REVIEW OF THE DOSSIER PENTABROMODIPHENYL ETHER (Penta-BDE)

Transcription

1 REVIEW OF THE DOSSIER PENTABROMODIPHENYL ETHER (Penta-BDE) Proposed for nomination to the UN-ECE LRTAP Protocal Reviewer A Summary: Introduction: PBDEs are produced by bromination of diphenyl ether in the presence of a Friedel-Craft catalyst in a solvent. PBDEs are however, typically produced at three different degrees of bromination, i.e., Penta-BDE, Octa-BDE and Deca-BDE, and classified according to their average bromine content. The bromination of diphenyl ether is rather specific due to the directing properties of the oxygen and steric hindrance and consequently resulting in a limited number of PBDE congeners are formed. The commercial Penta-BDE more than 70% of the product by weight is represented by only two major congeners, i.e., 2,2,4,4 -tetrabromodiphenyl ether (BDE-47) and 2,2,4,4,5- pentabromodiphenyl ether (BDE-99). Method: The dossier was examined for against the requirements outlined in the Executive Body Decision 1998/2 for scientific and technical content. The material was compared to the information available at the time of preparation of this document and recent developments in this field. In recent years the number of publications on PBDEs especially on congeners commonly found in the Penta-BDE formulation has increased exponentially. In fact today, it is very difficult to keep up to date with the literature in this field. Papers quoted adequately support the claims in this document; however additional information is available in the literature, including the Special Issue of Chemosphere on BFRs Volume 46, No.5 (February 2002), Special Issue of Environment International Volume 29-No.6 (August 2003), and for more recent information The 3 rd International Workshop on BFR ( are extremely good resources. POP characteristics in terms of the guidance and indicative numerical values provided in Executive Body 98/2 for: a) Potential for long-range atmospheric transport Even though the vapor pressures for the congeners of Pent-BDEs are low, they are within the same range of PCBs congeners commonly found in the Arctic. PBDEs in general have low water solubility resulting high Henry s Law Constant indicating that volatilization of lower brominated PBDEs are favored. Also experimental determinations and modeling exercises indicated that BDE-47 and -99 are transported in the vapor phase; which is facilitates the long range transport of these compounds. PBDEs have been determined in the Arctic at various locations (Sweden, Canada, and Russia). b) Toxicity In-vivo studies have shown nuerotoxicity at 0.8mg/kg for BDE-99 in a single dose for 10 days old mouse pups, similar results have been observed with PCBs. Other studies have shown that the liver is the main 1

2 organ affected by Penta-BDE at 1mg/kg/day. In-vitro studies showed that hydroxylated-bdes competing potential with thyroxin. BDE-47 has been shown to be acutely toxic to copepod and cause disturbance to larval development. c) Persistence In order for these compounds to be effective flame retardants they have to be stable during the life expectancy of the products they are in use. For example Penta-BDE should be stable for at least 10 years in the foam used in household furniture. According to various studies Penta-BDE compounds are not biodegradable in water and sediment. BDE-47 and -99 were measured in sediment cores corresponding to at least years old sediment indicating half-life >6 months. d) Bioaccumulation. PBDEs in general are combined with synthetic polymers, which have petrogenic origin. Penta- BDE formulation is mainly used in polyurethane foam. Since these are oil based material can only mix with lipophilic compounds (like dissolves like). It is not surprising that these compounds have Log K ow for these compounds are greater than 5 (for Penta-BDE Log K ow = ). Monitoring or equivalent scientific information suggesting long-range transboundary atmospheric transport Monitoring data reported in this dossier as well as the data published since then confirm that the main congeners of Penta-BDE has been observed in air and biota from the remote regions such as the arctic. Data reported by Law et al. (2003) and Ikonomou et al. (2002) indicated that the levels of Penta-BDE congeners are on the rise in the Arctic, doubling approximately every five years. Similar results have been observed in other parts of North America such as the biota from Great Lakes (Norstrom et al. 2002, Luross et al. 2000), Beluga from St. Lawrence Estuary (Lebeuf et al. 2003) and seals from San Francisco Bay area (She et al 2002). Sufficiency of the information to suggest that the substance is likely to have significant adverse human and/or environmental effects resulting from its long-range transboundary atmospheric transport Adverse environmental effects Results indicate that the levels of Penta-BDE congeners are on the rise in the Arctic. Considering its intrinsic toxicity and persistence in the environment pent-bde congener will bioaccumulate in biota and will move up the food web. This causes concern among the predator birds and terrestrial animals at the top of the wood web. Low level neurotoxicity would impair their ability to hunt, and would hinder their ability to survive. Adverse human effects Food is a source of PBDE exposure for general population. Individuals living in remote areas such as the Arctic rely more on fish and marine mammals harvested from these regions. Increased consumption of fatty fish and animal tissue represent an increased risk for this population. In recent studies PBDEs were observed in breast milk samples collected in the Arctic (Ryan et al. 2004). Unlike PCBs that only limited number of individuals would come in direct contact with these chemicals, humans are intimately in contact with PBDEs particularly with the Penta-BDE which is in their furniture. PBDEs including congeners of in Penta-BDE have been observed in 2

3 household dust in significant quantity. In cold climates where the indoor air is not exchanged frequently increases the exposure risk from dust. Conclusions on the technical content of the dossier This is a well prepared dossier. The references were up to date at the time of the preparation, and are sufficient to back the conclusions of this document. However the arguments can be further reinforced with the addition of new data available in the literature. Disclaimer The views expressed in this technical review are solely those of the reviewer and do not necessarily represent the views of any organization and/or government to which the reviewer is affiliated. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. Summary: Reviewer B Introduction The dossier reviews the POP properties of the commercial pentabromo diphenyl ether (pentabde) in relation to the screening criteria and gives some additional background information for consideration of its possible nomination as a new POP. Commercial pentabromo diphenyl ether (pentabde) is a highly viscous liquid mixture of tri-, tetra-, penta, hexa-, and heptabromo diphenyl ethers. The major components of pentabde products are 2,2,4,4 tetrabromo diphenyl ether (BDE-47) and 2,2,4,4,5 pentabromo diphenyl ether (BDE-99). PentaBDE is one of the three present commercial polybrominated diphenyl ethers (PBDEs). The other commercial mixtures are octabromodiphenyl ether and decabromodiphenyl ether. There are altogether 209 congeners in the group of PBDEs. The number of bromine atoms in the group varies between one and ten. Congeners with bromine amounts from three to ten are present in the commercial products. In this review, the term pentabromo diphenyl ether and the abbreviation pentabde refer to the commercial product if not otherwise stated. Polybrominated diphenyl ethers are hydrophobic so they are easily removed from the aqueous environment and are likely to sorb in or onto sediments and particulate matter, or to fatty tissues, aiding their distribution throughout the environment. PBDEs have some structural similarities to PCBs and DDT and, therefore, their chemical properties, persistence and distribution in the environment follow similar patterns (Rahman et al., 2001). Methods Firstly, the process of nomination was studied using documents from the UNECE website. Secondly, a number of related peer-reviewed articles on pentabde were read to get an overall impression of the compound. Subsequently, the dossier was read and the indicative values were reviewed carefully, and if necessary compared with that from open literature sources. 3

4 Potential for long-range atmospheric transport The information provided in the dossier is sufficient and in line with additional data provided here. PentaBDE meets the criteria mentioned in EB 1998/2. Toxicity and ecotoxicity The dossier provides references indicating that the substance is toxic or very toxic to aquatic organisms and may cause serious damage to health by prolonged exposure. This is confirmed by additional literature data on ecotoxicity, although the amount of data from the open literature is still limited. Literature on toxic effect focus on various endpoints. The information provided in the dossier is sufficient, but an update of the literature would strengthen the proposal. Persistence The dossier indicates that pentabde is very persistent. Experimental data are not presented in the dossier, but are lacking in more recent open literature as well. The information provided is sufficient and in line with the additional data in this review. Bioaccumulation The dossier concludes that pentabde fulfills the criteria for bioaccumulation, based on the log Kow value and the bioaccumulation data reported. Additional data presented in this review are in line with this conclusion. Experimental data are limited and difficult to interpret due to debromination of various compounds within the organism. Monitoring or equivalent scientific information suggesting long-range transboundary atmospheric transport (EB decision 1998/2-2a). The dossier on pentabde indicates that data from remote areas are still scarce but that they clearly show increasing concentrations of pentabde. New additional literature shows that PBDE congeners have been found in the arctic environment. From the monitoring data there is clear evidence of long-range atmospheric transport of the major components of pentabde to remote regions, supported by air analyses. Sufficiency of the information to suggest that the substance is likely to have significant adverse human and/or environmental effects resulting from its long-range transboundary atmospheric transport (EB decision 1998/2-2b).. The dossier does not provide much information on the likelihood of PBDE having significant adverse human and/or environmental effects resulting from its long-range transboundary atmospheric transport. It is questionable if such information should be aimed at, as adverse effects will already appear in industrial and highly populated areas in a much earlier stage. The present understanding of the environmental behavior of PBDEs is far from complete and further research is necessary to more fully understand their fate. Efforts should be focused on measuring physical-chemical properties of individual PBDE congeners, including half times, on obtaining monitoring data of environmental levels at various sampling sites (Palm et al., 2002, D Silva et al., 2004). It is pointed out by Rahman et al. (2001) that one way of release of PBDEs is through the waste disposal. It may leach out from there and can become a persistent source of emission of these compounds to the environment over many years. Because of the limited 4

5 information and the fact that concentrations seems to increase concern over their fate and effects is warranted. Effects in wildlife and man have not yet been observed Darnerud (2003). Conclusions on the technical content of the dossier The dossier is written in a compact and easy readable style and the literature is up-to-date until Additional literature supporting the dossier can be added and would strengthen the proposal on some points. A number of reviews on PBDEs have appeared since The dossier provides enough information for screening against the indicative values of the POP characteristics. Introduction: The dossier reviews the POP properties of the commercial pentabromo diphenyl ether (pentabde) in relation to the screening criteria and gives some additional background information for consideration of its possible nomination as a new POP. Commercial pentabromo diphenyl ether (pentabde) is a highly viscous liquid mixture of tri-, tetra-, penta, hexa-, and heptabromo diphenyl ethers. The major components of pentabde products are 2,2,4,4 tetrabromo diphenyl ether (BDE-47) and 2,2,4,4,5 pentabromo diphenyl ether (BDE-99). PentaBDE is one of the three present commercial polybrominated diphenyl ethers (PBDEs). The other commercial mixtures are octabromodiphenyl ether and decabromodiphenyl ether. There are altogether 209 congeners in the group of PBDEs. The number of bromine atoms in the group varies between one and ten. Congeners with bromine amounts from three to ten are present in the commercial products. In this review, the term pentabromo diphenyl ether and the abbreviation pentabde refer to the commercial product if not otherwise stated. Polybrominated diphenyl ethers are hydrophobic so they are easily removed from the aqueous environment and are likely to sorb in or onto sediments and particulate matter, or to fatty tissues, aiding their distribution throughout the environment. PBDEs have some structural similarities to PCBs and DDT and, therefore, their chemical properties, persistence and distribution in the environment follow similar patterns (Rahman et al., 2001). Methods: First, the explanation of the nomination process, and the backgrounds of the Protocol, the Task Force, the Working Group of Strategies and the Executive Body of the UNECE were downloaded from the UNECE website and were read to get a good impression of the reviewing process. Secondly, the dossier on pentabde was examined as a whole to get an impression of the contents of the dossier. Then a number of related peer-reviewed articles on pentabde were retrieved from the literature to get an impression of the compound(s) and the progress in studying the compound(s). Subsequently, the indicative values were reviewed carefully, and if necessary compared with that from open literature sources. POP characteristics in terms of the guidance and indicative numerical values provided in Executive Body 98/2 for: 5

6 Potential for long-range atmospheric transport In the EB decision 1998/2 the potential for long-range transboundary atmospheric transport is described as: Evidence that the substance has a vapor pressure below 1,000 Pa and an atmospheric half-life greater than two days. Alternatively, monitoring data showing that the substance is found in remote regions. The dossier indicates that the vapor pressure of pentabde is less than 1,000 Pa, but that pentabde components have very low volatility. Henry s Law constants of the lower brominated components suggest that these can be volatilized in significant amounts. The atmospheric half life times presented in the dossier were estimated from Structure Activity Relationships (SARs) and were retrieved from different sources. All half life times for pentabde in the atmosphere presented were much longer than two days. The dossier states that data from remote areas are still scarce, but they indicate clearly increasing concentrations of pentabde. The difference in the PBDE congener profiles from fish samples at a possible point source and a background area suggest that BDE-47 especially is susceptible to long-range transport via air. The total concentration of PBDEs in Arctic beluga whale showed a 7-fold increase between 1982 and Further data on the half life in air was provided by EMEP and were 7 and 11 days for BDE-47 and BDE-99, respectively (Vulykh et al., 2004). Gouin and Harner (2003). Estimated half life times in air of 11 and 20 days for BDE-47 and BDE-99, respectively. Wania and Dugani (2003) estimated the longe-range transport of PBDEs and indicated that their predictions should be supported by field measurements in order to have credibility. Field measurements of PBDEs from the literature generally support the model predictions in that they suggest a prevalence of the lighter PBDE congeners (BDE-47 and BDE-99) in samples from remote regions. Longe-range transport of PBDEs is also supported by data provided by Strandberg et al. (2001) Law et al. (2003) and Vorkamp et al. (2004), part of which from the arctic region. The dossier may be updated with these data. Conclusion: the information provided in the dossier is sufficient and in line with additional data provided here. PentaBDE meets the criteria mentioned in EB 1998/2. Toxicity and ecotoxicity Toxicity is described in the EB 1998/2 decision as: potential to adversely affect human health and/or the environment. No further criteria on toxicity are given in the EB 1998/2 decision. Results on toxicity were presented in the dossier under the heading adverse effects. The dossier cite studies on in vivo rat studies which indicate that the liver is the main target organ affected by pentabde with a NOAEL of 1 mg/kg/d and other in vivo studies which have found developmental neurotoxicity, and behavioral effects already after a single dose of 0.8 mg/kg BDE-99 to 10 days old mouse pups. 6

7 Furthermore, in vitro studies have shown i.a., the thyroxin competing potential of hydroxylated metabolites and other metabolites. Darnerud (2003) states in a review on the effects of polybrominated flame retardants on man and wildlife that generally pentabdes seem to cause adverse effects at the comparable lowest dose, whereas much higher doses are needed for effects of DecaBDE. Critical effects of pentabdes on neurobehavioral development (from 0.6 mg/kg bw) and on thyroid hormone levels in rats and mice at somewhat higher dose are mentioned in this review. Toxicological effects of pentabdes are summarized more extensively in Darnerud et al. (2001), Rahman et al. (2001), McDonald (2002) and Darnerud (2003), In the dossier BDE-47 was shown to be acutely toxic for a copepod Acartia tonsa in a standard 48 h study. Moreover, BDE-47 caused disturbances in larval development in much lower levels. The EC50 in a 5 day study was determined as 13 µg/l. Effects on rainbow trout fry sack growth presented in the dossier were found at the level of 16 µg/l. Based on the toxicity to copepod and fish pentabde fulfils the EU criteria for the classifications very toxic to aquatic organisms with the risk phrase R50. Subchronic effects of four polybrominated diphenyl ethers ([PBDEs]; BDE-28, BDE-47, BDE- 99, and BDE-100) on larval development of the marine copepod Acartia tonsa were studied by Wollenberger et al. (2005). PBDEs showed a 5-d EC 50 in the low µg/l range (1.2 µg/l for BDE- 100; 4.2 µg/l for BDE-99; 13 µg/l for BDE-28; and 13 µg/l for BDE-47). These concentrations were up to two orders of magnitude below the 48-h LC50 for acute adult toxicity (108 µg/l for BDE-28; 520 µg/l for BDE-100; 705 µg/l for BDE-99; and 2,370 µg/l for BDE-47). The acute toxicity of BDE-99 to Daphnia magna was tested by Evandri et al (2003). The 24-h EC50 value was µg/l and the 48-h EC50 values was 25 µg/l. Conclusion: The dossier provides references indicating that the substance is toxic or very toxic to aquatic organisms and may cause serious damage to health by prolonged exposure. This is confirmed by additional literature data on ecotoxicity, although the amount of data from the open literature is still limited. Literature on toxic effect focus on various endpoints. The information provided in the dossier is sufficient, but an update of the literature would strengthen the proposal. Persistence Persistence is described in the EB 1998/2 decision as: evidence that the substance's half-life in water is greater than two months, or that its half-life in soils is greater than six months, or that its half-life in sediments is greater than six months. Alternatively, evidence that the substance is otherwise sufficiently persistent to be of concern within the scope of the protocol may also fulfill this criterion. The dossier presents one experimental study on degradation. The study was carried out with aerobic activated sludge sewage treatment organisms and showed that pentabde is not readily biodegradable. No further studies have been reported for water, sediment or soil. Therefore results using structure-activity relationships (SARs) were used to estimate the half life time in various 7

8 compartments. Half life times were 60 days for water and 360 days for aerobic sediment and soil for both BDE-47 and BDE-99. The authors of the dossier indicate that the presence in remote areas and the presence in sediments where pentabde congeners have been deposited a few decades ago indicate a high persistence. Additional modeling data on persistence were provided by EMEP (Vulykh et al., 2004). The overall half life times in the environment were estimated to be 5.5 months for BDE-47 and 6.1 months for BDE-99 (Vulykh et al., 2004). The mass balance estimations presented in Alcock et al. (2003) highlights that soil is the ultimate sink of BDE-47 in the North American environment. Overall residence time in the environment is 125 days and is similar to those calculated for the UK. Experimental data on degradation rates are still lacking. Various authors stated that there was a need for such data as they provide information on the overall persistence of the substances and their potential for long-range transport. (Palm et al., 2002; Gouin and Harner, 2003; D Silva, 2004). Conclusion: the dossier indicates that pentabde is very persistent. Experimental data are not provided in the dossier, but are lacking in more recent open literature as well. The information provided is sufficient and in line with the additional data provided in this review. Bioaccumulation. Bioaccumulation is described in the EB 1998/2 decision as: (i) Evidence that the BCF or BAF for the substance is greater than 5,000 or the log Kow is greater than 5; or (ii) Alternatively, if the bio-accumulative potential is significantly lower than (i) above, other factors, such as the high toxicity of the substance, that make it of concern within the scope of the protocol. Log Kow values are presented in the chapter on bioaccumulation and more extensively in chapter 5.2 where log Kow values are presented for different PBDEs. All values are higher than 5, the range presented for pentabde is For carp (Cyprinus carpio) a bioconcentration factor of 27,400 L/kg is mentioned, whereas high bioconcentration is also reported for mussels (Mytilus edulis). The original reference mentions values of and for BDE-47 and BDE-99, respectively (Gustafsson et al., 1999). An overview experimental and estimated log Kow values for various PBDE congeners is given in Palm et al. (2002). Log Kow for BDE-47 varies between 6 and 7 and for the various pentabde congeners between 6 and 8. Experimental values for pentabde generated by Braekeveldt et al. (2003) are also between 6 and 8. Bioaccumulation and biotransformation of BDE congeners in Lake trouts (Salvelinus namaycush) was studied by Tomy et al. (2004). Half lives of the BDEs ranged from 38 to 173 days and biomagnification factors ranged from 1.6 to Tomy et al (2004) indicated that the bioaccumulation parameters should be viewed with caution because the values were influenced by debromination and the relative abundance of the individual BDEs to which the fish were exposed. 8

9 Debromination of higher brominated BDEs may lead to the formation of lower brominated BDEs which may hamper interpretation of the data. Conclusion: the dossier concludes that pentabde fulfills the criteria for bioaccumulation, based on the log Kow value and the bioaccumulation data reported. Additional data are presented in this review are in line with this conclusion. Experimental data are limited and difficult to interpret due to debromination of various compounds within the organism. Monitoring or equivalent scientific information suggesting long-range transboundary atmospheric transport (EB decision 1998/2-2a). The dossier on pentabde indicate that data from remote areas are still scarce but that they clearly show increasing concentrations of pentabde. Concentrations of BDE-47 and BDE-99 in whales have been reported in the ranges of ca. 66 to 864 ng/g lipid (BDE-47) and 24 to 169 ng/g lipid (BDE-99). An increasing temporal trend of PBDE concentrations in Arctic beluga whales (Delphinapterus leucas) has also been reported. In an additional study by Strandberg et al. (2001) PBDEs were found in samples from urban, but also from rural and remote sites, indicating that these compounds are widely distributed and that they can be transported through the atmosphere to remote areas. BDE congeners have also been found in the arctic environment (Law et al., 2003; Vorkamp et al., 2004). Palm et al (2002) concludes that there is clear monitoring evidence of contamination from remote regions and air analyses show that the major components of pentabde can be transported long-range by air. Sufficiency of the information to suggest that the substance is likely to have significant adverse human and/or environmental effects resulting from its long-range transboundary atmospheric transport (EB decision 1998/2-2b). The dossier does not provide much information on the likelihood of pentabde having significant adverse human and/or environmental effects resulting from its long-range transboundary atmospheric transport. However, the fact that pentabde is present in remote areas, and that their concentrations are increasing provide sufficient evidence that pentabde is likely to have significant adverse human and/or environmental effects. Hale et al (2001) concluded that PBDE concentrations in the environment appear to be increasing in some areas as well as in humans. Data on residence times of PBDEs in humans are not available (Hale et al., 2001). D Silva (2004) cites a study by Allchin and de Boer in which it was shown that the concentration of BDE-99 in UK sediments increased 10-fold between 1995 and Another study cited showed a 10-fold increase in PBDEs in sediments in Europe between 1992 and Law et al. (2003) report that the amount of pentabde in blubber of Beluga whales (Delphinapterus leucas) increased significantly during the 1990 s, average BDE concentrations more than doubled between the and the periods. PentaBDE is known to biomagnify in aquatic food webs and showed a transfer factor of 3 4 between earthworms and sediment (Leppänen and Kukkonen). 9

10 The present understanding of the environmental behavior of PBDEs is far from complete and further research is necessary to more fully understand their fate. Efforts should be focused on measuring physical-chemical properties of individual PBDE congeners, including half times, on obtaining monitoring data of environmental levels at various sampling sites (Palm et al., 2002, D Silva et al., 2004). It is pointed out by Rahman et al. (2001) that one way of release of PBDEs is through the waste disposal. It may leach out from there and can become a persistent source of emission of these compounds to the environment. Because of the limited information and the fact that concentrations seems to increase concern over their fate and effects is warranted. Effects of pentabdes in wildlife and man have not yet been observed Darnerud (2003). Conclusions on the technical content of the dossier 1. The dossier is written in a compact and easy readable style. 2. The literature used in the dossier is up-to-date until Newer references can be included and would strengthen the proposal. They do not change the conclusions of the proposal, but may facilitate the interpretation of some data. 3. A number of recent review articles are available, such as Rahman et al. (2001), De Wit (2002), Hardy (2002) and D Silva (2004). They may be included. 4. The dossier provides enough information for screening against the indicative values of the POP characteristics Disclaimer The views expressed in this technical review are solely those of the reviewer and do not necessarily represent the views of any organization and/or government to which the reviewer is affiliated. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. Literature 1. Alcock RE, Sweetman AJ, Prevedourosb K, Jones KC. (2003). Understanding levels and trends of BDE-47 in the UK and North America: an assessment of principal reservoirs and source inputs. Environ. Internat. 29, Braekeveldt E, Tittlemier SA, Tomy GT. (2003). Direct measurement of octanol-water partition coefficients of some environmentally relevant brominated diphenyl ether congeners. Chemosphere 51, Darnerud PO. (2003). Toxic effects of brominated flame retardants in man and in wildlife. Environ. Internat. 29, De Wit, CA. (2002). An overview of brominated flame retardants in the environment. Chemosphere 46, D Silva K, Fernandes A, Rose M. (2004). Brominated organic micropollutants. Igniting the flame retardant issue. Crit. Rev. Environ. Sci. Technol. 34, Evandri MG, Costa LG, Bolle P. (2003). Evaluation of brominated diphenyl ether-99 toxicity with Radhidocelis subcapitata and Daphnia magna. Environ. Toxicol. Chem. 22, Gouin T, Harner, T. (2003). Modelling the environmental fate of the polybrominated diphenyl ethers. Environ. Int. 29,

11 8. Gustafsson K, Bjork M, Burreau S, Gilek M. (1999). Bioaccumulation kinetics of brominated flame retardants (polybrominated diphenyl ethers) in blue mussels (Mytilus edulis). Environ. Toxicol. Chem. 18, Hale RC, La Guardia MJ, Harvey EP, Mainor TM, Duff WH, Gaylor MO. (2001). Polybrominated diphenyl ether flame retardants in Virginia freshwater fishes (USA). Environ. Sci. Technol. 35: Hardy ML. (2002. The toxicology of the three commercial polybrominated diphenyl oxide (ether) flame retardants. Chemosphere 46, Law RJ, Alaee M, Allchin CR, Boon JP, Lebeuf M, Lepom P, Stern GA. (2003). Levels and trends of polybrominated diphenylethers and other brominated flame retardants in wildlife. Environ. Int. 29, Leppänen MT, Kukkonen JVL. (2004) Toxicokinetics of sediment-associated polybrominated diphenylethers (flame retardants) in benthic invertebrates (Lumbriculus variegatus, oligochaeta) Environ. Toxicol. Chem. 23, Palm A, Cousins IT, Mackay D, Tysklind M, Metcalfe C, Alaee M. (2002). Assessing the environmental fate of chemicals of emerging concern: a case study of the polybrominated diphenyl ethers. Environ. Pollut. 117, Strandberg B, Dodder NG, Basu I, Hites RA. (2001). Concentrations and spatial variations of bolybrominated diphenyl ethers and other organohalogen compounds in Great Lakes air. Environ. Sci. Technol. 35, Tomy GT, Palace VP, Halldorson T, Braekeveldt E, Danell R, Wautier K, Evans B, Brinkworth L, Fisk AT. (2004). Bioaccumulation, biotransformation, and biochemical effects of brominated diphenyl ethers in juvenile Lake trout (Salvelinus namaycush). Environ. Sci. Technol. 38, Vorkamp K, Christensen JH, Riget F. (2004). Polybrominated diphenyl ethers and organochlorine compounds in biota from the marine environment of East Greenland. Sci. Total Environ. 331, Vulykh N, Dutchak S, Mantseva E, Shatalov V. (2004). EMEP contribution to the preparatory work for the review of the CLRTAP protocol on persistent organic pollutants. EMEP-MSC-E Information Note 10/ Wollenberger L, Dinan L, Breitholtz M. (2005). Brominated flame retardants: Activities in a crustacean development test and in an ecdysteroid screening assay. Environ. Toxicol. Chem. 24, Summary: REVIEWER C Introduction Commercial pentabromodiphenyl ether (PentaBDE) is a mixture of tri-, tetra-, penta-, hexa- and heptabromodiphenyl ethers. Its major components are 2,2,4,4 -tetrabromodiphenylether (BDE- 47) and 2,2,4,4,5- pentabromodiphenylether (BDE-99). PentaBDE belongs to the group of brominated flame retardants. At present, its only reported use is in different polyurethane applications. 11

12 Methods The dossier was examined in order to provide a scientific evaluation of the technical content of the proposal against the requirements outlined in Executive Body decision 1998/2. Concise information given in Chapter 3 and more detailed information provided in Chapter 5 and Annex 5 were carefully examined. Quoted papers and reports were examined. Articles and reports from open literature, mostly published after the dossier had been completed, were also examined. Comments below refer to the fundamental contents of the dossier. One additional reference has been indicated. POP characteristics in terms of the guidance and indicative numerical values provided in Executive Body 98/2 for: Potential for long-range atmospheric transport. According to the vapour pressure measured for the different homologue groups of the commercial product, pentabde volatilisation is expected to be very low, especially for heavier congeners. Nevertheless, water solubility values and Henry s Law constants indicate that volatilisation of lower brominated congeners from water may occur and be significant. Because of the measured sediment-water partition coefficients, there is an indication that heavier congeners may be transported bound to particles. Estimated half-lives in atmosphere for BDE 47 and 99 are compatible with the hypothesis of long-range transboundary atmospheric transport. The detection of BDE-47 and BDE-99 in the vapour phase of indoor and outdoor air samples also indicates that volatilisation may occur. Toxicity PentaBDE is very toxic to aquatic organisms (e.g. EC 50 = 14µg/l in a 48-hour Daphnia study). Adverse effects on earthworms have also been reported. Potential for human health effects are indicated by outcomes of different studies on animal models. Liver toxicity, developmental neurotoxicity, and the decrease of circulating thyroxin are observed in rodent models and identified as the most sensitive toxicological endpoints. Repeated dose oral studies in rodents indicate liver as the main target organ. Persistence According to the biodegradation study quoted, pentabde is not readily biodegradable. No experimental data is available on any kind of abiotic degradation. Estimated total (biotic and abiotic) half-lives for BDE 47 and 99 reported indicate that these congeners meet the criterion of persistence for aerobic sediments and water. The presence of PentaBDE in layers of marine sediments dated decades ago indicates environmental persistence. Bioaccumulation Log Kow > 5 are reported for the commercial product and for the different homologue groups. This data is confirmed by a more recent study 1 carried out on main individual congeners, for all of which log Kow > 5 have been measured. Bioconcentration factors > 5000 have been determined for different aquatic species (Mytilus edulis, Cyprinus carpio). Bioaccumulation potential is shown by the increasing levels with increasing age observed in pooled samples of the same species and by studies observing increasing concentrations with increasing trophic levels in aquatic biota from the same region. Biomagnification is also shown by PentaBDE levels assessed in both aquatic and terrestrial top food web predators. High levels of pentabde have been found in eggs of predator birds. 12

13 Measured half-lives of the main components of commercial PentaBDE mixtures in laboratory animals and resistance to metabolism observed in both in vivo and in vitro studies provide additional evidence of the bioaccumulative nature of these compounds. Monitoring or equivalent scientific information suggesting long-range transboundary atmospheric transport. Monitoring data presented shows that main congeners of commercial PentaBDE have been detected in background and remote regions, in all environmental compartments and in local biota. Information produced suggests long-range atmospheric transport as the source of contamination for these areas. The few available studies on temporal trends in remote areas show level increase (eventually followed by levelling off in the 90s) in biota and sediments. Sufficiency of the information to suggest that the substance is likely to have significant adverse human and /or environmental effects resulting from its long-range transboundary atmospheric transport. Adverse environmental effects Adverse environmental effects could result from PentaBDE presence in remote regions and its observed concentrations in some species of biota. PentaBDE may in fact cause long-term adverse effects in the aquatic environment, considering its intrinsic toxicity (EC 50 for Daphnia), lack of biodegradation and the high bioaccumulation potential observed. Also, the high PentaBDE levels observed in marine predators as well as in predator birds (and their eggs) of the terrestrial food web, provide reasons for concern for both the aquatic and the terrestrial compartment. Adverse human effects. Although data available does not allow to directly and adequately characterize a human health risk, reasons for concern are related to the toxicological endpoints identified as the most sensitive in animal models, to the presence of pentabde in human tissues, and to the bioaccumulative nature of this substance. General population exposure to PentaBDE mostly occurs via food, and fish consumption is reported to account for most of the dietary intake. For this reason, the possibility that consumption of fatty fish contaminated by PentaBDE could represent an incremental risk factor for specific population subgroups (e.g. high fish consumers living in arctic regions), particularly with respect to developmental effects in breast-fed children, must be taken into account. Conclusion on the technical content of the dossier The dossier contains the information required to support the candidature of PentaBDE as a global POP. Evidence is produced on its persistence and bioaccumulation potential. Physical and chemical properties and estimated half-lives in atmosphere are compatible with the occurrence of long-range atmospheric transport. Data set presented on levels of PentaBDE in remote regions is comprehensive and clear. Ecotoxicological and toxicological information produced is sufficient to identify endpoints of concerns and nature of the critical effects. Additional Reference 13

14 1) Braekevelt E., Tittlemier S., Tomy G. (2003). Direct measurement of octanol-water partition coefficients of some environmentally relevant brominated diphenyl ether congeners. Chemosphere 51, Disclaimer The views expressed in this technical review are solely those of the reviewer and do not necessarily represent the views of any organization and/or government to which the reviewer is affiliated. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. Summary REVIEWER D PeBDE is a brominated flame retardant most commonly used in the production of polyurethane foam. Research over the last two decades has indicated that levels of PeBDEs have been rising rapidly in the environment, biota, and humans. These monitoring results have been accompanied by increased information on potential toxicity from this family of chemicals. As a result of these concerns, commercial pentabromodiphenyl ether (PeBDE) has been proposed by Norway for consideration as a persistent organic pollutant (POP) under the UNECE-LRTAP POPs Protocol. The nomination process includes the preparation of a risk profile by the proponent Party, which, if considered acceptable by the LRTAP Executive Body, then undergoes one or more technical reviews, i.e., the genesis of this technical review. On the basis of the scientific information provided by Norway, I have reached the following conclusions regarding the risk profile on PBDEs: The risk profile would benefit from updating with more contemporary citations, although the information provided is accurate and adequate to reach the conclusions drawn. From the information provided, commercial PeBDE satisfies the following indicative numerical values provided in Executive Body Decision 98/2 for: Persistence: PeBDE is persistent in the environment, exceeding the LRTAP POPs guidance; Bioaccumulation: PeBDE bioaccumulates in the environment, exceeding the LRTAP POPs guidance; Long-range atmospheric transport: PeBDE has the potential for Long Range Atmospheric Transport; Toxicity: PeBDE has the potential to adversely affect human health and/or the environment. Under LRTAP EB Decision 1998/2 (2), sufficient information is available to conclude that: 14

15 (a) (b) The combination of physical properties and monitoring data in the air and biota indicate that PeBDE is undergoing long-range transboundary atmospheric transport. The combination of the potential for atmospheric transport, measured environmental and biotic levels, the exponential increases in these levels, and their relationship to toxic endpoints in humans and biota, indicate that PeBDEs exhibit similar reasons for concern as substances already listed as POPs under the LRTAP Protocol. Introduction: Commercial pentrabromodiphenyl ether (PeBDE) has been proposed by Norway for consideration under the United Nations Economic Commission for Europe (UNECE), Long Range Transboundary Air Pollution (LRTAP) Persistent Organic Pollutant (POPs) Protocol. Consistent with the text of the LRTAP POPs Protocol, a Party submitting a proposal shall provide the Executive Body with a risk profile on the substance, which shall then be subject to one or more technical reviews. This report constitutes such a technical review of the proposal, limited to the Track A review of POPs characteristics. Pentabromodiphenyl ether is a brominated flame retardant most commonly used in polyurethane foam (up to 30% of the polymer). Flame retardants have been critical components of modern materials design to reduce human mortality and morbidity from fires. However, increasing PBDE levels in the environment, biota, and humans have been documented, leading to regulatory actions in Europe and, more recently, proposed in the United States, and recommendations for alternative procedures and chemicals to reduce fire risks. The issue contemplated under this proposal is whether the human health and environmental risks posed by the long-range transboundary atmospheric transport of PBDEs warrants their consideration under the UNECE-LRTAP POPs Protocol. Before reviewing the risk profile, it is worthwhile clarifying some of the chemistry and nomenclature on polybrominated diphenyl ethers. These definitional issues will need to be considered by the Working Group on Strategies and Review (WGSR) should a decision be made to move ahead with PeBDE, in much the same way that definitional clarity was an issue for previous LRTAP POPs listings, such as the variety of hexachlorocyclohexanes. The Norwegian proposal is that the commercial pentabromodiphenyl ether product be listed as a POP. This commercial product is, however, comprised of a number of homologue groups of diphenylethers, particularly those with four bromines (tetrabromodiphenyl ethers; TeBDE), five bromines (pentabromodiphenyl ethers; PeBDE) and, to a lesser extent, six bromines (hexabromodiphenyl ethers; HxBDE) Within each of these homologue groups there are different congener arrangements of the bromine atoms, which may exhibit different toxicities (e.g., BDE-47 in the TeBDE group, BDE-99 in the PeBDE group, etc). Consideration will need to be given by the WGSR to preventing a company merely relabelling a penta product as tetra, or slightly modifying the product to increase the proportion of tetra homologue. 15

16 Method: As requested, this review has been conducted in a similar manner to those routinely undertaken for peer reviewed journal articles or government document preparation. The basic instructions were for the review to be transparent, and to include critical evaluation of such aspects as, inter alia, availability, reliability, completeness and relevance of the information and references. Reviewers were instructed to only address the information contained in the dossiers, to refrain from any elaboration of their content, and to avoid comments that could be considered to reflect policy. On clarification, it was agreed permissible to suggest additional citations and information for or against a scientific point, as done for a normal peer review, but not to engage in any revision of the proposal. This clarification is particularly important for PeBDE because the submitted dossier was apparently prepared over four years ago in 2000, and much relevant information has been published since this time. While recognizing that it is difficult and time consuming to maintain proposals in a contemporary fashion, this four plus year gap is excessive in this situation. That said, the newer information confirms the earlier concerns. Inclusion of this contemporary information in a revised dossier would enhance the case for POPs consideration. POP characteristics in terms of the guidance and indicative numerical values provided in Executive Body Decision 98/2 for: Persistence: The risk profile provides a limited number of references to laboratory test and structureactivity (SAR) information, along with evidence of persistence from environmental monitoring data. Test information on pentabde is limited (and still is) to the OECD 301B ready biodegradation test by Schaefer and Haberlein (1997), secondarily cited here to the European Union risk assessment report (COM, 2000). This document is not readily available for primary review. However, it is widely cited and indicates that PeBDE is not readily biodegraded in aerobic activated sludge at 29 days (~2.4% decrease at 93 days extension is reported in COM 2000). These results are apparently confirmed by Syracuse Research Corporation (HSDB, peer reviewed) which reports that no biodegradation was seen after 29 days in the rapid biodegradation study. Additional SAR information is cited from Palm (2001) that indicate long half-lives for a couple of congeners in environmental compartments, which exceed the LRTAP POPs guidance values. Unfortunately, Palm (2001) is a masters thesis that is not readily available for review. This paucity of replicable laboratory and field studies for persistence is, unfortunately, not unusual for many chemicals, although it is regrettable given the importance of actions and consequences on deeming a chemical a POP. Regarding persistence, the risk profile should reference the increasing literature on reductive debromination, much of which is for the deca product but with potential implications to congener mixes and persistence (see below under bioaccumulation). The risk profile also references some older citations to the prolonged presence of PeBDE congeners in sediments, which could be updated through the addition of newer literature. 16

17 Persistence in biota is also noted (de Boer et al. 1998; seal hepatic microsomes), which could be updated with the contemporary literature on this topic. Conclusion: PeBDE is persistent in the environment, exceeding the LRTAP POPs guidance. Bioaccumulation: The risk profile notes that the LogKow for PeBDE is greater than 5, that it has a composite, estimated, BCF of 27,400 (cited to COM 2000), a substantial biological half-life in rodent species, and that the bioaccumulation potential is dependent on the degree of bromination. This is all correctly cited, although the more contemporary literature provides additional information on the complexity of some of these relationships and may be important in considering what actions to take on PeBDE. For instance, the Kow for these large, brominated, molecules are approaching non-optimal levels for bioaccumulation. Bioaccumulation of PBDEs peaks at around the three to four bromine substitution level, but begins to taper off when more than five bromines are present (Braekvelt et al., 2003). Evidence is also available that PeBDE is undergoing debromination to TeBDE (Stapleton et al., 2004). These considerations factor into explaining why the congener patterns in biota (more TeBDE than PeBDE) differ from the primary commercial mixture and environmental residues. The possibility of biotransformation, via debromination, of higher homologues may also contribute to changed congener patterns (Tomy et al., 2004). An additional reference to consider on bioaccumulation and biomagnification is the publication by Hale et al. (2002). Conclusion: PeBDE bioaccumulates in the environment, exceeding the LRTAP POPs guidance. Potential for Long-Range Transboundary Atmospheric Transport: The risk profile provides evidence that the vapor pressure, atmospheric half-life and monitoring data satisfy the LRT guidance values. Regarding the atmospheric half-life table (Table 3), only the COM (2000) reference was readily obtainable (12.6 days using the SRC model). The other two citations are from a masters thesis and a personal communication. A more accessible route might have been to cite the 29 day half-life estimate provided on the Hazardous Substances Data Bank of the U.S. National Library of Medicine, cited to the estimation method of Meylan and Howard (1993). The evidence of long-range transport through measurements in air and accumulation in remote locations is also compelling, especially the time course data, with some of the levels in remote locations reaching into the high ppb range. The modeling by Palm (2001) is informative, again limited by its being a difficult to obtain masters thesis. Among the additional contemporary citations that should be included, the summary by Hites (2004) on the exponential rates of increase in the environment is particularly informative. Conclusion: PeBDE has the potential for long-range transboundary atmospheric transport. Toxicity: The toxicity information in the risk profile, although somewhat abbreviated, highlights a number of concerns posed by the PBDEs. The risk profile cites the Eriksson et al. (1998, 2001) 17