THE POLLUTION INSIDE US
Toxicologists examine the chemicals of modern life.
By: Peg Herring, Oregon’s Agricultural Progress

Forty years ago, chemical pollution was the stuff that spewed from tailpipes, smokestacks, and sewers. Rivers burned, fish died, and forests withered under acid rain until Congress passed strict laws to curb the flood of manmade chemicals pouring into our waterways and atmosphere.

Man-made and naturally occurring chemicals pervade modern life. Here are a few that have been linked to human health problems.

However, 40 years ago there was little consideration of the chemicals that we were pouring into our bodies. The chemicals we use to sanitize our hands, package our foods, and keep our beds from going up in flames have seeped into our bodies in ways that were unimaginable a generation ago. Today, we are marinating in antibacterials, hormone disruptors, and flame retardants.

Man-made and naturally occurring chemicals pervade modern life. Here are a few that have been linked to human health problems.

“There are more than 80,000 man-made chemicals in existence today, and an estimated 2,000 new chemicals are introduced each year,” said Craig Marcus, a toxicologist at Oregon State University. “We encounter thousands of them every day, in food, kitchenware, furniture, household cleaners, and personal care products. And very few of them have been adequately tested for safety.” Continue reading

By Erin Madeen, Ph.D. candidate and Project 1 Trainee

Erin Madeen working at the Lawrence Livermore National Laboratory.
Erin Madeen working at the Lawrence Livermore National Laboratory.

Using new technology at Lawrence Livermore National Laboratory (LLNL), Oregon State University researchers are able to perform a controlled study of the human metabolism of environmental contaminate PAHs for the first time.

The Williams Laboratory has studied PAHs (polycyclic aromatic hydrocarbons) for over a decade, traditionally relying on animal and in vitro models of metabolism and toxicity. PAHs are produced by the burning of carbon-containing materials, for example forest fires, charcoal grilling, and engine combustion. After production, PAHs cling to foods such as vegetables, cereal grains, or smoked meats. Some of these compounds cause cancer at high doses in animal models.

As a graduate student in the Williams Lab, one of my projects is to relate PAH data to human health.  With our partners at LLNL, a sensitive tool known as an AMS (accelerator mass spectrometer) is used to detect very small doses of PAHs in urine or blood plasma.  We gave a model PAH called DBC [Dibenzo (def,p) chrysene] to human volunteers in doses less than what can be found in a charbroiled burger. This research has not been possible until now because of potential toxicity risks.  Traditional non-AMS methods need a larger dose of DBC which could pose too high of a risk to study participants.

With the support of LLNL staff and the OSU Superfund Research Program, I received a K.C. Donnelly Externship Supplement through the NIEHS Superfund Research Program.  This award supported my travel to LLNL for this project. My experience at LLNL greatly solidified my understanding of and appreciation for AMS. Maintaining and continuously developing unique instrumentation, such as AMS, requires a highly specialized, dedicated, and flexible team.  The environment of a national laboratory is different from that of university research.  Most notably this difference is in the concentration of specialists in a particular field and the team approach to problem solving. It was humbling to observe the amount of time, resources, and effort that the LLNL AMS staff dedicated to training and to progress on our DBC project. This externship allowed me to experience being part of the AMS team and to process my own samples, providing valuable insight that will help guide further work on our projects.

Accelerator Mass Spectrometry (AMS) is an instrument traditionally used for carbon dating. It has been modified to detect stable isotopes in biological samples. The AMS at LLNL is unique because it is able to use liquid samples.  The liquid biological samples are separated according to the changes the body makes to DBC, known as DBC metabolites.  The carbon isotope added to the DBC chemical structure was used to identify several different metabolites in human urine and plasma.  This project is ongoing as we continue to develop a profile of the human metabolism of DBC over time.

Related journal publications:

From OSU Superfund Research Program

From LLNL

 

grilled meat

CORVALLIS, Ore. – Researchers at Oregon State University have discovered novel compounds produced by certain types of chemical reactions – such as those found in vehicle exhaust or grilling meat – that are hundreds of times more mutagenic than their parent compounds which are known carcinogens.

These compounds were not previously known to exist, and raise additional concerns about the health impacts of heavily-polluted urban air or dietary exposure. It’s not yet been determined in what level the compounds might be present, and no health standards now exist for them.

The findings were published in December in Environmental Science and Technology, a professional journal.

The compounds were identified in laboratory experiments that mimic the type of conditions which might be found from the combustion and exhaust in cars and trucks, or the grilling of meat over a flame.

“Some of the compounds that we’ve discovered are far more mutagenic than we previously understood, and may exist in the environment as a result of heavy air pollution from vehicles or some types of food preparation,” said Staci Simonich, a professor of chemistry and toxicology in the OSU College of Agricultural Sciences.

Dr. Staci Simonich, Project 5 Leader with the OSU Superfund Research Program
Dr. Staci Simonich, Project 5 Leader with the OSU Superfund Research Program

“We don’t know at this point what levels may be present, and will explore that in continued research,” she said.

The parent compounds involved in this research are polycyclic aromatic hydrocarbons, or PAHs, formed naturally as the result of almost any type of combustion, from a wood stove to an automobile engine, cigarette or a coal-fired power plant. Many PAHs, such as benzopyrene, are known to be carcinogenic, believed to be more of a health concern that has been appreciated in the past, and are the subject of extensive research at OSU and elsewhere around the world.

The PAHs can become even more of a problem when they chemically interact with nitrogen to become “nitrated,” or NPAHs, scientists say. The newly-discovered compounds are NPAHs that were unknown to this point.

This study found that the direct mutagenicity of the NPAHs with one nitrogen group can increase 6 to 432 times more than the parent compound. NPAHs based on two nitrogen groups can be 272 to 467 times more mutagenic. Mutagens are chemicals that can cause DNA damage in cells that in turn can cause cancer.

For technical reasons based on how the mutagenic assays are conducted, the researchers said these numbers may actually understate the increase in toxicity – it could be even higher.

These discoveries are an outgrowth of research on PAHs that was done by Simonich at the Beijing Summer Olympic Games in 2008, when extensive studies of urban air quality were conducted, in part, based on concerns about impacts on athletes and visitors to the games.

Beijing, like some other cities in Asia, has significant problems with air quality, and may be 10-50 times more polluted than some major urban areas in the U.S. with air concerns, such as the Los Angeles basin.

An agency of the World Health Organization announced last fall that it now considers outdoor air pollution, especially particulate matter, to be carcinogenic, and cause other health problems as well. PAHs are one of the types of pollutants found on particulate matter in air pollution that are of special concern.

Concerns about the heavy levels of air pollution from some Asian cities are sufficient that Simonich is doing monitoring on Oregon’s Mount Bachelor, a 9,065-foot mountain in the central Oregon Cascade Range. Researchers want to determine what levels of air pollution may be found there after traveling thousands of miles across the Pacific Ocean.

This work was supported by the National Institute of Environmental Health Sciences (NIEHS) and the National Science Foundation (NSF). It’s also an outgrowth of the Superfund Research Program at OSU, funded by the NIEHS, that focuses efforts on PAH pollution. Researchers from the OSU College of Science, the University of California-Riverside, Texas A&M University, and Peking University collaborated on the study.

[Credit: Oregon State University Press Release]

See video from KVAL news

Learn more about PAHs from the Superfund Research Program web site.

 

By Leah Chibwe, Project 5 Trainee

This past summer, through the KC Donnelly Externship Award Supplement, I conducted a collaborative research project at the University of North Carolina (UNC) in Chapel-Hill with Dr. Mike Aitken and Dr. Jun Nakamura.

Screen Shot 2013-10-25 at 2.42.10 PM
Leah Chibwe

The objective of my time at UNC was to learn the DT40 bioassay based on chicken cell lines and use it asses the toxicity of Polycyclic Aromatic Hydrocarbon (PAH)-contaminated soil after bioremediation. Though I was quite excited about the opportunity, I was initially intimidated about leaving the familiarity of the chemistry lab at Oregon State University (OSU) and flying cross country to immerse myself in the unfamiliar (and very sterile!) world of cells and assays. It was a definite humbling learning experience; working with living cells taught me just how much of a virtue patience is –something that has helped me develop personally and as a researcher.

The KC Donnelly Externship created a platform on which we were able to combine analytical chemistry, biological and environmental engineering, and toxicology to address a shared concern. I was really inspired by the integration of the different ideas and mindsets from the various fields as we developed this project.

Before the externship, I was analyzing PAHs in remediated soil samples. At UNC, I learned about the DT40 assay and actually got to see how a lab-scale bioreactor (meant to simulate ex situ bioremediation) operated. I feel I now have a better understanding of how bioremediation works and the toxicity concerns often associated with PAHs. The experience has really added more depth to my research at OSU.

The externship was a very intense three months, but I really believe it was a pivotal moment in my development as an environmental health scientist; and has made me more appreciative of my research project. I also just had a great time interacting with everyone at the UNC Superfund Research Program (SRP).

 

ZebrafishRobyn Tanguay, PhD (Project 3 ) focuses on examining the effects of selected chemicals and chemical classes on zebrafish development and associated gene expression pathways.

The Tanguay research group recently collaborated with Terrence J. Collins, PhD, a champion in the field of green chemistry at Carnegie Mellon University.

Collins and his collaborators showed that specific green chemicals (a group of molecules called TAML activators) used with hydrogen peroxide, can effectively remove steroid hormones from water after just one treatment. Steroid hormones are common endocrine disruptors found in almost 25 percent of streams, rivers, and lakes.  Collins needed to understand the safety of TAML activators to move forward on this problem.

Tanguay’s group exposed zebrafish embryos to seven different types of TAML activators. None of the TAML’s impaired embryo development at concentrations typically used for decontaminating water.

The collaboration resulted in a new journal publication in Green Chemistry.

These are important findings that contribute toward TAML activators getting commercialized for water treatment.

Endocrine disruptors and human health

Endocrine disruptors can disrupt normal functions of the endocrine system and impair development, by mimicking or blocking the activities of hormones in wildlife. Several animal studies suggest that endocrine disruptors can also affect human health, and may be involved in cancers, learning disabilities, obesity, and immune and reproductive system disorders.

Robyn Tanguay’s leadership in utilizing  zebrafish

Robyn Tanguay is Director of the Sinnhuber Aquatic Research Laboratory, which is the largest zebrafish toxicology lab in the world.

In 2012, Dr. Tanguay received an EPA grant award, “Toxicity Screening with Zebrafish Assay”.  The award is for three years and almost two million dollars in funding to examine the developmental toxicology of at least 1000 chemicals.

Dr. Tanguay and her research team  have tested over 3,000 compounds of interest to the National Toxicology Program (NTP), to complement the ongoing high-throughput screening efforts in the U.S. government’s multiagency Tox21 research program.

More Information:

Citation: Truong L, DeNardo MA, Kundu S, Collins TJ, Tanguay RL.  2013. Zebrafish assays as developmental toxicity indicators in the green design of TAML oxidation catalysts. Green Chem; doi:10.1039/C3GC40376A [Online 15 July 2013].