Top 10: July 2013

For the second quarter of 2013, we collectively selected ten topics from several dozen candidate news articles, journal articles, policy decisions and reports that have had a significant impact or are likely to have a significant impact on thinking and action in the field of environmental health. We consider these selections to be the biggest contributors toward new insights, toward changing the conversation or expanding the scope of the conversation on a topic to a new audience or awareness, or toward defining a new trend. Comments are welcome.

The selections, in no particular order:

  1. Chemical policy reform
    A significant development in federal chemicals policy reform occurred in late May when  Senator Frank Lautenberg (D-NJ) and David Vitter (R-LA) introduced a new, bipartisan bill called the Chemical Safety Improvement Act (CSIA). The introduction of the CSIA took many by surprise. Senator Lautenberg, who had been a champion for chemical policy reform for many years, passed away about a week later. CHE has compiled a selection of responses to this bill as well as links to other relevant sites for additional information: Chemical Policy Reform.
  2. Autism: New insights
    Several new studies have provided further understanding of environmental and genetic contributors to autism spectrum disorders. We list what we view as some of the most significant of these studies:

    1. Autism study finds link to environment, even in womb: A new study of twins suggests that environmental factors, including conditions in the womb, may be at least as important as genes in causing autism. See the study abstract: Genetic heritability and shared environmental factors among twin pairs with autism and related studies: Quantitative trait loci for interhemispheric commissure development and social behaviors in the BTBR T+ tf/J mouse model of autism and Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits.
    2. Study links autism with antidepressant use during pregnancy. See the study abstract: Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study.
    3. Epilepsy drug in pregnancy tied to autism risk: Women who take the epilepsy drug valproate during pregnancy are three times more likely to have a child with an autism spectrum disorder, suggests new research based on close to 700,000 babies born in Denmark. See the study abstract: Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism.
    4. US kids born in polluted areas more likely to have autism. See the study abstract: Perinatal air pollutant exposures and autism spectrum disorder in the Children of Nurses’ Health Study II participants.
  3. EHN special report: ‘chemicals of high concern’ found in thousands of children’s products
    An Environmental Health News analysis of thousands of reports from America’s largest companies shows that toys and other children’s products contain low levels of dozens of industrial chemicals. See the database: Children’s Safe Product Act Reports.
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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.

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Is the Environment Making Us Fat and Sick?

‘Obesogens’, other environmental factors contribute to metabolic syndrome

Based upon the May 7 CHE Partnership Call

Conventional wisdom says that the meteoric rise in obesity and related health conditions – the early stages of which are now called metabolic syndrome – is due to the West having a bad case of “couch potato syndrome.” That is, over the past few decades, we have been eating too much and not exercising enough.

While poor diet and inactivity play an undeniable role in fostering metabolic syndrome, that’s not the whole story. Clinical and epidemiological evidence increasingly implicates another culprit: the environment.

An insufficient explanation

Some scientists suspect that a combination of environmental factors, including a group of chemicals called obesogens, share the blame for the explosion of metabolic syndrome and its later stages: diabetes, obesity, cardiovascular disease, and even Alzheimer’s.    

“Despite what we’ve heard,” said Dr. Bruce Blumberg, Professor of Developmental and Cell Biology and Pharmaceutical Sciences at the Univeristy of California, Irvine, “diet and exercise alone are insufficient to explain the obesity epidemic.”   

A May 7 teleconference presented by the nonprofit Collaborative on Health and the Environment explored this urgent and compelling topic. This article is based upon that teleconference.
   
Metabolic syndrome is estimated to affect more than one-third of U.S. adults, 60% of them under 65 years old.

When environment collides with human biology

Speaker Dr. David Jacobs, Professor of Public Health at the University of Minnesota, a chronic-disease epidemiologist, defined metabolic syndrome as “a constellation of related metabolic abnormalities (body fatness, blood fat handling, insulin, glucose).”
   
Environmental factors suspected to contribute to metabolic syndrome include the food system, the transportation system, the built environment, air pollution, obesogens, other environmental contaminants, and socioeconomic stress.
   
These stressors alter pathways in the body, causing inflammation, oxidative stress, and disrupted insulin signaling. Altered pathways can, in turn, lead to diabetes, obesity, cardiovascular disease, and abnormal lipids (tied to dementia and Alzheimer’s).
   
You can think of metabolic syndrome as a crossroads, said speaker Dr. Jill Stein, co-founder of the Massachusetts Coalition for Healthy Communities, board member of Greater Boston Physicians for Social Responsibility, and co-author of the recent report Environmental Threats to Healthy Aging.
   
“This is where the environment meets human biology in the early stages of the disease process. You can think of environmental factors as kind of colliding with human biology here.” 
    

Chemical culprits

The obesity epidemic, as Dr. Bruce Blumberg pointed out, roughly correlates with the rise in the use of industrial chemicals (plastics, pesticides, etc.) in the years since World War Two.

Though, he reminded listeners, “correlation is not causation.”
   
Also, many environmental contaminants affect the endocrine system, which plays a big part in determining weight by controlling the appetite and metabolism, fat cell development, and lipid balance. These basic facts, plus suggestive laboratory research, has led scientists to propose an additional label for certain chemicals: obesogen.
   
Some time ago, Dr. Blumberg and his colleagues proposed “the obesogen hypothesis,” which defined obesogens as “chemicals that inappropriately stimulate adipogenesis and fat storage, exist and contribute to the obesity epidemic.”
   
Varioius studies have found that pre- and post-natal exposure to obesogens reprograms the metabolism of exposed animals, predisposing them to obesity later in life.   
   
Dr. Pete Myers, founder, CEO, and chief scientist of Environmental Health Sciences, began the teleconference by describing one such study, by Soo Lim et al., published in the journal PLoS One in April 2009. You can access the study at www.plosone.org/article/info:doi/10.1371/journal.pone.0005186
   
The study involved chronic exposure of rats to low levels of the common herbicide atrazine. After five months of exposure, the rats showed descreased basal metabolic rate, increased body weight, increased intra-abdominal fat, and increased insulin resistance. The effects were even stronger when the rats were fed a high-fat diet.
   
The scientists concluded that long-term atrazine exposure could contribute to the development of insulin resistance and diabetes in people, especially where high-fat diets are prevalent.
   
“The exposures they used were well within the range that people are often exposed to, “ said Dr. Myers, “especially within corn-growing areas. I think we’ll be hearing more about this line of research in the future.”    

POPS, diabetes, and metabolic syndrome

When the CDC tested the blood of 2,016 adults for the presence of six POPS (Persistent Organic Pollutants) as part of the National Health and Nutrition Examination Surveys (NHANES, 1999-2002), they found that each of the POPS was related to increasing occurrence of diabetes. People with POPS levels in the top quarter had a risk of developing diabetes 38 times greater than those with bottom-quarter levels.
   
Among non-diabetics in NHANES, people with organochlorine pesticide levels in the top quarter had five times the risk of metabolic syndrome compared to those in the bottom quarter.
   
These pollutants, though mostly banned in the 1970s, still linger in our foods. They are also found in computers, refrigerators, flame retardants, and waste dumps.        

What you can do

As far as prevention goes, Dr. Stein said, there are three major things you can do as an individual to reduce your risk of metabolic syndrome.

“The route that you take depends on the particulars of your life and your community. There are many dietary interventions – I’ll just throw out the Mediterranean diet because there is very compelling data about its effect in reducing not only metabolic syndrome but all the other conditions we’ve been talking about, and others beyond that. Taking general steps to reduce chemical exposures. Exercise.”
   
The Mediterranean diet is one composed of mostly fruits and vegetables, with lots of whole grains, fish, and olive oil, and very little processed food or red meat.    

What we can do

When asked for his thoughts on prevention, Dr. Jacobs underscored the need to think on a macro level.
   
“We really need the political will to examine our society,” he said, “and make some changes in it. They’re not going to come overnight. If you’re talking about reengineering where sidewalks are to encourage more physical activity, that’s difficult. If we’re talking about having an entirely different way of delivering food to the people other than the food industry, that’s a massive change.
   
“If we’re talking about the chemicals – they’re in computers. I like computers. They’re in refrigerators… The cleverness is to figure out how to have the things we want to have in our lives from industry without disrupting health.”
   
A final point to consider reminds us that we are only beginning to understand the complex relationship between our health and our environment.
   
Dr. Blumberg brought up the emerging paradigm of developmental origins of adult disease.
   
“Many of the afflictions we have as adults arise during development and early childhood,” he explained, “as a result of the foods we eat, the chemicals we’re exposed to, a variety of factors. We need a lot more research in this area to help us prevent chronic disease in later life.”

Does “the Dose Make the Poison?”

John Peterson Myers, PhD
CEO of Environmental Health Sciences

A core assumption of traditional toxicology is “the dose makes the poison.” Generations of toxicologists have begun their studies by learning this, countless experiments have provided support, and the laws protecting people from undue exposure all assume that it is true.

“The dose makes the poison” is taken to mean that the higher the dose, the greater the effect. And this implies that low exposures are less important. Indeed, based on “the dose makes the poison”, it is commonly argued that “background” levels of contamination aren’t worth worrying about.

Yet new evidence emerging from modern scientific research that combines toxicology, developmental biology, endocrinology and biochemistry is demonstrating that this assumption is wrong, at least in its simplest and most-widely used form. And the implications for this new realization are profound, because it means that the safety standards used to protect public health are built upon false assumptions and likely to be inadequate.

Two core patterns in this emerging research violate simplistic uses of “the dose makes the poison.”

  • One arises because sensitivity to contamination is not the same at all stages of the life of an individual. The same low dose that may pose no risk to an adult can cause drastic effects in a developing fetus.
  • The second involve dose-response curves in which low levels of a contaminant actually cause greater effects than higher levels, at the same stage of development. These dose-response curves, shaped like inverted-U’s, are called “nonmonotonic dose-response curves.”

Both of these patterns require a more sophisticated view of what it means for “the dose makes the poison.”

In the case of sensitivity varying from one stage of development to the next, “the dose makes the poison” is valid as long as one doesn’t wrongly assume that measurements at one stage can be extrapolated to another. The assumption holds true (as long as there is no nonmonotonic dose response curve, see below) within a stage of development, but not among them.

A recent dramatic example of this differential sensitivity was found in work comparing the impact of an herbicide on tadpoles vs. frogs. In frogs, the change from tadpole to frogs is exquisitely sensitive to chemical disruption of development. A dose of atrazine (a commonly used herbicide) 30,000 times lower than the lowest level known to affect adult frogs caused 20% of tadpoles to become hermaphroditic (containing both male and female sexual organs) in adulthood.

This pattern seen in frogs is not an exception. The scientific literature is full of examples demonstrating that in its early stages of development and organism can be more vulnerable than during adulthood. Thus it is important to realize that “the adult dose does not make the fetal poison.”

Inverted-U or nonmonotonic dose-response curves (NMDRCs) provide a more difficult challenge to the traditional interpretation of “the dose makes the poison,” i.e., that higher doses have greater impacts to lower doses. In NMDRCs, lower doses can have larger impacts than higher doses. One recent example arose in work on proliferation of prostate tumors:

A very low dose (1 nanomolar) of bisphenol A induces a stronger response than a much higher dose (100 nanomolar). The response to 1 nM is significantly greater than the control. 

Many examples of NMDRCs are now being published in the scientific literature (more). This raises three questions:

Why were they not found commonly before? Several factors may have contributed to the infrequency with which NMDRCs were reported previously in the scientific literature.

  • One may be simply that few scientists looked. Driven by “the dose makes the poison,” toxicologists would perform experiments at higher doses and work down the dose-response curve until they found a level at which no response was detectable. Experiments at doses 1/10th to 1/100th of that no-response level made no sense. But without experiments at much lower doses, the low-dose effects of NMDRCs could not be detected.
  • A second impediment arose from the statistical design used to analyze results in toxicology. Designs built on the assumption that “the dose makes the poison” are unlikely to find NMDRCs.

Why do they occur? This is an active area of research. Several ideas have been offered.

  • One is that within the range of very low doses showing NMDRC patterns, enzymatic defenses against chemical contaminants are not activated. The supposition here is that at these very low levels, the contaminants are at levels that are within the range where their biological activity resembles the normal hormonal mechanisms controlling development. As contaminant levels rise, defense mechanisms are activated, shutting down the original response.
  • Another is that as the low dose rises into a higher range, the contaminant stimulates new responses, perhaps activating different hormonal pathways that then operate in a negative feedback loop to shut down the system involved in the original response.

What do they mean for public health? NMDRCs are extremely troubling for regulatory toxicology because their presence undermines the validity of generations of toxicity testing that have been based on the assumption that “the dose makes the poison.” Prevailing federal safety standards are built upon research methods that are unlikely to find low-dose effects, and very few chemicals have been tested in ways that would reveal them.

For that reason NMDRCs were the subject of intense debate among scientists as it became clear they were not uncommon. The US National Toxicology Program went so far as to convene a special “low-dose panel” of scientists to conduct a full scale review. The panel’s findings, published in 2001, confirmed the reality of NMDRCs.

So what do NMDRCs mean for “the dose makes the poison”? In a literal sense, the dose still does, as for example, in the graph of prostate tumor proliferation above: A dose of 1 nanomolar bisphenol A produces a different response than does 100 nanomolar. Dose does matter. But with BPA and prostate proliferation, “a very low dose makes a higher poison.” It is no longer safe to assume that lower doses have lower impacts than higher doses. The science used to establish public exposure standards needs to incorporate this new concept.