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

Guidance on the Application of the CLP Criteria Version 3.0 - November 2012The system of classification is designed to ensure that a single classification applies to asubstance. In general it takes no account of the specific form since this can vary and is notintrinsic to the substance. The form in which the substance is placed on the market is takeninto account when deciding what label to apply and various derogations from labelling exist,e.g. the metals in the massive form. In the massive form the hazard may not be present andthe substance need not be labelled. The SDS will, however, indicate the classification andintrinsic hazardous properties to warn the user that subsequent transformation of the substancemay produce the hazardous form.For aquatic hazard classification, organic substances are generally tested in the dissolvedform. Exceptions to this approach include complex, multi-component substances and metalsand their compounds. Examples of alternative approaches include the use of WaterAccommodated Fractions (WAF) for complex, multi-component substances where thetoxicity cut-off is related to the loading, and a test strategy for metals and their compounds inwhich the specific form (i.e. particle size) used for testing is standardised and forms orphysical states are not further taken into account.1.3 SPECIFIC CASES REQUIRING FURTHER EVALUATION – LACK OFBIOAVAILABILITY1.3.1 DefinitionBioavailability is the rate and extent to which a substance can be taken up by an organism andis available for metabolism or interaction with biologically significant receptors.Bioavailability (biological availability) involves both release from a medium (if present) andabsorption by an organism (IPCS 2004).1.3.2 Bioavailability44Article 12Specific cases requiring further evaluationWhere, as a result of the evaluation carried out pursuant to Article 9, the following properties oreffects are identified, manufacturers, importers and downstream users shall take them into accountfor the purposes of classification:[…](b) conclusive scientific experimental data show that the substance or mixture is notbiologically available and those data have been ascertained to be adequate and reliable;[…]In general, bioavailability is not explicitly evaluated in hazard classification – the observationof systemic toxicity implicitly demonstrates a degree of bioavailability. On the other hand,when no toxicity is demonstrated in a test, this may be a result of either lack of intrinsictoxicity of the substance or lack of bioavailability in the test system employed. Nevertheless,as indicated in Article 12 (b) of CLP there may be cases where a specific evaluation ofbioavailability is warranted.In general terms, for a substance or mixture to have an effect on a biological or environmentalsystem, there must be some degree of bioavailability. Therefore, it follows that a substance ormixture need not be classified when it can be shown by conclusive experimental data frominternationally acceptable test methods, e.g. from Council Regulation (EC) No 440/2008, thatthe substance or mixture is not biologically available (UN GHS 1.3.2.4.5.1). A non