The Michigan State University (MSU) Center for Integrative Toxicology is directing a $14.1 million initiative to better understand how environmental contaminants called dioxins affect human health and to find new ways of removing them from the environment.

The project, led by Norbert Kaminski, director of the toxicology center and a professor of pharmacology and toxicology, is funded by a five-year grant from the Superfund Research Program of the National Institute of Environmental Health Sciences, and includes toxicologists, microbiologists, statisticians, engineers and others.

“More than 25 scientists are involved,” says Kaminski, “as well as many students, postdoctoral trainees and technicians. This funding gives us a rare opportunity to bring many different types of expertise together to focus on a single problem.”

Other institutions collaborating with MSU on the project include Rutgers University, Purdue University, the Hamner Institutes for Health Sciences, Texas A&M University and the U.S. Environmental Protection Agency.

From the Ground up

Dioxins are generally created as by-products from industrial processes, such as bleaching paper pulp or manufacturing pesticides, or combustion processes, such as waste incineration. Kaminski notes that dioxins can be detected virtually everywhere in the world, and they can remain in the environment for decades. “Dioxins can enter your body if you breathe contaminated air, consume contaminated soils, such as could be the case with small children, or eat contaminated food. In fact, about 90 percent of exposure to dioxins is from eating contaminated food. Dioxins are ubiquitous.”

The contamination begins when dioxins – which are not easily dissolved in water – form a chemical bond with soil or sediment in waterways. One team of researchers on the project is studying how dioxins react with different soils. “That will help us measure the human and ecological risks posed when various levels of dioxins are present in an area with a particular type of soil,” explains Stephen Boyd, MSU University Distinguished Professor of crop and soil sciences and team leader for the “geochemical” portion of the project.

“Until now, risk assessment models for exposure to environmental dioxins have made generic assumptions that all of the dioxin present could potentially be absorbed by humans and other animals, regardless of the soil characteristics,” he says. “We need to know if dioxins bind with clay, for example, in such a way that they are not absorbed. From there, we may also be able to identify how microorganisms in the environment might be used to clean contaminated sites.”

The scientists are also working with adults from the Saginaw-Tittabawassee Rivers Contamination Community Advisory Group and high school students in the Midland/Saginaw Valley area to collect and analyze soil data. The community-based experiments were designed to help residents learn about local dioxin contamination, and the effort may help researchers collect valuable environmental data.

“We have already developed materials for Midland High School students to teach them about dioxins,” says Kaminski. “By next fall, we hope to have them collecting soil samples and using fairly sophisticated methodologies to analyze the samples themselves for microorganisms possessing enzymes that can degrade dioxins and dioxin-like compounds.”

Dioxins and People

Krista Greenwood, MSU Alumna


Krista Greenwood, a former student who
now works for Dow Chemical, pulls cell stocks out of liquid nitrogen as part of an experiment in John LaPres’ lab. Photo: Kurt Stepnitz, MSU CABS.

While previous research on dioxins has involved mice and other animal models, the new project includes studies using donated human cells and tissue in an effort to more accurately understand how dioxins affect human health. “We know these contaminants impair antibody production and thereby compromise human and animal immune systems,” explains Kaminski. “What is really lacking in our understanding of dioxins is why certain individuals are more sensitive to dioxins than others.”

Researchers are also trying to understand the cause-and-effect relationship between chemical exposure and illness. John LaPres, associate professor of biochemistry and molecular biology, and his team are applying the toxicological principle of dose response — the relationship between the amount of poison one receives or is exposed to (the dose) and a toxic reaction (the response) to learn more about dioxins.
“We can make two important assumptions,” explains LaPres. “There is almost always a dose below which no response occurs or can be measured; and once a maximum response is obtained, any further dose will not result in an increased effect. Knowing the dose-response relationship for TCDD (tetrachlorodibenzo-p-dioxin) has huge implications for risk assessment and how we manage Superfund sites.”

Timothy Zacharewski is a professor of biochemistry and molecular biology and, like LaPres and Boyd, he is an MSU AgBioResearch scientist. His research will focus on the effects of human exposure to dioxins, especially how it drives the accumulation of fat in the liver.

“The chronic accumulation of fat in the liver can progress into more complex diseases such as non-alcoholic fatty liver disease and metabolic syndrome, which have been associated with diseases such as diabetes, obesity, cardiovascular disease and liver cancer.

“So far, we have found that dioxins work through a specific protein called the aryl hydrocarbon receptor to increase liver fat accumulation using fat from the food we eat. We believe that’s what is creating the problem,” said Zacharewski. He is also trying to determine whether there are enough dioxins and other chemical compounds in the environment, not necessarily in the hazardous waste sites, to cause this effect in humans.

For more information on the Superfund Project, visit the website here.`