TETRABROMOBISPHENOL A 1. Exposure Data 1.1.2 Structure and molecular formula, and relative molecular mass 1.1. Identification of the agent From NTP (2014), ECHA (2006) %U %U &+ 1.1.1 Nomenclature +2 & 2+ &+ Chem. Abstr. Serv. Reg. No.: 79-94-7 %U %U Chem. Abstr. Serv. Name: Tetrabromobis- phenol A Molecular formula: C15H12Br4O2 EINECS No.: 201-236-9 Relative molecular weight: 543.88 IUPAC Name: 2,2′,6,6′-Tetrabromo-4,4′- isopropylidenediphenol 1.1.3 Physical and chemical properties of the Synonyms: 2,2-Bis(3,5-dibromo-4-hydroxy- pure substance phenyl) propane; phenol, 4,4′−iso-propyl- idenebis, (dibromo-); 4,4′-isopropyl- Description: White crystalline powder at idene-bis(2,6-dibromophenol); phenol, 4,4′- 20 °C containing 58.4% bromine (1-methylethylidene)bis(2,6-dibromo-); Boiling point: ~316 °C (decomposes at 3,3′,5,5′-tetrabromobisphenol-A; tetrabromo- 200–300 °C) dihydroxy diphenylpropane Melting point: 181–182 °C Acronyms: TBBP-A; TBBP; TBBPA Density: 2.12 g/cm3 Volatility: Vapour pressure, 6.24 × 10–9 kPa at 25 °C Water solubility: 1.26 mg/L at 25 °C Octanol/water partition coefficient: log Kow, 5.9 Decomposition: When heated to decomposi- tion, emits bromine vapours Conversion factor: 1 ppm = 22.6 mg/m3 at 20 °C. 247 IARC MONOGRAPHS – 115 Fig. 1.1 Global market demand for tetrabromobisphenol A, 1995–2004 180 000 170 000 160 000 139 200 140 000 129 000 135 000 122 300 120 000 127 000 111 000 119 500 109 000 Market size Market size (tonnes) 100 000 104 000 80 000 1994 1996 1998 2000 2002 2004 Year From Covaci et al. (2009); numbers were calculated from data published in ECHA (2008) 1.2 Production and use total global production volume of tetrabromo- bisphenol A is estimated at > 100 000 tonnes per 1.2.1 Production year (ECHA, 2008). Except for a minor reduction (a) Production methods in production between 2000 and 2002, an overall increasing trend was observed in the estimated The production process for tetrabromo- global market demand for tetrabromobisphenol bisphenol A involves the bromination of A from 109 000 tonnes per year in 1975 to 170 000 bisphenol A in the presence of a solvent, such tonnes per year in 2004 (Fig. 1.1). as methanol, a halocarbon alone, or a halo- carbon with water, or 50% hydrobromic acid, or 1.2.2 Use aqueous alkyl monoethers (ECHA, 2006). Due to the nature of the process and the by-products Approximately 58% of tetrabromobisphenol (e.g. hydrobromic acid and methyl bromide) that A is used as a reactive brominated flame retardant can be formed, the production process is largely in epoxy, polycarbonate and phenolic resins in conducted in closed systems (Covaci et al., 2009). printed circuit boards, 18% is used for the prod- uction of tetrabromobisphenol A derivatives and (b) Production volume oligomers, while 18% is used as additive flame Tetrabromobisphenol A is a compound retardant in the manufacture of acrylonitrile– with a high production volume that is currently butadiene–styrene resins or high impact poly- produced in China, Israel, Japan, Jordan, and the styrene (Covaci et al., 2009). USA, but no longer in the European Union. The 248 Tetrabromobisphenol A (a) Reactive applications does not react chemically with the other compo- Tetrabromobisphenol A is used primarily as nents of the polymer, and may therefore leach an intermediate in the manufacture of polycar- out of the polymer matrix after incorporation bonate unsaturated polyester and epoxy resins, (Covaci et al., 2009). in which it becomes covalently bound in the polymer. Polycarbonates are used in commu- 1.3 Measurement and analysis nication and electronic equipment, electronic appliances, transportation devices, sports and Several studies have reported on different recreational equipment, and lighting fixtures methods for extraction of tetra-bromobisphenol and signs. Unsaturated polyesters are used in A from different environmental and biological the manufacture of simulated marble floor tiles, matrices (Table 1.1; Covaci et al., 2009). Solid- bowling balls, furniture, coupling compounds phase extraction on pre-packed C18 cartridges for sewer pipes, buttons, and automotive patching was the most commonly reported method for compounds. Flame-retardant epoxy resins may the extraction/clean-up of tetrabromobisphenol be used mainly for the manufacture of printed A from liquid samples, including water (Wang circuit boards (Lassen et al., 1999). Moreover, et al., 2015a), plasma (Chu & Letcher, 2013) epoxy resins containing tetrabromobisphenol and milk (Nakao et al., 2015). More aggressive A are used to encapsulate certain electronic extraction techniques such as Soxhlet extraction, components (e.g. plastic/paper capacitors, micro- pressurized liquid extraction, ultrasound-as- processors, bipolar power transistors, “inte- sisted extraction and microwave-assisted extrac- grated gate bipolar transistor power modules” tion were required for the efficient extraction and “application specific integrated circuits” on of tetrabromobisphenol A from solid samples, printed circuit boards) (ECHA, 2008). including dust (Abdallah et al., 2008), soil (Tang et al., 2014), sediment (Labadie et al., 2010), (b) Additive applications sewage sludge (Guerra et al., 2010), polymers Tetrabromobisphenol A is generally used (Vilaplana et al., 2009), and frozen animal tissues with antimony oxide for optimum performance (Tang et al., 2015). The inclusion of a relatively as an additive fire retardant IPCS,( 1995) that polar organic solvent (e.g. dichloromethane is applied in acrylonitrile–butadiene–styrene or acetone) was found to be necessary for the resins that are used in automotive parts, pipes efficient extraction of tetrabromobisphenol A and fittings, refrigerators, business machines (Covaci et al., 2009). Hyphenated chromato- and telephones (ECHA, 2008), and can also be graphic methods coupled to mass spectrometric applied to high-impact polystyrene resins used detection were commonly applied for the quan- in casings of electrical and electronic equipment, titative determination of tetrabromobisphenol A furniture, building and construction materials in various media (Table 1.1; Covaci et al., 2009). (IPCS, 1995). The largest additive use of tetra- Other methods of analysis including enzyme- bromobisphenol A is in television casings for linked immunosorbent assay (Bu et al., 2014) and which approximately 450 tonnes are used per year. capillary electrophoresis (Blanco et al., 2005) were Other uses include: personal computer monitor also reported for the determination of tetrabro- casings, components in printers, fax machines mobisphenol A in environmental samples. and photocopiers, vacuum cleaners, coffee machines and plugs/sockets (ECHA, 2008). As additive flame retardant, tetrabromobisphenol A 249 250 IARC MONOGRAPHSIARC 115 – Table 1.1 Overview of typical analytical procedures used for the determination of tetrabromobisphenol A in selected matrices Matrix Pretreatment Extraction procedure Extract purification Instrumental Recovery Limit of References (solvent) analysis (%) detection River water, Filtration HLB-SPE cartridge (2% SPE cartridge (2% formic LC-ESI-MS/MS 78–91 0.003 ng/mL Yang et al. (2014) tap water, ammonia in methanol) acid in methanol) waste water Surface water Filtration SPE-cartridge (ethyl – UHPLC-UV 76 0.081 ng/mL Kowalski & Mazur acetate) (2014) Air samples 125-mm glass Soxhlet (DCM, 8 h) SPE cartridge containing LC-ESI-MS/MS 89 0.027 ng/m3 Abdallah & Harrad fibre filters and acidified silica (44% (2010) PUF disks concentrated sulfuric acid) Dust Sieving (250 µm) Dispersive liquid–liquid – GC-MS 89 250 ng/g Barrett et al. (2015) microextraction Dust Sieving (63 μm) Ultrasonication Filtration and online clean- LC-APCI-MS/ 88 0.6 ng/g Kopp et al. (2012) (methanol:AcN:isopropanol up MS (1:1:2), 60 °C, 30 min) Soil Freeze-dried and PLE (DCM) Activated silica gel column LC-APCI-MS/ 82–96 0.025 ng/g Tang et al. (2014) sieved MS Soil Mixed with Soxhlet (hexane:acetone SPE cartridge GC-MS 84–122 0.19 ng/g Han et al. (2013) sodium sulfate (1:1), 24 h) Sediment Sieved (230 mesh PLE (hexane:DCM (1:3), Silica gel column LC-ESI-MS/MS 70–110 0.05 ng/g Lee et al. (2015) sieve) activated copper) Sediment Mixed with Ultrasonication Hydrochloric acid-activated GC-NCI-MS 93 0.05 ng/g Labadie et al. (2010) sodium sulfate (hexane:acetone (1:1), 20 copper strings and SPE min) cartridge Sewage sludge – Shaking with 5 mL SPE cartridge LC-ESI-MS/MS 106 – Song et al. (2014) methanol at 350 rpm, 60 min (3 cycles) Polymer Powdered/ MAE (isopropanol:hexane 0.45 mm Teflon filter HPLC-UV 74–96 1630 ng/g Vilaplana et al. fractions of granulated (1:1), 130 °C, 60 min) (2009) WEEE Human Formic acid LLE (hexane, ethanol then GPC with silica gel column GC-NCI-MS 87–99 0.2 ng/g Fujii et al. (2014b) serum, diethyl ether) human milk, dietary homogenate Table 1.1 (continued) Matrix Pretreatment Extraction procedure Extract purification Instrumental Recovery Limit of References (solvent) analysis (%) detection Tissues of Mixed with Soxhlet (DCM:hexane (3:1), GPC and LLE with sulfuric LC-ESI-MS/MS 93 0.0003 ng/g Johnson-Restrepo humans, sodium sulfate 16 h) acid and filtration et al. (2008) dolphins and sharks Fish tissues Freeze-dried, Soxhlet (hexane:acetone Sulfuric acid and silica gel LC-ESI-MS/MS 84–99 0.025 ng/g Tang et al. (2015) powdered (1:1), 48 h) column Scallops, gills Homogenization Soxhlet (hexane:DCM (4:1), SPE column LC-ESI-MS/MS 79 5 ng/g Hu et al. (2015b) and digestive sodium sulfate 12 h) glands Egg Homogenization Column extraction GPC and SPE column and LC-TOF-MS 79 0.02 ng/g Berger et al. (2004) sodium sulfate (acetone:cyclohexane (1:3), derivatization GC-LRMS 57 0.01 ng/g 1 h) GC-HRMS 0.001 ng/g Birds muscle Mixed with Soxhlet (hexane:acetone GPC with silica gel column LC-ESI-MS/MS 75 0.27 ng/g He et al.