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Carcinogenicity Workshop Scientific Program–Recorded Talks
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The workshop is broken into four sessions that cover the topics of "Problem Formulation", "Mode of Action", "Dose-Response", and "New Approach Methodologies" relating to the latest science in carcinogenesis hazard identification, classification, and risk assessment.

Each session will be recorded and available for attendee viewing by mid-November. This diverse array of presentations will give attendees a strong knowledge base in the topic area and will inform the live discussions among all attendees during the live, virtual sessions, December 7–10.

Each presentation is approximately 25 minutes in length.

 

Scientific Program and Session Details

 

Session Overview: The Problem Formulation session aims to set the stage to identify overarching needs and goals for carcinogenicity assessment as it relates new and existing models of hazard characterization and dose-response evaluation. Independent regulatory paradigms and scientific advancements will be explored to highlight key issues in the active practice of cancer risk assessment with a focus to define science-based challenges that arise in meeting the needs of agency decision makers. New approach methodologies will be discussed to explore their potential utility to address current challenges in safety assessment. Lastly, the speakers and panelists look forward to timely discussion focused on the challenges and opportunities we face in carcinogenicity assessment.

 

Moderator and Chair: Gina Hilton, PETA International Science Consortium

 

—Presentations—

 

International Perspective
Gina Hilton, PETA International Science Consortium

Workshop Problem Formulation and Key Decisions in Cancer Risk Assessment
Kelly Magurany, NSF International

Scientific Challenges within Cancer Risk Assessment
David Bussard, US EPA/ORD

Opportunities to Improve Cancer Risk Assessment
Warren Casey, NIEHS/NTP/NICEATM

 

Moderated Panel Discussion {Hosted during live virtual session on December 7, 2020}
All speakers + additional panelists:
Phil Botham, Syngenta;
Suzanne Fitzpatrick, US FDA/CFSAN


Session Overview: Understanding the mode of action in the human body after exposure to a chemical is key to characterizing the risk of carcinogenesis that may be introduced. The mode of action informs the propensity for direct or indirect mechanisms of DNA damage, the inhibition or promotion of repair or cell proliferation and the associated implications of dose and temporal relationships of exposure to tumor formation.  This session aims to provide an overview of our current understanding of cancer mode of action, the models available to inform our understanding and to characterize human relevance, implications and best practices for data interpretation and integration to inform dose-response evaluation and ultimately for the development of a modern decision framework for carcinogenicity risk assessment. Concepts introduced in this session will be illustrated by several case studies. 

 

Moderator and Chair: Kelly Magurany, NSF International

 

—Presentations—

 

Introduction to the Session
Phil Botham, Syngenta

What Is Mode of Action (versus Mechanism of Action)?
Rory Conolly

Genotoxic & Mutagenic MOAs
Andrea Hartwig, Karlsruher Institut für Technologie

Non-genotoxic MOAs
James Klaunig, Indiana University

Human Relevance
Natalia Ryan, Syngenta

Integration of Key Concepts for Chemical Assessment and Carcinogenicity Evaluation
Greg Akerman, US EPA/OPP

Case Study: Hexavalent Chromium
Chad Thompson, ToxStrategies Inc.

Case Study: Arsenic
Lynne Haber, University of Cincinnati, College of Medicine

Case Study: Atrazine
James Simpkins, West Virginia University

 

Moderated Panel Discussion {Hosted during live virtual session on December 8, 2020}
All speakers + additional panelists:
Rick Becker, American Chemistry Council;
Tiffany Bredfelt, Texas Commission on Environmental Quality;
Mirjam Luitjen, Rijksinstituut voor Volksgezondheid en Milieu (RIVM)


Session Overview: The goal of this session is to highlight the state of the science related to dose-response assessment for quantifying human carcinogenicity risk.  Data from the US NTP two-year rodent bioassay have been used for dose-response assessment and characterization of human carcinogenicity risk for more than 50 years. This session begins with an overview of bioassay history, application, and evolution. We present history of use of the linear no threshold (LNT) model for assessing low-dose cancer risks; we describe its origins, evidence for and against the model, and its current application. The subsequent talks present contemporary aspects of bioassay design including mechanistic and toxicokinetic considerations that can inform internal dosimetry and mode of action to make better use of modern science and knowledge of carcinogenesis. This session concludes with case studies illustrating the extent to which epidemiology data can be appropriately evaluated to inform extrapolation to low human exposures for quantitative cancer risk assessment.

 

Moderator and Chair: Virunya Bhat, ToxStrategies Inc.

 

—Presentations—

 

Introduction to the Session
Virunya Bhat, ToxStrategies Inc.

History, Application, and Evolution of the Cancer Bioassay
Rita Schoeny, Rita Schoeny LLC

The Linear No-Threshold Model: An Overview of Its History, Basis, and Use
David Eastmond, University of California, Riverside

Contemporary Considerations: Dose Selection Based on KMD and Internal Dosimetry
Alan Boobis, Imperial College London

Contemporary Considerations: Dose-Response Assessment Based on ≤ 13 Week Studies with Integrated MOA Endpoints
Doug Wolf, Syngenta

Dose-Response Assessment and Low-Dose Extrapolation from Epidemiology Data
Ellen Chang, Exponent Inc.

 

Moderated Panel Discussion {Hosted during live virtual session on December 9, 2020}
All speakers + additional panelists:
Lynn Flowers, US EPA/ORD;
Sabitha Papineni, Corteva Agriscience;


Session Overview: The assessment of human carcinogenic risk posed by xenobiotics is informed largely by results obtained from the two-year rodent bioassay. However, the rodent bioassay has some well-recognized shortcomings, including; uncertain translational relevance, large number of animals required, extensive time to conduct, and high costs. To address these and other shortcomings, new approach methodologies (NAMs) for carcinogenicity testing are being developed that incorporate important advances in the biomedical sciences and cancer biology made since the establishment of the rodent bioassay.  However, confidence must be established in NAMs for them to become adopted by industry and regulatory agencies.  This session will explore different approaches being developed for carcinogenicity hazard and risk assessment along with regulatory perspectives on what will be needed for establishing confidence in these new approaches. 

 

Moderator and Chair: Warren Casey, NIEHS/NTP/NICEATM

 

—Presentations—

 

Introduction to the Session
Warren Casey, NIEHS/NTP/NICEATM

Establishing Confidence in NAMs for Regulatory Decision Making
Bob Diderich, OECD

US EPA Viewpoints on NAMs
Anna Lowit, US EPA/OPP

Use of NAMs in Regulatory Assessment
Arun Pandiri, NIEHS/NTP

Exploring Transcriptomic and In Vitro Genotoxicity Data to Estimate a Point of Departure (POD) for Human Health Risk Assessment
Tara Barton-Maclaren, Health Canada

Utility of NAMs in Regulatory Assessment
Weihsueh Chiu, Texas A&M University

Utility of NAMs in Regulatory Assessment
Susanne Stalford, Lhasa Ltd 

Moderated Panel Discussion {Hosted during live virtual session on December 10, 2020}
All speakers + additional panelists:
Paul Brown, US FDA/CDER;
Susanne Hartigan, American Chemistry Council;
Fiona Sewell, NC3Rs;