Yourlastname 1 Student Name Professor Name Subject 2012 Brominated flame retardants Introduction Flame retardants are special

chemicals that are added to materials in order render them fire proof. Most widely used flame retardants belong to the group of brominated organic compounds. They are produced industrially by bromination of various organic substrates. BFRs can be classified by the way of incorporating into the target material: chemical bonding or physical mixing. BFRs closely resemble another group of industrial chemicals: polychlorinated biphenyls (PCBs). PCBs have been shown to be toxic for the environment. Therefore, the safety issue with regard to BFRs toxicology needs to be thoroughly evaluated with the help of modern methods of scientific research. Global annual production of BFR is estimated to be 5 million tonnes (Birnbaum & Staskal, 2004). The data provided in Table 1 indicate a steady increase in the production of BFRs, mostly at the expense of developing Asian markets. Table 1. Global production of BFRs between 1989 and 1999. (Alaeea et al., 2003). 1989 Europe Asia USA Total 28.0 28.7 50.0 106.7 1994 32.5 38.5 65 136 1999 30.9 113.9 58.7 203.5

Yourlastname 2 However, one of the disadvantages of polymers is their inherent flammability. That means they easily catch and propagate the fire. In order to render polymer materials non flammable different chemical additives are used. The combustion process consists of four stages: preheating, evaporation, decomposition and propagation. Flame retardants can act on any of the abovementioned stages. For example, aluminium hydroxide, one of the flame retardants, acts on the preheating phase. When heated above 200 degrees Celsius, the aluminium hydroxide undergoes dehydration (water removal), which is endothermic process. This leads to the temperature decrease and consequently to the extinguishment of the fire. Another mechanism of fire interruption is controlling fire propagation. The chemical reaction of fire propagation involves free radicals that start and support oxidation of organic substrates (polymers) in the presence of oxygen. The idea of the abovementioned technology is to trap those free radicals to stop the oxidation process. This is achieved with the help of halogens that are very efficient in capturing free radicals. The bigger the halogen atom is the larger its radical capturing activity. Therefore, the relative radical trapping activity increases in the following row:
F <Cl< Br< I

However, not all of the halogens from the given sequence can be successfully employed as flame retardants. Fluorine compounds, for instance, are very stable and produce fluorine radicals too late in the oxidation process. On the contrary, iodine compounds are very unstable and decompose too quickly before they can participate in the reaction. Therefore, bromine derivatives gained widespread usage as fire retardants. They are generally referred to as brominated flame retardants (BFR). Chemical structures of BFRs are shown in Fig 1.

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Fig 1. Chemical structures of (A) PBBs, (B) PBDEs, (C) HBCD, and (D) TBBPA. From (Birnbaum & Staskal, 2004). Production of BFRs Tetrabromobisphenol is produced by the bromination of bis-phenol-A according to the following reaction:

+ 2Br2

+ 4HBr (1)

Tetrabromobisphenol is chemically incorporated into the industrial polymers thus rendering them flame resistant. Polybrominated diphenylethers (PBDEs) PBDEs belong to the second most widely used group of so-called additive retardants, i.e. they are physically mixed with various polymers. They are synthesized by catalytic bromination of diphenyl ether in the organic solvent:

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+ Br2

The reaction given above is not selective, resulting in the mixture of products (Sjodin et al., 1998) Hexabromocyclododecane HBCD is produced by the bromination of cyclododecatriene . Reaction mixture contains three isomers (alpha, beta and gamma) with latter being the predominant product (Zegers et al., 2005). BFRs in the environment Many BFRs belong to additive compounds, i. e. they are not chemically bonded but physically mixed with plastics or textiles. That means that BFRs are more prone to leach from plastic matrix and to spread in the environment. There are several negative consequences of environmental pollution by BFRs briefly explained below. Bioaccumulation Bioaccumulation (or biomagnification) is a process of accumulation of organic pollutants through the entire food chain. BFRs with lower number of bromine atoms (from four to seven) in the carbon chain have higher bioaccumulative potential (de Wit, 2002). Analysis of BFRs concentrations in the fish samples from Swedish rivers showed BFRs enrichment by factor 15 (Sellstrom et al., 1998). Endocrine disrupting activity During last decades of human industrial activity thousands tonnes of different chemicals have been released into the environment. Some of those chemicals adversely affect human

Yourlastname 5 health. There is growing evidence in the scientific community that BFRs possess an endocrinedisrupting activity (Darnerud et al., 2001). Endocrine system is a system of glands that excretes special chemical substances called hormones directly into the blood. Those hormones regulate growth and development of the body, sexual functions and mood. Hormones play a crucial role in the maintaining homeostasis, growth and development of living organisms. Endocrinedisruptors are chemical compounds that interfere with biosynthesis, release, transport, binding and activation of natural hormones. Thyroid hormone is extremely important for the proper brain development, physiology and metabolism. One of the thyroid hormones is thyroxine T4 (Fig. 2). It is obvious that thyroxine shares chemical similarity with TBBPA. Thyroxine is a precursor for the biosynthesis of thyroid hormone 3,3,5-triiodothyronine. Structural similarity can explain observed effects of TBBPA interference with hormonal receptors.

Fig 2. Chemical structure of the thyroxine. Indeed, Marsh et al. (1998) showed that hydroxylated PBDEs bind thyroid hormone receptors TR and TR with stronger preference for the latter. One comprehensive study (Hamers et al., 2006) investigated in vitro ED activity of 27 individual BFRs to identify ED mode of action of different chemicals and to classify BFRs into

Yourlastname 6 groups with similar ED potencies. It has been demonstrated on the receptor level that BFRs possess endocrine disrupting properties, with some chemicals exhibiting even higher ED potency than natural hormones or clinical positive controls. Another study (Roze et al., 2009) investigated possible correlations between prenatal exposure to different organohalogens including BFRs and cognition abilities, motor and behavioural functions of school age children. Gas chromatography coupled to mass-spectrometry (GC-MS) analysis of serum samples taken from pregnant women revealed twelve organohalogenic compounds including brominated biphenyl ethers and

hexabromocyclododecane. The concentrations of those compounds in serum have been shown to positively correlate with worse neurodevelopmental outcomes of school children (5-6 years old) such as fine manipulative abilities and attention. However, the positive correlation with better visual perception, better coordination and better behaviour was observed suggesting that complex interactions between environmental chemicals and endogenous hormonal system exist. All above said suggests that the issue of possible endocrine disrupting activity of BFRs deserve further scientific investigation in order to clarify all possible effects of the environmental release of BFRs on humans and wildlife. Toxicity Screening studies for environmental pollutants indicate that PBDEs are persistent organic pollutants found in various animal species (Boer et al., 1998). Mammalian fetus is very susceptible to the maternal intake of xenobiotics. It is known that from the third trimester of pregnancy till second year of life the human brain undergoes intensive growth and development, named brain growth spurt (Davison & Dobbing, 1968). Brain growth spurt involves numerous biochemical changes that lead to the formation of mature brain structures. A wealth of scientific

Yourlastname 7 evidence suggests that many persistent environmental pollutants disturb brain functioning particularly in neonatal period of life. For example, various doses of PBDEs administered to tested animals (mice) resulted in permanent deviations in spontaneous behaviour (Eriksson et al. , 2001). Moreover, the response was dose dependent, meaning that higher doses of chemicals are more neurotoxic. In addition 2,2,4,4,5-pentabromodiphenylether (PBDE 99) also affected cognitive functions in adult animals. Another widely used BFR TBBPA was shown to be toxic to liver, probably by affecting mitochondria (Boecker et al., 2001). In vitro studies (Pullen et al., 2003) demonstrated immune suppressing activity of TBBBPA via inhibiting expression of immune related CD25 protein. Conclusion Polymer materials have gained wide acceptance in the modern society. They are lightweight, durable and electrically resistant. They are also much cheaper than comparable wood or metal analogues. Therefore nowadays polymers can be found almost everywhere including furniture, building materials, cars, electric cables insulation and textiles. However, plastic materials are highly flammable and need to be modified to become fire-proof. Several chemical additives are applied to polymers in the process of manufacturing. Brominated flame retardants belong to the group bromo substituted organic compounds that efficiently control the spread of fire. BFRs constitute the largest group of flame retardants currently in use due to their low cost and high fire fighting efficiency. However, scientific studies raise concerns over safety of BFRs. The fact that BFRs are detected at distances far away from the place of their use suggests a long range atmospheric transport of those chemicals. The high ratios of BFR in living organisms over background values

Yourlastname 8 indicate the bioaccumulation of BFR in the food chain. This is particularly important for humans since they are positioned on the top of food chain and are at higher risk of poisoning by BFRs. There is strong scientific evidence that BFRs mimic the action of hormones produced by endocrine system. Human endocrine system is of high importance for the brain development. Prenatal exposure to BFRs through the maternal intake can result in neurodevelopmental disorders. BFRs can also exert direct toxicity affecting liver mitochondria or by blocking the uptake of important neuromediators. Moreover, BRRs have been shown to accumulate in the biotic environment, with bioaccumulation ratio up to 18000. BFRs are structurally similar to polychlorinated biphenyls, both classes of compounds being very lipophilic. Lipophilicity (high affinity to fat) can explain why BFRs tend to overaccumulate in the lipoid tissues. Even though there are many scientific publications that address the issue of BFRs safety, there is still a lot of work that has to be done in future. Most studies performed with BFRs have been done in vitro, in artificial system that only slightly resembles real situation in vivo. Solid experiments with regard to carcinogenicity and reproduction toxicity of BFRs have not yet been properly addressed by the scientific community. It is also important to take into the account the possible synergism of BFRs, i. e. the effects of simultaneous action of various BFRs on living organisms. It is of high importance to closely monitor the levels of BFRs in the environment including human tissues over prolonged periods in order to assess long term effects of brominated flame retardants. To completely exclude any risk coming from environmental chemicals it is highly desirable to design and construct materials that do not require any dangerous additives to be safe environmentally friendly. This will help to reduce the risk of environmental pollution to the lowest possible level.

Yourlastname 9 References Alaeea, M, Ariasb, P., Sjodinc, A., Bergman, A. (2003). An overview of commercially used brominated flame retardants, their applications, their use patterns in different countries/regions and possible modes of release. Environment International, 29 683 689. Birnbaum, L. & Staskal, D. (2004). Brominated Flame Retardants: Cause for Concern? Brominated Flame Retardants: Cause for Concern? Environ Health Perspect. 112, 917. Boecker, R., H., Schwind, B., Kraus, V., Pullen, S., Tiegs, G. (2001). Cellular disturbances by various brominated flame retardants. Abstract. Presented at the Second International Workshop on Brominated Flame Retardants, 1416 May 2001, Stockholm, Sweden. Darnerud, P. O., Eriksen, G. S., Johanesson, T., Larsen, P. B., and Viluksela, M. (2001). Polybrominated diphenyl ethers: Occurrence, dietary exposure, and toxicology. Environ. Health Perspect. 109, 4968.). Davison, A., N. & Dobbing, J. Applied Neurochemistry. Oxford: Blackwell Science, 1968;178 221. de Boer J, Wester PG, Klamer HJC, Lewis WE, Boon JP. (1998). Do flame retardants threaten ocean life? Nature 394, 2829. de Wit, C. (2002). An overview of brominated flame retardants in the environment. Chemosphere 46, 583624. Eriksson, P., Jakobsson, E. & Fredriksson, A. (2001). Brominated Flame Retardants: A Novel Class of Developmental Neurotoxicants in Our Environment? Environ Health Perspect 109, 903908.

Yourlastname 10 Hamers, T., Kamstra, H.,Sonneveld, E., Murk, A., Kester, M., Andersson, P., Legler, J. & Brouwer, A. (2006). In Vitro Profiling of the Endocrine-Disrupting Potency of Brominated Flame Retardants. Toxicol. Sci., 92, 157-173. Legler, J. & Brouwer, A. (2003). Are brominated flame retardants endocrine disruptors? Environ. Int. 29, 879885. Marsh, G,, Bergman, A., Bladh, L., Glillner, M., Jackobsson, E. (1998). Synthesis of phydroxybromodiphnyl ethers and binding to the thyroid hormone receptor.

Organohalogen Compounds, 37, 305308. Pullen, S., Boecker, R., Tiegs, G. (2003). The flame retardants tetrabromobisphenol A and tetrabromobisphenol A-bisallylether suppress the induction of interleukin-2 receptor alpha chain (CD25) in murine splenocytes. Toxicology, 184, 1122. Roze, E., Meijer, L., Bakker, A., Van Braeckel, K., Sauer, P. & Bos, A. (2009). Prenatal exposure to organohalogens, including brominated flame retardants, influences motor, cognitive, and behavioral performance at school age. Environmental Health Perspectives, 117, 1953-1958. Sellstrom, U., Kierkegaard, A., de Wit, C., Jansson, B. (1998). Polybrominated diphenyl ethers and hexabromocycododecane in sediment and fish from a Swedish river. Environ Toxicol Chem 17,10651072. Sjodin, A, Jakobsson, E, Kierkegaard, A, Marsh, G, Sellstro, U. (1998). Gas chromatographic identification of polybrominated diphenyl ethers in a commercial product, Bromkal 705DE. J. Chromatogr. A, 822, 83 89. Zegers, B., N., Mets, A., Van Bommel, R., Minkenberg, C., Hamers, T., Kamstra, J. H., Pierce, G. J. & Boon, J., P. (2005). Stereo-isomer specific bioaccumulation of

Yourlastname 11 hexabromocyclododecane in small marine mammals. Environ. Sci. Technol. 39, 2095 2100.