Nickel Background EU Risk Assessment Report March 2008 Final Draft

7,677 views
7,597 views

Published on

Nickel compounds are considered as human carcinogens based on epidemiological studies, mechanistic information and evidence from animal studies. The overall findings indicate that nickel ions generated in target cells are determinants for the carcinogenic process.

Published in: Education
1 Comment
0 Likes
Statistics
Notes
  • Be the first to like this

No Downloads
Views
Total views
7,677
On SlideShare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
57
Comments
1
Likes
0
Embeds 0
No embeds

No notes for slide

Nickel Background EU Risk Assessment Report March 2008 Final Draft

  1. 1. Nickel and nickel compounds Background Document in support of individual RISK ASSESSMENT REPORTS of nickel compounds prepared in relation to Council Regulation (EEC) 793/93 Final version March 2008Chapters 0, 1, 2, 4, 5, 6 and 7 – human health only. Danish Environmental Protection Agency
  2. 2. R_NickelBackground_0308_hh_chapter0124567.docInformation on the Rapporteur.The Danish Environmental Protection Agency is the Rapporteur for the risk assessment reports of metallicnickel, nickel sulphate, nickel chloride, nickel nitrate and nickel carbonate. The Rapporteur is responsible for thecontents of this report.Contact persons:Poul Bo Larsen & Henrik TyleChemicals DivisionDanish Environmental Protection AgencyStrandgade 29DK-1401 Copenhagen KDENMARKTel: +45 72 54 40 00E-mail: HTY@mst.dk / PBL@mst.dk / DEPA-ESR@mst.dkAcknowledgements.The scientific assessments included in this Background report have been prepared by the following organisationsby order of the Rapporteur: • Danish National Working Environment Authority (Occupational Exposure, Chapter 4) • Danish Technological Institute (Aquatic effects Assessment, Chapter 3) • Department of Toxicology and Risk Assessment, Danish Food and Veterinary Research, (Consumer and Indirect Exposure, Human health effects, Chapter 4) • National Environmental Research Institute, Denmark (Terrestrial effects Assessment, Chapter 3). • URS Corporation, London, UK (Chapter 3, UK environment exposure)The Rapporteur would also like to acknowledge the contributions from the following individuals: • Professor Aage Andersen and Dr. Tom K. Grimsrud of the Cancer Registry of Norway, Institute of Population-based Cancer Research, for their assistance in the preparation of the section on nickel carcinogenicity in Chapter 4, • Ivor Kirman, London, UK for general information about nickel, • Drs. Hudson Bates, Adriana Oller, Katherine Heim, Lisa Ortego, and Chris Schlekat, NiPERA, Durham, North Carolina, USA, for providing information on the health and environmental effects of nickel, • Jim Hart, Sherborne, Dorset, UK, for the preparation of Chapters 1, and 2, and sections of Chapters 4 and 7, • Professor Torkil Menné MD, Gentofte Hospital, Copenhagen, Denmark for his assistance in the preparation and critical review of the sections on the sensitising effects of nickel in Chapter 4, • Dr. Sally Pugh Williams, Inco, Wales, UK for general information on nickel. 2
  3. 3. R_NickelBackground_0308_hh_chapter0124567.doc Foreword to Draft Risk Assessment ReportsRisk assessment of priority substances is carried out in accordance with Council Regulation (EEC) 793/93 (EEC,1993b) on the evaluation and control of the risks of “existing” substances. Regulation 793/93 provides asystematic framework for the evaluation of the risks to human health and the environment of these substances ifthey are produced or imported into the Community in volumes above 10 tonnes per year.There are four overall stages in the Regulation for reducing the risks: data collection, priority setting, riskassessment and risk reduction. Data provided by Industry are used by Member States and the Commissionservices to determine the priority of the substances which need to be assessed. For each substance on a prioritylist, a Member State volunteers to act as “Rapporteur”, undertaking the in-depth Risk Assessment and ifnecessary, recommending a strategy to limit the risks of exposure to the substance.Denmark is Rapporteur for five nickel substances: nickel metal, nickel sulphate, nickel chloride, nickel nitrateand nickel carbonate. This Background Report has been prepared by the Rapporteur for a number of reasons.Firstly, this Background report includes general information about nickel that is common to all the individualreports. This is particularly relevant for information about the release of nickel into the environment, and manyof the environmental properties of nickel. This background report also provides information about other nickelcompounds for which separate reports are not being prepared, but where information on their properties is usefulfor drawing conclusions on the hazards and risks of the five specific substances under review. Finally, this reportprovides a brief review of the other nickel compounds on the EU market to provide a starting point for furtherassessment of their hazards and risks.Draft Risk Assessment Reports on nickel metal and other nickel compounds are currently under discussion in theCompetent Group of Member State experts with the aim of reaching consensus. During the course of thesediscussions, the scientific interpretation of the underlying scientific information may change, more informationmay be included and even the conclusions reached in this draft may change. The Competent Group of MemberState experts seek as wide a distribution of these drafts as possible, in order to assure as complete and accuratean information basis as possible. The information contained in these Draft Risk Assessment Reports do not,therefore, necessarily provide a sufficient basis for decision making regarding the hazards, exposures or the risksassociated with the priority substances under consideration.This Draft Background Risk Assessment Report is the responsibility of the Member State rapporteur. In order toavoid possible misinterpretations or misuse of the findings in this draft, anyone wishing to cite or quote thisreport is advised to contact the Member State rapporteur beforehand. 3
  4. 4. R_NickelBackground_0308_hh_chapter0124567.docCONTENTS0. OVERALL RESULTS OF THE RISK ASSESSMENT........................... 91. GENERAL SUBSTANCE INFORMATION ......................................... 10 1.1 NICKEL AND NICKEL COMPOUNDS 10 1.2 PHYSICO-CHEMICAL PROPERTIES OF SELECTED NICKEL COMPOUNDS. 10 Solubility of nickel compounds................................................................................................ 12 1.2.1 Summary....................................................................................................................................... 13 1.2.2 1.3 CLASSIFICATION. 14 1.3.1 Current classification ................................................................................................................ 14 1.3.1.1 UN Transport labelling. 14 1.3.1.2 Classification according to Directive 67/548/EEC. 15 1.3.2 Proposed classification ............................................................................................................. 22 1.3.2.1 UN Transport labelling. 22 1.3.2.2 Classification according to Directive 67/548/EEC. 222. GENERAL INFORMATION ON EXPOSURE TO NICKEL AND NICKEL COMPOUNDS......................................................................... 24 2.1 SOURCES OF NICKEL. 24 2.1.1 Industrial production and use of nickel and nickel compounds...................................................... 24 2.1.1.1 Production. 24 2.1.1.1.1 Mining .............................................................................................................................. 24 2.1.1.1.2 Beneficiation and smelting ............................................................................................... 26 2.1.1.1.3 Refining............................................................................................................................ 26 2.1.1.1.4 Nickel chemicals production. ........................................................................................... 26 2.1.1.1.4.1 High production volume nickel containing chemicals. 26 2.1.1.1.4.2 Low production volume nickel containing chemicals. 28 2.1.1.1.4.3 Other low production volume nickel containing chemicals. 30 2.1.1.2 Nickel Use. 31 2.1.1.2.1 Uses of nickel and nickel compounds .............................................................................. 32 2.1.1.2.1.1 High production volume nickel-containing chemicals. 32 2.1.1.2.1.2 Low production volume nickel-containing chemicals. 33 2.1.1.2.1.3 Other low production volume nickel-containing chemicals. 34 2.1.1.2.2 Uses of nickel containing products................................................................................... 35 2.1.1.3 Disposal. 35 2.1.1.4 Nickel emissions from production and use of nickel and nickel-containing chemicals and products. 35 2.1.2 Other anthropogenic sources of nickel........................................................................................... 36 2.1.2.1 Non-ferrous metals production. 36 2.1.2.2 Combustion processes. 36 2.1.2.3 Other Industrial Processes. 37 2.1.2.4 Emission to soil. 38 2.1.3 Natural sources of nickel................................................................................................................ 38 2.1.3.1 Nickel emissions from natural sources. 39 2.1.4 Summary of nickel exposure information. ...................................................................................... 40 2.1.4.1 Trends in nickel emissions. 40 2.1.5 Nickel Lifecycle. ............................................................................................................................. 40 2.2 LEGISLATIVE CONTROLS. 41 2.2.1 General Measures. ......................................................................................................................... 41 2.2.1.1 Directive 67/548/EEC on dangerous substances. 41 2.2.1.2 Directive 1999/45/EC on dangerous preparations. 41 2.2.1.3 Other EU legislation. 41 2.2.1.4 National Initiatives. 42 2.2.2 Protection of workers. .................................................................................................................... 42 2.2.3 Protection of consumers. ................................................................................................................ 44 4
  5. 5. R_NickelBackground_0308_hh_chapter0124567.doc 2.2.3.1 Directive 98/83/EC on the quality of water intended for human consumption 45 2.2.3.2 Food contact materials, Food supplements, additives and contaminants. 45 2.2.3.3 Council Directive 90/385/EEC on active implantable Medical Devices, Council Directive 93/42/EEC on Medical Devices and Council Directive 98/79/EEC on in vitro-diagnostic Medical Devices 45 2.2.3.4 Council Directive 88/378/EEC on the Safety of Toys 46 2.2.3.5 Council Directive 89/106/EEC on Construction Products 46 2.2.3.6 Directive 2001/95/EC on general product safety 46 2.2.4 Emissions to water.......................................................................................................................... 46 2.2.4.1 Directive 96/61/EC concerning integrated pollution prevention and control (IPPC) 46 2.2.4.2 Directive 76/464/EEC on pollution of the aquatic environment by certain dangerous substances. 47 2.2.4.3 Directive 2000/60/EC establishing a framework for Community action in the field of water policy. 47 2.2.4.4 Directive 80/68/EEC on the protection of groundwater against pollution caused by certain dangerous substances 47 2.2.4.5 Directive 2000/76/EC on the incineration of waste. 48 2.2.4.6 National Legislation. 48 2.2.5 Emissions to air .............................................................................................................................. 49 2.2.5.1 Directive 96/61/EC concerning integrated pollution prevention and control (IPPC) 49 2.2.5.2 Directive 96/62/EC on ambient air quality assessment and management. 49 2.2.5.3 Directive 2000/76/EC on the incineration of waste. 50 2.2.5.4 Directive 2001/80/EC on Large Combustion Plant Directive. 50 2.2.5.5 UN ECE Protocol on heavy metals. 50 2.2.5.6 National Legislation. 50 2.2.5.7 Other measures. 50 2.2.6 Soil.................................................................................................................................................. 51 2.2.6.1 Directive 86/278/EEC on Sludge in Agriculture. 51 2.2.6.2 National Legislation. 51 2.2.7 Waste management......................................................................................................................... 52 2.2.7.1 Directive 96/61/EC concerning integrated pollution prevention and control 52 2.2.7.2 Council Directive 91/689/EEC of 12 December 1991 on hazardous waste 523. ENVIRONMENT .................................................................................... 534. HUMAN HEALTH ................................................................................. 54 4.1 HUMAN HEALTH (TOXICITY) 54 4.1.1 Exposure assessment. ..................................................................................................................... 54 4.1.1.1 General 54 4.1.1.2 Occupational exposure. 54 4.1.1.3 Consumer exposure. 54 4.1.1.3.1 Exposure to nickel in food................................................................................................ 54 4.1.1.3.2 Exposure to nickel in water .............................................................................................. 57 4.1.1.3.3 Combined exposure to nickel from food and drinking water. .......................................... 58 4.1.1.3.4 Exposure to nickel from smoking..................................................................................... 59 4.1.1.4 Indirect exposure via the environment 59 4.1.2 Human health effects assessment.................................................................................................... 59 4.1.2.1 Toxico-kinetics, metabolism and distribution 60 4.1.2.1.1 Absorption ........................................................................................................................ 60 4.1.2.1.1.1 Inhalation 60 4.1.2.1.1.1.1 Discussion and conclusion, absorption following inhalation ................................................ 62 4.1.2.1.1.2 Oral 64 4.1.2.1.1.2.1 Discussion and conclusion, absorption following oral administration .................................. 66 4.1.2.1.1.3 Dermal 67 4.1.2.1.1.3.1 Discussion and conclusion, absorption following dermal contact......................................... 68 4.1.2.1.1.4 Other routes 68 4.1.2.1.2 Distribution and elimination............................................................................................. 69 4.1.2.1.2.1 Transport 69 4.1.2.1.2.2 Distribution 69 4.1.2.1.2.3 Transplacental transfer 70 5
  6. 6. R_NickelBackground_0308_hh_chapter0124567.doc 4.1.2.1.2.4 Cellular uptake 71 4.1.2.1.2.5 Elimination 72 4.1.2.1.2.6 Transfer to the milk 73 4.1.2.1.3 Conclusions ...................................................................................................................... 744.1.2.2 Acute toxicity 75 4.1.2.2.1 Animal studies.................................................................................................................. 75 4.1.2.2.1.1 Inhalation 75 4.1.2.2.1.2 Oral 76 4.1.2.2.1.3 Dermal 76 4.1.2.2.1.4 Other routes 76 4.1.2.2.2 Human studies .................................................................................................................. 76 4.1.2.2.3 Discussion and conclusion ............................................................................................... 77 4.1.2.2.3.1 Inhalation 77 4.1.2.2.3.2 Oral 77 4.1.2.2.3.3 Dermal 774.1.2.3 Irritation /corrosivity 78 4.1.2.3.1 Animal studies.................................................................................................................. 78 4.1.2.3.1.1 Skin and eye irritation 78 4.1.2.3.1.2 Respiratory irritation 79 4.1.2.3.2 Human data....................................................................................................................... 79 4.1.2.3.2.1 Skin irritation 79 4.1.2.3.2.2 Respiratory irritation 80 4.1.2.3.2.3 Conclusion 804.1.2.4 Sensitisation 81 4.1.2.4.1 Skin sensitisation.............................................................................................................. 81 4.1.2.4.1.1 Animal studies 81 4.1.2.4.1.2 Human data 82 4.1.2.4.1.2.1 Nickel allergy........................................................................................................................ 82 4.1.2.4.1.2.2 Mechanism for the development of nickel allergy. ............................................................... 83 4.1.2.4.1.2.3 Immunological tolerance....................................................................................................... 83 4.1.2.4.1.2.4 Occurrence of nickel allergy ................................................................................................. 83 4.1.2.4.1.2.5 Hand eczema......................................................................................................................... 86 4.1.2.4.1.2.6 Experimental sensitisation .................................................................................................... 86 4.1.2.4.1.2.7 The ability of nickel salts, nickel and nickel alloys to elicit nickel allergy ........................... 86 4.1.2.4.1.2.7.1 Skin contact ................................................................................................................... 86 4.1.2.4.1.2.7.2 Oral challenge................................................................................................................ 89 4.1.2.4.1.2.7.3 Hyposensitisation .......................................................................................................... 90 4.1.2.4.1.2.8 Occupational nickel allergy .................................................................................................. 90 4.1.2.4.1.3 Conclusion on skin sensitisation 91 4.1.2.4.1.3.1 Thresholds for elicitation ...................................................................................................... 92 4.1.2.4.1.3.1.1 Skin................................................................................................................................ 92 4.1.2.4.1.3.1.2 Oral................................................................................................................................ 92 4.1.2.4.2 Respiratory sensitisation................................................................................................... 92 4.1.2.4.2.1 Conclusion on respiratory sensitisation 92 4.1.2.4.3 Conclusion........................................................................................................................ 934.1.2.5 Repeated dose toxicity 93 4.1.2.5.1 Animal studies.................................................................................................................. 93 4.1.2.5.1.1 Inhalation 95 4.1.2.5.1.1.1 NTP studies of nickel sulphate hexahydrate, nickel subsulphide and nickel oxide............... 95 4.1.2.5.1.1.1.1 16-day rat studies........................................................................................................... 95 4.1.2.5.1.1.1.2 16-day mouse studies..................................................................................................... 96 4.1.2.5.1.1.1.3 13-week rat studies ........................................................................................................ 97 4.1.2.5.1.1.1.4 13-week mouse studies.................................................................................................. 98 4.1.2.5.1.1.1.5 2-year rat studies............................................................................................................ 99 4.1.2.5.1.1.1.6 2-year mouse studies ..................................................................................................... 99 4.1.2.5.1.1.2 Other inhalation studies ...................................................................................................... 100 4.1.2.5.1.1.3 Supporting mechanistic data for lung effects ...................................................................... 101 4.1.2.5.1.2 Oral 102 4.1.2.5.1.3 Dermal 102 4.1.2.5.2 Conclusion...................................................................................................................... 102 4.1.2.5.2.1 Inhalation 102 4.1.2.5.2.2 Oral 103 4.1.2.5.2.3 Dermal 1034.1.2.6 Mutagenicity 103 6
  7. 7. R_NickelBackground_0308_hh_chapter0124567.doc 4.1.2.6.1 Summary of mutagenicity test results for the five selected nickel compounds. ............. 103 4.1.2.6.1.1 Summary of mutagenicity test results in vitro. 103 4.1.2.6.1.1.1 DNA damage and repair. .................................................................................................... 103 4.1.2.6.1.1.2 Gene mutation..................................................................................................................... 104 4.1.2.6.1.1.3 Chromosomal effects. ......................................................................................................... 105 4.1.2.6.1.1.4 Cell transformation. ............................................................................................................ 106 4.1.2.6.1.2 Summary of mutagenicity test results in vivo. 106 4.1.2.6.1.2.1 DNA damage and repair. .................................................................................................... 106 4.1.2.6.1.2.2 Gene mutations. .................................................................................................................. 107 4.1.2.6.1.2.3 Chromosomal effects. ......................................................................................................... 107 4.1.2.6.2 Genotoxicity of other nickel compounds........................................................................ 108 4.1.2.6.2.1 Other soluble nickel compounds. 108 4.1.2.6.2.2 Insoluble compounds. 108 4.1.2.6.3 Conclusions on the mutagenicity of the five selected nickel compounds....................... 1104.1.2.7 Carcinogenicity 112 4.1.2.7.1 Animal data .................................................................................................................... 112 4.1.2.7.1.1 Inhalation 112 4.1.2.7.1.1.1 Nickel sulphate ................................................................................................................... 112 4.1.2.7.1.1.2 Nickel metal........................................................................................................................ 112 4.1.2.7.1.1.3 Nickel chloride, nickel nitrate, and nickel carbonate .......................................................... 114 4.1.2.7.1.1.4 Nickel oxide........................................................................................................................ 114 4.1.2.7.1.1.5 Nickel subsulphide.............................................................................................................. 114 4.1.2.7.1.2 Oral 114 4.1.2.7.1.2.1 Nickel sulphate ................................................................................................................... 114 4.1.2.7.1.2.2 Nickel chloride, nickel nitrate, nickel carbonate, and nickel metal ..................................... 115 4.1.2.7.1.2.3 Nickel acetate...................................................................................................................... 115 4.1.2.7.1.3 Dermal 115 4.1.2.7.1.3.1 Nickel sulphate, nickel chloride, nickel nitrate, nickel carbonate, and nickel metal ........... 115 4.1.2.7.1.3.2 Other nickel compounds ..................................................................................................... 115 4.1.2.7.1.4 Other routes of administration 115 4.1.2.7.1.4.1 Nickel sulphate ................................................................................................................... 115 4.1.2.7.1.4.2 Nickel chloride.................................................................................................................... 116 4.1.2.7.1.4.3 Nickel nitrate....................................................................................................................... 117 4.1.2.7.1.4.4 Nickel carbonate ................................................................................................................. 117 4.1.2.7.1.4.5 Nickel metal........................................................................................................................ 117 4.1.2.7.1.4.6 Other nickel compounds ..................................................................................................... 118 4.1.2.7.1.5 Initiator-Promoter studies 118 4.1.2.7.1.5.1 Nickel sulphate ................................................................................................................... 118 4.1.2.7.1.5.2 Nickel chloride.................................................................................................................... 119 4.1.2.7.1.5.3 Nickel metal........................................................................................................................ 120 4.1.2.7.1.5.4 Nickel nitrate, nickel carbonate........................................................................................... 120 4.1.2.7.1.5.5 Other nickel compounds ..................................................................................................... 120 4.1.2.7.1.6 Discussion and conclusions, carcinogenicity in experimental animals 121 4.1.2.7.1.6.1 Inhalation ............................................................................................................................ 121 4.1.2.7.1.6.2 Oral ..................................................................................................................................... 123 4.1.2.7.1.6.3 Dermal ................................................................................................................................ 123 4.1.2.7.1.6.4 Other routes of administration ............................................................................................ 123 4.1.2.7.1.6.5 Initiator-Promoter studies ................................................................................................... 124 4.1.2.7.1.6.6 Conclusions in reviews on nickel compounds..................................................................... 125 4.1.2.7.1.6.6.1 CSTEE (2001) ............................................................................................................. 125 4.1.2.7.1.6.6.2 TERA (1999) ............................................................................................................... 125 4.1.2.7.1.6.6.3 IARC (1999)................................................................................................................ 125 4.1.2.7.1.6.6.4 NiPERA (1996) ........................................................................................................... 125 4.1.2.7.1.6.6.5 IPCS (1991) ................................................................................................................. 125 4.1.2.7.1.6.6.6 IARC (1990)................................................................................................................ 125 4.1.2.7.1.7 Conclusion, carcinogenicity in experimental animals 126 4.1.2.7.2 Human data..................................................................................................................... 126 4.1.2.7.2.1 Epidemiology 126 4.1.2.7.2.2 Exposures 127 4.1.2.7.3 Discussion ...................................................................................................................... 128 4.1.2.7.4 Overall Conclusion for carcinogenicity.......................................................................... 1304.1.2.8 Toxicity for reproduction 131 4.1.2.8.1 Effects on fertility........................................................................................................... 131 4.1.2.8.1.1 Animal studies 131 4.1.2.8.1.2 Human data 132 7
  8. 8. R_NickelBackground_0308_hh_chapter0124567.doc 4.1.2.8.2 Developmental toxicity .................................................................................................. 132 4.1.2.8.2.1 Animal studies 132 4.1.2.8.2.1.1 Oral exposure...................................................................................................................... 132 4.1.2.8.2.1.2 Inhalation ............................................................................................................................ 132 4.1.2.8.2.1.3 Other routes ........................................................................................................................ 133 4.1.2.8.2.2 Human data 133 4.1.2.8.3 Conclusions .................................................................................................................... 133 4.1.3 Risk characterisation.................................................................................................................... 134 4.2 HUMAN HEALTH (PHYSICO-CHEMICAL PROPERTIES) 134 4.2.1 Exposure assessment .................................................................................................................... 134 4.2.2 Effects assessment: ....................................................................................................................... 134 4.2.2.1 Explosivity 134 4.2.2.2 Flammability 134 4.2.2.3 Oxidising potential 134 4.2.3 Risk characterisation.................................................................................................................... 1345. CONCLUSIONS/RESULTS ................................................................. 1356. REFERENCES ...................................................................................... 1367. APPENDICES ....................................................................................... 154 7.1 WATER SOLUBILITY OF SELECTED NICKEL COMPOUNDS. 154 7.2 NICKEL AND NICKEL COMPOUNDS IN EINECS 155 7.2.1 Nickel, nickel compounds, and complex substances containing nickel included in EINECS. ...... 155 7.2.2 Nickel compounds included in Elincs ........................................................................................... 164 7.2.3 Additional Nickel compounds included in TSCA (through 08/2000) but not included in EINECS. ...................................................................................................................................................... 165 7.2.4 Additional Nickel compounds listed in ECICS (European Customs Inventory of chemical substances), but not included in EINECS or the TSCA Inventory. ............................................... 166 7.2.5 Additional Nickel compounds in Annex I to Directive 67/548/EEC but not in EINECS or TSCA.166 7.2.6 Additional nickel compound found in the course of compiling the inventory of nickel compounds ...................................................................................................................................................... 166 7.2.7 Additional nickel hydroxycarbonate compounds not included in the lists above ......................... 167 7.2.8 Nickel containing minerals (from IARC, 1990 and NiPERA, 1996)............................................. 167 7.3 NICKEL CONTENT IN FOOD. 168 8
  9. 9. R_NickelBackground_0308_hh_chapter0124567.doc0. OVERALL RESULTS OF THE RISK ASSESSMENTThe risk assessment of the production and use of metallic nickel, nickel sulphate, nickel chloride, nickelcarbonate and nickel nitrate is described in the individual risk assessment reports on these substances.A full risk assessment of the production and use of the other nickel compounds described in this report has notbeen attempted by the Rapporteur, as these other nickel compounds are not included in a priority list under theExisting Substances Regulation. However, the Rapporteur considers that the approach used in the riskassessments of the five nickel compounds listed above may prove helpful to others when preparing a riskassessment for specific nickel compounds.Risk characterisations of scenarios not directly related to the production and use of nickel and nickel compounds(e.g. combustion processes) where exposure to nickel occurs is outside the scope of these risk assessments. 9
  10. 10. R_NickelBackground_0308_hh_chapter0124567.doc1. GENERAL SUBSTANCE INFORMATION1.1 NICKEL AND NICKEL COMPOUNDSNickel can be found in a variety of oxidation states ranging from 0 to IV. However, Ni (II) is the only oxidationstate occurring in ordinary chemistry. Ni (III) and Ni (IV) occur in certain complexes and in specific oxidesystems, the higher oxidation states, however, being considerably less stable than Ni (II). Ni (0) and Ni (I)compounds are scarce (Cotton & Wilkinson, 1968, quoted from Carlsen, 2001a).Ni (II) forms a wide variety of compounds ranging from simple inorganic complexes (salts) to complexes withvarious organic ligands. Ni can be found in various oxides. It appears that in the aqueous chemistry Ni (II) is theonly oxidation state that has to be considered. In the absence of strong complexing agents Ni (II) appears inaqueous solution as the green hexaquonickel (II) ion Ni (H2O)62+ (Cotton & Wilkinson, 1968, quoted fromCarlsen, 2001a).There are over three hundred entries in EINECS for nickel and nickel compounds and other, often complex,substances containing nickel. These are shown in Appendix 7.2.1. It should be noted that the EINECS reportingrules (CEC, 1982) implicitly include hydrates of the anhydrous salts listed in EINECS. Hence the numbers ofsubstances (and the numbers of CAS numbers) implicitly included in EINECS is much greater than this figure.Three nickel compounds are included in Einecs (Appendix 7.2.2).An additional 40 nickel containing compounds not listed in EINECS but included in the US EPA TSCAinventory are shown in Appendix 7.2.3.A number of nickel compounds are included in the European Customs Inventory of Chemical Substances(ECICS, 1997). ECICS includes a numerical list showing correlations between the CAS number and the EUCUS number (a five-digit number). Appendix 7.2.1 also includes the CUS numbers where relevant. It can beseen that whilst most HPVC nickel compounds have individual CUS numbers, there are several LPVC chemicalsthat do not. Similarly, there are many nickel compounds that have individual CUS numbers, although accordingto the information in IUCLID, they do not appear to be marketed in significant quantities. Additional compoundslisted in ECICS (the European Customs inventory of chemical substances) not included in either EINECS orTSCA are shown in Appendix 7.2.4.Substances in the ECICS are included in the European Community’s Combined Nomenclature (eight digit CNcode). The CN is based on the “Harmonized Commodity Description and Coding System” emanating fromWCO, in use throughout the world. Nickel metal, nickel sulphate and nickel chloride have CN numbers thatidentify these substances individually. Nickel oxides and hydroxides are identified under a separate CN No.(2825 40 00). However, other nickel compounds are included in CN numbers that also include varying numbersof other non-nickel-containing compounds.Appendix 7.2.5 shows additional substances included as part of group entries in Annex I to Directive67/548/EEC but not included in the previous lists. Finally, other nickel containing compounds (includingminerals and other nickel compounds listed in IARC) not included in any of the lists above are shown inAppendices 7.2.6, 7.2.7 and 7.2.8.1.2 PHYSICO-CHEMICAL PROPERTIES OF SELECTED NICKEL COMPOUNDS.Table 1.2.A shows the physical-chemical properties of some nickel compounds shown in order of decreasingwater solubility. Data for the four high volume nickel compounds for which individual reports have beenprepared are included for comparison. This data has been compiled from a number of reviews of nickel andnickel compounds. A more detailed discussion of the water solubility of nickel and nickel compounds is given inthe following section.Table 1.2.A: Summary of physical properties of selected nickel compounds (compiled from UKHSE, 1987, IARC, 1990, NiPERA, 1996, TERA, 1999)Nickel Atomic Physical Melting Boiling Density Oxidation Watercompound: weight State Point (°C) Point (g/cm3) state Solubility (°C) 3) 10
  11. 11. R_NickelBackground_0308_hh_chapter0124567.docnickel chloride 237.70 solid - - 1.92 +2 2540 g/l at(hexahydrate) 20°C.nickel nitrate 290.79 solid 56.7 136.7 1) 2.05 +2 2385 g/l at(hexahydrate) 0°C.nickel sulphate 280.85 solid 99 - 1.95 +2 756 g/l at(heptahydrate) 20°C.nickel chloride 129.60 solid 973 2) 1001 3.55 +2 642 g/l at(anhydrous) 20°C.nickel sulphate 262.84 solid 53.3 - 2.07 +2 625 g/l at(hexahydrate) 20°C. 1)nickel 286.88 - +2 300 g/l atammonium 20°C.sulphate(anhydrous)nickel sulphate 154.75 solid 848 1) - 3.68 +2 293 g/l at(anhydrous) 20°C. 1)nickel acetate 176.78 solid 16.6 1.80 +2 166 g/l at(anhydrous) 20°C. 1)nickel acetate 248.84 solid 16 +2 160 g/l at(tetrahydrate) 20°C.nickel 394.94 - - 1.92 +2 104 g/l atammonium 20°C.sulphate(hexahydrate)nickel fluoride 96.69 solid +2 40 g/l at 25°C 1)nickel 340.42 solid 2.14 Solublefluoroborate(hexahydrate)nickel formate 184.76 solid 2.15 +2 soluble 1)nickel 322.95 solid 200 +2 Solublesulphamate(tetrahydrate)nickel 170.73 liquid - 25 43 1.32 0 0.18 g/l atcarbonyl 9.8°Cnickel 92.7 solid 230 1) - 4.15 +2 0.13 g/lhydroxide 1)nickel 118.70 solid - 5.822 +2 0.0093 g/lcarbonate at 25°C.nickel sulphide 90.75 solid 797 - 5.5 +2 0.003618(amorphous) g/lnickel 74.69 solid 1990 - 4.83 / +2 0.0011 g/lmonoxide 6.67 at 20°C. 1)basic nickel 376.17 solid 2.6 +2 Insolublecarbonate 1)nickel 587.67 solid - 2.6 +2 Insolublehydroxy-carbonatenickel 174.71 solid - - 5.82 +2 Insoluble inchromate waterNickelocene 188.88 solid 171-173 - +2 Insoluble 1)nickel titantate 154.57 solid 1000 - +2 Insoluble 11
  12. 12. R_NickelBackground_0308_hh_chapter0124567.docnickel 180.44 solid 1158 1400 1) NS 4) Insolubleantimonidenickel arsenide 133.61 solid 968 - 7.17 NS 4) Insoluble(NiAs)nickel selenide 137.65 solid red heat - NS 4) Insolublenickel 333.99 solid - - Insolublesubselenidenickel 240.19 solid 790 - 5.82 NS 4) Insoluble insubsulphide cold waternickel telluride 186.29 solid 600 – 900 1) - NS 4) Insoluble1) 2) 3) Decomposes. Sublimes Further details are given in the following section.4) NS: Not Specified; mixed formal oxidation states of nickel and/or complex coordination in the solid form.1.2.1 Solubility of nickel compounds.In the Table above, the water solubility of many of these compounds are described as either “soluble” or“insoluble”. Many substances commonly considered as “insoluble” are however sufficiently soluble undercertain conditions to give rise to effects of concern. This simple distinction is not always helpful.The available literature of the solubility of inorganic (Carlsen, 2001a) and organic (Carlsen, 2001b) Ni (II)species has been reviewed. This review was carried out in order to provide a systematic basis on which to groupin particular inorganic nickel compounds on the basis of their solubility in water.For inorganic nickel compounds, a grouping of inorganically based nickel species has been suggested. Nickelmetal and nickel metal compounds (see Appendix 7.1.1) can all be considered as insoluble. Nickel oxides andmixed metal oxides are also very similar in terms of their solubility (Carlsen, 2001a).In Table 1.2.B a grouping of the nickel ligands with Group 13, 14, 15, 16 and 17 ligands is suggested. The term‘insoluble’ means that the solubility of the species is less that 10-4 mol/l, ‘slightly soluble’ covers the solubilityrange 10-4 - 10-2 mol/l, ‘soluble’ the range 10-2 - 5·10-1 mol/l and ‘very soluble’ refers to solubility above 5·10-1mol/l (Carlsen, 2001a).The grouping made in Table 1.2.B is based exclusively on water as the medium. Thus, the apparent increasedsolubility of otherwise slightly - or even insoluble - nickel species observed in biological fluids (Maximilien,1989) is not covered in the grouping made below (Carlsen, 2001a).A few species, i.e., NiXN and NiTeO4 are not included in Table 1.2.B. No indications concerning the solubilityof these species have been retrieved (Carlsen, 2001a).Table 1.2.B: Grouping of nickel species based on inorganic ligands in water (Carlsen, 2001a). Group 13 Group 14 Group 15 Group 16 Group 17 Misc.Insoluble NiXBa NiXSia NiXPYa NiXSY Ni2Fe(CN)6 a NiXAs NiXSe NiXSbYa NiXTe Ni2P2O7 Ni3(AsO3)2a Ni3(AsO4)2 Ni(AsO3)2aSlightly Ni(CO)4 Ni3(PO4)2 NiSO3a Ni(IO3)2 Ni2Fe(CN)5NObsoluble Ni(CN)2 Ni[NiP2O7] NiSeO3 NiCO3 Ni(HCO3)2 12
  13. 13. R_NickelBackground_0308_hh_chapter0124567.docSoluble NiK2(SO4)2 NiF2Very NiB6O10 Ni(SCN)2 Ni(NO3)2 NiSO4 NiCl2soluble Ni(BF4)2 NiSiF6 Ni(H2PO2)2 Ni(SO3NH2)2a Ni(ClO3)2 NiSeO4 Ni(ClO4)2 NiBr2 Ni(BrO3)2 NiI2a No quantitative data have been retrievedb Placed due to the possible higher solubility as discussed by Linke (1965).It is noted that the solubility in general follows the ‘rules of thumb’ for inorganic salts. Thus, halides are easilysoluble, apart from the fluoride, nitrates are easily soluble, carbonates and phosphates are typically only slightlysoluble, hydroxides of non-alkali metals are often very slightly soluble, etc. (Carlsen, 2001a).In the study by Carlsen (2001a) the focus is on the concentration of the free nickel (II) ion, Ni(H2O)62+ asresponsible for biological effects of nickel compounds. However, the free ligands and/or the intact nickelcomplexes may also give rise to biological effects. It should be emphasized that the grouping in Table 1.2.B ismade without taking into account the possible lowering of the concentration of the free nickel ions due tocomplex formation. For hazard and risk assessment purposes this corresponds to a conservative approach to thepossible maximum concentration of Ni(H2O)62+ (Carlsen, 2001a).No comparable grouping of organic ligands has yet been carried out (Carlsen, 2001b). In contrast to theinorganic nickel compounds it is not obvious how to group the organically based species based on solubilityalone. Aqueous solubility is, not unexpectedly, seen to decrease with increasing molecular weight and increasingcarbon content of the ligand. On the other hand, the introduction of hydrophilic and/or polar functional groups,such as OH, C=O, COO-, NH, SH and SO3- cause increased solubility. Further it should be emphasized that thesolubility of the complexes cannot immediately be related to the solubility of the single ligands (Carlsen 2001b).Hence, it seems more appropriate to group organically based nickel complexes based on the stability of thecomplexes. As a first attempt, grouping the individual complexes based on the nature of the ligand appears as anobvious choice, even though significant variations in stability may prevail within the single groups.Monocarboxylic acids serve as an example to illustrate the applicability of this concept. It appears that thestability constant for the first complex typically is found in the range around 1 and the second in the range of 1-2.Significant outliers are the sulphur-containing acids thiolactic acid and (phenylthio)acetic acid. Apart from thesulphur-containing acids, it would seem appropriate to treat nickel monocarboxylate complexes as a singlegroup, based on the salts of formic and acetic acid. Both these salts are highly soluble: thus, the approach wouldbe conservative. In order to evaluate the possible concentration of free nickel ions, as well as other nickelcontaining species in solution, it is important to take the actual acidity of the solution into consideration (Carlsen,2001b).1.2.2 SummaryThe availability of physical chemical data for the nickel compounds in Appendix 7.1 is very variable. However,there is data available for the water solubility of many inorganic nickel (II) compounds, although there are manycomplex nickel-containing substances with no solubility data. Grouping many of the conventional inorganicnickel (II) compounds on the basis of their water solubility is fairly straightforward. Grouping the much largernumbers of organic complexes is a more complicated process.Many legislative controls group all nickel compounds together (see Chapter 2.2). In other cases, nickelcompounds are divided into groups on the basis of their water solubility (e.g. TERA, 1999). This grouping ofcompounds reflects the assumption that the biological effects of nickel reflect the activity of the nickel ion,Ni(H2O)62+. NiPERA (1996) groups nickel compounds into five main classes: metallic nickel, nickel carbonyl,oxidic nickel (e.g. nickel oxides, hydroxide, silicates, carbonates, complex nickel oxides), sulphidic nickel (e.g.nickel sulphide, nickel subsulphide), and water-soluble nickel compounds (e.g. nickel sulphate hexahydrate,nickel chloride hexahydrate). The group of “oxidic nickel” includes substances with a range of different watersolubility, from compounds of very low solubility (e.g. nickel oxide) to compounds with a water solubility ahundred times greater (e.g. nickel hydroxide). There is little difference in the water solubility of sulphidic nickeland that of nickel oxides. Whilst these groupings reflect the substances encountered in nickel metal production,they do not reflect well the wider range of HPVC and LPC substances seen in practice (see Chapter 2). 13
  14. 14. R_NickelBackground_0308_hh_chapter0124567.docHowever, it is important to be able to recognise similarities and differences in biological behaviour across groupsof chemically related compounds. Derogation statements by Industry for not carrying out testing for particularendpoints is based on the recognition of similarities in effects between nickel-containing compounds where datais available, and other related compounds where experimental data is not available. Assumptions are made in therisk assessment reports of the individual compounds reviewed by the Rapporteur about the possibility toextrapolate data between these compounds. The data reviewed for the five individual substances can also be usedas a basis for similar extrapolations to other related nickel compounds.1.3 CLASSIFICATION.1.3.1 Current classification1.3.1.1 UN Transport labelling.Four nickel compounds are included as specific entries in the UN Recommendations on the Transport ofDangerous Goods (UN, 2001) and ADR (UN ECE 2001b). UN Number Class Subsidiary Packaging risk GroupNickel carbonyl (nickel tetracarbonyl) 1259 6.1 3 INickel cyanide (Nickel (II) cyanide) 1653 6.1 IINickel nitrate (Nickel (II) nitrate, nickelous nitrate) 2725 5.1 IIINickel nitrite (Nickel (II) nitrite, nickelous nitrite) 2726 5.1 IIINone of these four entries are included in Annex B.2 – Appendix 4 of the ADN (UN ECE, 2001a).According to information supplied by Industry to the Rapporteur, nickel containing compounds and products areclassified under the following n.o.s. entries: UN Name UN Number Class Subsidiary Packaging risk Groupnickel carbonate Environmentally UN 3077 9 M7 III hazardous substance, solid, n.o.snickel chloride (solid) Toxic solid, inorganic. UN 3288 6.1 T5 III n.o.s.nickel chloride (liquid) Toxic liquid, inorganic. UN 3287 6.1 T4 III n.o.s.Lithium nickel Lithium batteries. UN 3091 9, M4 IIbatteriesnickel catalyst, dry, metal catalyst, dry, UN 2881 4.2 I / IInickel catalyst, spent flammable solid, organic UN 1325 4.1 III n.o.s.nickel metal powder metal powder, UN 3089 4.1 IIwith very fine particle flammable, n.o.s.size (e.g. INCO 210)nickel powder less Environmentally UN 3077 9 M7 III.than 100 microns hazardous substance, solid n.o.snickel sulphate Environmentally UN 3077 9 M7 III hazardous substance solid n.o.s.The Rapporteur has no information on the Transport classification used for other nickel compounds 14
  15. 15. R_NickelBackground_0308_hh_chapter0124567.doc1.3.1.2 Classification according to Directive 67/548/EEC.Thirteen nickel compounds are included in Annex I to Directive 67/548/EEC (EEC, 1992a) as separate entries.Three of these are notified substances. The classification of all these entries (including substances reviewed inthe individual risk assessment reports are shown below. In some cases, a number of different compounds havethe same classification.Individual entries are classified as follows:Nickel carbonyl: 028-001-00-1 (EC No.: 236-669-2, CAS No.: 13463-39-3) (25th ATP, EC 1998b) ClassificationF; R11 Carc. Cat. 3; R40 Repr. Cat. 2; R61 T+; R26 N; R50-53 LabellingSymbols F; T+; NR Phrases 61-11-26-40-50/53 (Nota E)S-Phrases 53-45-60-61Nickel: 028-002-00-7 (EC No.: 231-111-4, CAS No.: 7440-02-0) (19th ATP, EEC, 1993d 1) ClassificationCarc. Cat. 3; R40 R43 LabellingSymbols XnR Phrases 40-43S-Phrases (2-)22-36Nickel monoxide: 028-003-00-2 (EC No.: 215-215-7, CAS No.: 1313-99-1) (28th ATP, EC 2001e)Nickel dioxide: 028-004-00-6 (EC No.: 234-823-3, CAS No.: 12035-36-8) (28th ATP, EC 2001e)Nickel trioxide: 028-005-00-3 (EC No.: 215-217-8, CAS No.: 1314-06-3) (28th ATP, EC 2001e) 2 ClassificationCarc. Cat. 1; R49 R43 R53 LabellingSymbols TR Phrases 49-43-53S-Phrases 53-45-611 This entry has been revised in the 30th ATP which was adopted by a Technical Progress Committee inFebruary 2007, but not yet adopted by the Commission or published in the Official Journal. The revised entry isclassified as: Carc. Cat. 3; R40; T; R48/23 and R43. An additional entry for particle size < 1 mm includingcalssification as R52-53 has been agreed by the TC C&L and included in a draft 31 ATP sent for comment inJuly 2007.2 Changes to these entries have been agreed by the TC C&L and included in a draft 31 ATP sent for comment inJuly 2007. The revised entries are classified as: Carc. Cat. 1; R49; T; R48/23, R43 and R53. 15
  16. 16. R_NickelBackground_0308_hh_chapter0124567.docNickel sulphide: 028-006-00-9 (EC No.: 240-841-2, CAS No.: 16812-54-7) (28th ATP, EC 2001e) 3 ClassificationCarc. Cat. 1; R49 R43 N; R50-53 LabellingSymbols T; NR Phrases 49-43-50/53S-Phrases 53-45-60-61Nickel subsulphide 1: 028-007-00-4 (EC No.: 234-829-6, CAS No.: 12035-72-2) (28th ATP, EC 2001e) 3 ClassificationCarc. Cat. 1; R49 R43 N; R51-53 LabellingSymbols T; NR Phrases 49-43-51/53S-Phrases 53-45-611) Heazlewoodite given as a synonym by NiPERA (1996).Nickel dihydroxide: 028-008-00-X (EC No.: 235-008-5, CAS No.: 12054-48-7) (28th ATP, EC 2001e) 4 ClassificationCarc. Cat. 3; R40 Xn; R20/22 R43 N; R50-53 LabellingSymbols Xn; NR Phrases 20/22-40-43-50/53S-Phrases (2-)22-36-60-61Nickel sulphate: 028-009-00-5 (EC No.: 232-104-9, CAS No.: 7786-81-4) (25th ATP, EC 1998b) 5 ClassificationCarc. Cat. 3; R40 Xn; R22 R42/43 N; R50-53 LabellingSymbols Xn; NR Phrases 22-40-42/43-50/53S-Phrases (2-)22-36/37-60-613 Changes to this entry has been agreed by the TC C&L and included in a draft 31 ATP sent for comment in July2007. The revised entry is classified as: Carc. Cat. 1; R49; Muta. Cat. 3; R68; T; R48/23, R43 and N; R50-53.4 Changes to this entry has been agreed by the TC C&L and included in a draft 31 ATP sent for comment in July2007. The revised entry is classified as: Carc. Cat. 1; R49; Repr. Cat. 2; R61; Muta. Cat. 3; R68; Xn; R20/22; T;R48/23, Xi; R38; R42/43 and N; R50-53.5 This entry has been revised in the 30th ATP. The revised entry is classified as: Carc. Cat. 1; R49; Repr. Cat. 2;R61; Muta. Cat. 3; R68; Xn; R20/22; T; R48/23; (SCL of 1%); Xi; R38; (SCL of 20%); R42; R43 (SCL of0.01%) and N; R50-53. 16
  17. 17. R_NickelBackground_0308_hh_chapter0124567.docNickel carbonate 1: 028-010-00-0 (EC No.: 222-068-2, CAS No.: 3333-67-3) (25th ATP, EC 1998b) 6 ClassificationCarc. Cat. 3; R40 Xn; R22 R43 N; R50-53 LabellingSymbols Xn; NR Phrases 22-40-43-50/53S-Phrases (2-)22-36/37-60-611): NiPERA (1996) also lists two other substances, not mentioned in Annex I as included in the same Annex Ientry (028-010-00-0). These are the 1:2 nickel hydroxycarbonate, with the EINECS name: [carbonato(2-)]tetrahydroxytrinickel), CAS and EC Nos. 12607-70-4 and 235-715-9, and 2NiCO3.3Ni(OH)2.4H2O shown withCAS No. 12122-15-5 and EC No. 235-715-9 (for comments on these CAS & EC Nos. see risk assessment reporton nickel carbonate).Tetrasodium (c-(3-(1-(3-(e-6-dichloro-5-cyanopyrimidin-f-yl(methyl)amino)propyl)-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridylazo)-4-sulfonatophenylsulfamoyl)phtalocyanine-a,b,d-trisulfonato(6-))nickelato II, wherea is 1 or 2 or 3 or 4,b is 8 or 9 or 10 or 11, c is 15 or 16 or 17 or 18, d is 22 or 23 or 24 or 25 and where e and ftogether are 2 and 4 or 4 and 2 respectively: 607-288-00-2 (EC No.: 410-160-7, CAS No.: 148732-74-5) (26thATP, EC 2000a; repeated in 28th. ATP, EC 2001e) ClassificationXi; R36 R43 R52-53 LabellingSymbols XiR Phrases 36-43-52/53S-Phrases (2-)22-26-36/37-61Trisodium (1-(3-carboxylato-2-oxido-5-sulfonatophenylazo)-5-hydroxy-7-sulfonatophthalen-2-amido)nickel(II):611-103-00-0 (EC No.: 407-110-1, CAS No.: -) (29th ATP, EC 2004a) ClassificationXi; R41 R43 N; R51-53 LabellingSymbols Xi; NR Phrases 41-43-51/53S-Phrases (2-)24-26-37/39-61Hexasodium (di(N-(3-(4-[5-(5-amino-3-methyl-1-phenylpyrazol-4-yl-azo)-2,4-disulfo-anilino]-6-chloro-1,3,5-triazin-2-ylamino)phenyl)-sulfamoyl](disulfo)-phthalocyaninato)nickel: 611-122-00-2 (EC No.: 417-250-5, CASNo.: 151436-99-6) (29th ATP, EC 2004a) ClassificationXi; R41 LabellingSymbols XiR Phrases 41S-Phrases (2-)26-396 This entry has been revised in the 30th ATP. The revised entry is classified as: Carc. Cat. 1; R49; Repr. Cat. 2;R61; Muta. Cat. 3; R68; Xn; R20/22; T; R48/23; Xi; R38; R42; R43 and N; R50-53. 17
  18. 18. R_NickelBackground_0308_hh_chapter0124567.docIn addition, 25 other nickel compounds are included in Annex I to Directive 67/548/EEC as part of groupentries 7. The classification of these entries reflects the hazards of the main functional group forming the basis ofthe group entry, and is not based on hazards related to nickel.Nickel compounds in EINECS are included in group entries in Annex I to Directive 67/548/EEC for salts ofhydrogen cyanide (006-007-00-5), fluorosilicates (009-013-00-6), chromium (VI) compounds (024-017-00-8),arsenic compounds (033-002-00-5), salts of arsenic acid (033-005-00-1), selenium compounds (034-002-00-8),antimony compounds (051-003-00-9), barium compounds (056-002-00-7), lead compounds (082-001-00-6),uranium compounds (092-002-00-3) salts of oxalic acid (607-007-00-3) and metal salts of thiocyanic acid (615-032-00-6).EINECS name Annex I entry EC No. CAS No. Classificationnickel (II) 006-007-00-5 209-160-8 557-19-7 T+; R26/27/28 R32 N; R50-53cyanide (1)nickel(2+), 006-007-00-5 273-379-5 68958-89-4 T+; R26/27/28 R32 N; R50-53bis(1,2-ethanediamine-N,N)-,bis[bis(cyano-C)aurate(1-)]Copper(2+), 006-007-00-5 264-136-4 63427-32-7 T+; R26/27/28 R32 N; R50-53bis(1,2-ethanediamine-N,N)-, (SP-4-1)-tetrakis(cyano-C)nickelate(2-)(1:1)Nickelate(2-), 006-007-00-5 237-877-6 14038-85-8 T+; R26/27/28 R32 N; R50-53tetrakis(cyano-C)-, disodium,(SP-4-1)-silicate(2-), 009-013-00-6 247-430-7 26043-11-8 Xn; R22hexafluoro-,nickel(2+) (1:1)(1)nickel chromate 024-017-00-8 238-766-5 14721-18-7 Carc. Cat. 2; R49 R43 N: R50-53(1)nickel dichromate 024-017-00-8 239-646-5 15586-38-6 Carc. Cat. 2; R49 R43 N: R50-53(1)nickel diarsenide 033-002-00-5 235-103-1 12068-61-0 T; R23/25 N; R50-53(1)nickel arsenide 033-002-00-5 248-169-1 27016-75-7 T; R23/25 N; R50-53(1)nickel (II) 033-005-00-1 236-771-7 13477-70-8 Carc. Cat. 1; R45 T; R23/25 N; R50-53arsenate (1)Nickel selenide 034-002-00-8 215-216-2 1314-05-2 T; R23/25 R33 N; R50-53(NiSe) (1)selenious acid, 034-002-00-8 233-263-7 10101-96-9 T; R23/25 R33 N; R50-53nickel(2+) salt(1:1) (1)selenic acid, 034-002-00-8 239-125-2 15060-62-5 T; R23/25 R33 N; R50-53nickel(2+) salt(1:1) (1)antimony, compd. 051-003-00-9 234-827-5 12035-52-8 Xn; R20/22 N; R51-53with nickel (1:1)7 Two nickel acrylates and two nickel methacrylates were excluded from the Annex I group entries for thesecompounds in the 28th. ATP (EC 2001e) when the nomenclature was changed to specify monoalkyl or monoarylor monoalkylaryl esters only. 18
  19. 19. R_NickelBackground_0308_hh_chapter0124567.docantimony, compd. 051-003-00-9 235-676-8 12503-49-0 Xn; R20/22 N; R51-53with nickel (1:3)C.I. Pigment 051-003-00-9 232-353-3 8007-18-9 Xn; R20/22 N; R51-53Yellow 53,(Antimony nickeltitanium oxideyellow,) (2)antimony oxide 051-003-00-9 277-627-3 73892-02-1 Xn; R20/22 N; R51-53(Sb203), solidsoln. with nickeloxide (NiO) andtitanium oxidePriderite, nickel 056-002-00-7 271-853-6 68610-24-2 Xn; R20/22(1)Speiss, lead, 082-001-00-6 308-765-5 98246-91-4 Repr. Cat. 1; R61; Xn; N; R50-53nickel-contg. Repr. Cat. 3; R62 R20/22; R33Residues, copper- 082-001-00-6 310-050-8 102110-49-6 Repr. Cat. 1; R61; Xn; N; R50-53iron-lead-nickel Repr. Cat. 3; R62 R20/22;matte, sulfuric R33acid-insol.uranate(2-), 092-002-00-3 275-994-4 71767-12-9 T+; R26/28 R33 N; R51-53tetrakis(acetato-O)dioxo-,nickel(2+)(1:1),(OC-6-11)-uranic acid 092-002-00-3 239-876-6 15780-33-3 T+; R26/28 R33 N; R51-53(H2U3O10),nickel(2+) salt(1:1) (1)ethandioic acid, 607-007-00-3 243-867-2 20543-06-0 Xn; R21/22nickel salt (1)ethandioic acid, 607-007-00-3 208-933-7 547-67-1 Xn; R21/22nickel(2+) salt(1:1) (1)thiocyanic acid, 615-032-00-6 237-205-1 13689-92-4 Xn; R20/21/22 R32 N; R50-53nickel(2+) salt (1)1) Chemical included in draft 31st ATP2) Low production volume chemical. See chapter 2.1.1.1.4. Classification discussed in preparation of draft 31stATP (Hart, 2007).For nickel compounds not included in Annex I, Industry is required to evaluate the available data to assess thehazard, and to apply a provisional classification.Information is available from Industry for the provisional classifications of the HPVC nickel compoundsreviewed by the Rapporteur: 8Com- Classification ReferencepoundNickel T; R25 Xn; R40/20 Xi; R36/37 R42/43 N; R50 Eramet, 2002chlorideNickel O; R8 Xn; R22 R43 HEDSET8 These two compounds have now been included in the 30th ATP. Nickel dichloride is classified as: Carc. Cat. 1;R49; Repr. Cat. 2; R61; Muta. Cat. 3; R68; T; R23/25; T; R48/23; (SCL of 1%); Xi; R38; (SCL of 20%); R42;R43 (SCL of 0.01%) and N; R50-53. Nickel dinitrate is classified as: O; R8; Carc. Cat. 1; R49; Repr. Cat. 2;R61; Muta. Cat. 3; R68; Xn; R20/22; T; R48/23; (SCL of 1%). Xi; R38 (SCL of 20%); Xi; R41; R42; R43 (SCLof 0.01%) and N; R50-53 19
  20. 20. R_NickelBackground_0308_hh_chapter0124567.docnitrate (2002a) Carc. Cat. 1; R45 T; R23/24/25 C; R34 IUCLID, 2001 O; R8 Carc. Cat. 3; R40 Xn; R22 C; R34 R42/43 HEDSET (2002b) O; R8 Carc. Cat. 1; R45 Xn; R22 R43 HEDSET (1) (2003a) O; R8 Carc. Cat. 3; R40 Xn; R22 C; R34 R43 N; R50/53 IUCLID (2003b) O; R8 Carc. Cat. 3; R40 Xn; R22 R42/43 N; R50/53 IUCLID (2) (2003b) O; R8 Xn; R22 Xi; R38/41 HEDSET (2003b)1) The classification category is not shown. Category 1 is assumed on the basis of the IARC conclusion and thelack of any animal data.2) R42 is applied when the nickel solution is used as an aerosol (IUCLID, 2003b).Only one of the HPVC nickel compounds not specifically reviewed by the Rapporteur (see Table 2.1.1.C) isincluded in Annex I. This is nickel oxide (Annex I entry 028-003-00-2).None of the remaining 14 substances includes a provisional classification in the IUCLID database at the ECB(IUCLID 2002). Several of the files include the remark that “UVCB-Stoffe sind zum größten teil nichteingestuft” (UVCB substances are not normally classified). There is no derogation from the requirement forprovisional classification for complex UVCB substances in the Directive, and guidance on the classification ofthese substances is given in section 1.7.2.1. of Annex VI (EC, 2001e).However, some information is available. Section C.5 of the IUCLID file for “ferronickel manufacturing slags”(EC No. 273-729-7) considers the substance fulfils the criteria for classification as Carc. Cat 3; R40 and R43.Section 1.15. 5 of the IUCLID file for “nickel matte” (EC No. 273-746-9) recognises that the main component isnickel subsulphide which is classified as Carc. Cat. 1 in Annex I (Annex I entry 028-007-00-4). It states that thedust is irritating for the respiratory tract and that it may also be a respiratory sensitiser.A comment in the IUCLID file for “Frits, chemicals” (EC No. 266-047-6) notes that classification depends onthe composition of an individual product.One manufacturer’s IUCLID file for “Leach residues, zinc ore-calcine, cadmium-copper ppt.” (EC No. 293-311-8) includes a provisional classification as Xn; R20 (harmful by inhalation) (IUCLID, 1996). This provisionalclassification is not included in the main IUCLID file. (IUCLID 2002).One manufacturer’s IUCLID file for “Leach residues, zinc ore-calcine, iron contg.,” (EC No. 293-312-3)includes a classification with R45, R46 and R61 (May cause cancer, may cause heritable genetic damage, maycause harm to the unborn child). It also includes a classification as T; R23/25 (Toxic by inhalation and ifswallowed), Xn; R20/21/22) (Harmful by inhalation, in contact with skin and if swallowed); and R33 (danger ofcumulative effects). This evaluation is based on the classification of the main components, lead, cadmium andarsenic. (IUCLID, 1995). This provisional classification is not included in the main IUCLID file. This doeshowever include a comment under section 1.15 from another manufacturer noting a composite classificationbased on the properties of lead and arsenic (IUCLID 2002).These “classifications” are shown in the table below.Compound Classification ReferenceSlags, ferronickel- Carc. Cat. 3; R40 R43 C.5 in IUCLIDmanufg. (2002) (1)nickel matte Carc. Cat. 1; R45 Xi; R37 R42 from section 1.15.5 in IUCLID (2002)Leach residues, Xn; R20 IUCLID (1996)zinc ore-calcine,cadmium-copperpptLeach residues, Carc. Cat. 1; R45 T; R23/25 Xn; R21 R33 IUCLID (1995)zinc ore-calcine, Muta. Cat. 2; R46iron contg. Repr. Cat. 1; R61 20
  21. 21. R_NickelBackground_0308_hh_chapter0124567.doc Carc. Cat. 1; R45 Xn; R33 from section 1.15 in Repr. Cat. 1; R61 R20/22 IUCLID (2002)1 ) Chemical included in draft 31st ATPThere is no assessment of “Slimes and Sludges, copper electrolyte refining, decopperised, Ni sulfate”, EC No.295-859-3, in the IUCLID file (IUCLID, 2002), even though the EINECS description of the substance indicatesnickel sulphate which is included in Annex I (028-009-00-5) as a main component.Some HPVCs, such as Ceramic materials and wares, chemicals (EC No. 266-340-9) are regarded as non-hazardous. For others, e.g. Slags, copper smelting EC No. 266-968-3 the substance is not classified due a lack ofinformation on the effects of the substance.The nickel-containing LPVCs are listed in Table 2.1.1.D.Nickel hydroxide (028-008-00-X) and nickel sulphide (028-006-00-9) are both included in Annex I. C.I. PigmentYellow (EC No. 232-353-3) is an antimony compound and, as such is included in the group entry (051-003-00-9). Nickel, [carbonato(2-)]tetrahydoxytri- (EC No. 235-715-9) is regarded by NiPERA as included in the nickelcarbonate entry (028-010-00-0) although it is not actually listed as part of the entry.The IUCLID data sets are not available for LPVCs in ESIS (IUCLID, 2002). The 37 IUCLID data sets submittedby the producers of the 22 LPVCs not included in Annex I with specific entries have been supplied by the ECBto the Danish Rapporteur. The Table below summarises the classifications shown in these files.Compound Classification Reference.Nickel, [carbonato(2- Carc. Cat. 3; R40 Xn; R22 R43 IUCLID, 2003a (1))]tetrahydroxytri-Nickel fluoride (NiF2) Carc. Cat. 3; R40 Xn; R22 Xi; R36 R42/43 IUCLID, 2003a (2,3) Carc. Cat. 3; R40 R43Nickel bromide (NiBr2) no data available IUCLID, 2003a for classificationSulfamic acid, nickel(2+) Carc. Cat. 3; R40 Xn; R22 Xi; R36/38 R42/43 IUCLID, 2003a (2)salt (2:1) Carc. Cat. 3; R40 Xn; R22 R42/43Acetic acid, nickel(2+) salt Carc. Cat. 3; R40 R43 IUCLID, 2003aAcetic acid, nickel salt Carc. Cat. 3; R40 Xn; R22 R42/43 IUCLID, 2003aOctanoic acid, nickel(2+) Carc. Cat. 3; R40 Xn; C; R35 R42/43 IUCLID, 2003asalt R20/21/22Nickel, Xi; R39 Xi; R36 IUCLID, 2003a (2, 4, 5)bis(dibutylcarbamodithioato-S,S’)-, (SP-4-1)- no dangerous propertiesNickel, bis(3-amino-4,5,6,7- no dangerous IUCLID, 2003a (5)tetrachloro-1H-isoindol-1- propertiesone oximato-N(2)-,O(1))-Nickel, bis[2,3- no dangerous IUCLID, 2003a (5)bis(hydroxyimino)-N- propertiesphenylbutanamidato-N(2)-,N(3)-]-Nickel, bis[2,3- no dangerous IUCLID, 2003a (5)bis(hydroxyimino)-N-(2- propertiesmethoxyphenyl)butanamidato]-Nickel, [29H,31H- no data available IUCLID, 2003aphthalocyaninato(2-)-N(29)- for classification,N(30)-,N(31)-,N(32)-]-,(SP-4-1)-Nickel, (1- R52/53 IUCLID, 2003a (2) 21

×