The Use of Computational Methods in the Grouping and Assessment of Chemicals - Preliminary Investigations

This document presents a perspective of how computational approaches could potentially be used in the grouping and assessment of chemicals, and especially in the application of read-across and the development of chemical categories. The perspective is based on experience gained by the authors during 2006 and 2007, when the Joint Research Centre’s European Chemicals Bureau was directly involved in the drafting of technical guidance on the applicability of computational methods under REACH. Some of the experience gained and ideas developed resulted from a number of researchbased case studies conducted in-house during 2006 and the first half of 2007. The case studies were performed to explore the possible applications of computational methods in the assessment of chemicals and to contribute to the development of technical guidance. Not all of the methods explored and ideas developed are explicitly included in the final guidance documentation for REACH. Many of the methods are novel, and are still being refined and assessed by the scientific community. At present, many of the methods have not been tried and tested in the regulatory context. The authors therefore hope that the perspective and case studies compiled in this document, whilst not intended to serve as guidance, will nevertheless provide an input to further research efforts aimed at developing computational methods, and at exploring their potential applicability in regulatory assessment of chemicals. LIST OF ABBREVIATIONS AAR Activity-Activity Relationship BfR German Federal Institute for Risk Assessment BMD Benchmark Dose BMD LCL 95% lower confidence limit on the Benchmark Dose CAS Chemical Abstracts Service CEFIC (LRI) European Chemical Industry Council (Long Range Initiative) DNEL Derived No Effect Level EC European Commission ECB European Chemicals Bureau ECx% Effective Concentration x% EPA Environmental Protection Agency ESIS European chemical Substances Information System (ECB) ESR Existing Substances Regulation EINECS European Inventory of New and Existing Chemical Substances EU European Union HPV High Production Volume ITS Integrated (Intelligent) Testing Strategy JRC Joint Research Centre LCx% Lethal concentration % LDx% Lethal dose % LOAEL Lowest-Observed-Adverse-Effect-Level NOAEL No-Observed-Adverse-Effect-Level OECD Organisation for Economic Cooperation and Development PBT Persistent Bioaccumulative and Toxic vPvB very Persistent and very Bioaccumulative PCA Principal Components Analysis POR Partial Order Ranking QSAAR Quantitative Structure-Activity-Activity Relationship QMRF (Q)SAR Model Reporting Format (Q)SAR (Quantitative) Structure Activity Relationship REACH Registration, Evaluation, and Authorisation of Chemicals RIP REACH Implementation Project RTECS Register of Toxicology Effects of Chemical Substances SIAM OECD Screening Information Assessment Meeting SMILES Simplified Molecular Input Line Entry System TTC Threshold of Toxicological Concern TOR Total Order Ranking WoE Weight of Evidence