New PCBS? Throughout life, our bodies accumulate flame retardants, and scientists are starting to worry.

Polybrominated diphenyl ether (PBDE) is hardly a household phrase. Yet it probably should be. Household products ranging from kids' pajamas to computers release these brominated flame retardants. The chemicals have been turning up in house and yard dust, as well as in specimens collected from sewage sludge, streams, and even people's bodies. For 3 decades, manufacturers have been putting these chemicals into a wide variety of products to reduce the risk that these goods will catch fire.

And indeed, PBDEs have performed reliably, saving an estimated 300 or more lives each year in the United States alone. However, emerging data on the extent to which the chemicals pollute the environment have kindled concern that these useful compounds may have subtle toxic effects, despite having passed standard safety tests.

Most U.S. chemists trace their initial concern about these compounds to a report by Swedish scientists at an international chemistry conference in Stockholm 4 years ago. The researchers stunned the audience with data showing that PBDEs were present in samples of women's breast milk stored over the past quarter century and that the more recent the sample, the higher the concentration of the chemicals (SN: 10/13/01, p. 238).

Ronald A. Hites of Indiana University in Indianapolis, who attended that conference, remembers feeling immediate concern because of the close structural similarity between PBDEs and polychlorinated biphenyls (PCBs)--insulating oils that were banned in 1979 owing to their toxicity.

As soon as he got home from the meeting, Hites began surveying published studies that recorded PBDE concentrations in people. Data were available only for industrial countries. At an Environmental Protection Agency conference in Chicago this past August, he reported his findings: PBDE concentrations are 10 to 20 times as high in North Americans as they are in Europeans. And the Europeans' concentrations are about double those of people living in Japan. Moreover, Hites says, his calculations show that since the 1970s, these body concentrations have been "exponentially increasing, with a doubling time of 4 to 5 years"

So what? That's a question scientists and policy makers have been puzzling over. Animal data reported this summer support concerns that these useful compounds might, over the long term, prove toxic to people.

A record 80 papers on brominated flame retardants were presented in August at an international meeting in Boston called Dioxin 2003. Although presentations linked all five major classes of brominated flame retardants with some animal toxicity, the majority of studies focused on the three PBDE classes--related chemicals with different commercial applications and toxicity profiles. Especially troubling were reports indicating that relatively lowdose exposures to PBDEs in the womb or shortly after birth could irreparably damage an animal's reproductive and nervous systems. Earlier test-tube studies had indicated that the compounds could alter concentrations of thyroid hormones--agents that play a pivotal role in growth and development.

Blood concentrations of PBDEs eliciting some of these effects in animals are close to those now being measured in North Americans, observes Linda S. Birnbaum, EPA's director of experimental toxicology in Research Triangle Park, N.C. The animal studies are still preliminary and fall well short of proving that PBDEs pose a major threat to people, Birnbaum says. However, if people prove as vulnerable, the concentrations showing up in North Americans leave "no margin of safety," she told Science News.

BAMBI FACTOR To many toxicologists at the Boston meeting, most troubling were data indicating that human exposures to PBDEs begin in the womb. Hites had instructed delivery-room nurses to extract 10 milliliters of umbilical cord blood from each of 20 Indiana newborns. Each baby's mother also donated blood.

Concentrations of PBDEs in each mother and her baby were virtually identical. However, the values between mother-baby pairs varied widely. In the July Environmental Health Perspectives, the Indiana scientists report that although the average was around 40 parts per billion (ppb) of PBDEs in blood, some moms and babies showed concentrations up to 450 ppb.

For breastfed infants, mothers' milk continues the PBDE exposure. At the Boston dioxin meeting, Arnold Schecter of the University of Texas Health Sciences Center in Dallas previewed his team's data on PBDEs in breast milk recently donated by 47 women to Texas milk banks.

All PBDEs have a double-ring structure onto which bromine atoms attach at any of 10 positions. Of 209 different PBDEs, called congeners, Schecter and his colleagues focused on the 13 that occur most commonly in commercial products.

The Texas study is the first to detect the 10-bromine form of PBDE--a congener known as BDE-209--in human milk. BDE-209 is the primary ingredient of a commercial flame-retardant product known as the deca mix because the l0-bromine congener predominates. This congener, among the hardest to measure, has been studied only recently. Indeed, many toxicologists doubted its large molecules could enter the body in measurable amounts.

The milk of seven women had concentrations up to 8 ppb. That's disturbing, notes Birnbaum, a coauthor of the Texas study. Soon-to-be-published animal research, briefly described at the Boston meeting, indicates that deca may damage nerve cells during brain development, which in humans occurs not only in the womb, but also for up to 2 years after birth.

The milk's total mix of PBDEs--from 6.2 to 419 ppb, with an average of 73.9 ppb--proved similar to the totals that Hites' group had measured in blood. The Texas study is scheduled to appear in the November Environmental Health Perspectives.

An even newer, nationwide study by the Environmental Working Group, an advocacy organization based in Washington, D.C., searched samples of human breast milk from 20 first-time mothers for some 30 PBDE congeners. Every one turned up in at least one milk sample. Eighty percent contained BDE-2Og, though none at concentrations as high as recorded by Schecter's group.

The biggest surprise, says study author Sonya Lunder in the Environmental Working Group's Oakland, Calif., office, was the high-end exposures, the top 5 to 10 percent of samples. In most PBDE surveys, these samples have proved surprisingly high. "In Sweden, those much-higher levels may be 30 ppb," she notes. "In ours, they were above 500 ppb--with one above 1,000 ppb."

Highlighting these flame-retardant exposures to the youngest, most vulnerable segment of society constitutes "the ultimate Bambi factor," Hites notes. Lunder and others express hope that the new findings will make investigation of fetal and neonatal PBDE toxicity a high priority.

NEWFOUND RISKS At the Boston dioxin meeting, several researchers linked PBDEs to reproductive and brain problems. For example, Chris Talsness of Berlin's Free University reported on reproductive-system impairments in rats after exposures in the womb to BDE-99, a 5-bromine PBDE.

Her team injected the chemical into the stomachs of females on the sixth day of their pregnancies, when fetal organs begin developing. The rats received either 60 or 300 micrograms per kilogram of body weight. The latter, Birnbaum points out, is about 10 times the highest values for PBDEs reported in U.S. residents' blood or fat.

Although treated rat moms experienced a slightly higher miscarriage rate than did females that had received an equivalent amount of peanut oil, the big effects showed up once pups reached adulthood. Ovaries of daughters from both groups of BDE-treated moms sported cell abnormalities not seen in unexposed rats.

Some sons of treated animals exhibited low spleen weights, "a flag that the immune system may be affected," Talsness says. Compared with sons of untreated rats, exposed males also had testes weighing less and producing fewer sperm.

In a follow-up study, the researchers mated unexposed rats with offspring of treated moms. Abnormalities in the offspring of those crosses suggested that the BDE-99 had caused genetic changes, Talsness says. For example, daughters that had been exposed to the chemical as fetuses bore pups with unusual birth defects, such as missing vertebrae and skull bones. Sons exposed as fetuses showed decreased fertility. These problems turned up far less often in matings of unexposed pairs.

Per Eriksson of Uppsala University in Sweden and his coworkers also worked with BDE-99 in their recent studies. Two years ago, the scientists reported that this chemical, as well as the 4-bromine congener BDE-47 and various PCBs, could impair learning and memory in rodents if given at a critical period in brain development. In a newer study, Eriksson's group gave BDE-99 orally to mice 10 days affer birth, a period when baby rats are at about the same stage of development as a human fetus is during the third trimester of pregnancy. The researchers used a dose of either 0.8 or 8 milligrams per kilogram of an animal's body weight. When the pups reached adulthood, the researchers ran the animals through water-maze tests to evaluate their mental skills. Although animals in the lower-dose group performed much as untreated mice did, those getting the higher dose showed memory problems.

The scientists also observed how well each mouse familiarized itself to a new cage. An untreated or low-dose mouse would typically start out agitated, rapidly explore a novel cage, and then slow down within an hour. However, mice getting the higher PBDE dose became increasingly hyperactive through the hour. Tested again 2 months later, these animals became even more hyperactive during the cagefamiliarization test.

More disturbing, in Eriksson's view, was the outcome of a test in which mice got the low dose of BDE-99 and a similar subtoxic dose of a PCB. Early exposure to PCBs can cause lasting IQ deficits in children (SN: 6/16/O1, p. 374). In the new tests, animals performed even more poorly on learning and memory tests than had mice exposed to a dose of the PCB 10 times that given in this experiment. Says the toxicologist, "I was surprised the [flame retardant] had such a strong and pronounced interaction with the PCB" Indeed, he notes, the pollutants' comebined impact appeared "more than additive."

In a study due out soon in Toxicological Sciences, Eriksson's group shows that exposure to BDE-209 during that same early period of brain development elicits similar lasting neurobehavioral effects in mice.

Marcia L. Hardy, a toxicologist with Albemarle Corp., in Baton Rouge, La., which makes the deca-PBDE product, notes that she has been trying to see those BDE-209 data since 2001. Several months ago, her group obtained a draft version, but she notes that the report "still leaves a lot of questions unanswered" However, even if Eriksson's data hold up, the exposure a mother mouse needed to deliver PBDE concentrations in milk that are equivalent to what the pups received is "astronomically huge," she says. "I don't see how there could be any exposure like that"

WHAT TO DO? Almost 2 years ago, 126 nations, including the United States, endorsed a new international treaty to control the production and use of so-called persistent organic pollutants (POPs). The goal was to limit the release of agents that were toxic, long-lived, and able to travel long distances (SN: 6/2/01, p. 343). PCBs, dioxins, and DDT are among the first POPs slated to be banned worldwide under the treaty. Indeed, owing to their established toxicity, most of the initially listed chemicals had already been banned in the United States and other developed countries.

PBDEs and some other brominated flame retardants now in production also deserve such a global phaseout, argues Ake Bergman of Stockholm University. After all, he notes, most PBDEs are quite longlived (seep. 269) and long-distance travelers. As several research teams reported at the Dioxin 2003 meeting, PBDEs show up not only near where they were made or used but also in remote Arctic lakes. Many toxicologists have begun referring to PBDEs as "the next PCBs"

Bergman points out that when it comes to PBDEs' toxicity and persistence, "we know more about these than we knew about PCBs at the time they were banned in the 1970s"

The European Union will ban two of the three most popular PBDE formulations starting next year. These are the penta and octa mixes, containing primarily 5- and 8-bromine congeners, respectively. In September, California became the only U.S. jurisdiction to move against PBDEs. It passed a law to ban penta and octa mixes, but not unti1 2008. Elsewhere, production and use of these compounds remain unregulated, and no government has targeted the deca mix for controls.

Bergman expects the toxicity data emerging on the l0-bromine BDE-209 to change that. "I would be surprised if the deca [mix] isn't going to also be banned [in Europe] quite soon." However, a ban on the deca mix won't come easily, he concedes, "because there is tremendous pressure from industry to keep it"

Indeed, Hardy told Science News, data on the deca mix--which now accounts for some 80 percent of PBDEs used globally--indicate its toxicity is so low that "this is the flame retardant we should be using"

In the meantime, argues Leif Magnuson of EPA's pollutioncontrol program in San Francisco, manufacturers should try weaning themselves from brominated flame retardants. Already, he notes, the electronics companies NEC, Toshiba, Sony, and Fujitsu have announced a phaseout of the PBDEs from their products.

IKEA, the Swedish furniture maker, has eliminated brominated flame retardants from its product line. One U.S. maker of mattress foam, Hickory Springs in North Carolina, tried to switch to a nonbrominated flame retardant this year, but in summer, the new production processes turned the foam yellow. Mattress makers balked at accepting anything but snow-white foam.

Moreover, there are problems looming for the two major brominated flame retardants, ones unlikely to serve as replacements for any banned PBDEs. At the EPA and Dioxin 2003 meetings last August, toxicologists reported that tetrabromobisphenol-A impairs the liver and the immune, nervous, and endocrine systems, and hexabromocyclododecane is detrimental to the nervous system and also toxic to fish and other aquatic animals.

Manufacturers of flame retardants are already working on a host of potential alternatives. Though Lunder and others call for extensive safety reviews of whatever new flame retardants those companies come up with, Bergman argues that nothing should stall action against PBDEs.

Counters Hardy: "The real risk is fire" PBDEs have proved valuable at reducing fire risk, but she says that in discussions of any possible risks, "we're not really hearing much about their benefits"

"For heaven's sake,' Bergman counters, "didn't we learn anything from the issues of DDT and PCBs? It's really time to act."

Brominated Flame Retardants The top 5 of about 35 commercial products

TYPE                    GLOBAL / U.S. USE   Applications
                        (METRIC TONS)
Tetrabromobisphenol-A   119,000 / 18,000    Computer circuit boards,
                                            plastic housing for office
                                            equipment
Deca-BDE mix            56,100 / 24,500     Plastic housing and small
                                            parts in office equipment,
                                            rubber cables, paints,
                                            plastic electrical parts,
                                            fabric backings and
                                            coatings
Hexabromocyclododecane  16,700 / 2,800      Plastics, polystyrene
                                            foams and resins, cable
                                            and textile coatings,
                                            rigid-construction
                                            foams and blocks
Penta-BDE mix            7,500 / 7,100      Polyurethane foam,
                                            imitation wood, carpet
                                            padding, packaging,
                                            sound-insulating
                                            panels, cushioning, rubber
                                            cables, paints, plastic
                                            electrical parts, fabric
                                            backings
.                                           and coatings
Octa-BDE mix             3,790 / 1,500      Plastic housing and small
                                            parts in office equipment