Workshop on "In vitro comparative metabolism studies in regulatory pesticide risk assessment"

Parma, Italy
15 November 2018 to 16 November 2018

Introduction:

EFSA is organising a workshop for stakeholders involved in the peer review of pesticides and with experts in the field of in vitro metabolism studies.

The EU pesticides Regulation 283/2013 on data requirement established that “Comparative in vitro metabolism studies shall be performed on animal species to be used in pivotal studies and on human material (microsomes or intact cell systems) in order to determine the relevance of the toxicological animal data and to guide in the interpretation of findings and in further definition of the testing strategy”.

These studies are the basis for the identification of human metabolites. In addition, metabolism studies have a relevant role in understanding endocrine mediated mechanisms of toxicity and human relevance of animal data in a weight of evidence approach (e.g. endocrine mediated-thyroid toxicity).

Experts will :

  • Define the minimum amount of information that should be provided to satisfy the data requirement.
  • Define the information that should be included in the study protocols.
  • Discuss the key elements to be considered for the interpretation of the study(ies) outcome
  • Discuss how metabolism data can be used in a weight of evidence approach for endocrine mediated mechanisms of toxicity

 

This is the preliminary conference programme subject to changes.

Time Items Presenter
14.00
10 min

Opening remarks

Tamara Coja (AGES, EFSA PPR Panel)
1st general session: Chair: Tamara Coja (AGES, EFSA PPR Panel)
14.10
20 min

1. Introduction to the “In vitro comparative metabolism project” in the pesticide regulatory context

Juan Parra (EFSA Pesticides Unit)
14.30
30 min
2. A framework to characterize in vitro hepatic metabolism across species for regulatory applications Sandra Coecke (JRC, EURL-ECVAM, Ispra, Italy)
15.00
30 min
3. In vitro comparative metabolism studies to identify metabolites using microsomes: standards and criteria for acceptability and interpretation.

Khaled Abass (University of Oulu, Institute of Arctic Medicine, Finland)

15.30
30 min
4. In vitro comparative metabolism studies to identify metabolites using hepatocytes: standards and criteria for acceptability and interpretation. Stefano Fontana (Verona, Aptuit and Evotec Company)
16.00 Coffee break  
16.30
30 min
5. Identification of metabolites: analytical challenges for conducting in vitro metabolism characterization of pesticides

Ugo Zanelli
Discovery DMPK, Merck KGaA Darmstadt. Frankfurt Am Main Area, Germany.

17.00
30 min
6. Industry view: In vitro comparative metabolism studies to identify metabolites. Paul M. Whalley. Syngenta, Bracknell, UK on behalf of ECPA.
17.30
30 min
7. In vitro studies to assess liver enzyme induction across species. Standards and criteria for acceptability and interpretation. Simona Marzorati (Accelera SRL, Milano. Italy)
18.00
30 min
8. Investigating thyroid disruption through liver enzyme induction using hepatocytes Vicki Richardson (US EPA, Durham, North Carolina. USA)
Michael DeVito (NIH/NIEHS, Durham, North Carolina. USA)
  Closing remarks Andrea Terron (EFSA Pesticides Unit)
18.30 End of general session 1  
Time

 

Presenter

Break-out session 1:

  1. What is defining a unique human metabolite (e.g. threshold, species-specificity)?
  2. How to deal with quantitative differences of the same metabolite when observed in more than one species?
  3. What should be the criteria for selecting the most appropriate test system (primary hepatocytes, cell line, microsomes and cytosol)?
  4. What analytical method should apply (targeted vs untargeted)?
  5. Proposal for study protocol and interpretation.
Chair: Emanuela Testai (Istituto Superiore di Sanita, Italy)
Rapporteur: Marina Marinovich (EFSA PPR Panel)
9:00 Discussion  
13.00 Lunch  

Break-out session 2:

  1. Adverse Outcome Pathway for thyroid hormone disruption consequent to liver induction.
  2. What KE-KEs should be measured and how?
  3. Proposal for study protocol and interpretation
Chair: Sharon Munn (JRC, Italy)
Rapporteur: Alfonso Lostia (EFSA, Pesticide Unit)
 
9:00 Discussion  
13.00 Lunch  
2nd general session: Chair: Tamara Coja (AGES, EFSA PPR Panel)
14.00 Feedback from Break out session 1  
14.30 Open discussion  
15.00 Feedback from Break out session 2  
15.30 Open discussion  
16.00 Concluding remarks.  
16.30 End of the Workshop  

Who should attend

Stakeholders dealing with the peer review of pesticides and experts in the field of in vitro metabolism studies. The outcome of the workshop will be usedto developan EFSA guidance document. Participants will be selected to ensure a sufficient representation of the different stakeholders, fields of expertise, and geographical balance. Register here by 22 October.

Date and venue

The conference will be held on 15 and 16 November 2018 in Parma, Italy. The venue will be communicated to selected participants after the close of registrations.

Language

English will be the official language of the conference. No translation will be provided.

Contact

Feel free to contact us about any content-related matters or organisational and logistical issues at the following address: events [at] efsa.europa.eu.

Agenda (284.5 KB)