(4)Chapter 3.2 is replaced by the following:‘3.2.Skin corrosion/irritation3.2.1.Definitions and general considerations3.2.1.1.
3.2.1.2.In a tiered approach, emphasis shall be placed upon existing human data, followed by existing animal data, followed by in vitro data and then other sources of information. Classification results directly when the data satisfy the criteria. In some cases, classification of a substance or a mixture is made on the basis of the weight of evidence within a tier. In a total weight of evidence approach all available information bearing on the determination of skin corrosion/irritation is considered together, including the results of appropriate validated in vitro tests, relevant animal data, and human data such as epidemiological and clinical studies and well-documented case reports and observations (see Annex I, Part 1, Sections 1.1.1.3, 1.1.1.4 and 1.1.1.5).3.2.2.Classification criteria for substancesSubstances shall be allocated to one of the following two categories within this hazard class:3.2.2.1.Classification based on standard animal test data3.2.2.1.1.Skin corrosion3.2.2.1.1.1.A substance is corrosive to skin when it produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis in at least one tested animal after exposure for up to 4 hours.3.2.2.1.1.2.Corrosive substances shall be classified in Category 1 where data is not sufficient for sub-categorisation.3.2.2.1.1.3.When data are sufficient substances shall be classified in one of the three sub-categories 1A, 1B, or 1C in accordance with the criteria in Table 3.2.1.3.2.2.1.1.4.Three sub-categories are provided within the corrosion category: sub-category 1A — where corrosive responses are noted following up to 3 minutes exposure and up to 1 hour observation; sub-category 1B — where corrosive responses are described following exposure greater than 3 minutes and up to 1 hour and observations up to 14 days; and sub-category 1C — where corrosive responses occur after exposures greater than 1 hour and up to 4 hours and observations up to 14 days.Table 3.2.1Skin corrosion category and sub-categoriesCategory | CriteriaCategory 1 | Destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least one tested animal after exposure ≤ 4 hSub-Category 1A | Corrosive responses in at least one animal following exposure ≤ 3 min during an observation period ≤ 1 hSub-Category 1B | Corrosive responses in at least one animal following exposure > 3 min and ≤ 1 h and observations ≤ 14 daysSub-Category 1C | Corrosive responses in at least one animal after exposures > 1 h and ≤ 4 h and observations ≤ 14 days3.2.2.1.1.5.The use of human data is discussed in Sections 3.2.1.2 and 3.2.2.2 and also in Sections 1.1.1.3, 1.1.1.4 and 1.1.1.5.3.2.2.1.2.Skin irritation3.2.2.1.2.1.A substance is irritant to skin when it produces reversible damage to the skin following its application for up to 4 hours. The major criterion for the irritation category is that at least 2 of 3 tested animals have a mean score of ≥ 2,3 and ≤ 4,0.3.2.2.1.2.2.A single irritation category (Category 2) is presented in Table 3.2.2, using the results of animal testing.3.2.2.1.2.3.Reversibility of skin lesions is also considered in evaluating irritant responses. When inflammation persists to the end of the observation period in 2 or more test animals, taking into consideration alopecia (limited area), hyperkeratosis, hyperplasia and scaling, then a material shall be considered to be an irritant.3.2.2.1.2.4.Animal irritant responses within a test can be variable, as they are with corrosion. A separate irritant criterion accommodates cases where there is a significant irritant response but less than the mean score criterion for a positive test. For example, a test material might be designated as an irritant if at least 1 of 3 tested animals shows a very elevated mean score throughout the study, including lesions persisting at the end of an observation period of normally 14 days. Other responses could also fulfil this criterion. However, it should be ascertained that the responses are the result of chemical exposure.Table 3.2.2Skin irritation categorynotenoteCategoryCriteriaIrritation (Category 2)3.2.2.1.2.5.The use of human data is discussed in Sections 3.2.1.2 and 3.2.2.2 and also in Sections 1.1.1.3, 1.1.1.4 and 1.1.1.5.3.2.2.2Classification in a tiered approach3.2.2.2.1.A tiered approach to the evaluation of initial information shall be considered, where applicable, recognising that not all elements may be relevant.3.2.2.2.2.Existing human and animal data including information from single or repeated exposure shall be the first line of evaluation, as they give information directly relevant to effects on the skin.3.2.2.2.3.Acute dermal toxicity data may be used for classification. If a substance is highly toxic by the dermal route, a skin corrosion/irritation study is not practicable since the amount of test substance to be applied considerably exceeds the toxic dose and, consequently, results in the death of the animals. When observations are made of skin corrosion/irritation in acute toxicity studies and are observed up through the limit dose, these data may be used for classification, provided that the dilutions used and species tested are equivalent. Solid substances (powders) may become corrosive or irritant when moistened or in contact with moist skin or mucous membranes.3.2.2.2.4.In vitro alternatives that have been validated and accepted shall be used to make classification decisions.3.2.2.2.5.Likewise, pH extremes like ≤ 2 and ≥ 11,5 may indicate the potential to cause skin effects, especially when associated with significant acid/alkaline reserve (buffering capacity). Generally, such substances are expected to produce significant effects on the skin. In the absence of any other information, a substance is considered as corrosive to skin (Skin Corrosion Category 1) if it has a pH ≤ 2 or a pH ≥ 11,5. However, if consideration of acid/alkaline reserve suggests the substance may not be corrosive despite the low or high pH value, this needs to be confirmed by other data, preferably by data from an appropriate validated in vitro test.3.2.2.2.6.In some cases, sufficient information may be available from structurally related substances to make classification decisions.3.2.2.2.7.The tiered approach provides guidance on how to organize existing information on a substance and to make a weight of evidence decision about hazard assessment and hazard classification.Although information might be gained from the evaluation of single parameters within a tier (see Section 3.2.2.2.1.), consideration shall be given to the totality of existing information and making an overall weight of evidence determination. This is especially true when there is conflict in information available on some parameters.3.2.3.Classification criteria for mixtures3.2.3.1.Classification of mixtures when data are available for the complete mixture3.2.3.1.1.The mixture shall be classified using the criteria for substances, taking into account the tiered approach to evaluate data for this hazard class.3.2.3.1.2.When considering testing of the mixture, classifiers are encouraged to use a tiered weight of evidence approach as included in the criteria for classification of substances for skin corrosion and irritation (Sections 3.2.1.2 and 3.2.2.2), to help ensure an accurate classification as well as to avoid unnecessary animal testing. In the absence of any other information, a mixture is considered corrosive to skin (Skin Corrosion Category 1) if it has a pH ≤ 2 or a pH ≥ 11,5. However, if consideration of acid/alkaline reserve suggests the mixture may not be corrosive despite the low or high pH value, this needs to be confirmed by other data, preferably by data from an appropriate validated in vitro test.3.2.3.2.Classification of mixtures when data are not available for the complete mixture: bridging principles3.2.3.2.1.Where the mixture itself has not been tested to determine its skin corrosion/irritation potential, but there are sufficient data on the individual ingredients and similar tested mixtures to adequately characterise the hazards of the mixture, these data shall be used in accordance with the bridging rules set out in Section 1.1.3.3.2.3.3.Classification of mixtures when data are available for all ingredients or only for some ingredients of the mixture3.2.3.3.1.In order to make use of all available data for purposes of classifying the skin corrosion/irritation hazards of mixtures, the following assumption has been made and is applied where appropriate in the tiered approach:The “relevant ingredients” of a mixture are those which are present in concentrations ≥ 1 % (w/w for solids, liquids, dusts, mists and vapours and v/v for gases), unless there is a presumption (e.g., in the case of skin corrosive ingredients) that an ingredient present at a concentration < 1 % can still be relevant for classifying the mixture for skin corrosion/irritation.3.2.3.3.2.In general, the approach to classification of mixtures as corrosive or irritant to skin when data are available on the ingredients, but not on the mixture as a whole, is based on the theory of additivity, such that each skin corrosive or skin irritant ingredient contributes to the overall skin corrosive or skin irritant properties of the mixture in proportion to its potency and concentration. A weighting factor of 10 is used for skin corrosive ingredients when they are present at a concentration below the generic concentration limit for classification with Category 1, but are at a concentration that will contribute to the classification of the mixture as skin irritant. The mixture is classified as corrosive or irritant to skin when the sum of the concentrations of such ingredients exceeds a concentration limit.3.2.3.3.3.Table 3.2.3 provides the generic concentration limits to be used to determine if the mixture is considered to be corrosive or irritant to the skin.3.2.3.3.4.1.Particular care must be taken when classifying certain types of mixtures containing substances such as acids and bases, inorganic salts, aldehydes, phenols, and surfactants. The approach explained in Sections 3.2.3.3.1 and 3.2.3.3.2 may not be applicable given that many such substances are corrosive or irritant to the skin at concentrations < 1 %.3.2.3.3.4.2.For mixtures containing strong acids or bases the pH shall be used as a classification criterion (see Section 3.2.3.1.2) since pH is a better indicator of skin corrosion than the concentration limits in Table 3.2.3.3.2.3.3.4.3.A mixture containing ingredients that are corrosive or irritant to the skin and that cannot be classified on the basis of the additivity approach (Table 3.2.3), due to chemical characteristics that make this approach unworkable, shall be classified as Skin Corrosion Category 1 if it contains ≥ 1 % of an ingredient classified as Skin Corrosion or as Skin Irritation (Category 2) when it contains ≥ 3 % of an skin irritant ingredient. Classification of mixtures with ingredients for which the approach in Table 3.2.3 does not apply is summarised in Table 3.2.4.3.2.3.3.5.On occasion, reliable data may show that the skin corrosion/irritation hazard of an ingredient will not be evident when present at a level at or above the generic concentration limits mentioned in Tables 3.2.3 and 3.2.4 in Section 3.2.3.3.6. In these cases the mixture shall be classified according to that data (see also Articles 10 and 11). On other occasions, when it is expected that the skin corrosion/irritation hazard of an ingredient is not evident when present at a level at or above the generic concentration limits mentioned in Tables 3.2.3 and 3.2.4, testing of the mixture shall be considered. In those cases the tiered weight of evidence approach shall be applied, as described in Section 3.2.2.2.3.2.3.3.6.If there are data showing that (an) ingredient(s) is/are corrosive or irritant to skin at a concentration of < 1 % (skin corrosive) or < 3 % (skin irritant), the mixture shall be classified accordingly.Table 3.2.3Generic concentration limits of ingredients classified as skin corrosion (Category 1, 1A, 1B or 1C)/skin irritation (Category 2) that trigger classification of the mixture as skin corrosion/skin irritation where the additivity approach appliesSum of ingredients classified as: | Concentration triggering classification of a mixture as:| Skin corrosion | Skin irritation| Category 1 (see note below) | Category 2Skin corrosion Sub-Category 1A, 1B, 1C or Category 1 | ≥ 5 % | ≥ 1 % but < 5 %Skin irritation Category 2 | | ≥ 10 %(10 × Skin corrosion Sub-Category 1A, 1B, 1C or Category 1) + Skin irritation Category 2 | | ≥ 10 %Note:The sum of all ingredients of a mixture classified as Skin Corrosion Sub-Category 1A, 1B, or 1C respectively, shall each be ≥ 5 % in order to classify the mixture as either Skin Corrosion Sub-Category 1A, 1B or 1C. If the sum of the ingredients classified as Skin Corrosion Sub-Category 1A is < 5 % but the sum of ingredients classified as Skin Corrosion Sub-Category 1A + 1B is ≥ 5 %, the mixture shall be classified as Skin Corrosion Sub-Category 1B. Similarly, if the sum of ingredients classified as Skin Corrosion Sub-Category 1A + 1B ingredients is < 5 % but the sum of ingredients classified as Sub-Category 1A + 1B + 1C is ≥ 5 % the mixture shall be classified as Skin Corrosion Sub-Category 1C. Where at least one relevant ingredient in a mixture is classified as Category 1 without sub-categorisation, the mixture shall be classified as Category 1 without sub-categorisation if the sum of all ingredients corrosive to skin is ≥ 5 %.Table 3.2.4Generic concentration limits of ingredients that trigger classification of the mixture as skin corrosion/skin irritation, where the additivity approach does not applyIngredient: | Concentration: | Mixture classified as:Acid with pH ≤ 2 | ≥ 1 % | Skin corrosion Category 1Base with pH ≥ 11,5 | ≥ 1 % | Skin corrosion Category 1Other skin corrosive (Sub-Categories 1A, 1B, 1C or Category 1) ingredients | ≥ 1 % | Skin corrosion Category 1Other skin irritant (Category 2) ingredients, including acids and bases | ≥ 3 % | Skin irritation Category 23.2.4.Hazard Communication3.2.4.1.Label elements shall be used for substances or mixtures meeting the criteria for classification in this hazard class in accordance with Table 3.2.5.Table 3.2.5Label elements for skin corrosion/irritationClassification | Sub-Categories 1A/1B/1C and Category 1 | Category 2GHS Pictograms | |Signal Word | Danger | WarningHazard Statement | H314: Causes severe skin burns and eye damage | H315: Causes skin irritationPrecautionary Statement Prevention | P260P264P280 | P264P280Precautionary Statement Response | P301 + P330 + P331P303 + P361 + P353P363P304 + P340P310P321P305 + P351 + P338 | P302 + P352P321P332 + P313P362 + P364Precautionary Statement Storage | P405 |Precautionary Statement Disposal | P501 |
(5)Chapter 3.3 is replaced by the following:‘3.3.Serious eye damage/eye irritation3.3.1.Definitions and general considerations3.3.1.1.
3.3.1.2.In a tiered approach, emphasis shall be placed upon existing human data, followed by existing animal data, followed by in vitro data, and then other sources of information. Classification results directly when the data satisfy the criteria. In other cases, classification of a substance or a mixture is made on the basis of the weight of evidence within a tier. In a total weight of evidence approach all available information bearing on the determination of serious eye damage/eye irritation is considered together, including the results of appropriate validated in vitro tests, relevant animal data, and human data such as epidemiological and clinical studies and well-documented case reports and observations (see Annex I, Part 1, Section 1.1.1.3).3.3.2.Classification criteria for substancesSubstances are allocated to one of the categories within this hazard class, Category 1 (serious eye damage) or Category 2 (eye irritation), as follows:3.3.2.1.Classification based on standard animal test data3.3.2.1.1.Serious eye damage (Category 1)3.3.2.1.1.1.A single hazard category (Category 1) is adopted for substances that have the potential to seriously damage the eyes. This hazard category includes as criteria the observations listed in Table 3.3.1. These observations include animals with grade 4 cornea lesions and other severe reactions (e.g. destruction of cornea) observed at any time during the test, as well as persistent corneal opacity, discoloration of the cornea by a dye substance, adhesion, pannus, and interference with the function of the iris or other effects that impair sight. In this context, persistent lesions are considered those which are not fully reversible within an observation period of normally 21 days. Hazard classification as Category 1 also contains substances fulfilling the criteria of corneal opacity ≥ 3 or iritis > 1,5 observed in at least 2 of 3 tested animals, because severe lesions like these usually do not reverse within a 21-day observation period.3.3.2.1.1.2.The use of human data is discussed in Section 3.3.2.2 and also in Sections 1.1.1.3, 1.1.1.4 and 1.1.1.5.Table 3.3.1Serious eye damagenotenoteCategoryCriteriaCategory 1A substance that produces:3.3.2.1.2.Eye irritation (Category 2)3.3.2.1.2.1.Substances that have the potential to induce reversible eye irritation shall be classified in Category 2 (eye irritation).3.3.2.1.2.2.For those substances where there is pronounced variability among animal responses, this information shall be taken into account in determining the classification.3.3.2.1.2.3.The use of human data is addressed in Sections 3.3.2.2, and also in Sections 1.1.1.3, 1.1.1.4 and 1.1.1.5.Table 3.3.2Eye irritationnotenoteCategoryCriteriaCategory 2Substances that produce in at least 2 of 3 tested animals a positive response of:calculated as the mean scores following grading at 24, 48 and 72 hours after instillation of the test material, and which fully reverses within an observation period of normally 21 days.3.3.2.2.Classification in a tiered approach3.3.2.2.1.A tiered approach to the evaluation of initial information shall be considered where applicable, recognizing that not all elements may be relevant.3.3.2.2.2.Existing human and animal data shall be the first line of evaluation as they give information directly relevant to effects on the eye. Possible skin corrosion has to be evaluated prior to consideration of any testing for serious eye damage/eye irritation in order to avoid testing for local effects on eyes with skin corrosive substances. Skin corrosive substances shall be considered as leading to serious eye damage (Category 1) as well, while skin irritant substances may be considered as leading to eye irritation (Category 2).3.3.2.2.3.In vitro alternatives that have been validated and accepted shall be used to make classification decisions.3.3.2.2.4.Likewise, pH extremes like ≤ 2 and ≥ 11,5, may indicate serious eye damage, especially when associated with significant acid/alkaline reserve (buffering capacity). Generally such substances are expected to produce significant effects on the eyes. In the absence of any other information, a substance is considered to cause serious eye damage (Category 1) if it has a pH ≤ 2 or ≥ 11,5. However, if consideration of acid/alkaline reserve suggests the substance may not cause serious eye damage despite the low or high pH value, this needs to be confirmed by other data, preferably by data from an appropriate validated in vitro test.3.3.2.2.5.In some cases sufficient information may be available from structurally related substances to make classification decisions.3.3.2.2.6.The tiered approach provides guidance on how to organize existing information and to make a weight-of-evidence decision about hazard assessment and hazard classification. Animal testing with corrosive substances shall be avoided whenever possible. Although information might be gained from the evaluation of single parameters within a tier (see 3.3.2.1.1) consideration shall be given to the totality of existing information and making an overall weight of evidence determination. This is especially true when there is conflict in information available on some parameters.3.3.3.Classification criteria for mixtures3.3.3.1.Classification of mixtures when data are available for the complete mixture3.3.3.1.1.The mixture shall be classified using the criteria for substances, and taking into account the tiered approach to evaluate data for this hazard class.3.3.3.1.2.When considering testing of the mixture classifiers are encouraged to use a tiered weight of evidence approach as included in the criteria for classification of substances for skin corrosion and serious eye damage/eye irritation to help ensure an accurate classification, as well as to avoid unnecessary animal testing. In the absence of any other information, a mixture is considered to cause serious eye damage (Category 1) if it has a pH ≤ 2 or ≥ 11,5. However, if consideration of acid/alkali reserve suggests the mixture may not cause serious eye damage despite the low or high pH value, this needs to be confirmed by other data, preferably data from an appropriate validated in vitro test.3.3.3.2.Classification of mixtures when data are not available for the complete mixture: bridging principles3.3.3.2.1.Where the mixture itself has not been tested to determine its skin corrosivity or potential to cause serious eye damage/eye irritation, but there are sufficient data on the individual ingredients and similar tested mixtures to adequately characterise the hazards of the mixture, these data shall be used in accordance with the bridging rules set out in Section 1.1.3.3.3.3.3.Classification of mixtures when data are available for all ingredients or only for some ingredients of the mixture3.3.3.3.1.In order to make use of all available data for purposes of classifying the serious eye damage/eye irritation properties of the mixtures, the following assumption has been made and is applied where appropriate in the tiered approach:The “relevant ingredients” of a mixture are those which are present in concentrations ≥ 1 % (w/w for solids, liquids, dusts, mists and vapours and v/v for gases), unless there is a presumption (e.g. in the case of skin corrosive ingredients) that an ingredient present at a concentration < 1 % can still be relevant for classifying the mixture for serious eye damage/eye irritation.3.3.3.3.2.In general, the approach to classification of mixtures as seriously damaging to the eye/eye irritant when data are available on the ingredients, but not on the mixture as a whole, is based on the theory of additivity, such that each skin corrosive or serious eye damaging/eye irritant ingredient contributes to the overall serious eye damage/eye irritation properties of the mixture in proportion to its potency and concentration. A weighting factor of 10 is used for skin corrosive and serious eye damaging ingredients when they are present at a concentration below the generic concentration limit for classification with Category 1, but are at a concentration that will contribute to the classification of the mixture as eye irritant. The mixture is classified as seriously damaging to the eye or eye irritant when the sum of the concentrations of such ingredients exceeds a concentration limit.3.3.3.3.3.Table 3.3.3 provides the generic concentration limits to be used to determine if the mixture shall be classified as seriously damaging to the eye or as eye irritant.3.3.3.3.4.1.Particular care must be taken when classifying certain types of mixtures containing substances such as acids and bases, inorganic salts, aldehydes, phenols, and surfactants. The approach explained in Sections 3.3.3.3.1 and 3.3.3.3.2 might not work given that many such substances are seriously damaging to the eye/eye irritant at concentrations < 1 %.3.3.3.3.4.2.For mixtures containing strong acids or bases the pH shall be used as classification criterion (see Section 3.3.3.1.2) since pH will be a better indicator of serious eye damage (subject to consideration of acid/alkali reserve) than the generic concentration limits in Table 3.3.3.3.3.3.3.4.3.A mixture containing skin corrosive or serious eye damaging/eye irritating ingredients that cannot be classified based on the additivity approach (Table 3.3.3) due to chemical characteristics that make this approach unworkable, shall be classified as Serious Eye Damage (Category 1) if it contains ≥ 1 % of a skin corrosive or serious eye damaging ingredient and as Eye Irritation (Category 2) when it contains ≥ 3 % of an eye irritant ingredient. Classification of mixtures with ingredients for which the approach in Table 3.3.3 does not apply is summarised in Table 3.3.4.3.3.3.3.5.On occasion, reliable data may show that the effects of serious eye damage/eye irritation of an ingredient will not be evident when present at a level at or above the generic concentration limits mentioned in Tables 3.3.3 and 3.3.4 in Section 3.3.3.3.6. In these cases the mixture shall be classified according to those data (see also Articles 10 and 11). On other occasions, when it is expected that the skin corrosion/irritation hazards or the effects of serious eye damage/eye irritation of an ingredient will not be evident when present at a level at or above the generic concentration limits mentioned in Tables 3.3.3 and 3.3.4, testing of the mixture shall be considered. In those cases, the tiered weight of evidence approach shall be applied.3.3.3.3.6.If there are data showing that (an) ingredient(s) may be corrosive to the skin or seriously damaging to the eye/eye irritating at a concentration of < 1 % (corrosive to the skin or seriously damaging to the eye) or < 3 % (eye irritant), the mixture shall be classified accordingly.Table 3.3.3Generic concentration limits of ingredients classified as skin corrosion (Category 1, 1A, 1B or 1C) and/or serious eye damage (Category 1) or eye irritation (Category 2) that trigger classification of the mixture as serious eye damage/eye irritation where the additivity approach appliesSum of ingredients classified as: | Concentration triggering classification of a mixture as:Serious eye damage | Eye irritationCategory 1 | Category 2Skin corrosion Sub-Category 1A, 1B, 1C or Category 1 + Serious eye damage (Category 1) | ≥ 3 % | ≥ 1 % but < 3 %Eye irritation ( Category 2) | | ≥ 10 %10 × (Skin corrosion Sub-Category 1A, 1B, 1C or Skin corrosion Category 1 + Serious eye damage (Category 1)) + Eye irritation (Category 2) | | ≥ 10 %Table 3.3.4Generic concentration limits of ingredients that trigger classification of the mixture as serious eye damage (Category 1) or eye irritation (Category 2), where the additivity approach does not applyIngredient | Concentration | Mixture classified as:Acid with pH ≤ 2 | ≥ 1 % | Serious eye damage (Category 1)Base with pH ≥ 11,5 | ≥ 1 % | Serious eye damage (Category 1)Other ingredient classified as skin corrosion (Sub-Category 1A, 1B, 1C or Category 1) or serious eye damage (Category 1) | ≥ 1 % | Serious eye damage (Category 1)Other ingredient classified as eye irritation (Category 2) | ≥ 3 % | Eye irritation (Category 2)3.3.4.Hazard Communication3.3.4.1.Label elements shall be used for substances or mixtures meeting the criteria for classification in this hazard class in accordance with Table 3.3.5.Table 3.3.5Label elements for serious eye damage/eye irritationClassification | Category 1 | Category 2GHS Pictograms | |Signal Word | Danger | WarningHazard Statement | H318: Causes serious eye damage | H319: Causes serious eye irritationPrecautionary Statement Prevention | P280 | P264P280Precautionary Statement Response | P305 + P351 + P338P310 | P305 + P351 + P338P337 + P313Precautionary Statement Storage | |Precautionary Statement Disposal | |