GHS Classification Guidance for the Japanese Government
GHS Classification Guidance for the Japanese Government GHS Classification Guidance for the Japanese Government
3-2-9 Specific Target Organ Toxicity-Repeated Exposure (1)Definitions Definitions of Specific Targer Organ Toxicity-Repeated Exposure in UN GHS are as follows, and they are adopted in this guidance. 【GHS 2 nd revised edition】(3.9.1) 3.9.1.1 The purpose of this document is to provide a means of classifying substances that produce specific target organ toxicity arising from a repeated exposure. All significant health effects that can impair function, both reversible and irreversible, immediate and/or delayed are included. 3.9.1.2 Classification identifies the chemical substance as being a specific target organ toxicant and,as such, it may present a potential for adverse health effects in people who are exposed to it. 3.9.1.3 Classification depends upon the availability of reliable evidence that a repeated exposure to the substance has produced a consistent and identifiable toxic effect in humans, or, in experimental animals,toxicologically significant changes which have affected the function or morphology of a tissue/organ, or has produced serious changes to the biochemistry or haematology of the organism and these changes are relevant for human health. I t is recognized that human data will be the primary source of evidence for this hazard class. 3.9.1.4 A ssessment should take into consideration not only significant changes in a single organ or biological system but also generalized changes of a less severe nature involving several organs. 3.9.1.5 Specific target organ toxicity can occur by any route that is relevant for humans, i.e. principally oral, dermal or inhalation. 3.9.1.6 Non-lethal toxic effects observed after a single-event exposure are classified in the GHS as described in Specific target organ toxicity – Single exposure (Chapter 3.8) and are therefore excluded from the present chapter. Other specific toxic effects, such as acute /toxicity, serious eye damage/eye irritation,skin corrosion/irritation, respiratory or skin sensitization, carcinogenicity, germ cell mutagenicity, reproductive toxicity and aspiration toxicity are assessed separately in the GHS and consequently are not included here. 180
(2)Classification criteria A) Classification criteria based on JIS Classification Table 3-15: Hazard categories for specific target organ toxicity following repeated exposure Category 1: Substances that have produced significant toxicity in humans, or that, on the basis of evidence from studies in experimental animals can be presumed to have the potential to produce significant toxicity in humans following repeated exposure Placing a substance in Category 1 is done on the basis of : a) reliable and good quality evidence from human cases or epidemiological studies; or b) observations from appropriate studies in experimental animals in which significant and/or severe toxic effects of relevance to human health were produced at generally low exposure concentrations. Guidance dose/concentration values are provided below to be used as part of weight-of evidence evaluation (see Table 3.16). Category 2: Substances that, on the basis of evidence from studies in experimental animals can be presumed to have the potential to be harmful to human health following repeated exposure Placing a substance in Category 2 is done on the basis of observations from appropriate studies in experimental animals in which significant toxic effects, of relevance to human health, were produced at generally moderate exposure concentrations. Guidance dose/concentration values are provided below in order to help in classification (see Table 3.16). In exceptional cases, human evidence can also be used to place a substance in Category 2 (see Table 3.16). For both categories, the specific target organ/system that has been primarily affected by the classified substance may be identified, or the substance may be identified as a general toxicant. Attempts should be made to determine the primary target organ, organ/system of toxicity, and classify for that purpose, e.g. hepatotoxicants, neurotoxicants. One should carefully evaluate the data and, where possible, not include secondary effects, e.g. a hepatotoxicant can produce secondary effects in the nervous or gastro-intestinal systems. 181
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(2)<strong>Classification</strong> criteria<br />
A) <strong>Classification</strong> criteria based on JIS <strong>Classification</strong><br />
Table 3-15: Hazard categories <strong>for</strong> specific target organ toxicity following repeated exposure<br />
Category 1: Substances that have produced significant toxicity in humans, or that, on <strong>the</strong> basis of<br />
evidence from studies in experimental animals can be presumed to have <strong>the</strong> potential to produce<br />
significant toxicity in humans following repeated exposure<br />
Placing a substance in Category 1 is done on <strong>the</strong> basis of :<br />
a) reliable and good quality evidence from human cases or epidemiological studies; or<br />
b) observations from appropriate studies in experimental animals in which significant and/or<br />
severe toxic effects of relevance to human health were produced at generally low exposure<br />
concentrations. <strong>Guidance</strong> dose/concentration values are provided below to be used as part of<br />
weight-of evidence evaluation (see Table 3.16).<br />
Category 2: Substances that, on <strong>the</strong> basis of evidence from studies in experimental animals can be<br />
presumed to have <strong>the</strong> potential to be harmful to human health following repeated exposure<br />
Placing a substance in Category 2 is done on <strong>the</strong> basis of observations from appropriate studies in<br />
experimental animals in which significant toxic effects, of relevance to human health, were<br />
produced at generally moderate exposure concentrations. <strong>Guidance</strong> dose/concentration values are<br />
provided below in order to help in classification (see Table 3.16). In exceptional cases, human<br />
evidence can also be used to place a substance in Category 2 (see Table 3.16).<br />
For both categories, <strong>the</strong> specific target organ/system that has been primarily affected by <strong>the</strong><br />
classified substance may be identified, or <strong>the</strong> substance may be identified as a general toxicant.<br />
Attempts should be made to determine <strong>the</strong> primary target organ, organ/system of toxicity, and<br />
classify <strong>for</strong> that purpose, e.g. hepatotoxicants, neurotoxicants. One should carefully evaluate <strong>the</strong><br />
data and, where possible, not include secondary effects, e.g. a hepatotoxicant can produce secondary<br />
effects in <strong>the</strong> nervous or gastro-intestinal systems.<br />
181
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