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Frederick vom Saal is a respected American biology professor who keeps a running tally of the scientific literature investigating the health effects of bisphenol A, a chemical used in one of the world's most widely used plastics. By his count, 130 papers have been published on the effects of low-dose exposures to the chemical. Dr. vom Saal, a professor at the University of Missouri, found that more than 90 per cent of the government-financed studies noted adverse effects from the chemical, but not one of the 11 industry-backed ones.

The subject is of more than just passing academic interest because practically everyone is exposed to bisphenol A -- or BPA, for short -- on a daily basis. It is used to make a range of things, from tinted Nalgene bottles, to dental sealants for children's teeth, to coatings on compact discs and the sealants on the inside of most tin cans.

The widespread use of BPA wouldn't be a problem, except that the chemical doesn't stay put in products. It leaches out and gets into people, and trace amounts are now found in almost everyone. This worries many researchers because BPA, besides being good for making plastic, is a chemical that mimics the female estrogen hormone.

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Experiments on lab animals exposed to small doses of BPA have linked it to low sperm counts, the earlier onset of puberty, insulin resistance and diabetes, prostate abnormalities and skewed mammary gland development, among other effects. Some researchers, such as Dr. vom Saal, worry that these sorts of adverse effects, if they occur in people, seem to mirror recent human disease and health trends.This view is not shared by the chemical industry. "BPA is not a risk to human health at the extremely low levels at which people might be exposed from use of, for example, polycarbonate plastic," said Steven Hentges, a spokesman on BPA at the American Plastics Council, based in Arlington, Va.

Dr. vom Saal, one of the world's leading authorities on hormones and synthetic chemicals that act like them, begs to differ. "The chemical companies think they can lie with impunity about the published scientific literature," he said.

For academe, those are fighting words and they reflect the controversy enveloping BPA. Although humans carry trace amounts of many industrial chemicals in their tissues, there is intense scientific interest in contaminants such as BPA because they have an unusual property: When absorbed by living things, they act like hormones.

Because BPA has a shape similar to the estrogen hormone, it is able to fit into the same receptors that estrogen uses to signal cells to turn biological functions on and off. For Dr. vom Saal, the idea that the entire population is being given a dose of a synthetic estrogen through plastic "is supported by hundreds of published articles" and is "an extremely critical public health issue."

At the heart of safety disputes over BPA are the results of the low-dose experiments with animals and test-tube cell cultures.

The general public is most familiar with high-dose research, the traditional and rather crude tests in which lab animals are stuffed with large amounts of compounds to see how much it takes to kill them outright, to produce effects such as weight loss, or to induce cancer in them. Based on the results of high-dose U.S. experiments in 1982, BPA was not found to be excessively dangerous. At the time, researchers noted that the chemical caused weight loss in rodents at the lowest dose used; based on this observation, an exposure standard was established by the U.S. Environmental Protection Agency.

It set a safe daily exposure standard of 50 micrograms per kilogram of weight -- which would be about the size of two grains of sand consumed by an average-sized man.

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This may seem like a small amount, but Dr. vom Saal said 40 animal studies have found adverse health effects either at, or below, that EPA dose level, and some of them have been run using amounts similar to the exposures humans receive from consumer products. He believes the safety standard is completely outdated and needs to be lowered sharply.

According to Dr. vom Saal, the traditional tests did not capture the full range of BPA's possible effects because hormones, and synthetic chemicals that act like them, exert influences at extremely low exposures that, paradoxically, do not occur at higher levels. This is because natural hormones don't have what scientists call a traditional "dose response curve," in which increasingly high exposures cause increasingly more pronounced effects.

The response curve for a hormone, instead, looks more like a horseshoe shape, charting how effects appear suddenly, continue for a time, and then drop off sharply. This is because as hormone doses increase, many biological functions they trigger simply shut down temporarily. What is more, hormones also exert influence in exquisitely minute quantities, typically in parts per trillion. One part per trillion is the scientific equivalent of almost nothing.

BPA's ability to cause effects at extremely small amounts presents a major challenge to health standards based on high-dose tests. The U.S. experiments that set the standard, for example, used exposures more than a million times higher than the levels researchers have since determined can harm lab animals.

Health Canada has developed a "provisional," or temporary standard for BPA, at 25 micrograms daily for every kilogram of weight. The department believes this standard protects Canadians from all the PBA likely to be absorbed from cans and bottles, and it dismisses the amount leaking from such items as dental sealants and beverage containers as of no consequence. However, the Canadian standard was based on scientific evidence available up to 1999, before the avalanche of research showing low-dose effects.

In a statement in response to questions about BPA, Health Canada rejected the scientific papers showing low-dose effects because some experiments have not been successfully duplicated by other laboratories. It said the current standard is more than safe because Canadians typically ingest in their food an amount of BPA that is about 100 times less than the safety limit.

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That may seem like a good margin of safety, but it isn't when considering the exposures scientists found are able to cause adverse effects. The lowest dose to date was at exposures 1,000 times lower than the amount Health Canada deems safe. The results of that experiment, published last year by researchers at Tufts University in Boston, involved exposing pregnant mice to 25 parts per trillion of BPA, a minute amount that was still enough to skew the development of mammary gland tissue in their female pups when they reached puberty.

The mice developed an abnormal profusion of buds that grow into milk ducts. The same effect, if it occurred in humans, would lead to an increase in the number of sites where breast cancers may occur, leading to an increased cancer risk for women whose main exposure to the chemical was in utero while their mothers were pregnant.

But Mr. Hentges of the American Plastics Council discounts any implications for humans, saying that because the mice were exposed to BPA by injection, the experiment doesn't apply to humans, who typically ingest the chemical through food and beverages.

Dr. Ana Soto, a medical researcher at Tufts's department of anatomy and cellular biology who led the mouse experiment, said the doses used on the mice were similar to those people receive from consumer products.

TOMORROW: Chemicals are everywhere; how can you live contact free?

Plastics that put us at risk

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Bisphenol A, which is used to make many plastics, can be found in a number of consumer products, from dental sealants for children to compact discs. BPA has bee known to be a synthetic mimic of the female estrogen hormone.

Levels of bisphenol A leaching from consumer products

Although these are considered safe levels under current government standards, new research has found that bisphenol A can have adverse impacts at even lower levels than those present in many consumer goods. The lowest dose to date found to skew the development of laboratory animals is 0.025 parts per billion (25 parts per trillion).

Levels found in consumer goods:

Dental sealants: Up to 105 ppb found in saliva

New plastic baby bottles: Less than 5 ppb

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Office water bottles: 0.1 ppb to 4.7 ppb in water stored for up to 39 weeks

Plastic tableware: Less than 5 ppb

Food from cans: 37 ppb

Levels found in people:

Adult human blood: 0.3 ppb to 18.9 ppb

Human fetal blood: 0.2 ppb to 0.2 ppb

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The effect of bisphenol A on mammary glands of mice

Exposing pregnant mice to extremely small doses of bisphenol A in an experiment prompted explosive growth in the mammary glands of their female pups when they entered puberty. There was a dramatic increase in the number of milk ducts and terminal buds, changes that, if they also occurred in women, would correspond to increased breast cancer risk. The exposure used in the experiment was only 25 parts per trillion. The dose is a thousand times lower than the exposure Health Canada deems safe for humans.

SOURCE: BISPENOL A GLOBAL INDUSTRY GROUP, ENVIRONMENTAL HEALTH PERSPECTIVES, ENDOCRINOLOGY

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