The Heinz Center’s second Horizons@Heinz event at the University Club in Washington D.C. on the topic of green chemistry — the design of safe chemical products that can eliminate the use of harmful substances in manufacturing processes — to reduce the impacts of toxic chemicals on human and environmental health. The event featured Dr. Pete Myers, Heinz Center Board member and CEO and Chief Scientist of Environmental Health, Dr. Terry Collins, Teresa Heinz Professor of Green Chemistry & Director for the Institute of Green Science at Carnegie Mellon University, and Dr. John Warner, co-founder of the Warner Babcock Institute. Click here to view the videos.
For more information on Horizons@Heinz and The Heinz Center, go to www.heinzcenter.org.
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.
Thank you to everyone who participated in our photo competition. We had many amazing entries; it was hard to choose the winners! After much deliberation, we reached decision on a first, second, and two third place winners.
First place goes to Amy Cannon for her photo of teaching students green chemistry principles and experiments. Dr. Cannon says: “Perhaps one of the most important things we do is work with K-12 students to inspire future scientists and hopefully future green chemists.” She will win a package of fresh body butter and green tea body cream from Dirty Beauty Natural Skincare.
Second place goes to Sarah Dickerson with her entry of a photo with her green cleaning products. Sarah explains: “One of the simple ways I incorporate green chemistry into my life is by preparing non-toxic cleansers using natural alternatives. In this photo, I’m preparing an all-purpose general cleaner that harnesses the cleaning power of vinegar and baking soda. For a fresh scent, I like to add lemons and fresh rosemary from my organic garden.” Sarah will win a box from Susie’s Boxes.
An approach combining chemistry and biology improves the process to make important anti-clotting drugs known as heparins. The heparin medicines prevent dangerous blood clots from forming in veins and are needed for surgery and kidney dialysis.
The technique provides easier access to safer drugs that are now either processed from pigs and cows or synthesized in a long, costly lab process. The novel method described in the journal Science provides a realistic alternative to livestock for heparins and is likely to drop the cost of such pharmaceuticals.
The process is not yet ready for large-scale commercial use, but its product yields are impressive.
Many pharmaceutical drugs are processed from plants or animals rather than made in a laboratory. While such a strategy may seem more natural, animal-sourced drugs are susceptible to contamination.
Heparins are a family of drugs used for more than 50 years to prevent blood clots in people. These complex molecules come from three main sources. They can be collected from pig intestines or cow lungs, synthesized in a laboratory or collected from animals and then modified in a lab.
The sizes and uses of the three types vary. The animal-sourced drug is the largest. It degrades rapidly in the body and is used for kidney dialysis and surgery. The chemically-altered animal heparin and the synthetic varieties are smaller, longer-lived molecules. Patients with venous thrombosis – the tendency for blood clots to form in veins – take these to prevent the clots.
Safety is an issue with the animal-sourced heparin, the cheapest and most accessible available. In 2007, drug contamination resulted in at least 200 deaths in the United States and raised concerns over the source of heparin.
GlaxoSmithKline synthesizes the smaller-sized heparin under the brand name Arixtra. Their process requires about 50 steps and yields very low amounts of material– around 0.1 percent. As a consequence, this molecule cannot currently replace animal-based heparins for all applications because of its high price.
The risk of contamination and current cost of synthesizing heparin is driving the quest to find a more efficient and cheaper way to make heparin drugs.
A team of chemists from the United States applied a strategy called chemoenzymatic synthesis to fabricate the heparin molecule. The method borrows from both chemistry and biology fields.It is an attractive way to synthesize heparin medicines. The drug contamination in 2007 occurred because the heparin collected from animals had an unusual chemical structure. People became allergic and hypersensitive. These side-effects would be avoided using a chemoenzymatic system because the series of chemical and enzymatic reactions needed to produce the drug are much better controlled than those in the animal gut where many proteins can alter the drug-to-be molecule.
In this study, the researchers mimicked the process animals use to make heparins. They chemically synthesized a starting material then added enzymes that lengthened and built the whole heparin molecule. In other words, they transferred what happens in the pig gut into a beaker. This approach is superior to collecting directly from an animal because the reactions are controlled.
To see if the manufactured drugs were effective, the researchers tested them in two different ways in the lab. First, they put them with two key proteins responsible for coagulating blood. Then, they injected rabbits with them and collected the animal blood. The interactions with the proteins alone in a culture and in the blood from the rabbit were measured and compared with the activity of the commercial heparin Arixtra.
The researchers discovered they could produce two heparin molecules with the impressive yield of 45 and 37 percent, in 10 and 12 steps respectively. They were able to make several milligrams of the product.
The two newly synthesized heparin molecules were similar in size to as the current Arixtra drug. They also proved as active as Arixtra. The efficacy of the interaction between the drugs and coagulating proteins were similar to Arixtra.
The same was true when the newly developed heparins were tested with rabbits. The drugs interacted with the same proteins as Arixtra.
A more streamlined method to make anti-coagulant drugs may provide a realistic alternative to the animal-sourced pharmaceuticals, which are susceptible to contamination. The new process also produces more heparin product in shorter time and for less money than current synthetic preparations.
This means that the newly made heparins could be used in a wider range of applications than the current synthetic heparin Arixtra, because the reduced cost may open new markets.
This technique isolated 3.5 milligrams of heparin. The obvious next step will be to scale up this process to demonstrate that it is commercially feasible. It is estimated that 10 to 20 tons of heparin drugs are sold every year in the world.
The new drugs must also be tested and properly certified before they can be used commercially. However, the preliminary results of this research effort show that these two heparin molecules should be active anti-coagulant drugs with similar properties as the most popular synthetic version on the market today.
The type of synthesis – which merges chemistry techniques and biological enzyme actions – profiled here may be transferable to the manufacture of other drugs. Read more science at Environmental Health News.
Elizabeth Grossman has published a new piece in Chemical Watch, entitled “Chemicals fare well in US EPA’s 2013 budget proposals“, which reviews the proposed 2013 US EPA budget on chemicals-related issues.
Specifically related to green chemistry, she finds that,
“The budget allots $13.9m for chemical information collection, management and transparency; $14.9m for screening and assessing chemical risks; and $24.6m for reducing chemical risks. EPA says that in 2013 “the toxics programme will maintain its ‘zero tolerance’ goal in preventing the introduction of unsafe new chemicals into commerce” but notes that thousands of chemicals already in commerce remain unassessed.
The budget’s science and research priorities include an increase of $4.1m in funding for “sustainable molecular design of chemicals” to develop inherently safer processes and products. The budget also requests $20.9m for the EPA’s Pollution Prevention Program which encourages the use of “greener” chemicals, technologies, processes and products, among them the Design for Environment, Environmental Preferable Purchasing, Green Chemistry and Green Engineering programmes.”
For the full piece please go here.
See the EPA Budget webpage
By Lin Kaatz Chary, PhD, MPH, Executive Director, Great Lakes Green Chemistry Network
By Mana Sassanpour, 1/26/2011
After reading a book that mentioned the health benefits of ginkgo (leaf pictured right), I decided to see if there were any green chemistry related topics that involved this ancient and revered tree. The journal, Green Chemistry, has an article about a more efficient means of extracting the useful components of ginkgo (Qingyong Lang and Chien M. Wai Green Chem., 2003, 5, 415-420). The researchers developed a greener method of pressurized water extraction which is a “a more effective, selective, economical and environmentally benign technique.”
However, the article did not make clear WHY they were bothering to finding greener ways to extract these compounds – what does ginkgo do? I could pay £34 GBP ($52.50) to find out why, but I thought doing my own investigation would be more fun and less costly.
My research took me in several directions, including the Encyclopedia of Medicinal Plants by Andrew Chevallier, Rebecca’s Natural Food Store in Charlottesville, VA, and to a friend, John Soong, who knows a little something about everything.
First, some history: the ginkgo tree dates back about 200 million years to the time of the dinosaurs. Second, my friend John Soong explained that he had grown up eating ginkgo nuts in a rice porridge called congee (left). According to him, the philosophy behind eating ginkgo in Chinese cuisine is that “because the ginkgo tree has survived and lived for so long, if we eat it we will have the same longevity.”
There may be some science behind this belief: the active ingredients in ginkgo are purported to work together to produce a positive effect on the human body. The key ingredients are flavonoids, ginkgolide, and bilobalides. The Encyclopedia claims that ginkgo “improves circulation of blood to the head” which in turn leads to improved memory and is given to people with dementia. Ginkgo is also good for asthma and as an anti-inflammatory. Therefore it is not surprising that ginkgo has been noted as one of the bestselling medicines in Germany.
After my literature search, I drove to Rebecca’s Natural Food Store where one of the employees gave me an impromptu “Ginkgo 101” course. She explained that ginkgo is also a blood thinner and can help reduce the possibility of a stroke. In addition, she said it is “good for capillaries and oxygen uptake especially for those who always have cold hands and feet.” Hmmm: maybe I should start taking ginkgo?
Of course we are not qualified to make judgments or give advice on the medicinal value of ginkgo, but it seems like ginkgo is a very interesting plant. With such a wide array of potential health applications and valuable compounds, it makes sense to find more sustainable and cost effective methods of extraction.
1. Pressurized water extraction (PWE) of terpene trilactones from Ginkgo biloba leaves. Qingyong Lang and Chien M. Wai. Green Chem., 2003, 5, 415-420. DOI: 10.1039/B300496C
2. Encyclopedia of Medicinal Plants. By Andrew Chevallier – DK Pub. (1996) – Hardback – 336 pages – ISBN 0789410672
The Montreal Gazette prints 20 key points to help the public interpret chemical science but a scientist specializing in green chemistry explains why not all of them hit the mark.
In an article in the Montreal Gazette, Joe Schwarcz of McGill University lists 20 points he believes are important to address when interpreting chemistry for the public. His ideas – distilled from a year of lecturing to public audiences – touch on some very good points but also lack other key ideas.
In the article, Schwarcz welcomes criticism and comments of his personal views on the subject. My main concerns are with omissions in some of the individual points as well as a contradiction between his points.
• #2 – Everything is comprised of chemicals. Citing examples of common chemicals in nature – such as oxygen, water and kitchen salt – would have bolstered his point.
• #3 – There are no dangerous or safe chemicals. I would argue there are dangerous chemicals. A highly toxic or explosive chemical always has an inherent danger associated with it, irrespective of how it is used. This is one reason industrial processes – when using these chemicals to create other chemicals or products – will make them and then immediately react them to change them into a safer product. An example would be phosgene, a gas well known for its use as a chemical weapon in World War I. Because it reacts every quickly, it is used to produce polycarbonates. These widely used polymers are in glass lenses, for example. So phosgene is made but then directly converted into a safe product by reaction with other chemicals.
• #5 – Animal studies do not necessarily reflect humans. This paints a very limited picture. It is true that animal studies do not reveal everything about how chemicals might affect people. However, they do give some important indications, especially when acute toxicity – short-term toxic effects – is concerned. Brushed over is one of the main problems with current toxicology: adults respond differently than embryos and children at various stages of development. So even within humans, important differences in toxic responses are seen.
* #6 – Chemical presence does not equal risk. No, other issues matter, such as dose and those mentioned above: a person or animal and stage of life – embryo, young or adult – that is exposed to the chemical. All may respond differently.
• # 9 – Affirming there are hazardous chemicals appears to contradict point #3: There are no inherently dangerous or safe substances. Indeed, even kitchen salt can kill if taken in too high an amount. I would therefore describe “green chemistry” as replacing current chemicals with less hazardous ones.
• #16 – It is nonsense that the body can heal itself with the right natural substances. This idea should be carefully interpreted. As a scientist, I know we have a limited understanding of the human body. Maybe some day, science will help us better understand if and how naturally occurring chemicals could cure ailments. Scientific progress has a knack for proving the impossible possible.
I applaud the attempt to come up with a top 20 list of chemical science considerations for the public. While not an easy feat – and certainly one that easily draws criticism – it also generates constructive debate about important issues surrounding the public understanding of science. Read more science at Environmental Health News.