Commentary: 25 Years of Endocrine Disruptor Research – Great Strides, But Still a Long Way to Go

written by Laura N. Vandenberg, PhD
Assistant Professor and Graduate Program Director of Environmental Health Sciences, University of Massachusetts Amherst School of Public Health and Health Sciences

Laura Vandenberg (Credit: umass.edu)

Reprinted with permission from Environmental Health News

Cancer. Diabetes. Autism. Infertility. ADHD. Asthma. As the rates of these diseases increase over time, the public and researchers alike have focused on the role the environment might play in their cause and progression. Scientists in the field of environmental health sciences are not satisfied just to know that the environment contributes to human disease – they want to know how.

This week [ScienceSeptember 18-20], researchers, public health advocates, government officials, and industry spokespersons will meet at National Institutes of Health (NIH) to celebrate 25 years of scientific research on one aspect of environmental health: endocrine disrupting chemicals (EDCs). These are compounds that alter the way hormones act in the body, often by mimicking or blocking their actions. Just a few examples of widely used consumer products that contain EDCs are plastics, electronics, flooring, some personal care products, and furniture treated with some flame retardants.

Scientific Consensus Statements on the Role of Environmental Chemicals in Diabetes, Obesity, and Metabolism

written by Sarah Howard
Coordinator of the Diabetes-Obesity Working Group

Two worldwide gatherings of experts have published consensus statements on the role of environmental chemicals in diabetes, obesity, and metabolism:

• Parma Consensus Statement on Metabolic Disruptors, Heindel et al. Environmental Health. 2015 Jun 20;14:54.
• Uppsala Consensus Statement on Environmental Contaminants and the Global Obesity Epidemic, Lind et al. Environmental Health Perspectives. 2016 May 1;124(5):A81-3.

The Parma Statement was based on a workshop held in Parma, Italy, in May 2014, and the Uppsala Statement was based on a workshop held in Uppsala, Sweden, in October 2015.

Both focus on guiding future scientific research in the field, but also contain recommendations for policy makers, health care providers, and other professionals. Both call for reducing environmental chemical exposures, especially in early life, to help prevent the development of metabolic problems later in life.

Recap: IOM Workshop Meetings on Obesity

written by Sarah Howard
Coordinator of the Diabetes and Obesity Spectrum Working Group

Over the past 4 days there have been two IOM workshop meetings on obesity; here’s a brief update.

The first was last Thursday/Friday on developmental exposures and obesity (mostly nutrition), and the second was Monday/Tuesday on the environment and obesity (at NIEHS). The slides and presentations of these workshops will be posted online. I would recommend these talks, they were all very informative.

Exposures to a wide variety of environmental factors—from chemicals to lack of sleep to microbiome to inflammation to viruses to antibiotics to nutrition to famine to maternal BMI to hormones to paternal factors to beta cell hypersecretion to artificial sweeteners to fructose—are linked to a higher (or sometimes lower) risk of obesity later in life, especially if exposure occurs during development (or possibly during other vulnerable periods, such as puberty). Obesogens may make it harder to lose weight and easier to gain weight, increasing our susceptibility to obesity.

Top 10: 1st Quarter 2014

CHE offers this selection of research, news and announcements that were of special significance during the first quarter of 2014. Items include research that made a noteworthy contribution to the field, news and announcements that took a conversation to a new level and/or new audience and some welcome action. As before, we offer both the scientific report and media reporting on it, when available, to meet the needs of our various audiences.

1. Tobacco use
   Three items relating to tobacco use are of particular note this quarter:
   1. Historic smoking report marks 50th anniversary
      Those of us old enough to remember the Virginia Slims commercials from the 1970s will appreciate the irony of employing their slogan regarding changing the culture of smoking: “You’ve come a long way.” As described in this news article, “fifty years ago, ashtrays seemed to be on every table and desk. Athletes and even Fred Flintstone endorsed cigarettes in TV commercials. Smoke hung in the air in restaurants, offices and airplane cabins. More than 42 percent of US adults smoked, and there was a good chance your doctor was among them. The change of culture around smoking in public is one of the biggest public health success stories, done largely without heavy regulation.” This sea change in tobacco’s acceptance provides both hope and lessons for current campaigns. See a related article: Eight million lives saved since US alarm on smoking 50 years ago, the JAMA themed issue: 50 Years of Tobacco Control, and The Health Consequences of Smoking — 50 Years of Progress: A Report of the Surgeon General, 2014.
   2. Health effects of “thirdhand smoke”
      A growing body of research on harmful effects of smoke and ash residue shows that this is a health concern: Cigarette smoke toxins deposited on surfaces: implications for human health, Thirdhand smoke causes DNA damage in human cells, plus older but relevant Third-hand smoke exposure and health hazards in children and The impact of second-hand tobacco smoke exposure on pregnancy outcomes, infant health, and the threat of third-hand smoke exposure to our environment and to our children.
   3. Policy shifts in smoking
      CVS drugstores to stop selling cigarettes over health issues: “Drugstore chain CVS will stop selling cigarettes this year after corporate leaders decided that offering tobacco products is antithetical to the company’s goal of improving customer health. This decision came with an expected economic loss to the company.” A large review bolsters the case for such policy shifts: Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis.
2. Chlorinated persistent organic pollutants, obesity, and type 2 diabetes
   Not only does this article review the extensive evidence linking these conditions, it also explains puzzling findings in the field related to high vs low dose exposures and nonmonotonic dose-response curves, found in not only laboratory but also in epidemiological studies. It addresses the perplexing role of POPs in adipose tissue– perhaps a safer place to store them than in organs– but also causing harmful inflammatory effects in fatty tissue. It reviews the role of POPs as potential obesogens, as well as their potential interaction with gut microbiota, mitochondrial dysfunction, and other mechanisms. It outlines how future research may address some of the remaining questions in the field.
3. Research and controversy around BPA
   1. Bisphenol A (BPA) pharmacokinetics with daily oral bolus or continuous exposure via silastic capsules in pregnant rhesus monkeys: relevance for human exposures: This research addresses the ongoing controversy in BPA research about using silastic capsules versus oral bolus. This study suggests that oral bolus exposure is not an appropriate human exposure model. Differences in pharmacokinetics of dBPA were evident between pre-pregnancy, early and late pregnancy, likely reflecting changes in maternal, fetal and placental physiology.
   2. FDA finding on BPA: The FDA’s publication, Toxicity evaluation of bisphenol A administered by gavage to Sprague-Dawley rats from gestation day 6 through postnatal day 90 generated a great deal of comment. See opposing views of the review: BPA is A-OK, says FDA and Scientists condemn new FDA study saying BPA is safe: “it borders on scientific misconduct.” Also compare FDA’s finding to news from France: RAC proposes to strengthen the classification of bisphenol A.
4. The Elk River chemical spill in West Virginia
   This event and its repercussions kept water quality, chemical contamination, testing and regulation in Americans’ minds for weeks. Most notably it highlighted the failures of the Toxic Substances Control Act (TSCA) and need for chemical policy reform. Though there were dozens of news articles and analyses, one example of the reach and possible impact of this story is Data deficit on Elk River chemicals shows need for TSCA reform, legislators say. “Members of a House subcommittee pointed to the lack of toxicity and other data on chemicals that recently contaminated drinking water for hundreds of thousands of West Virginia residents as illustrating a key reason the Toxic Substances Control Act needs to be revised.”
5. Inheriting fear
   New research demonstrates that fear can be passed on from one generation of laboratory animals to the next. Epigenetic changes are most likely responsible, and this provocative study is bringing new challenges to how scientists think about behavior and evolutionary change.
   1. See the study: Parental olfactory experience influences behavior and neural structure in subsequent generations.
   2. See also similar research regarding “inherited” stress: Is stress contagious? Study shows babies can catch it from their mothers and the study: Stress contagion: physiological covariation between mothers and infants.
6. Fracking and health
   As more research and news regarding fracking emerges, the concerns and controversies about fracking’s potential impact on human health continue to deepen. In this last quarter, a few important new studies and reports were published:
   1. 4 states confirm water pollution from drilling: “In at least four states that have nurtured the nation’s energy boom, hundreds of complaints have been made about well-water contamination from oil or gas drilling, and pollution was confirmed in a number of them, according to a review that casts doubt on industry suggestions that such problems rarely happen.”
   2. Study shows fracking is bad for babies: researchers found that proximity to fracking increased the likelihood of low birth weight by more than half, from about 5.6 percent to more than 9 percent. The chances of a low Apgar score, a summary measure of the health of newborn children, roughly doubled, to more than 5 percent. See the study: Birth outcomes and maternal residential proximity to natural gas development in rural Colorado but also State questions study linking fracking to birth defects.
   3. Ohio earthquakes linked to fracking: “Ohio authorities shut down a hydraulic fracturing natural gas operation in Mahoning County on Monday after two earthquakes were felt in the area.”
   4. Report: Big Oil, Bad Air: Fracking the Eagle Ford Shale of South Texas: “an eight-month investigation found Texas regulators are largely ignoring air pollution problems caused by fracking the Eagle Ford Shale.” See also Planning for fracking on the Barnett shale: urban air pollution, improving health based regulation, and the role of local governments: “Using the community experience on the Barnett Shale as a case study, this article focuses on the legal and regulatory framework governing air emissions and proposes changes to the current regulatory structure.”
7. The Textbook of Children’s Environmental Health
   This textbook edited by Philip Landrigan, MD, MSc, and Ruth Etzel, MD, PhD, provides one of the most comprehensive overviews of the research and clinical applications to date and the scientific basis in clear and accessible language for why promoting children’s environmental health now is essential for a healthy, thriving society in the future. As the first course textbook of its kind, it could be used as the basis for the possible inclusion of questions on environmental health as part of the medical board certification process.
8. In many neighborhoods, the main obstacle to good health is poverty
   For decades, activists and scholars around the country have emphasized that focusing solely on changing individual behaviors is not enough to change the broader patterns of inequities in health. Researchers who study disparities have found that social and economic factors, such as employment, education, and social networks, also strongly influence whether people have the resources to protect their health. In racially segregated neighborhoods such as the one discussed in this article, with its crumbling infrastructure and history of institutional neglect, the main obstacle to good health is poverty. Though this is not news, we chose to include this piece because it highlights not just the problem, but shifts the conversation toward a more ecological model of health and includes possible solutions and some emerging evidence to bolster them as well.
9. Study questions fat and heart disease link
   “A large and exhaustive new analysis by a team of international scientists found no evidence that eating saturated fat increased heart attacks and other cardiac events.” This negates several decades of nutritional guidance and reopens a crucial conversation about what are the fundamentals of a healthy diet. See the study: Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis.
10. Climate risks as conclusive as smoking and lung cancer link – scientists
    In an unusual policy intervention, one of the world’s largest scientific bodies said evidence that the world is warming is as conclusive as the link between smoking and lung cancer. There has been much hyping from climate deniers of the uncertainty around climate science and predictions. This statement provides context for non-scientists. See the statement: What We Know and also the newest report from the Intergovernmental Panel on Climate Change: Climate Change 2014: Impacts, Adaptation, and Vulnerability.

Multiple and Interacting Contributors to Obesity

Written by Elise Miller, MEd
CHE Director

The obesity rate for children aged 2-5 years dropped a stunning 43% over the past decade, according to a report published last week by the Centers for Disease Control and Prevention (CDC). This is of course extremely good news. Researchers, however, are not sure what combination of factors may have contributed to this significant decrease. Some theories are that a number of programs, such as the federally-funded Women, Infants and Children (WIC) initiative, which now subsidizes proportionately more vegetables and whole grains, and First Lady Michelle Obama’s “Let’s Move” campaign, which focuses on improving exercise and eating habits in child care settings, are making a difference. Others suggest that former New York Mayor Bloomberg’s declaration that restaurants should no longer use transfats has played a role or that programs started in the 1980s when people became aware that there was a growing obesity problem are finally having a positive effect on this new generation.

You Are What Your Great-Grandmother Ate? Transmission of Obesity Across Generations

Sarah Howard
Coordinator of CHE’s Diabetes-Obesity Spectrum Working Group

Two important studies have been published this month on chemical exposures that cause obesity in subsequent generations of rodents, long after the exposure ends. Until now, no prior studies on transgenerational obesogen exposures had been published. The results are alarming.

In the first study, pregnant mice (F0 generation) were exposed to low doses of the known obesogen tributyltin (TBT) and bred for 3 generations (up to the F3 generation). Thus, the F0 generation was exposed directly, the F1 generation exposed in the womb, the F2 generationsl could have been primordially exposed as germ cells in the developing fetus, and the F3 generation was not exposed directly (changes in the F3 generation are considered truly transgenerational). The TBT exposure had obesity-promoting effects on fat deposition on the F1 through the F3 generation, including increasing the number of fat cells, fat cell size, fatty tissue weights, and fatty livers (similar to non-alcoholic fatty liver disease (NAFLD) in humans). Interestingly, TBT exposure reprogrammed stem cells to develop into fat cells instead of bone cells.

The study, entitled “Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal obesogen tributyltin in mice”, was written by Raquel Chamorro-García, Margaret Sahu, Rachelle J. Abbey, Jhyme Laude, Nhieu Pham, and Bruce Blumberg, of the University of California, Irvine.

Can Air Pollution Contribute to Diabetes or Weight Gain?

Sarah Howard,
National Coordinator of the Diabetes-Obesity Spectrum Working Group

Of course what you eat can affect your risk of diabetes and obesity, but how about what you breathe? Can air pollution influence the risk of diabetes and obesity? Surprisingly, it might.

Long-term exposure to traffic-related air pollution is associated with an increased risk of type 2 diabetes in a number of studies. For example, African-American women living in Los Angeles had a higher risk of diabetes if their homes were located in areas with higher traffic-related air pollution levels, after controlling for other diabetes risk factors such as age, body mass index, exercise, and family history (Coogan et al 2012). Adults in Denmark had an increased risk of diabetes when exposed to higher levels of the traffic-related air pollutant nitrogen dioxide (NO2)—expecially those who had a healthy lifestyle, were physically active, and did not smoke—factors that should be protective against type 2 diabetes (Andersen et al 2012). Elderly women in Germany had a higher risk of diabetes when living in areas of higher traffic-related air pollution, after adjusting for diabetes risk factors as well as several non-traffic-related sources of air pollution (Kramer et al 2010).

The Ecological Paradigm of Health: An Interview with Dr. Ted Schettler

Yes! Magazine’s Fall 2012 issue features an interview with Dr. Ted Schettler, CHE’s science director:

Talking with Dr. Ted Schettler is probably unlike any conversation you have had with your physician. Raise the topic of breast cancer or diabetes or dementia, and Schettler starts talking about income disparities, industrial farming, and campaign finance reform.

The Harvard-educated physician, frustrated by the limitations of science in combating disease, believes that finding answers to the most persistent medical challenges of our time—conditions that now threaten to overwhelm our health care system—depends on understanding the human body as a system nested within a series of other, larger systems: one’s family and community, environment, culture, and socioeconomic class, all of which affect each other.

Continue reading on the Yes! Magazine website.

New report: “Review of the Science Linking Chemical Exposures to the Human Risk of Obesity and Diabetes”

Sarah Howard
Coordinator of the CHE Diabetes and Obesity Spectrum Working Group

The UK nonprofit organization CHEM Trust (Chemicals, Health and Environment Monitoring Trust) just released a report on the links between chemicals and diabetes/obesity. Studies published in recent years provide compelling evidence that human chemical contamination can play a part in both conditions. The report concludes that the chemicals that we accumulate throughout life, via our everyday lifestyles, is likely to contribute to these modern epidemics. This is the same conclusion reached by the National Toxicology Program’s review of the scientific evidence on chemicals and diabetes/obesity, published last month.  

The CHEM Trust report, entitled Review of the Science Linking Chemical Exposures to the Human Risk of Obesity and Diabetes, is written by two of the world’s leading experts: Professor Miquel Porta, MD, MPH, PhD, of Spain and Professor Duk-Hee Lee, MD, PhD, of South Korea.

Science Pick: Gut Microbiota and Environmental Chemicals in Diabetes and Obesity

Sarah Howard,
CHE Diabetes-Obesity Spectrum Working Group Coordinator

CHE’s January 19th call was on the interactions between gut microbiota and environmental chemicals in diabetes and obesity, a new area of research. Separately, gut microbiota and environmental chemicals may both contribute to the development of diabetes and obesity; what about the effects in combination?

The presenters reviewed research that shows that gut microorganisms can affect the absorption, distribution, metabolism, and elimination of environmental chemicals. For example, gut microbiota can cause a leaky gut, increasing absorption of chemicals. Gut microbes can modify polyaromatic hydrocarbons (PAHs) to turn them into estrogenic compounds. Microbiota can also affect detoxification processes in the liver.

An individual’s gut microbes may affect the rate at which they clear chemicals from their body. Seventy five percent of diabetogenic and obesogenic chemicals can be metabolized by gut microbes.

The interactions between gut microbiota and environmental chemicals may be significant not only for diabetes and obesity, but also for other diseases as well. It is a topic sure to see more research in the future.

To access slides and papers, visit the call page.