toxcast

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.

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.

EPA: Taking Action on Toxics and Chemical Safety

For all of their beneficial uses, chemicals can also pose potential risks: manufacturing them can create emissions and waste, and exposure to them can impact our health and the environment. One of EPA’s highest priorities is making sure our children, our homes, and our communities are safer from toxic chemicals.

Last October, Administrator McCarthy asked EPA employees to log into GreenSpark, our internal online employee engagement platform, and share stories of the innovative and collaborative work that they are leading to take action on toxics and chemical safety. I’d like to share some of their exciting work with you.

CHEMdna

Developing Innovative Science: EPA’s Office of Research and Development, with support from the Office of Chemical Safety and Pollution Prevention, is working to change the way we evaluate chemical safety to make it quicker and easier to understand the potential toxic effects of chemicals on human health and the environment. Here are a couple of great examples:

We’ve developed the Toxicity Forecaster (ToxCast), which uses automated chemical screening technologies to understand the effects of chemical exposure. ToxCast evaluated more than 2,000 chemicals from a broad range of sources, including potentially “green” chemicals that could be safer alternatives to existing chemicals. Based on this work, the new Interactive Chemical Safety for Sustainability (iCSS) Dashboard provides a user-friendly web-based application that offers product manufacturers, researchers, and others a faster way to evaluate the safety of chemicals. ToxCast data is also being applied in the Endocrine Disruptor Screening Program to target priority chemicals and avoid expensive and time-consuming animal testing methods.

CHEMzebraAnother innovative approach that our Office of Research and Development scientists are developing is a program using zebrafish to rapidly screen standard chemicals and their green alternatives for their ability to affect developing embryos.

CHEMHorizMaking Use of Data: Several EPA programs work daily to make sure the public, communities, regulators and industry have access to data that keeps people safe. EPA’s Office of Environmental Information is working to integrate facilities data relating to chemical plants and their relationship to communities. This work, in collaboration with the Department of Homeland Security, Department of Labor, and other agencies supports Executive Order (EO) 13650: Improving Chemical Facility Safety and Security and helps inform planning and emergency preparedness and response for safer communities.

Providing Technical Assistance: Artisanal and small scale gold mining is the largest man-made source of mercury. Mercury exposure at high levels can harm the brain, heart, kidneys, lungs, and immune system. To reduce airborne mercury emissions from artisanal and small scale gold mining, EPA’s Office of International and Tribal Affairs worked with Argonne National Laboratory to develop a simple mercury capture system (MCS).

Data collected during site visits in the Amazon and high Andes areas of Peru showed that in shops with the installed MCS technology, mercury vapor concentrations were reduced by 80% compared to shops without the technology. We are now working to raise awareness of the mercury capture technology in developing countries through partnerships with key organizations.

CHEMpeoplestandingWorking in Collaborative Partnerships: Working with local partners including the New York State Department of Environmental Conservation (NYSDEC), EPA Region 2 is helping improve chemical management in high school and college laboratories and the adoption of green chemistry practices through hands-on training for high school science teachers and college faculty in New York. More than 200 teachers from 138 school districts and 29 college and university faculty have participated in trainings, and faculty participants have produced ten case studies on implementing green chemistry practices in college and university settings. This is just one example of the work that our Office of Chemical Safety and Pollution Prevention is leading along with our Regional Offices to promote innovations in green chemistry.

Please join me in thanking all of the talented, dedicated employees who have contributed to these and other amazing activities that improve the human health and environment of the communities we serve.

Editor's Note: The views expressed here are intended to explain EPA policy. They do not change anyone's rights or obligations.

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.

EPA: Taking Action on Toxics and Chemical Safety

The following was originally posted on EPA Connect, the Official Blog of EPA Leadership.

Innovative-Research

By Gwen Keyes Fleming

For all of their beneficial uses, chemicals can also pose potential risks: manufacturing them can create emissions and waste, and exposure to them can impact our health and the environment. One of EPA’s highest priorities is making sure our children, our homes, and our communities are safer from toxic chemicals.

Last October, Administrator McCarthy asked EPA employees to log into GreenSpark, our internal online employee engagement platform, and share stories of the innovative and collaborative work that they are leading to take action on toxics and chemical safety. I’d like to share some of their exciting work with you.

Developing Innovative Science: EPA’s Office of Research and Development, with support from the Office of Chemical Safety and Pollution Prevention, is working to change the way we evaluate chemical safety to make it quicker and easier to understand the potential toxic effects of chemicals on human health and the environment.

Read the rest of the post.

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

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.

Advancing Species Extrapolation: EPA’s “Sequence Alignment to Predict Across Species Susceptibility”

By Carlie A. LaLone, Ph.D.

Graphic illustration of molecule with shapes of animals in front. I have been working with a team of EPA colleagues to create an on-line tool, Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS), that will help both researchers and regulators readily use available protein sequence and structural knowledge to extrapolate chemical toxicity information across species. When complete, this innovative research tool will help predict potential chemical susceptibility to wildlife, including plants and animals.

Through the years, scientists have come to understand that the sensitivity of a species to a chemical is determined by a number of factors including chemical exposure, absorption, distribution, metabolism, elimination, and the organism’s life-history. Additionally, an important consideration for species susceptibility is the presence or absence of proteins that interact with chemicals. Those that interact can be referred to as “protein targets.” Researchers take advantage of such protein targets to develop or improve drugs and/or pesticides, however it is known that chemicals in the environment can interact with these protein targets in other non-target species leading to unintended adverse effects.

Chemicals such as pharmaceuticals and pesticides have relatively well-defined protein targets and a majority of these proteins are curated in the National Center for Biotechnology Information (NCBI) protein database maintained by the National Library of Medicine at the National Institutes of Health. The database contains information on millions of proteins from thousands of different species. Using this massive and continually expanding database, SeqAPASS helps identify whether a protein target is available for a chemical to act upon in a particular species, which could therefore potentially disrupt important biological processes. This method can be used, for example, to explore whether a pesticide developed to control a pest species would be predicted to affect other, non-target species such as pollinators or protected (threatened or endangered) species.

Overall, SeqAPASS provides us with a fast, efficient screening tool. Using it, we can begin to extrapolate toxicity information from a few model organisms (like mice, rats, zebrafish, etc.) to thousands of other non-target species to evaluate potential chemical susceptibility.

SeqAPASS provides an example of how EPA Chemical Safety for Sustainability researchers are leading the effort to usher in a new generation of toxicology practices that aspire to reduce the number of animals used, decrease costs, and increase the efficiency of chemical toxicity testing. The 21st century chemical toxicity testing strategy incorporates these ideals and has given rise to adverse outcome pathway (AOP) development and rapid, high-throughput chemical screening programs such as EPA’s ToxCast program.

We plan to make SeqAPASS publically available later this year. I am very passionate about the work we are doing and hope that future external engagement will enhance the SeqAPASS tool capabilities and its applications. As this project continues to evolve to incorporate the latest bioinformatic technologies for protein comparisons across species, we hope that SeqAPASS can be used to inform risk assessments, particularly in instances where toxicity data is lacking.

This research has been published in Aquatic Toxicology, Philosophical Transactions of the Royal Society B and Environmental Toxicology and Chemistry. Another paper has been drafted to coincide with public release of SeqAPASS via the internet.

About the Author: Carlie LaLone is a Postdoctoral Associate for the University of Minnesota Water Resources Center in Cooperative Training Partnership with EPA’s Office of Research and Development. She is the project lead for the development of the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool.

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

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.

Advancing Chemical Testing by the Thousands

Reposted from EPA Connect, the official blog of EPA leadership.

By Bob Kavlock

Bob Kavlock PortraitStudying thousands of chemicals at a time with the use of high-tech computer screening models and automated, often robot-assisted processes sounds like science fiction. But it’s not. EPA scientists are doing just that, leading the advancement of “high-throughput screening,” fast, efficient processes used to expose hundreds of living cells or isolated proteins to chemicals and then screen them for changes in biological activity—clues to potential adverse health effects related to chemical exposure.

This scientific advance is positioned to transform how we understand the safety of chemicals going forward. Twenty years ago, using high-throughput screening to test chemicals for potential human health risks seemed like technology that belonged in a science fiction television series rather than in real life.

Back then there were several large data gaps that would not allow us to extrapolate from the isolated biological changes we observe on a cellular level to adverse human health effects. However, through our computational toxicology (CompTox) research, which integrates, biology,

Robotic arm moving samples for screening

Robotic arm moves samples for automated chemical screening.

biotechnology, chemistry, and computer science, that is changing. We are helping to transform the paradigm of chemical testing from one that relies almost solely on expensive and time-consuming animal testing methods to one that uses the full power of modern molecular biology and robotics.

A significant part of this effort is the Toxicity Forecaster (ToxCast), launched in 2007. ToxCast allows us to prioritize potentially toxic chemicals for more extensive testing as well as giving us the opportunity to test newer, possibly safer alternatives to existing chemicals. By 2013, we evaluated more than 2,000 chemicals from industrial and consumer products to food additives using more than 500 high-throughput screening assays.

Read the rest of the post. 

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

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.

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.

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.

Science Matters: Predicting the Future of Children’s Health

Children's Health MonthTo observe October as Children’s Health Month, we will periodically post Science Matters feature articles about EPA’s children’s health research here on the blog.  Learn more about EPA’s efforts to protect children’s health by going to www.epa.gov/ochp.


According to the Centers for Disease Control and Prevention, approximately one in every 33 babies born in the United States is born with a birth defect. Birth defects can heighten the risk of long-term disability as well as increase the risk of illness, potentially impacting a child for the rest of his or her life. Unfortunately, the causes of most birth defects are unknown.

EPA researchers are tapping powerful, high-tech computer systems and models to better determine how prenatal exposure to environmental factors might impact embryo and fetal development. Working on EPA’s Virtual Embryo (v-Embryo™) project, they create computer models of developing body systems and combine them with data from a number of EPA studies and toxicity databases to “virtually” examine the effects of a variety of prenatal exposures.

Virtual Embryo simulates how chemicals and pesticides, including those that disrupt the endocrine system, interact with important biological processes that could disrupt fetal development.  The chemicals used in simulations are identified by EPA’s Toxicity Forecaster as having the potential to affect development.

The predictions from the computer simulations need to be further tested against non-virtual observations. However, the models provide scientists with a powerful tool for screening and prioritizing the chemicals that need to be more closely examined, greatly reducing the cost and number of targeted studies needed.

“We’ve built small prototype systems, now what we want to do is move into complex systems models that will be more relevant to environmental predictions,” said Thomas B. Knudsen, Ph.D., an EPA systems biologist who is leading the project.

Virtual Embryo models have focused on blood vessel development and limb development, but are being expanded to include early development of the male reproductive system, which is known to be particularly sensitive to endocrine disrupting chemicals.

Knudsen says that having more models is important because different chemicals can affect biological systems in various ways. Luckily, the time it takes to develop new models decreases as researchers’ model-developing knowledge grows.

“The important challenge for us is to try to integrate some of this work with other issues of broad importance to children’s health,” said Knudsen. “We’re focused primarily on embryonic development, but a person doesn’t stop developing at birth. We have to take what we are learning from the embryo and extend that information into life stages beyond birth.”

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

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.

Science Wednesday: EPA Teams Up with L’Oréal to Advance Research

Each week we write about the science behind environmental protection. Previous Science Wednesdays.

By Monica Linnenbrink

Now I can look great and feel good about using my favorite mascara. Why? Because EPA researchers are collaborating with L’Oréal to help end the need for animal testing. EPA is using its ToxCast program to screen chemicals to understand their potential impact on biological processes that may lead to adverse health effects.

EPA’s ToxCast program screens chemicals using state-of-the-art scientific methods (including robots!) to learn how these chemicals affect the human body. We’ve never tested chemicals found in cosmetics before, so this partnership with L’Oréal will expand the types of chemicals that ToxCast screens.

L’Oréal is providing EPA $1.2 million in collaborative research funding plus safety data from a set of representative substances used in cosmetics, which will expand the types of chemical use groups assessed by ToxCast. EPA will then compare its ToxCast results to L’Oréal’s data to determine if ToxCast is appropriate for use in assessing the safety of chemicals used in cosmetics.

Traditional chemical toxicity testing is very expensive and time consuming, so many chemicals in use today have not been thoroughly evaluated for potential toxicity. ToxCast, on the other hand, is able to rapidly screen thousands of chemicals via hundreds of tests and provide results that are relevant to various types of toxicity.

As someone who uses L’Oréal products, I’m excited that they are taking the initiative to better understand how chemicals in their cosmetics might interact with my body’s natural processes. I’m also excited to hear that they are exploring new ways of testing that could end the need for animal testing. Since I use their products on my face, it’s nice to know that L’Oréal is working to ensure their products are safe to use and are working to do this in an animal friendly way.

About the author: Monica Linnenbrink is a Public Affairs Specialist in EPA’s Office of Research and Development.

Editor’s Note: The opinions expressed in Greenversations 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.

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.

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.

Science Wednesday – Apps for the Environment: The New Way of Communicating Science and Information

Each week we write about the science behind environmental protection. Previous Science Wednesdays.
By Jing Zhang

Want to know the weather tomorrow, the next movie showing, or the latest Hollywood gossip? There’s an app for that! In the age of smart phones, answers are literally at your fingertips on your iPhone or Android device. There’s no need to scour the internet for solutions when you can simply download an app that will gather the relevant information for you in a user-friendly application on your phone.

Working in EPA’s Office of Research and Development, I constantly hear of the developments and data that Agency researchers and scientists have produced. These scientists work diligently year around on protecting the environment and human health as outlined in Administrator Lisa P. Jackson’s Seven Priorities. What better way is there for communicating the resources and discoveries of EPA researchers than in an easy-to-use app on your mobile device?

challengebanner_MThe EPA Apps for the Environment Challenge invites software developers to use EPA data to develop apps so the public can understand or protect the environment in their daily lives. Want to know the air quality where you live or which cars have the least amount of greenhouse gas emissions? There could be an app for that!

EPA has a lot of data that is publicly available. This data includes information from the Toxic Release Inventory which tells you facilities that dispose of or release toxic chemicals, real time air quality monitoring, green vehicle guide that gives environmental performance guides for vehicles, a Superfund website, and chemical toxicity information from the ToxCast database. Because these datasets are overwhelming for those with less technical and scientific knowledge like me, EPA held a series of webinars where data owners explained the information.

If you’re like me and don’t know the first thing about developing an app, you can still participate by submitting ideas for apps. These ideas are useful in providing developers and researchers a window of insight into the needs and wants of the public.

For more information and rules, visit the Apps for the Environment website. The deadline for submissions is September 16. In the meantime, you can find out the latest information on Twitter, just search #greenapps.

About the Author: Jing Zhang is a student services contractor working with the science communications team in EPA’s Office of Research and Development.

Editor’s Note: The opinions expressed in Greenversations 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.

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.

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.

Women in Science: Ann Richard

By Marguerite Huber

I have always envisioned myself working at EPA—out saving the planet. As a current intern, getting to interview those who actually do is particularly exciting to me.

Enter Ann Richard, an EPA computational chemist.

To get where she is today, Ann followed her talents in math and science to a PhD in physical chemistry. Before her post doc and EPA, she had stints working at an airport, and even an amusement park. But now, “I appreciate working for an agency that has the component of benefiting the public,” stated Ann while speaking of the EPA. She has been working here since 1987 (which is hard for me to imagine since that is longer than I have even been alive).

Today, Ann works in an area termed “chem-informatics,” a cross between chemistry and computer science that focuses the construction and use of chemical databases to address problems crossing the disciplines of chemistry, biology, and toxicology. Her greatest achievement has been the Distributed Structure-Searchable Toxicity (DSSTox) Public Database Network, sharing important information about chemicals with the public. It has been used by government, academia, and scientists worldwide. Furthermore, Ann manages the chemical informatics component of the ToxCast and Tox21 projects, which provide a foundation for improved toxico-chemoinformatics and structure-activity relationship capabilities in predictive toxicology.

In her career, Ann devotes a large effort to communicating across different disciplines. “You have to put yourself in the audience’s place and it is not easy, you have to work at it,” she said. In the end she finds it rewarding and worthwhile to try to bridge disciplines, even if she has to spend half a day on creating one perfect PowerPoint slide.

Her favorite part of her job is meeting amazing people from different countries. Ann has the opportunity to become acquainted with many talented people within her field worldwide. She derives a lot of satisfaction from knowing she has reached the point where she has gained the respect of her peers in her field.

Ann’s inspiration comes from ordinary people who do extraordinary things. While growing up, she never remembered being discouraged about being in the science field. If she was, it only made her more determined to succeed. “Don’t be intimidated,” are her wise words towards girls everywhere. In that case, I am going to pretend that toxico-chemoinformatics does not sound so intimidating!

About the author: Marguerite Huber is an intern from Indiana University currently working with the science communication team in EPA’s Office of Research and Development.

Editor’s Note: The opinions expressed in Greenversations 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.

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.

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.