US - scientists criticize EPA chemical screening program ...

Excerpt from The Dallas Morning News:

Scientists criticize EPA chemical screening program

27 May 2007

Experts worry agency's program will miss harmful effects on hormones; agency counters program developed in an open manner

Scientists say the Bush administration is developing a chemical testing program that favors the chemical industry when it comes to judging whether certain substances in the environment might cause cancer, infertility, or harm to babies in the womb.

What's billed as one of the most comprehensive screening programs ever to check whether chemicals can disrupt human hormones, scientists say, may instead prove to be a misleading $76 million waste.

Federal officials defend the program, which aims to identify so-called "endocrine disruptors."

They say that no tests can cover everything, and that the process of setting up the program has been open and transparent.

The critics agree that much is known about the tests – and, they say, the publicly available information is precisely what causes their concern.

They say the Environmental Protection Agency has:

• Allowed lab tests, using rodents, that are so badly designed, they're almost certain to miss harmful chemicals. For instance, the EPA favors using a breed of rat that is relatively insensitive to several known hormone-disrupting chemicals. And the EPA plans to allow those rats to be fed chow that could mask the effect of some chemicals.

• Failed to guarantee that tests will be conducted on prenatal exposure to chemicals. Last week, a group of 200 scientists signed a declaration warning that exposure to chemicals in the womb may make babies more likely to develop diabetes, obesity, attention deficit disorder and infertility. The group urged action from governments around the world.

• Demanded the wrong dosage range, also raising the odds that harmful effects will be missed.

• Said it might allow chemical companies to tailor certain aspects of the tests.

"If your objective is not to find anything, that's the perfect way to do it," said Fred vom Saal, a developmental biologist at the University of Missouri.

The National Resources Defense Council, an environmental advocacy group, says the EPA is bending to special interests.

"There certainly is industry influence," said Dr. Sarah Janssen, a reproductive biologist with the group in San Francisco. "What really is driving [the decisions] is the industry focus of the administration. That's why the EPA listens to them."

EPA officials respond that they have developed the program – called the Endocrine Disruptor Screening Program – in an open manner to protect it from special interests.

"You're always going to find people that think their issue is not given appropriate attention," said EPA biologist James Kariya, a coordinator of the screening program. "But if anything, this program has been very transparent, very open."

EPA officials say the agency has thoroughly and openly considered the test animal, test dose and animal chow issues. As for allowing the chemical industry to make decisions on how to test chemicals, the EPA said it is not worried about foul play.

"There are dishonest people, but that's not the experience with the community that we've been working with," Mr. Kariya said.

The EPA plans to begin chemical screening in 2008.

Wildlife abnormalities

Scientists began to suspect that manmade chemicals could interfere with hormones in the 1960s. Since then, scientists have documented wildlife abnormalities in areas contaminated with industrial chemicals.

For example, in a Florida lake contaminated with pesticides, male alligators produced female levels of testosterone, made abnormal sperm and had stunted sex organs. In ponds across the Midwest, male frogs are making eggs. Lab studies point to the herbicide atrazine as the culprit.

In seagull eggs exposed to the pesticide DDT, male chicks hatched with sex organs that were part female.

In all these cases, manmade chemicals interfered with the creatures' sex hormones, blurring the line between male and female.

Lab studies have also established that hormone-disrupting chemicals can cause abnormalities in mammals, namely rats and mice. And some studies have made correlations – but not cause-and-effect links – between hormone-disrupting chemicals and human deformities. As one example, reproductive organ abnormalities in baby boys track with levels of known hormone-disrupting chemicals in their mothers, according to 2005 research led by a scientist at the University of Rochester in New York.

Based on these multiple lines of evidence, researchers suspect long-term effects on people – such as lower sperm counts, abnormal genitals, infertility and cancer.

The Dallas-based Susan G. Komen for the Cure foundation has also shown concern, recently funding a research institute to compile research articles connecting hormone-disrupting chemicals to breast cancer.

But because it's impractical – not to mention unethical – to do experiments on people, human effects are hard to assess.

As part of the Food Quality Protection Act of 1996, Congress ordered the EPA to come up with an animal-screening program to see if pesticide chemicals had the potential to interfere with hormone systems in people. Substances such as those used in industrial processes or found in consumer products could also be tested at the EPA's request.

A few hormone-disrupting chemicals have already received attention in the media or from scientists, including bisphenol A and DES.

In one high-profile effort, the city of San Francisco failed to ban the sale of toys and child-care products made with bisphenol A, which is also found in the linings of some food cans. DES, or diethylstilbestrol, an anti-miscarriage drug, caused infertility and uterine cancer in women whose mothers took it during pregnancy. The drug is no longer used.

Yet it's unknown how many of the 80,000 registered chemicals are hormone disruptors. The EPA has already decreed safe levels for some chemicals, such as bisphenol A, although many scientists think the agency's levels are too high.

The 1996 act said the EPA had to implement the program within three years, but testing still has not begun. When the National Resources Defense Council sued the EPA for missing the deadline, the EPA said it interpreted "implement" to include validating the lab assays for the program, a process that is still ongoing.

Legislators have taken notice.

"Over 10 years ago, Congress passed two laws ordering EPA to test chemicals to see whether they are endocrine disruptors, but EPA has dragged its feet and failed to test even a single chemical under this program," said Sen. Barbara Boxer, D-Calif., chairwoman of the Senate's Environment and Public Works Committee.

"The time has come for EPA to test chemicals for these toxic effects and to ban or severely restrict toxins that can disrupt our hormone systems."

Even though delays are frustrating and the program is criticized, some environmentalists say the testing needs to proceed.

"There is never going to be a perfect program," said the Dr. Janssen of the National Resources Defense Council.

"Imperfect testing is better than no testing at all. To further delay it is not being of any use."

The EPA now anticipates that the first round of tests, on an initial battery of 50 to 100 chemicals, will begin early next year.

The success of any chemical screening program, scientists point out, lies in the design of the assays. Just as a doctor can't hear an erratic heartbeat with a broken stethoscope, lab tests that aim to pick up hormone-like chemicals simply won't if the tests aren't sensitive enough.

But what's sensitive enough for the EPA is far from enough in the minds of many independent researchers.

Doses of chemicals

The problems start, scientists say, with the doses of chemicals to be tested. It makes sense to most people that higher doses of a toxic chemical are the worst, and, as levels drop, effects diminish. That's what toxicologists had always assumed, and the EPA program is designed along that thinking. Proposed tests require starting with the highest dose that can be tolerated and dropping down a few notches from there.

That may be fine for what people think of as typical poisons, like lead or mercury, but it doesn't work for chemicals that interfere with hormones, researchers say.

"We need to put traditional toxicology on the back burner and find a better approach," said Theo Colborn, a zoologist with the University of Florida and president of the Endocrine Disruption Exchange, an independent research group.

Dr. Colborn was one of the first scientists to recognize that chemicals leaching into the environment were disrupting hormones in wildlife. "The assays that the EPA has proposed are still based on high doses."

Counter to what one might expect, hormones can have unexpected effects at lower doses, recent studies have found.

"Endocrine disruptors affect the endocrine system," said Wade Welshons, a biologist at the University of Missouri. And in that system, he said, "the lowest levels are the ones that are the most important."

For example, scientists have found that while high neonatal doses of the former anti-miscarriage drug DES cause weight loss in mice, low doses cause obesity later in life. Rat experiments on DEHP, a phthalate found in plastics and other consumer products, show that low doses suppress an enzyme needed for proper development of the male brain. High doses stimulate the enzyme.

Dr. Welshons says that even the well-known drug tamoxifen, given to treat certain breast tumors, is known to have opposite effects at different levels in the body. When a woman first starts taking tamoxifen and levels in the body are still low, the drug can actually cause a tumor to "flare," or grow. Only when levels build does tamoxifen slow tumor growth.

The doses to be tested under the EPA program are too high if the goal is to detect chemicals that interfere with hormones, say Dr. Welshons and other scientists. The EPA program will miss many low-dose effects, he said.

"You can't start from the top and go down," Dr. Welshons said. "You have to start from the bottom and go up."

In response to assertions that the agency is not testing at low enough doses, EPA officials cited conclusions from a 2001 National Toxicology Program report examining the evidence for low-dose effects of hormones.

The EPA stated in 2002 that, because of conflicting study results, "it would be premature to require routine testing of substances for low-dose effects in the Endocrine Disruptor Screening Program."

Richard Becker, a toxicologist with the American Chemistry Council, which represents the chemical industry, also dismissed the idea that hormone-like chemicals can have effects at low doses as not reproducible.

But since the agency's 2002 statement, dozens of research articles have been published showing that low doses of hormone-disrupting chemicals can have profound effects in rats and mice. EPA officials also said that using additional doses that would extend into the low-dose range would make assays cumbersome.

"You really are limited to a certain number of doses," Mr. Kariya said. Also, he added, "you don't want to be using lots and lots of doses for animal welfare concerns."

Rat chow

Problem No. 2, say critics of the EPA program, is the chow that the lab rats will eat. Typical rodent chows use soy as a protein source, and soy naturally contains compounds called phytoestrogens. These compounds are known to interfere with natural hormones. And, as endocrine disruptors themselves, the phytoestrogens can mask the effects of endocrine-disrupting chemicals the program is supposed to pick up.

The EPA said it would probably cap the level of two major phytoestrogens. But critics say the chosen level could easily mask some weaker ­ but nevertheless dangerous – hormone-disrupting chemicals.

"You use these diets, your chances of missing something are much greater," said Julius Thigpen, head of the Quality Assurance Laboratory at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. Dr. Thigpen was one of the first scientists to publicize findings that phytoestrogens in chow can make or break an experiment.

"Who in their right mind would want to use it?" she asked.

Researchers say there is no easy solution to the chow problem. Even chows that are soy-free contain chemicals that mimic estrogen, and there is a lot of batch-to-batch variation in hormone-like chemicals in any given chow formula. But in the absence of a perfect chow, scientists say, the EPA could at least demand that assays be conducted with lower phytoestrogen levels.

Dr. Becker of the American Chemistry Council noted that his organization funded a study that the EPA used in setting the limit of phytoestrogen levels. "The whole question of phytoestrogens and diet has been answered," he said.

A member of a committee that advises the EPA on the screening program said that fine control of the chow formulas isn't necessary.

"People seem to forget what the purpose of the tests are," said Paul Foster, a toxicologist at the National Institute of Environmental Health Sciences. Before working as a government scientist, Dr. Foster worked in the agrochemical and pharmaceutical industry.

"There are times where you should be careful and go to the extra expense, but I'm not sure that this is one of those times. This is for a yes-or-no answer."

The EPA's Mr. Kariya acknowledged that, given the complexity of rodent diets and how they affect body functions, the agency didn't know what the best chow is.

"We don't really know enough about the complex materials in feeds to know what makes a difference and what doesn't," he said. "To some extent, there's a resource issue for testing all the combinations of feed. That becomes an unmanageable feat."

The EPA's statements come at a time when the National Institute of Environmental Health Sciences is preparing a meeting summary warning researchers that many experiments, particularly those designed to measure effects of hormones, may be compromised when researchers unknowingly feed their rodents chow loaded with phytoestrogens.

Rat breed

The EPA says it will likely recommend that tests be done on a breed of rat known as the Sprague-Dawley (CD) rat. But there are many complaints about that choice. First, many scientists consider the Sprague-Dawley (CD) rat a sort of super-rat when it comes to hormone studies.

"It is an extremely bizarre animal," said Missouri's Dr. vom Saal. For some known hormone disruptors, "it is essentially unresponsive ... this is an animal that you would never use." It's possible that chemicals that are harmful to people may not register with the Sprague-Dawley (CD) rat, scientists have said.

"I am concerned that if we test the safety of chemicals on King Kong, we may underestimate their effects on you, me and Bambi," said Jimmy Spearow, a reproductive and toxicological geneticist at the University of California, Davis, in an e-mail interview.

And using a single strain of rat is a bad decision, too, Dr. Spearow said. In an EPA-requested document on choice of test animal, Dr. Spearow unsuccessfully urged the EPA to require testing several strains of animals.

People have a broad range of genetic variability, and one person's genetic makeup may make them especially sensitive to certain hormone-disrupting chemicals. Using a single strain of rat means that scientists are evaluating chemicals on a narrow slice of the genetic pie.

Using the Sprague-Dawley (CD) rat, Dr. Spearow said, "could legitimize levels of chemicals that could be detrimental to sensitive individuals."

The American Chemistry Council acknowledges that there was no perfect lab animal.

"There are always tradeoffs," Dr. Becker said. But the tests that the EPA has chosen have been validated on the Sprague-Dawley rats, he said.

And the EPA, for its part, said that it didn't necessarily agree with Dr. Spearow's argument that using multiple strains of rats would be better than using one strain. Mr. Kariya said more time and research would be needed to determine which strains to use – time the EPA said it did not have.

"Given the implementation of the screening program, we felt best to move forward," he said.

Industry influence

Although the EPA is leaning toward recommending the Sprague-Dawley (CD) rat, it may not require that the rat be used. The EPA said it is considering allowing chemical companies to decide which rat strain to test.

If that's the case, scientists wonder, what prevents a company from the choosing the breed that's least sensitive to its chemical?

"If they can go through and pick what strain they want," said Dr. Spearow, "that would be an absolute disaster."

But Mr. Kariya said he doesn't think a company would select a strain that serves its own financial interests.

"You're talking about people who want to game the program," he said. "We believe they will give us the information we are looking for."

Prenatal exposure

Scientists also want to investigate whether a pregnant animal's exposure to hormone-disrupting chemicals can harm the offspring. Next week, the EPA said, a scientific advisory board will send its recommendations on whether to include a prenatal assay in the first or second phase of the program.

If the test goes into the second phase, chemicals that pass the first phase would never be tested for fetal effects. This troubles some scientists, since recent studies suggest that certain fetal exposures can set the stage for cancer later in life and that fetal exposures can often affect not only an animal's "children" but also its grandchildren and great-grandchildren.

If the test is relegated to the second phase, "the possibility is that they're not going to pick up anything," said Retha Newbold, a biologist with the National Institute for Environmental Health Sciences. "Then we're not covering the unborn fetus."

Remaining issues

The complaints about the EPA program don't end with scientific issues. Crucial decisions remain, such as how to weigh conflicting evidence for a particular chemical – say if some tests show problems and other tests do not.

Other complaints include soliciting opinions from people who may have financial interest in the outcome of the tests. For instance, when the EPA solicited a white paper on which strain of animal to use, they went to a toxicologist who works for a company that does testing for the chemical industry.

"The livelihood of their company is completely dependent on ... good relationships with the chemical companies," said Missouri's Dr. Welshons.

Researchers disappointed with the screening program say they anticipate legal battles over any decisions unfavorable to the chemical industry.

"Once the tests are in place, there will be a whole new fight about which chemicals will be covered," said Dr. Ted Schettler, a physician with the Science and Environmental Health Network, and former member of a committee advising the EPA on the screening program. And as far as research goes, the public will have to rely on individual scientists' work to discover whether chemicals are harmful.

"Individual research groups will show effects, and chemicals will have to be removed one at a time," said Missouri's Dr. Welshons. "In spite of having passed the EDSP."

See - Scientists criticize EPA chemical screening program.

WHAT IS THE EDSP?

The Endocrine Disruptor Screening Program, being developed by the U.S. Environmental Protection Agency, is a battery of lab tests to check whether thousands of manmade chemicals are endocrine disruptors. Endocrine disruptors are chemicals that, in people and in wildlife, can interfere with natural hormones, including estrogen, testosterone and thyroid hormones. Known endocrine disruptors have been shown – either in laboratory or natural settings – to cause lower fertility, abnormal reproductive organs and cancer.

WHY IS IT IMPORTANT?

A variety of lines of evidence suggest that chemicals found in the environment – from plastics, pesticides, cosmetics and other sources – may be interfering with natural hormonal processes in wildlife and people. In 1996, Congress passed a law requiring the EPA to determine whether pesticides and possibly other chemicals are endocrine disruptors.

WHERE DOES THE EDSP STAND?

With input from government, independent, university and chemical industry scientists, the EPA has developed and standardized some of the lab assays to screen the chemicals; it is still working on others. The EPA says it hopes chemical screening will begin in 2008.

WHY ARE SCIENTISTS CONCERNED?

A large number of independent scientists – working at universities or in federal research labs – have said the proposed lab assays may miss harmful chemicals. Choices of test lab animal and their diet, as well as the chemical dose range to be tested, are stacked toward missing rather than detecting any harmful effects, scientists say.