Practical Guide 5: How to report (Q)SARs - ECHA - Europa

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1. INTRODUCTION Regulation (EC) No 1907/2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (hereafter, REACH) foresees the use of non test methods such as (Quantitative) Structure-Activity Relationships [(Q)SARs], grouping of substances and read-across for adaptation of the standard testing regimes. More specifically, Recital 47 of REACH determines the objectives of the Regulation with respect to avoidance of unnecessary testing on vertebrate animals: “[…] it is necessary to replace, reduce or refine testing on vertebrate animals. Implementation of this Regulation should be based on the use of alternative test methods, suitable for the assessment of health and environmental hazards of chemicals, wherever possible. The use of animals should be avoided by recourse to alternative methods validated by the Commission or international bodies, or recognised by the Commission or the Agency as appropriate to meet the information requirements under this Regulation.” These methods and other data sources have to be explored before considering vertebrate animal testing. This practical guide provides an overview of important aspects when predicting properties of substances using (Q)SAR models as defined in the REACH Regulation. More detailed information is available in the Guidance documents (see 3.1.). The information given in this practical guide does not describe the requirements to pass the technical completeness check which are illustrated in the Dossier Submission Manual (No. 05 - How to complete a technical dossier for registrations and PPORD notifications). 1
2. HOW TO GET STARTED WITH (Q)SARS The use of (Q)SAR models with software is rather straightforward. However, experience and a thorough understanding of (Q)SARs will be needed when it comes to the assessment of whether predictions are reliable and adequate for the purpose of classification and labelling and/or risk assessment and can thus be used instead of testing. 2.1. Substance characterisation The chemical structure needs to be well defined, following the Guidance on identification and naming of substances under REACH. All individual constituents of multi-constituent substances should be addressed. The composition of the well defined substances has to include also known impurities (and additives, if any). For UVCBs, expert judgement is needed to decide whether structures can be identified which are representative for the substance. In case of a stable transformation product, it should be identified. A suitable structural representation for the chemical (SMILES, mol file etc.) is usually required. Stereochemistry should be taken into account if necessary. 2.2. (Q)SAR models SAR and QSAR models, collectively referred to as (Q)SARs, are theoretical models that can be used to predict in a quantitative or qualitative manner the physico-chemical, biological (e.g. a (eco)toxicological) and environmental fate properties of compounds from the knowledge of their chemical structure. A SAR is a qualitative relationship that relates a (sub)structure to the presence or absence of a property or activity of interest. A QSAR is a mathematical model relating one or more quantitative parameters, which are derived from the chemical structure, to a quantitative measure of a property or activity. In order to predict a property of a chemical, the validity of the selected (Q)SAR model should be assessed, and it should be verified that the chemical falls within the applicability domain to give a reliable prediction. 2.3. Overall Assessment of adequacy and reporting In order to generate a reliable and adequate prediction of the presence or absence of a chemical’s property to fulfil the information requirements under REACH, (i) a (Q)SAR model should be used whose scientific validity has been established and (ii) the substance should fall within the applicability domain of the (Q)SAR model, (iii) the 2
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Practical Guide 5: How to report (Q)SARs - ECHA - Europa

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