The higher the dose, the more dangerous the toxin—that principle is the basis for most regulatory chemical testing in the United States. But a new report shows that even low doses of some toxins can be harmful, and that finding could have implications for the long-standing debate over the chemicals used in natural gas drilling and hydraulic fracturing.
The toxins surveyed in the report affect the endocrine system, which produces hormones, the small signaling molecules that control reproduction, brain development, the immune system and overall health.
Although the report doesn't specifically mention hydraulic fracturing, a separate peer-reviewed study released in September identified 649 chemicals used during natural gas production and found that at least 130 of those could affect the endocrine system. They include petroleum distillates, methanol and other, more obscure compounds with names like dibromoacetonitrile and ethoxylated nonylphenol.
Endocrine-disrupting chemicals have been linked to a variety of health problems, including obesity, diabetes, fetal development and infertility. Babies and young children are particularly vulnerable, said Laura Vandenberg, a postdoctoral research fellow at Tufts University and lead author of the new report. It was published last week in the peer-reviewed journal Endocrine Reviews.
"I can't think of a single tissue in the body that isn't affected in some way by hormones," she said.
Many of the chemicals in question are manmade. The food-packaging additive BPA, which mimics estrogen, is probably the best-known example. Dozens of cosmetics, pesticides and industrial chemicals found in the environment also affect the endocrine system.
The earlier study, which identified potential endocrine-disrupting chemicals used in natural gas production, was led by Theo Colborn, an environmental health analyst who also co-authored the new report. Colborn began studying endocrine disruption in the 1980's and has spent the past eight years researching the health effects of natural gas drilling.
It has been difficult for endocrinologists to research fracking-related health risks, because much of the information about fracking chemicals isn't available to the public, said Sonya Lunder, a senior analyst at Environmental Working Group, a nonprofit that advocates for public health. At least nine states have passed chemical disclosure laws, but all the regulations have loopholes that allow natural gas companies to keep the names or concentrations of certain chemicals as trade secrets.
Without an accurate understanding of how and where chemicals are used, "we don't know nearly enough ... to figure out the magnitude of human exposures and concerns," Lunder said.
Low-Dose Testing Uncommon
The new report confirms what scientists like Colborn have known for years—that small amounts of endocrine-disrupting chemicals can have big health impacts. Although the overall conclusion isn't new, the paper—which cites more than 840 research articles—is significant for its scope, said Louis Guillette, a doctor and endocrinologist at the Medical University of South Carolina who was not involved in the study.
"It's a monster review—it really has looked at a very large amount of literature out there," he said. The research cited came from laboratories around the world and includes experiments performed on cell cultures, animals and human epidemiologic studies. "This paper is critical because it's showing that there's a legacy, a history demonstrating that these are real effects, from many different labs."
Some endocrine-disrupting chemicals are already present in the environment at similar concentrations as naturally occurring hormones in the body. Since hormones function at concentrations of parts per billion or parts per trillion, "you can imagine that anything affecting it in a small way can have a drastic effect on health," Vandenberg said. She compared one part per trillion to a single drop of water in 20 Olympic-sized swimming pools.
Yet the importance of low-dose testing has been slow to catch on in regulatory agencies. Researchers generally test chemicals by giving lab animals large doses of a particular compound to see if it kills them, Vandenberg said. The scientists then calculate a smaller dose that's considered safe for human exposure—but they rarely test the lower doses to see whether they, too, might cause health effects.
Guillette said that's because "the whole belief system of toxicology, which is put up in every introductory class, is that 'the dose makes the poison.' There's a perception that as you increase the dose, things become more toxic."
While that's true for effects such as death, cancer and certain birth defects, endocrine-disrupting chemicals can act in more subtle ways. Some symptoms take years to materialize.
"There are effects at low doses you don't see at high doses," Vandenberg said. The high-dose tests don't look for the effects on brain development, for example, or prenatal exposure.
"During fetal development, if you don't have the right levels of [hormones] in the thyroid, you can have severe mental retardation. And the difference between enough and not enough is a very slim margin."
Because children and developing babies are particularly vulnerable, the endocrine-disrupting chemicals used during natural gas drilling may disproportionately impact local communities, said Lunder of the Environmental Working Group.
"In a community, you want to limit exposures...because someone's generally pregnant, or there are kids around. Those effects may be less for the healthy [adult] workers who are handling these products."
The chemical industry and some scientists say more evidence is needed about how low doses of endocrine-disrupting compounds affect human health. Last week, the American Chemistry Council, an industry trade group, issued a statement in response to the new report, saying it "has committed substantial resources to advancing science to better understand any potential effects of chemical substances on the endocrine system."
"We hear all the time that 'the dose isn't high enough to be toxic,'" said Guillette, the South Carolina endocrinologist. "We're trying to get physicians in the U.S. to be aware of how important environmental exposures are to health."
Some regulatory agencies are already on board. Last week, the peer-reviewed journal Environmental Health Perspectives ran an editorial by the director of the National Institute of Environmental Health Sciences (part of the National Institutes of Health) that emphasized the importance of low dose testing. And in early 2011, a group of scientific associations representing 40,000 researchers wrote an open letter to the journal Science about "the growing recognition that currently accepted testing paradigms and government review practices are inadequate for chemicals with hormone-like actions."
Vandenberg hopes the new report can help regulators design better safety tests, and raise awareness of the importance of endocrine-disrupting chemicals.
"BPA has been a way for people to understand how small amounts of a chemical...could be having an effect," she said. "But in general, the public probably doesn't realize how widespread the problem is."