It stands to reason that a two-pack-a-day smoker faces a far greater risk of developing lung cancer than someone who puffs just one pack, while anyone who indulges in the occasional cigarette is at little or no risk at all.
Among scientists, this notion that harm escalates as the exposure to something harmful increases seems so commonsensical that it's gone unchallenged since first postulated in the 16th century by Paracelsus, the Swiss alchemist considered the father of toxicology.
Immortalized as "the dose makes the poison," the concept is used by regulators around the world to determine the safety of compounds. It's why laboratories give test animals huge quantities of chemicals to establish what will damage them, then lesser amounts to determine at what point exposure is harmless.
But even pillars of science can be turned on their heads, Critics such as Pete Myers, chief scientist at Environmental Health Sciences, a public-health advocacy group based in Charlottesville, Va., argue that in at least one chemical category, toxicology has it all wrong. When it comes to synthetic substances able to mimic the hormones in our endocrine system, low doses only seem insignificant.
The idea that less of a chemical may pose an even greater threat seems "almost incredible," Dr. Myers admits - "until you understand the incredible potency of hormones."
Not only are small doses of hormone disruptors dangerous, he says, they may well explain the mysterious rash of modern ailments - attention-deficit disorders, thyroid problems, obesity, precocious puberty in girls, hormonally influenced cancers - that have gone from rare to commonplace.
Man-made compounds able to imitate or skew natural hormones are found everywhere, leaking from many consumer products to become uninvited visitors in the cells in our bodies. For instance, many chemicals used to make plastics and pesticides have, upon closer testing, been found to be able to play havoc with hormones.
One culprit is phthalates, the chemicals used to make that rubber-duck bath toy so supple. But the poster child for this controversy is bisphenol A, the reason so many Canadians have been pitching out their plastic water bottles, baby bottles and sippy cups. U.S. surveys are finding that more than 90 per cent of the public carries traces of BPA, while researchers studying its impact in tiny doses have discovered that it amounts to an extra dollop of estrogen, the female sex hormone - linked to everything from enlarged prostate glands and erectile dysfunction among men to increased risk of breast cancer.
Now, the question of whether tiny chemical residues should be alarming is about to get its first serious investigation - from the U.S. Food and Drug Administration. This represents a major change for the agency, which, for nearly half a century, has said BPA in small exposures is harmless, allowing it to spread to countless products, from DVDs to the plastic lining inside nearly every food and beverage can.
About 200 academic studies have linked low exposures of BPA to conditions including obesity, diabetes, cancer (breast, prostate and uterine), cardiovascular disease and asthma. Meanwhile, research financed by industry has found no such health threats.
As a result, FDA Commissioner Margaret Hamburg says, "the current literature cannot yet be fully interpreted for biological or experimental consistency, or for relevance to human health."
To settle the issue, the U.S. government has earmarked $30-million of stimulus spending for a crash-course study, lasting 18 to 24 months.
Health Canada, meanwhile, has declared BPA toxic. It banned baby bottles made from it two years ago. Yet it calls the ban a precaution to protect infants, and still allows BPA as an unlisted additive in practically all canned food or beverages, even though it is on the country's list of most dangerous substances.
In an e-mail response, a Health Canada official says that "current evidence does not support rejecting the assumption of increasing toxicity with increasing dose," although the agency supports "the need for further research."
Critics say Health Canada's position makes no sense when it comes to chemicals that can mimic or interfere with hormones, because the trouble can stem from trace amounts that are almost insignificant.
The lowest-dose study to date exposed laboratory rodents in the womb to BPA that was 1/1,000th of the level Health Canada considers safe. The result: double the growth of tissue in the creatures' mammary milk ducts, which are the primary site of breast cancer in woman.
That research, done in 2005 at Tufts University in Boston, used a daily dose of 25 parts per trillion. One part per trillion is roughly the same proportion as one second in 32,000 years. Surveys find that most people already have a thousand times that much BPA in their urine. As a result, Dr. Myers says, "there is a glaring hole" in the system used to regulate chemicals.
1990s mouse studiesset off alarm bells
Frederick vom Saal agrees. His is the research that has caused many Canadians to toss their old polycarbonate Nalgene bottles into the trash. A professor of reproductive biology at the University of Missouri, he has spent his 35-year career studying the effects of hormones during fetal development, triggering the flurry of interest in bisphenol A.
In 1997, he fed pregnant mice BPA less than one-10th the dose Health Canada considers safe. The resulting male offspring looked completely normal at birth, but entered adulthood with prostate glands 30 per cent larger than normal. Abnormal growth of the prostate, which produces seminal fluid and so is a key to male fecundity, increases the risk of cancer and is a common problem as men age. This finding sent shock waves through the research community, sparking hundreds of studies that led eventually to the FDA investigation.
According to Dr. vom Saal, hormones are, pound for pound, "pretty much" the most powerful biological agents in existence. As chemical messengers, they help to sculpt our bodies into males and females and shape our minds - even though if all them were wrung out of a person, it would amount to little more than a speck of dust. Female hormones such as estrogen course through us in parts-per-trillion amounts, male hormones such as testosterone at parts per billion, and stress hormones at parts per billion. It does not take much of a synthetic chemical rubbing off consumer products to produce comparable or even higher exposures.
As a researcher, Dr. vom Saal found out just how powerful hormones are through his discovery of what is known as the "intrauterine position" phenomenon. He noticed that lab mice could be almost identical genetically and still have markedly different personalities. Some females were passive while others had attitude, exhibiting male-like aggression; some males were loyal mates while others behaved like playboys.
Dr. vom Saal was able to trace the difference in behaviour back to the womb, where the character of one fetus could be affected by the gender of those next to it simply due to the slight impact their sex would have on fetal estrogen and testosterone levels.
Theo Colborn, president of the Endocrine Disruption Exchange, a Colorado-based research group, has a database of about 50,000 studies of chemical contaminants. From that list, she says, hundreds have been found to interfere with hormones: "We're up to about 966 chemicals now."
Many of those can be found in nearly every home in Canada. They include perfluorinated compounds used to make non-stick cookware and water- and stain-repellent clothing (linked to thyroid hormone imbalances); polybrominated flame retardants in electronic gadgets and mattresses (thyroid, again); and phthalates, which are added to vinyl products to make them pliable (linked to low testosterone).
But few of the estimated 60,000 chemicals currently in commercial use have been thoroughly evaluated for hormonal impacts at low dosages.
Dr. Myers worries that humanity is going through a giant, unregulated experiment. For him, the recent surge in maladies such as attention-deficit disorders among children is a sign that the experiment is going wrong. So is the rise in breast cancers by about 125 per cent in the U.S. since the 1940s, just before widespread use of hormonal contaminants began.
Dr. vom Saal adds, "This is one scary deal."
Not everyone agrees. Some scientists dismiss as "chemophobia" the idea that residue from a rubber duck or sippy cup can be harmful.
"Despite all of the alarmist scares," says Joe Schwarcz, director of McGill University's Office for Science and Society, "our life expectancy gets longer every year, and heart-disease and cancer rates are generally decreasing.
"It is ludicrous to be even talking about BPA when we allow cigarettes to be sold. They kill millions every year - not in theory, but in fact."
And, of course, Paracelsus would scoff at such concerns. But then, he also relied on astronomy as a medical tool and believed in the healing powers of mercury - one of the nastiest poisons in existence.
Martin Mittelstaedt is The Globe and Mail's environment reporter.
Searching for a substitute
Hard, clear and resistant to heat and impact, polycarbonate plastics made with bisphenol A "are excellent," says Joe Schwarcz, director of McGill University's Office for Science and Society, "and that's exactly the problem for suppliers now that BPA has become a dirty word."
So the race is on to make to make something just as good.
"If it was easy, somebody would have done it already," says Geoff Coates, a chemist at Cornell University and co-founder of Novomer, a company now testing technology he devised that produces something biodegradable, non-toxic and largely made of carbon dioxide.
According to Prof. Coates, cost is an issue, just as it is for products that employ polylactic acid, which is made from corn and biodegradable but melts at much lower temperatures.
Donald J. Darensbourg at Texas A&M University is, like Prof. Coates, chasing a successor that uses carbon dioxide, but so far can't offer a replacement for BPA. He points out that there are other hard, clear plastics on the market. One produced in Tennessee by Eastman Chemical Co. contains no BPA, but, again, it is more expensive and melts more readily. "These are totally fine for baby bottles and water bottles - I have one on my desk right now," Prof. Darensbourg says.
Meanwhile, Kyu Yong Choi of the University of Maryland is taking a different approach. He published a theoretical model last year for producing polycarbonates that minimize their BPA residue, he says, "fairly simply by controlling the reaction conditions." He has since done the lab work to prove that the process is chemically possible, and now is looking for about $500,000 (U.S.) to carry out a feasibility study.
The future is more promising for the other big source of BPA exposure, the plastic lining on tin cans. Prof. Coates's company is working with a Dutch firm on a carbon-dioxide-derived resin that Novomer chief executive officer Jim Mahoney says will be "very cost-competitive" - and should be on the market next year.
Special to The Globe and Mail