Research Engine

Researching the relationship between toxic chemicals and bad health outcomes

New study led by Brown epidemiologist seeks to uncover the way that a toxic chemical may disrupt the biologic processes

Courtesy for Brown University

Joseph Braun, Ph.D., an epidemiologist at the Brown University School of Public Health, was recently awarded a $2 million grant from NIH to continue his research on impacts of the toxic chemical PFOA on more than 200 mothers and their children in Cincinnati.

By Richard Asinof
Posted 2/15/16
A new $2 million award by NIH to fund research by Brown University epidemiologist Joseph Braun will further explore the biologic pathways disrupted by the toxic chemical known as PFOA, which has been associated with the development of child adiposity – excess fat.
When will research into the impact of toxic chemicals that have become persistent in the environment and bad health outcomes become a priority for public health? What are the new kinds of statistical tools that need to be developed to measure not just one toxic chemical in isolation but from a stew of harmful chemicals? What are the similarities between lead poisoning and toxic stress on brain development? What role can the Brown School of Public Health play in prioritizing more research on potential endocrine disruption by toxic chemicals, pesticides and herbicides and their relationship to bad health outcomes?
In Flint, in Cincinnati, in Hoosick Falls, as well as many other places in America, the threat to clean, safe drinking water is on the verge of becoming a public health crisis. In her proposed FY 2017 budget, Gov. Gina Raimondo proposed raiding the resources at the new state Infrastructure Bank [the former Clean Water agency] for millions in cash to invest in other budget priorities. Perhaps the R.I. General Assembly should consider keeping the money where it is and instead look to make infrastructure investments in preserving clean drinking water for Rhode Islanders. And, perhaps look to screen and protect residents from toxic chemicals such as PFOA.

PROVIDENCE – In a time of heightened sensitivity about the relationship of toxic chemicals in drinking water and poor health outcomes, in large part due to the continuing reverberations from the potential lead poisoning of more than 9,000 children in Flint, Mich., a new $2 million grant awarded by the National Institutes of Health to Brown University epidemiologist Joseph Braun promises to provide additional insights into the way that toxic chemicals may disrupt the body processes.

The new grant is a continuation of work that Braun first undertook as part of the Health Outcomes and Measures of the Environment, or HOME study, in Cincinnati, that was began in March of 2003.

In that study, a collaborative group of investigators sought to quantify the impact of low-level prenatal and childhood exposures to environmental chemicals on health, growth and neurobehavioral outcomes.

What Braun’s initial research showed, in a study of 204 Cincinnati mothers and their children that looked at the potential effects of perfluorooctanoic acid, or PFOA, a toxic industrial chemical used in the manufacture of products such as nonstick coatings, was that relatively high exposure with pregnant mothers resulted in a statistically significant association with the amount and pace of body fat gain in children during the first eight years of life, according to the report published in Obesity in November of 2015.

The study added to a growing body of evidence that man-made chemicals such as PFOA may trigger obesity, with the chemical passing from the pregnant mother to her child. Excess body fat in children may increase the risk of Type 2 diabetes later in life.

“Pregnant women [we] studied had a higher concentration of this chemical in their blood, in fact, two times higher than other pregnant women in the United States,” Braun said in an interview published by Brown University in November of 2015. “And children born to these women have a higher body mass index [BMI] and waist circumferences.”

The increased level of body fat in children, known as child adiposity, can pose a significant public health concern, according to Braun.

“There isn’t a threshold at which we say you shouldn’t add more fat mass – any more fat mass is bad fat mass,” Braun said in the November 2015 interview. “When you look at the risk of diabetes in adults, the risk is pretty much linear across the whole range of BMI.”

The new study
Work on the new, five-year NIH study officially began on Feb. 1, according to Braun. “We have found that pregnant women in this cohort have above-average concentrations of one of these perfluoroalkyl [chemical] substances, compared to women in the U.S.,” he said in a Feb. 2 interview with Brown University.

[The problems with PFOA were the topic of a major investigative story in the New York Times Magazine in January. In addition, PFOA contamination of the drinking water Hoosick Falls, N.Y., has led to interventions by N.Y. Gov. Andrew Cuomo, who has promised the state will spend $10 million to buy water filtration systems for the local residents. See link below to ConvergenceRI story.]

In the new study, Braun plans to investigate further into the possible ways that the toxic chemical interacts with the body’s processes, collecting detailed measures of the epigenetic and hormonal biomarkers.

Here is the ConvergenceRI interview with Joseph Braun, assistant professor of epidemiology at the Brown University School of Public Health, talking about the new study now underway.

ConvergenceRI: What are the specific mechanisms your new study will be looking at in regard to the how toxics such as PFOA are related to bad health outcomes, such as obesity, Type 2 diabetes and heart disease?
We’re going to look at biologic pathways; we’re going to look at hormones. We’re going to be looking at levels of cortisol in the mothers’ hair, to see if the PFOA inhibits the enzyme that breaks down cortisol. We’re also going to see if there are higher levels of cortisol in the fetus and placenta.

We’re also going to look at the epigenetics, figuring out the way that genes are regulated and expressed [in relationship to the toxic chemical].

If genetics programs the radio, epigenetics determines the volume.

How do these chemicals, which can act upon hormonal pathways, impact the epigenetic mechanisms – the expression of [DNA] and how it is regulated.

ConvergenceRI: Will you be looking at drinking water intake as a factor in the way that the toxic chemicals are ingested?
We are interested in this, looking at water as a source of additional, higher level of exposure than others in the U.S. We are quantifying [the levels of PFOA] in water samples taken during pregnancy [of the women in the study]. Those results are pending right now.

ConvergenceRI: Have you heard about what’s going in Hoosick Falls, N.Y., with drinking water contamination from PFOA?
I just learned about that recently.

ConvergenceRI: While your studies are targeting PFOA as a specific toxic chemical, is there a need to look at the interactions with a larger stew of toxics that may exist?
We’ve been talking about mixtures for a long time. People are trying to figure out what are the tools that are needed to study mixtures. Work is being done on this. I helped to organize a conference this past summer to start implementing statistical techniques related to mixtures.

It’s not simple; what you want to know depends on the tools you use, and it also depends on the questions you want to ask. Different questions have different meanings for regulations and public health.

ConvergenceRI: Will your new study encompass how PFOA acts as a potential endocrine disruptor and how it may impact the gut microbiome?
It depends on whom you ask. There appears to be endocrine disruption, specifically, in thyroid hormones and adrenal hormones, as well as in some of the fat cells and the deactivation of cortisol.

[In regard to the gut microbiome], is there are relationship, a risk factor, as a consequence of obesity? The jury is still out on that question.

In animals, there is a causal risk for energy metabolism changes; it humans, it’s not as clear.

In terms of chemicals, people are beginning to look at the gut microbiome. There is some interest, but no active projects yet.

ConvergenceRI: Much of the current health interventions around obesity have focused on activities such as diet, exercise, and reduced sugar and salt intake. In terms of potential interventions around toxics prevention, what do you recommend? Water filters?
Part of the problem is that it is difficult for individuals to reduce exposure to the multitude of chemicals they are exposed to in our environment.

Purchasing and using a water filter will reduce the concentration of contaminants.

This really goes back to thinking about whether the onus needs to be on individuals or on policies.

ConvergenceRI: PFOA was implicated in a recent investigative story in the New York Times Magzine, and the alleged dumping of that toxic chemical in West Virginia. It also revealed the fact that PFOA was not currently “regulated” under the federal toxics law. Is that a problem?
There is a provisional EPA water standard [for PFOA], but it’s not legally enforceable. Where it stands right now is that Dupont [the company that used PFOA in its product manufacturing] has voluntarily decided to phase out PFOA use this last year and is switching to another chemical, which has similar properties, but is slightly different in its structure.

I am not versed on policy; I do the science.

ConvergenceRI: As an epidemiologist, what are the lessons learned from what happened in Cincinnati, and for that matter, Flint? What do we need to focus on in terms of public health concerns?
In what regard? Flint is very different than Cincinnati. We didn’t know where [the toxic chemical] was coming from in Cincinnati and what caused the elevated levels.

It was really auspicious; when the study began, we had no idea [we would find] this chemical 10 years after the cohort was started.

That just happened to be fortunate, epidemiologically, and unfortunate for the people. It wasn’t [the result] of a failure of regulation, or the city’s changing the water supply.

ConvergenceRI: Before you became an epidemiologist, you first became a nurse. How did that change your perspective?
It gives you an appreciation and a clinical perspective, from the top to the bottom of populations, how research impacts everything from what we do at the policy level to what we do at the individual level of care.


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