Exciting Times for Toxicology: Creating New Predictive Models

By Dr. James H. Johnson, Jr.

image of a computer chip with wires coming offNext week, a number of my EPA colleagues will join toxicologists from across the world in San Diego, CA for the Society of Toxicology’s 54th Annual Meeting and “ToxExpo.” The gathering will feature more than 160 scientific sessions and 2,400 poster presentations, providing important insights into how the study of chemical toxicity can better protect public health and the environment.

Although this particular conference has been going on for more than half a century, these are exciting times for toxicologists. And I’m proud to say that EPA is helping lead the way.

Our researchers and their partners are ushering in a new generation of chemical testing and screening methods, developing “virtual embryos” and other complex models that use scientific data, computer power, and sophisticated calculations to mimic the potential effects of toxins on actual tissues and organs. With other federal partners, they are using robots to advance fast and efficient high-throughput-screening assays, greatly accelerating the pace of chemical screening while dramatically reducing the use of laboratory animals—and costs.

We are also supporting innovative, world-class research through our Science to Achieve Results (STAR) grant program. New STAR grants will be announced at the Society of Toxicology’s Annual Meeting (March 25 from 5:00 p.m. to 7:00 p.m.) when we will hold a kickoff meeting of our newly established Organotypic Cell Models for Predictive Toxicology Centers. This research is part of EPA’s Chemical Safety for Sustainability research program.

The research Centers are being established to develop three-dimensional models, sometimes called “organs-on-a-chip,” which can be used to replicate human biological interactions within tissues and organs. When developed and evaluated, these models known as Organotypic Culture Models (hence the name of the Centers) will help investigate the toxic effects of chemical substances. Such models are established from isolated cells or from tissue fragments, bridging the gap between conventional, single-layered cell cultures and whole-animal systems.

What the Centers learn will be used to develop computational models that can help predict responses and outcomes from chemical exposures, such as human disease and long-term effects on tissue and organ growth. The models they develop will also mimic biological functions such as a metabolic process.

If you are attending the Society of Toxicology’s 54th Annual Meeting and “ToxExpo” this year, you are welcome to come to the March 25th grantee kick-off meeting.

The impact of all this activity is a new wave of toxicology testing that is faster, more efficient, and far less costly. This will help us at EPA with our number one priority: protecting human health and the environment. That’s some pretty exciting news.

About the Author: Dr. James H. Johnson Jr. is the Director of EPA’s National Center for Environmental Research, which runs the Agency’s Science to Achieve Results (STAR) program as well as other grant, fellowship, and awards programs that support high quality research by many of our nation’s leading scientists and engineers.

Please note: We’ll be sharing more about EPA participation at the annual Society of Toxicology Meeting throughout next week, so please check back to learn more.

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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MCnest: Fly Away Home

Flying geese in a "V" formation against a sunset. By Thomas Landreth 

While recent winter weather storms may suggest otherwise, we are getting closer to the time that birds in this hemisphere begin their journey northward. Just like in the 1996 movie, Fly Away Home, last year’s crop of fledglings will begin their first return journey toward mating and nesting grounds.

However, a host of different variables can affect the success of these new populations year after year. Fly Away Home highlights how habitat loss might threaten migrating geese. But what about other, perhaps less obvious factors, such as those affecting bird breeding cycles?

EPA researchers have been working on a digital, easy-to-use model called the Markov Chain Nest Productivity Model, or MCnest, that estimates the impact of pesticide exposures on the reproductive success of bird populations.

MCnest combines existing avian (bird) toxicity test results, species life history information, and the timing of pesticide application(s) with breeding seasons to quantitatively estimate the potential impact of pesticide exposure on annual bird reproductive success.

McNest developer Matthew Etterson said, “This model is an important first step in moving avian pesticide risk assessment forward.”

Future MCnest results that indicate potential adverse affects on avian reproduction may be cited in Agency orders to regulate pesticide use under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA), and in support of the Endangered Species Act (ESA). The ESA is administered by the U.S. Fish and Wildlife Service and the National Marine Fisheries Service, and requires federal agencies to ensure that any action they authorize won’t jeopardize listed threatened or endangered species.

Though MCnest is still in its early stages of development, work continues on a more advanced version that will improve exposure estimates and more realistically describe the length of avian breeding seasons.  The researchers are also applying the concepts behind MCnest to develop a model for fish, and a similar model is possible for mammals.

As its capability grows to take in data about more species, MCnest can play a greater role in EPA’s approach to ecological risk assessment. In time, MCnest may provide a greater understanding of pesticides and their impact on wildlife and our environment.

Click here for more information on MCnest, data libraries and program instructions.

About the author: Thomas Landreth is a student services contractor working with EPA’s Office of Research and Development.

Editor’s note: for more information on McNest and other EPA ecosystems-related research, please see the latest edition of our newsletter, “Science Matters.”

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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Green Chemistry Class at Rio+20

By Bicky Corman

On Saturday, June 16, I had the pleasure of participating in a panel on Green Chemistry hosted by the United National Global Compact (UNGC) and United National Industrial Development Organization (UNIDO).

In his introduction, UNIDO’s Heinz Luenenberger warned us it was likely to be wonky, but it was actually quite energetic. The speakers included: Dr. Professor Rodrigo Souza, of Federal University of Rio de Janeiro, a green chemistry academic expert; Neil Hawkins from Dow; Peter White from Procter & Gamble; and Jorge Soto of Braskem. There was a palpable enthusiasm from all sectors on the huge transformations possible from understanding and applying green chemistry, which is a game-changer.

Green Chemistry, pioneered 20 years ago by Paul Anastas and John Warner, is based on the premise that toxicity and hazard are not necessary results of manufacture, use or disposal of chemicals; rather, those features are “design flaws” that can be resolved with thoughtful design and understanding of the habits of particular molecules. The application of green chemistry spurs innovation, as manufacturers rush to create these green alternatives. Doing so will save them money in production, use and disposal, and it will help them produce compounds that are safer for their workers and for the ultimate users. Green Chemistry is only gives manufacturers a competitive advantage; it’s also an important ingredient if we wish to promote economic growth and environmental protection.

When it was my turn to present, I had the honor of speaking about the contributions EPA has made in the field of Green Chemistry. EPA has been advancing green chemistry through research, collaboration and recognition for many years.

EPA’s Presidential Green Chemistry Award, which is given to honorees in industry, academia and NGOs, has stimulated innovative design of chemical products in both big and small companies. Dr. Hawkins commented that the receiving these awards has been quite meaningful to Dow, and we’ve seen what the winning technologies have accomplished: Since the program began, participating companies and academic institutions have together eliminated 544 million kilograms of hazardous chemicals and solvents each year, and are eliminating each year about 158 million kilograms of carbon dioxide releases to air.

Throughout the discussion the audience members were very engaged, and commented that the various presentations made them optimistic. I have to agree; this was certainly the most enjoyable chemistry class I have ever attended!

About the author: Bicky Corman is the Deputy Associate Administrator for the Office of Policy at the U.S. Environmental Protection Agency.

Editor's Note: The opinions expressed here are those of the author. They do not reflect EPA policy, endorsement, or action, and EPA does not verify the accuracy or science of the contents of the blog.

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