'Inherently toxic' chemical faces its future
Quibus_Licet
MARTIN MITTELSTAEDT
>From Saturday's Globe and Mail
April 7, 2007 at 12:44 AM EDT
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.
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.
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.
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.
"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.
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."
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.