19 Mar 2012

Scientists Warn of Low-Dose Risks of Chemical Exposure

A new study finds that even low doses of hormone-disrupting chemicals — used in everything from plastics to pesticides – can have serious effects on human health. These findings, the researchers say, point to the need for basic changes in how chemical safety testing is conducted.
By elizabeth grossman

Since before the publication of Rachel Carson’s Silent Spring 50 years ago, scientists have known that certain synthetic chemicals can interfere with the hormones that regulate the body’s most vital systems. Evidence of the health impacts of so-called endocrine-disrupting chemicals grew from the 1960s to the 1990s. With the 1996 publication of Our Stolen Future by Theo Colborn, Dianne Dumanoski, and J. Peterson Myers, many people heard for the first time how such exposures — from industrial pollution, pesticides, and contact with finished consumer products, such as plastics — were affecting people and wildlife. Since then public concern about these impacts has grown.

In 2009, the American Medical Association called for reduced exposure to endocrine- disrupting chemicals. Last year, eight scientific societies, representing some 40,000 researchers, urged federal regulators to incorporate the latest research on endocrine-disrupters into chemical safety testing.

Last week, 12 scientists – including such experts as Colborn and the University of Missouri’s Frederick vom Saalpublished a paper that they say significantly advances the debate. Their research, based on a review of
Some experts say there is not yet convincing proof that extremely low doses of these chemicals are harmful.
800 scientific studies, concludes that it is “remarkably common” for very small amounts of hormone-disrupting chemicals to have profound, adverse effects on human health. Hormone-disrupting chemicals, the paper explains, challenge a fundamental tenet of toxicology — “the dose makes the poison” — which contends that the greater the dose, the greater the effect. Hormone-disrupting chemicals don’t necessarily behave like this. Significant health effects, the researchers say, sometimes occur at low rather than high doses.

“Whether low doses of endocrine-disrupting compounds influence human disorders is no longer conjecture, as epidemiological studies show that environmental exposures are associated with human diseases and disabilities,” the paper’s authors write. The study, published in the journal Endocrine Reviews, maintains that the low-dose and special dose-response effects of hormone-disrupting chemicals means that “fundamental changes in chemical testing and safety determination are needed to protect human health.”

The study’s lead author, Laura Vandenberg, a post-doctoral associate at Tufts University’s Department of Developmental and Regenerative Biology, said in an interview said that this low-dose and special dose-response behavior “should be expected of any chemical that acts like a hormone.”

Not all experts in biology and toxicology agree with the study’s conclusions. Some scientists in academia, industry, and the U.S. Environmental Protection Agency said there is not yet convincing proof that extremely low doses of endocrine-disrupting chemicals have ill health effects or consistently produce low-dose effects that are not predicted by their effects at higher doses.

“There’s no question that both natural and synthetic compounds can mimic hormones,” said George Gray, director of the Center for Risk Science and Public Health at The George Washington University. But that a chemical produces effects at one level, no effects at another, and different effects at yet another level of exposure, “that’s not yet widely accepted in toxicology,” said Gray. “It’s something toxicologists are not yet convinced of and comfortable with,” he added.

Hundreds of such hormone-disrupting chemicals have now been identified, and exposure to these compounds is virtually ubiquitous. Among the chemicals the new paper discusses are bisphenol A, used in plastics, can
Among the chemicals cited are bisphenol A, used in plastics and can liners, and common pesticides.
liners, and receipt papers; common pesticides, including atrazine and chlorpyrifos; methyl paraben, a preservative used in cosmetics and personal care products; triclosan, an antibacterial agent used in soaps and toothpaste; nonylphenol, a detergent ingredient; the flame retardant PBDE-99; perchlorate, a fuel compound; and dioxin, an industrial and incineration by-product. The paper also cites DDT and PCBs — discontinued but very environmentally persistent compounds.

“This is the first time anyone’s tried to synthesize this whole field and show that this is not a single chemical issue,” Vandenberg said of the new study.

Very small amounts of hormones, including endocrine system hormones — those that regulate many of the body’s most important systems, among them development, metabolism, and reproduction — can have significant biological effects. So, it’s been discovered, can synthetic compounds with similar chemical compositions. Research indicates that exposure to a small amount of such a chemical at a particular stage of development can prompt effects that can impact not just that particular individual, but, in some cases, several generations.

“It’s not just sex hormones but also thyroid hormones, and insulin among others, that are involved,” said Vandenberg. “We’re really complicated instruments.”

The health effects documented in the studies the paper reviews have been observed in live animal and cell culture studies and in human epidemiological studies. Their effects include adverse impacts on reproductive and sexual development and fertility; cognition and neurological systems; immune system function; and metabolic effects, including diabetes and obesity. “The weight of the available evidence suggests that EDCs (endocrine-disrupting chemicals) affect a wide range of human health endpoints that manifest at different stages of life, from neonatal and infant periods to the aging adult,” write the authors.

Hormones interact with cellular receptors like locks and keys, explained Vandenberg. The hormone or hormone-like chemical is the key, and the receptor, the lock. “Touch the receptor and it starts to produce a response,” said Vandenberg. Too much chemical stimulus (the wrong-size key),
Linking a specific chemical exposure to an individual’s health disorder remains difficult.
however, can overwhelm the receptor, causing it to shut down and produce no response.

A key concept of the paper is that endocrine-disrupting chemicals are non-monotonic, meaning that the responses of animals or people to the chemicals do not necessarily intensify or diminish based on the dose. To illustrate this concept, Vandenberg said, “Picture a line of people, where those on the left have no exposure and those on the right have the most exposure. For endocrine-disrupting chemicals, where the greatest effects occur may not follow that line of increasing exposure level from left to right.”

While complex and challenging, the studies gathered in this paper demonstrate that this phenomenon is now well documented, say the authors. “I hope that this paper opens the door to the realization that the endocrine system is the overarching control system of all other body systems,” said Theo Colborn, president of the Endocrine Disruption Exchange, whose work has been instrumental in popularizing knowledge of endocrine-disrupting chemicals. “It controls how we develop, function, and reproduce from the moment we are conceived — in other words, the quality of our lives and our existence.”

While epidemiological studies show environmental exposure to EDCs are associated with human diseases, linking a specific environmental chemical exposure to an individual’s health disorder remains difficult, particularly given the many variables that contribute to health outcomes — life stage, genetics, and other environmental factors.

“There are different susceptibilities in different populations that may cause very minute amounts of a hormone to prompt effects in some people but not others,” said Linda Birnbaum, director of the National Institute of Environmental Health Sciences, who was one of the paper’s reviewers. This literature, she said, points to the importance of investigating low doses and timing of exposure when assessing chemicals for endocrine and other hormonal health outcomes, she explained in an interview.

Some scientists think more research is needed to confirm how endocrine disrupting chemicals behave. L. Earl Gray, Jr., a research biologist at the EPA’s Reproductive Toxicology Branch, said these low-dose effects are “certainly biologically plausible.” But he questioned whether there is
‘We don’t just know that these effects occur, we know how they occur,’ says the paper's lead author.
sufficient evidence to firmly establish the non-monotonic responses of endocrine-disrupting chemicals.

The American Chemistry Council (ACC), which represents chemical manufacturers, issued a statement saying that it “has committed substantial resources” to better understanding the potential effects of chemicals on the endocrine system, and cited a Michigan State University professor emeritus of toxicology who concluded that “low-dose effects have not been proven, and therefore should not be applied to real-world conditions and human exposures.”

To verify these effects, studies must prove the mechanism of these responses and be replicable, said Lorenz Rhomberg, principal at the Gradient Corporation, a private environmental and risk analysis consultancy. “In my experience that’s been lacking,” said Rhomberg, co-author of an ACC-funded study that found low doses of BPA to be without adverse human reproductive and developmental health effects.

But, said Vandenberg, that’s exactly what the new paper shows. “We don't just know that these effects occur, we know how they occur,” she said, noting that for some chemicals like BPA, non-monotonic responses are reported by dozens of labs.


A Warning by Key Researcher
On Risks of BPA in Our Lives

A Warning by Key Researcher On Risks of BPA in Our Lives
The synthetic chemical, BPA — found in everything from plastic bottles to cash register receipts — is a potent, estrogen-mimicking compound. In an interview, biologist Frederick vom Saal harshly criticizes U.S. corporations and government regulators for covering up — or ignoring — the many health risks of BPA.
Thomas Zoeller, a University of Massachusetts biologist and paper co-author, said that regulatory testing of chemicals for endocrine-disrupting impacts lags behind the growing evidence of the compounds’ health effects, particularly at levels to which people are routinely exposed. “There is a very large disconnect between regulatory toxicology and the modern science of endocrinology that is defining these issues,” said Zoeller.

How much will testing chemicals at low, environmentally relevant levels improve human health, the paper authors ask? While it’s not currently possible to quantify in dollars, current evidence “linking low-dose EDC exposures to a myriad of health problems, diseases, and disorders suggests that the costs of current low-dose exposures are likely to be substantial,” they conclude.

“People can easily get overwhelmed by this issue,” said Laura Vandenberg. “But from a public health perspective, we can’t see this problem as too big to deal with. We wouldn’t do that with any other medical problem.”

Correction: March 19, 2012: An earlier version of this article incorrectly stated the relationship between doses of hormone-disrupting chemicals and their impacts on the body; it should have stated that significant health effects sometimes occur at low rather than high doses. In addition, an earlier version of this article incorrectly used the term non-linear instead of non-monotonic. Endocrine-disrupting chemicals are non-monotonic, meaning that the responses of animals or people to the chemicals do not necessarily intensify or diminish based on the dose.


Elizabeth Grossman is the author of Chasing Molecules: Poisonous Products, Human Health, and other books. Her work has appeared in Scientific American, Salon, The Washington Post, The Nation, Mother Jones, Grist, and other publications. In earlier articles for Yale e360, she explored the potentially harmful health effects of flame retardants, and reported on recent studies suggesting a possible link between prenatal exposure to pesticides and the mental abilities of children.

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Thank you for this very informative article. It certainly will make decisions on what to buy easier.

Posted by Lilly Knuth on 19 Mar 2012

These toxins, unfortunalely, are all accumulative mostly stored in fat cells...

Posted by Joe Piazza on 26 Mar 2012

We have had 5 hyperthyroid cats out of 10 cats (3 different litters). Two of the humans in the family have had thyroid problems. Always wondered about the possible environmental toxins.

Posted by Kat on 29 Mar 2012

Very interesting. At the beginning of the 20th century homeopathy was the dominant school of medicine in the U.S. Homeopaths believe the most effective remedies are ones that include the tiniest possible detectable portions of the pharmacologically active ingredients, and so dilute and redilute their preparations many, many times when preparing them. That is counter-intuitive, but the observation in this article that sometimes the effects of toxins seems to be INCREASED at lower doses makes it seem there may be some valid principle in homeopathy we just don’t understand.

Posted by Barbara LaMorticella on 30 Mar 2012

The concentration ecefft up the food chain is a rational approach and a logical place to start on the subject of endocrine disruption in food, however I feel you have left out alot of useful information the CASCADE group has published. Your article cites animal fats as likely source of potential endocrine disruptors but your exclusion of other sources in the food chain is an oversimplification of this group's research.

Your article implies that animal products are the predominant problem and endocrine disruptors in other foods like organic plants is more dilute and safer. To the contrary, some food examples like soy and broccoli also have relatively high levels of phytoestrogens that can act as significant endocrine disruptors and contradict the eat lower on the food chain' recommendation. I agree with your point that animal products should be consumed in moderation (for a variety of reasons) however to be more precise, holistic, and less bias one should also mention non-animal foods containing significant sources of endocrine disruptors.

By focusing solely on animal products many of your vegetarian and vegan readers may not recognize the significance of this problem and may not have the opportunity to acknowledge the presence of endocrine disruptors in their own diet. Cheers, Logan Smith Davis, CA*P.s. Thank you for this fantastic resource. The Good Guide is a fantastic tool for building an informed democratic marketplace!

Posted by Ute on 02 Apr 2012

Having noticed the effects of different environments on my own health issues, I am interested to see the results of research being done on the effects of EDC exposure and cellular receptors. If I am interpreting this article correctly, the mechanism behind ETCs is the same as many of the synthetic hormones prescribed to replace or augment natural molecules. If your body recognizes a low dose of ETCs as normal, or if the strength of a response was limited by the number of available receptors, the dosage effect makes sense.

If constant, low-grade stimulation of endocrine receptors from ETCs causes obvious physiological effects like the deformities in frogs discussed in this study and one covered by another Yale 360 article (, what about ETCs that stimulate our natural emotional responses? I’m sure there will be more research into ETCs and heart disease, stroke, and other stress-related diseases. What about serotonin re-uptake and depression, or autoimmune disorders that are really reactions to ETCs?

The study has an extensive list of ETC effects ( on page 13), including emotional and behavioral issues. Perhaps the rising incidence of stress-related and behavioral disorders is directly linked to the increase of ETCs in our environment.

As the article points out, with so many variables in an individual’s health, it is going to be difficult to show a direct link between ETCs and disease. I am not surprised to see the ACC claim to have disproven the ETC theory themselves. The concept of a non-linear physiological response is hardly novel in many areas of medicine, but toxicology doesn’t seem to have accepted it where toxic substances are concerned. If this study encourages research into a common molecular mechanism behind the effects of ETCs, I think it will be a lot easier to convince skeptics that low-dose exposure to a specific chemical could be just as harmful as a toxic dose.

Posted by Talia on 20 Apr 2012

To answer Mirinda's question: The term "endocrine disrupting chemical" can be defined as any substance not produced by our bodies that can mimic (cause a similar effect as) the hormones our bodies naturally produce. Many of these "chemical" examples used in the above article, and in the media (e.g. pesticides, plants, animals, and BPA in plastic) are estrogen mimicking chemicals. The fear is that since many hormones in our bodies are balanced, "chemicals" that mimic estrogen in our bodies can "disrupt" our hormone regulatory system and cause this system to become unbalanced. The consequences of "too much" estrogen in our bodies is not completely understood but briefly includes harm to reproductive development in children, decreased fertility in adults, and a greater risk for estrogen based cancers (e.g. breast cancer). I believe that when the author suggests to "buy organic" he means that food under that organic label legally precludes pesticides (a common source of endocrine disrupting chemicals). For more detail see the authors link above to the CASCADE article on a similar topic.


Logan. University of California, Davis, USA

Posted by Kelebogile on 19 May 2012

It should be remembered by all who are attempting to get changes past some government bodies that a career can be made in government by preventing any change, especially any change that would make life more difficult or expensive for industry. Many agencies have a majority of technical employees who want to do the correct thing and have to deal with these internal roadblocks all of the time. I personally took early retirement rather than protect the industry from the public. In hindsight I should have stayed on and fought the good fight.

Posted by Jim H. White on 01 Jul 2012

I am curious now about whether the crop fields where I grew up, which were most likely sprayed with chemicals, could have somehow contributed to the psychological disorders I am now encumbered with at age 40.

Posted by Cheryl on 31 Jul 2012



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