serum from Norwegian individu-ls working at an electronics dismantling facility, in the productionf printed circuit boards and as laboratory personnel, the lattereing a control group. In that study, TBBP-A levels were elevatedignificantly (p < 0.05) in the dismantlers (1.3 ng/g lw), while inoth other groups the levels were lower (0.54 and 0.34 ng/g lw,espectively).

Data on TBBP-A in non-occupationally exposed individuals wasublished by Thomsen et al. [79], where time trends from 1977 to999 were also investigated. TBBP-A could not be found in the oldesterum pools (1977 and 1981), but was present in all other samples.urther, Thomsen et al. [79] also looked at age classes of the 1998-opulation. TBBP-A levels tended to be the highest in the age groupf 0–4 years. This was also the only age group where diMe-TBBP-Aas found, although at a level close to the LOQ. Further, no concen-

ration vs. age relationship could be observed. Concentrations inhat study ranged between 0.34–0.71 ng/g lw. After further methodptimization, the same samples were re-analyzed and Me-TBBP-Aas found in all samples [80].

In Japan, TBBP-A was analyzed in 24 blood samples from adultolunteers. TBBP-A was detected in only 14 of these samples withmean concentration of 1.35 ng/g lw [117].

Recently, Johnson-Restrepo et al. [68] measured the concen-rations of TBBP-A in 20 adipose tissue samples from New York,SA. The overall mean concentration (mean ± SD) of TBBP-A was.048 ± 0.102 ng/g lw, with a maximum concentration of 0.46 ng/g

w. TBBP-A correlated well with concentrations of HBCDs, but notith those of PBDEs. Moreover, concentrations of TBBP-A were 10-

old lower than HBCD concentrations and 3–4 orders of magnitudeower than PBDEs measured in the same samples.

Detection of TBBP-A in humans can be hampered by the shortiological half-life of the compound, which has been estimated toe 2 days [89,114]. This is not surprising since TBBP-A is a phenolhat can be rapidly conjugated and subsequently excreted [125].till, TBBP-A may accumulate in humans, but a continuous exposureo this BFR is required to maintain a detectable level in the humanubject.

. Concluding remarks

The LC–MS/MS method appears to be the method of choice forBBP-A analysis because no derivatization is required. Moreover,he use of 13C-labelled TBBP-A as an internal standard enhanceshe quality of the analytical data through compensation for matrix-elated effects that can affect analyte ion intensity, trueness andeproducibility.

Since TBBP-A is a reactive BFR, its release from treated goodss much less pronounced than for additive BFRs, such as HBCDsnd PBDEs. Consequently, this is reflected in the low concentrationseported in indoor dust, air and food stuffs, which makes humanxposure to TBBP-A via air inhalation, dust ingestion and diet faress significant than the estimated intake for additive BFRs, such asBCDs. This review also points that there are still knowledge gaps

egarding the presence of TBBP-A and its derivatives in indoor andutdoor air, in indoor dust and food, as well as regarding humanxposure via these pathways. The possibility of degradation in soilnd sediment, debromination and the possible pathways thereof,ogether with the factors affecting these processes, also requires

nvironmental fate and the human exposure around productionr usage sites, primarily in Asia. Such sites are seen as the worst-ase scenarios for occupational or accidental exposure, while thexposure of the general population seems to be very low given theow leaching capacity of TBBP-A from finished products.

3 atogr.

A

m(adof(oM

R


cknowledgements

The authors would like to thank Steve Dungey of the UK Environ-ent Agency for supplying a copy of the draft EU risk assessment

environment) document for TBBP-A. Adrian Covaci acknowledgespostdoctoral fellowship of the Funds of Scientific Research Flan-ers (FWO), while Tinne Geens was funded by the Research Fundsf the University of Antwerp. UK work (Robin Law) has beenunded by the Department for Environment, Food and Rural AffairsDefra). Mohamed Abdallah acknowledges gratefully the provisionf studentships from the Egyptian Government and the Egyptianinistry of Higher Education.

eferences

[1] European Risk Assessment Report on 2,2′ ,6,6′-tetrabromo-4,4′-isopropylidenediphenol(tetrabromobisphenol-A or TBBP-A). Part I,Environment, European Commission, Joint Research Centre, EuropeanChemicals Bureau, in draft, 2008.

[2] European Risk Assessment Report on 2,2′ ,6,6′-tetrabromo-4,4′-isopropylidenediphenol(tetrabromobisphenol-A or TBBP-A). Part II, Humanhealth, vol. 63, European Commission, Joint Research Centre, EuropeanChemicals Bureau, EUR22161E, 2006.

[3] Environmental Health Criteria 172, Tetrabromobisphenol A and Derivatives,International Programme on Chemical Safety, World Health Organization,Geneva, 1995.

[4] R.J. Law, C.R. Allchin, J. de Boer, A. Covaci, D. Herzke, P. Lepom, S. Morris, J.Tronczynski, C.A. de Wit, Chemosphere 64 (2006) 187.

[5] Bromine Science Environmental Forum, http://www.bsef.com (accessedDecember 15, 2007).

[6] H. Hakk, A Survey of Tetrabromobisphenol A. Second International Workshopon Brominated Flame Retardants, BFR 2001, Stockholm University, Sweden,2001.

[7] P.A. Arias, Presented at the Second International Workshop on BrominatedFlame Retardants BFR 2001, Stockholm, Sweden, May 14–16, 2001, p. 17.

[8] EBFRIP questions Norwegian proposal to restrict the use of TBBP-A and HBCDin consumer products, European Brominated Flame Retardant Industry Panel(EBFRIP), statement June 4, 2007.

[9] Flame Retardant Fact Sheet—Tetrabromobisphenol A (TBBP-A), EuropeanFlame Retardants Association (EFRA), http://www.cefic-efra.com (accessedDecember 15, 2007).

[10] Brominated flame retardants, Environmental Project 494, Danish Environ-mental Protection Agency, 1999.

[11] Directive 2002/95/EC of the European Parliament and of the Council of Jan-uary 27, 2003 on the restriction of the use of certain hazardous substances inelectrical and electronic equipment, Off. J. Eur. Comm. L 37 (2003) 19.

[12] G.W. Gribble, Environ. Sci. Pollut. Res. 7 (2000) 37.[13] Directive 2002/96/EC of the European Parliament and of the Council of January

27, 2003 on waste electrical and electronic equipment (WEEE), Off. J. Eur.Comm. L 037 (2003) 24.

[14] Regulation 2364/2000/EC of October 25, 2000 concerning the fourth list ofpriority substances as foreseen under Council Regulation (ECC) No. 793/93,Off. J. Eur. Comm. L 273 (2000) 5.

[15] Regulation (EC) No. 1907/2006 of the European Parliament and of the Councilof December 18, 2006 concerning the Registration, Evaluation, Authorisationand Restriction of Chemicals (REACH), establishing a European ChemicalsAgency, amending Directive 1999/45/EC and repealing Council Regulation(EEC) No. 793/93 and Commission Regulation (EC) No. 1488/94 as wellas Council Directive 76/769/EEC and Commission Directives 91/155/EEC,93/67/EEC, 93/105/EC and 2000/21/EC, Off. J. Eur. Comm. L 396 (2006) 1.

[16] S. Eisenreich, S. Munn, S. Pakalin, Proceedings of the 4th International Work-shop on Brominated Flame Retardants, Amsterdam, The Netherlands, April24-27, 2007 (unpaginated).

[17] Draft updated risk assessment of 4,4′-isopropylidenediphenol (bisphenol-A),European Chemicals Bureau (ECB), 2007, R325 0705 env1.

[18] Decision 2455/2001/EC of November 20, 2001. 1, Establishing the list of prior-ity substances in the field of water policy and amending Directive 2000/60/EC,Off. J. Eur. Comm. L 331 (2001) 1.

[19] K. Akutsu, M. Kitagawa, H. Nakazawa, T. Makino, K. Iwazaki, H. Oda, S. Hori,Chemosphere 53 (2003) 645.

[20] Y. Yoshida, T. Kawamura, K. Yamamoto, H. Sekii, S. Komoto, OrganohalogenCompd. 67 (2005) 2127.

[21] M.H. Wong, S.C. Wu, W.J. Deng, X.Z. Yu, Q. Luo, A.O.W. Leung, C.S.C. Wong, W.J.Luksemburg, A.S. Wong, Environ. Pollut. 149 (2007) 131.

[22] D. Gutzman, R. Chenier, J. Pasternak, L. Suffredine, K. Taylor, Proceedings ofthe Third International Workshop on Brominated Flame Retardants, BFR 2004,Toronto, ON, Canada, 2004.

[23] S. Kitamura, N. Jinno, S. Ohta, H. Kuroki, N. Fujimoto, Biochem. Biophys. Res.Commun. 293 (2002) 554.

[24] M. Ghisari, E.C. Bonefeld-Jorgensen, Mol. Cell. Endocrinol. 244 (2005) 31.

A 1216 (2009) 346–363

[25] M.H. Kester, S. Bulduk, H. van Toor, D. Tibboel, W. Meinl, H. Glatt, C.N. Falany,M.W. Coughtrie, A.G. Schuur, A. Brouwer, T.J. Visser, J. Clin. Endocrinol. Metab.87 (2002) 1142.

[26] I.A. Meerts, R.J. Letcher, S. Hoving, G. Marsh, A.A. Bergman, J.G. Lemmen, B.van Der Burg, A. Brouwer, Environ. Health Perspect. 109 (2001) 399.

[27] M. Samuelsen, C. Olsen, J.A. Holme, E. Meussen-Elholm, A. Bergmann, J.K.Hongslo, Cell Biol. Toxicol. 17 (2001) 139.

[28] C.M. Olsen, E. Meussen-Elholm, M. Samuelsen, J.A. Holme, J.K. Hongslo, Phar-macol. Toxicol. 92 (2003) 180.

[29] S. Kitamura, T. Kato, M. Iida, N. Jinno, T. Suzuki, S. Ohta, N. Fujimoto, H. Hanada,K. Kashiwagi, A. Kashiwagi, Life Sci. 76 (2005) 1589.

[30] I.A.T.M. Meerts, J.J. van Zanden, E.A.C. Luijks, I. van Leeuwen-Bol, G. Marsh, E.Jakobsson, Å. Bergman, A. Brouwer, Toxicol. Sci. 56 (2000) 95.

[31] T. Hamers, J.H. Kamstra, E. Sonneveld, A.J. Murk, M.H.A. Kester, P.L. Andersson,J. Legler, A. Brouwer, Toxicol. Sci. 92 (2006) 157.

[32] E. Mariussen, F. Fonnum, Neurochem. Int. 43 (2003) 533.[33] S. Pullen, R. Boecker, G. Tiegs, Toxicology 184 (2003) 11.[34] T. Reistad, E. Mariussen, F. Fonnum, Toxicol. Sci. 83 (2005) 89.[35] S. Strack, T. Detzel, M. Wahl, B. Kuch, H.F. Krug, Chemosphere 67 (2007) S405.[36] R.V. Kuiper, E.J. van den Brandhof, P.E.G. Leonards, L.T.M. van der Ven, P.W.

Wester, J.G. Vos, Arch. Toxicol. 81 (2007) 1.[37] Draft Risk Reduction Monograph No. 3, Brominated Flame Retardants, Organ-

isation for Economic Co-operation and Development, May 1994.[38] M. Ash, I. Ash, The Index of Flame Retardants, Gower Publishing Limited,

Aldershot, UK, 1997, ISBN 0-566-07885-6.[39] A.-M. Prins, C. Doumen, J. Kaspersma, Proceedings of the Flame Retardants

2000 Conference, London, February 8–9, 2000, p. 77.[40] Y. Bar Yaakov, L. Utevski, J. Reyes, P. Georlette, S. Bron, J.M. Lopez-Cuesta, Pro-

ceedings of the Flame Retardants 2000 Conference, London, February 8–9,2000, p. 87.

[41] D. De Schryver, T. DeSoto, R. Dawson, S.D. Landry, R. Herbiet, Proceedings of theFlame Retardants 2002 Conference, Interscience Communications Limited,London, 2002.

[42] B. Plaitin, A. Fonzé, R. Braibont, Proceedings of the Flame Retardants ‘98 Con-ference, London, February 3–4, 1998, p. 139.

[43] I. Watanabe, T. Kashimoto, R. Tatsukawa, Bull. Environ. Contam. Toxicol 31(1983) 48.

[44] U. Sellström, B. Jansson, Chemosphere 31 (1995) 3085.[45] J. de Boer, C. Allchin, B. Zegers, J.P. Boon, S.H. Brandsma, S. Morris, A.W. Kruijt, I.

van der Steen, J.M. van Hesselingen, J.J.H. Haftka, HBCD and TBBP-A in sewagesludge, sediments and biota, including interlaboratory study, RIVO Report No.C033/02, September 2002.

[46] A.S. Allard, M. Remberger, A.H. Neilson, Appl. Environ. Microbiol. 53 (1987)839.

[47] A. Covaci, S. Voorspoels, J. de Boer, Environ. Int. 29 (2003) 735.[48] A. Covaci, S. Voorspoels, L. Ramos, H. Neels, R. Blust, Chromatogr. A 1153 (2007)

145.[49] E. Eljarrat, D. Barcelo, Trends Anal. Chem. 23 (2004) 727.[50] R.A. Hites, Environ. Sci. Technol. 38 (2004) 945.[51] A. Covaci, A.C. Gerecke, R.J. Law, M. Kohler, N.V. Heeb, H. Leslie, C.R. Allchin, J.

de Boer, Environ. Sci. Technol. 40 (2006) 3679.[52] S. Suzuki, A. Hasegawa, Anal. Sci. 22 (2006) 469.[53] H. Gallart-Ayala, E. Moyano, M.T. Galceran, Rapid Commun. Mass Spectrom.

21 (2007) 4039.[54] H. Sambe, K. Hoshina, K. Hosoya, J. Haginaka, J. Chromatogr. A 1134 (2006) 16.[55] J. Tollbäck, C. Crescenzi, E. Dyremark, J. Chromatogr. A 1104 (2006) 106.[56] K. Inoue, S. Yoshida, S. Nakayama, R. Ito, N. Okanouchi, H. Nakazawa, Arch.

Environ. Contam. Toxicol. 51 (2006) 503.[57] S. Morris, C.R. Allchin, B.N. Zegers, J.J.H. Haftka, J.P. Boon, C. Belpaire, P.E.G.

Leonards, S.P.J. van Leeuwen, J. de Boer, Environ. Sci. Technol. 38 (2004) 5497.[58] S. Chu, G.D. Haffner, R.J. Letcher, J. Chromatogr. A 1097 (2005) 25.[59] R. Saint-Louis, E. Pelletier, Analyst 129 (2004) 724.[60] S.C. Quade, M. Alaee, C. Marvin, R. Hale, K.R. Solomon, N.J. Bunce, A.T. Fisk,

Organohalogen Compd. 62 (2003) 327.[61] J. Jin, H. Peng, Y. Wang, R. Yang, J. Cui, Organohalogen Compd. 68 (2006) 85.[62] R.J. Law, P. Bersuder, C. Allchin, J. Barry, Environ. Sci. Technol. 40 (2006) 2177.[63] S. Morris, P. Bersuder, C.R. Allchin, B. Zegers, J.P. Boon, P.E.G. Leonards, J. de

Boer, Trends Anal. Chem. 25 (2006) 343.[64] K. Granby, T. S Cederberg, Proceedings of the Fourth International Workshop

on Brominated Flame Retardants BFR 2007, Amsterdam, The Netherlands,2007.

[65] U. Berger, D. Herzke, T.M. Sandanger, Anal. Chem. 76 (2004) 441.[66] R. Cariou, J.P. Antignac, P. Marchand, A. Berrebi, D. Zalko, F. Andre, B. Le Bizec,

J. Chromatogr. A 1100 (2005) 144.[67] T. Hayama, H. Yoshida, S. Onimaru, S. Yonekura, H. Kuroki, K. Todoroki, H.

Nohta, M. Yamaguchi, J. Chromatogr. B 809 (2004) 131.[68] B. Johnson-Restrepo, D. Adams, K. Kannan, Chemosphere 70 (2008) 1935.[69] M. Schlummer, F. Brandl, A. Mäurer, R. van Eldik, J. Chromatogr. A 1064 (2005)

39.
[70] M. Pöhlein, A. Segura Llopis, M. Wolf, R. van Eldik, J. Chromatogr. A 1066 (2005)
111.[71] J. Llorca-Porcel, G. Martinez-Sanchez, B. Alvarez, M.A. Cobollo, I. Valor, Anal.

Chim. Acta 569 (2006) 113.[72] M. Polo, M. Llompart, C. Garcia-Jares, G. Gomez-Noya, M.H. Bollain, R. Cela, J.

Chromatogr. A 1124 (2006) 11.

http://www.bsef.com/

http://www.cefic-efra.com/

atogr.

[

[[

[

[[

[

[

[

[

[


[73] E. Blanco, M.C. Casais, M.C. Mejuto, R. Cela, Anal. Chem. 78 (2006) 2772.[74] C. Yu, B. Hu, J. Chromatogr. A 1160 (2007) 71.[75] A.M. Altwaiq, M. Wolf, R. van Eldik, Anal. Chim. Acta 491 (2003) 111.[76] S. Kikuchi, K. Kawauchi, S. Ooki, M. Kurosawa, H. Honjo, T. Yagishita, Anal. Sci.

20 (2004) 1111.[77] F.T. Dettmer, H. Wichmann, J. de Boer, M. Bahadir, Chemosphere 39 (1999)

1523.[78] A.S. Vasquez, A. Martin, J.M. Costa-Fernandez, J.R. Encinar, N. Bordel, R. Pereiro,

A. Sanz-Mendel, Anal. Bioanal. Chem. 389 (2007) 683.[79] C. Thomsen, E. Lundanes, G. Becher, Environ. Sci. Technol. 36 (2002) 1414.[80] C. Thomsen, V. Horpestad Liane, G. Becher, J. Chromatogr. B 846 (2007) 252.[81] J. de Boer, D.E. Wells, Trends Anal. Chem. 25 (2006) 364.[82] P. Korytár, A. Covaci, P.E.G. Leonards, J. de Boer, U.A.Th. Brinkman, J. Chro-

matogr. A 1100 (2005) 20.[83] L. Debrauwer, A. Riu, M. Jouahri, E. Rathahao, I. Jouanin, J.P. Antignac, R. Cariou,

B. Le Bizec, D. Zalko, J. Chromatogr. A 1082 (2005) 98.[84] K. Worrall, P. Hancock, A. Fernandes, M. Driffield, Organohalogen Compd. 69

(2007) 698.[85] R. Köppen, R. Becker, C. Jung, C. Piechotta, I. Nehls, Anal. Bioanal. Chem. 384

(2006) 1485.[86] M. Frederiksen, K. Vorkamp, R. Bossi, F. Riget, M. Dam, B. Svensmark, Int. J.

Environ. Anal. Chem. 87 (2007) 1095.[87] D. Zalko, C. Prouillac, A. Riu, E. Perdu, L. Dolo, I. Jouanin, C. Canlet, L. Debrauwer,

J.P. Cravedi, Chemosphere 64 (2006) 318.[88] E. Blanco, M.C. Casais, M.C. Mejuto, R. Cela, J. Chromatogr. A 1071 (2005) 205.[89] A. Sjödin, Occupational and dietary exposure to organohalogenated sub-

stances with special emphasis on polybrominated flame retardants, Ph.D.Thesis, Stockholm University, Sweden, 2000.

[90] O. Päpke, P. Fürst, T. Herrmann, Talanta 63 (2004) 1203.[91] H.M. Stapleton, J.M. Keller, M.M. Schantz, J.R. Kucklick, S.D. Leigh, S.A. Wise,

Anal. Bioanal. Chem. 387 (2007) 2365.[92] Å. Bergman, M. Athanasiadou, E. Klasson Wehler, A. Sjödin, Organohalogen

Compd. 43 (1999) 89.[93] A. Sjödin, H. Carlsson, K. Thuresson, S. Sjolin, A. Bergman, C. Ostman, Environ.

Sci. Technol. 35 (2001) 448.[94] H. Takigami, G. Suzuki, Y. Hirai, S. Sakai, Organohalogen Compd. 69 (2007)

2785.[95] Z. Xie, R. Ebinghaus, R. Lohmann, O. Heemken, A. Cabaa, W. Puttmann, Anal.

Chim. Acta 584 (2007) 333.[96] M. Alaee, D. Muir, C. Cannon, P. Helm, T. Harner, T. Bidleman, Contam. Assess.

1 Rep. 2 (2003) 116.[97] M. Abdallah, S. Harrad, C. Ibarra, M. Diamond, L. Melymuk, M. Robson, A.

Covaci, Environ. Sci. Technol. 42 (2008) 459.[98] S. Harrad, C. Ibarra, M. Diamond, L. Melymuk, M. Robson, J. Douwes, L. Roosens,

A.C. Dirtu, A. Covaci, Environ. Int. 34 (2008) 232.[99] D. Santillo, I. Labunska, H. Davidson, P. Johnston, M. Strutt, O. Knowles,

Greenpeace Research Laboratories technical note 01/2003 (GRL-TN-01-
2003) 2003, http://www.greenpeace.to/publications/housedust uk 2003.pdf(accessed January 4th 2008).
100] P.E.G. Leonards, D. Santillo, K. Brigden, I. van der Veen, J. von Hesselingen,J. de Boer, P. Johnston, Proceedings of the Second International Workshopon Brominated Flame Retardants BFR 2001, Stockholm, Sweden, May 14–16,2001, p. 299.

[

[

A 1216 (2009) 346–363 363

[101] S. Chernyak, S. Batterman, C. Godwin, C. Jia, S. Charles, Organohalogen Compd.69 (2007) 994.

102] M. Osako, Y.J. Kim, S.I. Sakai, Chemosphere 57 (2004) 1571.103] H. Peng, J. Jin, Y. Wang, W.Z. Liu, R.M. Yang, Chin. J. Anal. Chem. 35 (2007)

549.104] M. Schlabach, E. Fjeld, H. Gundersen, E. Mariussen, G. Kjellberg, E. Breivik,

Organohalogen Compd. 66 (2004) 3730.105] K. Öberg, K. Warman, T. Oberg, Chemosphere 48 (2002) 805.106] C. de Wit, K. Nylund, U. Eriksson, A. Kierkegaard, L. Asplund, Organohalogen

Compd. 69 (2007) 2686.[107] R.C. Brandli, T. Kupper, T.D. Bucheli, M. Zennegg, S. Huber, D. Ortelli, J. Muller,

C. Schaffner, S. Iozza, P. Schmid, U. Berger, P. Edder, M. Oehme, F.X. Stadelman,J. Tarradellas, J. Environ. Monit. 9 (2007) 465.

108] J. Voordeckers, D. Fennell, K. Jones, M. Haggblom, Environ. Sci. Technol. 36(2002) 696.

109] H.B. Lee, T.E. Peart, Water Qual. Res. J. Canada 37 (2002) 681.[110] T.A. Verslycke, A.D. Vethaak, K. Arijs, C.R. Janssen, Environ. Pollut. 136 (2005)

19.[111] E. Fjeld, M. Schlabach, J.A. Berge, T. Eggen, P. Snilsberg, G. Källberg, S.

Rognerud, E.K. Enge, A. Borgen, H. Gundersen, Kartlegging av utvalgte nyeorganiske miljøgifter-bromerte flammehemmere, klorerte parafiner, bisfenolA og trichlosan. Norsk institutt för vannforskning (NIVA), Rapport 4809-2004, Oslo, Norway (in Norwegian), 2004 (available from http://www.nilu.no).

[112] D. Herzke, U. Berger, R. Kallenborn, T. Nygard, W. Vetter, Chemosphere 61(2005) 441.

[113] K. Vorkamp, M. Thomsen, K. Falk, H. Leslie, S. Møller, P.B. Sørensen, Environ.Sci. Technol. 39 (2005) 8199.

[114] L. Hagmar, A. Sjödin, P. Häglund, K. Thuresson, L. Rylander, Å. Bergman,Organohalogen Compd. 47 (2000) 198.

[115] K. Jakobsson, K. Thuresson, L. Rylander, A. Sjödin, L. Hagmar, Å. Bergman,Chemosphere 46 (2002) 709.

[116] C. Thomsen, E. Lundanes, G. Becher, J. Environ. Monit. 23 (2001) 366.[117] J. Nagayama, H. Tsuji, T. Takasuga, Organohalogen Compd. 48 (2000) 27.[118] M. Frederiksen, K. Vorkamp, R. Bossi, B. Svensmark, Proceedings of the Fourth

International Workshop on Brominated Flame Retardants, BFR 2007, Amster-dam, The Netherlands, 2007.

[119] A. Sjödin D.G.Jr., Å. Patterson, Bergman, Environ. Int. 29 (2003) 829.120] K. Saito, A. Sjödin, C.D. Sandau, M.D. Davis, H. Nakazawa, Y. Matsuki, D.G.

Patterson Jr., Chemosphere 57 (2004) 373.[121] Food Standards Agency, Brominated chemicals: UK dietary intakes, Food

Survey Information Sheet 10/06, 2006a, 26 pp. (http://www.food.gov.uk/multimedia/pdfs/fsis1006.pdf).

122] Food Standards Agency, Brominated chemicals in farmed, wild fish, shell-fish and fish oil dietary supplements, Food Survey Information Sheet 04/06,2006b, 32 pp., http://www.food.gov.uk/multimedia/pdfs/fsis0406.pdf.

123] UK Committee on Toxicity of Chemicals in Food, Consumer products and the
Environment, http://www.food.gov.uk/multimedia/pdfs/fsis1006.pdf.
124] Advice of the scientific panel on contamination in the food chain on a requestfrom the Commission related to relevant chemical compounds in the groupof brominated flame retardants for monitoring in feed and food, EFSA J. 328(2006) 1.

125] H. Hakk, G. Larsen, Å. Bergman, U. Örn, Xenobiotica 30 (2000) 881.

http://www.greenpeace.to/publications/housedust_uk_2003.pdf

http://www.nilu.no/

http://www.nilu.no/

http://www.food.gov.uk/multimedia/pdfs/fsis1006.pdf




Analytical and environmental aspects of the flame retardant tetrabromobisphenol-A and its derivatives

Documents