The Globally Harmonized System of Hazard Classification and Labelling of Chemicals: Critical Aspects for Metals: Human Health

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1 The Globally Harmonized System of Hazard Classification and Labelling of Chemicals: Critical Aspects for Metals: Human Health Prepared By Bill Adams (Rio Tinto) & Hugo Waeterschoot (EINA) February 13,

2 So the UN GHS is Being Implemented Around the World Why should I care? What are the consequences? How do I comply with the rules? 2

3 So the UN GHS is Being Implemented Around the World Why should I care? - Classifications are used to select and discriminate product selection; especially CMR substances - MSDS and product labels will be prepared on the basis of the classification determinations - MSDS identifies the hazards associated with a product and indicates safe handling procedures - Labels serve similar purposes for transport 3

4 So the UN GHS is Being Implemented Around the World What are the consequences - A key product may be determined to be a CMR or Dangerous for the Environment - Loss of market segments and loss of sales - Your product is placed on a no-purchase list by major corporations 4

5 So the UN GHS is Being Implemented Around the World How do I comply with the rules? - Start early to review the requirements - Obtain a copy of the UN Purple Book - Get some help! 5

6 Irish Solution

7 Microsoft Solution Help please?

8 So the UN GHS is Being Implemented Around the World How do I comply with the rules? - Let s do a quick review - What does a MSDS look like? - Adherence to the rules for each county 8

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13 Arrangement of some MSDS sections will change under GHS Outcomes of self classification according to GHS rules as required by REACH must be included in the MSDS MSDS provide a direct link between REACH and GHS GHS by itself does not require additional testing it is designed to use the test results from REACH 13

14 So the UN GHS is Being Implemented Around the World How do I comply with the rules? - Adherence to the rules for each county - software is available from vendors to assist with Country specific rules and language (e.g., Atrion, Actio, Chem-Alert, MSDS Solutions, 3-E Ariel, etc.) 14

15 GHS Environmental Classification A short overview - For details consult the UN GHS Purple book 15

16 Environmental Classification : the challenges NEW endpoint for most jurisdictions (origin EU) Most metals produce ions that are ecotoxic Toxicity profile Health versus Environment is often very different (e.g., Silver ions are very ecotoxic ) GHS Classification presently restricted to Acute AQUATIC toxicity and default for Chronic Near future : CHRONIC toxicity based on toxicity data Future : TERRESTRIAL toxicity based on toxicity data No data can lead to classification : SAFETY NET 16

17 Classification : How ACUTE : based on toxicity measurements CHRONIC : (lack of) Potential for BIODEGRADATION Potential of BIOACCUMULATION SAFETY NET!!! 17

18 Environmental classification : HOW? BLM model fish (rainbow trout) BLM model algae (Raphidocelis) ACUTE : lowest of 3 standard groups of organisms FISH (OECD TG 203) Waterfleas (Daphnia) (OECD TG 202) Algae (OECD TG 201) Based on standard test, standard triggers and standard test duration BLM model water flea (Daphnids) ACUTE 1 : if lowest value is < 1mg/l ACUTE 2 : if lowest value is > 1 but < 10mg/l ACUTE 3 : if lowest value is >10 but < 100mg/l 18

19 Environmental classification : HOW? BLM model fish (rainbow trout) BLM model algae (Raphidocelis) CHRONIC : Acute toxicity category AND substance is : not rapidly degradable AND / OR bioaccumulative (BCF 500 or Log Kow>4) BLM model water flea (Daphnids) SAFETY NET : No data on the substance BUT Grounds for concern exist 19

20 UN vs EU -GHS Environmental Classification Categories Acute I GHS Class Acute I & Chronic I EU and GHS R-Code R50 Hazard Label Very Toxic to Aquatic Env. R50/53 Very Toxic to Aquatic Env Can cause long term effects Acute II & Chronic II Acute III & Chronic III Chronic I, II or III R51/R53 R52/R53 R53 Toxic to Aquatic Env. Can cause long term effects Harmful to Aquatic Env. Can cause long term effects Can cause long term effects Chronic IV (safety net) R53 (not( in EU) Can cause long term effects 20

21 Challenges for Env. Cl.&L for Metals Often Very (effects) DATA RICH So LOWEST value approach is not fair/relevant Classification based on INTRINSIC property metal ion All metal ions are ecotoxic Dose expressed as mg/l Metals dose is NOT mg/l but surface related!!! Test data on all metals and Read across to metal compounds required to avoid Safety Net (chronic 4) Read across between salts (easily) possible Mixtures are classified on basis of properties of constituents ALLOYS properties ARE not equal to sum of properties constituents 21

22 How to Deal With Metals (Compounds) Under GHS? GHS gave specific attention to metals Specific guidance (separate chapter in purple book) Amended test procedure Specific criteria Specific metals Guidance has been tested for many metals (Zn, Cu and Ni most extensively) MERAG contains detailed guidance for : Metal compounds Metals in massive and powder form Alloys! 22

23 MERAG Guidance on Classification MERAG Metal Risk Assessment Guidance Document (fact sheets) Published in 2007 International in nature and extensively reviewed and peer reviewed Objective Aimed at consolidation technical and scientific knowledge on metals which advanced significantly over last couple of years. Incorporation of new concepts and improvements for RA & Cl & L Bioavailability, statistical extrapolation, Critical Reference Surface Area Critical Particle Size MERAG is NOT a legal document but well recognised by EU and OECD for its specific metals guidance 23

24 Environmental Classification of Metals and Metal (Compounds) PRINCIPLES : - Soluble metal compounds : - All classified by the toxicity of the metal ion - Classification corrected for molecular weight - Metals and Insoluble metals : - Classification based on READ ACROSS comparing - Potential of the metal SSMC to release ions - Ion toxicity 24

25 How to Deal With Data Richness and Toxicity Data Variability Derivation of Ecotoxicity Reference value 1. Data selection FOCUS on HIGH QUALITY data 2. Data aggregation - GROUPING per species/endpoint - Geometric mean per species - Lowest value based on different endpoints/species 3. Data treatment Special ruling for data rich Correction for bioavailability 25

26 Derivation Ecotoxicity Reference Value a tiered approach Base approach : -Data compilation : reliability and relevance -Aggregation of high quality toxicity data -Select lowest for reference value for different ph classes Refined Tier : -Data compilation : reliability and relevance -Refined data aggregation techniques (SSD s ) -Normalisation of reference value using Bioavailability models -Normalise to reference ph values (eg. 8 or 6, ) Tiered approaches allow applying refinement when needed or data are available 26

27 Refined Data aggregation TRV = HC5 Cumulative probability 100% 80% 60% 40% 20% 0% Species Sensitivity Distribution (SSD) Concentration (μg/l) Microcystis Derivation of TRV-SSD approach Pimephales Daphnia 27

28 ph 6 ( group) Normalisation of Effects Data: Correction for ph Algae tox data ph 6b Algae tox data ph 7b Daphnids toxalgae data tox ph 8a data ph 7a Fish tox data ph 7b Daphnids tox Daphnids data ph 6btox data ph 7b Algae tox data ph 7a Daphnids tox data ph 7b Algae tox data ph 7b Fish tox data ph 7b Fish tox data ph 6a Fish tox data ph 7a Algae tox data ph 8aAlgae tox data ph 6a ph 8 ( group) Fish tox data ph 7a Daphnids tox data ph 7b Fish tox data Algae ph tox 8a data Daphnids ph 8b tox data ph 6a Algae tox data Algae ph 8a Daphnids tox data ph 7a tox data ph 8b Daphnids tox data ph 8b Fish Daphnids tox data tox ph data 6b ph 8b ph 7 ( group) Fish tox data ph 8b Daphnids tox data ph 8b Fish tox data ph 8a Fish tox data ph 8b 28

29 Refined Approaches Critical surface approach : Allows to classify any powder size based on solubility and surface area as an intrinsic properties of a substance Measure release rate over time using the OECD Transformation- Dissolution protocol (TDp) Enables self classification for massives, powders And limits potential testing needs under REACH Application of the TDp to : Other inorganics Originally developed for metals and sparingly soluble metals, but can be extended to other matrix type inorganics like alloys/ceramics/glasses,... 29

30 Env C&L of Massive Metal : TDp Method Transformation/dissolution (TDp) tests OECD protocol Exposure time : 1 d (screening); 7 d s (acute); 28 d s (Chronic) Powders/Massive : finest relevant powder is tested Shaking : 100 rpm, without causing abbrasion Exposure medium : OECD 203 modified, ph 6, 7 & 8 CO 2 regulator cylinder of 99.5% purityco 2 gas flow control valve Flow meter Intake Fan * Shaker's enclosed vessel container Test Vessels SHAKER Outflow Vent Result T/D 1,10, 100 mg/l L(E)C50 at ph 6,7,8 Classify Acute 1 Acute 2 Acute 3 nc 30

31 Methodology for Metal Massives vs Powders Classification - Standard Approach (Skeaff et al. 2000, ET&C,Vol 19 (6):1681) metal released at different loadings = ug/l Specific surface area = mm 2 /mg Dissolved Metal (mg/l) Time Log Dissolved Metal (mg/l) Log surface area loading mm3/l 31

32 Methodology for Powders Classification EXAMPLE - Standard Approach (Skeaff et al. 2000) Measured Specific Surface Area (m 2 /g) 32

33 A distinctive classification for powders can be obtained IF: 1. Metal Powder is produced in a different way than the massive 2. Normal handling and use of massive should not result in the release of large amounts of powder material 3. Distinctive solubility kinetics/equilibrium for the massive and the powder form 4. Dissolution of powder provides for a different classification compared to the massive at the default particle size of 1mm (e.g., Zn, Cu, Cd) Smallest representative Powder form on the market should be : Metal Powder Definition/Classification : the principles Tested with the OECD Transformation Dissolution protocol (TDp) and Classified by comparing TDp outcome at day 7 & 28 with acute and chronic ecotox reference points covering ph range of

34 Classification of Metal and Powder the Ni Metal Example 34

35 Testing Massive material and Smallest representative powder on EU market was tested Ni Metal Powder Classification Example EU-OECD Transformation dissolution protocol (TDp) was used for testing, at different ph Is a different classification for Ni massive versus powder justified? 1. Ni metal massive & powder are separately and differently produced! 2. Normal handling and use of massives does not lead to Ni powder release 3. Different dissolution kinetics/equilibrium demonstrated 4. Particles size above which no classification is required could be identified and is < 1mm (default value for massive testing) 35

36 Nickel Metal Powder Classification Toxicity Reference Value & Powder size/surface Toxicity reference for Ni metal powder classification : ACUTE reference toxicity value : 68 µg Ni/L CHRONIC toxicity reference value : 2,4 µg Ni/L Tested Ni powder : measured surface area 0.43 m 2 /g 36

Ni Metal Powder Classification Ni case Surface (m²/g) 0.1 1.

37 Ni Metal Powder Classification Ni case Surface (m²/g) Diameter (µm) Smallest representative Powder (Surface 0,43 m²/g) 37

38 Ni Metal Powder Classification Example WITHOUT TDp evidence : based on read across from ion tox Ni powder and Ni metal classified as ACUTE 1!!!! WITH TDp evidence : based on dissolution kinetics Ni powder classified as ACUTE 3 Ni massive NOT classified!!! 38

39 Classification of Complex Materials If insoluble in nature : Like Concentrates apply same rule as for powders/massives HOW : - Select a representative material - Determine typical size occurring during normal handling and use - Determine toxicity reference doses for all relevant metal ions - Conduct TDp (24 h screening, 7d and 28d) - Compare dissolution of all ions at mg/l with reference toxicity levels In case massive material (e.g., Ni matte) - Apply Critical Surface Approach 39

40 Conclusions GHS will introduce Environmental Classification as a new hazard endpoint for many jurisdictions GHS provides for this endpoint (for the first time) specific ruling for metals and metal compounds Concentrates, while exempt from Reach, require GHS classification in Europe by the end of 2010 Env. Hazard ID is complex. MERAG has therefore established guidance that allows classifications and read-across : - Among soluble metal metal species - Towards sparingly soluble metal species - Towards massives and powders; and amongst powders - Towards special preparations/mixtures like alloys 40

41 GHS Human Health Classification A short overview - For details consult the UN GHS Purple book 41

42 Health Hazards Classification Health Hazard Classes Hazard Category Acute Toxicity, Oral Acute Toxicity, Dermal Acute Toxicity, Inhalation Skin Corrosion/Irritation 1 1A/B/C 2 3 Eye Damage/Irritation 1 2 2A/B Respiratory Sensitisation Skin Sensitisation Germ Cell Mutagenicity A/B 2 Carcinogenicity 1 1A/B 2 Reproductive Toxicity 1 1A/B 2 Lactation Target Organ ST Single Dose Target Organ ST Repeat Dose 1 2 Aspiration Hazard 1 2 Optional Sub Categories Optional Categories 1 is more severe than 5 Separate Classifications 42

Human Health Pictograms/Phrases Acute Toxicity: Danger Acute Toxicity: Warning Skin Corrosion/Irritation: Warning (irritation) Eye Damage/Irritation:

Eye Damage/Irritation: Danger (Corrosion) Respiratory Sensitisation: Danger STOT Single : Danger (Cat 1), Warning (Cat 2) Germ Cell Mutagenicity:

43 Human Health Pictograms/Phrases Acute Toxicity: Danger Acute Toxicity: Warning Skin Corrosion/Irritation: Warning (irritation) Eye Damage/Irritation: Warning (irritation) Skin Sensitization: Warning STOT Single: Warning (Category 3) Corrosive to Metals Skin Corrosion/Irritation: Danger (Corrosion) Eye Damage/Irritation: Danger (Corrosion) Respiratory Sensitisation: Danger STOT Single : Danger (Cat 1), Warning (Cat 2) Germ Cell Mutagenicity: Danger, Warning STOT Repeated: Danger, Warning Carcinogenicity: Danger, Warning Toxic to Reproduction: Danger, Warning Aspiration Toxicity: Danger, Warning 43

44 Acute toxicity 44

45 Acute Toxicity: Classification Criteria for Substances Acute toxicity hazard categories and (approximate) LD50/LC50 values Route Unit Cat. 1 Cat. 2 Cat. 3 Cat. 4 Cat. 5** Oral mg/kg < 5 < 50 < 300 < 2000 < 5000 Dermal mg/kg < 50 < 200 < 1000 < 2000 < 5000* Inhalation Gas Vapour Dust/Mist ppm < 100 < 500 < 2500 < * mg/l/4h < 0.5 < 2 < 10 < 20 * mg/l/4h < 0.05 < 0.5 < 1 < 5 * ** Cat 5 Optional: For identification of substances of relative low toxicity which may present a danger to vulnerable populations * Equivalent doses to oral and dermal levels for Cat 5 May vary with Regulatory Authority 45

46 Classification for Mixtures (e.g., ore concentrates) Use test data for the mixture, when available Use Bridging Principles, if applicable Calculation Additivity (Acute Toxicity) Summation (Skin and Eye Irritation, Aquatic) Thresholds (Sensitisation, CMRs, STOT) 46

47 Acute Toxicity Mixtures Provides for the situation in which the mixture has not been tested, but a similar mixture has been tested. Similar can be defined in terms of: Dilution Batching Concentration of Acute components Interpolation Substantially similar mixtures 47

48 Acute Toxicity Mixtures (1): Bridging Example Dilution Mixture A (Tested) = Mixture or + Substance B (Classification known) Mixture of A+B (=C) (Not Tested) If B is water or is non-toxic* then classification of C can be calculated e.g. if LD 50 of A is 50 mg/kg (Acute Cat 2 ), and it is diluted 2x with water, then toxicity of C is estimated to be 100 mg/kg (Acute Cat 3) * > LD mg/kg 48

49 Acute Toxicity Mixtures (2): Additivity LD 50 Range Converted to Acute Toxicity Estimate (ATE) Classification converted to ATE when Concentration if unknown ingredients is < 10% 100 ATE mix = n i C ATE or when Concentration of unknown ingredients is > 10% i i ( C if > 10% ) = ATEmix 100 unknown n Ci ATEi 49

50 Acute Toxicity Mixtures (3) Conversion of Acute Oral Toxicity Data from a Range or Limited Dose study or from the Classification Category in the absence of actual data Oral (mg/kg bw ) Classification category or experimentally obtained acute toxicity range estimate 0 < Category < Category < Category < Category < Category Converted Acute Toxicity Point Estimate ATE

51 Sensitisation 51

52 Do bears in the Woods? They might Be sensitive

53 Sensitisation: Classification Criteria Substances - Category 1 Respiratory Sensitisers If there is evidence in humans that the substance can induce specific respiratory hypersensitivity and/or If there are positive results from an appropriate animal test. Skin Sensitisers If there is evidence in humans that the substance can induce sensitisation by skin contact in a substantial number of persons, or If there are positive results from an appropriate animal test. Lower cut-off used for optional communication 53

54 Sensitisation: Label Elements Skin Sensitiser Respiratory Sensitiser WARNING May cause an allergic skin reaction DANGER May cause allergy or asthma symptoms or breathing difficulties if inhaled 54

55 Mutagenicity, carcinogenicity, reproductive toxicity 55

56 Mutagenicity Substances Category 1A: Category 1B: Category 2: Mixtures Chemicals known to induce heritable mutations in germ cells of humans Chemicals which should be regarded as if they induce heritable mutations in the germ cells of humans. Chemicals which cause concern for humans owing to the possibility that they may induce heritable mutations in the germ cells of humans Ingredient classified as Cut-off/concentration limits triggering classification of a mixture as: Category 1 mutagen Category 1 Mutagen 0.1 % Category 2 mutagen Category 2 Mutagen 1.0 % 56

57 Carcinogenicity Substances Category 1A: KNOWN to have carcinogenic potential for humans; the placing of a chemical is largely based on human evidence. Category 1B: PRESUMED to have carcinogenic potential for humans; the placing of a chemical is largely based on animal evidence. Category 2: SUSPECTED human carcinogens Mixtures Ingredient classified as Category 1 Carcinogen Cut-off/concentration limits triggering classification of a mixture as: Category 1 Carcinogen Category 2 Carcinogen > 0.1 % Category 2 Carcinogen > 0.1 % > 1.0 % Lower cut-off used for optional communication 57

58 Reproductive Toxicity Substances Category 1A: KNOWN human reproductive toxicant Category 1B: Category 2: PRESUMED human reproductive toxicant SUSPECTED human reproductive toxicant EFFECTS ON LACTATION Mixtures Ingredient classified as Category 1 Category 2 Additional category for effects on or via lactation Category 1 Reproductive Toxicant Category 2 Reproductive Toxicant Additional category for effects on or via lactation > 0.1 % > 0.3 % > 0.1 % > 3.0 % > 0.1 % > 0.3 % Lower cut-off used for optional communication 58

59 CMRs: Label Elements Category 1A Category 1B Category 2 Effects on or via lactation No Pictogram DANGER DANGER WARNING No Signal Word Germ Cell Mutagenicity Carcinogenicity May cause genetic defects May cause cancer May cause genetic defects May cause cancer Suspected of causing genetic defects Suspected of causing cancer NEW Reproductive Toxicity May damage fertility or the unborn child May damage fertility or the unborn child Suspected of damaging fertility or the unborn child May cause harm to breast-fed children. (state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard) 59

60 Specific target organ systemic toxicity (STOT) 60

61 Specific Target Organ Systemic Toxicity (STOT) Category 1 Category 2 Category 3 SINGLE Exposure Substances that have produced significant toxicity in humans, or that, on the basis of evidence from animal studies, can be presumed to have the potential to produce significant toxicity in humans following single exposure 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 single exposure Transient Target organ effects (Only Narcotic Effects and Respiratory Tract Irritation) REPEATED Exposure (EU Toxic): Substances that have produced significant toxicity in humans, or that, on the basis of evidence from animal studies can be presumed to have the potential to produce significant toxicity in humans following repeated exposure (EU Harmful): 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. 61

62 A. Single Exposure STOT Route of exposure Units Guidance value ranges for Category 1 Category 2 Category 3 Oral (rat) mg/kg bw C < > C > 300 Dermal (rat or rabbit) mg/kg bw C < > C > 1000 Inhalation (rat) gas ppm C < > C > 2500 Inhalation (rat) vapour mg/l C < > C > 10 Guidance Values do not apply Inhalation (rat) dust/mist/fume mg/l/4h C < > C > 1.0 Lower cut-off used for optional communication 62

63 B. Repeated Exposure STOT Route of exposure Units Guidance value (dose/concentration) Category 1 Category 2 Oral (rat) mg/kg/bw/day C < > C > 100 Dermal (rat or rabbit) mg/kg/bw/day C < > C > 200 Inhalation (rat) gas ppm/6h/day C < > C > 250 Inhalation (rat) vapour mg/l/6h/day C < > C > 1 Inhalation (rat) dust/mist/fume mg/l/6h/day C < > C >

64 Conclusions 64

65 Key Considerations for GHS Classifications for Metals Identify Physical State e.g., metal salt, oxide, sulfide, etc. Identify Relevant Properties: Key physicalchemical parameters (e.g., solubility, adsorptivity, particle size, transformation/dissolution, and critical surface area) Identify at-risk substances: Known carcinogens/ mutagens/reproductive toxicants (CMRs), endocrine disruptors 65

66 Key Considerations for GHS Classifications for Metals Identify appropriateness of read-across (Note - not all territories recognise-read across & not all read-across methods are appropriate) Use Weight of Evidence approach Consider all available information together to make a classification Consider quality and consistency of data Consider site and mechanisms of action; positive and negative data; and synergistic, additive, and antagonistic effects Use expert judgment to interpret the available data for classification purposes 66

67 Conclusions: Classification Challenges Classify using data from the chemical form/species that is biologically relevant Do not use data from a soluble species when classifying an insoluble compound if it results in classification unless. Ensure global consistency among producers: Inconsistency of classification could lead to unfair competition in marketplace Some jurisdictions may adopt most conservative self - classifications proposed so industry agreement is important Classify using data from the chemical form/species; Labels and MSDS s must reflect the competent authorities interpretation of the purple book available from the UN (UNEP) 67

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69 Example: CROSS JURISDICTION COMPARISON : acute toxicity, oral 69

70 What are we doing to help? 70

Human Health Classification: General Considerations and Overview

Human Health Classification: General Considerations and Overview 1 Key considerations for GHS Classifications Focuses on Self Classification by industry Identify Physical State e.g., metal salt, oxide,