ECHA - Guidance of the application of CLP criteria [November 2012]

Guidance on the Application of the CLP Criteria Version 3.0 - November 2012It should be noted that the use of (Q)SAR results requires the user to be sufficiently skilled tounderstand the applicability of the selected (Q)SAR and to interpret the results in terms ofreliability and adequacy for the purpose of classification and labelling.Extensive guidance on the use of (Q)SARs for hazard identification is given in IR/CSA,Chapter R.6.1. Guidance on the use of (Q)SARs for classification and labelling according toDSD is also given in IR/CSA, Chapter R.6.1.4.2. This guidance is directly applicable to CLP.It should be noted that the (Q)SAR approach is not directly applicable to inorganicsubstances.1.4.2 GroupingGuidance on grouping of substances for the purpose of hazard evaluation is given in IR/CSA,Chapter R.6.2. Annex XI to REACH opens the possibility of evaluating substances not on aone-by-one basis, but by grouping substances in categories. A substance category is a groupof substances whose physico-chemical, human health, environmental and/or environmentalfate properties are expected to be similar or to follow a regular pattern as a result of structuralsimilarity.The use of grouping for hazard evaluation in the category approach means that not everysubstance needs to be tested for every hazard. Read across by interpolation can be used to filldata gaps, as well as trend analysis and (Q)SAR, and in addition the overall data for thatcategory must prove adequate to support the hazard assessment.Classification of all substances within an initially considered category may be inappropriateas substances may fall into more than one hazard classification category. Experience hasshown that, an effect can be present for some but not all members of an initially consideredcategory. One example is the glycol ethers, where some members of the category showreproductive toxicity whilst other members do not. In other cases, the category may show aconsistent trend where the resulting potencies lead to different classifications (IR/CSA,Chapter R.6.2.1.2). In such cases it is proposed to use sub-categories for the different hazardclasses where each sub-category receives the most appropriate classification.1.4.3 Read acrossRead across is the use of hazard specific information for one substance (“source”) to predictthe same hazard for another substance (“target”), which is considered to have similar physicochemical,environmental fate and/or (eco)toxicological properties. This can be based onstructural similarity (e.g. (Q)SAR) of a parent substance or its transformation products, andtheir bioavailability, bioaccessiblity, or known physico-chemical properties such as watersolubility. In principle, read across can be applied to characterise physico-chemical properties,environmental fate, human health effects and ecotoxicity. For certain substances without testdata the formation of common significant metabolites or information with those of testedsubstances or information from precursors may be valuable information (IR/CSA, ChapterR.6.2.5.2 and OECD 2004). For any hazard class, read across may be performed in aqualitative or quantitative manner. Extensive guidance on the use of read across is given inIR/CSA, Chapter R.6.2.2.1.Specific guidance for certain types of substances such as reaction products and multiconstituentsubstances, complex substances, isomers, metals and metal compounds and otherinorganic compounds is given in IR/CSA, Chapter R.6.2.5. This is because the concept ofsubstance categories has traditionally been widely used for hazard classification and to someextent also for risk assessment.48