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Bisphenol A is ingested by practically everyone in Canada who eats canned foods or drinks from a can or hard plastic water bottles.

Now a controversy is raging over the safety of widespread public exposure to the chemical, which is known to act like a synthetic female sex hormone.

At the heart of the intense debate over bisphenol A is that it challenges the main tenet of modern toxicology, the idea that the dose makes the poison, a principle credited to the 15th-century Swiss alchemist Theophrastus Paracelsus.

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Under this principle, a two-pack-a-day smoker is more at risk of cancer than a one-pack-a-day user, and the belief that rising doses make a substance more dangerous is the basis of all government regulations that seek to set safe exposures for harmful chemicals.

It seems obvious that a high dose of a poison would be more dangerous than a lower one, but bisphenol A is creating a stir because it doesn't follow this seemingly common-sense rule. Researchers say this oddity results from the fact that bisphenol A isn't a conventional harmful agent, such as cigarette smoke, but behaves in the unconventional way typical of hormones, where even vanishingly small exposures can be harmful.

This is why some environmentalists and scientists contend that bisphenol A, which leaches in trace amounts from food and beverage packaging, is among the scariest manufactured substances in use, an eerie modern version of the vaunted lead water pipes by which ancient Romans were unknowingly poisoned.

Extrapolating from the results of animal experiments, they suspect bisphenol A has its fingerprints all over the unexplained human health trends emerging in recent decades hinting at something going haywire with sex hormones, including the early onset of puberty, declining sperm counts, and the huge increase in breast and prostate cancer, among other ailments.

But manufacturers - which include some of the world's biggest chemical companies - insist bisphenol A is harmless and say those claiming otherwise have it wrong.

Welcome to the heated controversy over bisphenol A.

Derived from petroleum, bisphenol A is the chief ingredient in polycarbonate, the rigid, translucent hard plastic used in water bottles and many baby bottles. It's also used to make the resins that line most tin cans, dental sealants, car parts, microwaveable plastics, sports helmets and CDs.

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Environment Canada and Health Canada last year selected it as one of 200 substances that a preliminary review deemed possibly dangerous and in need of thorough safety assessments. The 200 were culled as the most worrisome chemicals from among about 23,000 substances in use in the 1980s and grandfathered from detailed safety studies when Canada adopted its first modern pollution laws.

Government scientists classified bisphenol A as "inherently toxic," and companies making it will be challenged by the assessment to prove that continued use is safe.

The assessment is expected to begin next month and provide a glimpse into one of the biggest public-health and scientific controversies in the world.

Some researchers with close-up views of bisphenol A are so shocked by its ability to skew development in their laboratory animals, even at among the lowest doses ever used in experiments, they aren't waiting for the government to ban it. In their personal lives, they can't run away from products containing it fast enough. "I would love to see it banished off the face of the Earth," Dr. Patricia Hunt, a Washington State University geneticist, said.

She began ditching her bisphenol-A-containing products after discovering that mere traces of the chemical were able to scramble the eggs of her lab mice. In humans, similar damage would lead to miscarriages and birth defects, such as Down syndrome. "I thought, 'Oh my God,'ƒ|" she said. "I'm going to throw out every piece of plastic in my kitchen."

Although it has been known, since a search for estrogenic drugs in the 1930s, to act like a sex hormone, bisphenol A has recently emerged as one extremely odd compound, perhaps the most unusual in widespread use. Research has found that it seems to turn modern toxicology on its head by being more dangerous at very low exposures than at high ones, a finding that is focusing attention on the possible health repercussions of the relatively small amounts leaching from consumer products.

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Bisphenol A also has a bizarre pattern of research results, with the funding source of a study the best predictor of whether scientists find it harmful or safe. All major industry studies into bisphenol A's safety, and they number about a dozen, haven't found anything worrisome in low-dose exposures.

However, about 90 per cent of studies by independent researchers over the past decade, numbering about 150, have found adverse effects, ranging from enlarged prostates to abnormal breast tissue growth.

Bisphenol A has been used in increasing amounts since the 1950s in food and beverage containers because it doesn't impart a plastic-like taste, although traces leach out. Plastics that use it are often identified by an industry triangle symbol and the number seven.

Because it is one of the highest-volume manufactured chemicals in the world and used in so many consumer products, bisphenol A exposure in Canadians is likely to be pervasive.

Urine testing in the United States suggests that about 95 per cent of the population have been exposed, and Ottawa began a survey in March to see if a similar figure applies to Canadians, a reasonable prospect given that the same products are used in both countries. Testing elsewhere in the world has also found it present in human blood, as well as in placentas and fetal cord blood.

Manufacturers say that exposures are nothing to worry about, contending that the amounts getting into people from what they eat and drink aren't of any consequence.

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"We know that human exposure to BPA is extraordinarily low, well below levels that have been shown to be safe," said Steven Hentges, spokesman for bisphenol A at the American Plastics Council, which comments on the health controversy over the chemical for four of the five North American manufacturers, GE Plastics, Sunoco Inc., Bayer AG, and Dow Chemical Co. The other producer is Hexion Specialty Chemicals.

He dismisses disease trends showing increasing numbers of hormonally linked ailments rising in tandem with bisphenol A use as "only a statistical association at best" that in no way implicates the industry's product. "You could co-relate those same disease trends with TV watching or coffee drinking or anything you want," he said.

While some companies insist that bisphenol A is harmless, others are just as adamant that it's among the biggest health hazards to which Canadians are unwittingly and routinely exposed.

For Rick Smith, executive director of Environmental Defence, a Toronto group that tracks the exposure of Canadians to pollutants, bisphenol A is the worst substance among the 200 Ottawa suspects may be dangerous. "I think bisphenol A is top of my list, even though there are others that I hate a lot," he said.

The group is so convinced the evidence already shows bisphenol A is a health hazard, it doesn't want Ottawa to wait until the assessment is finished, which could take years, to ban it, particularly in food contact uses. In March, after U.S. environmental groups found the chemical leaching from plastic baby bottles and into canned food, Environmental Defence asked the federal government to end its use, a step that if taken would make Canada the first country in the world to do so.

"If getting this chemical out of those products isn't priority No.ƒ|1, I don't know what is," says Mr. Smith, who in his personal life isn't waiting for Ottawa to act. With his five-month-old son's health in mind, he rid his home of bisphenol-A-containing baby bottles as a safety precaution.

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Currently, there are no regulations limiting bisphenol A leakage from consumer products. The Canadian Food Inspection Agency doesn't monitor canned goods or bottled water for its presence and Health Canada set a provisional exposure standard in 1999, just as the controversy over its health effects was beginning. Like the chemical industry, it has long insisted that the amounts people ingest aren't harmful.

However, there have been more than a dozen studies in laboratory animals since 1999 finding adverse effects from bisphenol A at levels below Canada's standard. One study, done in 2005, found the chemical able to change breast tissue in ways that predispose them to cancer at a dose 1,000 times lower than Canada's limit.

In living things, hormones latch ď onto receptors in cells, turning vital biological processes on or off much like a switch controls a light. When cells are exposed to low doses of hormones, whatever activity they control is stimulated, but at higher doses these receptors are overwhelmed and stop their activity. That is why a hormonally active compound may have one effect at a low dose and no effect at a higher exposure.

"At low doses hormones stimulate their own receptors," said Frederick vom Saal, a University of Missouri biologist and leading academic expert on bisphenol A. "At higher doses, they inhibit their responses."

Within the plastics industry, the idea that small amounts of bisphenol A are dangerous, perhaps more worrisome than larger amounts, isn't dismissed outright, but viewed as a something still at the stage of a hypothesis in need of further proof to be validated, Mr. Hentges said.

But Dr. vom Saal, pointing to the many studies finding harm, said the industry's position "is really stunning because you have this huge independent scientific literature showing adverse effects at stunningly low doses."

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Low doses come into play because hormones are active at minute, parts per trillion concentrations. (A part per trillion is the scientific equivalent of practically nothing, roughly equal to a grain of salt in a large swimming pool.) Surveys of how much bisphenol A comes out of cans and bottles into food have found parts per billion amounts, raising concerns that diet could cause exposures similar to natural hormone levels.

Like many scientists who've found health impacts from bisphenol A, Dr. vom Saal is personally so nervous about its safety that he doesn't eat canned food or use polycarbonate beverage containers any more. "We've done everything possible to try to limit our exposure to this," he said.

Dr. vom Saal helped make one of the earliest discoveries about low doses of bisphenol A, finding in 1997 that traces fed to mice caused a 30-per-cent increase in prostate size.

He's also tried to figure out why industry studies don't find the results that seem so readily apparent in the laboratories of academic scientists.

Dr. vom Saal contends that many industry experiments are flawed. In one case, he says a study funded by the plastics council and including researchers from GE, Dow, and Bayer, found no effects from low doses of bisphenol A, but used a strain of rats he says are hundreds of times less sensitive to estrogenic drugs than humans. The same study failed to use test animals that would have detected that the rats were relatively impervious to sex hormones.

The rats, known as the CD Sprague-Dawley variety, are produced by Charles River Laboratories Inc., of Wilmington, Mass., which said in a written statement that the "scientific literature is unclear and inconsistent" over whether the animals "are less estrogen sensitive than other outbred rat stocks."

Mr. Hentges defended the industry's research, saying it followed approved international guidelines and used a well regarded rat variety. He said a follow-up study using mice also failed to find adverse effects and included a test for estrogen sensitivity. Any suggestions that industry work is flawed "is just plain wrong," he said.

The contradictory findings on bisphenol A have produced a picayune scientific tit for tat between the industry and its critics on almost every aspect of each other's research. For instance, Mr. Hentges claims some academic studies are useless as predictors for human health effects because they used pumps to inject bisphenol A into animals, while human exposure is mainly oral through food.

But scientists counter that their work replicates better what occurs during fetal development, a time when most animals are uniquely sensitive to dangerous substances.

The industry says that when humans consume bisphenol A, most is converted in the gut into a form that isn't dangerous, although those worried about the substance say not all of it is dealt with in this way and diet is constantly replenishing exposures.

There are also disagreements over how potent a hormone mimic bisphenol A is. The industry calls it a weak estrogen because it is thousands of times less effective on some cell receptors. However, it is similar in strength on receptors on the surface of cells crucial for many biological functions.

Dr. vom Saal dismisses this controversy over the relative estrogenic strength of bisphenol A as mere hair splitting. "This is like saying, well Arnold Schwarzenegger is weak, relative to Superman," he said.

To date, international regulatory bodies, most recently the European Food Safety Authority in an assessment issued this year, have given the benefit of the doubt to the industry on these disputes.

Mr. Smith thinks the scientific debate over bisphenol A is part of a broad pattern that emerges whenever industries are threatened by new findings of harm from their products.

Similar disputes have occurred over smoking and cancer, the hazards of lead paint and global warming. But he said that waiting for all scientific disputes to be resolved could be disastrous, when human health is at stake.

"If we wait for absolute certainty, there is a very strong chance that a lot of people will be harmed."

Already, there have been a small number of scientific papers linking exposures to human health outcomes, such as miscarriages (women with miscarriages were found to have three times higher levels of bisphenol A than other women) and ovarian dysfunction, although the industry disputes the findings.

In March, the first U.S. class action lawsuit alleging harm from bisphenol A was launched, against five makers of baby bottles. It was filed in Los Angeles shortly after a U.S. environmental group found the hormone mimic leaching from the bottles when they are heated, something many parents do to formula or milk.

Coincidentally, one big industry player is getting out of the bisphenol A business. This year, GE announced it wanted to sell its plastic business, but the company says the sale has nothing to do with the health controversy.

Peter O'Toole, a spokesman, said the plastics business isn't growing as rapidly as other GE operations and "doesn't seem to be fitting in the current business model." He classifies any litigation risks with bisphenol A as "speculation. There have been risk assessments done on bisphenol A and there has never been evidence shown that it's harmful to human beings," he said.

Dr. vom Saal, for his part, expects that companies associated with bisphenol A will be the next tobacco industry, mired in expensive health litigation in U.S. courts. "This is a train wreck that is absolutely coming," he said.

But Mr. Hentges dismisses views that bisphenol A is about to be derailed. "He has some very unusual views," he said of Dr. vom Saal.

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