appendix_a.pdf

A-1APPENDIX A – HEALTH HAZARD CRITERIA (MANDATORY)A.0 GENERAL CLASSIFICATION CONSIDERATIONSA.0.1ClassificationA.0.1.1The term “hazard classification” is used to indicate that only the intrinsic hazardous properties of chemicals are considered. Hazard classification incorporates three steps:(a) identification of relevant data regarding the hazards of a chemical;(b) subsequent review of those data to ascertain the hazards associated with the chemical;(c) determination of whether the chemical will be classified as hazardous and the degree of hazard.A.0.1.2For many hazard classes, the criteria are semi-quantitative or qualitative and expert judgment is required to interpret the data for classification purposes.A.0.2Available data, test methods and test data qualityA.0.2.1 There is no requirement for testing chemicals.A.0.2.2The criteria for determining health hazards are test method neutral, i.e., they do not specify particular test methods, as long as the methods are scientifically validated procedures.A.0.2.3The term “scientifically validated” refers to the process by which the reliability and the relevance of a procedure are established for a particular purpose.A.0.2.4Existing test data are acceptable for classifying chemicals, although expert judgment also may be needed for classification purposes.A.0.2.5The effect of a chemical on biological systems is influenced, by the physico- chemical properties of the substance and/or ingredients of the mixture and the way in which ingredient substances are biologically available. A chemical need not be classified when it can be shown by conclusive experimental data from scientifically validated test methods that the chemical is not biologically available.A.0.2.6For classification purposes, epidemiological data and experience on the effects of chemicals on humans (e.g., occupational data, data from accident databases) shall be taken into account in the evaluation of human health hazards of a chemical.A-2A.0.3Classification based on weight of evidenceA.0.3.1For some hazard classes, classification results directly when the data satisfy the criteria. For others, classification of a chemical shall be determined on the basis of the total weight of evidence using expert judgment. This means that all available information bearing on the classification of hazard shall be considered together, including the results of valid in vitro tests, relevant animal data, and human experience such as epidemiological and clinical studies and well-documented case reports and observations.A.0.3.2The quality and consistency of the data shall be considered. Information on chemicals related to the material being classified shall be considered as appropriate, as well as site of action and mechanism or mode of action study results. Both positive and negative results shall be assembled together in a single weight of evidence determination.A.0.3.3Positive effects which are consistent with the criteria for classification, whether seen in humans or animals, shall normally justify classification. Where evidence is available from both humans and animals and there is a conflict between the findings, the quality and reliability of the evidence from both sources shall be evaluated in order to resolve the question of classification. Reliable, good quality human data shall generally have precedence over other data. However, even well-designed and conducted epidemiological studies may lack a sufficient number of subjects to detect relatively rare but still significant effects, or to assess potentially confounding factors. Therefore, positive results from well-conducted animal studies are not necessarily negated by the lack of positive human experience but require an assessment of the robustness, quality and statistical power of both the human and animal data.A.0.3.4Route of exposure, mechanistic information, and metabolism studies are pertinent to determining the relevance of an effect in humans. When such information raises doubt about relevance in humans, a lower classification may be warranted. When there is scientific evidence demonstrating that the mechanism or mode of action is not relevant to humans, the chemical should not be classified.A.0.3.5Both positive and negative results are assembled together in the weight of evidence determination. However, a single positive study performed according to good scientific principles and with statistically and biologically significant positive results may justify classification.A.0.4Considerations for the classification of mixturesA.0.4.1For most hazard classes, the recommended process of classification of mixtures is based on the following sequence:(a) Where test data are available for the complete mixture, the classification of the mixture will always be based on that data;(b) Where test data are not available for the mixture itself, the bridging principles designated in each health hazard chapter of this appendix shall be considered for classification of the 。