Presentation on theme: "Classification of substances and mixtures on the basis of health hazard Semira Hajrlahović Mehić, LL.M. Tatjana Humar – Jurič, M.Sc."— Presentation transcript:
1Classification of substances and mixtures on the basis of health hazard Semira Hajrlahović Mehić, LL.M. Tatjana Humar – Jurič, M.Sc.
2Content Introduction Classification of substance Classification of mixture
3General informationChemicals placed on the Serbian market shall be classified by using of:Harmonised classificationsSelf-classification by application of the criteriaUse of translation tablesUse of classification and labelling inventory
4General informationThe classification criteria are in Part 2-5 of Annex I to CLP/GHS Rulebook!For OLD system- Upostvo za klasufikacijo, pakovanje, obeležavanje i reklamiranje hemikalija (2010)For NEW system- GHS (CLP/GHS system ) in practiceEU Guidances on CLP- EU Guidance on application of the CLP (= EU GHS) criteria- EU FAQ regarding CLP in EU and useful links
5Example: Classification of Substance- Health hazards MethanolAnimal data:LD50 rat > 5,000 (mg/kg)No specific target organ toxicity (impairment of seeing ability) observed in rats, even in high dosesHuman experience:Broad human experience from many case reports about blindness following oral intake.Methanol is known to cause lethal intoxications in humans (mostly via ingestion) in relatively low doses: ” …minimal lethal dose in the absence of medical treatment is between 300 and 1000 mg/kg” (IPCS)
6Example: Classification steps Use of adequate and reliable human data, where animal data are not appropriateIndependent classification for STOT-SE and Acute toxicity due to different effectsTask:Acute toxicity classificationSTOT (SE) classification
7Methanol : Acute toxicity Animal data:The rat is known to be insensitive to the toxicity of methanol and is thus not considered to be a good model for human effects (different effect/mode of action)Classification not possible
8Methanol: Acute toxicity Human experienceAnnex I: Substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria shown in Table Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE). Explanatory notes are shown following Table 3.1.1See ableThe minimum lethal dose reported of 300 mg/kg is used as equivalent ATE; according to Table the resulting classification is Category 3
9Methanol: STOT (SE)Annex I , Classification criteria for Categories 1 and 2See Table : Categories for specific target organ toxicity-single exposureThe classification criteria for Category 1 are fulfilled: clear human evidence of a specific target organ toxicity effect which is not covered by Acute toxicity
10Methanol - ConclusionThe standard animal species for single exposure (acute) tests, the rat, is not sensitive, i.e. no appropriate species for this specific target organ effect.Methanol is classified independently for acute toxicity, since the impairment of vision is not causal for the lethality, i. e. there are different effects.Methanol - Health hazards classification :Acute Tox. 3STOT SE 1Other hazards ?
11Classification of mixtures CLP/GHS self-classificationDepending on the information available and on the hazard under considerationyou should classify using following approaches:Using data on the mixture itself (not for CMR!)Classification based on the application of bridging principlesClassification based on the concentration of individual ingredients,NOTE: make sure that you choose the most appropriate method for yourmixture for each hazard class or category!
12Classification of mixtures Bridging principles:when data are not available for all components= used for classifying untested mixtures, but there are sufficient data on the components and/or similar tested mixtures, these data can be used in accordance with the following bridging principles:DilutingBatchingConcentration of highly toxic mixturesInterpolation within one toxicity categorySubstantially similar mixturesAerosolsAll bridging principles do not apply to every health endpoint!
13Example 1 A B C B Starting point: Mixture X Mixture Y= ?Toxic Cat. 3TestedTwo mixtures with several different ingredients (A, B, C)Both mixtures have one common ingredient (B) at the same concentrationThe concentrations and toxicities (classifications) of the other (A, C) ingredients are the sameMixture X is classified based on testingABCB
14Example 1 Substantially similar mixtures: A B C B Mixture X Mixture Y= Toxic Cat. 3Toxic Cat. 3TestedThe unknown mixture Y is classified in the same way as the tested: Toxic Cat. 3ABCB
15Classification of mixtures Classification based on the concentration of individual ingredients:When available data for all componentsCalculations using formulas (acute toxicity) based on additivityConcentration limits (tables; other hazard classes than acute toxicity)
16Classification of mixture Cut-off values Indicate when the presence of a substance needs to be taken into account for the purpose of classification of a substance or mixture containing that hazardous substanceImpurity, additive in a substance or individual constituent in a mixture:Specific concentration limits, SCL (List of classified substances, Inventory)Generic concentration limits, GCL (Annex I)Generic cut-off values (Annex I, Table 1.1)M-Factors (enviromental hazard!)New: SCL shall be set by the suppliers !16
17Generic cut-off values These values are minimum concentration for substances to be taken into account forclassification (even they do NOT trigger classification of the mixture directly)– if is concentration of sub. > generic cut-off value then contribute to the classificationTable 1.1 (Annex I)Hazard classAcute Toxicity:- Category 1 - 3- Category 4Skin corrosion/irritationSerious damage to eyes/eye irritationGeneric cut-off values to betaken into account0,1 %1 %
18Classification of mixtures Data available for all ingredients:A hazardous substance needs to be taken into account for the purpose of classification of a mixture if it is present in the mixture above the cutt-off valueEach of these substances contribute to the hazardous properties of the mixtureUse the additivity formula: if the sum of the concentrations is above the limit values -> mixture is classified for that hazard classUsing additivity formula:Acute ToxicityUsing the additivity aprochSkin corrosion/irritationSerious eye damage/eye irritation
19Classification of mixture Calculations using formulas (acute toxicity) based on additivityAdditivity formulaThe ATE of the mixture is determined by calculation from the ATE values for the relevantingredients (for all three routs of exposure)Ci = concentration of ingredient ii = the individual ingredient from 1 to nn = the number of ingredientsATEi = Acute Toxicity Estimate of ingredientiå=nmixATEC100ATE:- LD50 or LC50-value, or- Converted value (point estimate) foracute toxicity from Table in Annex I,relating to a value from a range test or toa classification category19
20Acute toxicity LD50 or LC50-value or Converted value (point estimate) for acute toxicity from Table in Annex I, relating to a value from a range test or to a classification category
21Classification of mixtures Classification based on the concentration of individual ingredientsAdditive concentration limitsSkin corrosion/irritationSerious eye damage/eye irritationSTOT SE, Cat. 3Non- additive concentration limitsSensitisers (respiratory and skin)CMRSTOT SE and RE, Cat 1-2Aspiration hazard
22Example of generic concentration limits for skin corrosion/irritation Additivity approach appliesGeneric concentration limits of ingredients classified that trigger classification of the mixture- Table of Annex ISum of ingredientsclassified as:Concentration triggering classificationof a mixture as:Skin CorrosiveSkin IrritantCategory 1Category 2Skin Corrosive Categories 1A, 1B, 1C 5 % 1 % but < 5 %Skin irritant Category 2 10 %(10* x Skin Corrosive Category 1A, 1B, 1C) +* Weighing factor of 10 if Category 1 component ≥ 1% but ≤ 5% in a mixture22
23Example generic concentration limits for reproduction toxicity/Effects on or via lactation: Non-Additivity approach appliesGeneric concentration limits of ingredients classified that trigger classification ofthe mixture- Table of Annex IIngredientclassified as:Concentration triggering classification of a mixture as:Repro cat. 1ARepro cat. 1BRepro cat.2Effects on or via lactation 0,3 %Repro cat. 2 3,0 %23
24Oral (mg/kg bw) 0 < category 1 ≤ 5 5 < category 2 ≤ 50 Conversion values Where an ATE is not available for an ingredient of a mixture, but available information can provide a value derived from the conversion table, this conversion value may be used for calculation. Conversion from experiementally obtained acute toxicity range values (or acute toxicity hazard categories) to acute toxicity point estimates for classification of the respective routes of exposureTable 3.1.2Exposure routeClassification category orexperimentally obtained acutetoxicity range estimateConverted acutetoxicity pointestimateOral(mg/kg bw)0 < category 1 ≤ 55 < category 2 ≤ 5050 < category 3 ≤ 300300 < category 4 ≤ 20000,5510050024
25Example 2 How is classified mixture A? ConcentrationLD50 oralClassificationSubstance 11%225 mg/kgSubstance 23%100 mg/kgSubstance 310%Acute tox.category 3, oralWater76%
26Conversion from hazard category to point estimate: Table 3.1.2Exposure routeClassification category orexperimentally obtained acutetoxicity range estimateConverted acutetoxicity pointestimateOral(mg/kg bw)0 < category 1 ≤ 55 < category 2 ≤ 5050 < category 3 ≤ 300300 < category 4 ≤ 20000,5510050026
27Classification of a mixture ConcentrationLD50 oralClassificationSubstance 11%225 mg/kgSubstance 23%100 mg/kgSubstance 310%Acute tox, cat 3Water76%ATE: 100Ci100=∑ATEiATEmixturen1310100=++ATEmixture = 743 mg/kg bwATEmixture22510010027