Endocrine disrupting chemicals

Ushering In a New Generation of Chemical Screening

By Richard Judson

I work with EPA colleagues and other scientists around the world to integrate advances in biology, biotechnology, chemistry, and computer science to evaluate thousands of chemicals. Part of our research is supporting EPA’s Endocrine Disruptor Screening Program, exploring the potential for chemicals to disrupt normal growth and development in humans and other animals.

The work we do is helping usher in a new generation of faster, more efficient, and far less costly chemical screening methods. We use automated technologies, called high-throughput screening assays, to expose cells and proteins to chemicals. We then screen them to identify any that exhibited changes in biological activity that may suggest the potential for endocrine disruption.

My partners and I are excited to announce that we have recently published two papers on results of our work. We used the innovative methods described above to screen chemicals for their potential to mimic normal estrogen hormones, substances that direct development and reproduction. Exposure to chemicals that mimic estrogen pose a range of potential health risks, including birth defects and certain types of cancer.

The first paper, published in Nature Scientific Reports, describes the results of screening approximately 10,500 chemicals. The screening included 88 duplicates of the same chemicals, which validated the reliability of the assays. It also included 39 reference chemicals—those whose estrogen-receptor activity have been well established through traditional testing methods. Using the reference chemicals showed that the assays could accurately identify chemicals that were both positive and negative for their ability to mimic natural estrogens.

Robotic arm moving samples for screening

Robotic arm moves samples for automated chemical screening, part of the Tox 21 collaboration.

This paper is a product of Tox21, a federal collaboration pooling expertise and resources among EPA, the National Toxicology Program (National Institute of Environmental Health Sciences), the Food and Drug Administration, and the National Center for Advancing Translational Sciences (NCATS). Tox21 was established to study how high-throughput screening methods can be used to evaluate thousands of chemicals. These assays were run on the NCATS ultra-high-throughput robotic screening system (pictured).

The second paper (selected by the American Chemical Society’s Environmental Science and Technology journal as an editor’s choice) describes the results of screening 1,814 chemicals (including 36 reference chemicals). The screening was performed using a panel of 13 high-throughput estrogen receptor assays that use a diverse set of cell types and assay technologies.The results indicate that such a panel can accurately predict estrogenic responses. It demonstrates how the resulting data could be used for chemical prioritization as part of the Agency’s Endocrine Disruptor Screening Program.

In December 2013, we publicly released our high-throughput screening data through user-friendly web applications called interactive Chemical Safety for Sustainability (iCSS) Dashboards. I encourage anyone with an interest in this research to take a look at the data and to also participate in EPA’s Second ToxCast Data Summit. The summit is scheduled for September 29-30, 2014 in Research Triangle Park, NC.

The goal of the summit is to bring together the user community (industry, non-governmental organizations, academia, governmental agencies and more) to present their ideas for ways to use the large amount of high-throughput screening data to help inform chemical policy and regulatory decisions.

About the Author: EPA scientist Dr. Richard Judson develops databases and computer applications to model and predict toxicological effects of a wide range of chemicals. He is a member of the EPA Computational Toxicology research team where he leads the effort in bioinformatics. Dr. Judson has a BA in Chemistry and Chemical Physics from Rice University and an MA and PhD in Chemistry from Princeton University.

Information About the Papers

Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway. Ruili Huang, Srilatha Sakamuru, Matt T. Martin, David M. Reif, Richard S. Judson, Keith A. Houck, Warren Casey, Jui-Hua Hsieh, Keith Shockley, Patricia Ceger, Jennifer Fostel, Kristine L. Witt, Weida Tong, Daniel M. Rotroff,2 Tongan Zhao, Paul Shinn, Anton Simeonov, David J. Dix, Christopher P. Austin, Robert J Kavlock, Raymond R. Tice, Menghang Xia. Nature Scientific Reports

Predictive Endocrine Testing in the 21st Century Using in Vitro Assays of Estrogen Receptor Signaling Responses. Daniel M. Rotroff, Matt T. Martin, David J. Dix, Dayne L. Filer, Keith A. Houck, Thomas B. Knudsen, Nisha S. Sipes, David M. Reif, Menghang Xia, Ruili Huang, and Richard S. Judson. Environmental Science & Technology

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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Science Matters: Protecting Growth and Development

To 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. 

Children's Health MonthNormal growth and development, from conception and throughout pregnancy, to childhood and adolescence, depends on hormones.  These chemical messengers are produced by the body’s endocrine system and regulate growth, maturation, and reproduction.  

Scientists have learned that some exposures to hormone-like substances—what toxicologists refer to as endocrine disrupting chemicals (EDCs)—can be disruptive to normal health and development, leading to potentially serious disease, reproductive issues, and other abnormalities later in life. EDCs can be found in many everyday products, including some plastic bottles and containers, food from cans with certain kinds of liners, pesticides, and detergents.

Because their bodies and internal systems are still forming, developing babies, infants, and children can be particularly vulnerable to the adverse health effects of EDCs. Those risks can be compounded by the fact that, in proportion to their body size, babies and children drink, eat, and breathe more than adults and thus are likely to take in relatively more of these substances.

Protecting children and others from exposures to endocrine disrupting chemicals has been an EPA priority since the 1990s, when scientists hypothesized that “humans and wildlife species have suffered adverse health effects after exposure to endocrine-disrupting chemicals,” as outlined in the paper Research Needs for the Risk Assessment of Health and Environmental Effects of Endocrine Disruptors: A Report of the U.S. EPA-sponsored Workshop, (Environmental Health Perspectives. 1996 August, 104(4)).

Young family plays in the park.Since then, EPA researchers and grantees in universities have worked to understand the potential risks of EDCs to human health and wildlife.  The work includes prioritizing chemicals for testing through EPA’s innovative Endocrine Disruptors Screening Program and developing models to predict the biological pathways that can lead to endocrine disruption. The work also includes assessing the cumulative risk of chemical mixtures found in food, products, and drinking water. This work on chemical mixtures is important because the combined effects , even at low concentrations, might be different than they would be for individual chemicals..

By developing the tools and information needed to understand EDCs and their potential impacts on human health, Agency researchers and their partners are helping to protect the health of children, adults, and wildlife. The knowledge from the research has a variety of important impacts: it is valuable to manufacturers so they can ensure the safety of their products; it provides information to expectant mothers so that they can avoid EDC exposures before and during pregnancy; it offers parents, public health professionals, and decision makers at EPA and elsewhere science-based data and tools to make informed choices that will protect children, adults, and wildlife.

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.