CHEMICAL SAFETY REPORT

Transcription

1 CHEMICAL SAFETY REPORT Substance Name: C. I. Pigment Red 104 EC Number: CAS Number: Registrant's Identity: DCC Maastricht B. V. OR

2 Table of Contents Part A SUMMARY OF RISK MANAGEMENT MEASURES DECLARATION THAT RISK MANAGEMENT MEASURES ARE IMPLEMENTED DECLARATION THAT RISK MANAGEMENT MEASURES ARE COMMUNICATED... 1 Part B IDENTITY OF THE SUBSTANCE AND PHYSICAL AND CHEMICAL PROPERTIES Name and other identifiers of the substance Composition of the substance Physicochemical properties Category document MANUFACTURE AND USES Manufacture Identified uses Uses advised against CLASSIFICATION AND LABELLING Classification and labelling according to CLP / GHS Classification and labelling according to DSD / DPD Classification and labelling in Annex I of Directive 67/548/EEC Self classification(s) Other classification(s) ENVIRONMENTAL FATE PROPERTIES Degradation Abiotic degradation Hydrolysis Phototransformation/photolysis Phototransformation in air Phototransformation in water Phototransformation in soil Biodegradation Biodegradation in water Screening tests Simulation tests (water and sediments) Summary and discussion of biodegradation in water and sediment Biodegradation in soil Summary and discussion of degradation Environmental distribution Adsorption/desorption Volatilisation Distribution modelling Summary and discussion of environmental distribution Bioaccumulation Aquatic bioaccumulation Terrestrial bioaccumulation Summary and discussion of bioaccumulation Secondary poisoning HUMAN HEALTH HAZARD ASSESSMENT Toxicokinetics (absorption, metabolism, distribution and elimination) Non-human information Human information Summary and discussion of toxicokinetics Acute toxicity Non-human information Acute toxicity: oral Acute toxicity: inhalation Acute toxicity: dermal Acute toxicity: other routes CSR-PI CHEMICAL SAFETY REPORT ii

3 Human information Summary and discussion of acute toxicity Irritation Skin Non-human information Human information Eye Non-human information Human information Respiratory tract Non-human information Human information Summary and discussion of irritation Corrosivity Non-human information Human information Summary and discussion of corrosion Sensitisation Skin Non-human information Human information Respiratory system Non-human information Human information Summary and discussion of sensitisation Repeated dose toxicity Non-human information Repeated dose toxicity: oral Repeated dose toxicity: inhalation Repeated dose toxicity: dermal Repeated dose toxicity: other routes Human information Summary and discussion of repeated dose toxicity Mutagenicity Non-human information In vitro data In vivo data Human information Summary and discussion of mutagenicity Carcinogenicity Non-human information Carcinogenicity: oral Carcinogenicity: inhalation Carcinogenicity: dermal Carcinogenicity: other routes Human information Summary and discussion of carcinogenicity Toxicity for reproduction Effects on fertility Non-human information Human information Developmental toxicity Non-human information Human information Summary and discussion of reproductive toxicity Other effects Non-human information Neurotoxicity Immunotoxicity Specific investigations: other studies CSR-PI CHEMICAL SAFETY REPORT iii

4 Human information Summary and discussion of other effects Derivation of DNEL(s) and other hazard conclusions Overview of typical dose descriptors for all endpoints Selection of the DNEL(s) or other hazard conclusion for critical health effects HUMAN HEALTH HAZARD ASSESSMENT OF PHYSICOCHEMICAL PROPERTIES Explosivity Flammability Oxidising potential ENVIRONMENTAL HAZARD ASSESSMENT Aquatic compartment (including sediment) Fish Short-term toxicity to fish Long-term toxicity to fish Aquatic invertebrates Short-term toxicity to aquatic invertebrates Long-term toxicity to aquatic invertebrates Algae and aquatic plants Sediment organisms Other aquatic organisms Terrestrial compartment Toxicity to soil macro-organisms Toxicity to terrestrial plants Toxicity to soil micro-organisms Toxicity to other terrestrial organisms Atmospheric compartment Microbiological activity in sewage treatment systems Non compartment specific effects relevant for the food chain (secondary poisoning) Toxicity to birds Toxicity to mammals PNEC derivation and other hazard conclusions PBT AND vpvb ASSESSMENT Assessment of PBT/vPvB Properties PBT/vPvB criteria and justification Summary and overall conclusions on PBT or vpvb properties EXPOSURE ASSESSMENT (and related risk characterisation) Introduction Overview of uses and Exposure Scenarios Introduction to the assessment Environment Man via environment Workers Consumers Waste management Exposure scenario 1: Formulation - Distribution and mixing pigment powder in an industrial environment into solvent-based paints for non-consumer use. Pigment choice depends on product specifications on visibility, shade and colour, durability, other requirements and Regulations Environmental contributing scenario 1: Distribution and mixing pigment powder in an industrial environment into solvent-based paints for non-consumer use Conditions of use Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Delivery, storage and handling of closed bags with pigment powder (PROC 3) Conditions of use Exposure and risks for workers Worker contributing scenario 2: Pigment powder quality control / lab work (PROC 15) Conditions of use Exposure and risks for workers Worker contributing scenario 3: Manual dosing of pigment powder (PROC 8a) CSR-PI CHEMICAL SAFETY REPORT iv

5 Conditions of use Exposure and risks for workers Worker contributing scenario 4: Automated dosing of pigment powder (PROC 8b) Conditions of use Exposure and risks for workers Worker contributing scenario 5: Re-packaging of pigment powder (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 6: Mixing of pigment paste (PROC 5) Conditions of use Exposure and risks for workers Worker contributing scenario 7: Storage of pigment paste / Transfer of pigment paste through closed piping (PROC 2) Conditions of use Exposure and risks for workers Worker contributing scenario 8: Manual cleaning / scraping of mixing vessels, equipment and lids (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 9: Cleaning of vessel with solvent (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 10: Pigment paste testing by smearing (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 11: Pigment paste charging/discharging by gravity or manual handling (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 12: Pigment paste charging/discharging using a dedicated installation (PROC 8b) Conditions of use Exposure and risks for workers Worker contributing scenario 13: Pigment paste filling into drums/cans at a filling line (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 14: Mixing colour paste in closed drum mixing machine with automated dosing of paste (PROC 2) Conditions of use Exposure and risks for workers Worker contributing scenario 15: Mixing colour paste into paint in closed mixing vessel (PROC 3) Conditions of use Exposure and risks for workers Worker contributing scenario 16: Pigment paint filling into drums/cans at a filling line (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 17: Pigment paint charging/discharging using a dedicated installation (PROC 8b) Conditions of use Exposure and risks for workers Worker contributing scenario 18: Equipment cleaning: scraping and brushing (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 19: Dried pigment paint cleaning (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 20: Spray testing of pigment paint in industrial booth (PROC 7) CSR-PI CHEMICAL SAFETY REPORT v

6 Conditions of use Exposure and risks for workers Worker contributing scenario 21: Pigment paint testing by brushing/rolling (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 22: Pigment paste or paint laboratory operations (PROC 15) Conditions of use Exposure and risks for workers Exposure scenario 2: Use at industrial site - Industrial application of paints on metal surfaces (machines, vehicles, structures, signs, road furniture, coil coating). Pigment choice is governed by end product specifications on visibility, colour, durability, other technical requirements and Regulations Environmental contributing scenario 1: Industrial application of paints on metal surfaces (machines, vehicles, structures, signs, road furniture, coil coating) Conditions of use Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Laboratory handling of pigment paste and/or paints (PROC 15) Conditions of use Exposure and risks for workers Worker contributing scenario 2: Handling of packaged colour paste and/or paint, including distribution (PROC 2) Conditions of use Exposure and risks for workers Worker contributing scenario 3: Mixing colour paste with paint in closed mixing machine with automated dosing of paste (PROC 3) Conditions of use Exposure and risks for workers Worker contributing scenario 4: Equipment cleaning: scraping, brushing and wiping (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 5: Dried pigment paste and/or paint cleaning (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 6: Mixing of paste and/or coating with extra solvents or additives before use (PROC 5) Conditions of use Exposure and risks for workers Worker contributing scenario 7: Filling of equipment with pigment paint (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 8: Filling of spray equipment with pigment paints in dedicated settings (PROC 8b) Conditions of use Exposure and risks for workers Worker contributing scenario 9: Transfer of pigment paint to/from drums/cans e.g. at a filling line before application (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 10: Automated pigment paint spray application in an industrial booth (PROC 7) Conditions of use Exposure and risks for workers Worker contributing scenario 11: Manual pigment paint spray application in an industrial booth (PROC 7) Conditions of use Exposure and risks for workers Worker contributing scenario 12: Handling and manipulation of dried painted articles (PROC 21) CSR-PI CHEMICAL SAFETY REPORT vi

7 Conditions of use Exposure and risks for workers Worker contributing scenario 13: Pigment paint testing by brushing/rolling (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 14: Pigment paint application and heat curing (PROC 6) Conditions of use Exposure and risks for workers Exposure scenario 3: Use by professional worker - Professional, non-consumer application of paints on metal surfaces (machines, vehicles, structures, signs, road furniture) or as road marking. Pigment choice is governed by requirements on visibility, colour, durability, technical performance and Regulations Environmental contributing scenario 1: Professional, non-consumer application of paints on metal surfaces (machines, vehicles, structures, signs, road furniture) or as road marking Conditions of use Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Handling of packaged colour paste and/or paint, including distribution (PROC 2) Conditions of use Exposure and risks for workers Worker contributing scenario 2: Dosing of colour paste into paint premix (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 3: Mixing colour paste with paint in closed mixing machine with automated dosing of paste (PROC 3) Conditions of use Exposure and risks for workers Worker contributing scenario 4: Filling of spray equipment with colour paints (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 5: Pigment paint spray application in a make-shift booth on location (PROC 11) Conditions of use Exposure and risks for workers Worker contributing scenario 6: Pigment paint spray application in a professional spray booth (PROC 11) Conditions of use Exposure and risks for workers Worker contributing scenario 7: Mixing of pigment paint in an open vessel (PROC 5) Conditions of use Exposure and risks for workers Worker contributing scenario 8: Pigment paint application by rolling/brushing (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 9: Cleaning of wet pigment paint on equipment by wiping and brushing (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 10: Cleaning of dried pigment paint on equipment by wiping, brushing, scraping etc. (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 11: Manipulation of pigment painted articles (dry) (PROC 21) Conditions of use Exposure and risks for workers Exposure scenario 4: Service life (worker at industrial site) - Service life of coated articles. Performance and longevity depend on the pigment quality for bright lasting colours improving visibility and safety, light and weather fastness (durability), chemical fastness, impact resistance and heat stability Environmental contributing scenario 1: Sanding of painted/coated articles Conditions of use CSR-PI CHEMICAL SAFETY REPORT vii

8 Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Cutting painted metal sheet (dry) (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 2: Sanding of dried paint on machines, vehicles, other metal articles etc. (PROC 24) Conditions of use Exposure and risks for workers Worker contributing scenario 3: Welding, torchcutting of painted metal (dry) (PROC 25) Conditions of use Exposure and risks for workers Exposure scenario 5: Service life (professional worker) - Service life of coated articles. Performance and longevity depend on the pigment quality for bright lasting colours improving visibility and safety, light and weather fastness (durability), chemical fastness, impact resistance and heat stability Environmental contributing scenario 1: Leaching from painted metal surfaces (machines, vehicles, structures, signs, road furniture, coil coating) during service life Conditions of use Releases Exposure and risks for the environment and man via the environment Environmental contributing scenario 2: Sanding of painted/coated articles Conditions of use Releases Exposure and risks for the environment and man via the environment Environmental contributing scenario 3: Leaching from painted road marking during service life Conditions of use Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Cutting painted metal sheet (dry) (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 2: Sanding of dried paint on machines, vehicles, other articles etc. (PROC 24) Conditions of use Exposure and risks for workers Worker contributing scenario 3: Welding, torchcutting of painted metal (dry) (PROC 25) Conditions of use Exposure and risks for workers Exposure scenario 6: Formulation - Distribution and mixing pigment powder in an industrial environment into liquid or solid premix to colour plastic/plasticised articles. Pigment choice depends on product specifications on visibility, colour, heat stability, durability and Regulations Environmental contributing scenario 1: Distribution and mixing pigment powder in an industrial environment into a premix or pre-compound to add colour to plastic or plasticised articles Conditions of use Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Delivery, storage and handling of closed paper bags with pigment powder (PROC 3) Conditions of use Exposure and risks for workers Worker contributing scenario 2: Pigment powder quality control / lab work (PROC 15) Conditions of use Exposure and risks for workers Worker contributing scenario 3: Manual dosing of pigment powder (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 4: Automated dosing of pigment powder (PROC 8b) Conditions of use Exposure and risks for workers CSR-PI CHEMICAL SAFETY REPORT viii

9 Worker contributing scenario 5: Mixing of pigment with resins and additives to form a liquid pre-mix/pre-compound (PROC 5) Conditions of use Exposure and risks for workers Worker contributing scenario 6: Storage of premix/pre-compound / Transfer of pre-mix/pre-compound through closed piping (PROC 2) Conditions of use Exposure and risks for workers Worker contributing scenario 7: Premix/pre-compound charging/discharging by gravity or manual handling (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 8: Premix/pre-compound charging/discharging using a dedicated installation (PROC 8b) Conditions of use Exposure and risks for workers Worker contributing scenario 9: Premix/pre-compound filling into drums/cans at a filling line (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 10: Manual cleaning / scraping of mixing vessels, equipment and lids (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 11: Cleaning of vessel with resin (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 12: Premix/pre-compound quality control / lab work (PROC 15) Conditions of use Exposure and risks for workers Worker contributing scenario 13: Production of coloured plastic granules or masterbatch by extrusion, compression and/or pelletisation (PROC 14) Conditions of use Exposure and risks for workers Worker contributing scenario 14: Mixing pigment powder or premix/pre-compound into matrix in closed mixing vessel (PROC 3) Conditions of use Exposure and risks for workers Worker contributing scenario 15: Production of plastic articles by extrusion, injection moulding and other processes (PROC 14) Conditions of use Exposure and risks for workers Worker contributing scenario 16: Quality control / lab work with coloured plastics (PROC 15) Conditions of use Exposure and risks for workers Worker contributing scenario 17: Handling of articles and single coloured granules (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 18: Handling of mixed coloured granules and articles (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 19: Transfer of articles and single coloured granules (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 20: Transfer of articles and single coloured granules (PROC 8b) CSR-PI CHEMICAL SAFETY REPORT ix

10 Conditions of use Exposure and risks for workers Worker contributing scenario 21: Transfer of mixed coloured granules and articles (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 22: Transfer of mixed coloured granules and articles (PROC 8b) Conditions of use Exposure and risks for workers Worker contributing scenario 23: Pigment powder dosing before mixing (PROC 8b) Conditions of use Exposure and risks for workers Worker contributing scenario 24: Mixing of pigment powder with other solid additives (PROC 3) Conditions of use Exposure and risks for workers Worker contributing scenario 25: Filling of small packages with pigment powder (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 26: Manual handling of pigment contained in small sealed plastic bags (<1 kg) (PROC 1) Conditions of use Exposure and risks for workers Worker contributing scenario 27: Pigment powder manual cleaning, wiping, scraping etc. (PROC 19) Conditions of use Exposure and risks for workers Exposure scenario 7: Use at industrial site - Use of colour premixes and pre-compounds to colour plastic or plasticised articles for non-consumer use. Pigment choice depends on product specifications on visibility, colour, heat stability, chemical fastness, durability and Regulations Environmental contributing scenario 1: Use of colour premixes and pre-compounds to colour plastic or plasticized articles for non-consumer use Conditions of use Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Delivery, storage and handling of coloured plastic granules (PROC 3) Conditions of use Exposure and risks for workers Worker contributing scenario 2: Delivery, storage and handling of packed plastic premix or pre-compound (PROC 3) Conditions of use Exposure and risks for workers Worker contributing scenario 3: Transfer of articles and single coloured granules (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 4: Transfer of articles and single coloured granules (PROC 8b) Conditions of use Exposure and risks for workers Worker contributing scenario 5: Transfer of mixed coloured granules and articles (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 6: Transfer of mixed coloured granules and articles (PROC 8b) Conditions of use Exposure and risks for workers Worker contributing scenario 7: Charging/discharging of coloured plastic granules (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 8: Mixing coloured plastic granules in closed mixing vessel (PROC 3) CSR-PI CHEMICAL SAFETY REPORT x

11 Conditions of use Exposure and risks for workers Worker contributing scenario 9: Production of plastic articles by extrusion and injection moulding or other processes (PROC 14) Conditions of use Exposure and risks for workers Worker contributing scenario 10: Charging/discharging of coloured plastic premix or pre-compound (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 11: Charging/discharging of coloured plastic premix or pre-compound (PROC 9) Conditions of use Exposure and risks for workers Worker contributing scenario 12: Roll application and heat curing of coloured plastic paste (PROC 6) Conditions of use Exposure and risks for workers Worker contributing scenario 13: Handling and manipulation of pigment plastic articles and plastic coated textiles (PROC 21) Conditions of use Exposure and risks for workers Exposure scenario 8: Use by professional worker - Use of colour premixes and pre-compounds in the application of hotmelt road marking. Pigment choice depends on end product specifications on visibility & night time reflectivity, colour, heat stability, durability, chemical fastness and Regulations Environmental contributing scenario 1: Use of colour premixes and pre-compounds in the application of hotmelt road marking Conditions of use Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Charging/discharging premix or pre-compound (PROC 8a) Conditions of use Exposure and risks for workers Worker contributing scenario 2: Storage and mixing of plastic compounds in an open vessel before application (PROC 5) Conditions of use Exposure and risks for workers Worker contributing scenario 3: Application of hotmelt road marking (plastic compound) to road pavement (PROC 10) Conditions of use Exposure and risks for workers Worker contributing scenario 4: Handling and manipulation of coloured road marking (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 5: High energy manipulation/removal of coloured road marking using abrasive techniques like grinding, drilling or sanding (PROC 24) Conditions of use Exposure and risks for workers Exposure scenario 9: Service life (worker at industrial site) - Service life of coloured plastic or plasticised articles. Performance and longevity depend on pigment quality, for bright lasting colours improving visibility and safety, heat stability, durability, other technical specifications and Regulations Environmental contributing scenario 1: Industrial service life of coloured plastic or plasticised articles, including hotmelt road marking Conditions of use Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Handling and manipulation of pigment plastic articles, plastic coated textiles and coloured road marking (PROC 21) CSR-PI CHEMICAL SAFETY REPORT xi

12 Conditions of use Exposure and risks for workers Worker contributing scenario 2: High energy manipulation of pigment plastic articles, plastic coated textiles and coloured road marking using abrasive techniques like mechanical cutting, grinding, drilling or sanding (PROC 24) Conditions of use Exposure and risks for workers Exposure scenario 10: Service life (professional worker) - Service life of coloured plastic or plasticised articles. Performance and longevity depend on pigment quality, for bright lasting colours improving visibility and safety, heat stability, durability, other technical specifications and Regulations Environmental contributing scenario 1: Service life of coloured plastic and plasticised articles, including hotmelt road marking (leaching) Conditions of use Releases Exposure and risks for the environment and man via the environment Environmental contributing scenario 2: Removal of hotmelt road marking Conditions of use Releases Exposure and risks for the environment and man via the environment Worker contributing scenario 1: Handling and manipulation of pigment plastic articles, plastic coated textiles and coloured road marking (PROC 21) Conditions of use Exposure and risks for workers Worker contributing scenario 2: High energy manipulation of pigment plastic articles, plastic coated textiles and coloured road marking using abrasive techniques like mechanical cutting, grinding, drilling or sanding (PROC 24) Conditions of use Exposure and risks for workers RISK CHARACTERISATION RELATED TO COMBINED EXPOSURE Human health Workers Consumer Environment (combined for all emission sources) All uses (regional scale) Total releases Regional exposure Local exposure due to all wide dispersive uses Local exposure due to combined uses at a site CSR-PI CHEMICAL SAFETY REPORT xii

13 Part A 1. SUMMARY OF RISK MANAGEMENT MEASURES The operational conditions and risk management measures required for safe use are listed in Chapter 9 of this Chemical Safety Report. 2. DECLARATION THAT RISK MANAGEMENT MEASURES ARE IMPLEMENTED As the substance is only imported into the EU, the registrant has no own uses within the EU. The uses of the manufacturer are outside the jurisdiction of the REACH regulation. 3. DECLARATION THAT RISK MANAGEMENT MEASURES ARE COMMUNICATED The operational conditions and risk management measures will be communicated by means of the extended safety data sheet to the downstream users without undue delay after registration CSR-PI CHEMICAL SAFETY REPORT 1

14 Part B 1. IDENTITY OF THE SUBSTANCE AND PHYSICAL AND CHEMICAL PROPERTIES 1.1. Name and other identifiers of the substance The substance C. I. Pigment Red 104 is a mono constituent substance (origin: inorganic) having the following characteristics and physical chemical properties (see the IUCLID dataset for further details). The following public name is used: lead chromate molybdate sulfate red. Table 1. Substance identity EC number: EC name: CAS number (EC inventory): lead chromate molybdate sulfate red CAS name: C.I. Pigment Red 104 IUPAC name: Annex I index number: Molecular formula: Molecular weight range: Colour Index description lead chromate molybdate sulfate red Pb (Cr,S,Mo) O4 Lead molybdosulphochromate (PbMoSCrO4) with oxides of Lanthanides, Al, Ce, Sb, Si, Sn, Ti, Zn, Zr and Fluorine salts Structural formula: 1.2. Composition of the substance Name: lead chromate molybdate sulfate red Description: This substance is identified in the Colour Index by Colour Index Constitution Number, C. I Degree of purity: >= 80.0 <= % (w/w) CSR-PI CHEMICAL SAFETY REPORT 2

15 Table 2. Constituents Constituent Typical concentration Concentration range Remarks C.I. Pigment Red 104 EC no.: Table 3. Impurities >= 80.0 <= % (w/w) Impurity Typical concentration Concentration range Remarks Unknown substance Table 4. Additives >= 0.0 <= 1.0 % (w/w) Additive Function Typical concentration silicon dioxide EC no.: Diantimony trioxide EC no.: aluminium oxide (oxo(oxoalumanyloxy)alu mane) Concentration range stabiliser >= 1.4 <= 20.0 % (w/w) stabiliser >= 0.0 <= 4.8 % (w/w) stabiliser >= 0.0 <= 3.0 % (w/w) Remarks EC no.: Physicochemical properties Table 5. Physicochemical properties Property Physical state Melting / freezing point Description of key information The substance is a solid, described as a red odourless powder. Value used for CSA / Discussion Value used for CSA: solid at 20 C and kpa The melting point is derived Value used for CSA: 800 C at kpa by read across from supporting substances (lead chromate, lead molybdate, lead sulfate) on which the solid solution is based, which have melting points above 800 C. Boiling point In accordance with column 2 of REACH Annex VII, the boiling point does not need to be performed as the substance is a solid with the melting point above 300 C. Relative density The density ranges from 3.8 to 6.3 g/cm3 at 20 C. A mean value of ca. 5 g/cm3 is taken. Value used for CSA: 5 at 20 C CSR-PI CHEMICAL SAFETY REPORT 3

16 Property Granulometry Description of key information Mean Particle Size: C.I. Pigment Yellow 34: µm C.I. Pigment Red 104: µm Dustiness: For C.I. Pigment Red 104, the respirable fraction of the inhalable dustiness mass fraction is 1.2% Value used for CSA / Discussion Particle size distribution: The particle size distribution of C.I. Pigment Yellow 34 and C.I. Pigment Red 104 was measured using a Coulter LS Particle Size Analyser. Four different samples from each pigment were measured. The mean particle size ranged from µm for C.I. Pigment Yellow 34 and from µm for C.I. Pigment Red 104, under the conditions of this test. Pigme nt sample Mean particle size in μm %<D10 %<D50 %<D90 Mean (100%) C.I. PY Vapour pressure In accordance with column 2 of REACH Annex VII, the vapour pressure study does not need to be performed as the melting point is above 300 C. Partition coefficient n-octanol/water (log value) Water solubility In accordance with column 2 of REACH Annex VII, the partition coefficient does not need to be performed as the substance is inorganic. C.I. PR.104 Dustiness testing: The dustiness of DCC Orange 1629 (Regular Pigment Red 104) was investigated according to EN using the rotating drum method. The dustiness results of sample DCC Orange 1629 (Regular Pigment Red 104) are as follows (at 21ºC and RH of 44 +/-3%): The average inhalable dustiness mass fraction is 2201 mg kg-1 and is classified as moderate. The average thoracic dustiness mass fraction is 304 mg kg-1 and is classified as moderate. The average respirable dustiness mass fraction is 27 mg kg-1 and is classified as low. For C.I. Pigment Red 104, the respirable fraction of the inhalable dustiness mass fraction is 27/2201*100% = 1.2% The dissolved concentration Value used for CSA: 69.3 µg/l at 20 C of lead in a 1 mg/l mixture of C.I. Pigment Red 104 after 28 The transformation/dissolution of chromium and lead from CSR-PI CHEMICAL SAFETY REPORT 4

17 Property Description of key information days at ph 6 according to OECD test guideline 29 (Transformation/dissolution protocol) was 69.3 ug lead/l. After 28 days a plateau was reached. Value used for CSA / Discussion representative samples of C.I. Pigment Yellow 34 and C.I. Pigment Red 104 and from C.I. Pigment Yellow 34 used in paint and plastic matrix) was determined according to OECD guideline 29 under GLP using ICP-MS. The tests were performed at ph 6 and 8 in a screening test (24h) at 100 mg test item per liter and both Chromium and Lead were analysed. Surface tension In line with column 2 of REACH Annex VII, the surface activity does not need to be conducted as the water solubility is below 1 mg/l at 20 C. Based on the chemical structure, no surface activity is expected. Flash point In accordance with section 1 of REACH Annex XI, the flash point does not need to be tested as the substance is a solid (scientifically unjustified) and in accordance with column 2 of REACH Annex VII, the flash point does not need to be performed as the substance is inorganic (other justification). Autoflammability / self-ignition temperature In accordance with column 2 of REACH Annex VII, the auto flammability does not need to be conducted as the substance is a solid and self-heating of the substance Chromium dissolution was higher at ph 8 and lead dissolution was higher at ph 6. Overall the dissolution of lead was considerably higher than that of chromium. As the toxicity of lead also seems to be higher than that of chromium, it was decided that the full test should be carried out with lead at ph 6. The full test was performed with the pigments (1, 10 and 100 mg/l) and the paint and plastic matrix (100 mg/l). The dissolution of samples at 10 and 100 mg/l were followed for 1 week. For the pigment sample of 1 mg/l and the paint and plastic matrix the duration was 28 days. The curve of the dissolution over time shows that a plateau level was reached after 28 days. For C.I. Pigment Yellow 34 and C.I. Pigment Red 104 dissolved lead concentrations were found to be 36.8 and 69.3 ug/l after 28 days at a loading rate of 1 mg/l respectively. For the paint and plastic matrices, this was 28.9 and 1.1 ug/l. This represents circa 0.2% of the lead contents in all cases. When related to the surface area of the pigments, the dissolution was 5.1 and 7.2 mg lead/m2 after 28 days CSR-PI CHEMICAL SAFETY REPORT 5

18 Property Description of key information up to 400 C is excluded. Flammability In accordance with section 1 of REACH Annex XI, the flammability does not need to be performed as the substance is a non combustible solid, non flammable upon ignition. The substance has no pyrophoric properties and does not yield flammable gases on contact with water. Value used for CSA / Discussion Value used for CSA: non flammable Explosive properties In accordance with column 2 Value used for CSA: non explosive of REACH Annex VII, the explosiveness of the substance does not need to be tested, because there are no chemical groups associated with explosive properties in the molecule Oxidising properties EC Physico/Chemical Test A17, Oxidizing Properties (Solid) Test: not oxidising Stability in organic solvents and identity of relevant degradation products In accordance with column 2 of REACH Annex IX, the stability in organic solvents does not need to be performed as the substance is inorganic. Dissociation constant In accordance with section 1 of REACH Annex XI, the dissociation constant study does not need to be performed as the substance is not soluble in water and does not contain any ionic structure. Value used for CSA: Oxidising: no The oxidising properties of C.I. Pigment Red 104 were determined in accordance with the EC Physico/Chemical Test A17, Oxidizing Properties (Solid) Test. In the preliminary test, the burning time of C.I. Pigment Red 104 was determined to be more than the reference sample in the preliminary screening test. Therefore the full train test was conducted. In the full train test, the highest burning rate recorded from the six samples of C.I. Pigment Red 104 in cellulose was 0.36 mm/s, which was the sample with 80% of the test substance. This value should be compared to the highest burning rate of the reference substance Barium Nitrate, which was 0.85mm/s. It can be concluded that the sample of C.I. Pigment Red 104 should not be classed as an oxidizing substance since in any percentage of C.I. Pigment Red 104/Cellulose, it has a burning rate of less than that of Barium Nitrate/Cellulose per EC Physico/Chemical Test A17, Oxidizing Properties (Solid) Test CSR-PI CHEMICAL SAFETY REPORT 6

19 Property Description of key information Viscosity In accordance with section 2 of REACH Annex XI, the viscosity does not need to be performed as the substance is a solid. Data waiving Value used for CSA / Discussion Information requirement: Boiling point Reason: other justification Justification: In accordance with column 2 of REACH Annex VII, the boiling point does not need to be performed as the melting point is above 300 C. Information requirement: Vapour pressure Reason: other justification Justification: In accordance with column 2 of REACH Annex VII, the vapour pressure study does not need to be performed as the melting point is above 300 C. Information requirement: Partition coefficient n-octanol/water (log value) Reason: other justification Justification: In accordance with column 2 of REACH Annex VII, the partition coefficient does not need to be performed as the substance is inorganic. Information requirement: Surface tension Reason: other justification Justification: In line with column 2 of REACH Annex VII, the surface tension of the substance does not need to be tested because due to its chemical structure, no surface activity is predicted; in addition, the study does not need to be conducted as the water solubility is below 1mg/L at 20 C. Information requirement: Flash point Reason: study scientifically unjustified Justification: In accordance with section 1 of REACH Annex XI, the flash point does not need to be tested as the substance is a solid (scientifically unjustified) and in accordance with column 2 of REACH Annex VII, the flash point does not need to be performed as the substance is inorganic (other justification) Information requirement: Self-ignition temperature Reason: other justification Justification: In accordance with column 2 of REACH Annex VII, the auto flammability does not need to be conducted as the substance is a solid and self-heating of the substance up to 400 C is excluded. Information requirement: Flammability Reason: study scientifically unjustified Justification: In accordance with section 1 of REACH Annex XI, the flammability does not need to be performed as the substance is non combustible. Information requirement: Explosive properties Reason: study scientifically unjustified Justification: In accordance with column 2 of REACH Annex VII, the explosiveness of the substance does CSR-PI CHEMICAL SAFETY REPORT 7

20 not need to be tested, because there are no chemical groups associated with explosive properties in the molecule Information requirement: Stability in organic solvents and identity of relevant degradation products Reason: study scientifically unjustified Justification: In accordance with column 2 of REACH Annex IX, the stability in organic solvents does not need to be performed as the substance is inorganic. Information requirement: Dissociation constant Reason: study scientifically unjustified Justification: In accordance with section 1 of REACH Annex XI, the dissociation constant study does not need to be performed as the substance is not soluble in water and the substance does not contain any ionic structure Information requirement: Viscosity Reason: study technically not feasible Justification: In accordance with section 2 of REACH Annex XI, the viscosity study does not need to be conducted as the substance is a solid Category document Category document for C.I. Pigment Yellow 34 and C.I. Pigment Red Category definition and its members 1.1. Category definition 1.1.a Category hypothesis In the SVHC support documents for both C.I. Pigment Yellow 34 (Lead sulfochromate) and C.I. Pigment Red 104 (Lead moly sulfochromate), grouping of the lead sulfochromate based pigments family is proposed. C.I. Pigment Yellow 34 is a mixed phase crystal that contains lead sulphochromate with oxides of lanthanides, Al, Ce, Sb, Si, Sn, Ti, Zn, Zr and fluorine salts. C.I. Pigment Red 104 is a mixed phase crystal that contains lead molybdosulphochromate with oxides of lanthanides, Al, Ce, Sb, Si, Sn, Ti, Zn, Zr and fluorine salts. Both C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are inorganic substances that are used to add colour to paints and plastic and other matrices. The mentioned pigments can be considered as a group because of the similarity of the structures. For both pigments a small proportion of the substances may dissolve and release transformation products chromate (VI) and lead ions. Extensive information concerning the (eco)toxicity of these transformation products is available and should be taken into account when assessing the hazardous properties of the pigment substances. No hazards linked to the physico-chemical properties have been established for the pigments. Based on the fact that the pigments chemically belong to the same family and share chemical similarities, similar technical performances and similar uses, it is expected that they will have a similar hazard profile and classification and labelling. As (eco)toxicity will mainly depend on the toxicity of the transformation products, the extensive information available for these transformation products will be taken into account to define the hazard profiles of the pigments. 1.1.b Applicability domain of the category The category applies to pigment substances containing lead sulfochromate CSR-PI CHEMICAL SAFETY REPORT 8

21 1.1.c List of endpoint covered The category approach was applied for the following endpoints: - Eye irritation (Annex VII/VIII) - Skin irritation (Annex VII/VIII) - Skin sensitization (Annex VII) - Acute toxicity oral route (Annex VII) - Repeated dose toxicity (oral/dermal/inhalation) (Annex VIII) - Carcinogenicity (Annex X) - Toxicity to reproduction/developmental toxicity (Annex VIII) - Long-term toxicity testing on invertebrates (Annex IX) - Long-term toxicity testing on fish (Annex IX) - Adsorption/desorption screening (Annex VIII) - Bioaccumulation (Annex IX) - Effects on terrestrial organisms (Annex IX/X) - Long-term toxicity to sediment organisms (Annex X) 1.2. Category members For the purpose of REACH registration this category consists of pigment substances containing lead sulfochromate. The identification of each member is presented in the table below. Substances of the Group Pigments containing lead sulfochromate for data evaluation and REACH registration EINECS # CAS # EINECS NAME Name in this document lead sulfochromate yellow C.I. Pigment Yellow 34 lead chromate molybdate sulfate red C.I. Pigment Red 104 The group of pigment substances containing lead sulfochromate may be more extensive than the ones listed in the table. However, the pigments listed in this paragraph 1.2 are subject to REACH registration and authorisation and therefore constitute for that purpose this Category Purity / impurities Both C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have 1% unknown impurities, which are considered not relevant for classification and labelling. Purity is 90% for C.I. Pigment Yellow 34, and 91% for C.I. Pigment Red 104. The remaining 9% and 8% for PY.34 and PR.104, respectively, consist of additives that are used as stabilisers. The additives are not considered relevant for the classification and labelling of the pigments. 2. Category justification Both C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are mixed phase crystals containing lead chromate and lead sulphate. In addition, C.I. Pigment Red 104 also contains lead molybdate. Although the substances classify as insoluble in water, a small proportion of the substances will dissociate into transformation products chromate (VI) and lead ions, which are the substances that will mostly contribute to (eco)toxicity. The inorganic substances show similar physical/chemical properties based on these transformation products. The presence of lead molybdate in C.I. Pigment Red 104 does not have an influence on physical/chemical parameters but should be taken into account with regards to (eco)toxicity. The test results of the Transformation/Dissolution (IUCLID 4.8) and Bioelution (IUCLID 7.1.1) tests are crucial in the risk assessments. These tests quantify the dissolution of chromium and lead ions from C.I. Pigment Yellow 34 and C.I. Pigment Red 104 into an aqueous medium and simulated body fluids. Next to a risk assessment for the two pigments, the exposure of man and the environment to chromium and lead ions is used in the human and environmental risk assessment. The results of the screening tests for C.I. Pigment Yellow 34 and C.I. Pigment Red 104 showed that concentrations of lead and chromium ions detected in the medium compared very well between the two pigments. Therefore, the full tests were carried out only with C.I. Pigment Yellow CSR-PI CHEMICAL SAFETY REPORT 9

22 34 and the results were read across to C.I. Pigment Red Data matrix Physico-chemical and (eco)toxicological data are presented in the data matrix. 4. Conclusion per endpoint for C&L and PBT Physical/chemical properties Read across between the pigments in this category and their transformation products is considered justified because the pigments chemically belong to the same family and share chemical similarities, similar technical performances and similar uses. No hazards linked to the physico-chemical properties have been established for the pigments. Oxidizing properties Rationale & Experimental data The oxidising properties of C.I. Pigment Red 104 were determined in accordance with the EC Physico/Chemical Test A17, Oxidizing Properties (Solid) Test. In the preliminary test, the burning time of C.I. Pigment Red 104 was determined to be more than the reference sample in the preliminary screening test. Therefore the full train test was conducted. In the full train test, the highest burning rate recorded from the six samples of C.I. Pigment Red 104 in cellulose was 0.36 mm/s, which was the sample with 80% of the test substance. This value should be compared to the highest burning rate of the reference substance Barium Nitrate, which was 0.85mm/s. It can be concluded that the sample of C.I. Pigment Red 104 should be classed not an oxidizing substance since in any percentage of C.I. Pigment Red 104/Cellulose, it has a burning rate of less than that of Barium Nitrate/Cellulose per EC Physico/Chemical Test A17, Oxidizing Properties (Solid) Test. The results of the study with C.I. Pigment Red 104 can be read across to C.I. Pigment Yellow 34 as it can be assumed that the absence of lead molybdate in this pigment will not lead to differences in oxidising properties. Conclusion Based on read across to the results of the study on oxidising properties with C.I. Pigment Red 104, C.I. Pigment Yellow 34 can be considered not oxidising. Classification & Labelling C.I. Pigment Yellow 34 does not have to be classified for oxidising properties. Human toxicity Read across between the pigments in this category and their transformation products is considered justified because the pigments chemically belong to the same family and share chemical similarities, similar technical performances and similar uses. Extensive reviews that have been published for transformation products chromate (VI) and lead were used to provide data on some critical endpoints such as skin sensitisation, carcinogenicity and toxicity to reproduction and developmental toxicity. With regard to chromate, publications and reviews are (amongst others) available in an EU Risk Assessment Report (RAR) from 2005, from the Scientific Committee on Occupational Exposure Limits (SCOEL;2004), Seidler et al. (2012) and NTP, The Seidler el al. (2012) study, in which a health-based Risk Assessment for Hexavalent Chromium was presented, was used as a basis for the derivation of the DMEL for inhalation exposure. Several health effects are associated with occupational exposure to hexavalent chromium compounds, with carcinogenicity (specifically lung cancer) being the most serious. Therefore, lung cancer is taken as the critical effect upon which the occupational exposure limit was based. In addition, the excess lifetime intestinal cancer risk for workers after oral exposure to hexavalent chromium was calculated, based on the observation of excess risk after oral exposure in a well conducted NTP carcinogenicity study in mice. For lead, the voluntary Risk Assessment Report (vrar) from 2008 was taken into account, as well as the SCHER opinion on the vrar, which was published in The main effect that was taken into account for the pigments was the effect on reproduction and possible developmental neurotoxicological effects. Furthermore, the Panel on Contaminants in the Food Chain CSR-PI CHEMICAL SAFETY REPORT 10

23 (CONTAM) of the European Food Safety Authority published a scientific opinion on lead in food, in which a Benchmark Dose Level (BMDL) was determined for the effects of lead on neurobehavioral development. Eye irritation (Annex VII/VIII) Rationale & Experimental data An in vivo eye irritation study in accordance with OECD 405 and under GLP-conditions was performed with C.I. Pigment Red 104 in rabbits. Slight effects on cornea and conjunctivae were observed, however, they were all reversible within 14 days, and scores did not trigger classification. Therefore, C.I. Pigment Red 104 is not considered to be irritating to the eyes. The results of the study with C.I. Pigment Red 104 can be read across to C.I. Pigment Yellow 34 as it can be assumed that the absence of lead molybdate in this pigment will not lead to different eye irritation potential. Conclusion Based on read across to the results of the eye irritation study with C.I. Pigment Red 104, C.I. Pigment Yellow 34 can be considered not irritating to the eye. Classification & Labelling C.I. Pigment Yellow 34 does not have to be classified for eye irritation. Skin irritation (Annex VII/VIII) Rationale & Experimental data An in vivo skin irritation study in accordance with OECD 404 and under GLP-conditions was performed with C.I. Pigment Yellow 34. Very slight erythema was observed in two animals which was reversible within 72 hours, and scores did not trigger classification. Therefore, C.I. Pigment Yellow 34 is not considered to be irritating to the skin. The results of the study with C.I. Pigment Yellow 34 can be read across to C.I. Pigment Red 104. It can be assumed that the presence of lead molybdate in this pigment will not lead to different skin irritation potential, based on the absence of skin irritating properties reported in the disseminated REACH-dossiers of calcium molybdate and disodium molybdate. Conclusion Based on read across to the results of the skin irritation study with C.I. Pigment Yellow 34, C.I. Pigment Red 104 can be considered not irritating to the skin. Classification & Labelling C.I. Pigment Red 104 does not have to be classified for skin irritation. Skin sensitization(annex VII) Rationale & experimental data No information is available for the pigments C.I. Pigment Yellow 34 and C.I. Pigment Red 104. However, one of the transformation products of both pigments, i.e. chromium (Cr (VI)) is a known sensitiser, as is demonstrated in the RAR. In the RAR it is stated that skin sensitisation resulting from contact with Cr (VI) is relatively common in humans working with the compounds. Several investigations including patch testing of contact dermatitis patients and investigations of various occupational groups confirm this. In addition, standard and modified guinea pig maximisation tests and the mouse ear swelling test clearly demonstrate skin sensitisation potential. The available information for Cr (VI) can be read across to address the skin sensitising potential of both pigments, as it can be assumed that the skin sensitising properties of this transformation product will be responsible for the skin sensitising potential of the pigments. Conclusion Based on read across to transformation product Cr (VI), C.I. Pigment Yellow 34 and C.I. Pigment Red 104 can be considered to be sensitising to the skin. Classification & Labelling CSR-PI CHEMICAL SAFETY REPORT 11

24 C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have to be classified as sensitising to the skin. Acute toxicity oral route (Annex VII) Rationale & experimental data Two acute toxicity studies with C.I. Pigment Yellow 34 are available, both performed according to a method similar to OECD 401 and pre-glp. Both studies were performed as a limit test with a concentration of 10,000 mg/kg bw. No mortality was observed at this dose level. Therefore, C.I. Pigment Yellow 34 is not considered to be acutely toxic via the oral route. The results of the study with C.I. Pigment Yellow 34 can be read across to C.I. Pigment Red 104 as it can be assumed that the absence of lead molybdate in this pigment will not lead to an increase of acute toxicity. Conclusion Based on read across to the results of the acute toxicity studies with C.I. Pigment Yellow 34, C.I. Pigment Red 104 can be considered not to be acute toxic via the oral route. Classification & Labelling C.I. Pigment Red 104 does not have to be classified for acute toxicity via the oral route. Repeated dose toxicity (Annex VIII) Rationale & Experimental data Two sub-chronic repeated dose toxicity studies are available with C.I. Pigment Yellow 34, one in rats and one in beagle dogs. Rats and dogs were dosed at 2000, 5000 and 20,000 ppm in the feed in 90 day studies that are similar to OECD guideline 408 and 409, respectively, although ophthalmological examinations were not performed. Lead carbonate was given to the dogs as a positive control substance in concentrations of 100, 300 or 1000 ppm in the diet. In rats, mortality was not significantly elevated and effects involved mainly increased relative weight of the kidneys, although without histopathological changes. In dogs, all but one of the high dose animals died. Treatment-related changes involved mainly the kidney and the liver. Hematological changes were also observed in a dose-dependent manner. In both rats and dogs, blood lead concentrations were elevated in a dose-related manner. The mid dose was determined as the NOAEL in the rat study (5000 ppm), whereas in the dog study, no NOAEL could be determined. The LOAEL in this study was determined to be 2000 ppm. The results of the study with C.I. Pigment Yellow 34 can be read across to C.I. Pigment Red 104 as it can be assumed that the absence of lead molybdate in this pigment will not lead to a higher repeated dose toxicity. Conclusion Based on read across to the results of the sub-chronic repeated dose toxicity studies with C.I. Pigment Yellow 34, a NOAEL of mg/kg bw/day (5000 ppm) in rats and a LOAEL of 80.4 mg/kg bw/d (2000 ppm) in dogs can be expected for C.I. Pigment Red 104. Classification & Labelling Based on the accumulation of lead ions in different tissues in a time and dose-dependent manner in the study with C.I. Pigment Yellow 34, C.I. Pigment Red 104 needs to be classified as R33 or STOT repeated exposure Cat. 2, in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC, respectively. Further classification is not warranted because of the R45 / Carc. Cat. 1B categorization (see carcinogenicity). Carcinogenicity (Annex X) Rationale & Experimental data For both C.I. Pigment Yellow 34 and C.I. Pigment Red 104 studies have been included in the dossier. Both substances have been classified by the EU as carcinogenic (R45/Carc Cat 1B) in accordance with lead chromate (CAS ), based on the presence of chromate (VI) in these substances. For Chromate (VI) compounds, Seidler et al. (2012) systematically reviewed the scientific literature and quantified the respiratory cancer risk for occupational exposure to hexavalent chromium. Seidler et al. (2012) included 5 studies in their paper, each providing more than one level of occupational Cr (VI) exposure, considering the confounder smoking and using CSR-PI CHEMICAL SAFETY REPORT 12

25 adequate methodology. Linear regressions models were used to calculate relative risks and to estimate excess absolute risks. The absolute excess lung cancer risk was found to be 4 excess lung cancer cases per 100,000 workers for life time exposure to hexavalent chromium at a Cr(VI) concentration of 0.01 ug/m3. The Scientific Committee on Occupational Exposure Limits published a recommendation in 2004 (SCOEL/SUM/86). In this document a large number of epidemiological studies and other Risk Assessments of occupational exposure to Hexavalent Chromium were reviewed. Based on this information, the SCOEL calculated that the numbers of excess lung cancers per 1000 male workers exposed for a working lifetime to 50 µg/m3 of hexavalent chromium and followed to age 85 years are predicted to be in the range of Estimated ranges of excess lung cancers for exposure levels of 25, 10, 5 and 1 µg/m3 have been estimated at 2-14, 1-6, and , respectively. In addition, SCOEL prepared a recommendation with regard to the occupational exposure limits for Lead Chromates (SCOEL/SUM/117, 2004). In this document reference is made to the SCOEL recommendation for Chromate (VI) compounds. The very low solubility of Lead Chromate (0.06 g/l), is mentioned as explanation for the apparently low carcinogenic potential compared to other hexavalent Chromium compounds. However, as mutagenicity and clastogenicity were observed after solubilisation of Lead Chromates, carcinogenicity potential cannot be excluded. With respect to the excess lifetime intestinal cancer risk for workers after oral exposure to hexavalent chromium, a review on the carcinogenicity dose-response analysis of Cr(VI)- and As-containing substances from ECHA (ECHA project SR11) was used for read across. The data was deduced from a well conducted NTP carcinogenicity study in mice. The reviews by Seidler et al. (2012), SCOEL for hexavalent Chromium compounds and Lead Chromate are read across to C.I. Pigment Yellow 34 and C.I. Pigment Red 104 as the reviews are crucial for the hazard assessment and derivation of the DMEL for inhalation. The review by ECHA and NTP carcinogenicity study for hexavalent Chromium compounds are read across to C.I. Pigment Yellow 34 and C.I. Pigment Red 104 as the reviews are crucial for the hazard assessment and derivation of the DNEL via oral exposure. Conclusion In accordance with the current EU classification for C.I. Pigment Yellow 34 and C.I. Pigment Red 104, which was based on read across from other more soluble hexavalent chromium compounds, C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are classified for carcinogenicity, although the likelihood of carcinogenicity risk is considered very low due to very poor bioavailability of these two substances. Three epidemiological studies in lead chromate pigment manufacturing plants "did not produce evidence supporting any association between lead chromate [pigments] and lung cancer". However limitations in cohort size, due to the limited number of workers in this industry, limits the use of such studies. Nonetheless as the worst case, the carcinogenicity risk of these two pigments will be assessed in this application for authorization, using the carcinogenic properties of hexavalent chromium compounds as described by Seidler et al. (2012) for Cr(VI) compounds. However, the very poor solubility and bioavailability of C.I. Pigment Yellow 34 and C.I. Pigment Red 104 should be taken into account when deriving the DMEL. With respect to the excess lifetime intestinal cancer risk for workers after oral exposure to hexavalent chromium, the review by ECHA and NTP carcinogenicity study for hexavalent Chromium compounds are taken into account. Classification & Labelling C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are included in Annex VI of the CLP-regulation and should be classified as Carcinogenic, Category 1B. Toxicity to reproduction/developmental toxicity (Annex VIII) Rationale & Experimental data No reliable studies with regard to toxicity to reproduction/developmental toxicity are available for C.I. Pigment Yellow 34 and C.I. Pigment Red 104. However, both substances are included in Annex VI of the CLP-regulation and should be classified as Repr. 1A (H360Df), based on the CSR-PI CHEMICAL SAFETY REPORT 13

26 developmental effects observed for transformation product lead. In the voluntary Risk Assessment Report for lead and inorganic lead compounds, lead compounds were found to have effects on male fertility, female reproductive parameters, and on neurobehavioral development, which was the most critical effect. Effects on neurobehavioral performance after pre-natal and post-natal exposure have been reported in several animal studies. However, the available data are inadequate to establish dose-effect relationships. The vrar suggest a blood lead level above 10 µg/dl (in females) to take into account for the risk assessment with regard to developmental effects. In the opinion of the Scientific Committee on Health and Environmental Risks (SCHER) on the voluntary Risk Assessment Report (vrar), it is concluded that the health part of the vrar is of good quality, comprehensive, and that the exposure and effects assessment follow the Technical Guidance Document. In the risk assessment on lead from food which was performed by the European Food Safety Authority (EFSA, 2010), the Bench Mark Dose approach (BMD) is used to estimate the BMDL01, which is the blood-lead concentration corresponding to the 1 -percentile of the Confidence Interval of the chosen Bench Mark Response of an IQ deficit of 1 IQ point. The BMR is chosen and set at 1 IQ point by the CONTAM panel of EFSA. Using this approach, the BMDL01 for lead was estimated to be 1.2μg/dL (mentioned as 12μg/L by EFSA). The reviews on available information in the vrar, SCHER-opinion, and EFSA-opinion are read across to C.I. Pigment Yellow 34 and C.I. Pigment Red 104 as the reviews are crucial for the hazard assessment and derivation of the DMEL. Conclusion Based on read across to the vrar, SCHER-opinion, and EFSA-opinion with respect to the toxic properties of lead compounds with respect to development and reproduction, C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are considered to have effects on neurobehavioral development. Classification & Labelling C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are included in Annex VI of the CLP-regulation and should be classified as Repr. 1A (H360Df). Environmental fate and ecotoxicological endpoints In the environment C.I. Pigment Yellow 34 and C.I. Pigment Red 104 may release small amounts of Pb 2+ and CrO 4 2- under certain conditions. Therefore, the toxicity of these two transformation products will serve as the basis for the environmental risk assessment. The results of the 28day Transformation/Dissolution test with 1 mg of C.I. Pigment Yellow 34 (ph 6) showed that a plateau level was reached after 28 days. This is considered as a 'worst case' of the amount of lead ions that will dissolve in time in the environment. The estimated concentrations in the receiving environmental compartments are converted to proportional concentrations of lead and chromium ions that will then distribute further into the environment. It turned out that the dissolution of chromium was higher with ph 8, whereas the dissolution of lead was higher at ph 6. Since the PNECs for lead were generally lower than for chromium, lead was finally taken as the lead compound for the risk characterisation. For lead, information from the Voluntary RAR (vrar) of lead and lead compounds (2008) was used to determine toxicity to the environment. The lead vrar was produced by industry on the basis of the principles applied in the Existing Substances Regulation and has been reviewed by the Technical Committee on New and Existing substances (TC NES) in For the ecotoxicological properties of chromium, information from the EU Risk Assessment Report (RAR) on chromium trioxide, sodium chromate, sodium dichromate, ammonium dichromate and potassium dichromate (2005) was used, which was produced in the context of EU Existing Substances Regulation EEC no 793/93 by the UK Rapporteur, agreed by the Technical Committee on New and Existing substances and published by the European Communities in Next to lead and chromium, C.I. Pigment Red 104 also contains 1 to 3% of Molybdenium. The PNECs of molybdenium are compared to those for lead and chromium, as far as these are based on experimental data, see table below. The toxicity of molybdenium is far less than that of lead and chromium. Only the toxicity for soil organisms is somewhat lower for molybdenium than for lead CSR-PI CHEMICAL SAFETY REPORT 14

27 (a factor of 4). In view of the very low concentration and the lower toxicity, molybdenium has not been considered for the risk assessment. Summary of PNEC s for molybdate, lead, and chromium Molybdate Lead Chromium (disseminated PNECs, ECHA site) PNECaqua 12.7 mg/l 2.7 µg/l 3.4 µg/l (freshwater) PNECaqua (marine) 1.91 mg/l 0.27 µg/l 3.4 µg/l PNECaqua µg/l 3.4 µg/l (intermittent) PNEC STP 21.7 mg/l 0.1 mg/l 0.21 mg/l PNEC sediment (freshwater) 174 mg/kg sediment dw PNEC sediment (marine water) 17.4 mg/kg sediment dw PNEC soil 39 mg/kg soil dw 166 mg/kg soil dw Based on the information above, PNECs were extracted for both lead and chromium. Long-term toxicity testing on invertebrates (Annex IX) For both lead and chromium, available information in the vrar of lead and lead compounds and in the RAR of hexavalent chromium compounds was read across to determine the potential long-term toxicity to invertebrates of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. Long-term toxicity testing on fish (Annex IX) For both lead and chromium, available information in the vrar of lead and lead compounds and in the RAR of hexavalent chromium compounds was read across to determine the potential long-term toxicity to fish of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. Adsorption/desorption screening (Annex VIII) Due to the poor solubility of C.I. Pigment Yellow 34 and C.I. Pigment Red 104, their adsorption/desorption cannot be determined. Yet a small fraction will transform into chromium and lead ions. For both lead and chromium, available information in the vrar of lead and lead compounds and the RAR of hexavalent chromium compounds was used instead to determine the adsorption/desorption potential of the transformation products released from C.I. Pigment Yellow 34 and C.I. Pigment Red 104. Bioaccumulation (Annex IX) For both lead and chromium, available information in the vrar of lead and lead compounds and in the RAR of hexavalent chromium compounds was used instead to determine the bioaccumulation potential of the transformation products released from C.I. Pigment Yellow 34 and C.I. Pigment Red 104. Effects on terrestrial organisms (Annex IX/X) For both lead and chromium, available information in the vrar of lead and lead compounds and in the RAR of hexavalent chromium compounds was read across to determine the potential toxicity to terrestrial organisms of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. Long-term toxicity to sediment organisms (Annex X) For both lead and chromium, available information in the vrar of lead and lead compounds and in the RAR of hexavalent chromium compounds was read across to determine the potential long-term toxicity to sediment organisms of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. Classification & Labelling for the environment Based on the ecotoxicological profile of lead and chromate, C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have been officially classified by the EU as Aquatic Acute 1 (H400) and Aquatic CSR-PI CHEMICAL SAFETY REPORT 15

28 Chronic 1 (H410). PBT A PBT assessment is not relevant, since the substances are inorganic CSR-PI CHEMICAL SAFETY REPORT 16

29 2. MANUFACTURE AND USES Table 6. Quantities (in tonnes/year) Year Total tonnage Uses exempted from CSR Used for article 2008 Manufactured: Imported: Directly exported: Uses as intermediate under strictly controlled conditions (on-site): Used as intermediate under strictly controlled conditions (transported): Imported in articles: Tonnage in produced articles: 2009 Manufactured: Imported: Directly exported: Used for research purposes: Uses as intermediate under strictly controlled conditions (on-site): Used as intermediate under strictly controlled conditions (transported): Imported in articles: Tonnage in produced articles: 2010 Manufactured: Imported: Directly exported: Used for research purposes: Uses as intermediate under strictly controlled conditions (on-site): Used as intermediate under strictly controlled conditions (transported): Imported in articles: Tonnage in produced articles: 2011 Manufactured: Imported: Directly exported: Used for research purposes: Uses as intermediate under strictly controlled conditions (on-site): Used as intermediate under strictly controlled conditions (transported): Imported in articles: Tonnage in produced articles: 2012 Manufactured: Imported: Directly exported: Used for research purposes: Uses as intermediate under strictly controlled conditions (on-site): Used as intermediate under strictly controlled conditions (transported): Imported in articles: Tonnage in produced articles: 2013 Manufactured: Imported: Directly exported: Used for research purposes: Uses as intermediate under strictly controlled conditions (on-site): Used as intermediate under strictly controlled conditions (transported): Imported in articles: Tonnage in produced articles: 2.1. Manufacture Used for research purposes: No information available on manufacture CSR-PI CHEMICAL SAFETY REPORT 17

30 No information available on manufacturing process related to the specified manufacture(s) No information available on production of articles covered by the specified use(s) 2.2. Identified uses Table 7. Formulation Identifiers Use descriptors Other information F-1: Distribution and mixing pigment powder in an industrial environment into solvent-based paints for non-consumer use. Pigment choice depends on product specifications on visibility, shade and colour, durability, other requirements and Regulations. Environmental release category (ERC): ERC 2: Formulation of preparations Process category (PROC): PROC 2: Use in closed, continuous process with occasional controlled exposure PROC 3: Use in closed batch process (synthesis or formulation) PROC 5: Mixing or blending in batch processes for formulation of preparations and articles (multistage and/or significant contact) PROC 7: Industrial spraying PROC 8a: Transfer of substance or preparation (charging/discharging) from/to vessels/large containers at non-dedicated facilities PROC 8b: Transfer of substance or preparation (charging/discharging) from/to vessels/large containers at dedicated facilities PROC 9: Transfer of substance or preparation into small containers (dedicated filling line, including weighing) PROC 10: Roller application or brushing PROC 15: Use as laboratory reagent PROC 21: Low energy manipulation of substances bound in materials and/or articles Product Category formulated: PC 9a: Coatings and paints, thinners, paint removes Technical function of the substance during formulation: Colouring agents, pigments Remarks: Tonnage of substance: Number of sites: Substance supplied to that use: As such In a mixture C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are unique in their value in use proposition. They combine superb colouristic properties such as a wide range of clean, vivid shades for visibility, colour stability, excellent coverage or hiding power with technical performance requirements such as low rheology, light and weather fastness (durability), chemical fastness, non-bleeding/migration, impact resistance and heat stability. This combination cannot be guaranteed through the use of other pigments or combination of pigments. Their superior performance coupled with price position, make alternatives less favourable. Colour shade spectrum: C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have a wide shade spectrum covering shades from green shade yellow up to blue shade red. No other pigment chemistry, other than cadmium-based products, have such a broad colour shade spectrum. As such, it is often not possible to match certain shades without the use of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. The colour palette of end users will be limited without these pigments. Opacity/hiding power: one of the main functions of a paint or coating is to colour/hide CSR-PI CHEMICAL SAFETY REPORT 18

31 Identifiers Use descriptors Other information F-2: Distribution and mixing pigment powder in an industrial environment into liquid or solid premix to colour plastic/plasticised articles. Pigment choice depends on product specifications on visibility, colour, heat stability, durability and Regulations. the substrate it is covering. The more opaque a paint or coating is, the less number of coatings are required to hide the substrate. The more coatings that are required results in a higher environmental impact as more solvents, resins, additives and energy will be used. When taking into account the target colour shade that is required, alternatives to C.I. Pigment Yellow 34 and C.I. Pigment Red 104 often require more coating applications to achieve the same level of hiding. As such, alternatives often have an indirect environmental impact through the need to apply more coatings leading to the use of more energy, solvents and resins. Durability: durability or weather fastness is a critical technical requirement for many coatings applications. If the colour of a paint changes by fading or darkening it can lead to the need for repainting or disposal of the painted article. This can lead to environmental issues through the use of more paint (and thus more energy, solvents and resins) or through waste disposal at landfill. Environmental release category (ERC): ERC 3: Formulation in materials Process category (PROC): PROC 1: Use in closed process, no likelihood of exposure PROC 2: Use in closed, continuous process with occasional controlled exposure PROC 3: Use in closed batch process (synthesis or formulation) PROC 5: Mixing or blending in batch processes for formulation of preparations and articles (multistage and/or significant contact) PROC 8a: Transfer of substance or preparation (charging/discharging) from/to vessels/large containers at non-dedicated facilities PROC 8b: Transfer of substance or preparation (charging/discharging) from/to vessels/large containers at dedicated facilities PROC 9: Transfer of substance or preparation into small containers (dedicated filling line, including weighing) PROC 10: Roller application or brushing PROC 14: Production of preparations or articles by tabletting, compression, extrusion, pelletisation PROC 15: Use as laboratory reagent PROC 19: Hand-mixing with intimate contact and only PPE available. PROC 21: Low energy manipulation of substances bound in materials and/or articles Product Category formulated: PC 32: Polymer preparations and compounds PC 34: Textile dyes, finishing and impregnating products; including bleaches and other processing aids Technical function of the substance during formulation: Colouring agents, pigments Remarks: Tonnage of substance: Number of sites: Substance supplied to that use: As such In a mixture C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are unique in their value in use CSR-PI CHEMICAL SAFETY REPORT 19

32 Identifiers Use descriptors Other information Table 8. Uses at industrial sites proposition. They combine superb colouristic properties such as a wide range of clean, vivid shades for visibility, colour stability, excellent coverage or hiding power with technical performance requirements such as light and weather fastness (durability), chemical fastness, non-migration, impact resistance and heat stability. This combination cannot be guaranteed through the use of other pigments or combination of pigments. Their superior performance coupled with price position, make alternatives less favourable. Colour shade spectrum: C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have a wide shade spectrum covering shades from green shade yellow up to blue shade red. No other pigment chemistry, other than cadmium-based products, has such a broad colour shade spectrum. As such, it is often not possible to match certain shades without the use of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. The colour palette of end users will be limited without these pigments Durability: durability or weather fastness is a critical technical requirement for many applications. If the colour of a matrix changes by fading or darkening it can lead to endangering the public and industrial safety and to the increased need for repair or disposal of the article. This will subsequently lead to environmental issues through the use of more additives, plasticisers and resins, through the use of more energy or through waste disposal at landfill or incineration. Identifiers Use descriptors Other information IW-1: Industrial application of paints on metal surfaces (machines vehicles,structures,si gns,road furniture,coil coating).pigment choice is governed by end product specifications on visibility,colour,dura bility,other technical requirements and Regulations. Environmental release category (ERC): ERC 5: Industrial use resulting in inclusion into or onto a matrix Process category (PROC): PROC 2: Use in closed, continuous process with occasional controlled exposure PROC 3: Use in closed batch process (synthesis or formulation) PROC 5: Mixing or blending in batch processes for formulation of preparations and articles (multistage and/or significant contact) PROC 6: Calendering operations PROC 7: Industrial spraying PROC 8a: Transfer of substance or preparation (charging/discharging) from/to vessels/large containers at non-dedicated facilities PROC 8b: Transfer of substance or preparation (charging/discharging) from/to vessels/large containers at dedicated facilities PROC 9: Transfer of substance or preparation into small containers (dedicated filling line, including weighing) PROC 10: Roller application or brushing PROC 15: Use as laboratory reagent PROC 21: Low energy manipulation of substances bound in materials and/or articles Product Category used: PC 9a: Coatings and paints, thinners, paint removes Sector of end use: SU 15: Manufacture of fabricated metal products, except machinery and equipment Tonnage of substance: Number of sites: Substance supplied to that use: In a mixture Subsequent service life relevant for that use: yes Link to the subsequent service life: A-1: Service life of coated articles. Performance and longevity depend on the pigment quality for bright lasting colours improving visibility and safety, light and weather fastness (durability), chemical fastness, impact resistance and heat stability CSR-PI CHEMICAL SAFETY REPORT 20

33 Identifiers Use descriptors Other information SU 17: General manufacturing, e.g. machinery, equipment, vehicles, other transport equipment SU 19: Building and construction work Technical function of the substance during formulation: Colouring agents, pigments IW-2: Use of colour premixes and pre-compounds to colour plastic or plasticised articles for non-consumer use. Pigment choice depends on product specifications on visibility, colour, heat stability, chemical fastness, durability and Regulations. Remarks: Paints and coatings containing C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are applied in particular to equipment or substrates to ensure a long life-time of the paint/coating for optimal protection, visibility and safety, and to maintain the replacement value of the end product. Other motivation to use this type of paint/coating is the extreme durability and quality of the paint/coating which reduces the need to repair or repaint on places that are difficult to reach, in dangerous situations, or where idle time of equipment would incur high costs. The desired combination of colouristic properties (such as a wide range of clean, vivid shades for visibility, colour stability, excellent coverage or hiding power) together with technical performance characteristics (such as rheology, light and weather fastness (durability), chemical fastness, non-bleeding/migration, impact resistance) cannot be guaranteed through other pigments or combination of pigments. Their superior performance coupled with price position, make alternatives less favourable. Colour shade spectrum: C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have a wide shade spectrum covering shades from green shade yellow up to blue shade red. No other pigment chemistry, other than cadmium-based products, has such a broad colour shade spectrum. As such, it is often not possible to match certain shades without the use of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. The colour palette of end users will be limited without these pigments Opacity/hiding power: one of the main functions of a paint or coating is to colour/hide the substrate it is covering. With a more opaque paint or coating, a lower number of coating layers is required to hide the substrate. When more coating layers are required, more solvents, resins, additives and energy will be used resulting in a higher environmental impact. When taking into account the target colour shade that is required, alternatives to C.I. Pigment Yellow 34 and C.I. Pigment Red 104 often require more coating applications to achieve the same level of hiding. As such, alternatives often have an indirect environmental impact through the need to apply more coatings leading to the use of more energy, solvents and resins. Durability: durability or weather fastness is a critical technical requirement for many coatings applications. If the colour of a paint/coating changes by fading or darkening it can lead to the need for repainting or disposal of the painted/coated article. This can lead to environmental issues through the use of more paint/coating (and thus more energy, solvents and resins) or through waste disposal at landfill. Environmental release category (ERC): ERC 5: Industrial use resulting in inclusion into or onto a matrix Process category (PROC): PROC 3: Use in closed batch process (synthesis or formulation) PROC 6: Calendering operations PROC 8a: Transfer of substance or preparation (charging/discharging) from/to vessels/large containers at non-dedicated facilities PROC 8b: Transfer of substance or preparation (charging/discharging) from/to vessels/large containers at dedicated facilities PROC 9: Transfer of substance or preparation into Tonnage of substance: Number of sites: Substance supplied to that use: In a mixture Subsequent service life relevant for that use: yes Link to the subsequent service life: A-2: Service life of coloured plastic or plasticised articles. Performance and longevity CSR-PI CHEMICAL SAFETY REPORT 21

34 Identifiers Use descriptors Other information small containers (dedicated filling line, including weighing) PROC 14: Production of preparations or articles by tabletting, compression, extrusion, pelletisation PROC 21: Low energy manipulation of substances bound in materials and/or articles Product Category used: PC 32: Polymer preparations and compounds PC 34: Textile dyes, finishing and impregnating products; including bleaches and other processing aids Sector of end use: SU 12: Manufacture of plastics products, including compounding and conversion SU 19: Building and construction work Technical function of the substance during formulation: Colouring agents, pigments Remarks: Table 9. Uses by professional workers depend on pigment quality for bright lasting colours improving visibility and safety, heat stability,durability, chemical fastness, tenchical requirements and Regulations C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are unique in their value in use proposition. They combine superb colouristic properties such as a wide range of clean, vivid shades for visibility, colour stability, excellent coverage or hiding power with technical performance requirements such as light and weather fastness (durability), chemical fastness, non-migration, impact resistance, heat stability and night time reflectivity. This combination cannot be guaranteed through the use of other pigments or combination of pigments. Their superior performance coupled with price position, makes alternatives less favourable. Colouring with C.I. Pigment Yellow 34 and C.I. Pigment Red 104 is applied to ensure optimal visibility, for safety reasons, as well as long-term protection of the article against degradation. Colour shade spectrum: C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have a wide shade spectrum covering shades from green shade yellow up to blue shade red. No other pigment chemistry, other than cadmium-based products, have such a broad colour shade spectrum. As such, it is often not possible to match certain shades without the use of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. The colour palette of end users will be limited without these pigments Durability: durability or weather fastness is a critical technical requirement for many applications. If the colour of a matrix changes by fading or darkening it can lead to endangering the public and industrial safety and to the increased need for repair or disposal of the article. This will subsequently lead to environmental issues through the use of more additives, plasticisers, and resins, through the use of more energy or through waste disposal at landfill or incineration. Identifiers Use descriptors Other information PW-1: Professional,non-con sumer application of paints on metal surfaces (machines,vehicles,st ructures,signs,road Environmental release category (ERC): ERC 8c: Wide dispersive indoor use resulting in inclusion into or onto a matrix ERC 8f: Wide dispersive outdoor use resulting in inclusion into or onto a matrix Tonnage of substance: Substance supplied to that use: In a mixture Subsequent service life relevant CSR-PI CHEMICAL SAFETY REPORT 22

35 Identifiers Use descriptors Other information furniture) or as road marking. Pigment choice is governed by requirements on visibility,colour,dura bility,technical performance and Regulations. Process category (PROC): PROC 2: Use in closed, continuous process with occasional controlled exposure PROC 3: Use in closed batch process (synthesis or formulation) PROC 5: Mixing or blending in batch processes for formulation of preparations and articles (multistage and/or significant contact) PROC 9: Transfer of substance or preparation into small containers (dedicated filling line, including weighing) PROC 10: Roller application or brushing PROC 11: Non industrial spraying PROC 21: Low energy manipulation of substances bound in materials and/or articles Product Category used: PC 9a: Coatings and paints, thinners, paint removes Sector of end use: SU 12: Manufacture of plastics products, including compounding and conversion SU 19: Building and construction work Technical function of the substance during formulation: Colouring agents, pigments Remarks: for that use: yes Link to the subsequent service life: A-1: Service life of coated articles. Performance and longevity depend on the pigment quality for bright lasting colours improving visibility and safety, light and weather fastness (durability), chemical fastness, impact resistance and heat stability. Paints and coatings containing C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are applied in particular to equipment or substrates to ensure a long life-time of the paint/coating for optimal protection, visibility and safety, and to maintain the replacement value of the end product. Other motivation to use this type of paint/coating is the extreme durability and quality of the paint/coating which reduces the need to repair or repaint on places that are difficult to reach, in dangerous situations, or where idle time of equipment would incur high costs. The desired combination of colouristic properties (such as a wide range of clean, vivid shades for visibility, colour stability, excellent coverage or hiding power) together with technical performance characteristics (such as rheology, light and weather fastness (durability), chemical fastness, non-bleeding/migration, impact resistance) cannot be guaranteed through other pigments or combination of pigments. Their superior performance coupled with price position, make alternatives less favourable. Especially for road markings in the airport area but also on public roads, time plays an important and critical role. The applied paint or coating needs to perform in one application and needs to dry as quickly as possible, as work is done whilst operational. Paints and coatings based on other pigments do not meet these critical requirements. Colour shade spectrum: C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have a wide shade spectrum covering shades from green shade yellow up to blue shade red. No other pigment chemistry, other than cadmium-based products, has such a broad colour shade spectrum. As such, it is often not possible to match certain shades without the use of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. The colour palette of end users will be limited without these pigments. Opacity/hiding power: one of the main functions of a paint or coating is to colour/hide the substrate it is covering. With a more opaque paint or coating, a lower number of coating layers is required to hide the substrate. When more coating layers are required, more solvents, resins, additives and energy will be used resulting in a higher CSR-PI CHEMICAL SAFETY REPORT 23

36 Identifiers Use descriptors Other information PW-2: Use of colour premixes and pre-compounds in the application of hotmelt road marking. Pigment choice depends on end product specifications on visibility & night time reflectivity, colour, heat stability, durability, chemical fastness and Regulations. environmental impact. When taking into account the target colour shade that is required, alternatives to C.I. Pigment Yellow 34 and C.I. Pigment Red 104 often require more coating applications to achieve the same level of hiding. As such, alternatives often have an indirect environmental impact through the need to apply more coatings leading to the use of more energy, solvents and resins. Durability: durability or weather fastness is a critical technical requirement for many coatings applications. If the colour of a paint/coating changes by fading or darkening it can lead to the need for repainting or disposal of the painted/coated article. This can lead to environmental issues through the use of more paint (and thus more energy, solvents and resins) or through waste disposal at landfill. Environmental release category (ERC): ERC 8c: Wide dispersive indoor use resulting in inclusion into or onto a matrix ERC 8f: Wide dispersive outdoor use resulting in inclusion into or onto a matrix Process category (PROC): PROC 5: Mixing or blending in batch processes for formulation of preparations and articles (multistage and/or significant contact) PROC 8a: Transfer of substance or preparation (charging/discharging) from/to vessels/large containers at non-dedicated facilities PROC 10: Roller application or brushing PROC 21: Low energy manipulation of substances bound in materials and/or articles PROC 24: High (mechanical) energy work-up of substances bound in materials and/or articles Product Category used: PC 32: Polymer preparations and compounds PC 34: Textile dyes, finishing and impregnating products; including bleaches and other processing aids Sector of end use: SU 19: Building and construction work Technical function of the substance during formulation: Colouring agents, pigments Remarks: Tonnage of substance: Substance supplied to that use: In a mixture Subsequent service life relevant for that use: yes Link to the subsequent service life: A-2: Service life of coloured plastic or plasticised articles. Performance and longevity depend on pigment quality for bright lasting colours improving visibility and safety, heat stability,durability, chemical fastness, tenchical requirements and Regulations C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are unique in their value in use proposition. They combine superb colouristic properties such as a wide range of clean, vivid shades for visibility, night time reflectivity, colour stability, excellent coverage or hiding power with technical performance requirements such as heat stability, light and weather fastness (durability), chemical fastness, non-migration and impact resistance. This combination cannot be guaranteed through the use of other pigments or combination of pigments. Their superior performance coupled with price position, make alternatives less favourable. Colouring with C.I. Pigment Yellow 34 and C.I. Pigment Red 104 is applied to ensure optimal visibility, for safety reasons, as well as long-term protection of the plastic road marks against degradation. Colour shade spectrum: C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have a wide shade spectrum covering shades from green shade yellow up to blue shade red. No CSR-PI CHEMICAL SAFETY REPORT 24

37 Identifiers Use descriptors Other information Table 10. Article service life other pigment chemistry, other than cadmium-based products, has such a broad colour shade spectrum. As such, it is often not possible to match certain shades without the use of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. The colour palette of end users will be limited without these pigments. Durability: durability or weather fastness is a critical technical requirement for many applications. If the colour of the matrix changes by fading or darkening it can lead to endangering the public and industrial safety and to the increased need for repair. This will subsequently lead to environmental issues through the use of more additives, plasticisers and resins, through the use of more energy or through waste disposal at landfill or incineration. Identifiers Use descriptors Other information SL-1: Service life of coated articles. Performance and longevity depend on the pigment quality for bright lasting colours improving visibility and safety, light and weather fastness (durability), chemical fastness, impact resistance and heat stability. Article category related to subsequent service life (AC): AC 1: Vehicles AC 2: Machinery, mechanical appliances, electrical/electronic articles AC 4: Stone, plaster, cement, glass and ceramic articles AC 7: Metal articles Exposure related description of article: Articles with foreseeable exposure to dust and fumes during maintenance and recycling processes, e.g. abrasive surface cleaning, dismantling and milling Articles with particular waste collection and treatment schemes, e.g. electronic equipment Environmental release category (ERC): ERC 10a: Wide dispersive outdoor use of long-life articles and materials with low release ERC 10b: Wide dispersive outdoor use of long-life articles and materials with high or intended release (including abrasive processing) ERC 11a: Wide dispersive indoor use of long-life articles and materials with low release ERC 11b: Wide dispersive indoor use of long-life articles and materials with high or intended release (including abrasive processing) ERC 12a: Industrial processing of articles with abrasive techniques (low release) ERC 12b: Industrial processing of articles with abrasive techniques (high release) Process category (PROC): PROC 21: Low energy manipulation of substances bound in materials and/or articles PROC 24: High (mechanical) energy work-up of substances bound in materials and/or articles PROC 25: Other hot work operations with metals Technical function of the substance during formulation: Colouring agents, pigments Article used by: workers Tonnage of substance: Typical concentration of the substance in article: CSR-PI CHEMICAL SAFETY REPORT 25

38 Identifiers Use descriptors Other information SL-2: Service life of coloured plastic or plasticised articles. Performance and longevity depend on pigment quality for bright lasting colours improving visibility and safety, heat stability,durability, chemical fastness, tenchical requirements and Regulations Remarks: Paints and coatings containing C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are applied in particular to equipment or substrates to ensure a long life-time of the coating and the coated object for optimal protection, visibility and safety, and to maintain the replacement value of the object. Other motivation to use this type of paint/coating on objects is the extreme durability and quality of the paint/coating which reduces the need to repair or repaint on places that are difficult to reach, in dangerous situations, or where idle time of equipment would incur high costs. The desired combination of colouristic properties (such as a wide range of clean, vivid shades for visibility, colour stability, excellent coverage or hiding power) together with technical performance characteristics (such as rheology, light and weather fastness (durability), chemical fastness, non-bleeding/migration, impact resistance) cannot be guaranteed through other pigments or combination of pigments. Their superior performance coupled with price position, make alternatives less favourable Colour shade spectrum: C.I. Pigment Yellow 34 and C.I. Pigment Red 104 have a wide shade spectrum covering shades from green shade yellow up to blue shade red. No other pigment chemistry, other than cadmium-based products, has such a broad colour shade spectrum. As such, it is often not possible to match certain shades without the use of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. The colour palette of end users will be limited without these pigments. Opacity/hiding power: one of the main functions of a paint or coating is to colour/hide the substrate it is covering. The more opaque a paint or coating is, the less number of coating layers are required to hide the substrate. The more coating layers that are required results in a higher environmental impact as more solvents, resins, additives and energy will be used. When taking into account the target colour shade that is required, alternatives to C.I. Pigment Yellow 34 and C.I. Pigment Red 104 often require more coating applications to achieve the same level of hiding. As such, alternatives often have an indirect environmental impact through the need to apply more coatings leading to the use of more energy, solvents and resins. Durability: durability or weather fastness is a critical technical requirement for many coatings applications. If the colour of a paint/coating changes by fading or darkening it can lead to the need for repainting or disposal of the painted/coated article. This can lead to environmental issues through the use of more paint (and thus more energy, solvents and resins) or through waste disposal at landfill. Article category related to subsequent service life (AC): AC 13: Plastic articles Exposure related description of article: Articles with particular waste collection and treatment schemes, e.g. electronic equipment Articles with foreseeable exposure to dust and fumes during maintenance and recycling processes, e.g. abrasive surface cleaning, dismantling and milling Environmental release category (ERC): ERC 10a: Wide dispersive outdoor use of long-life articles and materials with low release ERC 10b: Wide dispersive outdoor use of long-life articles and materials with high or intended release (including abrasive processing) ERC 11a: Wide dispersive indoor use of long-life articles and materials with low release ERC 11b: Wide dispersive indoor use of long-life articles and materials with high or intended release (including abrasive processing) Article used by: workers Tonnage of substance: Typical concentration of the substance in article: CSR-PI CHEMICAL SAFETY REPORT 26

39 Identifiers Use descriptors Other information ERC 12a: Industrial processing of articles with abrasive techniques (low release) Process category (PROC): PROC 21: Low energy manipulation of substances bound in materials and/or articles PROC 24: High (mechanical) energy work-up of substances bound in materials and/or articles Technical function of the substance during formulation: Colouring agents, pigments Remarks: 2.3. Uses advised against Table 11. Formulation C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are unique in their value in use proposition. They combine superb colouristic properties such as a wide range of clean, vivid shades for visibility, night time reflectivity, colour stability, excellent opacity or hiding power with technical performance requirements such as light and weather fastness (durability), chemical fastness, non-migration, impact resistance and heat stability. This combination cannot be guaranteed through the use of other pigments or combination of pigments. Indeed most alternatives fail in one or more of the above technical characteristics. The superior performance of C.I. Pigment Yellow 34 and C.I. Pigment Red 104 coupled with price position, make alternatives less favourable. These pigments are used in plastic objects to ensure a long-lasting high quality colour and protection or to ensure high visibility related to occupational or public safety. Alternative and less effective pigments often lead to the use of more UV-stabilisers and plasticisers due to inadequate weather fastness or higher oil adsorption. In addition, due to their lower opacity (more transparency), the alternative pigments will demonstrate lower night time reflectivity causing potential safety issues in road marking matrices. Identifiers F-5: Formulation of pigment in paints, plastics and plasticised articles for consumer use Use descriptors Environmental release category (ERC): ERC 2: Formulation of preparations ERC 3: Formulation in materials Product Category formulated: PC 9a: Coatings and paints, thinners, paint removes PC 9c: Finger paints PC 32: Polymer preparations and compounds PC 34: Textile dyes, finishing and impregnating products; including bleaches and other processing aids Technical function of the substance during formulation: Colouring agents, pigments Other information Remarks: Use is restricted in Annex XVII of REACH, as C.I. Pigment Yellow 34 and C.I. Pigment Red 104 fall into the criteria of entries 28 and 30 of this Annex. Column 1 Designation of the substance, of the group of substances or of the mixture 28. Substances which appear in Part 3 of Annex VI to Regulation (EC) No 1272/ CSR-PI CHEMICAL SAFETY REPORT 27

40 Identifiers Use descriptors classified as carcinogen category 1A or 1B (Table 3.1) or carcinogen category 1 or 2 (Table 3.2) and listed as follows: - Carcinogen category 1A (Table 3.1)/ carcinogen category 1 (Table 3.2) listed in Appendix 1 - Carcinogen category 1B (Table 3.1)/ carcinogen category 2 (Table 3.2) listed in Appendix 2 Table 12. Consumer uses Identifiers 30. Substances which appear in Part 3 of Annex VI to Regulation (EC) No 1272/2008 classified as toxic to reproduction category 1A or 1B (Table 3.1) or toxic to reproduction category 1 or 2 (Table 3.2) and listed as follows: - Reproductive toxicant category 1A adverse effects on sexual function and fertility or on development (Table 3.1) or reproductive toxicant category 1 with R60 (May impair fertility) or R61 (May cause harm to the unborn child) (Table 3.2) listed in Appendix 5 - Reproductive toxicant category 1B adverse effects on sexual function and fertility or on development (Table 3.1) or reproductive toxicant category 2 with R60 (May impair fertility) or R61 (May cause harm to the unborn child) (Table 3.2) listed in Appendix 6 Column 2 Conditions of restriction Without prejudice to the other parts of this Annex the following shall apply to entries 28 to 30: 1. Shall not be placed on the market, or used, - as substances, - as constituents of other substances, or, - in mixtures, for supply to the general public when the individual concentration in the substance or mixture is equal to or greater than: - either the relevant specific concentration limit specified in Part 3 of Annex VI to Regulation (EC) No 1272/2008, or, - the relevant concentration specified in Directive 1999/45/EC. Without prejudice to the implementation of other Community provisions relating to the classification, packaging and labelling of substances and mixtures, suppliers shall ensure before the placing on the market that the packaging of such substances and mixtures is marked visibly, legibly and indelibly as follows: Restricted to professional users. 2. By way of derogation, paragraph 1 shall not apply to: (a) medicinal or veterinary products as defined by Directive 2001/82/EC and Directive 2001/83/ EC; (b) cosmetic products as defined by Directive 76/768/EEC; (c) the following fuels and oil products: - motor fuels which are covered by Directive 98/70/EC, - mineral oil products intended for use as fuel in mobile or fixed combustion plants, - fuels sold in closed systems (e.g. liquid gas bottles); (d) artists paints covered by Directive 1999/45/ EC; (e) the substances listed in Appendix 11, column 1, for the applications or uses listed in Appendix 11, column 2. Where a date is specified in column 2 of Appendix 11, the derogation shall apply until the said date. Use descriptors C-5: Consumer use Environmental release category (ERC): of paints, plastics and ERC 8c: Wide dispersive indoor use resulting in inclusion into or onto a matrix plasticised articles ERC 8f: Wide dispersive outdoor use resulting in inclusion into or onto a matrix containing the pigment Product Category used: PC 9a: Coatings and paints, thinners, paint removes CSR-PI CHEMICAL SAFETY REPORT 28

41 Identifiers Use descriptors PC 9c: Finger paints PC 34: Textile dyes, finishing and impregnating products; including bleaches and other processing aids Technical function of the substance during formulation: Colouring agents, pigments Other information Remarks: Use is restricted in Annex XVII of REACH, as C.I. Pigment Yellow 34 and C.I. Pigment Red 104 fall into the criteria of entries 28 and 30 of this Annex. Column 1 Designation of the substance, of the group of substances or of the mixture 28. Substances which appear in Part 3 of Annex VI to Regulation (EC) No 1272/2008 classified as carcinogen category 1A or 1B (Table 3.1) or carcinogen category 1 or 2 (Table 3.2) and listed as follows: - Carcinogen category 1A (Table 3.1)/ carcinogen category 1 (Table 3.2) listed in Appendix 1 - Carcinogen category 1B (Table 3.1)/ carcinogen category 2 (Table 3.2) listed in Appendix Substances which appear in Part 3 of Annex VI to Regulation (EC) No 1272/2008 classified as toxic to reproduction category 1A or 1B (Table 3.1) or toxic to reproduction category 1 or 2 (Table 3.2) and listed as follows: - Reproductive toxicant category 1A adverse effects on sexual function and fertility or on development (Table 3.1) or reproductive toxicant category 1 with R60 (May impair fertility) or R61 (May cause harm to the unborn child) (Table 3.2) listed in Appendix 5 - Reproductive toxicant category 1B adverse effects on sexual function and fertility or on development (Table 3.1) or reproductive toxicant category 2 with R60 (May impair fertility) or R61 (May cause harm to the unborn child) (Table 3.2) listed in Appendix 6 Column 2 Conditions of restriction Without prejudice to the other parts of this Annex the following shall apply to entries 28 to 30: 1. Shall not be placed on the market, or used, - as substances, - as constituents of other substances, or, - in mixtures, for supply to the general public when the individual concentration in the substance or mixture is equal to or greater than: - either the relevant specific concentration limit specified in Part 3 of Annex VI to Regulation (EC) No 1272/2008, or, - the relevant concentration specified in Directive 1999/45/EC. Without prejudice to the implementation of other Community provisions relating to the classification, packaging and labelling of substances and mixtures, suppliers shall ensure before the placing on the market that the packaging of such substances and mixtures is marked visibly, legibly and indelibly as follows: Restricted to professional users. 2. By way of derogation, paragraph 1 shall not apply to: (a) medicinal or veterinary products as defined by Directive 2001/82/EC and Directive 2001/83/ EC; (b) cosmetic products as defined by Directive 76/768/EEC; (c) the following fuels and oil products: - motor fuels which are covered by Directive 98/70/EC, - mineral oil products intended for use as fuel in mobile or fixed combustion plants, - fuels sold in closed systems (e.g. liquid gas bottles); (d) artists paints covered by Directive 1999/45/ EC; CSR-PI CHEMICAL SAFETY REPORT 29

42 Identifiers Use descriptors (e) the substances listed in Appendix 11, column 1, for the applications or uses listed in Appendix 11, column 2. Where a date is specified in column 2 of Appendix 11, the derogation shall apply until the said date CSR-PI CHEMICAL SAFETY REPORT 30

43 3. CLASSIFICATION AND LABELLING 3.1. Classification and labelling according to CLP / GHS Name: lead chromate molybdate sulfate red Implementation: EU State/form of the substance: powder Related composition: lead chromate molybdate sulfate red Classification The substance is classified as follows: Table 13. Classification and labelling according to CLP / GHS for physicochemical properties Endpoint Hazard category Hazard statement Reason for no classification Explosives: Flammable gases: Flammable aerosols: Oxidising gases: Gases under pressure: Flammable liquids: Flammable solids: Self-reactive substances and mixtures: Pyrophoric liquids: Pyrophoric solids: Self-heating substances and mixtures: conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification CSR section*) CSR-PI CHEMICAL SAFETY REPORT 31

44 Substances and mixtures which in contact with water emit flammable gases: Oxidising liquids: Oxidising solids: Organic peroxides: Corrosive to metals: conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification *) Justification for (non) classification can be found in the CSR section indicated Table 14. Classification and labelling according to CLP / GHS for health hazards Endpoint Hazard category Hazard statement Reason for no classification Acute toxicity - oral: Acute toxicity - dermal: Acute toxicity - inhalation: Skin corrosion / irritation: Serious damage / eye irritation: Respiration sensitization: Skin sensitisation: Aspiration hazard: Reproductive Toxicity: Reproductive Toxicity: Effects on or via Resp. Sens. 1 Skin Sens. 1 Repr. 1A H334: May cause allergy or asthma symptoms or breathing difficulties if inhaled. H317: May cause an allergic skin reaction. H360: May damage fertility or the unborn child <state specific effect if known > <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. conclusive but not sufficient for classification CSR section*) data lacking data lacking conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification and data lacking CSR-PI CHEMICAL SAFETY REPORT 32

45 lactation: Germ cell mutagenicity: Carcinogenicity: Carc. 1B Specific target organ toxicity - single: Specific target organ toxicity - repeated: STOT Rep. Exp. 2 Affected organs: Cardiovascular system, liver, kidney H350: May cause cancer <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H373: May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. data lacking conclusive but not sufficient for classification and *) Justification for (non) classification can be found in the CSR section indicated Table 15. Classification and labelling according to CLP / GHS for environmental hazards Endpoint Hazard category Hazard statement Reason for no classification Hazards to the aquatic environment (acute/short-ter m): Hazards to the aquatic environment (long-term): M-Factor acute: 1 M-Factor chronic: 1 Hazardous to the ozone layer: Aquatic Acute 1 Aquatic Chronic 1 H400: Very toxic to aquatic life. H410: Very toxic to aquatic life with long lasting effects. *) Justification for (non) classification can be found in the CSR section indicated Labelling Signal word: Danger Hazard pictogram: GHS08: health hazard CSR section*) data lacking 7.6 GHS09: environment CSR-PI CHEMICAL SAFETY REPORT 33

46 Hazard statements: H350: May cause cancer <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H360: May damage fertility or the unborn child <state specific effect if known > <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H317: May cause an allergic skin reaction. H334: May cause allergy or asthma symptoms or breathing difficulties if inhaled. H373: May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H410: Very toxic to aquatic life with long lasting effects. Notes: Note Classification and labelling according to DSD / DPD Classification and labelling in Annex I of Directive 67/548/EEC Chemical name: lead chromate molybdate sulfate red Remarks: Official Annex VI classification - please note that the substance is also considered to be a skin and respiratory sensitiser but this is not included below as it is not part of the official classification. Therefore the reason for no classification for this endpoint is set to 'data lacking'. Classification The substance is classified as follows: Table 16. Classification and labelling in Annex I of Directive 67/548/EEC for physicochemical properties Endpoint Classification Reason for no classification Explosiveness: Oxidising properties: Flammability: Thermal stability: conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification conclusive but not sufficient for classification CSR section*) *) Justification for (non) classification can be found in the CSR section indicated Table 17. Classification and labelling in Annex I of Directive 67/548/EEC for health hazards CSR-PI CHEMICAL SAFETY REPORT 34

47 Endpoint Classification Reason for no classification Acute toxicity: Acute toxicity - irreversible damage after single exposure: Repeated dose toxicity: Irritation / Corrosion: conclusive but not sufficient for classification conclusive but not sufficient for classification CSR section*) R33 Danger of cumulative effects conclusive but not sufficient for classification and Sensitisation: data lacking Carcinogenicity: Carc. Cat. 2; R45 May cause cancer Mutagenicity - Genetic Toxicity: Toxicity to reproduction - fertility: Toxicity to reproduction - development: Toxicity to reproduction - breastfed babies: data lacking Repr. Cat. 3; R62 Possible risk of impaired fertility Repr. Cat. 1; R61 May cause harm to the unborn child. *) Justification for (non) classification can be found in the CSR section indicated data lacking Table 18. Classification and labelling in Annex I of Directive 67/548/EEC for the environment Endpoint Classification Reason for no classification Environment: N; R50/53 Dangerous for the environment; Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment. CSR section*) 7.6 *) Justification for (non) classification can be found in the CSR section indicated Labelling Indication of danger: T - toxic N - dangerous for the environment R-phrases: R45 - May cause cancer R61 - May cause harm to the unborn child R62 - Possible risk of impaired fertility R33 - Danger of cumulative effects R50/53 - Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment Notes: Note CSR-PI CHEMICAL SAFETY REPORT 35

48 Self classification(s) No relevant information available Other classification(s) No relevant information available CSR-PI CHEMICAL SAFETY REPORT 36

49 4. ENVIRONMENTAL FATE PROPERTIES General discussion of environmental fate and pathways: After release of C. I. Pigment Yellow 34 and/or C. I. Pigment Red 104 into the environment, a small fraction consisting of chromate ions (CrO 4 2- ) and lead ions (Pb 2+ ) will dissociate from the solids and partition in the environmental compartments. Both lead and chromium will bioaccumulate in fish and other aquatic organisms. The (median) BCF fish for lead was 23 L/kg whereas the 50th percentile for a mixed diet was 1553 L/kg. Chromium (VI) appears to be reduced to chromium (III) once it has been taken up in the organisms. Therefore a BCF of 100 was estimated from the total chromium concentration in biota / chromium (VI) concentration in water. Mean BAFs for earthworm were 0.11 and 0.10 kg/kg ww for chromium and lead, respectively. The relatively high Kd-values for lead and chromium indicate that both moieties may adsorb to suspended particles and soil. The partitioning of lead and chromium depends on ph, Fe-oxide, mineral particles and DOC-contents of water and soil. At neutral ph lead mostly forms carbon-lead complexes, whereas at low ph lead exists predominantly in the more mobile ionic form. Soil ph has a comparable effect on chromium; with increasing ph the adsorption of chromium increases. Furthermore, at neutral ph CrO 4 2- ions are expected to be reduced to the less mobile chromium III in the environment. The mobility of both ions decreases with increasing proportion of organic matter in soils Degradation Abiotic degradation Hydrolysis Data waiving Information requirement: Hydrolysis Reason: study scientifically unjustified Justification: The substance is inorganic and possesses no hydrolysable groups. Furthermore the water solubility is very low (waiving according to Column 2 in Annex VIII, ). Discussion The following information is taken into account for any hazard / risk / persistency assessment: According to structural properties, hydrolysis is not expected or probable Phototransformation/photolysis Phototransformation in air No relevant information available Phototransformation in water No relevant information available Phototransformation in soil No relevant information available Biodegradation Biodegradation in water CSR-PI CHEMICAL SAFETY REPORT 37

50 Screening tests Data waiving Information requirement: Biodegradation in water: screening test Reason: study technically not feasible Justification: Not applicable; C. I. Pigment Red 104 is an inorganic substance (waiving according to Column 2 in Annex VII, ) Simulation tests (water and sediments) Data waiving Information requirement: Simulation testing for biodegradation in water and sediment Reason: study technically not feasible Justification: Not applicable; C. I. Pigment Red 104 is an inorganic substance (waiving according to Column 2 in Annex VII, ) Summary and discussion of biodegradation in water and sediment Discussion (screening testing) The following information is taken into account for any hazard / risk / persistency assessment: The substance is inorganic and therefore a study on the biodegradation is not required (Column 2 in Annex VII, ). Discussion (simulation testing) The following information is taken into account for any hazard / risk / persistency assessment: The substance is inorganic and therefore a study on the biodegradation is not required (Column 2 in Annex VII, ) Biodegradation in soil Data waiving Information requirement: Soil simulation testing Reason: study technically not feasible Justification: Not applicable; C. I. Pigment Red 104 is an inorganic substance (waiving according to Column 2 in Annex VII, ) Discussion The following information is taken into account for any hazard / risk / persistency assessment: The substance is inorganic and therefore a study on the biodegradation is not required (Column 2 in Annex VII, ) Summary and discussion of degradation Abiotic degradation C. I. Pigment Red 104 is an inorganic substance. Due to the lack of hydrolysable groups hydrolysis is not expected. Biotic degradation C. I. Pigment Red 104 is an inorganic substance. Therefore biodegradation is not expected and biodegradation rates cannot be calculated CSR-PI CHEMICAL SAFETY REPORT 38

51 4.2. Environmental distribution Adsorption/desorption The studies on adsorption/desorption are summarised in the following table: Table 19. Studies on adsorption/desorption Method Results Remarks Reference Study type: adsorption (sediment) Adsorption coefficient: calculated The partitioning of trace metals in rivers were investigated. The coefficients were modelled using a combination of WHAM and SCAMP models (Tipping 1994, Lofts and Tipping 1998). Observed and predicted log Kd were compared. Study type: adsorption (soil) calculation Soil-liquid partitioning coefficients were compiled from studies. Multiple linear regressions were performed with the data in order to predict Kd values. Discussion log Kd: (first value: observed; second value: predicted) Kd: (recalculated from predicted log Kd (as cited in publication)) Partitioning coefficients (Kd in L /kg): Chromium Kd: 14920, log10 Kd 4.17 Lead Kd: , log10 Kd (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Chromium and lead Lofts S, Tipping E. (2000) Sauvé S, Hendershot W, Allen HE (2000) Data on adsorption of C. I. Pigment Yellow 34 and C. I. Pigment Red 104 are not available. However, chromate ions (CrO 4 2- ) and lead ions (Pb 2+ ) may dissociate from the substance and adsorb to suspended particles and soil. Experimental and calculated log Kd-values for lead and chromium indicate that both moieties may adsorb to suspended particles and soil. However, the partitioning of lead and chromium depends on ph, Fe-oxide, mineral particles and DOC-contents of water and soil. At neutral ph lead mostly forms carbon-lead complexes, whereas at low ph lead exists predominantly in the more mobile ionic form. Soil ph has a comparable effect on chromium; with increasing ph the adsorption of chromium increases. Furthermore, at neutral ph CrO 4 2- ions are expected to be reduced to the less mobile chromium III in the environment. The mobility of both ions decreases with increasing proportion of organic matter in soils. The following log Kd values for lead (resulting from investigations for rivers (Lofts and Tipping, 2000)) were reported: 5.41 (observed) (predicted). For chromium the mean of calculated log Kd values for ph ranging from 2-10 (from Sauve et al, 2000) was For the risk assessment, use is made of the extensive work carried out for the risk evaluations of chromium and lead at the EU level. The Kd values used for PEC and PNEC calculations for chromium (EU RAR) and lead (vrar) are presented in the Table. When available, also Kd values given in the ECHA Guidance Appendix R Metals are included CSR-PI CHEMICAL SAFETY REPORT 39

52 Substance Type Kd (L/kg) remarks Chromium (VI) Kd (suspended matter water) 2000 Acid conditions 200 Neutral-alkaline conditions Kd (sediment water) 1000 Acid conditions 100 Neutral-alkaline conditions Kd (soil water) 50 Acid conditions 2 Neutral-alkaline conditions Chromium (III) Kd (suspended matter water) Kd (sediment matter water) Acid conditions Neutral-alkaline conditions Acid conditions Neutral-alkaline conditions Kd (soil water) 800 Acid conditions Neutral-alkaline conditions Lead Kd (suspended matter water) L/kg Freshwater data 50th percentile n= 12, from vrar (same value reported in REACH guidance Appendix R Metals) L/kg Estuarine data L/kg Marine data 50th percentile n= 19, from vrar 50th percentile n= 22, from vrar Kd (sediment water) L/kg 50th percentile n= 5 (REACH guidance Appendix R Metals) CSR-PI CHEMICAL SAFETY REPORT 40

53 Substance Type Kd (L/kg) remarks Chromium L/kg Average of two median Kd values derived from datasets with many measured background and ambient concentrations (vrar) Kd (soil water) 6400 L/kg 50th percentile n= 60 (REACH guidance Appendix R Metals) 6400 L/kg Average of two median measured Kd, n= 60 from vrar The Kd for chromium (VI) and chromium (III) are based on the available measured data. Kd could not be derived from a statistical distribution due to the lack of sufficient data. Instead the Rapporteur of the EU RAR selected the values by inspection of the available data set to reflect the available information under acid (ph < 5) and neutral-alkaline (ph > 6) conditions. Lead A large number of measured sorption data is available for lead. 10th, 50th and 90th percentile Kd have been derived from the fitted distributions in the vrar. Median Kd have been used for the derivation of PEC and PNEC. This is in agreement with the REACH guidance in Appendix R : Environmental risk assessment for metals and metal compounds. Kd suspended matter water was determined separately for freshwater, estuarine and marine data for lead. The 10th, 50th, and 90th percentiles of the fitted distributions were reported in the vrar lead. In line with REACH guidance the median values should be used for PEC and PNEC derivation. The 10th and 90th percentiles could be used for an uncertainty analysis. Kd sediment is derived from the REACH Guidance document Appendix R.7.13 Metals, Table A similar value was proposed for Kd sediment in the vrar based on the average of two median Kd derived from respectively environmental concentration distributions for background or ambient lead concentrations in surface water and sediment (Kd sediment). Similarly Kd soil was determined as the average of two medians derived from two data sets where Kd was based on measured concentrations of lead in pore water and Kd was normalised to a typical soil with ph 6.5, 2% organic matter content and 27.4 mgpb/kg soil. The following information is taken into account for any environmental exposure assessment: For the risk assessment of the pigments, the Kd values for lead are used to estimate partitioning to suspended matter, sediment and soil Volatilisation No relevant information available Distribution modelling No relevant information available CSR-PI CHEMICAL SAFETY REPORT 41

54 Summary and discussion of environmental distribution C. I. Pigment Red 104 is a solid, inorganic substance and will therefore not evaporate into the atmosphere. The solubility of the substance is very low and thus the substance will not dissolve in water. Furthermore the undissolved substance is not expected to adsorb to sediment and soil. Chromate ions (CrO4 2- ) and lead ions (Pb² + ) may dissociate from the substance. Lead and chromium may adsorb to suspended particles, sediment and soil. Thus, when released to the environment moieties dissolving from the parent substance will probably mainly be found in sediment and soil. A minor part of the dissolved metal ions may be found in water Bioaccumulation C. I. Pigment Red 104 is poorly water soluble and therefore the potential for bioaccumulation is expected to be low Aquatic bioaccumulation The studies on aquatic bioaccumulation are summarised in the following table: Table 20. Studies on aquatic bioaccumulation Method Results Remarks Reference Selenastrum capricornutum, Daphnia magna, Poecilia reticulata aqueous (freshwater) flow-through Total uptake duration: 4 wk A tri-trophic food chain including algae, Daphnia and fish was established. The three species were exposed to a solution of leadnitrate in four separate but connected compartments of the test apparatus. In the first compartment algae were bread. Via a discharge test solution and algae were flowing into a second tank where Daphnia were bred. Via a discharge a third tank where fish were kept received test solution and Daphnia. A fourth tank with fish received only test solution via an overflow. The fish in the fourth tank were fed with untreated Daphnia. Salmo gairdneri (new name: Oncorhynchus mykiss) concentration factor in fish fed with contaminated Daphnia: 1900 (14 days of exposure) concentration factor in fish fed with contaminated Daphnia: 3600 (28 days of exposure) concentration factor in fish fed with uncontaminated Daphnia: 700 (14 days of exposure) concentration factor in fish fed with uncontaminated Daphnia: 1100 (28 days of exposure) concentration factor in fish fed with contaminated Daphnia: 600 (14 days of exposure) concentration factor in fish fed with contaminated Daphnia: 1000 (28 days of exposure) concentration factor in fish fed with uncontaminated Daphnia: 280 (14 days of exposure) concentration factor in fish fed with uncontaminated Daphnia: 360 (28 days of exposure) 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead nitrate 2 (reliable with restrictions) Vighi M. (1981) Fromm PO and Stokes RM (1962) aqueous (freshwater) static key study read-across from CSR-PI CHEMICAL SAFETY REPORT 42

55 Method Results Remarks Reference Total uptake duration: d Two tests were performed. In a first test fish were exposed to several concentrations of chromium for 15, 24 days and 30 respectively. Chromium contents in fish were determined. In order to investigate the uptake route and mode of action of chromium the oxygen consumption of pyloric caeca, liver and kidney tissues were determined. Furthermore blood lactic acid and glucose and muscle glycogen were determined. Gillichthys mirabilis aqueous (saltwater) semi-static Total uptake duration: 120 d Tissues of lead-exposed fish in seawater were analysed for accumulation and decay of lead. Tests were performed in natural or lead-dosed sea water. Tests were performed at different lead levels, temperature and salinity. Mytilus edulis sediment (saltwater) static Type of sediment: natural sediment Total uptake duration: 7 d Total depuration duration: 21 d supporting substance (structural analogue or surrogate) Test substance: Chromium 2 (reliable with restrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead acetate 2 (reliable with restrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test substance: Cr (III), Cr (VI) Somero GN, Chow TJ, Snyder Y, Snyder CB (1977) Wang W_X, Griscom SB, Fisher NS (1997) The bioaccumulation of Cr (III) and Cr(VI) in phytoplankton was investigated by exposing phytoplanton species to different concentrations of chromium. Cell growth and accumulated Cr was measured periodically. Potamonautes perlatus (freshwater) field study Type of sediment: natural BSAF: (whole body w.w.) (steady state) BCF: ca. 500 L/kg (whole body w.w.) (steady state) 2 (reliable with restrictions) supporting study read-across from supporting substance Reinecke AJ, SNyman RG, Nel JAJ (2003) CSR-PI CHEMICAL SAFETY REPORT 43

56 Method Results Remarks Reference sediment The lead contamination of Eerste River in South Africa and the accumulation of Pb in Potamonautes perlatus was determined Terrestrial bioaccumulation No relevant information available Summary and discussion of bioaccumulation Aquatic bioaccumulation (structural analogue or surrogate) Test substance: Lead Due to the very low solubility of C. I. Pigment Red 104 in water the bioavailability of the substance is expected to be low. Therefore, the bioaccumulation potential of the substance is expected to be low. However, a small proportion of the parent substance may dissolve and release chromate ions (CrO4 2- ) and lead ions (Pb² + ). The Transformation/Dissolution study showed that at ph 6 less than 1% of the lead incorporated in a paint or plastic matrix actually dissolved and less than 0.1% of lead dissolved at ph 8 and less than 0.1% of chromium dissolved at both phs. The following information is taken into account for any hazard / risk / bioaccumulation assessment: Significant accumulation of C. I. Pigment Red 104 in organisms is not expected. A small proportion of the parent substance C. I. Pigment Red 104 or C. I. Pigment Yellow 34 may dissolve and release chromate ions (CrO 4 2- ) and lead ions (Pb 2+ ). The IUCLID data set includes results from a literature search on the bioaccumulation of both chromium and lead. Both moieties of the pigments may accumulate in organisms (Tulasi et al. 1992, Avenant-Oldewage and Marx 2000). For lead a concentration factor of 360 was detected in Poecilia reticulata after 28 days of exposure to 50 µg lead/l (Vighi, 1981). Generally biomagnification of lead is not expected. Similarly the BCF in the crab Potamonautes perlatus was circa 500 L/kg after exposure to µg lead/l. The bioconcentration factor for the sediment was 3.5 (dimensionless, Reinecke et al., 2003). For chromium (VI) a BCF of 1 l/kg was determined (Fromm and Stokes 1962). However, CrO 4 2- ions will be reduced to less reactive chromium (III) ions under most environmental conditions. Chromium (III) is less bioavailable and therefore chromium (III) is expected to be less bioaccumulative. In general the bioaccumulation of both metal ions increases with rising temperature, alkalinity and lower water salinity. Both lead and chromium have been discussed extensively under the EU-Existing Chemicals Regulation and the results were reported in a Risk Assessment Report (RAR 2005) for Chromium and the voluntary RAR for Lead (2008). The bioconcentration factor for lead from the vrar (2008) and the bioconcentration factors for chromium (VI) and chromium (III) proposed in the EU RAR (2005) are presented in the table: Substance Species Remarks Chromium (VI) Fish 1 L/kg Used to estimate concentration of chromium (VI) in fish based food chain Mussels 1820 L/kg Based on measured values CSR-PI CHEMICAL SAFETY REPORT 44

57 Substance Species Remarks in marine species Chromium (III) Fish 100 L/kg Used to estimate concentration of chromium (III) in fish resulting from uptake and subsequent reduction in biota of chromium (VI) Mussels 560 L/kg Based on measured values in marine species Lead Fish 23 L/kg 50th percentile of range in BCFfish Chromium: Mollusc diet 675 L/kg 50th percentile of range in BCFmolluscs Mixed diet 1553 L/kg 50th percentile of range in BCFmixed food diet The BCF values for chromium VI and III were derived from values measured in a variety of systems. The available data indicated that the BCF for chromium (VI) in fish was low (around 1 L/kg). However, it was noticed that chromium (VI) appears to be reduced to chromium (III) once it has been taken up in the organisms. Therefore a BCF of 100 was estimated from the total chromium concentration in biota / chromium (VI) concentration in water. Direct uptake of chromium (III) from the water phase was not assumed because of the low water solubility and strong sorption of chromium (III) to sediment under most environmental conditions. It should be noted however that secondary poisoning for chromium (III) is not assessed in the risk characterisation (and hence the BCF for chromium (III) has not been used). The uptake of chromium by aquatic species may be ph dependent, but it was concluded in the EU RAR that there was not sufficient information available to take this into account for the BCF. Lead: The BCF values for lead were derived from field studies taking into account all exposure routes as this was considered to be more environmentally realistic. BCF of lead in fish and invertebrates were dependent on the exposure concentration in water because of the active regulation of internal Pb body concentrations in the organisms. Therefore only BCF of studies with realistic dissolved Pb concentrations (between 0.18 and 15 µg/l) were selected for the BCF evaluation. The median BCF fish of the resulting database was 23 L/kg whereas the median BCF mussel of the remaining studies was 675 L/kg. The 50th percentile for a mixed diet was calculated as 1553 L/kg. This value was used for the calculation of PECoral in the mussel-based food chain in the vrar as it was considered to be more environmentally realistic. It should be noted that the risk characterisation for secondary poisoning of lead was not included in the vrar because there was no agreement on the PNECoral to be used. The following information is taken into account for any hazard / risk / bioaccumulation assessment: The median BCF fish for LEAD in the database of the vrar was 23 L/kg whereas the median BCF mussel of the remaining studies was 675 L/kg. The 50th percentile for a mixed diet was calculated as 1553 L/kg. The latter value was considered more CSR-PI CHEMICAL SAFETY REPORT 45

58 environmentally realistic. Value used for CSA: BCF: 1553 L/kg ww Terrestrial bioaccumulation Chromium A range of values for uptake of chromium (VI) in earthworms is presented in the EU RAR and the mean of the middle of various ranges reported in literature was used to estimate the concentrations in worms. This mean BCF worm for chromium was calculated as 0.11 kg/kg ww. Lead A large amount of bioaccumulation data for terrestrial organisms is available as well for lead. The mean BCF earthworm derived from a reliable dataset of 101 BAF values was reported as 0.10 kg dw/kg ww. However, it should be noted that the earthworm food chain was not addressed, neither in the EU RAR for chromium and nor in the vrar for lead. The following information is taken into account for any hazard / risk / bioaccumulation assessment: The mean BCF earthworm derived from a reliable dataset of 101 BAF values for lead was 0.10 kg dw/kg ww. (dimension NOT Liter/kg ww) Value used for CSA: Terrestrial BCF: Secondary poisoning Due to the fact that the substance is not bioaccumulative, it is unlikely that a secondary poisoning risk will occur by this substance. Therefore and for reasons of animal welfare, the assessment of secondary poisoning of this substance will be based on mammalian data. For the transformation products Chromium (VI) and Lead, the following PNECoral were derived: Chromium (VI): PNEC oral 17 mg/kg food Lead: PNEC oral 0.5 mg/kg food Interpretation of the available data with regard to the potential to bio-accumulate in the food chain: Chromium(VI): The very low bioconcentration factors for fish (BCF usually around 1 L/kg) do not trigger the evaluation of secondary poisoning. However since chromium (VI) uptake from water, sediment and soil has been reported for a wide range of organisms, the PNECoral derived in the EU RAR has been used here as well. The PNEC is based on the lowest available chronic NOAEL (20 mg Cr VI/kg body weight/ day for effects on the testes in mice by exposure via oral gavage) and the lowest available chronic LOAEL (20 mg Cr VI/kg body weight/ day for developmental effects in mice via the drinking water route). Converting this value of 20 mg/kg with conversion factor 8.3 gives a NOECfood of 166 mg/kg. Application of an AF of 10 results in the PNECoral of 16.6 mg chromium VI / kg food. Chromium(III): PNEC oral was not derived in EU RAR (2005) because of the absence of a review of mammalian data for chromium (III). In the toxicity studies used for the PNECoral for chromium (VI), organisms were exposed through gavage or drinking water. Therefore little conversion of chromium (VI) to chromium (III) was expected (according to the EU RAR). Lead: Application of AF of 300 to the lowest NOEC for mammals (150 mg/kg food, Rattus sp., ref Kao & Forbes, 1973)) resulted in PNECoral of 0.5 mg/kg for mammals. It should be noted that the latter value is in the range of natural background concentrations. The SCHER also discusses the use of lead concentrations in blood and an SSD approach but concludes that more work is required before a proper assessment of the risk of secondary poisoning could be conducted CSR-PI CHEMICAL SAFETY REPORT 46

59 5. HUMAN HEALTH HAZARD ASSESSMENT 5.1. Toxicokinetics (absorption, metabolism, distribution and elimination) Non-human information The results of studies on absorption, metabolism, distribution and elimination are summarised in the following table: Table 21. Studies on absorption, metabolism, distribution and elimination Method Results Remarks Reference in vitro study not applicable, in vitro studies Not applicable Exposure regime: Gastric fluid: 2 hours Interstitial, intercellular and perspiration fluid: 24h and 168h (7 days) Doses/conc.: Loading rate: Gastric fluid: 0.2 g/l Interstitial, intracellular and perspiration fluid: 2 g/l Standard Operating Procedure (SOP) for the Bio-accessibility Testing Programme of Eurometaux (November 10, 2010), based on ASTM D : standard test method for determining the extractability of metals from art materials - ASTM, 2007 The bio-elution potential of C.I. Pigment Yellow 34 and C.I. Pigment Red 104 was determined in four kinds of simulated body fluids (gastric, interstitial, intracellular and perspiration fluid), to determine bioavailability of chrome and lead for absorption. Results show highest bio-elution in gastric fluid, in which 22-24% of chromium and 23-26% of lead dissolved. For chromium, the percentages dissolved were 8.34 and 1.33% in interstitial, 3.44 and 3.77% intracellular and 0.07 and 0.08% in perspiration fluid, for C.I. Pigment Yellow 34 and C.I. Pigment Red 104 respectively. For lead, the percentages dissolved were 0 and 0.02% in interstitial, 4.17 and 9.37% in intracellular and 1.64 and 1.8% in perspiration fluid, for C.I. Pigment Yellow 34 and C.I. Pigment Red 104 respectively. 1 (reliable without restriction) key study experimental result Test material: C.I. Pigment Red 104 Form: powder Brouwers, T. (2013a) Brouwers, T. (2013b) Brouwer, T. (2013) Brouwers, T. (2013c) Brouwers, T. (2013d) Brouwers, T. (2013e) Brouwers, T. (2013f) Brouwers, T. (2013g) CSR-PI CHEMICAL SAFETY REPORT 47

60 Method Results Remarks Reference rat (Sprague-Dawley) male/female oral: gavage Exposure regime: once Doses/conc.: mg/kg bw determination tissue distribution of lead after acute oral treatment of test rats with test substance rat (Sprague-Dawley) male/female oral: feed Doses/conc.: 0, 2000, 5000 and ppm in diet (corresponding to appr , and mg/kg bw per day considering mean daily food consumption of , 77.5 and 80.1 g/kg and mean body weight of 274.3, and g) OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) protocol including determination of blood lead level and tissue distribution of lead dog (Beagle) male/female oral: feed Doses/conc.: 0, 2000, 5000 and ppm in diet (corresponding to appr. 75.4, and mg/kg bw per day considering mean weekly food consumption of 264, and g/kg) After single oral administration, no additional lead is resorbed from the pigment than the part that would have been soluble in 0.25 M HCl, although in the case of Chromgelb pigments, a higher amount had to be administered compared to lead acetate. This could be a consequence of a shorter retention period and subsequent cracking of the pigments in the gastro-intestinal tract, compared to lead(ii)acetate. Noticeable increases were observed in the blood lead concentrations of all test animals after 30, 60, and 84 days of testing. The increases in blood lead concentrations were dose-related. The lead content of the bone and kidney samples was markedly increased among animals fed 2000 ppm or more test substance. The brain lead content (males only) and liver lead content (males and females) were slightly increased when compared with control values. Increases in chromium content were noted in the kidney and liver tissues among most test animals. The brain chromium content was slightly increased among a few females fed 2000 ppm or more and among the males fed ppm. Brain chromium content among male test animals fed 2000 or 5000 ppm was either less than or comparable to that of the controls. Increases in chromium content in bone samples from animals fed either 5000 or ppm were due to detectable amounts in 1 of 5 males fed 5000 ppm and in 1 of 5 females fed ppm. No detectable amount of chromium was found in the bone samples from any of the 2000 ppm animals Blood lead concentrations at all three levels of either lead carbonate or test substance were elevated in a dose-correlated manner. The lead content of liver, kidney, bone and brain tissues was elevated at all levels of either compound. Increases were directly proportional to length of time on test and/or dietary concentration. In dogs fed the 3 levels of lead carbonate, chromium content in all 4 tissues was comparable to that seen in untreated controls, either below detectable limits or found in trace amounts 2 (reliable with restrictions) key study experimental result Test material (internal name): Chromgelb 62 F 2 (reliable with restrictions) key study experimental result Test material (CI name): CI Pigment Yellow 34 2 (reliable with restrictions) key study experimental result Test material (CI name): CI Pigment Yellow 34 BASF AG (1974a) BASF Farben & Fasern AG (1976a) BASF Farben & Fasern AG (1976b) CSR-PI CHEMICAL SAFETY REPORT 48

61 Method Results Remarks Reference only. OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity in Non-Rodents) protocol including determination of blood lead level and tissue distribution of lead Human information No relevant information available Summary and discussion of toxicokinetics No toxicokinetics study is available for C. I. Pigment Red 104, but information on distribution is available from repeated dose toxicity studies. Furthermore, bioelution studies with C. I. Pigment Red 104 were performed in simulated gastric, interstitial, intracellular and perspiration fluid to determine bioavailability for absorption via the oral, inhalation and dermal route. Information from repeated dose toxicity studies In the first rat study the animals received one treatment (10000 mg/kg bw; Chromgelb 62 F, Chromgelb 72 GS and the equivalent amount of lead in the form of lead(ii) acetate as positive control) test substance by gavage (BASF AG, 1974). In the remaining studies the animals received 0, 2000, 5000 and ppm test substance (CI Pigment Yellow 34) in diet (corresponding to appr. 0, 152.9, and mg/kg bw per day in rats and to appr. 0, 75.4, and mg/kg bw per day in dogs). In the first study, lead content levels were determined (atomic absorption spectroscopy; detection limit 1 µg) in kidneys and bone (femur) 14 days after treatment. In the second and third studies, tissues and body fluids sampled - blood (lead); liver, kidney, brain, and bone (lead and chromium) were analyzed using atomic absorption spectrophotometry (limits of detection and quantification: Pb µg/g; Cr µg/g in brain tissue; Cr µg/g in bone, liver, and kidney). Additional groups fed lead carbonate as positive control were also evaluated. Blood Lead determination: In both oral subchronic studies, noticeable and dose-related increases were observed in the blood lead concentrations of all test animals after 30, 60, and 84 days of testing with test and positive control substances. Tissue distribution: 1) Lead: 14 days after single oral administration of the test substance and the equivalent amount of lead in the form of lead(ii) acetate, the metal was detectable in kidneys and femurs of exposed animals. The lead content of the bone and kidney samples was markedly increased at all levels in the subchronic studies. The brain lead content (males only) and liver lead content (males and females) were slightly increased when compared with control values in the rat subchronic study and in all sexes in the dog subchronic study. Increases were generally directly proportional to length of time on test and/or dietary concentration. 2) Chromium: 2) Increases in chromium content were noted in the kidney and liver tissues among most test animals. In the rat subchronic study, the brain chromium content was slightly increased among a few females fed 2000 ppm or more and among the males fed ppm. Brain chromium content among male test animals fed 2000 or 5000 ppm was either less than or comparable to that of the controls. Increases in chromium content in bone samples from animals fed either 5000 or ppm were due to detectable amounts in 1 of 5 males fed 5000 ppm and in 1 of 5 females fed ppm. No detectable amount of chromium was found in the bone samples from any of the CSR-PI CHEMICAL SAFETY REPORT 49

62 2000 ppm animals. Following observations were made in the dog subchronic study: - At 2000 ppm test substance, chromium content was elevated in all 4 tissues examined, the liver showing the highest concentration, kidneys the next highest, then bone; brain tissue showed the lowest concentration. - At 5000 ppm, a similar pattern of elevations was seen, with the concentrations in kidney, bone and brain tissues essentially comparable to those found in 2000 ppm animals. However, in liver tissue, the chromium content in 2000 ppm animals was considerably higher than that found in 5000 ppm animals, though both levels were tested for 90 days. - At ppm, chromium content of liver and kidney tissues was much lower than that found in either 2000 or 5000 ppm dogs and in bone, chromium was below detectable limits. These findings correlate with the short time (3 weeks) the animals were on test. In brain tissue, however, chromium content was comparable to concentrations found at the 2 lower levels. Bio-elution studies The bio-elution potential of C.I. Pigment Yellow 34 and C.I. Pigment Red 104 was determined in four kinds of simulated body fluids (gastric, interstitial, intracellular and perspiration fluid), to determine bioavailability of chrome and lead for absorption. Incubation times were 2h for gastric fluid, and 24h and 7 days for interstitial, intracellular and perspiration fluid. Chrome and lead concentrations were measured by ICP-MS analysis. Results show highest bio-elution in gastric fluid, in which 22-24% of chromium and 23-26% of lead dissolved. For chromium, the percentages dissolved were 8.34 and 1.33% in interstitial, 3.44 and 3.77% in intracellular and 0.07 and 0.08% in perspiration fluid, for C.I. Pigment Yellow 34 and C.I. Pigment Red 104 respectively. For lead, the percentages dissolved were 0 and 0.02% in interstitial, 4.17 and 9.37% in intracellular and 1.64 and 1.8% in perspiration fluid, for C.I. Pigment Yellow 34 and C.I. Pigment Red 104 respectively. The values may be used to determine bioavailability of lead and chrome for absorption via the different exposure routes. The relatively high percentage of dissolved chrome and lead in simulated gastric fluid indicates that the highest bioavailability will result from oral exposure. Interstitial fluid may be a measure for dissolution in lung fluid and bioavailability after inhalation. The low dissolution of lead in this fluid indicates that lead will not be very bioavailable via this route, whereas for chromium bioavailability is relevant via inhalation. Bioavailability via dermal absorption may be indicated by dissolution in perspiration fluid. This is very low for chromium (<0.1%) and therefore dermal absorption will not be relevant for chromium. Lead dissolution from C. I. Pigment Yellow 34 and C. I. Pigment Red 104 in perspiration fluid is less than 1.8%. Therefore, bioavailability of lead for dermal absorption will also be very low. The following information is taken into account for any hazard / risk assessment: BIOAVAILABILITY FOR ABSORPTION Bioelution test with simulated gastric, interstitial, intracellular and perspiration fluid show highest bioavailability of both lead and chromium for oral absorption. The low dissolution of lead in interstitial fluid indicates that lead will not be very bioavailable via this route, whereas for chromium bioavailability is relevant via inhalation. Bioavailability via dermal absorption may be indicated by dissolution in perspiration fluid. This is very low for chromium and therefore dermal absorption will not be relevant for chromium. Lead concentrations in perspiration fluid are <2%, therefore bioavailability for dermal absorption will also be very low. DISTRIBUTION OF TEST SUBSTANCE METABOLITES Blood lead, chromium and/or molybdenum blood absorption and tissue distribution were observed in oral subchronic toxicity studies in rat (BASF AG, 1974; Report No: XXIV/61, BASF Farben & Fasern AG, 1976; Report No: ) and in dogs (BASF Farben & Fasern AG, 1976; Report No: ) Acute toxicity Non-human information Acute toxicity: oral CSR-PI CHEMICAL SAFETY REPORT 50

63 The results of studies on acute toxicity after oral administration are summarised in the following table: Table 22. Studies on acute toxicity after oral administration Method Results Remarks Reference rat (Sprague-Dawley) male/female oral: gavage equivalent or similar to OECD Guideline 401 (Acute Oral Toxicity) (test substance evaluated at unique mg/kg dose level) rat (Sprague-Dawley) male/female oral: gavage equivalent or similar to OECD Guideline 401 (Acute Oral Toxicity) (test substance evaluated at unique mg/kg dose level) Acute toxicity: inhalation Data waiving LD50: > mg/kg bw (male/female) (no mortality at this unique dose level) LD50: > mg/kg bw (male/female) (no mortality at this unique dose level) Information requirement: Acute toxicity after inhalation exposure Reason: study scientifically unjustified 2 (reliable with restrictions) key study experimental result Test material (internal name): Chromgelb 72 GS 2 (reliable with restrictions) key study experimental result Test material (internal name): Chromgelb 62 F BASF AG (1974b) BASF AG (1974c) Justification: The substance is a genotoxic carcinogen. Appropriate measures are taken to prevent exposure Acute toxicity: dermal Data waiving Information requirement: Acute toxicity after dermal administration Reason: study scientifically unjustified Justification: The substance is a genotoxic carcinogen. Appropriate measures are taken to prevent exposure. Information requirement: Acute toxicity after dermal administration Reason: study scientifically unjustified Justification: The substance is a genotoxic carcinogen. Appropriate measures are taken to prevent exposure Acute toxicity: other routes No relevant information available Human information No relevant information available Summary and discussion of acute toxicity The following information is taken into account for any hazard / risk assessment: CSR-PI CHEMICAL SAFETY REPORT 51

64 Two secondary source studies are available (ECB, 1993&1996), where the LD50 is reported to be higher than 5000 and than mg/kg bw respectively. The acute oral toxicity can also be evaluated based on the structure analogy to CAS No: (LD50 = mg/kg). Justification for classification or non classification Based on the available information, C.I. Pigment Red 104 does not have to be classified for acute oral toxicity in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC Irritation Skin Non-human information The results of studies on skin irritation are summarised in the following table: Table 23. Studies on skin irritation Method Results Remarks Reference rabbit (Vienna White) Coverage: occlusive (intact/shaved and abraded) The test substance was applied to a 2.5 x 2.5 cm application site of white Vienna rabbits for 20 h under occlusive conditions. The skin was intact. Animals were observed for 8 days and skin changes were observed on working days. Findings were recorded after 24, 48, 72 hours and until the end of the observation period. Findings were graded as described in OECD test guideline 404. rabbit (Vienna White) Coverage: semiocclusive (clipping of the fur at least 15 hours before the beginning of the study) Vehicle: water OECD Guideline 404 (Acute Dermal Irritation / Corrosion) Human information not irritating Erythema score: 0 of max. 4 (mean) (Time point: hour) (not applicable) (only red to brawn coloration of the skin by test substance was observed. No adverse effects observed) Edema score: 0 of max. 4 (mean) (Time point: 24 hour) (not applicable) not irritating No relevant information available Erythema score: 0 of max. 4 (mean) (Time point: hour) (not applicable) Edema score: 0 of max. 4 (mean) (Time point: hour) (not applicable) 2 (reliable with restrictions) key study experimental result Test material (IUPAC name): lead chromate molybdate sulfate red 1 (reliable without restriction) key study experimental result Test material (IUPAC name): lead chromate molybdate sulfate red BASF AG (1967) BASF AG (1992) CSR-PI CHEMICAL SAFETY REPORT 52

65 Eye Non-human information The results of studies on eye irritation are summarised in the following table: Table 24. Studies on eye irritation Method Results Remarks Reference rabbit (Vienna White) Vehicle: unchanged (no vehicle) BASF test not irritating Cornea score: 0 of max. 4 (mean) (Time point: hour) (not applicable) Iris score: 0 of max. 2 (mean) (Time point: hour) (not applicable) Conjunctivae score: 0 of max. 3 (mean) (Time point: hour) (not applicable) 2 (reliable with restrictions) key study experimental result Test material (Common name): Molybdate red BASF AG (1967) rabbit (New Zealand White) Vehicle: unchanged (no vehicle) OECD Guideline 405 (Acute Eye Irritation / Corrosion) Chemosis score: 0 of max. 4 (mean) (Time point: hour) (not applicable) not irritating Cornea score: 0.44 of max. 4 (mean) (Time point: hour) (fully reversible within: 72 hours) Iris score: 0 of max. 2 (mean) (Time point: hour) (not applicable) Conjunctivae score: 1.25 of max. 3 (mean) (Time point: hour) (fully reversible within: 72 hours, 7 days and 14 days, respectively in the 3 tested animals) Chemosis score: 0.67 of max. 4 (mean) (Time point: hour) (fully reversible within: 72 hours and 7 days, respectively in the 2 tested animals with positive responses) 1 (reliable without restriction) key study experimental result Test material (Common name): Molybdate Orange Ciba-Geigy Limited (1986) Human information No relevant information available CSR-PI CHEMICAL SAFETY REPORT 53

66 Respiratory tract Non-human information No relevant information available Human information No relevant information available Summary and discussion of irritation Skin irritation: In the first study conducted according to the OECD guideline 404 (Acute Dermal Irritation/Corrosion; BASG AG, 1992: 18H0017/91090), although the 4 hour reading could not be performed due to staining of the skin by the test substance, no animal exhibited erythema or edema (grade 0) from the 24 h reading onward. In the second study (BASF AG, 1967: XVII/217) the test substance was applied to a 2.5 x 2.5 cm application site (intact skin) of white rabbits for 20 h under occlusive conditions and the animals were observed for 8 days. Findings were recorded after 24, 48, 72 hours and until the end of the observation period, and graded as described in OECD test guideline 404. The erythema and edema scores were 0 during the entire course of the observation period, and, apart from red to brawn coloration of the skin by test substance, no adverse effects observed. Eye irritation: In the first study conducted according to the OECD guideline 405 (Acute Eye Irritation/Corrosion; Ciba-Geigy Ltd, 1986: TK 1304/1B), following observations (mean hour scores) were made: cornea score (0.44), iris score (0), conjunctiva score (redness; 1.25) and chemosis score (0.67), and were all fully reversible within 3 to 14 days. In the second study BASF study (#XVII/217) 50 mg test substance was applied the right eye of 2 test animals (no wash out; for negative control, the left eyes of the same animals were treated with 50 mg talcum powder) and the animals were observed for 8 days. Findings were recorded after 24, 48, 72 hours and until the end of the observation period, and graded as described in OECD test guideline 405. Test substance coloration of the eyes was observed up to 3 hours after treatment with slight chemosis (score: 1 after 1 hour in one animal and after 3 hours in the second, but completely reversible after 3 and 24 hours respectively). From 24 hours onwards, all irritation parameters (cornea score, iris score, conjunctiva score and chemosis score) were 0 during the entire course of the observation. Respiratory irritation: No data available The following information is taken into account for any hazard / risk assessment: Two skin irritation studies are available, one according to the OECD guideline 404 (BASF AG, 1992; #AG18H0017/912090) and one non-guideline study (BASF AG, 1976; #XVII/217; test substance applied 20 h under occlusive conditions on intact skin, 8 days observation period). Two eye irritation studies are also available (BASF AG, 1976: #XVII/217; Ciba-Geigy, 1986: #TK13047/1B), one a according to OECD guideline 405 (Ciba-Geigy). The substance is neither irritating to the eye nor to the skin. Value used for CSA: Skin irritation / corrosion: No adverse effect observed (not irritating) Eye irritation / corrosion: No adverse effect observed (not irritating) Justification for classification or non classification Based on the available data classification for this endpoint is not warranted Corrosivity Non-human information CSR-PI CHEMICAL SAFETY REPORT 54

67 Please refer to Chapter Human information Please refer to Chapter Summary and discussion of corrosion Please refer to Chapter Sensitisation Skin Non-human information The results of studies on skin sensitisation are summarised in the following table: Table 25. Studies on skin sensitisation Method Results Remarks Reference review of available information Review based on different types of study sensitising 2 (reliable with restrictions) key study European Union (2005) Induction: review of available information Challenge: review of available information Vehicle: not applicable Information from European Risk Assessment Report in which available information on skin sensitising properties of hexavalent chromium compounds was reviewed. read-across based on grouping of substances (category approach) Test material: Chromium compounds Form: not applicable Human information No relevant information available Respiratory system Non-human information No relevant information available Human information No relevant information available Summary and discussion of sensitisation Skin sensitisation In the European Union Risk Assessment Report (RAR) on Chromium trioxide, Sodium chromate, Sodium CSR-PI CHEMICAL SAFETY REPORT 55

68 dichromate, Ammonium dichromate, and Potassium dichromate, the skin sensitizing potential of these Chromium compounds was reviewed. Skin sensitization has been demonstrated in workers who were exposed to hexavalent Chromium compounds. Patch testing of contact dermatitis patients and other investigations of different occupational groups confirm skin sensitizing potential. Furthermore, available animal studies, including standard and modified guinea pig maximization tests and a mouse ear swelling test, confirm the skin sensitizing potential of hexavalent Chromium compounds. The following information is taken into account for any hazard / risk assessment: Review hexavalent Chromium compounds: skin sensitiser Value used for CSA: Adverse effect observed (sensitising) Respiratory sensitisation In the European Union Risk Assessment Report (RAR) on Chromium trioxide, Sodium chromate, Sodium dichromate, Ammonium dichromate, and Potassium dichromate, the respiratory sensitizing potential of these Chromium compounds was reviewed. Based on the available case reports and evidence from well-conducted bronchial challenge tests, it is concluded that hexavalent Chromium compounds can cause occupational asthma and should therefore be classified as respiratory sensitiser. The following information is taken into account for any hazard / risk assessment: Review hexavalent Chromium compounds: respiratory sensitising Value used for CSA: Adverse effect observed (sensitising) Justification for classification or non classification Based on the skin and respiratory sensitising properties of hexavalent Chromium compounds, C. I. Pigment Red 104 should be classified as skin and respiratory sensitiser in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC Repeated dose toxicity Non-human information Repeated dose toxicity: oral The results of studies on repeated dose toxicity after oral administration are summarised in the following table: Table 26. Studies on repeated dose toxicity after oral administration Method Results Remarks Reference rat (Sprague-Dawley) male/female subchronic (oral: feed) 0, 2000, 5000 and ppm in diet (corresponding to appr. 153, 288 and 1600 mg/kg bw per day considering mean daily food consumption of , 77.5 and 80.1 g/kg and mean body weight of 274.3, and g) (nominal in diet) Vehicle: unchanged (no vehicle) Exposure: 90 days (daily) NOEL: 288 mg/kg bw/day (actual dose received in diet) (male/female) LOAEL: ca mg/kg bw/day (actual dose received in diet) (male/female) (overall effects organ weights, solely based on the impaired kidney and liver weight) 2 (reliable with restrictions) key study experimental result Test material (CI name): CI Pigment Yellow 34 BASF Farben & Fasern AG (1976c) TSCATS (1992) CSR-PI CHEMICAL SAFETY REPORT 56

69 Method Results Remarks Reference equivalent or similar to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) (blood lead level and tissue distribution of lead were also evaluated) dog (Beagle) male/female subchronic (oral: feed) 0, 2000, 5000 and ppm in diet (corresponding to appr. 75.4, and mg/kg bw per day considering mean weekly food consumption of 264, and g/kg) (nominal in diet) Vehicle: unchanged (no vehicle) Exposure: 90 days (daily) LOAEL: ca mg/kg bw/day (actual dose received in diet) (male/female) (hematological changes; lesions involving the kidney, bone marrow, intestines and liver) 2 (reliable with restrictions) key study experimental result Test material (Common name): CI Pigment Yellow 34 BASF Farben & Fasern AG (1976d) Christofano GE, Kennedy GL, Gordon JrDE, Keplinger ML and Calandra JC (1976) equivalent or similar to OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity in Non-Rodents) (blood lead level and tissue distribution of lead were also evaluated) rat (Sprague-Dawley) male/female subchronic (oral: feed) 0, 2000, 5000 and ppm in diet (corresponding to appr , and mg/kg bw per day considering mean daily food consumption of 77.7, 74.3 and 77.2 g/kg and mean body weight of 276.9, and g) (nominal in diet) Vehicle: unchanged (no vehicle) Exposure: 90 days (daily) equivalent or similar to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) (blood lead level and tissue distribution of lead were also evaluated) rat (albino rats) male/female subchronic (oral: feed) 0, 2000, 5000 and ppm in diet (corresponding to appr. 160, 400 and 1600 mg/kg bw per day considering daily food consumption of 22.1 g per animal and mean body weight of LOAEL: mg/kg bw/day (actual dose received in diet) (male/female) (organ weight change: slight increase in kidney weights; histopathologica change: tubular epithelial cell alteration (hypertrophy of epithelial cells and desquamation of degenerate or necrotic cells into the lumen of the affected tubules were observed)) Increased kidney weight and kidney to body weight ratios were observed at all levels with white lead, at the midand high-dose with molybdate orange and light chrome yellow, and at the high dose with medium chrome yellow and primrose chrome yellow. 2 (reliable with restrictions) supporting study experimental result Test material (Common name): Molybdate Orange 2 (reliable with restrictions) supporting study experimental result Test material (Common name): Dry Color Manufaturers Association (1975a) Kennedy JL, Konoshita DrFS, Keplinger YL and Calandra JC (1975a) CSR-PI CHEMICAL SAFETY REPORT 57

70 Method Results Remarks Reference g) (nominal in diet) Vehicle: unchanged (no vehicle) Exposure: 90 days (daily) equivalent or similar to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) (blood lead level and tissue distribution of lead were also evaluated) dog (Beagle) male/female subchronic (oral: feed) 0, 2000, 5000 and ppm in diet (corresponding to appr. 80.4, and mg/kg bw per day considering weekly mean food consumption of 295.5, and g/kg respectively) (nominal in diet) Vehicle: unchanged (no vehicle) Exposure: 90 days (daily) Histopathological effects were Molybdate Orange also observed in kidneys. In all cases the blood lead levels achieved with white lead were higher than those resulting from equal levels of the other pigments, higher than would be anticipated on the basis of lead content alone. This suggests that the lead in the test pigments is less readily absorbed. The lowest levels were obtained with medium chrome yellow which has the lowest content of acid soluble lead. LOAEL: ca mg/kg bw/day (actual dose received in diet) (male/female) (lesions involving the kidney, bone marrow, intestines and liver) 2 (reliable with restrictions) supporting study experimental result Test material (Common name): Molybdate Orange Dry Color Manufaturers Association (1975b) equivalent or similar to OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity in Non-Rodents) (blood lead level and tissue distribution of lead were also evaluated) dog (Beagle) male/female subchronic (oral: feed) 0, 2000, 5000 and ppm in diet (corresponding to appr. 70, 180 and 700 mg/kg bw per day considering daily food consumption of 246 g per animal and mean body weight of 6.9 kg) (nominal in diet) Vehicle: unchanged (no vehicle) Exposure: 90 days (diets were offered ad libitum during a 5 hour period on each of 90 consecutive days) equivalent or similar to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) All of the pigments investigated exerted effects which were qualitatively analogous to those seen with white lead. The effects observed were those to be expected from excessive exposure to lead and were less severe or slower to appear with the test pigments than with equal doses of white lead. This also was to be expected in view of the lower lead content of the test pigments and the lower solubility of this lead in dilute acid. It is apparent, however, that the lead as it exists in the test pigments is available for absorption to some extent. 2 (reliable with restrictions) supporting study experimental result Test material (Common name): Molybdate Orange Kennedy JL, Konoshita DrFS, Keplinger YL and Calandra JC (1975b) CSR-PI CHEMICAL SAFETY REPORT 58

71 Method Results Remarks Reference (blood lead level and tissue distribution of lead were also evaluated) Repeated dose toxicity: inhalation No relevant information available Repeated dose toxicity: dermal No relevant information available Repeated dose toxicity: other routes No relevant information available Human information No relevant information available Summary and discussion of repeated dose toxicity Rats and dogs were dosed at 2000, 5000 and 20,000 ppm in the feed (corresponding to appr , and mg/kg bw per day considering mean daily food consumption of 77.7, 74.3 and 77.2 g/kg in rats and to appr. 80.4, and mg/kg bw per day considering weekly mean food consumption of 295.5, and g/kg respectively) in 90 day studies. Lead carbonate was given to the rats as a positive control substance in concentrations of 2000, 5000 or ppm and to dogs in concentrations of 100, 300 or 1000 ppm in the diet. In the study in rats, mortality was not significantly elevated and no untoward behavioral reactions were noted among any of the animals in the study. Body weight gains at ppm test substance level were noticeably lower and statistically different from the control groups. The body weight gains at 5000 ppm were also lower when compared to the controls (body weight gains for males were generally lower than those seen for females). Body weight data collected in the males and females from the PC-I and T-1 levels (both 2000 ppm) did not differ from the control groups. Total food intake at 5000 ppm and ppm was reduced compared to the controls after 13 weeks of testing. The hemoglobin concentration, hematocrit value, mean corpuscular volume, mean corpuscular hemoglobin and the mean corpuscular hemoglobin concentration of males and females fed 2000, 5000, and ppm test substance were slightly to markedly reduced, in most cases, after 30 days (20000 ppm only) and 84 days of testing when compared to the controls. Animals treated with ppm test substance also exhibited slight reductions in erythrocyte counts (as well as slight to moderate variations in size, shape, or color after 84 days) at 30 and 84 days. Slight increases in serum alkaline phosphatase and serum glutamic-oxalacetic transaminase (only female animals, also in the 5000 ppm group) activity, as well as slight reductions in serum glutamic-pyruvic transaminase activity (at day 30 only), were exhibited by the animals fed ppm test substance after 84 days of testing. Urinary aminolevulinic acid () concentrations were elevated at the highest level of test substance after 30 days of treatment. The males and females fed 2000 ppm test substance and all animals fed 5000 or ppm (weights and ratios) test substance exhibited slight increases in kidney weights. Lesions (hidtopathology) observed from the lowest dose level involved mainly the kidneys - organ weight change: slight increase in kidney weights; histopathological change: tubular epithelial cell alteration (hypertrophy of epithelial cells and desquamation of degenerate or necrotic cells into the lumen of the affected tubules were observed).. In the study on dogs, signs of toxicity were observed at the 2 highest levels of test substance (early symptoms being lethargy, anorexia, dehydration and emaciation, generally followed by hyperirritability, disorientation, motor ataxia and convulsions in the affected animals), as well as high mortality rate (4/8 at 5000 ppm, 8/8 at CSR-PI CHEMICAL SAFETY REPORT 59

72 ppm). Test substance also caused severe body weight loss at ppm, slight (females) to moderate (males) body weight gain suppression at 5000 ppm and slight body weight gain suppression at 2000 ppm, whereas food consumption was only severely depressed at ppm. Treatment-related hematological effects were the following: hemoglobin (decrease), hematocrit (decrease), mean corpuscular volume (decrease), mean corpuscular hemoglobin (decrease), banded neutrophils (increase), erythrocyte morphology (nucleation, size, shape, color). Urinary aminolevulinic acid () concentrations were elevated at the 2 higher levels of test substance, whereas the dogs fed 2000 ppm of test substance exhibited increased concentrations only at Day 84. Direct treatment related changes were observed in kidney (focal tubular nephrosis), bone marrow (hypercellularity of marrow elements with a significant increase in erythrocytic precursor cells) and brain (perivascular and perineuronal edema and were attributed to hypoxia and anoxia in the highest dose group). In a 90 study with C. I. Pigment Yellow 34 as test material, rats (20/sex/dose) were fed dietary concentrations of 2,000, 5,000 or 20,000 ppm of the test substance, which corresponds to approximately 160, 400 and 1600 mg test substance/kg bw, respectively. Treatment related mortality did not occur and food consumption as well as body weights were comparable to control animals. Hematology, clinical blood chemistry and gross pathological findings did not differ significantly between the dose group and control group animals. Aminolevulinic acid was slightly elevated among males fed 2,000 ppm at examination days 30 and 60 only. Blood lead concentrations were elevated in a dose-related manner. The lead content of the bone and kidney samples was markedly increased among the test animals. The brain lead content (males only) and liver lead content (males and females) were only slightly increased when compared with those of the controls. The chromium content was increased in the kidney and liver tissues among most test animals. Brain chromium content was slightly elevated among a few females fed 2,000 ppm or more and among the males fed 20,000 ppm. Brain chromium content among males fed 2,000 or 5,000 ppm was either less than, or comparable to, that of the controls. Increases in chromium content in bone samples from animals fed either 5,000 or 20,000 ppm were due to detectable amounts in the bone samples from 1 animal from each of these levels. No detectable amount of chromium was found in the bone samples from any of the animals fed 2,000 ppm. The absolute liver and relative kidney and liver weights were significantly elevated in males fed 20,000 ppm, however, treatment-related histopathological changes were not noted upon microscopic examination. In a further 90 day study with C. I. Pigment Yellow 34, beagle dogs (4/sex/dose) were fed dietary concentrations of either 2,000, 5,000 or 20,000 ppm (ca. 70, 180 and 700 mg/kg bw, respectively) of the test material (groups T-I, T-II and T-III,) or 100, 300 or 1,000 ppm of lead carbonate (groups PC-I, PC-II and PC-III). All but one of the T-III animals were sacrificed in extremis which precluded a meaningful examination of these animals. Body weight development was not affected in animals fed 2,000 ppm of the test material or 100 ppm of lead carbonate. Animals of the other T- or PC-groups showed a dose-related increase in body weight suppression, severely so in T-III animals. Abnormal behavioral reactions were not observed in any of the T-group or PC-group animals. The lead content of liver, kidney, bone and brain tissues was elevated at all levels of either compound. Increases were directly proportional to the length of time on test and/or dietary concentration. In dogs fed the 3 levels of lead carbonate, chromium content in all 4 tissues was comparable to that seen in untreated controls, either below detectable limits or found in trace amounts only. At 2,000 ppm test material, chromium content was elevated in all 4 tissues examined, the liver showing the highest concentration, kidneys the next highest, then bone; brain tissue showed the lowest concentration. At 5,000 ppm, a similar pattern of elevations was seen, with the concentrations in kidney, bone and brain tissues essentially comparable to those found in 2,000 ppm animals. However, in liver tissue, the chromium content in 2,000 ppm animals was considerably higher than that found in 5,000 ppm animals, though both levels were tested for 90 days. At 20,000 ppm, chromium content of liver and kidney tissues was much lower than that found in either 2,000 or 5,000 ppm dogs and in bone, chromium was below detectable limits. These findings correlate with the short time (3 weeks) the animals were on test. In brain tissue, however, chromium content was comparable to concentrations found at the 2 lower levels. Hematological studies revealed treatment related effects in parameters related to hematopoiesis (hemoglobin, hematocrit: decrease) and additionally, a decrease in the mean corpuscular volume, segmented neturophils, banded neutrophils and changes in the erythrocyte morphology (nucleation, size alteration, color alteration) were observed. Blood chemistry revealed no relevant changes related to the treatment with either lead carbonate or the test substance. Organ weights were unaffected by the treatment with the test substance. Treatment-related lesions observed by light microscopy occurred in dogs fed either lead carbonate or the test substance. The nature and severity of the lesions varied, but, in most instances, these lesions were related to either the compound fed, dose level, or length of exposure. Renal and bone marrow lesions occurred among dogs fed 1,000 ppm of lead carbonate (PC-III group). The kidney lesions consisted of focal degenerative tubular changes which affected all dogs in this group. Dose-related lesions involving either the kidney, bone marrow, and/or liver were present among dogs in all groups CSR-PI CHEMICAL SAFETY REPORT 60

73 fed the test material. There were focal degenerative lesions present involving kidney tubules which affected a few T-I and most T-II and T-III dogs. Hypocellularity of the sternal bone marrow occurred in 2 of the T-III animals. The liver lesion, present in 6 of the 8 T-III animals, was characterized by degeneration and necrosis of hepatocytes located predominantly in the centrilobular region of the liver lobules. Testicular lesions consisting of either hypospermatogenesis, focal testicular degeneration, or both, occurred among most of the males of all 3 dose groups of dogs fed lead carbonate. No adverse effects were noted in the ovaries and uterus of females after they were fed lead carbonate for 90 days. The exact cause for the gonadal lesions among males fed lead carbonate was not determined. These lesions probably resulted from impairment in their nutritional status with delayed development of puberty. These lesions were regarded as an indirect effect rather than a direct effect of lead carbonate on the testes. Males of all 3 test groups had focal testicular degeneration which was most severe among the T-III group. The gonadal lesions present among animals fed the test substance appeared to be primarily related to the age of animal at time of sacrifice and only indirectly related to ingestion of the test material. In the gastrointestinal tract of some of the positive control and test animals, there was increased mitotic activity of the mucosal epithelial cells located in the glandular crypts. This finding was regarded as a regenerative change indicative of an increased rate of proliferation of mucosal cells. It was noted throughout the gastrointestinal tract, but was most pronounced in the distal portion (ileum) of the small intestine. In conclusion, the test substance's bioavailability was conclusively shown by findings of lead and chromate ions in several tissues, independent of the species tested. Also, although the dog seems to be the more sensitive species, the target organs (liver and kidney) seem to be identical. Hematopoiesis was affected in the dog and early signs (increase in) was also seen in the rat. Although neurotoxicity was not specifically assessed, abnormal behavior was not noted in either the rat or the dog. The dog study with C. I. Pigment Yellow 34 yielded a slightly lower LOAEL and MTD while the effects were qualitatively similar and are therefore taken forward for the risk assessment. The following information is taken into account for any hazard / risk assessment: Two subchronic studies, one conducted in rats and one in beagle dogs, were conducted similar to OECD guideline 408 and 409, respectively, although ophthalmological examinations were not performed and the composition of test substance not specified. In the rat study, the LOAEL was the lowest tested dose level (appr mg/kg), mainly based on tubular epithelial cell alteration in the kidneys. In the dog study, the LOAEL was also the lowest tested dose level (appr mg/kg), mainly based on lesions observed in the kidneys, bone marrow, intestines and liver. In the additional 2 available studies (Kennedy et al. 1975) the subchronic toxicity of lead pigments in Albino rats or Beagle dogs was comparatively evaluated, but no NOAEL/LOAEL was determined. Lead and lead containing pigments were evaluated. Although the exerted effects were qualitatively similar, they were in general more severe or earlier in appearance with white lead than with the pigments of lower lead content. The effects could not be quantitatively related to lead or chromium content or to acid soluble lead. Additional studies with C. I. Pigment Yellow 34 are also available. Two subchronic studies are used for endpoint assessment, one in rats (BASF Farben & Fasern AG, 1976; Report No ) and one in beagle dogs (BASF Farben & Fasern AG, 1976; Report No ). Rats and dogs were dosed at 2000, 5000 and 20,000 ppm in the feed in 90 day studies that are similar to OECD guideline 408 and 409. Value used for CSA (via oral route - systemic effects): (LOAEL: 70 mg/kg bw/day) Target organs: cardiovascular / hematological: hematopoiesis; digestive: liver; urogenital: kidneys Justification for classification or non classification The accumulation of lead ions in different tissues in a time and dose-dependent manner justifies a classification with R33 according to EU-criteria and STOT repeated exposure Cat. 2. A further classification is not warranted because of the R45 / Carc. Cat. 1B categorization (see carcinogenicity) Mutagenicity Non-human information In vitro data The results of in vitro genotoxicity studies are summarised in the following table: CSR-PI CHEMICAL SAFETY REPORT 61

74 Table 27. In vitro genotoxicity studies Method Results Remarks Reference bacterial reverse mutation assay (e.g. Ames test) (gene mutation) Salmonella typhimurium TA 98, 100, 1535, 1537 and 1538 (met. act.: without) Test concentrations: 2 mg (spot test) Positive control substance(s): a couple of polycyclic aromatic hydrocarbons were also tested, including benzo(a)pyrene and benz(a)anthracene Test results: positive (only TA 100)(Salmonella typhimurium TA 98, 100, 1535, 1537 and 1538) ; met. act.: without ; vehicle controls valid: yes; negative controls valid: yes; positive controls valid: yes 2 (reliable with restrictions) key study experimental result Test material (Common name): Molybdenum Orange De Flora S (1981) Ames test (spot test, because of the low solubility of the test substance; i.e. placement of 2 mg of the test material in the middle of a plate) bacterial reverse mutation assay (e.g. Ames test) (gene mutation) S. typhimurium TA 100 (met. act.: with and without) Test concentrations: 50, 100, or 500 µg/plate (assuming complete solubility) Positive control substance(s): sodium azide (10 μg/plate) and cyclophosphamide (1000 μg/plate) were used as positive controls without and with S9, respectively test substance at different degrees of encapsulation (with amorphous silica) was assayed for mutagenicity in Ames test in the absence / presence of the chelating agent nitrilotriacetic acid (NTA) sister chromatid exchange assay in mammalian cells (DNA damage and/or repair) pseudodiploid CHO Kt Chinese hamster fibroblast line (kindly supplied by Dr. Nuzzo F, Inst of Biochemical and Evolutionary Genetics, CNR,Pavia, Italy) (met. act.: with and without) Test concentrations: 0.1µg/ml Test results: positive (only in the presence of NTA, with (500 µg/plate) and without (100 µg/plate) metabolic activation (see table 1)) for S. typhimurium TA 100(all strains/cell types tested (Salmonella typhimurium TA100)) ; met. act.: with and without ; cytotoxicity: yes (undiluted test substance solution (500 µg/plate) was cytotoxic in the presence of NTA (without S-9 mix)) ; vehicle controls valid: yes; positive controls valid: yes Test results: positive (the frequency of SCE was directly increased (Table 1), due to the relatively long exposure times (30 h) and the ability of mammalian cells to take up insoluble Cr particles by endocytosis. NTA increases the ability of all the Cr(VI) compounds to induce SC) for Chinese hamster Ovary 2 (reliable with restrictions) supporting study experimental result Test material: Molybdate orange 2 (reliable with restrictions) key study experimental result Test material (Common name): Molybdenum orange Connor TH and Pier SM (1990) Venier P, Montaldi A, Gava C, Zentilin L, Tecchio G, Bianchi V, Psglialunga (1985) CSR-PI CHEMICAL SAFETY REPORT 62

75 Method Results Remarks Reference Positive control substance(s): Additional test compounds showed positive results equivalent or similar to OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells) in vitro mammalian chromosome aberration test and sister chromatid exchange assay in mammalian cells (DNA damage and/or repair) CHO-Zellen (met. act.: without) Test concentrations: 0, 5, 25 and 150 µg/ml Positive control substance(s): see above Method: other: Levis AG et al. (1979). Br J Cancer 40: In vivo data (CHO)(all strains/cell types tested) ; met. act.: with and without ; cytotoxicity: not determined ; vehicle controls valid: yes; negative controls valid: yes; positive controls valid: not applicable Test results: positive (see Table 1 below)(all strains/cell types tested) ; met. act.: without ; cytotoxicity: no (cell growth was 85% of control at highest concentration level of 150 µg/ml (100% at lower concentrations levels)) ; vehicle controls valid: yes; negative controls valid: yes; positive controls valid: additional compounds were also tested showing positive results (Table 1) 2 (reliable with restrictions) key study experimental result Test material (Common name): chromium yellow The results of in vivo genotoxicity studies are summarised in the following table: Table 28. In vivo genotoxicity studies Levis AG and Majone F (1981) IARC Monographs (1990) Method Results Remarks Reference micronucleus assay (chromosome aberration) mouse (ICL-ICR) female intraperitoneal 25, 50, 100 and 2x 100 mg/kg bw (actual injected (ip)) Positive control substance(s): mitomycin C - Route of administration: ip - Doses / concentrations: 2.5 mg/kg bw Mouse bone marrow micronucleus test Test results: Genotoxicity: negative (No significant induction of micronuclei was observed in bone marrow erythrocytes of mice treated with any of the pigments (Table 1). In contrast, the animals treated with sodium dichromate showed a significantly increased number MNPCEs) (female); toxicity: no effects (the compounds, ZPC (zinc potassium chromate) and ZTO (zinc tetroxychromate), also examined in the study showed cytotoxicity at the highest dose levels as evidenced by the significant reduction in PCEs frequency.) ; vehicle controls valid: yes; negative controls valid: some of the chemicals tested also show negative results; positive controls valid: 2 (reliable with restrictions) key study experimental result Test material (Common name): Molybdenum Red Odagiri Y et al. (1989) CSR-PI CHEMICAL SAFETY REPORT 63

76 Method Results Remarks Reference Human information No relevant information available yes Summary and discussion of mutagenicity In vitro: Several mutagenicity tests in are available that were done with and without S9 metabolic activation. Neither test followed a specific guideline. The mutagenicity test was positive either at low concentration level (up to 500 µg/plate) in the presence of a solubilizing agent (Connor and Pier, 1990) or when elevated concentration of test substance (2 mg/plate) was evaluated (De Flora, 1981). Two sister chromatid exchange assays, the first of which was conducted similar to the OECD guideline 479 protocol (only one dose level tested, limited detail of test protocol provided), were positive in Chinese hamster ovary cells at concentrations of 0.1 (Venier et al., 1985) or µg/ml (Levy and Majone, 1981). The exposure of the same cell line in chromosomal aberration test led to a slight increase in chromosomal aberrations at concentrations of µg/l (Levy and Majone, 1981). In vivo: The only in vivo micronucleus test available conducted at concentrations of 15, 50 and 2x 100 mg/kg bw with intraperitoneal administration of test substance in comparison with soluble chromates was negative (Odagiri et al., 1989). The soluble compounds (zinc potassium chromate, zinc tetroxy chromate and sodium dichromate) were all tested positive at concentrations up to 50 mg/kg bw. The following information is taken into account for any hazard / risk assessment: Several in vitro studies addressing Ames-mutagenicity (De Flora 1981; Carcinogenesis 2: , Connor and Pier, 1990; Muta Res 249: ), sister chromatid exchange (Venier et al., 1985; Mut Res 156: ) and chromosomal aberration (Levy and Majone, 1981; Br J Cancer 44: ) are available. Most of them do not follow a guideline but all give a positive result (particularly when the test material was tested in the presence of a solubilizing agent). In contrary, a negative response was observed in an in vivo micronucleus test (Odagiri et al., 1989; Jpn J Ind Health 31: ), where the test substance was administered intraperitoneally (25, 50 and 100 mg/kg bw) to test animals (mice). Justification for classification or non classification Although most in vitro genotoxicty tests were positive, a genotoxic potential could not be verified in vivo. Therefore, a classification is probably not warranted. However, the negative results in the micronucleus test of the test substance, which presented a very low water solubility (1%; as opposed to 6-8% for zinc potassium chromate or to 2380 g/l for sodium dichromate), are likely not reliable, because the treatment with the chemical did not show evidence for absorption and transport to the bone marrow, as evidenced by a lack of reduction in PCEs frequency. Thus, although the in vivo genetic toxicity test gave negative, chromium and its compounds, particularly chromium(vi), may cause chromosomal effects, indicating carcinogenic potential because interactions with DNA have been linked with the mechanism of carcinogenicity Carcinogenicity Non-human information Carcinogenicity: oral The results of studies on carcinogenicity after oral administration are summarised in the following table: Table 29. Studies on carcinogenicity after oral administration CSR-PI CHEMICAL SAFETY REPORT 64

77 Method Results Remarks Reference mouse (B6C3F1) male/female oral: drinking water Group 1 (nominal in water (14.3 mg/l (males and females))) Group 2 (nominal in water (28.6 mg/l (males); 57.3 mg/l (females))) Group 3 (nominal in water (85.7 mg/l (males); 172 mg/l (females))) Group 4 (nominal in water (257.4 mg/l (males); 516 mg/l (females))) Exposure: 2 years (daily, through drinking water) Carcinogenicity: inhalation No relevant information available Carcinogenicity: dermal No relevant information available Carcinogenicity: other routes No relevant information available Occupational Exposure Limit (carcinogenicity): ca mg/kg bw/day (male/female) based on: test mat. (An oral "reference value" of 0.22 µg Cr(VI)/kg body weight/day was derived) Neoplastic effects: yes (See details on results) 2 (reliable with restrictions) key study read-across based on grouping of substances (category approach) Test material (other): Hexavalent chromium The results of studies on carcinogenicity (other routes) are summarised in the following table: Table 30. Studies on carcinogenicity (other routes) I. Dewhurst (2013) Author unknown (2008) Method Results Remarks Reference rat (Sprague-Dawley) male/female (subcutaneous) 30 mg/animal (corresponding to 120 mg/kg bw assuming a mean body weight of 250 g for adult animals) (actual injected) Vehicle: water Exposure: only one treatment (single application) the only dose evaluated was carcinogenic (carcinogenicity): 30 mg/animal (male/female) (Rhabdomyosarcomas and fibrosarcomas were locally observed in 36/40 animals) 2 (reliable with restrictions) key study experimental result Test material (Common name): Lead chromate Maltoni C et al (1999) Maltoni C (1976a) Maltoni C (1976b) TSCATS (1983a) evaluation of carcinogenicity of test substance in rats after subcutaneous injection rat (Wistar) male/female (intratracheal implantation) see below (ca 250 mg/animal (corresponding to ca 1000 mg/kg bw assuming mean body weight of 250 g the only dose evaluated indicated possible carcinogenicity (carcinogenicity): ca mg/kg bw (contained in the implanted pellet) (male/female) (No bronchial 2 (reliable with restrictions) key study experimental result Levy LS, Martin PA and Bidstrup PL (1986) TSCATS (1983b) CSR-PI CHEMICAL SAFETY REPORT 65

78 Method Results Remarks Reference for adult rats; see below)) Vehicle: cholesterol (50:50 suspension with test substance, 10 g each) Exposure: 2 years (continuous (the pellet implantation enables a selected zone of bronchial epithelium to be exposed to a putative carcinogen for a continuing period. The pellet implantation enables a selected zone of bronchial epithelium to be exposed to a putative carcinogen for a continuing period)) conducted in accordance with the guidelines published by the Food and Drug Administration (FDA) in a document entitled "Nonclinical laboratory studies-proposed regulations for good laboratory practice" (1976). rat (Wistar) male/female (intra-bronchially) Vehicle: test substance was suspended in cholesterol acting as an inert carrier material Exposure: The stainless-steel wire-mesh pellets were designed to progressively released the test substance (once) A stainless-steel wire-mesh pellet with anchoring hooks is loaded with of test substance was surgically implanted (intra-bronchially) into the lower left bronchus of rat. This enables a selected zone of bronchial epithelium to be exposed for a continuing period. The rat was then allowed to live for two years at which time the study is terminated and the lung and any abnormal tissue examined. Review on studies from public literature reporting on occupational Cr(VI) exposure and cancers of the respiratory tract (review of inhalation exposure) Exposure: Not applicable carcinoma observed, but the incidence of lung squamous metaplasia was higher compared to controls (2x)) It is felt that the present study more accurately represents the potential of lead chromate-containing materials as possible lung carcinogens, and that lead chromate is non-carcinogenic or has an extremely low carcinogenic potential under the conditions of this bioassay system. However, given the rarity of squamous bronchial carcinoma in control rats, it is important to consider the relevance of this carcinogenic potential. Occupational Exposure Limit (OEL) (carcinogenicity): ca µg/m3 (male/female) based on: test mat. (Occupational Exposure Level (OEL) associated with 4 excess lung cancer case per 100,000 workers for life time exposure to hexavalent chromium of 0.01 µg/m3) Test material (IUPAC name): lead chromate molybdate sulfate red 2 (reliable with restrictions) key study experimental result Test material (Common name): lead chromate 2 (reliable with restrictions) key study read-across based on grouping of substances (category approach) Test material Levy LS, Martin PA, and Bidstrup PL (1985) Seidler et al. (2012) CSR-PI CHEMICAL SAFETY REPORT 66

79 Method Results Remarks Reference review of all available information on animal and human data (review of all available routes of exposure) Exposure: Not applicable (Not applicable) review of all available information on animal and human data (review of all available routes of exposure) Human information Occupational Exposure Limit (OEL) (carcinogenicity): ca ug/m3 (male/female) based on: test mat. (Occupational Exposure Level (OEL) associated with 1 excess lung cancer case per 100,000 workers for life time exposure to hexavalent chromium of 1/(100*0.6) = µg/m3) Occupational Exposure Limit (OEL) (toxicity): ca. 100 ug/m3 (male/female) based on: test mat. (Occupational Exposure Level (OEL) based on neurobehavioural adverse effects in workers exposed to lead, equivalent to a concentration of 25 μg Cr/m3. The carcinogenic potential is expected to be low, based on the low solubility of lead chromate.) (other): Hexavalent chromium compounds 2 (reliable with restrictions) supporting study read-across based on grouping of substances (category approach) Test material: Hexavalent Chromium compounds 2 (reliable with restrictions) supporting study read-across based on grouping of substances (category approach) Test material: Lead Chromate The exposure-related observations in humans are summarised in the following table: Table 31. Exposure-related observations on carcinogenicity in humans Scientific Committee on Occupational Exposure Limits (2004a) Scientific Committee on Occupational Exposure Limits (2004b) Method Results Remarks Reference Study type: cohort study (prospective) Type of population: occupational Details on study design: HYPOTHESIS TESTED (if cohort or case control study): respiratory tract tumor deaths induced by the test material METHOD OF DATA COLLECTION - Type: recensement STUDY PERIOD: Jan 1, December STUDY POPULATION - Total population (total no. of persons in cohort from which the subjects were drawn): 251 active workers during the study period (working in the factory at least for 6 months, starting before 1978 EXPOSURE - Average concentrations: could not be determined due to the changes (ameliorations) occurring progressively in the production. INCIDENCE / CASES - Incidence/ Number of cases for each disease / parameter under consideration: 30 (from a total of 50) deaths were attributable to pulmonary tumor (11), infarct (3), vasculocerabral accident (2), cerebral tumor (2), suicide (2), pulmonary acute edema (1), acute respiratory insufficiency (1), pancreatite (1), arterite (1), accident (1), intoxication (1), 2 (reliable with restrictions) key study Test material (Common name): lead chromate Haguenoer JM, Dubois G, Frimat P, Cantineau A, Lefrancois H and Furon D (1981) CSR-PI CHEMICAL SAFETY REPORT 67

80 Method Results Remarks Reference and still alive in 1958). - Selection criteria: workers in the factory at least for 6 months, still alive in 1958 and having start the work in the plant before Sex/age/race: man - Total number of subjects at end of study: 201 COMPARISON POPULATION - Type: population of the department of North, France - Details: statistics of the reference population were available (from 1958 to 1977), with the numbers of respiratory tract (non secondary tracheal, bronchial and pulmonar) tumor related, as well as total deaths, each 10 years. HEALTH EFFECTS STUDIED - Disease(s): respiratory tract tumor - Diagnostic procedure: cytology and histology (Biopsy). Endpoint addressed: carcinogenicity renal insufficiency (1), liver tumor (1), gastrointestinal tumor (2). The reason for the remaining deaths could not be determined Summary and discussion of carcinogenicity Several review reports or articles are available with respect to the carcinogenicity of hexavalent chromium compounds. In the key study, Seidler et al. (2012) systematically reviewed the scientific literature and quantified the respiratory cancer risk for occupational exposure to hexavalent chromium. Seidler et al. (2012) included 5 studies in their paper, each providing more than one level of occupational Cr (VI) exposure, considering the confounder smoking and using adequate methods. Linear regressions models were used to calculate relative risks and to estimate excess absolute risks. The absolute excess lung cancer risk was found to be 4 excess lung cancer cases per 100,000 workers for life time exposure to hexavalent chromium at a Cr(VI) concentration of 0.01 ug/m3. The OEL derived by Seidler et al (2012) for hexavalent chromium compounds will be used as the starting point for the derivation of the DMEL. The OEL for hexavalant chromium of 0.01 µg/m3 corresponds to a concentration of µg/m3 for both C. I. Pigment Yellow 34 and C. I. Pigment Red 104, taking into account a maximum hexavalent chromium content of 15% in both pigments. It should be noted that data for poorly soluble hexavalent chromium compounds indicate that these compounds have lower carcinogenic potency than soluble compounds, which may be explained by the relative low bioavailability. The review by the Scientific Committee on Occupational Exposure Limits (SCOEL, 2004), which is included as a supporting study, defined highly soluble compounds such as sodium and potassium chromates and dichromate (water solubility >100 g/l), sparingly soluble compounds such as strontium, calcium and zinc chromate (water solubility g/l), and poorly soluble compounds such as lead and barium chromate (<1 g/l). From the bio-elution studies, summarized in the toxicokinetics section (7.7.1), the biosolubility of C. I. Pigment Yellow 34 and C. I. Pigment Red 104 could be deduced. At a loading of 2 g/l and after 6 days of incubation in simulated interstitial lung fluid, the chromium concentrations from C. I. Pigment Red 104 and C. I. Pigment Yellow 34 were g/l and g/l, respectively. This concentration is at least 44.4 times lower than the limit of 1 g/l for poorly soluble compounds as defined by SCOEL. The excess lung cancer risk can only be attributed to the respirable fraction of the hexavalent chromium compound. The non-respirable fraction will be cleared from the respiratory tract and swallowed in the gastrointestinal tract. From the particle size distribution and dustiness tests for C. I. Pigment Yellow 34 and C. I CSR-PI CHEMICAL SAFETY REPORT 68

81 pigment Red 104 (see section 4.5) it can be estimated that the respirable fraction is < 2% for both pigments. This implies that the inhalable, non-respirable fraction must be evaluated for excess cancer risk by the oral route of exposure. In the report on the carcinogenicity dose-response analysis of Cr(VI) - and As-containing substances (ECHA project SR11), it was concluded that for exposures above 0.22 µg Cr(VI) / kg body weight/day an excess lifetime intestinal cancer risk = 8 x 10^-4 per µg Cr(VI) / kg body weight/day applies. For oral exposures below 0.22 µg Cr(VI) / kg body weight/day it is considered that physiological processes will be able to reduce Cr(VI) to Cr(III), that a threshold for intestinal carcinogenicity exists and that the risks of carcinogenicity are negligible. The assessment is based on linear extrapolation from intestinal tumour data in mice. The estimate applies to both occupational and general public exposures and is based on a 70 year exposure scenario (every day) and a 70 year life expectancy. SCOEL (2004) also reviewed the available information on the possible health effects of Lead Chromate. In addition to the information on Lead Chromate, SCOEL Summary Documents on both Lead and Lead Compounds (SCOEL/SUM 83) and hexavalent Chromium compounds (SCOEL/SUM 86) were taken into account. Compared to other chromates, Lead Chromate has low carcinogenic potential, based on its poor solubility, although mutagenicity and clastogenicity have been reported after solubilisation. However, SCOEL concludes that the risk for lung tumours induced by Lead Chromate must be distinctly lower than the risk calculated for hexavalent Chromium compounds in general. Therefore, SCOEL based the OEL for Lead Chromate on the information available for Lead and Lead compounds, resulting in an OEL of 100μg Pb/m3 (ambient air) and BLV of 30μg Pb/dl blood. The OEL of 100μg Pb/m3 would be equivalent to a concentration of 25μg Cr/m3. Supporting studies available for C. I. Pigment Yellow 34 are summarized below. In a study by Maltoni (1976; only one dose group, only one treatment), the test substance was injected in subcutaneous tissue of the middle right flank (30 mg test substance in 1 ml water, (corresponding to appr. 120 mg/kg bw assuming a mean body weight of 250 g for adult animals). All the animals were kept under observation until spontaneous death. The spontaneous incidence of subcutaneous sarcomas and of the different sarcoma histotypes, in the historical controls of the authors' breed of Sprague-Dawley rat were used as a comparison. Gross pathology was made at spontaneous death and all macroscopic lesions observed at the control were recorded. A complete autopsy was made on each animal and all major organs examined histopathologically. 26/40 rats developed sarcoma (rhabdomyosarcoma and fibrosarcoma) at the site of injection. Local carcinogenicity effects were also observed when a group of Cr6+-containing substances where intra-tracheally administered to (a metal wire pellet containing the test material is surgically implanted into the left bronchus of an anaesthetised rat; Levy et al., 1986). Of the 20 test materials, three groups gave statistically significant numbers of bronchial carcinomas. Two of these were groups receiving different samples of strontium chromate which gave 43/99 and 62/99 tumours. The third group, zinc chromate (low solubility), gave 5/100 bronchial carcinomas. A further zinc chromate group (Norge composition) produced 3/100 bronchial carcinomas which was not statistically significant. TSS 711 Calcium chromate (used as Positive control) particularly induced 25% bronchial carcinoma in all animals tested with ppm of Cr6+ content and can be considered as T25 of local tumor formation. The following information is taken into account for any hazard / risk assessment: Review hexavalent Chromium compounds: carcinogen (lung tumours) Value used for CSA (route: oral): No adverse effect observed Value used for CSA (route: dermal): No adverse effect observed Value used for CSA (route: inhalation): Adverse effect observed Target organs: respiratory: lung Justification for classification or non classification In accordance with the current EU classification for C. I. Pigment Yellow 34 and C. I. Pigment Red 104, which was based on read across from other more soluble hexavalent chromium compounds, C. I. Pigment Yellow 34 and CSR-PI CHEMICAL SAFETY REPORT 69

82 C. I. Pigment Red 104 are classified for carcinogenicity (R45 or CLP Cat 1B), although the likelihood of carcinogenicity risk is considered very low due to very poor bioavailability of these two substances. Three epidemiological studies in lead chromate pigment manufacturing plants "did not produce evidence supporting any association between lead chromate [pigments] and lung cancer". However limitations in cohort size, due to the limited number of workers in this industry, limits the use of such studies. Nonetheless as the worst case, the carcinogenicity risk of these two pigments will be assessed in this application for authorization, using the carcinogenic properties of hexavalent chromium compounds as described by Seidler et al. (2012) for Cr(VI) compounds. However, the very poor solubility and bioavailability of C.I. Pigment Yellow 34 and C.I. Pigment Red 104 should be taken into account when deriving the DMEL Toxicity for reproduction Effects on fertility Non-human information The results of studies on fertility are summarised in the following table: Table 32. Studies on fertility Method Results Remarks Reference dog (Beagle) male/female subchronic oral: feed 0, 2000, 5000 and ppm in diet (corresponding to appr. 75.4, and mg/kg bw per day considering mean weekly food consumption of 264, and g/kg) (nominal in diet) Vehicle: unchanged (no vehicle) Exposure: 90 days (daily) sexual maturity (subchronic study): (male) (Males of all 3 test groups had focal testicular degeneration which was most severe among the T-III group) 2 (reliable with restrictions) key study experimental result Test material (CI name): CI Pigment Yellow 34 BASF Farben & Fasern AG (1976b) equivalent or similar to OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity in Non-Rodents) with evaluation of sexual organs Not applicable, review of all available data (voluntary Risk Assessment Report vrar) Review of all available data Not applicable, review of all available data Exposure: Not applicable, review of all available data (Not applicable, review of all available data) Information from the voluntary Risk Assessment Report: a review of all available information on developmental toxicity and toxicity NOAEL (P): 45 ug/dl blood (male) based on: test mat. (Impact on semen quality (based on concentration of lead in blood)) NOAEL (P): 30 ug/dl blood (female) based on: test mat. (Pregnancy outcome (increased spontaneous abortions) (based on concentration of lead in blood)) 2 (reliable with restrictions) key study read-across based on grouping of substances (category approach) Test material: Lead and some inorganic Lead compounds Form: not applicable Boreiko, C., Battersby, R. (2008) CSR-PI CHEMICAL SAFETY REPORT 70

83 Method Results Remarks Reference to reproduction of lead and lead compounds. not applicable (not applicable), Review of available data by European Food Safety Authority (EFSA) not applicable not applicable (not applicable) Vehicle: not applicable Exposure: Not applicable (Not applicable) BMDL01 (F1): 0.5 µg/kg bw/d (male/female) based on: test mat. (Neurobehavioural development (loss of 1 IQ-point)) BMDL01 (F1): 1.2 ug/dl blood (male/female) based on: test mat. (Neurobehavioural development (loss of 1 IQ-point)) 2 (reliable with restrictions) key study read-across based on grouping of substances (category approach) Test material: Lead European Food Safety Authority (EFSA) (2010) Not applicable Not applicable, Opinion of the Scientific Committee on Health and Environmental Risks (SCHER) In the opinion of the Scientific Committee on Health and Environmental Risks (SCHER) on the voluntary Risk Assessment Report (vrar), it is concluded that the health part of the vrar is of good quality, comprehensive, and that the exposure and effects assessment follow the Technical Guidance Document. 2 (reliable with restrictions) supporting study read-across based on grouping of substances (category approach) Test material: Lead and Lead compounds Scientific Committee on Health and Environmental Risks (SCHER) (2009) Toxicity to reproduction: other studies No relevant information available Human information No relevant information available Developmental toxicity Non-human information Data waiving Information requirement: Developmental toxicity / teratogenicity Reason: study scientifically unjustified Justification: The substance is considered to be a carcinogen (CLP Cat. 1B, DSD R45); appropriate measures are therefore taken to prevent exposure. Information requirement: Developmental toxicity / teratogenicity Reason: other justification Justification: Summaries of the results of the voluntary Risk Assessment Report for lead and inorganic lead compounds, the SCHER opinion on the vrar, and the EFSA opinion on lead in food are provided in the toxicity to reproduction section. In these reports, all available studies in humans and experimental animals have been evaluated for the observed effect of lead upon sexual maturation and semen quality, pregnancy outcome, and neurobehavioural effects of prenatal and postnatal lead exposure. Effects on development have CSR-PI CHEMICAL SAFETY REPORT 71

84 been included in the summaries provided in the toxicity to reproduction section Human information No relevant information available Summary and discussion of reproductive toxicity Effects on fertility In the voluntary Risk Assessment Report for lead and inorganic lead compounds, all available studies in humans and experimental animals have been evaluated for the observed effect of lead upon sexual maturation and semen quality, pregnancy outcome, and neurobehavioural effects of prenatal and postnatal lead exposure. Lead compounds were found to have effects on male fertility, female reproductive parameters, and on neurobehavioural development, which was the most critical effect. Developmental toxicity In the voluntary Risk Assessment Report for lead and inorganic lead compounds, all available studies in humans and experimental animals have been evaluated for the observed effect of lead upon sexual maturation and semen quality, pregnancy outcome, and neurobehavioural effects of prenatal and postnatal lead exposure. Lead compounds were found to have effects on male fertility, female reproductive parameters, and on neurobehavioural development, which was the most critical effect. Effects on neurobehavioural performance after pre-natal and post-natal have been reported in several animal studies. However, the available data are inadequate to establish dose-effect relationships. Observed effects are upon early measures of mental and physical development, but could not be associated with impacts upon measures such as IQ. Furthermore, effects of prenatal lead exposure can be difficult to dissociate from those of postnatal exposure. Effects of pre-natal lead exposure are secondary in magnitude to those produced by exposures after birth. The vrar suggest a blood lead level above 10 µg/dl (in females) to take into account for the risk assessment with regard to developmental effects. In the opinion of the Scientific Committee on Health and Environmental Risks (SCHER) on the voluntary Risk Assessment Report (vrar), it is concluded that the health part of the vrar is of good quality, comprehensive, and that the exposure and effects assessment follow the Technical Guidance Document. In the risk assessment on lead from food which was performed by the European Food Safety Authority (EFSA, 2010), the Bench Mark Dose approach (BMD) is used to estimate the BMDL01, which is the blood-lead concentration corresponding to the 1 -percentile of the Confidence Interval of the chosen Bench Mark Response of an IQ deficit of 1 IQ point. The BMR is chosen and set at 1 IQ point by the CONTAM panel of EFSA. Using this approach, the BMDL01 for lead was estimated to be 1.2μg/dL (mentioned as 12μg/L by EFSA). A supporting study is included in the dossier in which adverse changes were observed when female Swiss albino mice were treated with potassium dichromate at 0, 53.2, 101.1, and mg of eq. chromium(vi) /kg/day in drinking at days 6 14 of gestation (Junaid et al., 1996). The number of dead fetuses (higher in the high-dose group), fetal weight (lower in both intermediate- and high-dose groups; high dose = 1.06 g, intermediate dose = 1.14 g) were changed as compared to the control value of 1.3 g. A dose-response relationship was also observed in the number of resorption sites (0.31 for controls, 1.00 for the low dose, 1.70 for the intermediate dose, and 2.30 for the high dose), as well as a significantly greater incidence of post-implantation loss (in the two highest-dose groups of 21 and 34.60% as compared to control value of 4.32%). The gross structural abnormalities observed were drooping of the wrist (carpal flexure) and subdermal hemorrhagic patches on the thoracic and abdominal regions (in 16% in the offspring of the high-dose group). Significant reduced ossification in nasal frontal, parietal, interparietal, caudal, and tarsal bones were observed only in the mg chromium(vi) /kg/day-treated animals The following information is taken into account for any hazard / risk assessment: Developmental toxicity of lead and lead compounds: 1.2 ug/dl blood lead level, or 0.5 ug/kg bw/day CSR-PI CHEMICAL SAFETY REPORT 72

85 Value used for CSA (route: oral) Adverse effect observed Justification for classification or non classification Based on the available information and in accordance with the EU-classification, C. I. Pigment Red 104 should be considered as toxic to reproduction and the development, in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC (DSD: Repr. Cat. 1; R61 and Repr. Cat. 3; R62, CLP: Repr. 1A; H360Df) Other effects Non-human information Neurotoxicity No relevant information available Immunotoxicity No relevant information available Specific investigations: other studies No relevant information available Human information No relevant information available Summary and discussion of other effects Derivation of DNEL(s) and other hazard conclusions Overview of typical dose descriptors for all endpoints Table 33. Available dose-descriptor(s) per endpoint as a result of its hazard assessment Endpoint Route Dose descriptor or qualitative effect characterisation; test type Acute toxicity oral No adverse effect observed Acute toxicity dermal No adverse effect observed Irritation / Corrosivity Irritation / Corrosivity skin eye No adverse effect observed (not irritating) No adverse effect observed (not irritating) Sensitisation skin Adverse effect observed (sensitising) Sensitisation Repeated dose toxicity respiratory tract oral Carcinogenicity oral Adverse effect observed (sensitising) LOAEL: 70 mg/kg bw/day (subchronic; dog) Target organs: cardiovascular / hematological: hematopoiesis; digestive: liver; urogenital: kidneys Adverse effect observed The OEL for Chromium VI was set at 0.22 µg Reference to selected study (see footnotes for justification) CSR-PI CHEMICAL SAFETY REPORT 73

86 Endpoint Route Dose descriptor or qualitative effect characterisation; test type Carcinogenicity dermal Carcinogenicity inhalation Cr(VI)/ kg body weight/day by ECHA No adverse effect observed Adverse effect observed Reference to selected study (see footnotes for justification) Reproductive toxicity: developmental toxicity oral The OEL for Chromium VI was set at 0.01 µg/m3 by Seidler et al. (2012) Adverse effect observed The BMDL01 for lead was estimated to be 1.2μg/dL (mentioned as 12μg/L) by EFSA Justification for endpoint selection: - Sensitisation (skin): Conclusion on skin sensitisation was based on the skin sensitising properties of hexavalent Chromium compounds. - Sensitisation (skin): Conclusion on skin sensitisation was based on the respiratory sensitising properties of hexavalent Chromium compounds. - Carcinogenicity (inhalation): Conclusion on carcinogenicity was based on the carcinogenic properties of hexavalent Chromium compounds. - Carcinogenicity (oral): Conclusion on carcinogenicity was based on the carcinogenic properties of hexavalent Chromium compounds. - Reproductive toxicity: developmental toxicity (oral): Based on the review of available information by the European Food Safety Authority Selection of the DNEL(s) or other hazard conclusion for critical health effects Table 34. Hazard conclusions for workers Route Type of effect Hazard conclusion Most sensitive endpoint Inhalation Systemic effects - Long-term Inhalation Systemic effects - Long-term Inhalation Systemic effects - Acute Inhalation Local effects - Long-term Inhalation Local effects - Acute Dermal Dermal Systemic effects - Long-term Systemic effects - Acute DMEL (Derived Minimum Effect Level): 4.44 µg/m³ DMEL (Derived Minimum Effect Level): 5.8 µg/m³ No hazard identified High hazard (no threshold derived) No hazard identified DMEL (Derived Minimum Effect Level): 5 mg/kg bw/day No hazard identified carcinogenicity (By inhalation) developmental toxicity / teratogenicity (By inhalation) respiratory sensitisation developmental toxicity / teratogenicity (Oral) CSR-PI CHEMICAL SAFETY REPORT 74

87 Route Type of effect Hazard conclusion Most sensitive endpoint Dermal Local effects - Long-term Dermal Local effects - Acute Oral Systemic effects - Long-term Medium hazard (no threshold derived) No hazard identified Eyes Local effects No hazard identified DNEL (Derived No Effect Level): 1.47 µg/kg bw/day skin sensitisation carcinogenicity (Oral) Further explanation on hazard conclusions: - Inhalation Systemic effects - Long-term: The DMELsystemic, long-term, inhalation is based on the most critical effect: carcinogenicity caused by hexavalent chromium compounds. However, the DMEL for effects on neurobehavioural development caused by lead compounds should also be taken into account when assessing the risks, although this DMEL is higher: 5.8 ug/m3. For justification and comments, reference is made to the discussion section. - Inhalation Local effects - Long-term: Chromium compounds are classified for respiratory sensitisation. - Dermal Systemic effects - Long-term: The DMELsystemic, long-term, dermal is based on the most critical effect: effects on neurobehavioural development caused by lead compounds. - Dermal Local effects - Long-term: Chromium compounds are classified for skin sensitisation. Table 35. Further explanation on DNEL derivation for workers Route / Type of effect Inhalation Systemic effects - Long-term DNEL derivation DNEL derivation method: DMEL was derived based on the OEL for hexavalent Chromium compounds as proposed by Seidler et al. (2012) corrected for the chromium amount in the pigment (15%) Assessment factors (AF) for DNEL derivation Not applicable Dermal Systemic effects - Long-term Dose descriptor starting point: OEL µg/m³ DNEL derivation method: DMEL was derived based on the BMDL01 as presented in the Scientific Opinion on lead in food by the European Food Safety Authority (EFSA, 2010) Not applicable Dose descriptor starting point: BMDL µg/kg bw/day Justification for route-to-route extrapolation: - Inhalation Systemic effects - Long-term: A correction factor of 44.4 was applied based on the very poor solubility of C. I. Pigment Yellow 34 in simulated interstitial lung fluid, as bioelution tests indicate that the pigment is at least 44.4 times less soluble than poorly soluble hexavalent chromium compounds in general (as mentioned in the SCOEL report; 2004). - Dermal Systemic effects - Long-term: The BMDL01 of 0.5 µg/kg bw/day was corrected for the poor dermal CSR-PI CHEMICAL SAFETY REPORT 75

88 absorption of pigments (0.01%), arriving at a DMEL long-term systemic dermal of 5000 µg/kg bw/day or 5 mg/kg bw/day. Discussion Carcinogenicity In accordance with the current EU classification for C. I. Pigment Yellow 34 and C. I. Pigment Red 104, which was based on read across from other more soluble and more respirable hexavalent chromium compounds, C. I. Pigment Yellow 34 and C. I. Pigment Red 104 are classified for carcinogenicity, although the likelihood of carcinogenicity risk is considered very low due to very poor bioavailability of these two substances. Three epidemiological studies in lead chromate pigment manufacturing plants "did not produce evidence supporting any association between lead chromate [pigments] and lung cancer". However limitations in cohort size, due to the limited number of workers in this industry, limits the use of such studies. Nonetheless as the worst case, the carcinogenicity risk of these two pigments will be assessed, using the carcinogenic properties of hexavalent chromium compounds as described by Seidler et al. (2012) and in the SCOEL (2004) documents for Cr(VI) compounds. The very poor solubility and bioavailability of these two lead sulfochromate pigments should be taken into account when deriving the DMEL. Several health effects are associated with occupational exposure to hexavalent chromium compounds, with carcinogenicity (specifically lung cancer) being the most serious. Therefore, lung cancer is the critical effect upon which to base an occupational exposure limit. In 2012, Seidler et al. published a review and quantification of respiratory cancer risk for occupational exposure to Hexavalent Chromium. Seidler et al. reviewed a large number of epidemiological studies and selected 5 studies from 2 cohorts for their Risk Assessment, based on the presence of multiple exposure levels, consideration of smoking as confounder and overall adequate methodogy used. They calculated that the numbers of excess lung cancers per 1000 male workers exposed for a working lifetime to 1 µg/m3 of hexavalent chromium and followed to age years are predicted to be in the range of This means that Seidler et al. (2012) derive an Occupational Exposure Level (OEL) associated with 4 excess lung cancer cases per 100,000 workers for life time exposure to hexavalent chromium of 0.01 µg/m3. Based on a maximum chromium level of 15% in C. I. Pigment Yellow 34 and C. I. Pigment Red 104, this value corresponds to a Cr (VI) exposure for both pigments of µg/m3. Unfortunately, the available epidemiological data do not allow for a reliable ranking of the carcinogenic potency of the various hexavalent chromium compounds encountered in industry. The data indicate, however, that poorly soluble hexavalent chromium compounds have a lower carcinogenic potency than soluble compounds. The relatively lower bioavailability of chromium ions to the intracellular target in the respiratory epithelium might explain this effect. The Scientific Committee on Occuptional Exposure Levels (SCOEL/SUM/086, 2004) distinguishes three classes of hexavalent chromium compounds based on water solubility and defines them as: poorly soluble (<1g/L), sparingly soluble (1-10g/L); highly soluble (>100g/L) compounds. In addition, SCOEL published a health-based Risk Assessment for lead chromate (SCOEL/SUM/117, 2004). In this document it is concluded that, based on the specific data available for lead chromate, the OEL could be based on the information on inorganic lead compounds in general, as, based on the low solubility (a value of 0.06 g/l is mentioned), the likelihood of risk of genotoxicity and carcinogenicity is considered low. SCOEL recommends an OEL of 100μg Pb/m3 ambient air (corresponding to a Blood Lead Value (BLV) of 30μg Pb/dl blood. This value would be equivalent to a concentration of 25μg Cr/m3. Despite the SCOEL recommendations for lead chromate and hexavalent chromium, it is decided to use the hexavalent chromium OEL from Seidler et al. (2012) as a basis for the DMEL for C. I. Pigment Yellow 34 and C. I. Pigment Red 104, taking into account the differences in solubility. The solubility of Cr(VI) derived from C. I. Pigment Yellow 34 and C. I. Pigment Red 104 in aqueous media ranges from 3*10^-6 to 2,3*10^-2 g/l, depending on the Transformation/Dissolution or bio-elution protocol in aqueous solvents (ECTX studies X02d-022 and X02d-023). These solubility values are about 40 30,000 times lower than the limit for poorly soluble of 1 g/l in the SCOEL report. The most relevant aqueous medium (simulated interstitial lung fluid) showed Cr(VI) solubilities from C. I. Pigment Red 104 and C. I. Pigment Yellow 34 of g/l and g/l, respectively. This is at least times less soluble than the level for low solubility given in the SCOEL report. For this reason, it is considered justified to correct the OEL by a factor of 44.4 to arrive at a DMEL long-term CSR-PI CHEMICAL SAFETY REPORT 76

89 systemic inhalation of 2.96 µg/m3 for both C. I. Pigment Yellow 34 and C. I. Pigment Red 104. The excess lung cancer risk from Cr(VI) exposure can only be attributed to the respirable fraction of the hexavalent chromium compound. The non-respirable fraction will be cleared from the respiratory tract and swallowed in the gastrointestinal tract. From the particle size distribution and dustiness tests for C. I. Pigment Yellow 34 and C. I. Pigment Red 104 (see section 4.5) it can be estimated that the respirable fraction is < 2% for both pigments. This implies that the inhalable, non-respirable fraction must be evaluated for excess cancer risk from exposure by the oral route. It should be noted that the distribution of respirable and non-respirable fractions may vary among different uses, based on the formulation of the pigments. This will be taken into account in the risk assessment. In the report on the carcinogenicity dose-response analysis of Cr(VI) - and As-containing substances (ECHA project SR11), it was concluded that for oral exposures above 0.22 µg Cr(VI) / kg body weight/day an excess lifetime intestinal cancer risk of 8 x 10^-4 per µg Cr(VI) / kg body weight/day applies. For oral exposures below 0.22 µg Cr(VI) / kg body weight/day it is considered that physiological processes will be able to reduce Cr(VI) to Cr(III), that a threshold for intestinal carcinogenicity exists and that the risks of carcinogenicity are negligible. The assessment is based on linear extrapolation from intestinal tumour data in mice. The estimate applies to both occupational and general public exposures and is based on a 70 year exposure scenario (every day) and a 70 year life expectancy. Based on a maximum chromium level of 15% in C. I. Pigment Yellow 34 and C. I. Pigment Red 104, this oral Cr(VI) value corresponds to a Cr (VI) exposure for both pigments of 0.22/0.15 = 1.47 µg/kg body weight/day. This value will be used as an oral DNEL in the risk assessment to determine the risk due to swallowed non-respirable dust. Toxicity to reproduction/developmental toxicity From the available data it is evident that the carcinogenicity risk will occur via the inhalation route only. However, effects of the inorganic lead in C. I. Pigment Yellow.34 and C. I. Pigment Red.104 should also be assessed to exclude all possible effects. Therefore, the available information with regard to effects on development and reproduction of inorganic lead compounds were assessed. In the voluntary Risk Assessment Report for lead and inorganic lead compounds, all available studies in humans and experimental animals have been evaluated for the observed effect of lead upon sexual maturation and semen quality, pregnancy outcome, and neurobehavioural effects of prenatal and postnatal lead exposure. Based on the available data it is concluded that effects on neurobehavioural performance after pre-natal and post-natal exposure to inorganic lead, are the most critical effects, although a dose-effect relationship was not observed. This conclusion was based on a meta-analysis of several cohort studies correlating blood-lead concentrations to IQ deficits (Lanphear et al and other studies). The result showed that IQ points were lost at blood-lead concentrations of < 10μg/dL and < 7.5μg/dL and that there was no indication of a threshold below these levels. In the risk assessment on lead from food which was performed by the European Food Safety Authority (EFSA, 2010), the Bench Mark Dose approach (BMD) is used to estimate the BMDL01, which is the blood-lead concentration corresponding to the 1-percentile of the Confidence Interval of the chosen Bench Mark Response of an IQ deficit of 1 IQ point. The BMR is chosen and set at 1 IQ point by the CONTAM panel of EFSA. Using this approach, the BMDL01 for lead was estimated to be 1.2μg/dL (mentioned as 12μg/L by EFSA) and must be regarded as a DMEL for minimal IQ loss due to neurodevelopmental toxicity. This DMEL can be converted from 1.2μg/dL to 0.5μg/kg body weight/day, which corresponds to 35μg/day for a 70 kg person. Oral 35μg/day corresponds to 3.5μg/m3 (inhalation worker is 10 m3 per workday). This value can be compared to the DMEL for carcinogenic effects, corrected for the percentage of lead (maximally 60%) in both pigments. The maximum lead exposure for workers exposed to the DMEL of 4.4μg/m3 (total pigment) is 2.64μg/m3, which is lower than the BMDL01 of 3.5 µg/m3. Therefore it can be concluded that the DMEL for carcinogenicity will be valid for neurodevelopmental effects as well (decrease in IQ of less than 0.75 IQ point). In order to perform a combined risk assessment for the effects on neurobehavioural development, a DMEL of 5.8 µg/m3 can be taken into account, based on maximally 60% lead in pigment. With regard to dermal exposure, the VRAR mentions that lead uptake rates via the dermal route are <0.01%, both for adults and for children. This is supported by an in vitro skin absorption study (HERAG Fact Sheet 01, Occupational dermal exposure and dermal absorption, 2007; Toner and Roper, 2006) and bio-elution studies showing <2% solubility of C. I. Pigment Yellow.34 and C. I. Pigment Red.104 in artificial sweat. Therefore it can be assumed that dermal exposure will not contribute to higher blood lead levels to a large extent. However, to CSR-PI CHEMICAL SAFETY REPORT 77

90 exclude possible effects from dermal exposure, a DMEL was derived based on the BMDL01 for oral exposure as presented in the EFSA report. This value of 0.5 µg/kg bw/day should be corrected for dermal absorption, arriving at a DMEL long-term systemic dermal of 5000 µg/kg bw/day or 5 mg/kg bw/day. Table 36. Hazard conclusions for the general population Route Type of effect Hazard conclusion Most sensitive endpoint Inhalation Systemic effects - Long-term Inhalation Systemic effects - Acute Inhalation Local effects - Long-term Inhalation Local effects - Acute Dermal Dermal Systemic effects - Long-term Systemic effects - Acute Dermal Local effects - Long-term Dermal Local effects - Acute Oral Oral Systemic effects - Long-term Systemic effects - Acute Not relevant Not relevant Not relevant Not relevant Not relevant Not relevant Not relevant Not relevant Not relevant Not relevant Eyes Local effects Not relevant Further explanation on hazard conclusions: - Inhalation Systemic effects - Long-term: Not relevant as no consumer uses are anticipated and no consumer exposure is expected - Inhalation Systemic effects - Acute: Not relevant as no consumer uses are anticipated and no consumer exposure is expected - Inhalation Local effects - Long-term: Not relevant as no consumer uses are anticipated and no consumer exposure is expected - Inhalation Local effects - Acute: Not relevant as no consumer uses are anticipated and no consumer exposure is expected - Dermal Systemic effects - Long-term: Not relevant as no consumer uses are anticipated and no consumer exposure is expected - Dermal Systemic effects - Acute: Not relevant as no consumer uses are anticipated and no consumer exposure is expected - Dermal Local effects - Long-term: Not relevant as no consumer uses are anticipated and no consumer CSR-PI CHEMICAL SAFETY REPORT 78

91 exposure is expected - Dermal Local effects - Acute: Not relevant as no consumer uses are anticipated and no consumer exposure is expected - Oral Systemic effects - Long-term: Not relevant as no consumer uses are anticipated and no consumer exposure is expected - Oral Systemic effects - Acute: Not relevant as no consumer uses are anticipated and no consumer exposure is expected - Eyes Local effects: Not relevant as no consumer uses are anticipated and no consumer exposure is expected Discussion Not relevant as no consumer uses are anticipated and no consumer exposure is expected CSR-PI CHEMICAL SAFETY REPORT 79

92 6. HUMAN HEALTH HAZARD ASSESSMENT OF PHYSICOCHEMICAL PROPERTIES 6.1. Explosivity Data waiving: see CSR section 1.3 Physicochemical properties. Discussion The following information is taken into account for any hazard / risk assessment: In accordance with column 2 of REACH Annex VII, the explosiveness of the substance does not need to be tested, because there are no chemical groups associated with explosive properties in the molecule 6.2. Flammability Flammability The available information on flammability is summarised in the following table: Table 37. Information on flammability Method Results Remarks Reference other: conclusive Evaluation of results: non flammable Study results: Ignition on contact with air: no 2 (reliable with restrictions) supporting study experimental result GESTIS (2007) Remarks: non combustible solid Test material (IUPAC name): lead chromate molybdate sulfate red Data waiving: see CSR section 1.3 Physicochemical properties. Discussion The following information is taken into account for any hazard / risk assessment: In accordance with section 1 of REACH Annex XI, the flammability does not need to be performed as the substance is a non combustible solid, non flammable upon ignition. The substance has no pyrophoric properties and does not yield flammable gases on contact with water. Flash point Data waiving: see CSR section 1.3 Physicochemical properties. Discussion The following information is taken into account for any hazard / risk assessment: In accordance with section 1 of REACH Annex XI, the flash point does not need to be tested as the substance is a solid (scientifically unjustified) and in accordance with column 2 of REACH Annex VII, the flash point does not need to be performed as the substance is inorganic (other justification) CSR-PI CHEMICAL SAFETY REPORT 80

93 6.3. Oxidising potential The available information on the oxidising potential is summarised in the following table: Table 38. Information on oxidising potential Method Results Remarks Reference Contact with: powdered cellulose (> 45 <= 600 s) EU Method A.17 (Oxidising Properties (Solids)) Discussion Evaluation of results: no oxidising properties maximum burning rate of reference mixture: ca mm/s (60% reference mixture/cellulose) maximum burning rate of test mixture: ca mm/s (All mixtures of C.I. Pigment Red 104 and Cellulose indicated soldering when burned. The three concentrations with the highest burning rates are 60%, 70% and 80%, 80% having the highest burning rate.) Remarks: Preliminary test The burning time of C.I. Pigment Red 104 was determined to be more than the reference sample in the preliminary screening test. Therefore the full train test was conducted. Full train test The highest burning rate recorded from the six samples of C.I. Pigment Red 104 in cellulose was 0.36 mm/s, which was the sample with 80% of the test substance. This value should be compared to the highest burning rate of the reference substance Barium Nitrate, which was 0.85mm/s. It can be concluded that the sample of C.I. Pigment Red 104 should be classed not an oxidizing substance since in any percentage of C.I. Pigment Red 104/Cellulose, it has a burning rate of less than that of Barium Nitrate/Cellulose per EC Physico/Chemical Test A17, Oxidizing Properties (Solid) Test. 1 (reliable without restriction) key study experimental result Test material (Common name): C.I. Pigment Red 104 Form: powder Umbrajkar, S.M. (2013) The oxidising properties of C. I. Pigment Red 104 were determined in accordance with the EC Physico/Chemical Test A17, Oxidizing Properties (Solid) Test. In the preliminary test, the burning time of C. I. Pigment Red 104 was determined to be more than the reference sample in the preliminary screening test. Therefore the full train test was conducted. In the full train test, the highest burning rate recorded from the six samples of C. I. Pigment Red 104 in cellulose was 0.36 mm/s, which was the sample with 80% of the test substance. This value should be compared to the highest burning rate of the reference substance Barium Nitrate, which was 0.85mm/s. It can be concluded that the sample of C. I. Pigment Red 104 should be classed not an oxidizing substance since in any percentage of C. I. Pigment Red 104/Cellulose, it has a burning rate of less than that of Barium Nitrate/Cellulose per EC Physico/Chemical Test A17, Oxidizing Properties (Solid) Test CSR-PI CHEMICAL SAFETY REPORT 81

94 The following information is taken into account for any hazard / risk assessment: EC Physico/Chemical Test A17, Oxidizing Properties (Solid) Test: not oxidising Justification for classification or non-classification: Based on the available information, C. I. Pigment Red 104 does not have to be classified as oxidising, in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC CSR-PI CHEMICAL SAFETY REPORT 82

95 7. ENVIRONMENTAL HAZARD ASSESSMENT 7.1. Aquatic compartment (including sediment) Due to the very low solubility of C. I. Pigment Red 104 in water the bioavailability of the substance is expected to be low. However, a small proportion of the parent substance may dissolve and release chromate ions (CrO 4 2- ) and lead ions (Pb ²+ ). For the ecotoxicological tests, a saturated solution of 100 or 125 mg C. I. Pigment Red 104 per liter was stirred and filtered (0.2 micrometer). The concentrations of chromium and lead in the eluate were determined, see table below. For comparison, the table also presents the results for the same tests with the similar substance C. I. Pigment Yellow 34. No effects were observed in any of the tests on both pigments. C. I. Pigment Red 104 Test with eluate Eluate of Cr (mg/l) Pb (mg/l) Ba (mg/l) Reference 96h-LC50 10 g/l n. d. n. d. n. d. BASF AG 1988 Leuciscus idus 48h-EC mg/l n. d. BASF AG 2000 Daphnia magna 72h-EC50/NOE C Desmodesmus subspicatus 125 mg/l <0.005 (1) <0.005 (2) 0.13 (1) (2) n. d. BASF AG min-ec50 Pseudomonas putida non filtered =<10 g/l n. d. n. d. n. d. BASF AG 1988 C. I. Pigment Yellow 34 Test with eluate Eluate of Cr (mg/l) Pb (mg/l) Ba (mg/l) Reference 96h-LC50 10 g/l n. d. n. d. n. d. BASF AG 1988 Leuciscus idus 48h-EC mg/l BASF AG 2000 Daphnia magna 72h-EC50/NOE C Desmodesmus subspicatus 125 mg/l (1) (2) (1) (2) 2.0 (1) 1.7 (2) BASF AG min-ec50 Pseudomonas putida non filtered =<10 g/l n. d. n. d. n. d. BASF AG CSR-PI CHEMICAL SAFETY REPORT 83

96 No chronic data are available for C. I. Pigment Red 104. No long term toxicity studies are available with the pigments. Instead, reference is made to the long/term aquatic toxicity of lead and chromium. The water solubility of the pigment in water is very low and no acute toxicity was observed. No chronic data are available for C. I. Pigment Yellow 34 or C. I. Pigment Red 104. As shown in the Transformation/Dissolution study, a small proportion of the parent substance may dissolve and release chromate ions (CrO 4 2 -, determined as Cr ions) and lead ions (Pb 2 + ). Data on lead and chromium are summarised below for aquatic invertebrates and fish. Chromium Endpoint Comments Fish Pimephales promelas 412d-NOECmort 1 mg/l (most sensitive endpoint) 60d-NOECmort/growth rate 1 mg/l 412 days first generation + 60 days second generation Pickering 1980 Daphnia magna 3wk-EC16 repro 330 µg/l Biesinger & Christensen d-NOEC repro 0.7 mg/l Kuhn et al Lead Endpoint Comments Fish Onchorhynchus mykiss 3 wk-loec 13 µg/l Hematological effects Hodson & Blunt 1978 Daphnia magna 3wk-EC16 repro 30 µg/l Biesinger & Christensen Fish Short-term toxicity to fish The results are summarised in the following table: Table 39. Short-term effects on fish Method Results Remarks Reference Leuciscus idus freshwater static DIN L15, German standard test guideline, comparable to OECD 203. Discussion LC50 (96 h): ca mg/l test mat. (nominal) based on: mortality (concentrations above water solubility. Tested as dilutions of a filtered leachate) 2 (reliable with restrictions) key study experimental result Test material (IUPAC name): lead chromate molybdate sulfate red BASF AG (1988a) The toxicity of C. I. Pigment Red 104 to fish was tested in a static test system set up according to German standard DIN 38412, part L15. Leuciscus idus was exposed to the substance for 96 hours. At test termination a LC50 of ca mg/l was determined. The test solutions contained undissolved test material and were cloudy and coloured (BASF AG, 1988, reliability 2) CSR-PI CHEMICAL SAFETY REPORT 84

97 The following information is taken into account for acute fish toxicity for the derivation of PNEC: In a short-term toxicity test on the fish Leuciscus idus, no effects were observed in test concentrations up to 1000 mg/l. The 96h-LC50 is above 2.5 g/liter (nominal). Value used for CSA: LC50 for freshwater fish: 2500 mg/l Long-term toxicity to fish The results are summarised in the following table: Table 40. Long-term effects on fish Method Results Remarks Reference Oncorhynchus mykiss (reported as Salmo gairdneri) freshwater adult fish: (sub)lethal effects flow-through Acute lethal and chronic sublethal toxicity was tested in continous-flow bioassays. (Method according to Sprague J. B. (1969) Measurement of pollutant toxicity to fish. I. Bioassay methods for acute toxicity. Water Res. 3, ) Three different experiments were conducted Pimephales promelas freshwater early-life stage: reproduction, (sub)lethal effects flow-through The effect of chromium on hatching, growth and survival was tested. Lead concentrations in body tissue of fish increased linearly with the lead concentration in water. Starting at a lead concentration of 13 µg/l lead accumulation in fish tissues occurred throughout all tested concentrations. Whereas the lead concentrations in the tissues did not increase when the lead concentrations in food were enhanced. Hematological effects were detected in fish exposed to lead via water of at least 13 µg lead/l. The authors conclude from their data that lead induced an accelerated mortality and removal of mature red cells and an acceleration of hemopoiesis. Furthermore they suggest that a reduction of cellular hemoglobin occurred. NOEC (412 d): 1 mg/l test mat. (meas. (not specified)) based on: mortality NOEC (412 d): 3.95 mg/l test mat. (meas. (not specified)) based on: growth rate NOEC (412 d): > 3.95 mg/l test mat. (meas. (not specified)) based on: reproduction NOEC (60 d): 1 mg/l test mat. (meas. (not specified)) based on: mortality (second 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead nitrate 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Potassium dichromate Hodson PV, Blunt BR, Spry DJ (1978) Pickering QH (1980) CSR-PI CHEMICAL SAFETY REPORT 85

98 Method Results Remarks Reference Discussion generation) NOEC (60 d): 1 mg/l test mat. (meas. (not specified)) based on: growth rate (second generation) Due to the low water solubility of C. I. Pigment Red 104 adverse chronic effects of the substance to aquatic organisms are not expected. However, a minor part of the substance may dissolve and chromate (CrO 4 2- ) and lead ions (Pb² + ) may dissociate from the parent substance. Both substances may have chronic effects on fish Aquatic invertebrates Short-term toxicity to aquatic invertebrates The results are summarised in the following table: Table 41. Short-term effects on aquatic invertebrates Method Results Remarks Reference Daphnia magna freshwater static OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test) Discussion EC50 (48 h): > 100 mg/l loading of the test material (nominal) based on: mobility (concentrations above water solubility. Tested as dilutions of a filtered leachate) 2 (reliable with restrictions) key study experimental result Test material (IUPAC name): lead chromate molybdate sulfate red BASF AG (2000a) The acute toxicity of C. I. Pigment Red 104 to Daphnia magna was tested in a guideline study following OECD 202 (Reliability 2, acceptable restrictions). The test substance was not prepared according to the OECD 29 dissolution protocol (07/2001). An eluate was prepared by stirring 100 mg C. I. Pigment Red 104 per liter for 24 hours and filtration over 0.2 micrometer. The concentrations of dissolved metals in the eluate were determined. The eluate contents for dissolved chromium and lead were mg chromium/l and 0.5 mg lead/l. The 48h-EC50 for daphnia was above the loading rate of 100 mg C. I. Pigment Red 104 per liter (BASF AG, 2000). The following information is taken into account for short-term toxicity to aquatic invertebrates for the derivation of PNEC: In a short-term toxicity test with Daphnia magna, no effects were observed in test concentrations up to 100 mg/l. Therefore the LC50 is above the loading rate of 100 mg test substance/liter. Value used for CSA: EC50/LC50 for freshwater invertebrates: 100 mg/l Long-term toxicity to aquatic invertebrates The results are summarised in the following table: Table 42. Long-term effects on aquatic invertebrates CSR-PI CHEMICAL SAFETY REPORT 86

99 Method Results Remarks Reference Daphnia magna freshwater static Toxicity of several metals was tested. Acute and chronic studies were performed. Daphnids were exposed for 3 weeks, survival, reproduction and fitness were analysed. Daphnia magna freshwater static Toxicity of several metals was tested. Acute and chronic studies were performed. Daphnids were exposed for 3 weeks, survival, reproduction and fitness were analysed. 16 % reproduction impairment (3 wk): 30 µg/l test mat. (lead) (nominal) based on: reproduction LC50 (3 wk): 300 µg/l test mat. (lead) (nominal) based on: mortality 50 % reproductive impairment (3 wk): 100 µg/l test mat. (lead) (nominal) based on: reproduction LC50 (3 wk): 2000 µg/l test mat. (chromium) (nominal) based on: mortality 16 % reproduction impairment (3 wk): 330 µg/l test mat. (chromium) (nominal) based on: reproduction 50 % reproduction impairment (3 wk): 600 µg/l test mat. (chromium) (nominal) based on: reproduction 16 % reproduction impairment (3 wk): 30 µg/l test mat. (lead) (nominal) based on: reproduction LC50 (3 wk): 300 µg/l test mat. (lead) (nominal) based on: mortality 50 % reproductive impairment (3 wk): 100 µg/l test mat. (lead) (nominal) based on: reproduction LC50 (3 wk): 2000 µg/l test mat. (chromium) (nominal) based on: mortality 16 % reproduction impairment (3 wk): 330 µg/l test mat. (chromium) (nominal) based on: reproduction 50 % reproduction impairment (3 wk): 600 µg/l test mat. (chromium) (nominal) based on: 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead, Chromium 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead, Chromium Biesinger KE and Christensen GM (1972) Biesinger KE and Christensen GM (1972) CSR-PI CHEMICAL SAFETY REPORT 87

100 Method Results Remarks Reference Daphnia magna freshwater semi-static 21 day reproduction test Discussion reproduction NOEC (21 d): 0.7 mg/l test mat. (nominal) based on: reproduction 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance Chromium chloride Kuehn R, Pattard M, Pernak K-D, Winter A (1989) Due to the low water solubility of C. I. Pigment Red 104 adverse chronic effects of the substance to aquatic organisms are not expected. However, a minor part of the substance may dissolve and chromate (CrO 4 2- ) and lead ions (Pb² + ) may dissociate from the parent substance. Both substances may have chronic effects on aquatic invertebrates Algae and aquatic plants The results are summarised in the following table: Table 43. Effects on algae and aquatic plants Method Results Remarks Reference Desmodesmus subspicatus (reported as Scenedesmus subspicatus) (algae) freshwater static OECD Guideline 201 (Alga, Growth Inhibition Test) EC50 (72 h): > 100 mg/l test mat. (nominal) based on: growth rate NOEC (72 h): 1 mg/l test mat. (nominal) based on: measured fluorescence before growth rate calculation (Report states NOEC but there is no concentration-effect relation) NOEC (72 h): >= 100 mg/l test mat. (nominal) based on: growth rate (Re-evaluated - Concentrations above the water solubility; tested as dilutions of a filtered leachate) 2 (reliable with restrictions) key study experimental result Test material: Sicomin Rot L 2922 BASF AG (2000b) Desmodesmus subspicatus (reported as Scenedesmus subspicatus) (algae) EC10 (72 h): 6.89 mg/l test mat. (nominal) based on: growth rate (Report states EC10 but there is no concentration-effect relation) EC50 (72 h): > 100 mg/l test mat. (nominal) based 2 (reliable with restrictions) BASF AG (2000c) CSR-PI CHEMICAL SAFETY REPORT 88

101 Method Results Remarks Reference freshwater static OECD Guideline 201 (Alga, Growth Inhibition Test) Discussion Effects on algae / cyanobacteria on: growth rate NOEC (72 h): 3 mg/l test mat. (nominal) based on: measured fluorescence before growth rate calculation (Report states NOEC but there is no dose-effect relation) NOEC (72 h): >= 100 mg/l test mat. (nominal) based on: growth rate (Re-evaluated - Concentrations above the water solubility; tested as dilutions of a filtered leachate) EC10 (72 h): 11.9 mg/l test mat. (nominal) based on: growth rate (Report states 11.9 mg/l, but there is no dose-effect relation) supporting study experimental result Test material: Sicomin Rot L 2922 Two guideline studies on the acute toxicity of C. I. Pigment Red 104 to the aquatic alga Desmodesmus subspicatus are available (OECD 201, 1984, reliability 2, acceptable restrictions). The test substance was not prepared according to the OECD 29 dissolution protocol (07/2001). It was prepared by stirring 125 mg C. I. Pigment Red 104 per liter for 24 hours and filtration over 0.2 micrometer. The concentrations of dissolved metals in the eluate were determined. The eluate contents for dissolved chromium and lead were < mg chromium/l and 0.13 to 0.16 mg lead/l, respectively. No dose-related effects on the growth rate were observed (see attached graphs). The 72h-EC50 for Desmodesmus subspicatus was above the loading rate of 100 mg C. I. Pigment Red 104 per liter. The 72h-NOEC for Desmodesmus subspicatus was at or above the loading rate of 100 mg C. I. Pigment Red 104 per liter (BASF AG, 2000). The following information is taken into account for effects on algae / cyanobacteria for the derivation of PNEC: No dose-related effects on the growth rate of Desmodesmus subspicata were observed after 72 h exposure to test concentrations up to 100 mg C. I. Pigment Red 104/l. Therefore the LC50 is above the loading rate of 100 mg test substance/liter and the NOEC is at or above 100 mg/l. Value used for CSA: EC50/LC50 for freshwater algae: 100 mg/l EC10/LC10 or NOEC for freshwater algae: 100 mg/l Sediment organisms The results are summarised in the following table: CSR-PI CHEMICAL SAFETY REPORT 89

102 Table 44. Long-term effects on sediment organisms Method Results Remarks Reference Hediste diversicolor saltwater long-term toxicity (laboratory study) static Rag worms were collected and fed on organic matter in sediment. Lead concentrations were determined Mytilus edulis saltwater short-term toxicity (laboratory study) static The bioaccumulation of Cr (III) and Cr(VI) in phytoplankton was investigated by exposing phytoplanton species to different concentrations of crhomium. Cell growth and accumulated Cr was measured periodically. Discussion LC50 (10 d): 48 mg/l test mat. (nominal) based on: mortality (size class mm) LC50 (28 d): 19 mg/l test mat. (nominal) based on: mortality (size class mm) LC50 (10 d): 65 mg/l test mat. (nominal) based on: mortality (size class mm) LC50 (28 d): 28 mg/l test mat. (nominal) based on: mortality (size class mm) The dry weight concentration factors (DCF) calculated for the phytoplankton decreased with cell growth. The DCFs for CrIII was generally higher than the DCF for CrVI (DCF CrIII: ; CR VI ). The Cr assimilation of mussels did not vary between the different sediments (of different organic matter content) but different with the ingested phytoplankton species. Mussels rapidly egested Cr. The uptake rate of Cr VI from the dissolved phase was three times higher than that of CrIII. The efflux rate constant was d-1 for mussels following 7 d dissolved uptake of Cr(VI) and d-1 following 8 d ingestion of Cr(III)-labeled diatoms. 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: lead (II) nitrate 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Cr (III), Cr (VI) Bat L, Guendogdu A, Akbulut M, Culha M, Satilmis HH (2001) Wang W_X, Griscom SB, Fisher NS (1997) The effect of the test substance on the sediment compartment and sediment organisms was not tested. C. I. Pigment Yellow 34 and C. I. Pigment Red 104 are very stable in the environment but a low proportion of the substance may dissociate and release chromate and lead ions. The bioavailability of these ions is assumed to be very low. It depends on sediment ph, the amount of organic matter or mineral particles and alkalinity (chapter 5.4). Therefore, the bioavailability of dissociating chromate and lead ions is presumably limited. However, data on the influence of chromate and lead demonstrate that both metals have detrimental effects on sediment organisms CSR-PI CHEMICAL SAFETY REPORT 90

103 In a study on lead uptake from sediment by river crabs accumulation of lead was determined. Smaller crabs had a higher lead concentration as larger crabs (mean /- 59 µg/g and 3.6 +/- 1.3 µg/g respectively) (Reinecke et al. 2003). Comparable results were demonstrated by a second study on lead uptake by polychaetes. The sensitivity of smaller animals was higher compared to larger individuals. After 28 days of exposure a LC50 of 19 mg/l was determined for smaller polychaetes whereas for larger animals a LC50 (28 d) of 28 mg/l was detected (Bat et al. 2001). The bioaccumulation of chromium in phytoplankton and mussels was investigated using radio labeled chromium (III) and chromium (VI) (Wang et al.1997). Chromium (III) and, to a smaller extent, chromium (VI) was concentrated by phytoplankton (DCF Cr(III): ; DCF Cr(VI): ). Comparable concentration rates were measured for mussels Other aquatic organisms No relevant information available 7.2. Terrestrial compartment Data on the effect of C. I. Pigment Yellow 34 and C. I. Pigment Red 104 on terrestrial organisms are not available. Generally the substances are very stable in the environment. However, a low proportion of the substance may dissociate and release chromate and lead ions to the environment. The bioavailability of these ions depends on factors like ph and the presence of organic matter or mineral particles c. f. chapter 5.4. Thus, the availability of lead and chromate ions released by the substance is probably very limited. Results on the toxicity of lead and chromate on terrestrial organisms indicate that both ions have detrimental effects on terrestrial flora and fauna. Both moieties of the pigments are taken up by earthworms. EC50 values that are only available for chromium predict a mortality rate of 50 % at a concentration of 20 mg Cr/l Toxicity to soil macro-organisms The results are summarised in the following table: Table 45. Effects on soil macro-organisms Method Results Remarks Reference Lubricus terrestris and Aporectodea spec. (annelids) long-term toxicity (field study) Substrate: natural soil In a first experiment the metal concentrations of earthworms from soil treated with sewage sludge containing heavy metals was tested. In the second experiment the long-term effects of heavy metal addition were tested. The addition of sewage sludge to the test field occured several years before the tested earthworms were sampled. Pheretina posthuma (annelids) short-term toxicity (laboratory study) Substrate: natural soil Earthworms were exposed to soil mixed with potassium dichromate. Worms from soils amended with sludge contained significantly more Pb (1.2 times) than worms from control soils. The storage ratio of lead was ; with increasing soil metal content the relative amounts in worms decreased. Thus, lead is not concentrated by worms. The results observed in the three experimental sets are inconsistent. Mortalities decreased with increasing chromium concentrations. However, earthworms seem to be intolerant to chromium (VI). Regarding the effect of chromium (VI) on reproduction very heterogeneous results were 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Beyer WN, Chaney RL, Mulhern BM (1982) Soni R and Abbasi SA (1981) CSR-PI CHEMICAL SAFETY REPORT 91

104 Method Results Remarks Reference Folsomia candida (Collembola (soil-dwelling springtail)) short-term toxicity (laboratory study) Collembola were exposed to lead contaminated soil. The test was replicated at two different ph. Surviving adults and produced juveniles were counted detected and no linear relationship can be determined. EC50 (4 wk): EC50 test mat. (nominal) based on: reproduction (ph 6) EC50 (4 wk): EC50 test mat. (nominal) based on: reproduction (ph 5) EC50 (4 wk): EC50 test mat. (nominal) based on: mortality (ph 4.5) Discussion of effects on soil macro-organisms except arthropods potassium dichromate 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead nitrate Sandifer RD and Hopkin SP (1996) Data on the toxicity of C. I. Pigment Red 104 to soil macro-organisms are not available. The substance is generally assumed to be not bioavailable to terrestrial organisms due to its low solubility and its stability. As stated in chapter 5.0 Chromate (CrO 4 2- ) and lead ions (Pb² + ) may dissociate from the substance. Tests on the toxicity of both ions to earthworms indicate that lead and chromium ions are taken up by earthworms. A study conducted by Beyer et al. (1982) demonstrated that lead was taken up by earthworms but was not concentrated by the animals. Comparable results were determined for chromium. At a concentration of 20 mg/l a mortality rate of 50 % was determined after 28 days of exposure (Soni and Abbasi, 1981). Discussion of effects on soil dwelling arthropods Since C. I. Pigment Yellow 34 and C. I. Pigment Red 104 are highly insoluble, exposure of terrestrial organisms to the substance is not expected. Therefore, no data exist on the toxicity of the substance to terrestrial arthropods. However, a minor part of C. I. Pigment Red 104 may dissolve and release lead and chromate ions. The toxicity of chromium to the fig moth was investigated in a feeding test. Trivalent and hexavalent chromium had little effect on fecundity and survival of fig moths. However, for hexavalent chromium lethal mutations were detected at concentrations of 150 and 200 mg Cr/ kg food (Al-Hakkak and Hussain 1990). The toxicity of lead was tested in a study on the survival and reproduction of Collembola. The animals were exposed to lead via soil at different ph. After 4 weeks of exposure an EC50 (reproduction) of 2970µg lead/g soil of ph 6 was detected (Sandifer and Hopkin 1996) Toxicity to terrestrial plants The results are summarised in the following table: Table 46. Effects on terrestrial plants Method Results Remarks Reference Zea mays (Monocotyledonae (monocots)) long-term toxicity (field study) seedling emergence toxicity / vegetative vigour test Substrate: natural soil Zea mays was grown in soil treated with lead acetate. Seedling emergence, lead concentrations of plants and yield were determined. Neither germination nor plant height and yield were affected by lead addition to soil. Lead was taken up by the plants. Lead was absorbed by the roots and translocated in the plant. However, no increased lead concentrations were detected in the corn grain. 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead acetate Baumhardt GR and Welch IF (1972) CSR-PI CHEMICAL SAFETY REPORT 92

105 Method Results Remarks Reference Lycopersicon esculentum (Dicotyledonae (dicots)) Lactuca sativa (Dicotyledonae (dicots)) Lactuca sativa: NOEC (2 wk): 0.35 mg/kg soil dw test mat. (nominal) based on: growth (loam) 2 (reliable with restrictions) key study Adema DMM and Henzen L (1989) (Monocotyledonae (monocots)) short-term toxicity (laboratory study) seedling emergence toxicity test Substrate: artificial soil equivalent or similar to OECD Guideline 208 (Terrestrial Plants Test: Seedling Emergence and Seedling Growth Test) Lactuca sativa: EC50 (2 wk): 1.8 mg/kg soil dw test mat. (nominal) based on: growth (loam) Lycopersicon esculentum: NOEC (2 wk): 3.2 test mat. (nominal) based on: growth (loam) Lycopersicon esculentum: EC50 (2 wk): 6.8 mg/kg soil dw test mat. (nominal) based on: growth (loam) read-across from supporting substance (structural analogue or surrogate) Test substance: Potassium bichromate Avena sativa: NOEC (2 wk): 3.5 mg/kg soil dw test mat. (nominal) based on: growth (loam) long-term toxicity (laboratory study) seedling emergence toxicity / vegetative vigour test Substrate: natural soil The test substance was added to soil, subsequently test plants were sown. Phytotoxical effects of the test substance on plant development were recorded. Avena sativa: EC50 (2 wk): 7.4 mg/kg soil dw test mat. (nominal) based on: growth Effect of Potassiumdichromate on plant species. EC50 values are given in mg/kg soil Sinapis alta: 100 Brassica napus: 10 Brassica rapa: 10 Brassica chinensis: 10 Raphanus sativus: 100 Vicia sativa: 100 Phaseolus aureus: 100 Trifolium pratense: 10 Trinelis mellotus-coerulea: 100 Lolium perenne: 100 Avena sativa: 100 Triticum aestivum: 100 Sorghum vulgare: 100 Lepidium sativum: 10 Lactuca sativa: 10 2 (reliable with restrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test substance: Potassium dichromate Pestemer W, Auspurg B, Günther P (1987) The emergence and germination of all plant species were reduced by 100 % at 1000 mg/kg soil exept for Avena sativa. Potassiumdichromate strongly reduced growth of Avena sativa at an early developmental stage CSR-PI CHEMICAL SAFETY REPORT 93

106 Discussion Since no data on the toxicity of C. I. Pigment Yellow 34 or C. I. Pigment Red 104 to terrestrial plants are available. The toxicity of Chromate (CrO 4 2- ) and lead ions (Pb² + ) that may dissociate from the substance was examined. Both ions are taken up by plants. Baumhardt and Welch (1972) detected uptake and translocation of lead in maize plants but determined no effect on seedling germination and plant growth. In a guideline study comparable to OECD 208 seedling emergence and growth of Avena sativa, Lycopersicon esculentum and Lactuca sativa in presence of chromium were investigated. Lactuca sativa was the most susceptible plant species regarding chromium addition; a NOEC (14 d) of 0.35 mg/kg soil dw was determined for Lettuce. For Avena sativa and Lycopersicon esculentum a NOEC of 3.5 and 3.2 respectively was determined. EC50 (14 d) values for all three plant species ranged from mg/kg soil dw (Adema and Henzen 1989). A comparable study was conducted by Pestemer et al. (1987). The study focused on the effect of chromium on seedling emergence and shoot wet weight of several plant species. For Avena sativa an EC50 of 100 mg/kg soil was determined. Thus the EC50 value was appr. 100 times higher compared to the study by Adema and Henzen (1989), however strong reduction of the early growth of Avena sativa was reported by both studies Toxicity to soil micro-organisms The results are summarised in the following table: Table 47. Effects on soil micro-organisms Method Results Remarks Reference Species/Inoculum: soil The community composition of microorganisms from soil samples collected at different distances from a secondary Pb semlter was analysed. Species/Inoculum: soil Organic amendments were added to soil that was previously treated with potassium chromate. CO2 evolution was determined as a measure of microbial activity. In a second experimetn the effect of organic matter on reduction of hexavalent chromium to chromium III and the effect of chromium III on microbial activity was tested. In a third experiment the effect of chromium on the composition of the microorganism communitiy in soil was tested Discussion Total number of microorganisms increased with increasinf distance from the smelter CO2 evolution was slightly decreased at 20 mg/l and decreased further at 50 and 100 mg/l. Chromium VI was rapidly reduced to chromium III, the reduction was increased in treatments with organic amendments. The total number of microorganisms was not affected by chromium addition, however the composition of microbial community was affected. The number of fungi increased whereas the number of actinomycetes decreased. 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Lead 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Potassium chromate Bisessar S (1982) Ueda K, Kobayashi M, Takahashi E (1988) Due to the low solubility of C. I. Pigment Yellow 34 and C. I. Pigment Red 104, significant exposure of soil microorganisms to the substance is not expected. However, since a small fraction of the substance may dissolve and chromium and lead ions may dissociate from the substance, the toxicity of these two ions to soil microorganisms is considered here. The toxicity of chromium to soil microorganisms was evaluated by measuring CSR-PI CHEMICAL SAFETY REPORT 94

107 CO2 evolution of soil exposed to Potassium chromate for 28 days. Furthermore the composition of the microbial community was determined. Chromium did not affect total numbers but caused a shift towards a fungi dominated microbial community. CO2 evolution was decreased by chromium addition. The reduction was detectable at a concentration of 20 mg/l and increased further at higher concentrations (Ueda et al. 1987). A study investigating the community composition of microorganisms in increasing distance from a secondary Pb smelter detected a notable decrease in the total numbers of Bacteria, Actinomycetes and Fungi with decreasing distance from the smelter (Bisessar 1982). Thus both ions trigger a decrease in total numbers and in the overall community composition of soil microorganisms Toxicity to other terrestrial organisms The results are summarised in the following table: Table 48. Effects on terrestrial arthropods Method Results Remarks Reference Application method: oral Ephestia cautella (Lepidoptera) long-term toxicity (laboratory study) Moth eggs were hatched and larvae were reared on a diet mixed with chromium salts Discussion Both chromium salts had little effect on femal fecundity and mean age of male and female animals. Trivalent chromium has no mutagenic effect, whereas hexavalent chromium had mutagnic activity at concentrations of 150 and 200 mg/kg. The level of dominant lethal mutations was increased by the substance Please refer to Chapter Toxicity to soil macro-organisms Atmospheric compartment No relevant information available 2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test substance: Chromic sulfate, Potassium dichromate 7.4. Microbiological activity in sewage treatment systems The results are summarised in the following table: Table 49. Effects on micro-organisms Al-Hakkak ZS and Hussain AF (1990) Method Results Remarks Reference Pseudomonas putida freshwater static Oxygen consumption according to ROBRA EC10 (30 min): 6390 mg/l test mat. (nominal) based on: respiration rate EC50 (30 min): > mg/l test mat. (nominal) based on: respiration rate 2 (reliable with restrictions) weight of evidence experimental result Test material (IUPAC name): lead chromate molybdate sulfate red BASF AG (1988b) Pseudomonas putida EC10 (30 min): 390 mg/l 2 (reliable with BASF AG (1988c) CSR-PI CHEMICAL SAFETY REPORT 95

108 Method Results Remarks Reference freshwater static Oxygen consumption according to ROBRA Discussion test mat. (nominal) based on: respiration rate EC50 (30 min): > mg/l test mat. (nominal) based on: respiration rate restrictions) weight of evidence experimental result Test material (IUPAC name): lead chromate molybdate sulfate red The results of two toxicity tests on respiration inhibition induced by C. I. Pigment Red 104 in Pseudomonas putida indicate that the substance does not inhibit the activiy of microorganisms. The EC50 determined in both sutdies was > mg/l (BASF AG, 1988) Non compartment specific effects relevant for the food chain (secondary poisoning) Toxicity to birds Data waiving Information requirement: Toxicity to birds Reason: other justification Justification: long-term or reproductive toxicity tests on birds do not need to be conducted due to the facts that - a mammalian dataset is available - direct exposure to soil is unlikely Toxicity to mammals No relevant information available 7.6. PNEC derivation and other hazard conclusions To perform the environmental risk assessment, the pigment and its transformation products were taken into account. PNECs were therefore derived for Lead, Chromium (VI) and C.I. Pigment Red 104, and summarized in the tables below. Table 50. Hazard assessment conclusion for the environment - Lead Compartmen t Freshwater Hazard conclusion PNEC aqua (freshwater): 2.7 µg/l Remarks/Justification Assessment factor: 3 Extrapolation method: statistical extrapolation Lead: Statistical extrapolation has been used for the PNEC derivation as the database for lead fulfills the requirements stipulated in the REACH guidance with respect to input data, taxonomic groups, number of data, treatment of multiple data for the same species and fit to distribution. The derived HC5 was reported as 8.0 µg/l based on species means. AF of 3 was applied to the HC5 taking into account the remaining uncertainty. There are some limitations to the data set as discussed in the EU RAR. Use CSR-PI CHEMICAL SAFETY REPORT 96

109 Compartmen t Hazard conclusion Marine water PNEC aqua (marine water): 0.27 µg/l Remarks/Justification of AF of 3 and the HC5 of 8.0 µg/l results in a PNEC of 2.7 µg/l for dissolved lead. In the vrar PNEC of 4.0 ug/l dissolved lead was used as well in the risk characterisation due to the use of AF of 2. Assessment factor: 30 Extrapolation method: statistical extrapolation Intermittent releases to water Sediments (freshwater) PNEC aqua (intermittent releases): 2.7 µg/l PNEC sediment (freshwater): 174 mg/kg sediment dw Lead: A PNEC for the marine environment was not proposed in the vrar. A conservative approach has been selected for the purpose of this hazard assessment using PNEC freshwater with AF 10. For a tier 2 assessment, an indicative HC5-50 value of 6.1 ug/l dissolved lead was derived from the combined saltwater freshwater dataset in the vrar. This dataset fulfilled the requirements outlined in the REACH guidance for the use of a sensitivity distribution method with the main uncertainty relating to the limited availability of marine ecotoxicity data as discussed in the vrar. The REACH guidance recommends an AF between 1 and 5 to be applied on the HC5-50. Application of AF 5 to take into account this uncertainty would result in PNEC marine water of 1.2 ug/l. Assessment factor: 3 Extrapolation method: statistical extrapolation Lead: PNEC for intermittent releases was not derived in the vrar. Therefore the PNEC derived for the aquatic freshwater compartment has been used as well as PNEC for intermittent releases. It should be realized that this is a worst case approach as this PNEC is based on long term studies, whereas in the case of intermittent releases the environmental exposure will be limited in time. Assessment factor: 3 Extrapolation method: statistical extrapolation Sediments PNEC sediment (marine water) (marine water): 17.4 mg/kg sediment dw Lead: The PNEC is based on the species sensitivity distribution of long term experimental data for sediment organisms covering various endpoints, habitats and feeding habits (dry weight normalised). HC5-50% of 522 mg/kg dw was derived from the SSD on the basis of long term sediment toxicity data (expressed as total lead). This HC5 and AF of 3 resulted in the PNEC sediment of 174 mg total lead/kg sediment dw. Alternatively, the most conservative PNEC derived in vrar was based on the lowest long term NOEC and an assessment factor. This PNEC was not used in the risk characterisation of the vrar - it was at the level of the background concentrations: PNEC = 57.3 mg/kg dw, based on lowest long term NOEC and AF of 10. Assessment factor: 30 Extrapolation method: statistical extrapolation Sewage PNEC STP: 0.1 mg/l Assessment factor: 10 Lead: PNEC sediment (marine water) was not discussed in the vrar. In the absence of data for marine sediment species the default approach of the REACH guidance has been used. An additional factor of 10 has been applied to the PNECsediment (freshwater) to take into account the larger species diversity in the marine environment. Comparison of freshwater and marine toxicity data revealed that there were no indications of marine species being consistently more sensitive than fresh water species. The difference in metal chemistry in the marine and freshwater environment has not been taken into account. Alternatively, CSR-PI CHEMICAL SAFETY REPORT 97

110 Compartmen t treatment plant Hazard conclusion Remarks/Justification Extrapolation method: assessment factor Soil PNEC soil: 166 mg/kg soil dw Lead: The PNEC was derived from the lowest observed NOEC/L(E)C10 in the database for micro-organisms in STPs. The NOEC of 1.06 mg/l dissolved Pb for inhibition of respiration and AF of 10 resulted in PNEC = 0.1 mg/l for dissolved lead in effluent. Assessment factor: 2 Extrapolation method: statistical extrapolation Air Secondary poisoning Lead: Reliable experimental terrestrial toxicity data were available for plants (n=18), invertebrates (n=12) and microflora (n=18). A leaching/aging correction factor of 4.2 was applied to the NOECs determined in laboratory studies to take into account difference in Pb toxicity between spiked soils and field contaminated soils. The log-normal distribution of the SSD (based on species mean) resulted in HC5 of 333 mg/kg. The PNEC of 166 mg/kg was derived from the HC5 and AF of 2. No hazard identified: Lead: Effects due to exposure of organisms to lead in air, airborne particulates and aerosols are not expected because of the low atmospheric emissions from the production and uses of lead in the vrar. This applies as well to the emissions of lead from the production and uses of C.I. pigment Red 104 and C.I. Pigment Yellow 34. Contribution to abiotic effects such as global warming, ozone depletion in the stratosphere, ozone formation in the troposphere or acidification is not expected. PNEC oral: 0.5 mg/kg food Assessment factor: 300 Lead: Application of AF of 300 to the lowest NOEC for mammals (150 mg/kg food, Rattus sp., ref Kao & Forbes, 1973)) resulted in PNECoral of 0.5 mg/kg for mammals. It should be noted that the latter value is in the range of natural background concentrations. The SCHER also discusses the use of lead concentrations in blood and an SSD approach but concludes that more work is required before a proper assessment of the risk of secondary poisoning could be conducted. Table 51. Hazard assessment conclusion for the environment Chromium (VI) Compartmen t Freshwater Hazard conclusion PNEC aqua (freshwater): 3.4 µg/l Remarks/Justification Assessment factor: 3 Extrapolation method: statistical extrapolation Chromium(VI): Statistical extrapolation was used for the PNEC derivation as the database for chromium (VI) fulfills the requirements stipulated in the REACH guidance with respect to input data, taxonomic groups, number of data, treatment of multiple data for the same species and fit to distribution. The derived HC5-50% was reported as 10.2 µg/l. AF of 3 was applied to the HC5 taking into account that there are some limitations to the data set as discussed in the EU RAR. The PNEC refers to the added dissolved concentration of Cr (VI). Chromium(III): PNECaqua(freshwater = 4.7 µg/l, Extrapolation method. Since acute and long term toxicity data are available for the three taxonomic groups (fish, invertebrates, algae), AF of 10 has been applied to the lowest available NOEC (invertebrates). The PNEC of 4.7 µg/l applies to soft water. A PNEC of 13 µg/l would be derived from the NOEC determined in the same invertebrate study at a hardness of 100 mg/l, suggesting that CSR-PI CHEMICAL SAFETY REPORT 98

111 Compartmen t Hazard conclusion Marine water PNEC aqua (marine water): 3.4 µg/l Remarks/Justification toxicity may be reduced at greater hardness levels. The PNEC refers to the added dissolved water concentrations. It should be noted that water soluble forms of chromium (III) have been tested in the experimental studies, whereas chromium (VI) will be reduced to forms of chromium (III) with limited water solubility associated predominantly with particulates in the environment. Assessment factor: 3 Extrapolation method: statistical extrapolation Intermittent releases to water Sediments (freshwater) PNEC aqua (intermittent releases): 3.4 µg/l PNEC sediment (freshwater): 0.7 mg/kg sediment dw Chromium(VI): The comparison of the toxicity data for freshwater and saltwater species in the EU RAR revealed that freshwater species are more sensitive than saltwater species. At very low salinity (< 2%) the sensitivity appears to become comparable with that of freshwater species. Therefore no separate PNEC was proposed for marine species in the EU RAR. The PNEC for freshwater has been used as a worst case for the marine environment as well. Chromium(III): PNECaqua-marine = 4.7 ug/l. PNEC was not derived separately for marine species in the EU RAR. The PNEC freshwater (soft water) of chromium (III) is considered to be protective for the marine environment as well because the available data suggest that chromium (III) is less toxic in hard water and saltwater than in soft water. Assessment factor: 3 Extrapolation method: statistical extrapolation Chromium(VI): A separate PNEC for intermittent releases was not proposed in the EU RAR. Therefore the PNEC derived for the aquatic freshwater compartment has been used as well as PNEC for intermittent releases. It should be realized that this is a worst case approach as this PNEC is based on long term studies, whereas in the case of intermittent releases the environmental exposure will be limited in time. Chromium(III): PNECaqua-intermittent = 4.7 ug/l. A separate PNEC for intermittent releases was not proposed in the EU RAR. Therefore the PNEC derived for the aquatic freshwater compartment has been used as well as PNEC for intermittent releases. It should be realized that this is a worst case approach as this PNEC is based on long term studies, whereas in the case of intermittent releases the environmental exposure will be limited in time. Extrapolation method: partition coefficient Chromium(VI): PNEC sediment (freshwater) is derived from PNEC freshwater, dissolved (3.4 µg/l) using the equilibrium partitioning method and the experimentally determined Ksuspended matter. For the calculations a distinction has been made between the Ksuspended matter for acidic conditions (Kp 500) and the Kpsuspended matter for other conditions (Kp 5000). Hence two PNECs have been derived as representative for different environmental conditions: PNECsediment-freshwater-acid = 1.5 mg/kg ww ~ 7 mg/kg dw and PNECsediment-freshwater-other conditions = 0.15 mg/kg ww ~ 0.7 mg/kg dw Chromium(III): PNECsediment (freshwater) = 31 mg/kg ww for acidic conditions and 307 mg/kg ww for other conditions. Converted to dry weight this is 143 mg/kg dw for acidic conditions and 1412 mg/kg dw for other conditions. PNEC sediment (fresh water) is derived from PNEC freshwater, dissolved (4.7 µg/l) using the equilibrium partitioning method and the experimentally determined Ksuspended matter. For the calculations a distinction has been made between the Ksuspended matter CSR-PI CHEMICAL SAFETY REPORT 99

112 Compartmen t Hazard conclusion Sediments PNEC sediment (marine water) (marine water): 0.7 mg/kg sediment dw Sewage treatment plant PNEC STP: 0.21 mg/l Remarks/Justification for acidic conditions (Kp 7500) and the Kpsuspended matter for neutral and alkaline conditions (Kp 75000). Hence two PNECs have been derived as representative for different environmental conditions. Chromium(VI): The comparison of the toxicity data for freshwater and saltwater species in the RAR revealed that freshwater species are more sensitive than saltwater species. At very low salinity (< 2%) the sensitivity appears to become comparable with that of freshwater species. Therefore no separate PNEC was proposed for marine species in the EU RAR. Here we use the PNEC freshwater sediment for other conditions for the marine environment as these conditions reflect the marine environment as well. (Chromium(III): PNECsediment-marine = 307 mg/kg ww ~ 1412 mg/kg dw. PNEC was not derived separately for marine species in the EU RAR. The PNEC freshwater sediment for neutral and alkaline conditions has been selected as being most representative of salt water. Assessment factor: 1 Extrapolation method: assessment factor Soil PNEC soil: mg/kg soil dw Air Secondary poisoning Chromium(VI): PNEC was not derived separately for marine species in the EU RAR. The PNEC freshwater sediment for neutral and alkaline conditions has been selected as being most representative of salt water. Chromium(III): PNEC = 10 mg/l, Extrapolation with assessment factor 1. Chromium III seems to be much less toxic to micro-organisms than Chromium VI. Some growth inhibition was observed at test concentrations of 100 mg/l, while growth rates higher than controls were observed for some species at test concentrations of 10 mg/l for Chromium III. In the absence of further relevant data, a PNEC of 10 mg/l was used in the EU RAR. Assessment factor: 10 Chromium(VI): The PNEC is based on experimental data for terrestrial organisms. Long term terrestrial toxicity tests are available for plants, earthworms and soil processes (soil micro-organisms) with plants being the most sensitive organisms. The PNEC was derived from the lowest NOEC plant of around 0.35 mg/kg dw of soil for plants and AF of 10. Chromium(III): PNECsoil = 3.2 mg/kg dw. Extrapolation method with AF 10. The PNEC is based on experimental data for terrestrial organisms. Long term terrestrial toxicity tests are available for plants, earthworms and soil processes (soil micro-organisms) with plants being the most sensitive organisms. The PNEC was derived from the lowest NOEC earthworm of 32 mg/kg dw of soil and AF of 10. It should be noted that the PNEC for chromium (III) is based on experimental studies where a highly soluble (and thus bio available) form of chromium III has been tested, whereas chromium VI is likely to be reduced to forms chromium (III) with low solubility and bioavailability. No hazard identified: Chromium(VI) and Chromium(III): Effects due to exposure of organisms to chromium in air, airborne particulates and aerosols are not expected because of the low atmospheric emissions arising from the production and uses of chromium according to the EU RAR. This applies as well to the emissions of chromium arising from the uses of C.I. Pigment Yellow 34 and C.I. Pigment Red 104. Contribution to abiotic effects such as global warming, ozone depletion in the stratosphere, ozone formation in the troposphere or acidification is not expected. PNEC oral: 17 mg/kg food Assessment factor: 10 Chromium(VI): The very low bioconcentration factors for fish (BCF CSR-PI CHEMICAL SAFETY REPORT 100

113 Compartmen t Hazard conclusion Remarks/Justification usually around 1 L/kg) do not trigger the evaluation of secondary poisoning. However since chromium (VI) uptake from water, sediment and soil has been reported for a wide range of organisms, the PNECoral derived in the EU RAR has been used here as well. The PNEC is based on the lowest available chronic NOAEL (20 mg Cr VI/kg body weight/ day for effects on the testes in mice by exposure via oral gavage) and the lowest available chronic LOAEL (20 mg Cr VI/kg body weight/ day for developmental effects in mice via the drinking water route). Converting this value of 20 mg/kg with conversion factor 8.3 gives a NOECfood of 166 mg/kg. Application of an AF of 10 results in the PNECoral of 16.6 mg chromium VI / kg food. Chromium(III): PNEC oral was not derived in EU RAR (2005) because of the absence of a review of mammalian data for chromium (III). In the toxicity studies used for the PNECoral for chromium (VI), organisms were exposed through gavage or drinking water. Therefore little conversion of chromium (VI) to chromium (III) was expected (according to the EU RAR). Table 52. Hazard assessment conclusion for the environment C.I. Pigment Red 104 Compartmen t Freshwater Hazard conclusion PNEC aqua (freshwater): 0.1 mg/l Remarks/Justification Assessment factor: 1000 Extrapolation method: assessment factor Marine water PNEC aqua (marine water): 0.01 mg/l The calculation of the PNEC aqua (freshwater) is based on the nominal results (loading) for C.I. Pigment Red 104 obtained in a study testing the acute toxicity to Daphnia magna (EC50 >100 mg/l). Assessment factor: Extrapolation method: assessment factor Intermittent releases to water PNEC aqua (intermittent releases): 1 mg/l The calculation of the PNEC aqua (marine waters) is based on the nominal results (loading) for C.I. Pigment Red 104 obtained in a study testing the acute toxicity to Daphnia magna (EC50 >100 mg/l). Assessment factor: 100 Extrapolation method: assessment factor Sediments (freshwater) No data available: testing technically not feasible Sediments No data available: (marine water) testing technically not feasible Sewage treatment plant PNEC STP: 1000 mg/l The calculation of the PNEC aqua (freshwater) is based on the nominal results (loading) for C.I. Pigment Red 104 obtained in a study testing the acute toxicity to Daphnia magna (EC50 >100 mg/l). The risk characterisation will be performed for lead. The risk characterisation will be performed for lead. Assessment factor: 10 Extrapolation method: assessment factor Soil No data available: testing technically The calculation of the PNEC STP is based on an EC50 >10000 assessed in toxicity testing using Pseudomonas putida as test organism. The risk characterisation will be performed for lead CSR-PI CHEMICAL SAFETY REPORT 101

114 Compartmen t Air Secondary poisoning Hazard conclusion not feasible No hazard identified: Remarks/Justification Due to the fact that the substance is not bioaccumulative, it is unlikely that a secondary poisoning risk will occur by this substance. Therefore and for reasons of animal welfare, the assessment of secondary poisoning of this substance will be based on mammalian data. Environmental classification justification C.I. Pigment Red 104 is not acutely toxic to aquatic organisms, as an inorganic substance not biodegradable and has no relevant bioaccumulation potential. Nevertheless the official EU classification which has been derived from lead and chromate toxicities accounts to N, R50/53 (Aquatic Acute 1 H400, Aquatic Chronic 1 H410). In order to avoid discrepancies the official classification will be maintained. General discussion In the environment C. I. Pigment Yellow 34 and C. I. Pigment Red 104 may release small amounts of Pb 2+ and CrO 4 2- under certain conditions. The PNECs for lead have been extracted from the Voluntary RAR (vrar) of lead and lead compounds (2008). The lead vrar was produced by industry on the basis of the principles applied in the Existing Substances Regulation. The lead vrar has been reviewed by the Technical Committee on New and Existing substances (TC NES) in In the environment C. I. Pigment Yellow 34 and C. I. Pigment Red 104 may release small amounts of Pb 2+ and CrO 2-4 under certain conditions. The hexavalent chromates yield dissolved chromate and dichromate ions in the environment, with the equilibrium depending on ph. Since chromium (VI) can be reduced to chromium (III) in the environment, the possible effects of chromium (III) have been addressed as well. This is especially important for the soil and sediment compartment where the majority of chromium will be converted to chromium (III). It should be noted that chromium (III) is an essential element in animal nutrition and for some microbes, whereas it is not considered essential for plant growth. The toxicity of chromium (III) to aquatic organisms is briefly summarised in the EU RAR (2005). From the available data, it can be seen that chromium (III) appears generally to be less toxic than chromium (VI) in waters of medium hardness (>50 mg CaCO3). The PNECs for chromium have been extracted from the EU Risk Assessment Report (RAR) on chromium trioxide, sodium chromate, sodium dichromate, ammonium dichromate and potassium dichromate (2005). The chromium RAR was produced in the context of EU Existing Substances Regulation EEC no 793/93 by the UK Rapporteur, agreed by the Technical Committee on New and Existing substances and published by the European Communities in CSR-PI CHEMICAL SAFETY REPORT 102

115 8. PBT AND vpvb ASSESSMENT 8.1. Assessment of PBT/vPvB Properties PBT/vPvB criteria and justification Not applicable Summary and overall conclusions on PBT or vpvb properties Overall conclusion: PBT assessment does not apply. Justification: C. I. Pigment Red 104 is an inorganic substance and therefore PBT and vpvb criteria do not apply to the substance CSR-PI CHEMICAL SAFETY REPORT 103

116 9. EXPOSURE ASSESSMENT (and related risk characterisation) 9.0. Introduction Overview of uses and Exposure Scenarios Tonnage information: Assessed tonnage: tonnes/year based on: 3000 tonnes/year imported This tonnage is the total combined tonnage for C.I. Pigment Yellow 34 and C.I. Pigment Red 104, as the environmental assessment for these substances is conducted in the same way and should be combined to give a complete overview of the exposure and risk characterisation for these substances. In order to assess the aggregated worker health risk associated with the use of the pigment in the socio-economic analysis (SEA) the tonnage of 900 tonnes per year was used, as this is the tonnage of C.I. Pigment Red 104 for which authorization is requested. This is not relevant for the CSA of the substance as a CSA has a clear focus on the health impact for individual workers. For an individual worker the amount of substance handled per day, the concentration of the pigments in mixtures and the particle size of exposure determines the health effect and not the total tonnage handles within the EU. However as the SEA refers to this CSR, the information was included in Table 53. Tonnage used for the environmental assessment: Paints and coatings (PC 9a: Coatings and Paints, Thinners, paint removers): 1200 tonnes/year for the environmental assessment (40% of the total tonnage of C.I. Pigment Yellow 34 and C.I. Pigment Red 104, which is 3000 tonnes/year combined). For the environmental assessment it is assumed that the entire volume is used in each step of the life cycle stage. This is the most conservative approach. Colouration of plastic or plasticised articles (PC 32: Polymer Preparations and Compounds; PC 34: Textile dyes, finishing and impregnating products; including bleaches and other processing aids): 1800 tonnes/year for the environmental assessment (60% of the total tonnage of C.I. Pigment Yellow 34 and C.I. Pigment Red 104, which is 3000 tonnes/year combined). For the environmental assessment it is assumed that the entire volume is used in each step of the life cycle stage, except for the professional use stage (500 tonnes/year). This is in general the most conservative approach. Tonnage used for the aggregated worker risk (SEA monetization): Paints and coatings For the worker assessment in the formulation stage, 360 tonnes/year was used to determine the aggregated risk (40% of the total tonnage of C.I. Pigment Red 104, which is 900 tonnes/year). For the human health assessment in the SEA an assessment was made of which volume will be used in which life cycle stage, based on the information gathered in the supply chain. It is assumed that 80% of the volume can be assigned to industrial use and 20% to professional use. For the service life, 10% of the formulated volume is assumed to be serviced per year. 20% of this volume is serviced in an industrial setting and 80% in a professional setting. Plastics For the worker assessment in the formulation stage, 640 tonnes/year was used to determine the aggregated risk (60% of the total tonnage of C.I. Pigment Red 104, which is 900 tonnes/year). For the human health assessment in the SEA an assessment was made of which volume will be used in which life cycle stage, based on the information gathered in the supply chain. It is assumed that 80% of the volume can be assigned to industrial use and 20% to professional use. For the service life, 10% of the formulated volume is assumed to be serviced per year. 20% of this volume is serviced in an industrial setting and 80% in a professional setting. The table below lists all the exposure scenarios (ES) assessed in this CSR, including the applicable volumes. Table 53. Overview of exposure scenarios and contributing scenarios CSR-PI CHEMICAL SAFETY REPORT 104

117 Identifiers Market Sector Titles of exposure scenarios and the related contributing scenarios Tonnage used Tonnage in used in environmental assessment assessment of aggregate (tonnes per worker risk year) (tonnes per year) ES1 - F1 PC 9a Formulation - Distribution and mixing pigment powder in an industrial environment into solvent-based paints for non-consumer use. Pigment choice depends on product specifications on visibility, shade and colour, durability, other requirements and Regulations. - Distribution and mixing pigment powder in an industrial environment into solvent-based paints for non-consumer use (ERC 2) - Delivery, storage and handling of closed bags with pigment powder (PROC 3) - Pigment powder quality control / lab work (PROC 15) - Manual dosing of pigment powder (PROC 8a) - Automated dosing of pigment powder (PROC 8b) - Re-packaging of pigment powder (PROC 9) - Mixing of pigment paste (PROC 5) - Storage of pigment paste / Transfer of pigment paste through closed piping (PROC 2) - Manual cleaning / scraping of mixing vessels, equipment and lids (PROC 21) - Cleaning of vessel with solvent (PROC 10) - Pigment paste testing by smearing (PROC 10) - Pigment paste charging/discharging by gravity or manual handling (PROC 8a) - Pigment paste charging/discharging using a dedicated installation (PROC 8b) - Pigment paste filling into drums/cans at a filling line (PROC 9) - Mixing colour paste in closed drum mixing machine with automated dosing of paste (PROC 2) - Mixing colour paste into paint in closed mixing vessel (PROC 3) - Pigment paint filling into drums/cans at a filling line (PROC 9) - Pigment paint charging/discharging using a dedicated installation (PROC 8b) - Equipment cleaning: scraping and brushing (PROC 10) - Dried pigment paint cleaning (PROC 21) - Spray testing of pigment paint in industrial booth (PROC 7) - Pigment paint testing by brushing/rolling (PROC 10) - Pigment paste or paint laboratory operations (PROC 15) ES2 - IW1 PC 9a Use at industrial site - Industrial application of paints on metal surfaces (machines, vehicles, CSR-PI CHEMICAL SAFETY REPORT 105

118 Identifiers Market Sector Titles of exposure scenarios and the related contributing scenarios structures, signs, road furniture, coil coating). Pigment choice is governed by end product specifications on visibility, colour, durability, other technical requirements and Regulations. - Industrial application of paints on metal surfaces (machines, vehicles, structures, signs, road furniture, coil coating) (ERC 5) - Laboratory handling of pigment paste and/or paints (PROC 15) - Handling of packaged colour paste and/or paint, including distribution (PROC 2) - Mixing colour paste with paint in closed mixing machine with automated dosing of paste (PROC 3) - Equipment cleaning: scraping, brushing and wiping (PROC 10) - Dried pigment paste and/or paint cleaning (PROC 21) - Mixing of paste and/or coating with extra solvents or additives before use (PROC 5) - Filling of equipment with pigment paint (PROC 8a) - Filling of spray equipment with pigment paints in dedicated settings (PROC 8b) - Transfer of pigment paint to/from drums/cans e.g. at a filling line before application (PROC 9) - Automated pigment paint spray application in an industrial booth (PROC 7) - Manual pigment paint spray application in an industrial booth (PROC 7) - Handling and manipulation of dried painted articles (PROC 21) - Pigment paint testing by brushing/rolling (PROC 10) - Pigment paint application and heat curing (PROC 6) Related subsequent service life: ES4; ES5 Tonnage used Tonnage in used in environmental assessment assessment of aggregate (tonnes per worker risk year) (tonnes per year) ES3 - PW1 PC 9a Use by professional worker - Professional, non-consumer application of paints on metal surfaces (machines, vehicles, structures, signs, road furniture) or as road marking. Pigment choice is governed by requirements on visibility, colour, durability, technical performance and Regulations Professional, non-consumer application of paints on metal surfaces (machines, vehicles, structures, signs, road furniture) or as road marking (ERC 8f) - Handling of packaged colour paste and/or paint, including distribution (PROC 2) - Dosing of colour paste into paint premix (PROC 9) CSR-PI CHEMICAL SAFETY REPORT 106

119 Identifiers Market Sector Titles of exposure scenarios and the related contributing scenarios - Mixing colour paste with paint in closed mixing machine with automated dosing of paste (PROC 3) - Filling of spray equipment with colour paints (PROC 9) - Pigment paint spray application in a make-shift booth on location (PROC 11) - Pigment paint spray application in a professional spray booth (PROC 11) - Mixing of pigment paint in an open vessel (PROC 5) - Pigment paint application by rolling/brushing (PROC 10) - Cleaning of wet pigment paint on equipment by wiping and brushing (PROC 10) - Cleaning of dried pigment paint on equipment by wiping, brushing, scraping etc. (PROC 21) - Manipulation of pigment painted articles (dry) (PROC 21) Related subsequent service life: ES4; ES5 Tonnage used Tonnage in used in environmental assessment assessment of aggregate (tonnes per worker risk year) (tonnes per year) ES4 - SL-IW1 PC 9a Service life (worker at industrial site) - Service life of coated articles. Performance and longevity depend on the pigment quality for bright lasting colours improving visibility and safety, light and weather fastness (durability), chemical fastness, impact resistance and heat stability. - Sanding of painted/coated articles (ERC 12b) - Cutting painted metal sheet (dry) (PROC 21) - Sanding of dried paint on machines, vehicles, other metal articles etc. (PROC 24) - Welding, torchcutting of painted metal (dry) (PROC 25) ES5 - SL-PW1 PC 9a Service life (professional worker) - Service life of 1200 coated articles. Performance and longevity depend on the pigment quality for bright lasting colours improving visibility and safety, light and weather fastness (durability), chemical fastness, impact resistance and heat stability. - Leaching from painted metal surfaces (machines, vehicles, structures, signs, road furniture, coil coating) during service life (ERC 10b) - Sanding of painted/coated articles (ERC 10b) - Leaching from painted road marking during service life (ERC 10b) - Cutting painted metal sheet (dry) (PROC 21) - Sanding of dried paint on machines, vehicles, other articles etc. (PROC 24) - Welding, torchcutting of painted metal (dry) (PROC 25) CSR-PI CHEMICAL SAFETY REPORT 107

120 Identifiers ES6 - F2 Market Sector PC 32; PC 34 Titles of exposure scenarios and the related contributing scenarios Tonnage used Tonnage in used in environmental assessment assessment of aggregate (tonnes per worker risk year) (tonnes per year) Formulation - Distribution and mixing pigment powder in an industrial environment into liquid or solid premix to colour plastic/plasticised articles. Pigment choice depends on product specifications on visibility, colour, heat stability, durability and Regulations. - Distribution and mixing pigment powder in an industrial environment into a premix or pre-compound to add colour to plastic or plasticised articles (ERC 3) - Delivery, storage and handling of closed paper bags with pigment powder (PROC 3) - Pigment powder quality control / lab work (PROC 15) - Manual dosing of pigment powder (PROC 8a) - Automated dosing of pigment powder (PROC 8b) - Mixing of pigment with resins and additives to form a liquid pre-mix/pre-compound (PROC 5) - Storage of premix/pre-compound / Transfer of pre-mix/pre-compound through closed piping (PROC 2) - Premix/pre-compound charging/discharging by gravity or manual handling (PROC 8a) - Premix/pre-compound charging/discharging using a dedicated installation (PROC 8b) - Premix/pre-compound filling into drums/cans at a filling line (PROC 9) - Manual cleaning / scraping of mixing vessels, equipment and lids (PROC 21) - Cleaning of vessel with resin (PROC 10) - Premix/pre-compound quality control / lab work (PROC 15) - Production of coloured plastic granules or masterbatch by extrusion, compression and/or pelletisation (PROC 14) - Mixing pigment powder or premix/pre-compound into matrix in closed mixing vessel (PROC 3) - Production of plastic articles by extrusion, injection moulding and other processes (PROC 14) - Quality control / lab work with coloured plastics (PROC 15) - Handling of articles and single coloured granules (PROC 21) - Handling of mixed coloured granules and articles (PROC 21) - Transfer of articles and single coloured granules (PROC 8a) - Transfer of articles and single coloured granules CSR-PI CHEMICAL SAFETY REPORT 108

121 Identifiers ES7 - IW2 Market Sector PC 32; PC 34 Titles of exposure scenarios and the related contributing scenarios (PROC 8b) - Transfer of mixed coloured granules and articles (PROC 8a) - Transfer of mixed coloured granules and articles (PROC 8b) - Pigment powder dosing before mixing (PROC 8b) - Mixing of pigment powder with other solid additives (PROC 3) - Filling of small packages with pigment powder (PROC 9) - Manual handling of pigment contained in small sealed plastic bags (<1 kg) (PROC 1) - Pigment powder manual cleaning, wiping, scraping etc. (PROC 19) Tonnage used Tonnage in used in environmental assessment assessment of aggregate (tonnes per worker risk year) (tonnes per year) Use at industrial site - Use of colour premixes and pre-compounds to colour plastic or plasticised articles for non-consumer use. Pigment choice depends on product specifications on visibility, colour, heat stability, chemical fastness, durability and Regulations. - Use of colour premixes and pre-compounds to colour plastic or plasticized articles for non-consumer use (ERC 5) - Delivery, storage and handling of coloured plastic granules (PROC 3) - Delivery, storage and handling of packed plastic premix or pre-compound (PROC 3) - Transfer of articles and single coloured granules (PROC 8a) - Transfer of articles and single coloured granules (PROC 8b) - Transfer of mixed coloured granules and articles (PROC 8a) - Transfer of mixed coloured granules and articles (PROC 8b) - Charging/discharging of coloured plastic granules (PROC 9) - Mixing coloured plastic granules in closed mixing vessel (PROC 3) - Production of plastic articles by extrusion and injection moulding or other processes (PROC 14) - Charging/discharging of coloured plastic premix or pre-compound (PROC 8a) - Charging/discharging of coloured plastic premix or pre-compound (PROC 9) - Roll application and heat curing of coloured plastic paste (PROC 6) - Handling and manipulation of pigment plastic articles and plastic coated textiles (PROC 21) Related subsequent service life: ES9; ES CSR-PI CHEMICAL SAFETY REPORT 109

122 Identifiers ES8 - PW2 ES9 - SL-IW2 ES10 - SL-PW2 Market Sector PC 32; PC 34 PC 32; PC 34 PC 32; PC 34 Titles of exposure scenarios and the related contributing scenarios Tonnage used Tonnage in used in environmental assessment assessment of aggregate (tonnes per worker risk year) (tonnes per year) Use by professional worker - Use of colour premixes and pre-compounds in the application of hotmelt road marking. Pigment choice depends on end product specifications on visibility & night time reflectivity, colour, heat stability, durability, chemical fastness and Regulations. - Use of colour premixes and pre-compounds in the application of hotmelt road marking (ERC 8f) - Charging/discharging premix or pre-compound (PROC 8a) - Storage and mixing of plastic compounds in an open vessel before application (PROC 5) - Application of hotmelt road marking (plastic compound) to road pavement (PROC 10) - Handling and manipulation of coloured road marking (PROC 21) - High energy manipulation/removal of coloured road marking using abrasive techniques like grinding, drilling or sanding (PROC 24) Related subsequent service life: ES9; ES10 Service life (worker at industrial site) - Service life of coloured plastic or plasticised articles. Performance and longevity depend on pigment quality, for bright lasting colours improving visibility and safety, heat stability, durability, other technical specifications and Regulations. - Industrial service life of coloured plastic or plasticised articles, including hotmelt road marking (ERC 12a) - Handling and manipulation of pigment plastic articles, plastic coated textiles and coloured road marking (PROC 21) - High energy manipulation of pigment plastic articles, plastic coated textiles and coloured road marking using abrasive techniques like mechanical cutting, grinding, drilling or sanding (PROC 24) Service life (professional worker) - Service life of coloured plastic or plasticised articles. Performance and longevity depend on pigment quality, for bright lasting colours improving visibility and safety, heat stability, durability, other technical specifications and Regulations. - Service life of coloured plastic and plasticised articles, including hotmelt road marking (leaching) (ERC 10b) - Removal of hotmelt road marking (ERC 10b) - Handling and manipulation of pigment plastic articles, plastic coated textiles and coloured road marking (PROC 21) CSR-PI CHEMICAL SAFETY REPORT 110

123 Identifiers Market Sector Titles of exposure scenarios and the related contributing scenarios - High energy manipulation of pigment plastic articles, plastic coated textiles and coloured road marking using abrasive techniques like mechanical cutting, grinding, drilling or sanding (PROC 24) Tonnage used Tonnage in used in environmental assessment assessment of aggregate (tonnes per worker risk year) (tonnes per year) Manufacture: M-#, Formulation: F-#, Industrial end use at site: IW-#, Professional end use: PW-#, Consumer end use: C-#, Service life (by workers in industrial site): SL-IW-#, Service life (by professional workers): SL-PW-#, Service life (by consumers): SL-C-#.) Manufacture: M-#, Formulation: F-#, Industrial end use at site: IW-#, Professional end use: PW-#, Consumer end use: C-#, Service life (by workers in industrial site): SL-IW-#, Service life (by professional workers): SL-PW-#, Service life (by consumers): SL-C-#.) Introduction to the assessment Environment Scope and type of assessment The scope of exposure assessment and type of risk characterisation required for the environment are described in the following table based on the hazard conclusions presented in section 7. Table 54. Type of risk characterisation required for the environment Protection target Type of risk characterisation Hazard conclusion (see section 7) Freshwater Quantitative PNEC aqua (freshwater) = 2.23 µg/l Sediment (freshwater) Quantitative PNEC sediment (freshwater) = 174 mg/kg sediment dw Marine water Quantitative PNEC aqua (marine water) = 0.27 µg/l Sediment (marine water) Quantitative PNEC sediment (marine water) = 17.4 mg/kg sediment dw Sewage treatment plant Quantitative PNEC STP = 0.1 mg/l Air Not needed No hazard identified Agricultural soil Quantitative PNEC soil = 162 mg/kg soil dw Predator Not conducted (see explanation below) No or insufficient data available at present Comments on assessment approach: After release of C.I. Pigment Yellow 34 and/or C.I. Pigment Red 104 into the environment, a small fraction consisting of chromate ions (CrO 4 2- ) and lead ions (Pb 2+ ) will dissociate from the solids and partition to the environmental compartments. Both lead and chromium may bioaccumulate in fish and other organisms. The relatively high Kd-values for lead and chromium indicate that both moieties may adsorb to suspended particles and soil. Chromium and lead CSR-PI CHEMICAL SAFETY REPORT 111

124 The metals chromium and lead are ubiquitously present in the environment due to both natural and anthropogenic processes, resulting in background concentrations in all environmental compartments including biota. The levels of these metals in the environment can vary widely due to differences in natural background concentrations and historical emissions. Different approaches dealing with background concentrations have been used in the EU RAR for chromium and the vrar for lead. The EU RAR for chromium focussed on the added contribution of industrial activities. The measured data indicated a large spread in ambient environmental concentrations and it was judged that a plausible representative background concentration could not be derived. Therefore the added risk approach was used as a pragmatic solution to have an understanding of the importance of the industrial emissions. With the added risk approach, Clocal (modelled according to the REACH guidance/euses) is compared to 'PNECadded' derived in the EU RAR for chromium, thus the risk characterisation is based on the ratio Clocal/PNECadded. In the EU RAR for chromium, a risk characterisation for the regional scale has not been performed. The risk characterisation in the vrar for lead was based on the conventional comparison of PEC with PNEC. Alternative higher tier approaches were elaborated in the vrar as well including for example a bioavailability correction for sediment (use of AVS/SEM concept). C.I. Pigment Yellow 34 and C.I. Pigment Red 104 For the risk assessment of C.I. Pigment Yellow 34 and C.I. Pigment Red 104, lead was identified as the lead substance indicator. The content of lead in the pigments is higher than the chromium content by a factor of 4, the dissolution from the pigments is higher by a factor of 4 to 100 and the PNECs for lead were generally lower. PNECs and PECregional for lead were taken from the vrar for lead. Conservative PNECs have been selected if there was still some debate concerning various PNECs by EU Member States with respect to the most recent publicly available vrar. Risk characterisation for lead According to the REACh guidance, PEClocal is calculated as Clocal + PECregional. For lead, PECregional was based on modelled data or the median of large datasets of ambient measured concentrations. The selected PECregional values (vrar lead) are presented in table Chapter 10. An initial screening of the regional concentrations showed that the background level of lead is significant as compared to the PNECs. In that case, according to the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Appendix R (Metals and metal compounds) the 'added risk approach' can be used. Therefore, PNEC is corrected for the background levels in the test medium (PNECadd) and compared to the estimated PEClocal without addition of the earlier established background concentration (see Scope and type of assessment above for the PNECadded values used). The calculations were performed using EUSES (in CHESAR). The use volume of the pigments was converted to represent the content of lead ion in the substance (60%). Calculation of PEClocal During/after use, pigment powder may be released to the environment. However, only a small fraction of the lead in the pigment will be transformed and diluted into the water phase. The calculations focus on the fate and behaviour of the dissolved lead. The results of the Transformation/Dissolution study showed that at low concentrations (1 mg/l) up to 10% of the lead content in the pigments is dissolved. Without any further correction, the concentrations of lead in effluent would be overestimated by a factor of 10 and subsequently this is also the case for the concentrations in surface water, sediment and fish. This is illustrated in the below figure, where for the sake of the illustration 167 g pigment was discharged to the STP, equalling 100 g pigment-bound lead CSR-PI CHEMICAL SAFETY REPORT 112

125 Illustration of the correction for transformation/dissolution of lead from C.I. Pigment Red 104 and C.I. Pigment Yellow 34 Since the concentration in the effluent is lower, the amount going to the sludge will be somewhat higher and subsequently, the concentration in agricultural soil is higher. The transformation/dissolution of the pigments will also occur in the soil, and then the transformed/dissolved lead will partition between pore water and the soil solids. With pigment concentrations in the range of 10 mg/l, the transformation/dissolution would be circa 2%. As shown in the figure, without correction, the pore water concentration for lead would also be overestimated by a factor of circa 10. The correction for the limited transformation/dissolution from the pigments to lead (10%), as well as for the lead content (60%) has been included in the calculations directly at the start by reducing the use volume of lead entering the environment by two reduction factors. This is visible in each contributing scenario under the heading Conditions of use Product (article) characteristics; as well as in the difference between the initial release factor and the final release factor. Secondary poisoning The PNECoral for lead as included in section 7.6 has been derived according to the ECHA guidance. However, already in the vrar it was recognised that this PNECoral would result in the prediction of risk well below the lead background concentrations. It was concluded that the generic recommended method to derive a PNECoral was not suitable and that more research was needed (Pb RAR, draft of January 2006). In addition, it was concluded that the generic approach to base the assessment on exposure concentrations in food was not suitable, but that an assessment based on internal concentrations was more appropriate (e.g., blood lead levels). This approach cannot be modelled with the current tools. Therefore the assessment of secondary poisoning has not been performed Man via environment Scope and type of assessment In the vrar, indirect exposure of man through the environment was based on measured concentrations food, water, air, soil and dust, products in addition to their occupational exposure. As indicated above and under section the modelling of sections including the regional compartment are of CSR-PI CHEMICAL SAFETY REPORT 113