Burned by Flame Retardants?

 Our bodies are accumulating chemicals from sofas, computers, and television sets

 Two years ago, unnerving news from researchers in Stockholm hit the European press. An analysis of samples of women's breast milk since 1972 showed dramatic increases in a class of relatively unknown chemicals that toxicologists liken to the notorious pollutants polychlorinated biphenyls (PCBs).

 The lesser-known chemicals, polybromo diphenyl ethers (PBDEs), had been noted a year earlier in the Swedish food supply. Soon, researchers in North America also documented an accumulation of PBDEs in women's milk. They observed PBDEs in fat, too, where the chemicals lodge. Furthermore, PBDEs have been reported in human tissue in Japan, Israel, and Spain.

 Studies in Lake Ontario and the Baltic Sea find that PBDE concentrations in fish are rising rapidly, as they are in the fat of marine mammals in California and the Northwest Territories of Canada. The chemicals move up the marine food chain. Concentrations in Baltic Sea species increase successively in herring, salmon, and seals.

 Trace amounts of PBDEs leach into the air and sewage, probably from plastics in appliances and computers, foam in upholstery, and fabric of carpets and draperies. Between 5 and 35 percent of such items by weight consist of PBDE flame retardants.

"This stuff is everywhere," says John Jake Ryan of Health Canada in Ottawa.

 Much of the animal data on the toxicity of PBDEs is incomplete, and next to nothing is known about their effects on people. But the results of the animal studies so far lead toxicologists to an unsettling assessment. Says Ilonka A.T.M. Meerts of Wageningen University and Research Center in the Netherlands, "The complete toxic profile is very much like PCBs," the now-banned chemicals that cause birth defects, thyroid imbalances, and neurological damage in animals and people.

 Since the 1970s, PBDEs have been in widespread use as fire retardants in plastics, foam, and textiles. According to the Bromine Science and Environmental Forum, an industry group based in Brussels, Belgium, 148 million pounds of these chemicals are produced each year. Workers in electronics-recycling facilities face unusually high exposures to PBDEs.

 The estimated daily intake of PBDEs by people from air and food is far below amounts now known to be toxic to animals. Furthermore, concentrations of PBDEs in human tissue and breast milk are still only one-tenth to one-hundredth the concentrations of PCBs present.

 Despite PBDEs' relative scarceness today, evidence that the chemicals are accumulating in people and the environment raise concerns, given PBDEs' potential for health effects, says Thomas A. McDonald, a toxicologist at the California Environmental Protection Agency in Oakland. "If concentrations in some marine mammal and human populations continue to rise, PBDEs may be the PCBs of the future," he says.

 In response to such assessments, governments in Europe have moved toward control of the chemicals. On Sept. 6, the European parliament voted to ban the use, manufacture, and import of some forms of PBDE over the next few years. The legislation still requires passage by the European Council of Ministers before it becomes law. The United States and Canada don't currently regulate the manufacture, distribution, or disposal of PBDEs.

 Toxic effects

 Concerns about toxic effects of PBDEs arise from many lines of research. In 1998, Per Ola Darnerud of Sweden's National Food Administration in Uppsala and his colleagues reported to the Nordic Council of Ministers that PBDEs were in the Swedish food supply, tainting fish, milk, and eggs.

 The next year, Ake Bergman of Stockholm University, Daiva Meironyte Guvenius of the Karolinska Institute in Stockholm, and their colleagues reported a 60-fold increase in concentrations of these chemicals detected in women's milk sampled between 1972 and 1997.

 Researchers in North America documented what appeared to be a similar, dramatic increase in PBDE concentrations in women's milk. Ryan and Benoit Patry of Health Canada tested breast-milk samples obtained from several Canadian cities. At the Dioxin 2000 meeting in Monterey, Calif., they reported that milk samples from 1992 contained concentrations of PBDEs 100 times as high as in samples obtained a decade earlier. Preliminary data indicate there were PBDEs in milk from New York women in 1997.

 Health officials, however, note that the benefits of breastfeeding an infant outweigh the risks associated with the presence of PBDEs and PCBs in the milk.

 Other scientists have examined fat from women in San Francisco. Samples contained a wide range of PBDE concentrations-from 0.017 to 0.462 microgram/gram of body fat. These samples averaged three times as much PBDE as in samples from women in Sweden, Jianwen She of California's Environmental Protection Agency in Berkeley and his colleagues report in an upcoming issue of Chemosphere. The United States has strict flame-retardant standards for furniture and other household items and uses much of the world's PBDEs.

 In animal studies, PBDE exposure results in pronounced effects on the nervous system. Per Eriksson at Uppsala University in Sweden tested a pair of penta-PBDE compounds. He administered single doses of the compounds to mice 10 days after birth, a critical time in nervous system development. When the mice had grown to adults, Eriksson tested their movement, learning ability, and memory.

 Mice that were exposed to any dose of a penta-PBDE compound, from the lowest in the study (0.7 Mg/g of body weight) to the highest (12 Mg/g), showed abnormal behavior. Those receiving the highest dose of one of the compounds also performed poorly in navigating a maze. Eriksson and his colleagues report their results in the September Environmental Health Perspectives.

 At all doses, the nervous system defects worsened as the mice aged. Eriksson's group has done similar studies with PCB compounds. Describing effects on the nervous system of developing animals, he says, "The PBDEs are as toxic as the PCBs we have investigated."

 Exactly how either PBDEs or PCBs affect the nervous system is unclear. But toxicologists suspect that imbalances in thyroid hormone might play a role. In people and animals, proper regulation of this hormone is critical to the developing nervous system.

 Many studies have found that rodents fed high amounts of PBDEs have thyroid hormone deficiencies. In one recent study, a group led by Kevin M. Crofton at the University of North Carolina in Chapel Hill examined thyroid hormone concentrations in blood from rats fed penta-PBDE for 4 days. In rats fed 9 to 13 Mg/g of body weight per day, the researchers observed a 20 percent reduction in T4, the primary thyroid hormone in circulating blood. Doses of about 100 Mg/g reduced T4 by 70 percent, the scientists reported in the May Toxicological Sciences.

 In Crofton's preliminary assessment: "It appears as if the PBDEs are slightly less potent than the PCBs."

 To put the thyroid studies into perspective, Darnerud estimates that the concentrations of PBDEs that produce an effect on thyroid hormones in animals are 1 million times greater than current exposures in people. It's hard to compare short-term dosage studies with chronic low-level exposure, he notes, but the gap between animal exposures in the lab and human exposure is immense.

 McDonald agrees with Darnerud's assessment but says, "There is reason to think that the gap might narrow." He also suggests that people with slight thyroid imbalances might be affected by even small doses of PBDEs. He notes, too, that some animal studies show that toxic effects of PBDEs and PCBs add to each other.

 Similar to hormones

 Some of the toxic effects of PCBs and PBDEs may derive from their structural similarity to thyroid hormones. PCBs, PBDEs, and thyroid hormones all consist of two six-carbon rings decorated with halogens. Bromine attaches to the carbon rings of PBDEs, chlorine to those of PCBs, and iodine to those of thyroid hormone. In PBDEs, an atom of oxygen bridges the rings, whereas the rings of PCBs and thyroid hormones are linked by carbon- carbon bonds.

 The similarity between PBDEs and PCBs, however, doesn't mean they exert exactly the same effects in the body, cautions Darnerud. "I think it's perhaps too simple to say that these compounds are alike," he says.

 It's the bromine atoms in the PBDEs that make them good fire retardants. They quench flames by scavenging electrons. The number and the placement of the bromine atoms determine the type of PBDE. The maximum number of bromines, 10, occurs in deca-PBDE. This substance, which manufacturers use primarily in hard plastics, accounts for more than 80 percent of PBDEs in use today.

 Deca-PBDE accumulates in human and animal tissue at far lower concentrations than its cousins with fewer bromines do. In several analyses, deca-PBDE also seems to have much less toxicity. However, Eriksson and his colleagues have found that mice exposed to deca-PBDE as weanlings show behavioral changes equivalent to those exposed to penta-PBDE. The researchers presented their data at the Society for Toxicology meeting in March in San Francisco.

 Penta-PBDE, which has five bromines, is the most common form in foam products. But commercial formulations of penta-PBDE contain about 45 percent tetra-PBDE, with four bromines. Penta- and tetra-PBDE appear to break down into potentially more toxic compounds in the body.

 Meerts and her colleagues have examined the interaction of PBDE breakdown products, or metabolites, with a blood protein that ushers T4 around the body. The protein, called transthyretin, is one of several T4 escorts in the bloodstream.

 In the July 2000 Toxicological Sciences, Meerts reports that PBDE metabolites bind to transthyretin, as PCB metabolites do. Compounds predicted to be metabolic breakdown products of tetra-PBDE bind even more tightly than T4 itself.

 Scientists who study PCBs have speculated that transthyretin has a special role in carrying PCBs to the fetus and especially its brain.

 Despite PBDEs' structural similarity to thyroid hormones, McDonald says that "thyroid hormone disruption is not the whole story."

 He notes that laboratory studies of PCBs show that they can upset the intricate balance of nerve cells' chemical communication system. Preliminary data from Prasada Rao S. Kodavanti of the Environmental Protection Agency in Research Triangle Park, N.C., and his colleagues suggest that PBDEs may disrupt some of the same communication processes, reports McDonald in an upcoming issue of Chemosphere.

 Millions of sources

 How PBDEs from sofas, carpets, computer monitors, and television sets get into people is an open question. "You have millions of point sources in every home, every bus, every car, and they are slowly making their way into the environment and up the food chain," says McDonald.

 After analyzing food in Ottawa grocery stores, Ryan estimates that the average person there eats 0.044 Mg of PBDE per day in meat and dairy. But scientists don't yet know how food gets contaminated in the first place.

 In the United States, spreading sewage waste on farmland as fertilizer may send PBDEs along to the dinner table. Robert C. Hale of the Department of Environmental Science in Gloucester Point, Va., and his colleagues measured PBDEs in U.S. sewage sludge. They report in the July 12 Nature that each kilogram of sludge, by dry weight, carries 1.1 to 2.3 milligrams of PBDEs with five or fewer bromines. That exceeds 100,000 times the concentration that other researchers found in some European sludge samples. About 4 million tons of sewage sludge were applied last year to land in the United States, according to EPA.

 Discarded furniture may contribute to the pollution in sludge, suggests Hale. As they degrade, couch and chair cushions release large amounts of penta-PBDE into dirt, sewers, and sediments, he suspects.

 Flame-suppression standards save lives, says Robert Campbell of the American Chemistry Council in Arlington, Va.

"We may have to look at issues of risk tradeoff, but . . . there are flame retardants other than PBDEs," says Linda Birnbaum, director of the human studies division at EPA's National Health and Environmental Effects Research Lab in Research Triangle Park, N.C. She notes, "We banned the production of PCBs when we had less information than we do now of the PBDEs."

 Fire-squelching substitutes for PBDEs include other bromine-containing compounds and silicon or phosphorus-based chemicals. Some of these may gradually degrade in products, weakening their fire-retardant properties, notes Campbell.

 Birnbaum adds that some substitutes may themselves be toxic.

 Less ambiguous are the data that show PBDEs accumulating at a rapid rate in the fat of people and animals in North America. "Current concentrations [of PBDEs] are still quite low," says Crofton. Like many other toxicologists, he is particularly concerned about the future.

 Adds Darnerud, "I don't want to see levels get as high as PCB levels."