HESI Workshop on Framework Approaches to Risk Assessment

  • Start Date/Time :
  • End Date/Time :
  • Location : Nice, France
  • Venue : Le Meridien Hotel

A Workshop in Three Parts

  • Special Session: DNA ADDUCTS IN RISK ASSESSMENT: November 14, 2005: 1:00 pm – 5:00 pm
  • Workshop #1: RODENT LIVER TUMORS AS A PREDICTOR OF HUMAN CANCER RISK?: November 15, 2005: 9:00 am – 5:00 pm
  • Workshop #2: AGRICULTURAL CHEMICAL SAFETY ASSESSMENT: November 16, 2005: 9:00 am – 5:00 pm

The complete workshop program is available here.

What Are the Workshop Objectives?

This 3-day HESI workshop will demonstrate how science-based safety assessment is advanced through cooperative partnerships among government, industry, and academia. Each session will feature an overview of HESI’s activities on the topic, presentations from international experts, and panel discussions which include government, industry, and academic scientists from the US  and Europe.

Who Will Participate as Speakers?

Internationally recognized experts in toxicology and risk assessment will participate as speakers, moderators, and panelists at the workshop.  Some of the confirmed speakers include:

  • Dr. Robert Baan, Senior Scientist, Unit of Carcinogen Identification and Evaluation, IARC Monographs Program
  • Dr. Lewis Smith, Global Head of Product Development, Syngenta Ltd.
  • Dr. Julian Preston, Director of Environmental Carcinogenesis Division, US Environmental Protection Agency
  • Dr. Helmut Greim, Director of the Institute of Toxicology and Environmental Hygiene, Technische Universität München and Vice Chairman of the Scientific Advisory Committee on Toxicology, Ecotoxicology and the Environment of the General Directorate Health and Consumer Protection of the European Commission
  • Dr. Neil Carmichael, Global Head of Toxicology, Bayer CropScience

Who Should Attend?

The meeting is open to participants from industry, academia, and government from Europe and abroad.  The workshop programs will be of interest across sectors, and diverse perspectives will be offered.  HESI encourages participation from both those familiar or affiliated with the HESI organization and those who would like to learn more about HESI programs.

Monday, November 14, 2005

Special Session:  DNA Adducts in Risk Assessment

With recent advances in analytical detection techniques for DNA adducts comes the need to address recurring questions about the mechanistic and toxicological relevance of low-concentration measured adducts.  Despite the abundance of research in this field, the diversity of opinions as to the role of DNA adducts in cellular processing, repair mechanisms, and mutagenesis (and vice versa) suggests the need for a mechanism to reach scientific consensus.  Concurrent with the increasingly widespread collection of DNA adduct measurements as human biomarker data, the scientific community is also currently debating the relevance of these data for risk assessment.  This special session will address activities undertaken by HESI to further public discussion and consensus on the use of DNA adducts for risk assessment.


Welcome and Introduction
Ms. Syril Pettit or Dr. Michael Holsapple (HESI) (confirmed)


Chair:  Dr. Bennett van Houten (US National Institute of Environmental Health Sciences) 

Available Tools for Measuring DNA Adducts
Dr. David Shuker (Open University, UK)

DNA Adducts in Risk Assessment
Dr. Elizabeth Martin (AstraZeneca)

US Regulatory Perspective
Dr. Julian Preston (US Environmental Protection Agency National Health and Environmental Effects Research Laboratory)

European Regulatory Perspective
Dr. Peter Kasper (Federal Institute for Drugs and Medical Devices, Germany)

Panel Discussion

Moderator:  Dr. Bobby Kroes (Utrecht University) (confirmed)
Rapporteur:  Dr. Jay Goodman (Michigan State University) (confirmed)


Dr. Jean Cadet (French Atomic Energy Commission) (confirmed)
Prof. Dr. Helmut Greim (University of Munich) (confirmed)
Dr. Ben Van Houten (US National Institute of Environmental Health Sciences) (confirmed)
Dr. Veronique Thybaud (sanofi-aventis) (confirmed)
Dr. Robert Baan (International Agency for Research on Cancer) (confirmed)

Tuesday, November 15, 2005

Workshop #1:  Rodent Liver Tumors as a Predictor of Human Cancer Risk?

From 1989 (the year that HESI was founded) until 1994, HESI hosted a series of five Mouse Liver Tumor Workshops, each of which were co-sponsored with the US Environmental Protection Agency.  During the fifth and final workshop in this series, participants began to consider a key question: “What constitutes a definition of robust evidence for a mode-of-action that would be sufficient to override a default regulatory posture?”  This early HESI work  provided a critical foundation for the development of a mode-of-action (MoA) framework.  The first step in this framework is to establish the key biochemical and cellular events, temporal occurrence, and dose-response concordance relationships for the MoA in animals.

The next step is to assess the biological plausibility of the key events in humans.  The final step is to consider kinetic and dynamic factors to establish the relevance of the MoA in humans.  This MoA framework has been previously applied to rodent liver tumors associated with exposure to peroxisome proliferators mediated through the alpha receptor (Klaunig et al., 2003, Crit. Rev. Toxicol., 33:655-780).  In May 2004, HESI co-organized a workshop to apply this framework approach to several additional MoAs for rodent liver tumor development including cytotoxicity, P-450 induction, hormone-mediated events, porphyrogenicity, and metal overload.  This workshop will focus on the outcomes and recommendations emerging from the May 2004 HESI workshop on the human relevance of rodent liver tumors.


Welcome and Introduction:
Dr. Michael Holsapple (HESI) 


Chair:  Dr. Lewis Smith (Syngenta Ltd.)

Overview on Multi-stage Hepatocarcinogenicity
Dr. Rolf Schulte-Hermann (Medical University of Vienna) 

Introduction to the Mode-of-action Framework Approach
Dr. James Klaunig (Indiana University)

Peroxisome Proliferation
Dr. Ruth Roberts (AstraZeneca) 

Dr. Sam Cohen (University of Nebraska Medical Center)

Prof. Alan Boobis (Imperial College London)

Dr. Timothy Pastoor (Syngenta CropScience) 

US Government Perspective
Dr. Vicki Dellarco (US Environmental Protection Agency Office of Pesticide Programs)
Dr. David Jacobson-Kram (US Food and Drug Administration Center for Drug Evaluation and Research) 

European Government Perspective
Dr. Jan Willem van der Laan (National Istitute of Public Health and the Environment, Germany) (confirmed)

Panel Discussion

Moderator:  Dr. Ernie Harpur (sanofi-synthelabo) (confirmed)
Rapporteur:  Dr. Andy Smith (MRC/University of Leicester) 


Dr. Beatriz Silva Lima (National Institute for Pharmacy and Medicines and University of Lisboa, Portugal) 
Dr. Robert Baan (International Agency for Research on Cancer) 
Dr. Gerd Bode (Atlanta Pharma AG)
Dr. Klaus Olejniczak (Federal Institute for Risk Assessment, Germany)  
Dr. Bette Meek (Health Canada) 
Dr. Jay Goodman (Michigan State University)
Dr. Dominique Masset (European Agency for the Evaluation of Medicinal Products, AFSSAPS, France) 

Wednesday, November 16, 2005

Workshop #2:  Agricultural Chemical Safety Assessment

In 2004, the HESI Technical Committee on Agricultural Chemical Safety Assessment (ACSA), an international group of government, academic, and industry scientists, completed a multi-year project to develop an improved testing strategy for assessing the safety of crop protection chemicals.  The tiered testing approach integrates metabolic and kinetic data into the safety assessment process; takes an integrated approach to evaluating life stage effects, systemic toxicity, and kinetics; and is guided by human exposure predictions.  During this workshop, leaders of the ACSA Technical Committee described the tiered testing strategy and its underlying scientific basis, logic, and flexibility.  In addition, speakers quantified the reduction in the number of experimental animals required to perform a sound assessment using this approach and summarized government reception to the proposal to date.


Welcome and Introduction
Nancy G. Doerrer, MS (HESI)


Chair:  Dr. Neil Carmichael (Bayer CropScience) (Presentation)

Dr. Hugh Barton (US Environmental Protection Agency National Center for Computational Toxicology) (Presentation)

Systemic Toxicity
Dr. John Doe (Syngenta CTL) (Presentation)

Life Stage
Ms. Lorraine Irvine (toXcel International) (Presentation)

Integration of Approaches
Dr. Neil Carmichael (Bayer CropScience) (Presentation)

US Government Perspective
Dr. Vicki Dellarco (US Environmental Protection Agency Office of Pesticide Programs) (Presentation)

"OECD Perspective"
Dr. Drew Wagner (Organisation for Economic Cooperation and Development) (Presentation)

Panel Discussion

Moderator:  Prof. Alan Boobis (Imperial College London)
Rapporteur:  Dr. Angelo Moretto (University of Padua)


Dr. Vicki Dellarco (US Environmental Protection Agency Office of Pesticide Programs)
European Food Safety Authority Representative (invited)
Dr. Claire Franklin (University of Ottawa; formerly with Health Canada)
Dr. James Klaunig (Indiana University School of Medicine)
Dr. Roland Solecki (Federal Institute for Risk Assessment, Berlin)
Dr. Drew Wagner (Organisation for Economic Cooperation and Development)

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Health and Environmental Sciences Institute (HESI)

Phone: +1-202-659-8404
Fax: +1-202-659-3859

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