User Guide to Thresholds and Classification - Environmental ...

210User Guide for Thresholds and Classificationsunscheduled DNA synthesis test (UDS) in testicular cells.Genotoxicity tests in somatic cells include the:liver UDS in vivo (OECD Test Guideline 486); andmammalian bone marrow sister chromatid exchanges (SCE)In vitro mutagenicity tests include the:in vitro mammalian chromosome aberration test (OECD Test Guideline 473);in vitro mammalian cell gene mutation test (OECD Test Guideline 476); andbacterial reverse mutation tests (OECD Test Guideline 471).The classification of individual substances should be based on the total weight of evidence available, usingexpert judgement. When a single well-conducted test is used for classification, it should provide clear andunambiguously positive results. If new, well-validated tests arise, these may also be used in the total weightof evidence to be considered. The relevance of the route of exposure used in the study of the chemicalcompared with the route of human exposure should also be taken into account.14.3. Classification of mixtures14.3.1. Classification of mixtures when data are available for the complete mixtureThe classification of mixtures is based on the available test data for the individual ingredients of the mixtureusing cut-off values or concentration limits for the ingredients classified as germ cell mutagens.The classification may be modified on a case-by-case basis based on the available test data for the mixtureas a whole. In such cases, the test results for the mixture as a whole must be shown to be conclusive, takinginto account dose and other factors such as duration of exposure, observations, and analysis (for example,statistical analysis and test sensitivity) of germ cell mutagenicity test systems.14.3.2. Classification of mixtures when data are not available for the complete mixture:bridging principlesWhen the mixture itself has not been tested to determine its germ cell mutagenicity hazard, but there aresufficient data on the individual ingredients and similar tested mixtures to adequately characterise thehazards of the mixture, these data will be used in accordance with the following agreed bridging rules. Thisensures the classification process uses the available data to the greatest extent possible in characterisingthe hazards of the mixture without needing additional testing in animals.a. DilutionIf a mixture is diluted with a diluent that is not expected to affect the germ cell mutagenicity of otheringredients, then the new mixture may be classified as equivalent to the original mixture.b. BatchingThe germ cell mutagenic potential of one production batch of a complex mixture can be assumed to besubstantially equivalent to that of another production batch of the same commercial product produced byJanuary 2012 EPA0109