Congratulations to the lab of Dr. Robert Tanguay, Project 3 Leader!
The manuscript, Multidimensional In Vivo Hazard Assessment Using Zebrafish, accepted October 2013 in Toxicological Sciences, has been published in the January 2014 journal (in the Safety Evaluation section) with an Editor’s Highlight.

January 2014 Toxicological Sciences journal
January 2014 Toxicological Sciences journal

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

Abstract

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.

rb_210_img3Learn more about Tanguay’s zebrafish research

 

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).

 

The OSU Superfund Center’s Community Engagement Core is fortunate to have an established partnership with the Confederated Tribes of the Umatilla Indian Reservation (CTUIR).

The recently produced CTUIR – OSU 2012-2013 Newsletter shares the background, summary, and findings of a collaborative research project to understand polycyclic aromatic hydrocarbon (PAH) exposure related to smoked salmon.

salmon
Salmon fillet

Salmon, a first food, is important to the subsistence of Native Americans living in the Pacific Northwest. Smoking salmon is one of the traditional ways to preserve this seasonally abundant food and make it available year round.

People can be exposed to PAHs from breathing contaminated air or eating smoked foods although many other exposure pathways exist.

Each volunteer wore air sampling equipment and turned it on every time they went into the smoking structures.

The data showed the air in the tipi and the smoke shed contained PAHs.

tipi        tipifire       smokehouse

Pictured above from left: Traditional tipi, volunteer tending the fire in the tipi wearing an air sampler in black bag on his hip, traditional smoke shed.

The findings from this study were published in the Journal of Agricultural & Food Chemistry.
B, Harris S, Matzke M, Cardenas A, Waters K, Anderson K. (2012). Effect of Native American fish smoking methods on dietary exposure to polycyclic aromatic hydrocarbons and possible risks to human health. Journal of Agricultural & Food Chemistry, 60(27), 6899-6906. doi: 10.1021/jf300978m

Indigenous cultures perceive the natural environment as an essential link between traditional cultural practices, social connectedness, identity, and health. Many tribal communities face substantial health disparities related to exposure to environmental hazards. We asked 27 volunteers who were members of the CTUIR their opinions on meanings of health and how their environment interacts with their health.

The findings from the focus group discussions were published in the journal Environmental Justice.

Schure M, Kile ML, Harding AK, Harper B, Harris S, Uesugi S, Goins T. Perceptions of environment and health among community members of the Confederated Tribes of the Umatilla Indian Reservation.  Environmental Justice. June 2013, 6(3): 115-120. doi:10.1089/env.2013.0022.

In addition, the CTUIR – OSU 2012-2013 Newsletter shares recently appointed members of the Tribal Advisory Board.

We hope you enjoy the newsletter!

This year Carlos Manzano received his PhD from the Simonich lab (Project 5), and moved on from the OSU Superfund Research Center (SRC).

His research with the SRC focused on the development of new analytical techniques for the analysis of PAHs in complex environmental samples. With Dr. Simonich, he developed an analytical method using comprehensive two dimensional GC (GCxGC/ToF-MS) to analyze around 90 PAHs in one chromatographic run, using a highly orthogonal column combination.  For his PhD thesis, they wanted to focus specifically on oxy-PAHs and alkyl-PAHs, which were part of other SRP projects at OSU. They got some standards from other groups, and regularly collaborated with other cores and projects.

During his training, he received a prestigious 2012 Student Paper Award from the American Chemical Society (ACS).   His work was published in ES & T.

Manzano C, Hoh E, Simonich SM. Optimization of Column Selection for Separation of Complex Polycyclic Aromatic Hydrocarbons Mixtures using GCxGC/ToF-MSEnvironmental Science and Technology, 46, 7677-7684.

Manzano’s PhD thesis helped him get his current position. He is now holding a postdoctoral Visiting Fellowship in Canadian Laboratories, working in the Canada Centre for Inland Waters as part of the Aquatics Contaminants Research Division of Environment Canada, located in Burlington, Ontario.  His research focuses on novel methods and analysis of polycyclic aromatic compounds in oil sands sediments, precipitation and snow samples. The goals are to expand the list of PACs to match reported industry emissions and to identify new PACs that characterize atmospheric emissions from bitumen upgraders as well as dust from mining and refinery waste.

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Carlos Manzano (far right) was able to visit with members of the Simonich lab again when he came to the 2013 International Symposium on Polycyclic Aromatic Compounds (ISPAC 2013) conference at OSU from Sept. 8 – 12.

Thanks to the SRP funding and meetings I was also able to meet my
current supervisors and share with them my research interests (I met
them at SETAC Long Beach in 2012).

~Carlos Manzano

ZebrafishRobert 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.

Robert Tanguay’s leadership in utilizing  zebrafish

Robert 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 his 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].