User Guide to Thresholds and Classification - Environmental ...

268User Guide for Thresholds and Classificationsand neurotoxicants). One should carefully evaluate the data and, where possible, not include secondary effects (forexample, a hepatotoxicant can produce secondary effects in the nervous or gastro-intestinal system).Table 17C.2: Comparison of Globally Harmonized System of Classification and Labelling of Chemicals (GHS) andHSNO Act specific target organ toxicity (repeat exposure)GHS specific target organ toxicity repeat exposure classificationCategory 1: Substances that have produced significant toxicity in humans, or that, on the basis ofevidence from studies in experimental animals can be presumed to have the potential to producesignificant toxicity in humans following repeated exposureHSNO ActequivalentcategoryPlacing a substance in category 1 is done on the basis of:reliable and good quality evidence from human cases or epidemiological studies; or6.9Aobservations from appropriate studies in experimental animals in which significant and/orsevere toxic effects, of relevance to human health, were produced at generally low exposureconcentrations. Guidance dose–concentration values are used as part of the weight-ofevidenceevaluation.Category 2: Substances that, on the basis of evidence from studies in experimental animals canbe presumed to have the potential to be harmful to human health following repeated exposurePlacing a substance in category 2 is done on the basis of observations from appropriate studies inexperimental animals in which significant toxic effects, of relevance to human health, wereproduced at generally moderate exposure concentrations. Guidance dose–concentration valuesare provided to help in classification. In exceptional cases, human evidence can also be used toplace a substance in category 2.6.9BNote: For both categories, the specific target organ or system that has been primarily affected by the classifiedsubstance may be identified, or the substance may be identified as a general systemic toxicant. Attempts shouldbe made to determine the primary target organ of toxicity and classify for that purpose (for example, hepatoxicantsand neurotoxicants). One should carefully evaluate the data and, where possible, not include secondary effects (forexample, a hepatotoxicant can produce secondary effects in the nervous or gastrointestinal system).ReferencesUnited Nations 2007. The Globally Harmonized System of Classification and Labelling of Chemicals (GHS),2nd revised edition. United Nations, Geneva.January 2012 EPA0109