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Health risks of PBDEs

Mother's Milk: Health risks of PBDEs

September 23, 2003

A growing body of research in laboratory animals has linked PBDE exposure to an array of adverse health effects including thyroid hormone disruption, permanent learning and memory impairment, behavioral changes, hearing deficits, delayed puberty onset, decreased sperm count, fetal malformations and, possibly, cancer. Research in animals shows that exposure to brominated fire retardants in-utero or during infancy leads to more significant harm than exposure during adulthood, and at much lower levels. And some of these studies have found toxic effects at levels lower than are now detected in American women. Many questions remain, but new evidence raises concerns that low levels of PBDE exposure pose a significant health risk to developing animals, and may pose a health risk to fetuses, infants and children at levels currently detected in American women.

The indication that PBDEs can cause subtle neurological deficits in developing animals echoes what researchers have learned over the past 20 years about the structurally similar, but much better studied, PCBs. Used primarily as electrical insulators, PCBs were found to be rapidly building up in people and animals before they were banned in 1977. Although levels are now declining, PCBs persist in the environment and cause a number of well-documented health problems. Recent studies have shown that PBDEs can act in concert with PCBs and other chemicals through similar mechanisms to increase their effects. [60, 61, 62]

Many of the known health effects of PBDEs are thought to stem from their ability to disrupt the body's thyroid hormone balance, by depressing levels of the T3 and T4 hormones, which are important to normal metabolism. In adults, hypothyroidism can cause fatigue, depression, anxiety, unexplained weight gain, hair loss and low libido. This can lead to more serious problems if left untreated, but the consequences of depressed thyroid hormone levels on developing fetuses and infants can be devastating. [63] One study, for instance, found that women whose levels of T4 measured in the lowest 10 percent of the population during the first trimester of pregnancy were more than 2.5 times as likely to have a child with an IQ of less than 85 (in the lowest 20 percent of the range of IQs) and five times as likely to have a child with an IQ of less than 70, meeting the diagnosis of "mild retardation." [64] An IQ less than 85 can be associated with serious consequences. Two-thirds of children who drop out of high school have IQs below 85.

Even short-term exposures to commercial PBDE mixtures or individual congeners can alter thyroid hormone levels in animals, and the effects are more profound in fetuses and young animals than in adults. [65, 66, 67, 68, 69, 70] These results aren't surprising, but are ominous as data in humans indicate that pregnancy itself stresses the thyroid, and developing fetuses and infants do not have the thyroid hormone reserves adults do to help buffer insults to the system. [71]

Most studies on thyroid hormone disruption by PBDEs have been short-term, with exposures of 14 days or less. The real question is how low doses over the long term affect the body's thyroid hormone balance. The answer is important, because the entire U.S. population is exposed daily to low levels of PBDEs, and studies of other thyroid hormone disrupters have found that long-term exposures can cause more serious harm at lower levels of exposure. [72] Although no direct link could be made, one study found higher rates of hypothyroidism among workers exposed to brominated fire retardants on the job. [73]

Because the developing brain is known to be extremely sensitive to neurotoxicants, researchers have begun to examine whether short-term exposures to PBDEs at critical times could have long-term effects. The results are troubling: small doses administered to fetal or newborn mice and rats caused deficits in learning, memory and hearing, changes in behavior, and delays in sensory-motor development. Many of these effects were found to worsen with age, and the effects were seen with the higher-weight PBDEs (the usually less harmful Deca) as well as the more readily absorbed lower-weight congeners.[7, 74, 75]

Harm at one dose?

Experiments have shown that just one dose of PBDEs at a critical point in brain development can cause lasting harm. [7, 74, 75] In two different studies, a small dose — as little as 0.8 milligrams per kilogram of body weight per day (mg/kg-day) — given to 10-day-old mice caused "deranged spontaneous behavior," significant deficits in learning and memory and reduced ability to adapt to new environments, with these problems often becoming more pronounced with age. [7, 75] This research also demonstrated the heightened sensitivity of the brain at certain critical phases of development. While earlier exposures caused "significantly impaired spontaneous motor behavior" and "persistent neurotoxic effects," no effects were seen in mice that were exposed later in development, despite having similar levels of PBDEs (or their metabolites) in the brain. [7]

Other animal studies have shown that early-life exposures to PBDEs, often at relatively low levels, can lead to delays in sensory-motor development, hearing deficits, as well as changes in activity levels and fear responses. [74, 76, 77] At this point, scientists do not understand exactly how PBDEs affect neurological development. But there is evidence that PBDEs and/or their metabolites are in fact acting through several different mechanisms, including mimicking thyroid hormones, increasing their rate of clearance in the body and interfering with intracellular communication. [78]

In addition to their effects on thyroid hormones and neurological development, PBDEs have been linked to a gamut of other health impacts in laboratory animals, from subtle to dramatic. For example, several new studies found that early-life exposure to PBDEs has significant reproductive effects including delaying the onset of puberty in male and female rats and decreasing the weight of male rat reproductive organs and sperm count. [79, 80, 81, 82] In studies of pregnant animals, PBDE exposure was associated with retarded weight gain, enlarged livers and raised serum cholesterol. [83, 84] In-utero exposures have also been associated with serious harm to the fetus, including limb and ureter malformation, enlarged hearts, bent ribs, fused stemebrae, delayed bone hardening, and lower weight gain. [83, 84, 85, 86] The malformations of the fetus were consistently seen at levels much lower than doses harmful to the mouse mothers — the lowest being 2 and 5 mg/kg-day, respectively. But more subtle reproductive effects, such as decreased sperm count and changes in the sub-cellular structure of the ovaries, were seen at incredibly low doses — just 0.06 mg/kg-day. [82]

The few studies that have looked at changes in organ structure have found that semi-chronic PBDE exposure can cause thyroid hyperplasia (overgrowth of thyroid tissue) and enlarged livers at relatively low doses (10 mg/kg-day) and other adverse effects such as abnormal cell functioning, localized cell death and deformation in the kidney, changes in the liver's cellular structure, decreased hemoglobin and red blood cell counts at higher doses. [83, 85, 87, 88] Only one commercial PBDE mixture has been tested for its ability to cause cancer, in a single study more than 15 years ago. High doses of Deca given to rats and mice caused liver, thyroid and pancreas tumors. [88] Deca-BDE is the least easily absorbed and the most rapidly eliminated of the PBDEs, and recent research indicates that other congeners can cause genetic recombination in cells, which raises concern for carcinogenicity. [89] As a result, scientists believe that the congeners with fewer bromines are likely to be more carcinogenic than deca-BDE and have urged that such tests be conducted. [78]

PBDEs cause adverse effects in rodents at low doses.


PBDE congener

Test animal

PBDE concentration in fat tissue

PBDE dose (mg/kg-day)

Toxic effect

Source

PBDE-99

Mice

12 ppb in brain lipid*

0.8 (single dose)

Effects on learning and memory, spontaneous motor behavior and habitutation capability that worsened with age

[75, 7]

Commercial Penta Mixture (DE-71)

Mice

Not measured

0.8 (single dose)

Significant decrease in thyroid hormone (T4) levels

[65]

PBDE-99

Rats

Not measured

0.06 (single dose)

Decreased sperm count

[82]

PBDE-99

Rats

Not measured

0.06 (single dose)

Changes in the subcellular structure of ovaries

[113]


Levels of fire retardants in breast milk detected in some participants are higher than levels in mouse brain lipid levels that have been linked to adverse health effects. The relationship between contaminat levels in the lipid of breast milk and brain tissue is not known.
* Assuming that a rodent brain is 30% lipid [8]

PBDE body burdens nearing threshold for harmful effects

A growing body of animal research shows a very low threshold for PBDEs to cause permanent impacts to the nervous system. One of the lowest harmful doses of PBDEs was found in a 2002 study of newborn mice which showed neurodevelopmental damage at concentrations of just 4 ppb in brain tissue or about 12 ppb in brain fat. This study exposed lab animals to a single dose of one type of PBDE, called PBDE-99. Thirty percent of the participants in our study and almost 20 percent of women in the Texas study had more than 12 ppb of PBDE-99 in the fat of their breast milk, but no studies have investigated the relationship between contaminant levels in lipid of brain tissue and lipids from breast milk or other body tissues, making it difficult to determine if human exposures exceed levels known to permanently damage rodent brains.[7, 8] Scientists are most concerned about the neurological impacts of PBDEs on the fetus and young child. These impacts are inherently difficult to detect in rodent studies, which can't measure subtle impacts to learning, memory and behavior. The fact that we are seeing these effects in lab animals heightens concerns for human health. [90]

A scientist at the California Environmental Protection Agency's Office of Environmental Health Hazard Assessment (OEHHA) combined all the data on PBDE body burdens in tissue, blood and breast milk from women across the country available in April 2003 to project PBDE levels in the entire U.S. population. If the data used in the model are representative of the American population, as many as 15 million Americans would have a body burden more than 400 ppb for all PBDEs. [8] Our study measured much higher contaminant levels than those included in the model, indicating that these calculations might underestimate exposures to the American public.

PBDEs have been shown to impact the same body systems as their notorious cousins, the PCBs. [7, 62] For example, a recent study showed that a low dose of a single PBDE congener given to pregnant rats along with a low dose of a single PCB conger caused neurodevelopmental deficits in offspring that were not seen when the same doses of the congeners were given alone. [60]

While PCB levels are declining, they still harm infant development at levels commonly detected in the American population. Current body burdens of PBDEs in U.S. mothers' breast milk are thought to be slightly lower than levels of PCBs, and PBDEs are thought to be less potent toxicants. However, the rapid increase in PBDE levels and significant number of highly-exposed people, both indicate that PBDEs could soon eclipse PCBs as the predominant persistent toxin in our bodies. If the increase in the fire retardant body burdens continues at its current rate, levels of PBDEs will soon exceed levels of PCBs associated with a six-point deficit in IQ points in children (>1,250 ppb in lipid.) [91]

If fire retardant body burdens are found to be causing adverse neurological effects, either alone or in concert with exposures to other common bioactive chemicals, the potential costs of this damage could be significant. Government agencies considering protection and standards for lead and PCBs have attempted to calculate the societal costs of reduced learning capacity — effects associated with exposure to these chemicals for young children. They attempt to quantify the impact to society in terms of increased special education and reduced lifetime earnings capacity, as measured by subtle deficits in learning and memory measured by IQ and other tests. Their estimates vary widely depending on the impact measured. A one-point loss in IQ over an entire population of newborn children in the United States has been calculated to cost $55 to 65 billion per year. [92] Given that learning, developmental and behavioral disabilities already affect nearly 12 million U.S. children [93], it is prudent to control avoidable sources of contamination that threaten permanent effects on our children's health.