Research Highlight: Unexpected Results in a Study of Dietary Chemical Exposures

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When people are exposed to harmful chemicals, pollution, and other substances in the environment, some people get sick and some people don’t. It’s even true that people who are part of certain groups are more likely to have bad health effects from being exposed to harmful chemicals than people from other groups. The groups that are more vulnerable are known as susceptible populations.

Examples of susceptible populations include unborn fetuses, children, pregnant women, the elderly, the malnourished, those who have a certain version of a specific gene, and people who have chronic diseases such as cancer, asthma, or diabetes.

Center members who work in the Susceptible Populations (SSP) ARE focus on environmental exposures in these vulnerable groups. Specifically, SSP ARE researchers study reproductive toxicology (for example, chemical exposures that affect fertility); embryonic and fetal development and teratology (the study of substances that cause birth defects); infant and child development; and, the susceptibilities of aging.

Investigators in the SSP ARE are also interested in learning how environmental exposures during prenatal development and childhood contribute later in life to adult disease.

CEEH Investigator Dr. Sheela Sathyanarayana
One of the members of the SSP ARE, researcher and pediatrician Dr. Sheela Sathyanarayana, studies the health effects of being exposed in utero and in childhood to the endocrine-disrupting chemicals (EDCs) phthalates and bisphenol A (BPA).

Phthalates and bisphenol A are used in common products and industrial processes, and most humans in the industrialized world are exposed to them. Phthalates are added to plastics to add flexibility. Exposure to phthalates during gestation is associated with male reproductive tract abnormalities; exposure during childhood has been associated with increased risk of asthma and eczema. Exposure to BPA has been studied in pregnant animals and their babies, and is associated with abnormal development.

Sheela Sathyanarayana and her team conducted a small study to learn whether eating an organic diet prepared without plastics versus being given educational materials about avoiding plastics would reduce exposure to phthalates and BPA. Ten families with 40 family members in all participated. Families were randomly chosen to (1) eat an organic diet provided to them that had been prepared without using plastic tools or storage containers or (2) receive educational material about how to reduce exposure to EDCs in the diet.

Urine samples were taken before, during, and after the 5-day intervention to measure phthalates and BPA. The researchers predicted that levels of the chemicals would be lower in the group that ate organic food.

The title of the paper that reports this study is Unexpected results in a randomized dietary trial to reduce phthalate and bisphenol A exposures.1 The unexpected result was that the urine phthalate levels of the participants who ate the organic diet spiked to 25 times their phthalate levels before they ate the diet. Participants who followed advice from educational materials showed no significant change in their phthalate levels.

To understand how those who ate the organic diet had consumed phthalates, the food ingredients used in the organic replacement diet were tested. Slightly higher than expected levels of phthalates were found in some of the dairy products, as well as in ground cinnamon and cayenne pepper. However, ground coriander spice was found to have an astronomical phthalate concentration of 21,400 ng/g, forty times the concentration in the dairy products.

The team calculated that the total daily intake of the children who ate the organic food prepared with contaminated coriander was 9 times the oral Reference Dose (RfD). The RfD is the maximum acceptable oral dose of a toxic substance, as determined by the Environmental Protection Agency.

Dr. Sathyanarayana and her colleagues drew two conclusions:
  1. Providing written recommendations and guidelines is not enough to change people’s exposure to phthalates, and 
  2. Governmental or industry regulation to reduce phthalates and BPA in food may be needed to keep the food supply safe from contamination.
Dr. Sathyanarayana received CEEH Pilot Award funding in 2009-2011 to study the effect of phthalate exposure and genetic variation on male genital development.

  1. Sathyanarayana S, Alcedo G, Saelens BE, Zhou C, Dills RL, Yu J, Lanphear B. Unexpected results in a randomized dietary trial to reduce phthalate and bisphenol A exposures. Journal of exposure science & environmental epidemiology. 2013;23(4):378-84. Epub 2013/02/28. doi: 10.1038/jes.2013.9. PubMed PMID: 23443238.
  2. http://www.epa.gov/risk/glossary.htm#r


Research Highlight: Exposure to Air Pollution Early in Life Could Lead to Heart and Lung Disease in Adulthood

Center investigators are exploring links between diesel exhaust exposure and several chronic diseases.

Our Center has been researching respiratory susceptibility since the Center was founded in 1995. For the first eight years, we focused primarily on air pollution and asthma. In 2003, we began to look at how environmental factors can increase the risk of other conditions, such as cardiopulmonary and cardiovascular diseases.

The public health impacts of cardiopulmonary and cardiovascular disease are huge. Atherosclerosis, the buildup of cholesterol and fats in the coronary arteries that supply blood to the heart, is the #1 killer of both men and women in the United States.1 In recent years, it has become clear that environmental factors play a major role in the risk of cardiovascular disease, and that these factors could potentially be modified to reduce risk. The Center’s Cardiovascular Toxicology Area of Research Emphasis (ARE) brings together several researchers who are working in this promising field.

Cardiovascular toxicology is the study of the adverse health effects of toxic chemicals on the heart or blood systems. An important component of cardiovascular toxicology is identifying the exact mechanisms by which chemicals cause harm to the body. Several CEEH investigators are exploring possible mechanisms using engineered animal models. For example, ongoing projects in the Cardiovascular Toxicology ARE explore the roles of genetic susceptibility and gene expression in an effort to understand precisely how ambient particulate matter can contribute to cardiovascular and pulmonary diseases. Particulate matter refers to the complex mixture of very small particles and liquid droplets present in air.

Dr. Michael Chin
One example of this research is a study of diesel engine exhaust exposure, epigenetic changes and heart failure in mice. The project began as a CEEH Pilot Project Award in 2013, led by Cardiovascular Toxicology ARE researcher and cardiologist Dr. Michael Chin. The Center funds four to six small pilot projects each year. Pilot project grants are designed to help investigators to obtain preliminary data that will be useful for competitive, full-scale grant applications. CEEH has awarded a total of 74 pilots since 1995, investing approximately $1.85 million to date in these small, innovative research projects.

Dr. Chin and his team, which included Chad Weldy, Yonggang Liu, Yi-Chi Chang, Ivan Medvedev, Julie R Fox, Timothy Larson, and Wei-Ming Chien, studied exposure to diesel exhaust (DE) because DE is the greatest source of traffic-related fine particulate air pollution. Exposure to DE has been shown to be associated with an increased risk of cardiovascular disease and death. However, little research has been done on the potential long-term effects of exposure to DE in the womb (in utero) and during early development. Dr. Chin and his team wanted to know if in utero and very early life exposures could increase susceptibility to heart disease later in life.

To explore this question, the research team exposed mice to either filtered air or DE only during in utero and early life development. The researchers found that when the mice exposed to DE were raised to adulthood, they were significantly more susceptible to heart failure. Following a surgery to induce heart failure, these mice showed greater enlargement of the heart, worse contractile function, extensive fibrosis (build up of scar tissue within the heart), and lung congestion. They also showed a change in the inflammatory response in the lung, suggesting that environmental challenges during these developmental windows may be important not just to the heart, but also to the lungs.

Dr. Chad Weldy enjoys a rare moment away from the lab.
The researchers concluded that exposure to diesel exhaust air pollution in utero and in early life increases susceptibility to heart failure in adult mice. These results suggest that the effects of air pollution on cardiovascular disease in humans may originate from very early life exposures.2

A more recent paper in PLoS ONE links in utero exposure to DE to weight gain and changes in blood pressure, as well as increased risk of heart failure.3

Dr. Chad Weldy, Senior Fellow within the Division of Cardiology and lead author, says: “This work expands our understanding of how environmental exposures during early life development contribute to disease. As we learn that in utero development is critical for setting adult health, we need to further investigate how common environmental exposures may adversely impact development and increase lifelong risk of disease. I hope to see this work continue as epidemiological studies, where we can determine if these effects we see in the lab are also occurring in human populations. These future studies may prove to be crucial for setting regulatory policy, reducing environmental exposures, and improving public health.”

References:
  1. http://www.nhlbi.nih.gov/health/health-topics/topics/atherosclerosis/atrisk.html.
  2. Weldy CS, Liu Y, Chang YC, Medvedev IO, Fox JR, Larson TV, Chien WM, Chin MT. In utero and early life exposure to diesel exhaust air pollution increases adult susceptibility to heart failure in mice. Particle and fibre toxicology. 2013;10(1):59. Epub 2013/11/28. doi: 10.1186/1743-8977-10-59. PubMed PMID: 24279743.
  3. Weldy CS, Liu Y, Liggitt HD, Chin MT (2014) In Utero Exposure to Diesel Exhaust Air Pollution Promotes Adverse Intrauterine Conditions, Resulting in Weight Gain, Altered Blood Pressure, and Increased Susceptibility to Heart Failure in Adult Mice. PLoS ONE 9(2): e88582. doi:10.1371/journal.pone.0088582