PBDE Polybrominated diphenyl ether
What Fate for Brominated Fire Retardants?
Rebecca Renner / Environmental Science and Technology 1may00 
A publication of the American Chemical Society

The widespread distribution and environmental effects of these persistent chemicals are driving preventive measures.

The presence of polybrominated diphenyl ether (PBDE) flame retardants throughout the world environment has begun to attract international attention. Researchers and environmental groups are concerned about emerging pollution problems, pointing both to the growing body of evidence that PBDEs are ubiquitous in the environment and to evidence suggesting that low-level exposures may produce detrimental health effects in humans and animals.

European scientists and governments are at the forefront of this issue, but the problem is global, according to Mehran Alaee, a research scientist at Canada's National Water Research Institute, in Burlington, Ontario, whose group is responsible for most of the PBDE measurements in North America. "It's global because so far, everywhere we look we find measurable amounts of PBDEs," Alaee says.

Although European governments are poised for action, PBDE manufacturers claim that such measures are premature and simplistic. Producers argue that bans and actions to remove these chemicals from the marketplace are overly cautious and are based on inadequate data. Legislative and regulatory control initiatives fail to account for the benefits of flame retardants in preventing fires, and little is known about the environmental fate and transport of proposed substitutes, according to Marcia Hardy, who chairs the Brominated Flame Retardants Industry Panel at the Chemical Manufacturers Association in Washington, DC.

The study prompting the most activity so far is a finding by researchers at Sweden's Karolinska Institute (1) that there are low levels of PBDEs in mothers' milk and that, although levels of other persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and DDT, are decreasing, levels of PBDEs are increasing. Results such as these are the rationale for a draft European Union (EU) Human Health Risk Assessment's recommendation that action be taken to curb the use of penta-BDE (2), which is sold in relatively small quantities.

"Penta is damned," says Gwynne Lyons, Toxics and Policy Advisor to Worldwide Fund for Nature-UK, "The political decision-making process, at least in Europe, will respond to the fact that no mother on earth wants her breast milk to be contaminated with flame-retardant chemicals." The EU includes restrictions against PBDEs under the European ecolabeling scheme and is likely to propose a much broader ban on their use in electrical and electronic equipment under a forthcoming directive on scrap from electronic devices.

The Swedish research results are also prompting action in the United States, according to Larry Needham, Centers for Disease Control and Prevention (CDC) director of toxicology. Needham notes that CDC will begin gathering data on U.S. exposure this summer.

Unlike many persistent and ubiquitous organic pollutants such as PCBs or DDT, which are largely a legacy of the past, brominated flame retardants are in current, widespread use to prevent or deter fires in electronic devices, furniture, and textiles. PBDEs have been found in the body fat of many wildlife species, including sperm whales in the Atlantic Ocean (3). The latter finding suggests that even the deep ocean is now contaminated. Prompted by such findings, Sweden and Denmark have called for a ban on two types of flame retardants—polybrominated biphenyls (PBBs) and PBDEs—and are urging international action.

The largest-volume PBDE product on the market today is deca-BDE. But because PBDE toxicity decreases as the number of bromines increase, the deca-brominated compound is, at first glance, the least likely to present a problem (4). Many researchers and environmental groups believe, however, that in the environment, deca-BDE can break down to lower congeners. "The toxicity of octa- and deca-BDE, coupled with the concerns about their potential breakdown to penta, is enough to warrant their removal from the market," argues Lyons.
Consumption and use Brominated diphenyl ethers are a group of aromatic brominated compounds in which 1-10 hydrogen atoms in the diphenyl oxide structure are replaced by bromine atoms. Commercially available products are not pure substances—flame-retardant formulations consist of PBDEs containing anywhere from 3 to 10 bromine atoms. Three different flame retardants are available and are sold in the marketplace as penta-, octa-, and decabromodiphenyl ether; each product is actually a mixture of brominated diphenyl ethers.

PBBs, PBDEs, and tetrabromobisphenol A (TBBPA) are the main types of brominated compounds used as flame retardants. PBDEs are the focus of current concerns for several reasons. PBBs—the first brominated organic compounds to be used—have been voluntarily phased out by manufacturers because of environmental issues. PBDEs have taken their place but are now being replaced, to some extent, by TBBPA. There is very little information available concerning TBBPA (4).

The estimated annual global consumption of PBDEs in 1992 was 40,000 metric tons and consisted of 30,000 metric tons of decabromodiphenyl ether, 6000 metric tons of octabromodiphenyl ether, and 4000 metric tons of pentabromodiphenyl ether (2). Total PBDE consumption in that year corresponded to about 30% of the world market for all types of brominated fire retardants used. In western Europe, consumption of PBDEs accounted for about 26% of the European market for brominated flame retardants in 1996 (5). A 1999 analysis indicated that the share of PBDEs in the European market decreased to about 11% in 1998 (5); the decrease in consumption of PBDEs is especially pronounced in Germany, the Netherlands, and Nordic countries (5).
Members of the German Association of Chemical Industries voluntarily halted production of PBDEs and PBBs (5) in 1986. In recent years, leading European companies in the electric and electronic industries have proclaimed an official policy of avoiding the use of PBDEs and PBBs in their products.

PBDEs are currently used in plastic components of computers and televisions, circuit boards, seats of cars and buses, and textiles (4). It is important to distinguish between additive and reactive uses. Reactive fire retardants such as TBBPA, are covalently bonded to the plastic itself, while additives, such as PBDEs, are only dissolved in the material. This means that reactive flame retardants are less likely to leach out or volatilize, whereas additives are more easily released.
Additive flame retardants are incorporated as components of plastic mixtures either before, during, or, more frequently, following polymerization. They are sometimes volatile and can tend to bleed, so flame retardancy may be gradually lost. High molecular-weight, plastic products, developed to enable plastics to be made more permanently fire retardant, use the additive method for fire-retardant protection. The most widely used brominated flame retardant additives are PBDEs.

Ubiquity and a mystery PBDEs were first discovered in the environment in 1981, when they were found in pike from western Sweden. Subsequent reports, based on analyses of sediments, document the ubiquitous distribution of PBDEs in the environment, wildlife andfish, human adipose tissue, blood, and mother's milk (4). According to Alaee, the presence of PBDEs in air samples from Alert, Northwest Territories and from Duai, in Siberia confirm that, despite their relatively low volatility, long-range atmospheric transport of these compounds occurs.
Until recently, PBDE concentrations detected in wildlife and humans have been below concentrations of PCBs and DDT. However, for certain species, contamination levels are in the same range as for the PCB congeners, according to a study by researchers from Sweden and the United States, which was presented at the Dioxin '99 meeting (6). The researchers compared PCB and PBDE levels in Steelhead trout from Lake Michigan and Baltic salmon from the Baltic Sea (see Figure 1, (7, 8)).

Despite the fact that human PBDE concentrations are significantly lower than those of PCBs or DDT in mothers' milk, over the past 25 years, PBDE levels in breast milk have climbed to around 4 µg/kg of lipid content (1) (see Figure 2, (9)). The predominant PBDEs in milk are tetra-BDEs, followed by penta-BDEs. A higher PBDE concentration (28 µg/kg) was found by Swedish researchers in one sample, but even this level of exposure is well below the level so far shown to cause adverse effects on brain development in animals.

Another Swedish study found levels up to 70 times higher than normal in the blood serum of staff at an electronics dismantling plant (10). The results show that PBDEs are bioavailable, according to the study, and that "occupational exposure to PBDEs occurs at the dismantling plant." The study also found deca-BDE in individuals who were exposed at work. This is an important observation, according to the authors, "because it has been claimed that this compound is unlikely to bioaccumulate because of its high relative molecular mass."
Although deca-BDE accounts for most PBDE consumption, it is the lower congeners—tetra-BDE and penta-BDE, and in particular 2,4,2´,4´-tetra-BDE and 2,4,5,2´,4´-penta-BDE—that are most commonly found in the environment.

To explain this discrepancy, scientists theorize that higher congeners break down in the environment. Such debromination has been demonstrated in the laboratory, according to Åke Bergman, professor of chemistry at Stockholm University, in Sweden, although there are few published results to back this up. There are also indications that debromination occurs in fish during metabolism, according to Bo Jansson, at the Institute of Applied Environmental Research, in Stockholm (11).

But Hardy, who is also an environmental chemist at PBDE manufacturer Albemarle Corp., in Baton Rouge, LA, disagrees that debromination happens in the environment. She theorizes that the congeners found in the environment are the result of historic emissions that have ceased. Penta-BDE was used for off-shore oil drilling on a trial basis in the early 1990s. Until the late 1980s, it was also used as a hydraulic fluid by the coal mining industry in Germany. Hardy notes, for example, that sediment samples from the Mersey River in England contain deca-BDE, tetra-BDE, and penta-BDE, but no other congeners. "If deca-BDE is breaking down, then why does it degrade down to a few specific congeners and then just stop?" she asks. If deca-BDE were being degraded, all of the intermediate congeners would be expected, she said.

In an attempt to address this question, a 36-week study to test whether deca-BDE can debrominate in the environment is being performed as part of the EU ecotoxicological risk assessment. Results are expected to be available this year.

Sources and trends Although PBDE levels in mothers' milk appear to be increasing, the trend of levels in the environment is unclear, according to Steven Dungey, at UK's Environment Agency. "This is a very tricky area," he says. "Although there are now quite a lot of data available, few have been analyzed statistically for trends." Since the early 1990s, Dungey has been reviewing published and unpublished data as part of the EU ecotoxicity risk assessment. Most of the monitoring data indicate that although there may have been an increase in the levels of the most common tetra- and penta-BDE congeners in biota over the 1980s, this has now stabilized or is decreasing.
There are few data on PBDE emissions to the environment, according to Dungey. Production and processing facilities may discharge PBDEs; high levels are found downstream from some factories. Releases can occur throughout the life cycle—including recycling, landfilling, or incineration—of products that contain PBDEs; few quantitative data exist for these potential emissions sources.
In the EU ecotoxicity risk assessment, a series of "realistic worst case" assumptions were made based on comparison with the behavior of similar chemicals that are added to polymeric materials. A study by the Danish EPA aimed at identifying the flow of PBDEs into and out of Denmark encountered a similar lack of information about sources. The study, based on product information and scientific literature, concluded on the basis of model estimates that the major source of PBDEs to the environment is evaporation from products in use (5).

Another possible source for PBDEs in the environment could be their natural synthesis, mainly by marine organisms, according to Jan Boon at the Netherlands Institute for Sea Research, in Texel. A vast range of naturally occurring organobromine compounds are produced by marine and terrestrial plants, marine animals, bacteria, fungi, and even humans (12). Marine sponges are known to produce methoxylated PBDE (13). Although the specific PBDEs of concern have not yet been found in nature, a natural source is possible, according to Hardy, because only a small number of the world's diverse organisms have been examined for their chemical content.

Toxicity and unresolved issues There is little information available about PBDE effects of toxicity on organisms in the environment (4). One study is reported in which a young man developed symptoms similar to that of dioxin exposure, which included chloracne on the head and back, chronic pain in the face and skull, and lesions on the sides of his feet (4). At the age of 13, he developed these health problems after playing computer games for hours a day in an unventilated room. When he was 21, PBDEs were found in his fat and in different parts of the computer monitor. However, since eight years elapsed between the possible exposure to PBDEs and the sampling, there is no clear-cut answer to the question of whether PBDEs played a role in affecting his health.
A study investigating possible neurobehavioral effects in neonatal mice indicated that effects on brain development can occur at low doses, if exposure occurs during a period of rapid brain development. Per Eriksson and co-workers at Uppsala University in Sweden found that even a single dose of tetra-BDE (0.7 mg/kg bw) or penta-BDE (0.8 mg/kg bw) given to young mice affected their behavior in later life (14). But the study suffers from limitations in statistical analysis and reporting, so it is difficult to draw any firm conclusions, according to the draft EU human health risk assessment of penta-BDE (2).

Several studies indicate that commercially obtained penta- and tetra-BDE are endocrine disrupters, which can exert effects on the thyroid system (4). The effects of penta-BDE on thyroxine and the thyroid gland are considered to be principally due to the induction of liver enzymes, although several mechanisms may operate. The liver appears to be sensitive, and for penta-BDE, a no-observed-adverse-effect level of 1 mg/kg bw/day has been determined, with effects evident at 2 mg/kg bw/day. The exposure range for humans via food has been calculated as 0.2-0.7 mg per day.
For the past two years, political interest in PBDEs has been high in Europe. Taking the bold political initiative, Sweden and Denmark called for bans in the midst of the EU risk assessment process. In the United Kingdom, the Department of Trade and Industry in 1998 released a study (15) praising flame retardants for preventing fires and saving lives and labeling opponents as "chemophobes". The study, which only considered flame retardants in the home, not in the environment, caused embarrassment to the United Kingdom's Environment Agency, which is responsible for the environmental risk assessment.

Unresolved scientific issues concerning PBDEs are currently the topic of research efforts, which should soon yield preliminary results. Findings of the debromination study should be out this spring. A detailed study of PBDE levels in suspended particulate matter, sediments, and biota from Dutch freshwater and coastal locations is due to be presented at the Society of Environmental Toxicologists and Chemists World Meeting in Brighton, United Kingdom, in May. An interlaboratory study on the analysis of PBDEs is to be presented at the Dioxin 2000 symposium in Monterey, CA, in August.

In northern Europe, since 1996, there has been a trend (see box, Ecolabs drive the search for substitutes) to substitute other flame retardants for PBDEs. Whether the recommended ban on penta-BDE will be extended to cover the other PBDE flame retardants remains to be seen.

References
1. Darnerud, P.; Bergman, A.; Noren, K. Organohalogen Comp. 1998, 35, 387-390.
2. Diphenyl ether, pentabromo derivative, draft human health assessment under EU existing substances regulation; 793/93/EEC; Health and Safety Executive: Stanley Precinct, Bootle, Merseyside, U.K., 1999.
3. deBoer, J., et al. Nature 1998, 394 (6688), 28-29.
4. deBoer, J.; deBoer, K.; Boon, J. P. Polybrominated Biphenyls and Diphenyl Ethers. In The Handbook of Environmental Chemistry; Paasivirta, J. Ed.; Springer Verlag: New York, 1999.
5. Danish Environmental Protection Agency Brominated Flame Retardants—Substance Flow Analysis and Assessment of Alternatives 1999. http://www.mst.dk (accessed Dec. 1999).
6. Asplund, L., et al. Levels of polybrominated diphenyl ethers (PBDEs) in fish from the Great Lakes and Baltic Sea. Presented at Dioxin '99; Venice, 1999.
7. Asplund, L., et al. Organohalogen Comp. 2000, in press.
8. Asplund, L., et al. Ambio 1999, 28, 67.
9. Meironyté, D.; Norén, K.; Bergman, Å. J. Toxicol. Environ. Health (Part A) 1999, 58 (6) 329-341.
10. Sjodin, A., et al. Environ. Health Persp. 1999, 107 (8), 643-648.
11. Kierkegaard, A., et al. Environ. Sci. Technol. 1999, 33 (11), 1612-1617.
12. Gribble, G. W. Acc. Chem. Res. 1998, 31 (3), 141-152.
13. Gribble, G.W. Chem. Soc. Rev. 1999, 28 (5), 335-346.
14. Eriksson, P.; Jakobsson, E.; Fredriksson A. Organohalogen Comp. 1998, 35, 375-377.
15. Stevens, G. C.; Mann, A. H. Risks and benefits of the use of flame retardants in consumer products; University of Surrey Polymer Research Centre Report, U.K. Department of Trade and Industry: Guildford, Surrey, U.K., 1999. Rebecca Renner is a contributing editor of ES&T.
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Developmental Neurotoxicity of Polybrominated Diphenyl Ethers:
Mechanisms and Effects
Zürich University 5dec00
Polybrominated diphenyl ethers (PBDE) are increasingly used as flame retardants (presently 180,000 tons/year). They bioaccumulate in marine mammals, birds and humans. Levels in human milk recently started to rise sharply, up to 4 ng/g lipid. The presence of lipophilic compounds in maternal milk reflects the body burden of the maternal organism and indicates the possibility of prenatal transplacental exposure als well as postnatal exposure through milk. In contrast to polychlorinated biphenyls (PCB), very little information is available on the toxicity of PBDE. This is particularly true for developmental neurotoxicity, but recent experimental evidence by one of the project partners indicates a potential of adverse effects on the developing nervous system. The present project is designed to study developmental effects of PBDE on nervous system in rodents and in in vitro models. In order to relate these observations to known effects of PCB, a technical PCB mixture (Aroclor 1254) is used as a positive control. Endpoints include behavioral development, neurotransmitter systems and receptors, intracellular signal transduction pathways, neuroendocrine mechanisms and possible effects on glial function.
Since certain PCB congeners interfere with endocrine mechanisms, this question will be addressed also for PBDE. Our laboratory investigates effects of PBDE and of the PCB mixture on neuroendocrine development in male and female Long Evans rat offspring, with focus on sexual differentiation of brain and peripheral organs. The program aims to link alterations in sexual functions of both sexes (sexually dimorphic behaviors, gonadal functions) with developmental changes in molecular endpoints, in particular regulation of sex hormone-dependent gene expression in brain regions and genital organs, and steroidogenic enzymes. Landmarks of postnatal sexual ontogeny will also be monitored.
* Prof. Walter Lichtensteiger (Project Leader) lichtens@pharma.unizh.ch
* PD Dr. Margret Schlumpf (Project Leader) schlumpm@pharma.unizh.ch
* Supported By EU
Fifth Framework Program (EU), Quality of Life and Management of Living Resources
* Research Program EU
* In Collaboration With University of Düsseldorf, Düsseldorf, Germany / University of Rome, Rome, Italy / University of Uppsala, Uppsala, Sweden / University of Valencia, Valencia, SpainResponsible
* Project Leader: Prof. Walter Lichtensteiger, PD Dr. Margret
* Professor or Research Area Leader: Prof. Dr. W. Lichtensteiger
* Institute or Clinic: Pharmakologie und Toxikologie, Institut für
* Faculty: Medizinische Fakultät
* Comments to uniresearch