Low Dose Effects and Non-Monotonic Dose Responses for Endocrine Active Chemicals: Science to Practice
An International Workshop
September 11-13, 2012
Charité Universitätsmedizin, Berlin, Germany
Background
There have been extensive discussions in Europe and the United States to identify and develop methods to translate scientific findings of endocrinology to human health risk assessment. A recent review paper ( http://edrv.endojournals.org/content/early/2012/03/14/er.2011-1050.abstract ) in Endocrine Reviews suggests that low dose effects and non-monotonic dose responses are to be expected for chemicals with endocrine disrupting activity and that these responses may occur frequently enough to be a concern. This review focuses in part on the many observations of the link between current human exposures to various chemicals and specific diseases and contends that these observations are supported by mechanistic and animal studies.
This workshop seeks to lay out the evidence for low dose effects and non-monotonic dose responses in relation to endocrine active chemicals, with the goal of establishing whether the current observations are sufficient to re-examine the ways in which chemicals are tested for endocrine disrupting properties and how risk to human health may be managed.
Within this context the goals of this workshop are the following:
- To present and discuss the state of the science for low dose effects and non-monotonic dose response curves for chemicals with endocrine activity.
- To define research needs required to move closer to scientific agreement on low dose effects and non-monotonic dose responses for endocrine active substances.
- To define how research programs, especially those funded by public agencies, could support studies that would produce data most useful for a science-based risk assessment.
- To start a discussion on the implications of low dose effects and non-monotonic dose response curves to risk assessment.
- To develop a plan to continue discussions between basic researchers and risk assessment scientists beyond the current workshop.
The workshop is sponsored by The National Institute of Environmental Health Sciences (NIEHS)/ NIH, The Oak Foundation, the European Commission, The French Agency for Food, Occupational and Environmental Health (ANSES) , The Federal Environment Agency (UBA) in Germany, the Danish Ministry of the Environment and National Food Institute from Denmark and Charite Medical University, Berlin.
Who should attend: Toxicologists, environmental health scientists, regulatory agencies and risk assessors interested in all aspects of endocrine disruptors/endocrine disruption.
Meeting Location
The meeting will be hosted by Prof. Dr. Gilbert Schönfelder of the Institute of Clinical Pharmacology and Toxicology of the Charié-Universitätsmedizin Berlin.
The meeting will be held in south Berlin at Campus Benjamin Franklin (CBF) of the Charié-Universitätsmedizin Berlin:
Address: Campus Benjamin Franklin (CBF), Hindenburgdamm 30, 12203 Berlin
Contacts
Meeting Organizers:
- Jerrold J. Heindel, NIEHS, USA
- Sharon Munn, European Commission, Ispra, Italy
- John Bucher, NIEHS, USA
- Thaddeus Schug, NIEHS, USA
- Tom Zoeller, University of Massachusetts, USA
- John Peterson Myers, Environmental Health Sciences, USA
- Laura Vandenberg, Tufts University, USA
- Andreas Kortenkamp, Brunell, UK
- Andreas Gies, Wolfgang Straff, UBA, Germany
- Gilbert Schonfelder, Charite University, Germany
- Ulla Hass, National Food Institute, Denmark
- Claire Beausoleil and Jean-Nicolas Ormsby, ANSES, France
- Bernd Schaefer, BfR, Germany
- Marie Louis Holmer, Danish Ministry of the Environment
- Tom Neltner, Maricell Maffini, Pew Trust, USA
Scientific Contacts:
- Jerry Heindel, heindelj@niehs.nih.gov
- Sharon Munn, sharon.munn@ec.europa.eu
Local Arrangement Contact:
- Gilbert Schonfelder, gilbert.schoenfelder@charite.de
Agenda
Day 1: September 11, 2012
Opening: Welcome and Meeting Goals
- 8:30 - 8:45
- Welcome
- Sharon Munn, Joint Research Centre- Institute for Health and Consumer Protection, European Commission, Italy
- Jerry Heindel, The National Institute of Environmental Health Sciences (NIEHS), USA
- Detlev Ganten, Chairman of the Board of the Charité Foundation and President of the World Health Summit, Germany
- 8:45 - 9:00
- Opening Comments
- Linda Birnbaum, Director NIEHS, USA (via video)
- Elke Anklam, Director, Joint Research Centre-Institute for Health and Consumer Protection, European Commission, Italy
- 9:00 – 9:10
- Meeting Goals
- Sharon Munn, European Commission, Italy
- Jerry Heindel, NIEHS, USA
Session I: Update on Recent Workshops / Activities
- 9:10 - 9:25
- EC Update on EDC Activities
- Peter Korytar, DG Environment, European Commission, Belgium
- 9:25 - 9:40
- April 2012 Workshop Sponsored by The Pew Charitable Trusts, Nature Journal, and the Institute of Food Technologists
- Tom Neltner, The Pew Charitable Trusts, USA
- 9:40 - 10:05
- June 2012 Colloquium Sponsored by European Food Safety Authority (EFSA)
- Iona Pratt, Food Safety Authority of Ireland
- 10:05 - 10:25
- Break
Session II: Developing a Common Language and Understanding
- 10:25 - 10:55
- How Hormones and Endocrine Disruptors Act
- Fred vom Saal, University of Missouri, USA
- 10:55 - 11:15
- Principles of Pharmacology Related to Low Dose Effects and Non-Monotonic Dose Responses
- Scott Belcher, University of Cincinnati, USA
- 11:15 - 11:45
- Practical Principles of Risk Assessment
- Theo Vermeire, National Institute for Public Health and the Environment (RIVM), Netherlands
- 11:45 - 12:15
- Facilitated Discussion
- Discussion Leader: RESOLVE
- 12:15 - 13:15
- Lunch (on site)
Session III: Occurrence of Low Dose Effects and Non-monotonic Dose Responses for Endocrine Active Chemicals
- 13:15 - 13:55
- State of the Science of Low Dose Effects of Endocrine Active Chemicals
- Tyrone Hayes, University of California Berkeley, USA
- 13:55 - 14:35
- State of the Science of Non-Monotonic Dose Responses in Animal and Human Studies
- Laura Vandenberg, Tufts University, USA
- 14:35 - 15:00
- Break
- 15:00 - 15:30
- Computational Modeling of Non-monotonic Dose-Responses: Insights into Minimum Requirements
- Rory Conolly, US Environmental Protection Agency (US EPA), USA
- 15:30 - 15:45
- An Example that Shows the Need to Develop a Strategy for Interpreting Non-Monotonic Responses in Guideline Studies
- Heather Patisaul, North Carolina State University, USA
- 15:45 - 16:15
- Mechanisms for Non-monotonic Dose Responses
- Ana Soto, Tufts University, USA
- 16:15 - 17:00
- Facilitated Discussion
- Discussion Leader: RESOLVE
- 17:00-17:30
- Introduction to Break-out Sessions and Polling
- Paul De Morgan, RESOLVE, USA
Evening Reception
- 19:00
- Henry Ford Bau of the Freie Universität Berlin
Day 2: September 12, 2012
Session IV: Report on Current Activities
- 8:30 - 8:45
- French Agency for Food, Environmental and Occupational Health (ANSES) Activities Related to Low Dose/Non-monotonic Dose Responses for EDCs
- Claire Beausoleil, ANSES, France
- 8:45 - 9:10
- U01 BPA consortium/Tox 21
- Kembra Howdeshell, NIEHS/National Toxicology Program (NTP), USA
- 9:10 - 9:25
- Endocrine Society Statement of Principles
- Ana Soto, Tufts University, USA (on behalf of The Endocrine Society)
- 9:25 - 9:40
- US EPA Update on Low Dose-related Activities
- Mark Miller, US EPA, USA
- 9:40 - 10:00
- Break
Session V: Implications of Low Dose and Non-Monotonic Dose Responses for Risk Assessment
- 10:00 - 10:20
- How EFSA Works and Performs Risk Assessment
- Alexandre Feigenbaum, EFSA, Italy
- 10:20 - 10:50
- Impact of Low Dose and Non-Monotonic Dose Responses on Risk Assessment
- Jim Bridges, Chair, Scientific Committee on Emerging and Newly Identified Health Risks, European Commission
- 10:50-11:10
- OECD Test Guidelines and Endocrine Endpoints
- Olwenn Martin, Brunel University, UK
- 11:10 - 11:40
- Facilitated Discussion
- Discussion Leader: RESOLVE
Session VI: Day 2 Breakout Session
- 11:40-12:00
- Charge to Breakout Groups
- Paul De Morgan, RESOLVE
- 12:00-16:00
- Breakout Groups (working lunch)
- Each breakout group has a RESOLVE facilitator, a chair who will lead discussion, and a rapporteur who will report results
- 16:00-16:30
- Break
- 16:30-18:15
- Reports from Day 2 Breakout Groups in General Session
Evening Poster Session on Site with Refreshments
- 18:30-20:00
- Location: Südfoyer of the Campus Benjamin Franklin of the Charité
Day 3: September 13, 2012
Session VII: Day 3 Breakout Session
- 8:30 - 8:50
- Charge to Breakout Groups
- Paul De Morgan, RESOLVE
- 9:00 - 12:00
- Breakout Groups
- Each breakout group has a RESOLVE facilitator, a chair who will lead discussion, and a rapporteur who will report results
- 12:00 - 13:00
- Lunch
- 13:00 - 15:00
- Reports from Day 3 Breakout Groups in General Session
Session VII: Wrap-up
- 15:00 - 15:30
- Overall Summary and Path Forward to Continue the Dialogue
- Sharon Munn, European Commission, Italy
- Jerry Heindel, NIEHS, USA
- 15:30
- Meeting Adjourns
Sponsors
