Small doses can have big health effects. That is a main finding of a new report, three years in the making, published Wednesday by a team of 12 scientists who study hormone-altering chemicals. Dozens of substances that can mimic or block hormones are found in the environment, the food supply and consumer products, including plastics, pesticides and cosmetics. One of the biggest controversies is whether the tiny doses that most people are exposed to are harmful. Researchers led by Tufts University’s Laura Vandenberg concluded after examining hundreds of studies that health effects “are remarkably common” when people or animals are exposed to low doses. “Fundamental changes in chemical testing are needed to protect human health,” they wrote.
By Marla Cone
Editor in Chief
Environmental Health News
March 15, 2012
Small doses can have big health effects. 
That is a main finding of a report, three years in the making, published Wednesday by a team of 12 scientists who study hormone-altering chemicals.
Dozens of substances that can mimic or block estrogen, testosterone and other hormones are found in the environment, the food supply and consumer products, including plastics, pesticides and cosmetics. One of the biggest, longest-lasting controversies about these chemicals is whether the tiny doses that most people are exposed to are harmful.
In the new report, researchers led by Tufts University’s Laura Vandenberg concluded after examining hundreds of studies that health effects “are remarkably common” when people or animals are exposed to low doses of endocrine-disrupting compounds. As examples, they provide evidence for several controversial chemicals, including bisphenol A, found in polycarbonate plastic, canned foods and paper receipts, and the pesticide atrazine, used in large volumes mainly on corn.
The scientists concluded that scientific evidence “clearly indicates that low doses cannot be ignored.” They cited evidence of a wide range of health effects in people – from fetuses to aging adults – including links to infertility, cardiovascular disease, obesity, cancer and other disorders.
“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,” they wrote.
The scientists concluded that scientific evidence “clearly indicates that low doses cannot be ignored.” They cited evidence of a wide range of health effects in people – from fetuses to aging adults – including links to infertility, cardiovascular disease, obesity, cancer and other disorders.In addition, the scientists took on the issue of whether a decades-old strategy for testing most chemicals – exposing lab rodents to high doses then extrapolating down for real-life human exposures – is adequate to protect people.
They concluded that it is not, and so they urged reforms. Some hormone-like chemicals have health effects at low doses that do not occur at high doses.
“Current testing paradigms are missing important, sensitive endpoints” for human health, they said. “The effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.”
The report was published online Wednesday in the scientific journal Endocrine Reviews. Authors include scientists University of Missouri’s Frederick vom Saal, who has linked low doses of bisphenol A to a variety of effects, Theo Colborn, who is credited with first spreading the word about hormone-disrupting chemicals in the late 1980s and University of California, Berkeley’s Tyrone Hayes, who has documented effects of atrazine on frogs.
The senior author is Pete Myers, the founder of Environmental Health News and chief scientist of Environmental Health Sciences.
Linda Birnbaum, director of the National Institute of Environmental Health Sciences, said the new report is valuable “because it pulls a tremendous amount of information together” about endocrine-disrupting compounds. Her agency is the main one that studies health effects of contaminants in the environment.
Linda Birnbaum, director of the National Institute of Environmental Health Sciences, said in many cases, industry is still asking “old questions” about chemical safety even though “science has moved on.” Birnbaum said she agrees with their main finding: All chemicals that can disrupt hormones should be tested in ultra-low doses relevant to real human exposures, she said.
In many cases, chemical manufacturers still are asking “old questions” when they test the safety of chemicals even though “science has moved on,” she said. “Some of the testing paradigms have not advanced with the state of the science.” Birnbaum wrote an editorial on Wednesday referencing the new report.
Nevertheless, for most toxicologists, Birnbaum said the report does not offer a big shift from what they are doing. The NIEHS already conducts low-dose testing of chemicals, including looking for multi-generational effects such as adult diseases that are triggered by fetal exposures.
“Some people keep slamming the toxicologists. But you can’t paint everyone with the same brush,” Birnbaum said.
However, the scientists who wrote the report said that low-dose science “has been disregarded or considered insignificant by many.” They seemed to aim much of their findings at the National Toxicology Program and the U.S. Food and Drug Administration. The FDA in 2008 discounted low-dose studies when it concluded that bisphenol A (BPA) in consumer products was safe. Two years later, the agency shifted its opinion, stating that they now will more closely examine studies showing low-dose effects. The National Toxicology Program in 2008 found that BPA poses “some risks” to human health but rejected other risks because studies were inconsistent.
Several of the report’s authors have been criticized by some other scientists and industry representatives because they have become outspoken advocates for testing, regulating and replacing endocrine-disrupting compounds. The scientists, however, say they feel compelled to speak out because regulatory agencies are slow to act and they are concerned about the health of people, especially infants and children, and wildlife.
Industry representatives say that just because people are exposed to traces of chemicals capable of altering hormones doesn’t mean there are any harmful effects. They say that the studies are often contradictory or inconclusive.
“Based on the evidence, it is concluded that these ‘low dose’ effects have yet to be established [and] that the studies purported to support these cannot be validly extrapolated to humans.” -Michael Kamrin, Michigan State University In a statement, the American Chemistry Council, which represents chemical companies, said Wednesday that the industry “has committed substantial resources to advancing science to better understand any potential effects of chemical substances on the endocrine system. While we have not had an opportunity to fully review this paper, Michael Kamrin, emeritus professor of Michigan State University, has concluded ‘low dose’ effects have not been proven, and therefore should not be applied to real-world conditions and human exposures.”
“Based on the evidence, it is concluded that these ‘low dose’ effects have yet to be established [and] that the studies purported to support these cannot be validly extrapolated to humans,” Kamrin, a toxicologist, wrote in the International Journal of Toxicology in 2007.
But vom Saal and other scientists have said that tests that do not find low-dose effects of chemicals such as BPA are often industry-funded, and they often have tested the wrong animals or the wrong doses, or don’t expose the animals during the most vulnerable time of fetal growth.
Endocrinologists have long known that infinitesimal amounts of estrogen, testosterone, thyroid hormones and other natural hormones can have big health effects, particularly on fetuses. It comes as no surprise to them that manmade substances with hormonal properties might have big effects, too.
“There truly are no safe doses for chemicals that act like hormones, because the endocrine system is designed to act at very low levels,” Vandenberg, a postdoctoral fellow at Tufts University’s Levin Lab Center for Regenerative and Developmental Biology, told Environmental Health News.
But many toxicologists subscribe to “the dose makes the poison” conventional wisdom. In other words, it takes a certain size dose of something to be toxic. They also are accustomed to seeing an effect from chemicals called “monotonic,” which means the responses of an animal or person go up or down with the dose.
The scientists in the new review said neither of those applies to hormone-like chemicals.
“Accepting these phenomena should lead to paradigm shifts in toxicological studies, and will likely also have lasting effects on regulatory science,” they wrote.
In the report, the scientists were concerned that government has determined ”safe” levels for “a significant number of endocrine-disrupting compounds” that have never been tested at low levels. They urged “greatly expanded and generalized safety testing.”
“Accepting these phenomena should lead to paradigm shifts in toxicological studies, and will likely also have lasting effects on regulatory science,” the scientists wrote.”We suggest setting the lowest dose in the experiment below the range of human exposures, if such a dose is known,” they wrote.
Vandenberg said that there may be no effect or a totally different effect at a high dose of a hormonal substance, while a lower dose may trigger a disease.
The breast cancer drug tamoxifen “provides an excellent example for how high-dose testing cannot be used to predict the effects of low doses,” according to the report. At low doses, it stimulates breast cancer growth. At higher ones, it inhibits it.
“Imagine taking 100 individuals that are representative of the American population and lining them up in order of exposure to an EDC [endocrine-disrupting compound] so that the person on the far left has the least exposure and the person on the far right has the most. For many toxic chemicals, individuals with the highest levels of exposure, at the right end of the line, have the highest incidence of disease. But for some EDCs, studies suggest that people in the middle of the line have the highest risk,” Vandenberg said.
She compared hormones, which bind to receptors in the body to trigger functions such as growth of the brain or reproductive organs, to keys in a lock.
“The more keys that are in the locks, the more of an effect that is seen. But at some point, the locks are overwhelmed and stop responding to the keys. Thus, in the lower range, more keys equals more of an effect, but in the higher range, more keys equals less of an effect,” she said.
Vandenberg predicted the report “will start conversations among academic, regulatory and industry scientists about how risk assessments for EDCs can be improved.”
“The question is no longer whether these phenomena exist, but how to move forward and deal with them.” Read more science at
Environmental Health News.
I recently said this to my favorite cyclist when discussing that he may not want to apply chamois cream containing parabens (the junk) to his junk. Male cyclists are repeatedly applying (maybe daily, for 5-7 hours at a time) these paraben containing creams to their reproductive parts. Research is showing that maybe they should reconsider.
New stain repellent chemical doubling in blood every 6 years.
Sunday, December 2nd, 2012Glynn, A, U Berger, A Bignert, S Ullah, M Aune, S Lignell and PO Darnerud. 2012. Perfluorinated alkyl acids in blood serum from primiparous women in Sweden: Serial sampling during pregnancy and nursing, and temporal trends 1996-2010. Environmental Science and Technology http://dx.doi.org/10.1021/es301168c.
What did they do?
What did they find?
What does it mean?
Resources
More new science from EHN
As the phased-out stain repellent PFOS steadily decreases in people, its replacement is rising rapidly at levels that are doubling every six years, a Swedish study shows. Levels of perfluorobutane sulfonate (PFBS) in the women’s blood rose 11 percent per year between 1996 and 2010. Whether there are any potential health effects of these exposures — which are still far lower than PFOS levels — is unknown.
Context
Polyfluorinated and perfluorinated chemicals (PFASs) are applied to clothing, furniture, carpeting, cookware and food packaging to make the products stain repellent. PFASs – commonly referred to as PFCs – are a large group of chemicals that are unique because they repel both grease and water.
The PFAS chemicals used in commercial products fall into two main categories: the large fluorinated polymers that are used in clothing, furniture and carpet treatments and the phosphate surfactants that are used to coat paper.
Commercial products often contain the parent PFAS chemicals used to make the polymers and phosphate surfactants – called precursors – as impurities. PFASs break down in the atmosphere and in our bodies to form very long-lived perfluorinated alkyl acids (PFAAs).
People are exposed to PFAAs and their precursors mainly through food, air and water. Studies suggest the chemicals may contribute to kidney damage, and prenatal exposures have been linked to low birth weight.
Two of the most well-known and well-studied PFAA varieties are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). In addition to forming as breakdown products, small amounts of PFOS and PFOA were directly produced for specialized products. PFOS was used in fire-fighting foams as well as in the semiconductor industry. PFOA was used in the production of Teflon, but is typically not detected in the final products.
In 2002, the 3M Company – a leading manufacturer of PFOS and PFOA – voluntarily stopped manufacturing both PFOS and the chemicals that degrade to form PFOS because they were accumulating in humans globally and in animals – such as polar bears – that live in remote areas (Hansen et al. 2001; Giesy and Kannan 2001; Butt et al. 2010).
The company has substituted PFOS-based chemicals with another PFAA variety that is based on perfluorobutane sulfonate (PFBS). PFBS has four carbons whereas PFOS has eight. Otherwise, their molecular makeup is identical.
The smaller PFBS clears from the human body much faster than PFOS. PFOS has a half-life in people of 4 – 5 years, but PFBS’s half-life is only 26 days (Olsen et al. 2009).
After 3M stopped making PFOS-based compounds, production of other compounds made by another manufacturing process rapidly increased. These are called fluorotelomer-based chemicals. The fluorotelomer compounds are used for the same purpose as the PFOS-based compounds were: to make fluorinated polymers and surfactants. However, these chemicals degrade to form perfluorinated carboxylates (PFCAs), including PFOA.
Due to the increasing concern about PFOA, the eight major manufacturers have committed to eliminate PFOA emissions by 2015.
What did they do?
The research is part of a larger study that examined time trends of persistent organic pollutants in the blood and breast milk of pregnant and nursing women in Uppsala County, Sweden.
Blood samples were collected from first-time mothers, aged 19 – 41 years, three weeks after delivery. Samples were collected each year between 1996 and 2010, except in 2003 and 2005. For each year, several individual blood samples were pooled together for analysis. In general, three pooled samples per year were analyzed.
The study investigated levels of 13 PFAAs, including PFBS and PFOS. The study also measured perfluorooctane sulfonamide (FOSA), which is known to degrade to PFOS.
A unique aspect of this study was the ability to measure PFBS levels at very low levels. It was this improved analytical capability that allowed the researchers to detect the PFBS trends over time.
In addition to examining time trends, the study also investigated PFAA trends at different stages during pregnancy and after delivery.
What did they find?
The study showed that PFBS blood concentrations in the Swedish women increased by 11 percent per year between 1996 and 2010. The levels doubled every 6.3 years. This is the first study to show increasing PFBS levels in humans.
However, during the same time period, PFOS levels decreased by 8.4 percent per year. The study also showed decreasing levels of perfluorodecane sulfonate (PFDS), PFOA and FOSA.
In contrast, blood levels of two PFCAs – perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) – increased by 4.3 percent and 3.8 percent, respectively, from 1996 to 2010.
The study also looked for longer-chain length PFCAs: perfluorododecanoate (PFDoA), perfluorotridecanoate (PFTrA) and perfluorotetradecanoate (PFTA). But these PFCAs were not found in the women’s blood.
What does it mean?
Perfluorobutane sulfonate or PFBS – the chemical that replaced the PFOS-based fluorinated chemicals used as stain repellents – is building up in human blood with levels doubling every six years. This is the first study to show increasing PFBS levels in humans.
The study showed that PFBS levels in Swedish women are rapidly increasing. This means that humans are widely exposed to PFBS and its precursors. Exposure to these chemicals has increased dramatically from 1996 to 2010.
These findings were surprising because it was thought that PFBS would not accumulate in humans due to its very short half-life (26 days). But the new research shows that PFBS is building up at an alarming rate.
However, PFBS levels are still about 75 times lower than PFOS.
The study did not investigate whether there were any health effects associated with the increasing PFBS levels. There have been few toxicology studies on PFBS, and the toxic effects are generally less than PFOS and PFOA (Lieder et al. 2009).
PFBS-based chemicals were introduced as replacements for PFOS-based chemicals after 3M stopped their manufacture in 2002. In the current study, PFBS levels did not start increasing until 2002. Presumably, this increase in PFBS blood levels is a reflection of increased use of PFBS precursors in commercial products and their release into the environment after 2002.
The new study also showed that PFOS and FOSA levels are decreasing in Swedish women’s blood. FOSA is formed when PFOS precursors are metabolized in the body.
These results show that 3M’s PFOS ban in 2002 had a rapid effect on PFOS blood levels. Studies from the United States (Kato et al. 2011; Olsen et al. 2012) and Norway (Haug et al. 2009) have also shown decreasing PFOS blood levels after the 3M ban.
In contrast, PFNA and PFDA levels were shown to increase in the Swedish women. These chemicals are breakdown products of fluorotelomer-based compounds that are used in some polymers and surfactants. They have similar uses as the PFOS-related chemicals. In addition, PFNA is used in the production of polyvinylidene fluoride (PVDF) and trace amounts can be detected in the final products. Production of fluorotelomer chemicals increased after the 3M PFOS ban. The increasing blood levels of these chemicals most likely represents the increased use of their precursors in commercial products.
Because the study only monitored Swedish women, it will be necessary to confirm the trends in other regions of the world. This is because fluorinated chemical use varies in different areas of the world. For example, China began producing PFOS-chemicals in 2003. Their production in China may represent a new source of PFOS to the world.
Scientists are concerned when blood levels of a chemical increase in our bodies because it shows that our exposure is increasing. However, it is necessary to determine if the contaminant levels are enough to cause harmful effects in wildlife and people. Future research is needed to determine if the increasing PFBS levels are affecting human health.
Resources
Buck, RC, J Franklin, U Berger, JM Conder, IT Cousins, P de Voogt, AA Jensen, K Kannan, SA Mabury and SPJ van Leeuwen. 2011. Perfluoroalkyl and polyfluoroalkyl substances in the environment: Terminology, classification, and origins. Integrated Environmental Assessment and Management 7:513-541.
Butt, CM, U Berger, R Bossi and GT Tomy. 2010. Levels and trends of poly- and perfluorinated compounds in the arctic environment. Science of the Total Environment 408:2936-2965.
Giesy, JP and K Kannan. 2001. Distribution of perfluorooctane sulfonate in wildlife. Environmental Science & Technology 35:1339-1342.
Hansen, KJ, LA Clemen, ME Ellefson and HO Johnson. 2001. Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices. Environmental Science & Technology 35:766-770.
Haug, LS, C Thomsen and G Bechert. 2009. Time trends and the influence of age and gender on serum concentrations of perfluorinated compounds in archived human samples. Environmental Science & Technology 43:2131-2136.
Kato, K, LY Wong, LT Jia, Z Kuklenyik and AM Calafat. 2011. Trends in exposure to polyfluoroalkyl chemicals in the U.S. population: 1999-2008. Environmental Science & Technology 45:8037-8045.
Lieder, PH, RG York, DC Hakes, S-C Chang and JL Butenhoff. 2009. A two-generational gavage reproduction study with potassium perfluorobutanesulfonate (K+PFBS) in Sprague Dawley rat. Toxicology 259:33-4.
O’Connor, Mary Catherine. Greenpeace scolds outdoor apparel makers for chemical use. Outside Magazine Nov 12, 2012.
Olsen, GW, SC Chang, PE Noker, GS Gorman, DJ Ehresman, PH Lieder and JL Butenhoff. 2009. A comparison of the pharmacokinetics of perfluorobutanesulfonate (PFBS) in rats, monkeys, and human. Toxicology 256:65-74.
Olsen, GW, CC Lange, ME Ellefson, DC Mair, TR Church, CL Goldberg, RM Herron, Z Medhdizadehkashi, JB Nobiletti, JA Rios, WK Reagen and LR Zobel. 2012. Temporal trends of perfluoroalkyl concentrations in American Red Cross adult blood donors, 2000-2010. Environmental Science & Technology 46:6330-6338.
Tags: chemicals of concern, endocrine disruptors, worker EHS
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