National Center for Computational Toxicology

Which Ounces of Prevention? Predictive Toxicology Using Organotypic Models

By Shane Hutson

VPROMPT team members (left-to-right) Shane Hutson, Dmitry Markov, John Wikswo and Lisa McCawley. Photo courtesy of Vanessa Allwardt.

VPROMPT team members (left-to-right) Shane Hutson, Dmitry Markov, John Wikswo and Lisa McCawley. Photo courtesy of Vanessa Allwardt.

Everyone knows that “an ounce of prevention is worth a pound of cure,” but think about that saying’s application to environmental chemical exposure. There are tens of thousands of chemicals in common use. If we don’t prioritize that list, it quickly adds up to a few tons of prevention.

There is no doubt that prevention is the best medicine when you know exactly what needs to be prevented, but how do we know? How do we predict which chemicals are toxic – and at which exposure levels? Those questions are why I became involved in toxicology research.

For 40+ years, the gold standard for those questions has been expensive, time consuming, animal-based (primarily mice and rats) laboratory exposure studies where results are not clearly predictive of effects in humans. Are we stuck with such studies? A large number of scientists are working to answer that question with “No, we can do better.”

I became involved in this effort during a year at EPA’s National Center for Computational Toxicology. My interests lie in developmental toxicity – understanding how chemical exposures affect the developing fetus – so I worked with EPA researchers on the Virtual Embryo Project to build computational models of specific developmental events and how they go awry during chemical exposure. When combined with high-throughput screening efforts such as ToxCast, computational models do have some predictive ability. But we still have a lot to learn.

That brings me to my current efforts. I’ve teamed up with a talented group of colleagues at Vanderbilt and the University of Pittsburgh to found VPROMPT – Vanderbilt-Pittsburgh Resource for Organotypic Models for Predictive Toxicology.

The word “models” pops up again here, but these are not computational. VPROMPT is using diverse expertise in biology, chemistry, physics and engineering to grow “models” that are three dimensional assemblies of multiple human cell types in carefully perfused microfluidic chambers. Such models are designed to be “organotypic,” that is, matching the microenvironment that cells experience in a living organ. This will enable our model to more closely mimic human responses to chemical exposure.

Our plans focus on developmental toxicity with models for liver, mammary gland, developing limb, and fetal membrane. The latter is a key model for investigating chemicals’ links to preterm birth.

VPROMPT is just getting started. We have lots to do in terms of engineering, fabricating and validating our models, but we also have high hopes for their predictivity. Will they help us make sure we only need that reasonable ounce of prevention? Stay tuned and let’s see where the science takes us!

About the Author: Shane Hutson is an Associate Professor of Physics at Vanderbilt University and Deputy Director of the Vanderbilt Institute for Integrative Biosystems Research & Education.

Editor's Note: The opinions expressed here are those of the author. They do not reflect EPA policy, endorsement, or action.

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EPA Researchers Win Best Toxicological Paper Awards

EPA scientists Yong Ho Kim, Christina Powers, and Russell S. Thomas

EPA scientists Yong Ho Kim, Christina Powers, and Russell S. Thomas were recognized by the Society for Toxicology.

By Dina Abdulhadi

EPA researchers will be honored March 22, 2015 at the Society of Toxicology’s 54th annual meeting and ToxExpo in San Diego, CA for their work to advance understanding of the effects of chemicals on human and environmental health. Having worked in a toxicology lab at EPA for the past year, I can appreciate the significant amount of hours and effort that go into producing publishable scientific work.

The first authors on the papers receiving the honors are Russell S. Thomas, Director of EPA’s National Center for Computational Toxicology, Yong Ho Kim and Christina Powers.

Thomas and his co-authors won the Best Paper in Toxicological Sciences Award. Their work used risk assessment models to understand how chemicals affect the way our genetic information translates into molecules and results in cancer and non-cancer effects. This type of so-called “omics” data (such as transcriptomics data) can be used to help make decisions on regulating chemicals. The paper, “Temporal Concordance between Apical and Transcriptional Points of Departure for Chemical Risk Assessment” was published in Toxicological Sciences, the official journal of the Society of Toxicology.

Kim and Powers each received a Best Postdoctoral Publication Award, provided to early-career scientists for their contributions in toxicology.

Kim’s paper addressed how the size of particulate matter, an air pollutant from peat fires, may affect the type of health impact. Larger particles were linked to respiratory effects, while smaller particles were linked to cardiovascular effects. The paper, “Cardiopulmonary Toxicity of Peat Wildfire Particulate Matter and the Predictive Utility of Precision Cut Lung Slices,” was published in Particle and Fibre Toxicology.

The study also found a way to decrease the animals needed for an experiment. That’s a big plus for both the effort to reduce the use of animals in research and cost. Cultured lung tissue slices (ex vivo) of an animal produced similar lung toxicity data when compared to a whole animal (in vivo).

Powers received an award for a paper that connects research planning to risk assessments of certain chemicals in the environment. The research focused on multi-walled carbon nanotubes, which are used in a variety of consumer products as flame retardants. The paper, “Sparking Connections: Toward Better Linkages between Research and Human Health Policy — An Example with Multiwalled Carbon Nanotubes” is published in Toxicological Sciences.

The Society of Toxicology (SOT) will formally award the researchers at an awards ceremony. SOT is an organization of over 7,600 scientists whose goal is to create a safer and healthier world by advancing the science of toxicology.

If you are attending this year’s Society of Toxicology annual meeting, I encourage you to find out more about EPA’s advances in toxicology research. EPA’s research will be featured during SOT sessions, symposia, workshops, platform presentations, poster sessions and at EPA’s booth in the exhibit hall. To find out when EPA’s research will be featured at SOT, you can visit EPA’s SOT web page at: For more information on the awards and the Society of Toxicology, check out the press release.

About the Author: Dina Abdulhadi is a student contractor currently working with the science communication team in EPA’s Office of Research and Development.

Editor's Note: The opinions expressed here are those of the author. They do not reflect EPA policy, endorsement, or action.

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Release the Data! New Chemical Data, Workshops, and Challenges

By Matthew T. Martin

Scientist prepares a well-plate for high-throughput screening.

Scientist preparing a well-plate for high-throughput screening.

Ever open that cabinet under the kitchen sink, grab that bright blue bottle of window cleaner and wonder exactly what sort of chemicals are floating around in it? Many of you have at one time or another, and for those of you who have never given it a second thought rest assured that my colleagues and I at EPA are dedicated to identifying and categorizing all of the chemicals we might be exposed to on any given day. However, due the expensive, time-consuming process of traditional testing, which assesses one chemical at a time, only a small fraction of the tens of thousands of chemicals currently in commerce have been adequately assessed for potential human and environmental health risks.

To close this data gap and better evaluate potential health risks, we have worked hard in recent years to accelerate the pace of chemical testing. I am proud to say that we have now completed phase two of the multi-year Toxicity Forecaster (ToxCast) project and are publically releasing ToxCast data on 1,800 chemicals evaluated in over 700 high-throughput screening assays. This is a significant accomplishment that we want to share with the scientific community.

The new data is accessible through the new interactive Chemical Safety for Sustainability (iCSS) Dashboard, a web-based application for users to access and interact with the data freely at their own discretion. Users can select the chemicals and data of interest and then score the information to help inform chemical safety decisions.

As part of the data release, I hope the scientific community will take advantage of this new windfall of data and become involved in the ToxCast project by participating in the Predictive Toxicology Challenges. The first two challenges of the series, available through TopCoder and InnoCentive crowd sourcing technology, will ask the scientific and technology community to develop new algorithms to predict lowest effect levels (LELs) of chemicals using the new ToxCast data. Winners will receive monetary prizes to help fund their own planned research, and their solutions will help us determine innovative ways to use ToxCast data to inform decisions made about the chemical safety.

Also, beginning January 14,we are also hosting several stakeholder outreach workshops and webinars to address potential challenges with data translation, accessibility, and any other troubleshooting issues that might arise during the initial data launch. This is an opportunity for the scientific community to provide input on data usage and offer immediate feedback about the new data and the iCSS dashboard.

About the author: Matthew T. Martin is a research biologist within EPA’s National Center for Computational Toxicology, where he is part of the ToxCast team and leads the CSS task for developing predictive models of toxicity using high-throughput screening data. He also serves as the project lead for developing the new CSS Dashboard Web Application.

Editor's Note: The opinions expressed here are those of the author. They do not reflect EPA policy, endorsement, or action.

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EPA Scientists Presented Open Science at White House

By Tina Bahadori

From weather forecasts, air quality advisories, and portable GPS navigation devices, to waterfowl migration, and the mapping of the human genome, the use of government and government-supported science and data have vastly improved our lives. They have also sparked countless new private businesses and industries leading to economic growth and opportunity for innovators and entrepreneurs in every region of the country.

Recognizing the power and potential of such Open Science, on June 20, 2013 the White House invited four EPA scientists—Drs. Richard Judson, Keith Houck, Matt Martin, and Ann Richard—to present research posters describing their efforts to provide public access to massive amounts of data from chemical safety studies. The scientists presented their posters after the White House’s “Champions of Change” award ceremony. The award ceremony recognized 13 Champions of Change for their efforts to provide the public access to innovative science.

In addition to the 13 Champions of Change, the White House selected 12 scientists (including the EPA researchers) to present posters describing their vision and commitment to Open Science.

EPA scientists at the White House poster session.

EPA scientists Ann Richard and Matt Martin at the White House poster session.

The select group of 25 was chosen from hundreds of nominations submitted to the White House’s request for innovative Open Science leaders. The White House event highlighted outstanding individuals, organizations, and research projects promoting and using open scientific data and publications to accelerate progress.

To exemplify Open Science work, the four EPA scientists presented how they are using advances in computational toxicology to provide open and accessible chemical safety data to help better protect human health and the environment. Each of the EPA scientists are working to harness the power of computer science and innovative new chemical safety assessment methods and tools to provide open, transparent public access to chemical information. For example:

  • Dr. Matt Martin leads a team of Agency scientists and partners who developed the Toxicity Reference database (ToxRefDB). ToxRefDB contains 30 years and $2 billion worth of pesticide registration studies. The database allows scientists and others to search and download thousands of toxicity testing results on hundreds of chemicals that were previously only available on paper or microfiche.
  • Dr. Ann Richard is the leader behind another open, accessible database, the Distributed Structure-Searchable Toxicity Database (DSSTox). DSSTox provides open-access to information on the physical and structural properties of chemicals and links this information to toxicity potential. This is key information for assessing the potential risk of chemicals to human health and the environment.
  • Dr. Richard Judson leads a team of scientists who developed the Aggregated Computational Toxicology online Resource (ACToR). ACToR is EPA’s online warehouse of all publicly available chemical data aggregated from more than 1,000 public sources on more than half a million chemicals. ACToR can be used to query a specific chemical and find available public hazard, exposure, and risk assessment data as well as previously unpublished studies related to cancer, reproductive, and developmental toxicity.
  • Dr. Keith Houck is the driving force behind EPA’s Toxicity Forecaster (ToxCast), a research program advancing the use of automated, rapid chemical tests (called “high-throughput screening assays”) to screen thousands of chemicals in more than 650 assays for toxicity potential. This includes the development of the ToxCast Database (ToxCastDB) which provides publicly accessible, searchable, and downloadable access to all the screening data generated by ToxCast.

These four scientists have led the effort to democratize access to knowledge and information and level the playing field for all those involved and interested in protecting public health and the environment. By doing so, they exemplify the spirit of Open Science celebrated by President Obama’s Champions of Change program.

About the Author: Tina Bahadori, Sc.D. is the National Program Director for EPA’s Chemical Safety for Sustainability research program.  Learn more about her on EPA’s Science Matters: Meet our Scientists web page.

Editor's Note: The opinions expressed here are those of the author. They do not reflect EPA policy, endorsement, or action.

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