CADASTER CAse studies on the Development and Application of in-Silico Techniques for Environmental hazard and Risk assessment Grant agreement no.: 212668 Collaborative Project Sub-Priority ENV2007 3.3.1.1: In-silico techniques for hazard-, safety-, and environmental risk-assessment Final workshop and guidelines for model development (report + book) (Deliverable 5.7) Start date of project: 1 January 2009 Duration: 4 years Due date of deliverable: December 31, 2012 Actual submission date: December 31, 2012 Lead Contractor: Corresponding author of the document: Igor V. Tetko1, Willie Peijnenburg2 1. Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany ([email protected]) 2. RIVM, Laboratory for Ecological Risk Assessment - P.O. Box 1 3720 BA Bilthoven, The Netherlands ([email protected]) Deliverable no: 5.7 (Workshop on the use of QSARs in REACH) Nature: Report publicly available Project co-funded by the EU Commission within the Seventh Framework Programme Dissemination Level PU Public X RE Restricted to a group specified by the consortium (including the Confidential,Commission Services)only for members of the consortium (including the CO Commission Services) 1 Content ! Content&................................................................................................................................&2! WP&5:&QSPR0THESAURUS:&Web&site&and&standalone&tools&for&dissemination&of&project&results &.............................................................................................................................................&3! Summary!....................................................................................................................................................................................!3! Overview!of!the!workshop!.................................................................................................................................................!5! October(7th(...................................................................................................................................................................................(5! October(8th(...................................................................................................................................................................................(6! Acknowledgements!................................................................................................................................................................!7! Annex&1:&List&of&workshop&materials&submitted&for&peer0review&publication&in&ATLA&journal&.&8! Annex&2:&List&of&Participants&..................................................................................................&9! Annex&3:&Oral&presentations&...............................................................................................&10! Annex&4:&Poster&presentations&............................................................................................&11! Annex&5:&CADASTER&Workshop&materials&............................................................................&12! 2 WP 5: QSPR-THESAURUS: Web site and standalone tools for dissemination of project results Task 5.7 CADASTER Workshop on the development and application of QSAR models with respect to the REACH guidelines (Deliverable 5.7) Summary The second CADASTER workshop (http://www.cadaster.eu/workshop) was organized by the Helmholtz Zentrum Muenchen and took place in its premises from October 7th to 9th 2012. A booklet with agenda of the workshop, abstracts of all presentations, short CVs of lectors and description of the cultural program is provided as Annex 5. The workshop was aimed to provide a tutorial to all interested partners, including industry and SMEs, on how to develop new models for the assessment of REACH-end points (in particular for new scaffolds of compounds for which there are no reliable QSAR models) and how to use the software developed by the project participants. According to the previous decision of the CADASTER General Assembly (February 2012, Madrid), materials of the workshop will be published as a dedicated issue of the ATLA journal (see Annex 1 with a list of submitted manuscripts). These materials summarize the expertise of all participants by providing clear guidelines on how to use applicability domain and experimental design to select an informative set of molecules, how to develop models and to estimate their applicability domain, and how to integrate different testing strategies following a critical analysis of four case studies considered in the CADASTER grant. The workshop was attended by 52 participants (see list of participants in Annex 2), including invited speakers from JRC - Institute for Health & Consumer Protection (Italy), EPA – Environmental Protection Agency (USA), Umwelt Bundesamt (Germany) and coordinators of the FP7 funded projects OSIRIS (Prof. G. Schüürmann) and COSMOS (Prof. M. Cronin). Dr. Barry Hardy, coordinator of the partner FP7 funded OpenTox project, had to cancel his participation due to personal reasons and sent his apologizes. 3 The meeting was started with a welcome reception on Sunday, October 7th, which was followed by a cultural program. There were two main thematic areas of the workshop: 1) Data collection and QSAR Model development for REACH (October 8th) and 2) Case studies and use of QSARs in the risk assessment (October 9th). The lectures of project participants were followed by lecture of invited speakers, thus providing a better understanding to the participants of a framework for the CADASTER project studies within similar activities of other EU projects and daily work of environmental protection agencies. Lectures presented during the workshop are provided in Annex 3. A poster session was organized during the first day of the workshop. The session included 20 posters from CADASTER partners and workshop participants (see Annex 4). 4 Overview of the workshop October 7th Dr. Igor Tetko and Prof. W. Peijnenburg opened the workshop and welcomed participants and invited lectors. In the first lecture Prof. Peijnenburg provided a summary of the project goals, achievements and lessons. In the absence of Dr. B. Hardy (OpenTox) Dr. Igor Tetko provided an overview of data modeling tools on the Internet, their differences, as well as of the place of the CADASTER QSPR- THESAURUS web site within this emerging field. Dr. Durjava described lessons that were learnt during the CADASTER project with respect to collection of experimental data and experimental testing. Prof. Schüürmann (UFZ, Leipzig) overviewed the activities within the FP7 funded OSIRIS project with respect to development of integrated testing strategy (ITS) approaches. The activities of the CADASTER project with respect to development of models according to the OECD principles using case studies for brominated flame retardants and perfluorinated compounds were presented by Dr. E. Papa. This lecture was followed by case studies on development of models for TAZ/BTAZ and triazoles given by Mrs. S. Kovarich, who is finishing her PhD within the CADASTER project at the University of Insubria. After a short break for lunch, Prof. M. Cronin (Liverpool John Moores University, UK) provided an overview of methods for the grouping of chemicals. These methods are important to make predictions by read-across and have received considerable interest for use in REACH and are increasingly being used, and accepted, for regulatory assessment. Dr. U. Sahlin described the theoretical basis of the uncertainty in QSAR predictions and importance of its use in risk assessment and/or in contexts of other decision-making processes. The lecture of Dr. Sushko overviewed methods for applicability domain assessment of QSAR models and their importance for the evaluation of uncertainty of quantitative and qualitative predictions. The majority of the presented approaches are available at the QSPR THESAURUS web site. The on-line demonstration by Dr. Tetko and Mr. Brandmaier was provided to demonstrate the practical use of the tools developed within the CADASTER project. Dr. Tetko concentrated on data upload, model development, application and interpretation. Mr. Brandmaier exemplified the use of experimental design approaches, which were developed and implemented on the CADASTER QSPR THESAURUS web site and are part of his PhD thesis. 5 The theoretical and on-line training was followed by the poster session. There were more than 20 posters presenting work of CADASTER partners as well as of workshop participants. The second day of the workshop was finished with a Workshop dinner. October 8th The invited lecture from Dr. A. Richard (USA, Environmental Protection Agency) overviewed ToxCast and Tox21 projects which probe high-throughput screening (HTS) technologies for toxicity prediction and modeling. The subsequent lecture of Mrs. L. Golstein was devoted to case studies for estimation of Maximum Permissible Emission (MPE) using example of triazoles. The influence of parameter uncertainties on the decision making process were exemplified. This work within the CADASTER project is a part of the PhD thesis of the lector. As an invited lecture, Dr. M. Brandt (Umweltbundesamt, Germany) described practical the use of QSAR methodology in the German Environmental Protection Agency. Dr. T. Aldenberg described how the uncertainty of QSAR predictions can be incorporated to improve the estimation of the Species Sensitivity