The NIEHS Superfund Research Program (SRP) is hosting a Risk eLearning webinar series highlighting research that may be useful as new approaches and methodologies for evaluating the safety of chemicals. In the third session, presenters will discuss new and emerging strategies for chemical safety evaluation. This will include new and emerging in vivo, in vitro, and in silico models to address population variability, and how in vitro high-throughput assays can provide useful information for hazard assessment of complex mixtures.

This series coincides with recent initiatives found in the U.S. Environmental Protection Agency's New Draft Strategic Plan and the National Toxicology Program’s Strategic Roadmap.

William Suk, Ph.D., director of the SRP, will describe other SRP efforts to address the complex challenges posed by hazardous pollutants and mixtures of chemicals. The SRP is well positioned to lead the way in the use of 21st century science to protect human health. This includes development of rapid tools to evaluate hazard, exposure, and environmental fate, as well as approaches to integrate these methods to evaluate risk.

Weihsueh Chiu, Ph.D., leader of the Texas A&M SRP Center Decision Science Core, will discuss new and alternative approaches to addressing human variability and susceptibility. Characterizing population variability, including identifying susceptible populations and quantifying their increased susceptibility, is an important aspect of chemical risk assessment, but one that is challenging with traditional experimental models and risk assessment methods. This presentation will discuss some new and emerging in vivo, in vitro, and in silico models to address population variability and advance human health hazard and dose-response assessments. A number of case studies providing proof of principle as well as some key challenges will be highlighted.

Michael DeVito, Ph.D., acting chief of the National Toxicology Program Laboratory, will discuss evaluation of mixtures in Tox21. Traditional testing methods alone cannot provide the answers to the challenges in understanding potential effects of mixtures. Both component-based approaches and whole mixture approaches have been employed in Tox21. Using these high-throughput screening (HTS) approaches, we have evaluated 69 mixtures of 18 estrogen and androgen receptor agonists. The 18 chemicals range from high efficacious and potent to negative in the different assays. The mixtures ranged from binary to all 18 chemicals at a variety of mixing ratios. The HTS approach allowed for the evaluation of dose addition under a broad range of mixing ratios and chemicals. Dose addition models consistently provided adequate fits to the data. These data demonstrate the advantage of the HTS approach to mixtures toxicology.

Michelle Heacock. Ph.D., an SRP health scientist administator, will moderate the session.

Presenters:

William Suk, Ph.D., M.P.H., Superfund Research Program, National Institute of Environmental Health Sciences (suk@niehs.nih.gov or 984-287-3325)
William Suk, Ph.D., M.P.H., is director of both the Superfund Research Program (SRP) and the Hazardous Substances Research Branch in the NIEHS Division of Extramural Research and Training. Suk has served as director of the SRP, a program established by Congress as part of the reauthorization of Superfund in 1986, since its inception. The SRP fosters interdisciplinary research approaches to address the problems associated with potentially hazardous environmental exposures. His affiliation with a number of organizations and committees include: Roundtable on Environmental Health Sciences, Research, and Medicine, Institute of Medicine, National Academy of Sciences; International Advisory Board of the Chulabhorn Research Institute, Bangkok, Thailand; and World Health Organization Consultation on Scientific Principles and Methodologies for Assessing Health Risks in Children Associated with Chemical Exposures. He is also a member of a number of trans-NIH committees. He received his Ph.D. in microbiology from the George Washington University Medical School, and his master's in public health in health policy from School of Public Health at the University of North Carolina at Chapel Hill.

Weihsueh Chiu, Ph.D., Texas A&M University (wchiu@cvm.tamu.edu or 979-845-4106)
Weihsueh A. Chiu, Ph.D. is a professor in the Department of Veterinary Integrative Biosciences at Texas A&M University, where he is actively involved in research, teaching, and service in the areas of toxicology, chemical risk assessment, and regulatory science. He received a bachelor's degree in Physics from Harvard University, and earned PhD in Physics from Princeton University, as well as a Certificate in Science, Technology, and Environmental Policy from the Woodrow Wilson School.

Dr. Chiu spent the first 16 years of his career in government service, first at the U.S. Government Accountability Office, and then at the U.S. EPA. Throughout his career, he has been involved in a diverse span of risk-related topics, such as defense against chemical-biological warfare agents, radioactive contamination in biosolids, human health risks from environmental chemical exposures, and the interface between science and policy. His recent research has focused on human health risk assessment, particularly with respect to toxicokinetics, mechanisms of toxicity, physiologically-based pharmacokinetic modeling, dose-response assessment, and characterizing uncertainty and variability. He has a particular interest in the development and use of Bayesian and probabilistic methods. Dr. Chiu has served on a variety of expert review panels for federal and state government agencies, as well as workgroups for the World Health Organization, Organization for Economic Cooperation and Development, Health Canada, and the U.S. National Academies of Sciences, Engineering and Medicine.

Michael DeVito, Ph.D., National Toxicology Program Laboratory (michael.devito@nih.gov or 984-287-4215)
Michael DeVito, Ph.D., is serving as the Acting Chief, National Toxicology Program (NTP) Laboratory. DeVito was most recently in the NTP Toxicology Branch leading the Experimental Toxicology Group, where his group was characterizing the toxicologic and/or carcinogenic potential of chemicals and agents nominated to the National Toxicology Program. He also served as the discipline leader for NTP pharmacokinetic modeling efforts.

Prior to coming to NTP in 2009, DeVito was a principal investigator in the Pharmacokinetics Branch of the National Health and Environmental Effects Research Laboratory at the US Environmental Protection Agency. From 2002-2009 DeVito was Chief of the Pharmacokinetic Branch. DeVito served as one of the lead health effects researchers on the US EPA's Dioxin Reassessment from 1991-2009. DeVito's research interests include developing quantitative model to understand the relationships between exposure to environmental chemicals, tissue dose and toxicity for use in risk assessments. DeVito received a Ph.D. in toxicology from the Joint Graduate Program in Toxicology at Rutgers, the State University of New Jersey in 1992.

Moderator:

Michelle L. Heacock, Ph.D., NIEHS Superfund Research Program (heacockm@niehs.nih.gov)
Michelle Heacock, Ph.D., is currently serving as the acting branch chief of the Hazardous Substances Research Branch, and is a health science administrator where she oversees Superfund Research Program (SRP) grants that span basic molecular mechanisms of biological responses from exposures to hazardous substances, movement of hazardous substances through environmental media, detection technologies, and remediation approaches. Dr. Heacock received her doctorate from Texas A&M University for her work on the interplay between DNA repair proteins and telomeres. Her postdoctoral work was conducted at NIEHS where she studied the DNA repair pathway, base excision repair. She has been with the NIEHS since 2007.

Webinar Slides and References:

• Slide Presentation for William Suk, Ph.D., Superfund Research Program, National Institute of Environmental Health Sciences (4.72MB/PDF)
• Slide Presentation for Weihsueh Chiu, Ph.D., Texas A&M University:
  • Adobe Acrobat format (7.81MB/PDF)
  • Microsoft PowerPoint format (7.61MB/PPTX)
• Slide Presentation for Michael DeVito, Ph.D., National Toxicology Program Laboratory:
  • Adobe Acrobat format (1.12MB/PDF)
  • Microsoft PowerPoint format (1.82MB/PPTX)

Webinar Slides and References:

• Slide Presentation for William Suk, Ph.D., Superfund Research Program, National Institute of Environmental Health Sciences (4.72MB/PDF)
• Slide Presentation for Weihsueh Chiu, Ph.D., Texas A&M University:
  • Adobe Acrobat format (7.81MB/PDF)
  • Microsoft PowerPoint format (7.61MB/PPTX)
• Slide Presentation for Michael DeVito, Ph.D., National Toxicology Program Laboratory:
  • Adobe Acrobat format (1.12MB/PDF)
  • Microsoft PowerPoint format (1.82MB/PPTX)

Additional Resources:

• NIEHS Superfund Research Program Risk e-Learning Webinar Series: New Approaches and Alternatives for Toxicity Testing
• Superfund Research Program Research Briefs
• National Toxicology Program Toxicology in the 21st Century (Tox21) Toolbox
• EPA Tox21/ToxCast Dashboard
• National Center for Advancing Translational Sciences: Tox21
• Advancing chemical risk assessment decision-making with population variability data: challenges and opportunities
• New rodent population models may inform human health risk assessment and identification of genetic susceptibility to environmental exposures
• Population-based dose-response analysis of liver transcriptional response to trichloroethylene in mouse
• A tiered, Bayesian approach to estimating of population variability for regulatory decision-making
• Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study
• Physiologically based pharmacokinetic (PBPK) modeling of interstrain variability in trichloroethylene metabolism in the mouse