By Sara Mishamandani
As the environmental health science field strives to better understand the complexity of personal chemical exposures, NIEHS-funded researchers at the Oregon State University (OSU) Superfund Research Program (SRP) led by Kim Anderson, Ph.D., have developed a simple wristband and extraction method that can test exposure to 1,200 chemicals.
Our Center is multi-investigator, multi-disciplinary and multi-institutional. In partnership with Pacific Northwest National Laboratories (PNNL), and other stakeholders and collaborators, we are developing new technologies to identify and quantitate known and novel polycyclic aromatic hydrocarbons (PAHs) found at many of the nation’s Superfund sites and assess the risk they pose for human health.
The research projects in our Center collect large amounts of molecular and chemical data. This data includes measuring PAH mixtures in environmental samples, determining toxicity of PAH mixtures, and the mechanism(s) of action for these toxic endpoints.
Our Biostatistics and Modeling Core, lead by Dr. Katrina Waters, greatly enhances our Center by providing expert statistical and bioinformatics data analysis support and software solutions for data management and interpretation.
Katrina Waters recently became the Deputy Director for the Biological Sciences Division at the Pacific Northwest National Lab (PNNL). Her expertise is in computational biology, and she works collaboratively with all of the research projects and co-authors with them.
This multidisciplinary training of toxicology students and fellows at OSU and PNNL is a unique strength of our program. Our SRP Trainees have benefited greatly from the PNNL partnership. Students have gone to the lab in Richland, WA to be trained in Bioinformatics, Statistics and Study Design. More training workshops are being scheduled for this summer and fall.
Waters presented at SOT’s FutureTox II: In Vitro Data and In Silico Models for Predictive Toxicology on January 16, 2014. Her talk was entitled Computational Tools for Integration of High Throughout Screening (HTS) Data. She utilized examples from the collaboration with Robert Tanguay and his zebrafish assay for toxicity testing (Project 3).
Dr. Susan Tilton, also from PNNL, presented at FutureTox as well. The title of her presentation was ‘Pathway-based prediction of tumor outcome for environmental PAH mixtures’. In this study, they developed a mechanism-based approach for prediction of tumor outcome after dermal exposure to PAHs and environmental PAH mixtures. Their model was successfully utilized to distinguish early regulatory events during initiation linked to tumor outcome and shows the utility of short-term initiation studies in predicting the carcinogenic potential of PAHs and PAH mixtures.
“Dr. Waters and her group have proven to be of great value in not just the interpretation of extremely large and complicated data sets, but also in the “front-end” study design, which results in enrichment of the subsequent data obtained.”
– Dr. David Williams, OSU SRP Center Director
A new monthly seminar series will be held on the third Thursday of each month to highlight the research of the trainees. The presentations begin at 12 noon and will be in the Hallie Ford Center room 115 on the OSU Campus. Our partners at the Pacific Northwest National Laboratory (PNNL) will participate via video conferencing. All are welcome to the presentations.
Mobile maps, apps, and augmented reality for personalized air quality informatics
Andy Larkin, Ph.D. candidate, SRP Trainee
Dept. of Environmental and Molecular Toxicology
Human in vivo kinetics and dynamics of high molecular weight PAH, dibenzo(def,p) chrysene, utilizing liquid sample accelerator mass spectrometry
Erin Madeen, Ph.D. candidate, SRP Trainee
Dept. of Environmental and Molecular Toxicology
If you have questions or need special assistance, please contact Naomi Hirsch, 541-737-8105.
The Tanguay group uses the embryonic zebrafish model to demonstrate the utility of high throughput screening for toxicology studies. The group evaluated the 1060 US EPA ToxCast Phase 1 and 2 compounds on 18 distinct outcomes. With four doses for each compound the group generated a dizzying number of data points highlighting the importance of bioinformatics analysis in these types of studies. The study shows how it is now possible to screen many of the tens of thousands of untested chemicals using a whole animal model in which one can literally see developmental malformations. —Gary W. Miller
There are tens of thousands of man-made chemicals in the environment; the inherent safety of most of these chemicals is not known. Relevant biological platforms and new computational tools are needed to prioritize testing of chemicals with limited human health hazard information. We describe an experimental design for high-throughput characterization of multidimensional in vivo effects with the power to evaluate trends relating to commonly cited chemical predictors. We evaluated all 1060 unique U.S. EPA ToxCast phase 1 and 2 compounds using the embryonic zebrafish and found that 487 induced significant adverse biological responses. The utilization of 18 simultaneously measured endpoints means that the entire system serves as a robust biological sensor for chemical hazard. The experimental design enabled us to describe global patterns of variation across tested compounds, evaluate the concordance of the available in vitro and in vivo phase 1 data with this study, highlight specific mechanisms/value-added/novel biology related to notochord development, and demonstrate that the developmental zebrafish detects adverse responses that would be missed by less comprehensive testing strategies.
Learn more about Tanguay’s zebrafish research
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.
“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]
Learn more about PAHs from the Superfund Research Program web site.