Download PROVISIONAL GUIDANCE ON USE OF CHEMICAL CATEGORIES

Nickel compounds – a category approach for metals in EU legislation
Jim Hart, Consultant
prepared on behalf of the Danish Environmental Protection Agency
January 2008
PREFACE:
This report was commissioned by the Danish EPA, and describes the use of a categories approach to the
classification and labelling of a group of nickel compounds.
The Danish EPA is the Rapporteur for the risk assessment of nickel and four nickel compounds (nickel
sulphate, nickel dichloride, nickel dinitrate and nickel carbonate) under the EU Existing Chemicals
Regulation (EEC) 793/93. Part of this work included data collection and evaluation of a number of other
nickel compounds such as the nickel oxides and sulphides.
As a result of this work, classification and labelling proposals for the five nickel compounds evaluated under
the EU Existing Chemicals Regulation have been prepared by the Danish EPA, and, after discussion in the
EU Technical Committee for Classification and Labelling, new and revised entries for the five compounds
have been included in Annex I to Directive 67/548/EEC (List of Dangerous Substances), which was adopted
by a Technical Progress Committee in February 2007 as part of the 30th Adaptation to Technical Progress of
the Directive (ECB, 2007a).
In addition, proposals for updating the existing entries for some of the other nickel compounds in Annex I to
Directive 67/548/EEC (nickel hydroxide, nickel oxides and nickel sulphides) were also prepared by the
Danish EPA, and agreed by the EU Technical Committee for Classification and Labelling for inclusion in the
31st Adaptation to Technical Progress of the Directive.
Based on the agreed classification for these individual substances, the Danish EPA then prepared a
classification proposal covering more than 100 nickel compounds. This proposal reflected the group approach
already used for a number of metals in Annex I, but refined the approach by proposing classifications based
on a number of different subgroups. After discussion and further refinement, this proposal was also agreed by
the EU Technical Committee for Classification and Labelling in 2006 for inclusion in the 31st Adaptation to
Technical Progress of the Directive (ECB, 2007b).
This report describes these proposals and the discussions in the EU Technical Committee. The experience of
this discussion, and the relevance of the approach used here for a Category approach to metals has formed
part of the development of guidance for the use of a Category approach in both the EU and the OECD.
This report is an updated version of Example F in Chapter 3.2 “Guidance on the Development and Use of
Chemical Categories in the HPV Chemicals Programme”, in the OECD “Manual For Investigation of HPV
Chemicals”. This guidance document was prepared by the OECD Secretariat based on the agreements
reached in the OECD Existing Chemicals Programme up to May 2005.
The experience in the development of these proposals is also reflected in the EU Technical Guidance
Document to Industry on the Information Requirements for REACH (RIP 3.3 project).
This report reflects the status of the discussion of the classification and labelling of these nickel compounds
at the time of publication in December 2007. The report reflects the proposals for the Annexes to the 31st
ATP as shown on the ECB website.
The subheadings used in this document reflect the stepwise procedure described in the OECD 2005
guidance, but do not necessarily reflect the stepwise approach proposed in the latest (2007) OECD or
guidance or the draft RIP 3.3 guidance.
2
INDEX
PREFACE:...................................................................................................................................................... 2
INTRODUCTION .......................................................................................................................................... 4
IDENTIFICATION OF STRUCTURE-BASED CATEGORY AND ITS MEMBERS: ............................... 6
GATHER PUBLISHED AND UNPUBLISHED DATA FOR EACH CATEGORY MEMBER. ................ 8
EVALUATE DATA FOR ACCURACY. ...................................................................................................... 8
CONSTRUCT A MATRIX OF DATA AVAILABILITY............................................................................. 8
PERFORM AN INTERNAL ASSESSMENT OF THE CATEGORY. ....................................................... 10
THE NEED FOR FURTHER TESTING...................................................................................................... 17
FILL DATA GAPS BY READ-ACROSS, EXTRAPOLATION, INTERPOLATION ETC. ..................... 17
REFINEMENT OF THE CATEGORY........................................................................................................ 18
REFINEMENT OF THE READ-ACROSS.................................................................................................. 23
ADVICE WHEN READ-ACROSS IS NOT NECESSARILY APPLICABLE. .......................................... 29
CONCLUSIONS........................................................................................................................................... 31
REFERENCES ............................................................................................................................................. 32
TABLE 1: INVENTORY OF NICKEL COMPOUNDS.............................................................................. 36
TABLE 1.1: Nickel and Nickel Compounds in Einecs. ............................................................................ 36
TABLE 1.2: Nickel compounds included in Elincs. ................................................................................. 48
TABLE 1.3: Additional Nickel compounds, and complex substances containing nickel included in TSCA
(through 08/2000) but not included in Einecs. .......................................................................................... 49
TABLE 1.4: Additional Nickel compounds listed in ECICS (European Customs Inventory of chemical
substances), but not included in Einecs or the TSCA Inventory. .............................................................. 51
TABLE 1.5: Additional Nickel compounds in Annex I to Directive 67/548/EEC but not in Einecs or TSCA.
................................................................................................................................................................... 51
TABLE 1.6: Additional nickel compound found in the course of compiling the inventory of nickel
compounds. ............................................................................................................................................... 51
TABLE 1.7: Additional nickel hydroxycarbonate compounds not included in the lists above. ............... 52
TABLE 1.8: Nickel containing minerals (from IARC, 1990 and NiPERA, 1996). .................................. 52
3
INTRODUCTION
1.
A category approach for compounds of concern is widely used in Annex I to Directive 67/548/EEC.
Annex I is a list of dangerous substances with a harmonised classification and labelling agreed by the
Members States according to the classification criteria adopted by formal EU legislative procedures. A list of
the nearly 100 group entries already included in Annex I is given in the RIP 3.3. scoping study in the TAPIR
final report Appendix 9. These entries are called “group” entries, and the term “category” is not used in the
EU legislation.
2.
Many of these group entries date from very early versions of Annex I and reflect the general
concern for metal compounds, irrespective of the precise chemical composition of the actual compound. The
concern for the hazard of these metal compounds is also reflected in the often very low concentration limits
for certain metals to be considered as “Toxic” or “Harmful” included in the Paints and Varnishes Directive
(EEC, 1977). These specific concentration limits were carried over into Annex I of Directive 67/548/EEC in
the 12th ATP (EEC, 1991) with the introduction of the Preparations Directive in 1988 (EEC, 1988). Many of
these limits still apply today.
3.
Some of the entries are defined in quite general terms, such as “arsenic acid and its salts”. Other
entries are equally general, but do make some exceptions to the general entry. An example is “antimony
compounds, with the exception of the tetroxide (Sb2O4), pentoxide (Sb2O5), trisulfide (Sb2S3), pentasulfide
(Sb2S5) and those specified elsewhere in this Annex”. The wording indicates that whilst the entry is
considered generally applicable, certain compounds (in this case the oxides and sulfides) are excluded. Other
entries are more specific. “Triethyltin compounds, with the exception of those specified elsewhere in this
Annex” is a narrowly defined group of compounds. Finally, the elemental metal may be included as a
separate entry.
4.
Prior to the establishment of Einecs and other inventories of chemicals on the market, it was often
impossible to develop comprehensive lists of the compounds covered by these group entries. In some cases
(e.g. the proposals for a group entry for inorganic nickel compounds proposed by Norway and for chrom(VI)
compounds proposed by Germany) the proposals were accompanied by a list of the compounds that were
intended to be covered by the group entry. Now, increasing ease of carrying out computerised searches has
made it possible to list the specific individual compounds included in these group entries. One source of this
information is the N-Class database developed by Sweden and accessed from the ECB Classification and
Labelling home page. This shows that in some cases the group entry includes a very heterogeneous group of
compounds. As an example, N-Class identifies 464 individual compounds covered by the group entry 082001-00-6 for “lead compounds with the exception of those specified elsewhere in this Annex”. This includes
the twelve lead compounds covered by the Voluntary Risk Assessment carried out by Industry in
collaboration with the Netherlands. In addition to a large number of other lead(II) salts, the group also
includes a range of organic lead compounds (not including the lead alkyls which have separate entries in the
Annex), spinels, slags, wastes and other residues.
5.
The Danish EPA has reviewed five selected HPV nickel compounds under the EU existing
chemicals programme. The five substances are nickel (metal), nickel sulfate, nickel dichloride, nickel
dinitrate and nickel carbonate. This has led to the classification of these five substances in Annex I based on
the conclusions of the hazard assessment. Apart from metallic nickel, the four nickel compounds considered
are all classified for hazards that are regarded with particular concern in the EU. These classifications include
concern for carcinogenicity (Category 1), mutagenicity (Category 3) and Reproductive toxicity (Category 2)
according to the EU criteria 1 . These revised classifications are included in the 30th Adaptation to Technical
1
References to the EU classification criteria refer in all cases to Annex VI to Directive 67/548/EEC, and not to the
implementation of GHS criteria in EU legislation.
4
Progress of Directive 67/548/EEC 2 . This review has also led to the revision of the classification of the other
nickel compounds already included in Annex I. Revised classifications for the nickel sulfides and nickel
oxides have been agreed for inclusion in the 31st ATP currently in preparation (ECB, 2007b). No change in
the existing classification for nickel carbonyl was considered necessary.
6.
Given that a large number of other nickel compounds that are not covered by these entries in Annex
I may also be on the market, the Danish EPA considered that additional proposals for classification of
relevant nickel compounds based on a category approach was required (Danish EPA, 2005a). If only some
nickel compounds are included in Annex I as Category 1 carcinogens this might lead to market distortions,
since if nickel compounds with similar properties are not included in Annex I, they could be perceived to be
safer than those with a harmonised classification, and lead to unjustified substitution of nickel compounds
currently in use by others not included in Annex I. This would not be beneficial for either the regulatory
community or the industries concerned.
7.
Two earlier classification proposals for group entries for nickel compounds have been made by
Norway and Sweden but were not discussed in the relevant EU Technical Committees. A Norwegian proposal
(W031) (ECB1/46/95 – Add. 12.) for a group classification of inorganic nickel compounds in Einecs included
a list of approximately 125 inorganic nickel compounds in Einecs. More recently, Sweden has made a
proposal for the environmental classification of metals which includes an entry for “Inorganic compounds of
nickel” (ECBI/89/04). The Danish category approach to classification was presented as a refinement of these
earlier, less specific, category approaches to metals classification, in a deliberate attempt to avoid the
heterogeneity seen in some of the group entries described above.
8.
The Danish EPA classification proposal (2005a) listed the nickel compounds that would potentially
be included in the category approach individually, and includes a rationale for the classification proposed for
each entry. The proposal also included additional background information, including a modified version of
the OECD Example F and information on the current provisional classification of nickel compounds. The
revised Danish EPA proposal (2006a) includes a revised rationale for the classification proposed for each
entry.
9.
In developing these classification proposals, MSDS from a number of different suppliers of nickel
compounds were found on the Internet. The approach taken in this proposal is consistent with the approach
taken by Industry in compiling Material Safety Data Sheets, in that, for a number of nickel compounds, most
MSDS identify hazards on the basis of read-across rather than on the basis of actual data.
10.
The five individual HPV nickel compounds reviewed by the Danish EPA were discussed by the
OECD at SIAM 24 3 . The health part of the SIAP for the five specific nickel compounds was discussed and
revised at the meeting, and no comments to these SIAPs have been received by the OECD by the deadline for
final endorsement. The description below is based on the work of the Danish EPA under the EU existing
chemicals programmes and, in particular, the discussions held in the EU Classification and Labelling
Technical Committees. This work has led to the adoption of proposals for a legally binding harmonised
classification and labelling of a large number of nickel compounds using a category approach. These
proposals have been agreed by the TC C&L and are being considered by the Commission for inclusion in the
31st ATP of the EU Classification and Labelling Directive 67/548/EEC currently under preparation. Some
modifications to a number of the individual entries have been suggested by the Commission and the resulting
proposals have been posted on the ECB website (ECB, 2007b).
2
The 30th ATP received a favourable opinion at a meeting of the Committee on the Adaptation to Technical Progress of
the Directives for the Elimination of Technical Barriers to Trade with Dangerous Substances and Preparations held on 16
February 2007. The Directive has not yet been adopted by the Commission. The relevant classification proposals are
available on the ECB website (ECB, 2007a).
3
One HPV pigment, CI Pigment Yellow 53 has been assessed by the OECD previously. This compound is further
discussed in paragraph 64 below.
5
IDENTIFICATION OF STRUCTURE-BASED CATEGORY AND ITS MEMBERS:
11.
The category is defined as “nickel and nickel compounds”. This description is a category already
widely used in EU legislation. Table 1 shows a list of the nickel compounds identified. “Nickel and nickel
compounds” includes over 300 compounds of very diverse chemical structure.
12.
The list was primarily based on compounds in the European Inventory of Existing commercial
Chemical Substances, Einecs (EU Commission, 1990). A number of different searches were made. Whilst the
majority of the substances shown in the final list were found as the result of a single search, different searches
identified a number of compounds not included in other searches (Table 1.1). There are also three nickel
compounds included in Elincs with agreed classifications in Annex I to Directive 67/548/EEC up to the 30th
ATP (Table 1.2). These lists were supplemented by a search in TSCA (up to and including August, 2000)
(Table 1.3) which identified an additional forty compounds on the US market which are not reported to be on
the EU market. Additional compounds were identified in ECICS (Table 1.4) as well as in the Swedish NClass database and other data sources (Table 1.5) and in the course of the discussions (Table 1.6). In
discussions on the identity of the HPV “nickel carbonate”, a number of nickel hydroxycarbonate compounds
were identified (Table 1.7). Finally, a number of nickel ores have been identified from the IARC monograph
(Table 1.8).
13.
Whilst Table 1 probably includes most of the nickel compounds actually on the market, this cannot
be considered a definitive list 4 .
14.
Numerically, organic nickel compounds outnumber inorganic nickel compounds. The category also
includes a number of complex nickel-containing compounds, many of which are waste products.
15.
A second type of grouping of nickel compounds is also used administratively. This divides nickel
compounds into five groups: Metallic nickel, oxidic nickel, sulfidic nickel, soluble nickel and nickel carbonyl.
These groups reflect the main nickel compounds seen during nickel refinery production, rather than the wider
range of nickel chemicals on, or potentially on, the market. These different categories have been used in some
countries as the basis for different Occupational Limit Values (OELs) based on differences in the types and
potency of different mammalian toxicological effects.
16.
The wide diversity of chemical types suggests that whilst “nickel and nickel compounds” is useful
as a category in identifying compounds that contain nickel and may therefore potentially be a source of nickel
release, it requires further refinement in order to provide a basis for a read-across approach that can identify
hazards that may be common to all members of the (sub-)category. This refinement step, identifying firstly
appropriate sub-categories and secondly nickel compounds that can reasonably be considered as members of
these different sub-categories is an essential part of this category approach.
17.
There are a number of assumptions underlying any grouping of nickel compounds for estimating
their biological properties. The main assumption is that it is the nickel ion that is responsible for the effects to
be assessed. This is considered to be a reasonable assumption for the majority of the inorganic anions of
nickel compounds and for some organic anions. This implies that in the case of inorganic metal salts, the
hazard assessment is based on the known toxicity of the hydrated cation.
18.
The primary basis of any grouping would therefore be the water solubility of the nickel salt. Two
reports prepared for the Danish EPA have collected and assessed the available data for water solubility of
inorganic nickel compounds (Carlsen, 2001a) and organic compounds (Carlsen, 2001b).
19.
In the table below, a grouping of the inorganic 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 than 10-4 mol/L,
4
This is confirmed by the fact that the ECB have carried out further searches since the conclusion of the discussions and
have found additional nickel-containing compounds. These have not been included in this document.
6
‘slightly soluble’ covers the solubility range 10-4 - 10-2 mol/L, ‘soluble’ the range 10-2 - 5·10-1 mol/L and ‘very
soluble’ refers to solubility above 5·10-1 mol/L.
20.
It should be noted that the group of “insoluble” compounds, with solubility < 10-4 mol/L covers a
range of solubility. Nickel oxides and mixed metal oxides are in general characterised as insoluble. Nickel
metal and nickel metal compounds are also characterised by their very limited solubility. Nickel sulfide and
subsulfide are normally also considered as insoluble. However, as the following discussion shows, substances
conventionally thought of as “insoluble” by chemists or toxicologists may still be sufficiently soluble to
produce effects on the aquatic environment and human health that can lead to hazard classification.
Grouping of nickel species based on inorganic ligands in water (from Carlsen, 2001a).
Insoluble
Group 13
Group 14
Group 15
Group 16
NiXB
NiXSi
NiXPY
NiXSY
NiXAs
NiXSe
NiXSbY
NiXTe
Group 17
Misc.
Ni2Fe(CN)6
Ni2P2O7
Ni3(AsO3)2
Ni3(AsO4)2
Ni(AsO3)2
Slightly
soluble
Ni(CO)4
Ni3(PO4)2
NiSO3a
Ni(CN)2
Ni[NiP2O7]
NiSeO3
Ni(IO3)2
Ni2Fe(CN)5NO
NiCO3
Ni(HCO3)2
Soluble
Very
soluble
NiK2(SO4)2
NiB6O10
Ni(BF4)2
Ni(SCN)2
NiSiF6
Ni(NO3)2
Ni(H2PO2)2
NiF2
NiSO4
NiCl2
a
Ni(SO3NH2)2
Ni(ClO3)2
NiSeO4
Ni(ClO4)2
NiBr2
Ni(BrO3)2
NiI2
21.
No comparable grouping of organic ligands has yet been carried out (Carlsen, 2001b). In contrast to
the inorganic nickel compounds it is not obvious how to group the organically based species based on
solubility alone. Aqueous solubility is not unexpectedly seen to decrease with increasing molecular weight
and increasing carbon 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 the solubility of the complexes cannot immediately be related to the solubility of the single
ligands. Hence, it seems more appropriate to group organically based nickel complexes based on the stability
of the complexes.
22.
The organic nickel compounds have been reviewed, and a number of organic nickel compounds
have been included in the group of compounds for which classification has been agreed. These compounds
are considered to a) have a solubility similar to comparable inorganic compounds and b) to be compounds
where the nickel is not significantly complexed to the organic part of the molecule to invalidate comparison
with the data obtained from the inorganic reference compounds.
7
GATHER PUBLISHED AND UNPUBLISHED DATA FOR EACH CATEGORY MEMBER.
23.
There is a vast database on the human health effects of nickel compounds. A search in Toxline gave
2538 hits for nickel and toxicity, 5077 hits for nickel and effects and about 16000 hits for nickel and
sensitisation. However, the data available for any individual nickel compounds can vary considerably. The
two compounds for which there is data that covers most endpoints are the two soluble compounds, nickel
dichloride and nickel sulfate. Much of the database relating to nickel metal is linked to sensitisation. On the
other hand, there is virtually no data at all for most nickel compounds. In particular, data on the organic nickel
compounds is extremely limited.
EVALUATE DATA FOR ACCURACY.
24.
Much of these human health data have been reviewed in good quality reviews including UK HSE
(1987), IARC (1990), Environment Canada and Health Canada, (1994), IPCS (1991, 1996), US ATSDR
(1997) and a Nordic Expert Group (Aitio, 1995). NiPERA in collaboration with Eurométaux have also
produced a criteria document for nickel and nickel compounds for the European Commission (NiPERA
1996). Toxicology Excellence for Risk Assessment (TERA) has prepared a toxicological review of soluble
nickel salts for Metal Finishing Association of Southern California Inc., US-EPA and Health Canada (TERA
1999).
25.
In depth reviews of health effects of metallic nickel, nickel sulfate, nickel chloride, nickel nitrate
and nickel (hydroxy)carbonate and a background report in support of the individual have been prepared by
the Danish EPA (Danish EPA 2005b, 2005c, 2005d, 2005e, 2005f and 2006d). Reports covering the
environmental aspects of these five compounds are currently being finalised.
CONSTRUCT A MATRIX OF DATA AVAILABILITY.
26.
A matrix of available data included in the draft risk assessment reports prepared under the OECD
SIDS and the EU existing chemicals programmes is shown below for nickel metal, nickel sulfate, nickel
chloride, nickel nitrate and nickel carbonate 5 .
27.
Data is also available for the other nickel compounds included in Annex I. One of these is another
HPV substance, nickel oxide and another, nickel sulfide, is an LPVC substance. Data has been included from
the reviews quoted above, in particular from the Background report is support of the individual risk
assessment reports (Danish EPA, 2006d). This data is summarised in the matrix of available data shown
below.
5 The compound reported as a HPV chemical to IUCLID was nickel carbonate (CAS No. 3333-67-3). In the course of
subsequent discussions with the Industry, it became clear that the marketed product was in fact a nickel
hydroxycarbonate and not nickel carbonate. For administrative purposes, the commercial product is considered to be the
1:2 hydroxycarbonate, [carbonato(2-)] tetrahydroxytrinickel, (CAS No. 12607-70-4, EC No. 222-068-2) which is also
included in the TSCA Inventory. The evaluation also covers the 2:3 basic carbonate (CAS No. 12122-15-5). As it is not
always clear from the study reports which precise carbonate has been tested, the results are shown as “nickel carbonate”.
8
√
√
√
(√)
√
√
-
√
-
-
√
√
Reproductive
Toxicity
√
Carcinogenicity
-
Repeated
dose
-
Acute
-
Daphnid
chronic
Skin
Sensitisation
dissolution
protocol
transformation test
screening
test
Daphnid
acute
Irritation
nickel
metal**
nickel oxide
Mutagenicity
MATRIX OF DATA AVAILABILITY ON SELECTED NICKEL COMPOUNDS.
EnvironEcological effects*
Human Health effects
mental fate
Fish acute
Nickel
compound
(√)
-
√
-
nickel
√
√
√
√
√
sulfide
/
subsulfide
screening
nickel
√
√
(√)
dihydroxide test
(-)
dissolution
“nickel
(√)
(√)
√
protocol.
carbonate”
soluble
nickel
√
√
√
√
√
√
√
√
√
√
sulfate
soluble
nickel
(√)
√
√
√
√
√
√
√
√
√
dichloride
soluble
nickel
(√)
√
√
√
√
√
√
dinitrate
soluble
nickel
√
√
carbonyl
Key: “√” denotes that sufficient data are available for the substance/endpoint for hazard identification. “(√)” indicates that
there is some data, but this is not sufficient to draw a conclusion directly. In some cases additional data may be needed. “(-)”
indicates only very limited data from which no conclusions can be drawn. “-” denotes no data available.
In all cases except for “√” and for the carcinogenicity of nickel metal, read across has been performed to varying extents as
described in more detail below.
Shaded areas show six possible subcategories (the five subcategories shown in paragraph 15 and a sixth sub-category which
includes sparingly soluble nickel hydroxide and carbonate).
*: data concerning other endpoints and species are available and are being considered.
**: nickel metal powder (INCO123) and nickel granules have been tested. Only the powder has been tested in the 28 d
dissolution test.
28.
The nickel compounds for which most data is available are the three soluble nickel salts, nickel
oxides and nickel sulfides. Less information is available for nickel metal, the semi-soluble compounds nickel
carbonate and nickel hydroxide, and for nickel carbonyl. Whilst the soluble and semi-soluble salts tested are
all in the Ni(II) oxidation state, some of the sulfides and oxides may be in mixed formal oxidation states of
nickel and/or complex coordination in the solid form (IARC, 1990). Nickel metal and nickel carbonyl are
both in the Ni(0) oxidation state.
29.
The nickel compounds included in the matrix of available data are mainly those directly associated
with the (refinery) production of metallic nickel, and nickel alloys. There is a IUCLID file available of one of
the intermediate products (nickel matte) but this contains no data. The other main intermediate product, ferronickel, is not included in Einecs, as at the time Einecs was compiled it was agreed that this was an alloy.
30.
The data on “downstream” nickel compounds not directly associated with the production processes,
and in particular, the organic nickel compounds, is very limited. The EU provisional classification supplied
by the producer/importer in the IUCLID file is available for a number of other nickel compounds, including a
number of organic compounds and complex waste products such as slimes and sludges. However, there is no
actual data in these IUCLID submissions, and it is not clear whether these provisional classifications have
been based on experimental evidence or on assumptions about the properties of the compounds (i.e.
application of a category approach). In some cases Safety Data Sheets are available, and there is a very
limited amount of original information available from these. In most cases, the hazards have been identified
using read-across from the hazards considered to be relevant for nickel compounds.
9
PERFORM AN INTERNAL ASSESSMENT OF THE CATEGORY.
31.
The following paragraphs evaluate the classifications for the compounds listed in the matrix of data
availability as assessed against the EU classification criteria and included either the 28th. ATP (EC, 2001b) or
the 30th ATP 6 , or agreed by the EU TC NES for possible inclusion in 31st. ATP (currently in preparation).
The corresponding hazard statements based on the GHS classification criteria are shown in footnotes. The
conversion between EU and GHS hazard statements is based on the Table of Equivalence included in a report
for the EU Commission on GHS (Milieu, 2005b). The hazards of the five HPV nickel compounds have also
been reviewed directly against the GHS criteria as part of the preparation for the workshop on experience in
applying the GHS criteria for classification and labelling using SIDS documents (Danish EPA, 2007). It
should be noted that whilst the EU classification proposals have been reviewed and agreed by an EU
Technical Committee, this is not the case for the GHS classifications which are those proposed by the Danish
EPA.
32.
In applying the aquatic hazard classification rules for nickel compounds, the evaluation is based on
the values of an EC50 of 0.068 mg/L for the acute aquatic toxicity of the nickel ion and an EC10 of 2.4 μg/L for
the chronic toxicity. For the soluble compounds, no Transformation/Dissolution (T/D) protocol is required.
For less soluble compounds, the use of the T/D protocol, i.e. solubility dependency of pH at environmentally
realistic pHs has been used.
The soluble nickel compounds, including nickel carbonyl, are classified as N; R50-53 7 .
Nickel carbonate and nickel hydroxide were both tested in a T/D protocol screening test, and classified as N;
R50-53 in the 28th. ATP (EC, 2001b).
Nickel sulfide and nickel subsulfide were both tested in a T/D protocol screening test. Nickel sulfide was
classified as N; R50-53 and nickel subsulfide as N; R51-53 8 in the 28th ATP (EC, 2001b). Following
agreement on the values for the acute and chronic toxicity, it was agreed that both should now be classified as
N; R50-53.
The nickel oxides are substantially less soluble and are classified with R53 9 . Although this classification was
adopted in the 28th ATP (EC, 2001b), NiPERA (2006) pointed out that the average concentration for nickel
oxide from the T/D protocol was 2 μg/L and, as such, below the figure for chronic toxicity. Hence, nickel
oxide and analogous substances should not be classified as causing long-term adverse effects to the aquatic
environment. The Danish EPA (2006b) noted that for this escape clause to be applied, data from a 28-day
dissolution protocol was needed, and this data was not available. At the TC C&L Environment meeting in
April 2006, other Member States supported this view and the default classification with R53 remained
unchanged.
It has been agreed that metallic nickel does not fulfil the criteria for classification for hazards to the aquatic
environment. However, there is agreement that fine metal powders prepared by the Mond process do fulfil the
criteria for classification as R52-53 10 . The fine metal powders have been defined on the basis of particle size
6
Whilst adopted by the Technical Committee, this has not yet been adopted by the Commission or published in the
Official Journal.
7
Classification with N; R50-53 corresponds to the GHS Chronic Category 1. This classification also corresponds to the
GHS Acute Category 1, this is not used as an additional classification in the EU classification system.
8
Classification with N; R51-53 corresponds to the GHS Chronic Category 2. This classification also corresponds to the
GHS Acute Category 2, this is classification is not included in the EU classification system.
9
Classification with R53 corresponds to the GHS Chronic Category 4.
10
Classification with R52-53 corresponds to the GHS Chronic Category 3. This classification also corresponds to the
GHS Acute Category 3, this is classification is not included in the EU classification system.
10
diameter < 1 mm in the Annex I entry in the 31st ATP currently in preparation (ECB, 2007b). In the Danish
GHS proposal, these powders are defined on the basis of an average specific surface area ≥ 0.1 m2/g.
33.
There is data for acute oral toxicity for all the reference compounds with exception of nickel
carbonyl. The acute oral toxicity decreases with decreasing water solubility and is of concern for soluble and
slightly soluble compounds, whilst less soluble compounds (e.g. sulfides, oxides and the metal) do not give
rise to concern for this effect.
Whilst most of the figures for the soluble and sparingly soluble compounds lie in the range of the criteria for
Xn; R22 11 (GHS Category 4), nickel dichloride has been classified separately as T; R25 12 as the LD50 is <
200 mg/kg. Nickel sulfate has been classified as Xn; R22 according to the EU criteria, whilst the LD50 of <
300 mg/kg leads to a more stringent classification in the GHS Category 3 together with nickel dichloride.
However, there is no direct correlation between the acute toxicity values and water solubility. The
approximate value of the LD50 for nickel dinitrate, one of the most soluble nickel compounds, is closer to the
values for the slightly soluble carbonate and hydroxide than the other, more soluble compounds.
34.
There is data for acute inhalational toxicity for nickel carbonyl, and this is classified as T+; R26 13 .
This appears to be no acute inhalational toxicity (LC50) data available for any of the other nickel compounds
considered here. However, there is evidence from sub-acute inhalational studies as well as from toxicokinetic
considerations that indicates that this route of administration is of concern for those nickel compounds where
there is concern for acute toxicity by the oral route. Nickel hydroxide is already classified for acute toxicity in
the EU by both oral and inhalation routes of administration.
With the exception of nickel carbonyl, the EU TC C&L agreed that the concern for oral and inhalational
toxicity should be considered as comparable 14 . In applying the GHS criteria, classification is also proposed in
the same toxicity category for both the oral and inhalation routes 15 .
35.
There is no data for acute dermal toxicity for any of the compounds reviewed. There is however no
grounds for concern for this effect, due to the low systemic uptake of these compounds by this route.
36.
Whilst animal studies with nickel sulfate show no significant irritating effect on the skin, human
data shows that solutions of nickel sulfate at concentrations > 20% are irritating. A similar effect in humans is
also seen with nickel dichloride (Environment Canada and Health Canada, 1994). An Annex V animal study
with nickel nitrate shows irritation which fulfils the criteria for classification as Xi; R38 16 . There is no human
or animal data for nickel carbonate on irritation, but information on the pH of its solutions is available that
shows that the pH is not so extreme that this would in itself lead to classification for irritation.
11
Classification with Xn; R22 corresponds approximately to the GHS Acute toxicity Cat. 4 (oral). There is however a
difference in the criteria where the EU cut-off for the LD50 is 200 mg/kg, and the GHS cut-off is 300 mg/kg.
12
Classification with T; R25 corresponds approximately to the GHS Acute toxicity Cat. 3 (oral). See comment above
concerning the difference in cut-off.
13
The range of classification with T+; R26 corresponds to either the GHS Acute toxicity Cat. 1 or 2 (inhalation),
depending on the actual data. Based on the data for nickel carbonyl toxicity, the appropriate GHS classification is Acute
toxicity Category 1.
14
Classification with T; R25 is accompanied by classification with T; R23; classification with Xn; R22 with Xn; R20..
15
It should be noted that Section 3.1.3.6 Classification of mixtures based on ingredients of the mixture (Additivity
formula) of the GHS criteria explicitly allows for extrapolation between oral, dermal and inhalation acute toxicity
estimates where data is lacking. However, this extrapolation is not included in the actual criteria for substance
evaluation. An Industry proposal for the GHS classification of nickel sulfate makes the same extrapolation, although to a
lower classification category for acute inhalation toxicity (Acute category 4).
16
Classification with Xi; R38 corresponds to the GHS Skin irritant category 2.
11
The EU TC C&L has agreed that the soluble and sparingly soluble salts should be classified as Xi; R38.
A specific concentration limit of 20% for this effect has been set for the three soluble compounds based on
the human data for nickel sulfate.
There is no concern for skin irritation for nickel carbonyl or the less soluble sulfide, subsulfide, oxides or
metal.
37.
There is a marked difference in the results of animal studies on eye irritation with nickel sulfate and
nickel dinitrate. Whilst there is little sign of irritation with nickel sulfate, animal data shows severe eye
irritation with nickel nitrate. It has been suggested that this is related to the oxidising potential of the
compound.
The EU TC C&L Technical Committee has agreed that nickel nitrate should be classified as Xi; R41 17 . None
of the other compounds have been classified for eye irritancy.
38.
Nickel is a well-known skin sensitiser. The soluble salts show considerable potency as initiators of
this effect. Skin sensitisation appears to occur across a very wide range of water solubility, and the even the
insoluble nickel oxides are considered to meet the criteria for classification as skin sensitisers. Release of
nickel from nickel-containing metal surfaces is related to direct and prolonged skin contact and to the rate of
nickel release to the skin.
The EU TC C&L has agreed that all the nickel compounds specifically discussed, with the exception of nickel
carbonyl, should be classified as R43 18 .
A specific concentration limit of 0.01% for this effect has been set for the three soluble compounds based on
human data, reflecting the high potency of the nickel ion in inducing skin sensitisation.
39.
Unlike the extensive documentation for skin sensitisation, the data for respiratory sensitisation is
very limited. Nickel sulfate is considered to be a respiratory sensitiser in humans, based on a limited number
of cases. There are no data for nickel dichloride, nickel dinitrate or nickel carbonate. There are a limited
number of case reports associated with exposure to nickel metal, and the IUCLID file for nickel matte, which
consists mainly of nickel subsulfide, includes a statement (but no data) that this effect may be of concern. The
Ni2+ ion is considered exclusively responsible for the immunological effects of nickel. As nickel sulfate is
considered to induce respiratory sensitisation it must be assumed that nickel chloride, nickel dinitrate, nickel
carbonate and nickel hydroxide also may have the potential to induce respiratory sensitisation and thus,
should be regarded as respiratory sensitisers.
The EU C&L Technical Committee has agreed to classify soluble and slightly soluble compounds with the
exception of nickel carbonyl as R42 19 . but agreed that the data for metallic nickel is not sufficient to lead to
classification with R42. The nickel oxides and sulfides were not classified for this effect.
40.
There is data showing repeated dose toxicity following inhalation for nickel sulfate, nickel chloride,
nickel subsulfide, nickel oxide and metallic nickel. Inhalational repeated dose toxicity is shown by both
soluble and insoluble nickel compounds. The available studies show that the effects seen on the lung occur at
lower levels in nickel sulfate than with nickel subsulfide or nickel oxide.
The EU C&L Technical Committee has agreed that all the nickel compounds specifically discussed, with the
exception of nickel carbonyl, should be classified as T; R48/23.
17
Classification with Xi; R41 corresponds to the GHS Serious eye damage category 1
18
Classification with R43 corresponds to the GHS Skin Sensitiser
19
Classification with R42 corresponds to the GHS Respiratory Sensitiser
12
A specific concentration limit of 1% for this effect has been set for the three soluble compounds based on the
data for nickel sulfate.
41.
There is evidence of in vitro mutagenicity for a number of soluble and insoluble compounds. There
is much less data from in vivo studies. The three soluble compounds have been extensively tested in vivo, and
there are also in vivo data for nickel sulfide. There is very limited data for metallic nickel, nickel carbonate or
nickel hydroxide. There is some human data on chromosome aberrations in humans, mainly based on studies
carried out on refinery workers. In general, the evidence for insoluble compounds is much less than for
soluble compounds.
The in vitro data shows positive results across the range of solubility, particularly in tests that show effects on
chromosomes. The in vivo data is conflicting. The data has been extensively discussed in both the context of
the EU existing chemicals assessment with respect to possible additional testing, and in the EU TC C&L with
respect to classification. The mutagenicity of the soluble compounds and nickel carbonate was discussed by
the EU Specialised Experts in April, 2004 (European Commission, 2004). The Specialised Experts concluded
that nickel sulfate, nickel chloride and nickel nitrate should be classified as Muta. Cat. 3; R68 20 . This
conclusion is based on evidence of in vivo genotoxicity in somatic cells, after systemic exposure, and, hence
the possibility that the germ cells are affected cannot be excluded. However further testing of effects on germ
cells was not considered practicable. Concerning nickel carbonate, the experts concluded that there was
insufficient evidence for classification for this substance.
In the subsequent discussions, the EU TC C&L agreed to classify the soluble nickel compounds as Muta. Cat.
3; R68. The semi-soluble compounds, nickel carbonate and nickel hydroxide were also classified as Muta.
Cat. 3; R68, taking into account a derogation statement from Industry for nickel carbonate (Laine, 2003).
Nickel sulfide and nickel subsulfide were also classified as Muta. Cat. 3; R68 on the basis of data, not least
the results of positive in vivo Comet assays in the lung.
In the absence of adequate data on which to make a proposal, classification of metallic nickel, nickel oxides
and nickel carbonyl was not considered. There is agreement that further testing for nickel metal may be
required, depending on the result of inhalational carcinogenicity studies currently being carried out.
It should be noted that the acute oral toxicity of both nickel carbonate and nickel hydroxide shows that there
is systemic uptake of both these compounds, and that therefore, like the more soluble compounds, the nickel
ion may be systemically available to the germ cells, and that for nickel carbonate and nickel hydroxide the
possibility that the germ cells are affected cannot be excluded. There is no evidence of similar systemic
uptake for the less soluble nickel sulfides, subsulfides, oxides and metallic nickel. Concern for genotoxicity in
these cases is more related to concerns for carcinogenicity at the target cells than for concern for effects on
germ cell mutagenicity.
42.
Nickel sulfide, subsulfide and the nickel oxides have long been recognised as human carcinogens,
and classified as Carc. Cat. 1; R49 21 . A positive effect has been seen in animals with nickel subsulfide and
nickel oxide, but not with nickel sulfate. The available data for inhalational carcinogenicity is not adequate to
assess the effects of the metal. The data following other routes of administration is very limited but there is a
recent study on nickel sulfate following oral administration which is negative.
The cancer epidemiology was discussed by the EU Specialised Experts in April, 2004 (European
Commission, 2004). The Specialised Experts concluded that nickel sulfate and nickel chloride should be
considered as human carcinogens (Carc. Cat. 1). The data was considered to be sufficient to establish a causal
association between the human exposure to the substances and the development of lung cancer. There was
supporting evidence for this conclusion from more limited data on nasal cancer.
20
Classification with Muta. Cat. 3; R68 for effects on germ cells corresponds to the GHS Germ cell mutagen Category 2.
21
Classification with Carc. Cat. 1; R49 corresponds to the GHS Carcinogen Category 1 (“by inhalation”)
13
In drawing this conclusion regarding lung cancer, it was recognised that the epidemiological data showed a
clear exposure response relationship for water-soluble compounds, consistency across and within studies and
time periods, and high strength of association. Improved exposure characterisation based on personal air
sampling and improved analysis of the water-soluble fractions added to the reliability of the findings.
Confounding factors such as co-exposure to insoluble nickel compounds and smoking were adequately
addressed, and did not lower the level of confidence in reaching the conclusion.
The Specialised Experts also agreed that nickel nitrate and nickel carbonate should be classified as Carc. Cat.
1. In reaching this conclusion for nickel nitrate the Specialised Experts recognised that the water solubility of
this compound was sufficiently similar to that of nickel sulfate and nickel chloride to justify the same
classification. Since both the water soluble nickel compounds considered at this meeting and the insoluble
inorganic nickel compounds already classified in Annex I are considered as human carcinogens consequently
also the nickel carbonate was considered to be a human carcinogen.
In the subsequent discussions, the EU TC C&L initially agreed to classify all the nickel compounds under
discussion with the exception of nickel metal and nickel carbonyl as Carc. Cat. 1.
It was also agreed that R49 rather than R45 22 was appropriate, as the human evidence on which the
conclusion was based was following inhalational exposure, and the oral study with nickel sulfate was
negative. It was also noted that the tumours seen were local rather than systemic. As a result of further
discussion (see paragraph 80), it was agreed to classify the nickel compounds covered by the group proposal
as Carc. Cat. 2; R49.
Discussion of the current classification for metallic nickel as Carc. Cat. 3; R40 23 was postponed until the
results of inhalational carcinogenicity studies currently in progress are available 24 .
Possible revision of the current classification for nickel carbonyl as Carc. Cat. 3; R40 was not discussed.
43.
Nickel carbonyl is already classified as Repr. Cat. 2; R61 25 . Studies on both fertility and
development are available for nickel sulfate and nickel dichloride, but no relevant studies on nickel carbonate,
nickel nitrate, nickel sulfide, nickel oxide or metallic nickel have been found. The data for nickel sulfate and
nickel chloride fulfil the criteria for classification as Repr. Cat. 2; R61.
In the subsequent discussions, the EU TC C&L agreed to classify the soluble nickel compounds as Repr. Cat.
2; R61. Although there is no data available for the other nickel compounds, this classification was also
considered appropriate for the sparingly soluble compounds (nickel carbonate and nickel hydroxide) but not
for the compounds of lower solubility (nickel sulfide, subsulfide, oxides or metal). As for mutagenicity, it
should also be noted that the acute oral toxicity of both nickel carbonate and nickel hydroxide shows that
there is systemic uptake of both these compounds, and that therefore, like the more soluble compounds, the
nickel ion may be systemically available. There is no evidence of similar systemic uptake for the less soluble
nickel sulfides, subsulfides, oxides and metallic nickel.
44.
The conclusions of these discussions in the EU TC C&L was that classification proposals were
agreed for all endpoints discussed above for all the nickel compounds listed in the matrix of data availability.
The conclusion for nickel sulfate and metallic nickel was to revise the entries for these two substances in
Annex I and to include new entries for nickel dichloride and nickel dinitrate in the 30th. ATP (ECB, 2007a).
22
Classification with Carc. Cat. 1; R45 corresponds to the GHS Carcinogen Category 1 but without any limitation on the
route of administration.
23
Classification with Carc. Cat. 3; R40 corresponds to the GHS Carcinogen Category 2. This classification in the EU
system does not include any possibility of including a particular route of administration.
24
These results are expected in 2007.
25
Classification with Repr. Cat. 2; R61 corresponds to the GHS Reproductive toxicant Category 1 (“May damage the
unborn child”)
14
No change in the current classification of nickel carbonyl was considered necessary. For the other
compounds, (nickel hydroxide, nickel sulfides, nickel subsulfide, and the nickel oxides) there was agreement
in the EU TC C&L on a revision of the current Annex I entries in the 31st ATP currently under preparation
(ECB, 2007b).
45.
The agreed classifications for the substances listed in the matrix of data availability are shown in the
Table below:
Substance (1)
nickel sulfate
EU Classification
Carc. Cat. 1; R49;
Repr. Cat. 2; R61;
Muta. Cat. 3; R68;
Xn; R20
Xn; R22;
T; R48/23; (SCL of 1%).
Xi; R38; (SCL of 20%)
R42
R43 (SCL of 0.01%
N; R50-53
nickel dichloride
Carc. Cat. 1; R49;
Repr. Cat. 2; R61;
Muta. Cat. 3; R68;
T; R23
T; R25
T; R48/23; (SCL of 1%).
Xi; R38; (SCL of 20%)
R42
R43 (SCL of 0.01%)
N; R50-53
nickel dinitrate
O; R8
Carc. Cat. 1; R49;
Repr. Cat. 2; R61;
Muta. Cat. 3; R68;
Xn; R20
Xn; R22;
T; R48/23; (SCL of 1%).
Xi; R38 (SCL of 20%)
Xi; R41;
R42
R43 (SCL of 0.01%)
N; R50-53
nickel carbonate
Carc. Cat. 1; R49;
Repr. Cat. 2; R61;
Muta. Cat. 3; R68;
Xn; R20
Xn; R22;
T; R48/23;
Xi; R38;
R42
R43
N; R50-53
GHS Classification (2)
Carcinogen Category 1 by inhalation
Reproductive toxicant Category 1 (“May damage the unborn
child”)
Germ cell mutagen Category 2
Acute toxicity Cat. 3 (inhalation)
Acute toxicity Cat. 3 (oral) (3)
STOST (Repeated exposure) Category 1 (inhalation)
Skin irritant category 2
Respiratory Sensitiser
Skin Sensitiser
Hazards to the aquatic environment: Acute and Chronic
Category 1 (4)
Carcinogen Category 1 by inhalation
Reproductive toxicant Category 1 (“May damage the unborn
child”)
Germ cell mutagen Category 2
Acute toxicity Cat. 3 (inhalation)
Acute toxicity Cat. 3 (oral)
STOST (Repeated exposure) Category 1
Skin irritant category 2
Respiratory Sensitiser
Skin Sensitiser
Hazards to the aquatic environment: Acute and Chronic
Category 1 (4)
Oxidizing solid Cat. 2
Carcinogen Category 1 by inhalation
Reproductive toxicant Category 1 (“May damage the unborn
child”)
Germ cell mutagen Category 2
Acute toxicity Cat. 4 (inhalation)
Acute toxicity Cat. 4 (oral)
STOST (Repeated exposure) Category 1
Skin irritant category 2
Serious eye damage category 1
Respiratory Sensitiser
Skin Sensitiser
Hazards to the aquatic environment: Acute and Chronic
Category 1 (4)
Carcinogen Category 1 by inhalation
Reproductive toxicant Category 1 (“May damage the unborn
child”)
Germ cell mutagen Category 2
Acute toxicity Cat. 4 (inhalation)
Acute toxicity Cat. 4 (oral)
STOST (Repeated exposure) Category 1
Skin irritant category 2
Respiratory Sensitiser
Skin Sensitiser
Hazards to the aquatic environment: Acute and Chronic
Category 1 (4)
15
nickel dihydroxide
Carc. Cat. 1; R49;
Repr. Cat. 2; R61;
Muta. Cat. 3; R68;
Xn; R20
Xn; R22;
T; R48/23;
Xi; R38;
R42
R43
N; R50-53
nickel sulfide
/nickel subsulfide
Carc. Cat. 1; R49;
Muta. Cat. 3; R68;
T; R48/23;
R43
N; R50-53
nickel oxide
/nickel dioxide
/nickel trioxide
Carc. Cat. 1; R49;
T; R48/23;
R43
R53
Carc. Cat. 3; R40;
T; R48/23
R43
R52-53(5)
metallic nickel
nickel carbonyl
F; R11
Carc. Cat. 3; R40;
Repr. Cat. 2; R61;
T+; R26;
N; R50-53
Carcinogen Category 1 by inhalation
Reproductive toxicant Category 1 (“May damage the unborn
child”)
Germ cell mutagen Category 2
Acute toxicity Cat. 4 (inhalation)
Acute toxicity Cat. 4 (oral)
STOST (Repeated exposure) Category 1
Skin irritant category 2
Respiratory Sensitiser
Skin Sensitiser
Hazards to the aquatic environment: Acute and Chronic
Category 1 (4)
Carcinogen Category 1 by inhalation
Germ cell mutagen Category 2
STOST (Repeated exposure) Category 1
Skin Sensitiser
Hazards to the aquativ environment: Acute and Chronic
Category 1 (4)
Carcinogen Category 1 by inhalation
STOST (Repeated exposure) Category 1
Skin Sensitiser
Hazards to the aquatic environment: Chronic Category 4
Carcinogen Category 2 (inhalation)
STOST (Repeated exposure) Category 1
Skin Sensitiser
Hazards to the aquativ environment: Acute and Chronic
Category 3 (4) (6)
Flammable liquid Cat. 2
Carcinogen Category 2
Reproductive toxicant Category 1 (“May damage the unborn
child”)
Acute toxicity Cat. 1 (inhalation) (7)
Hazards to the aquatic environment: Acute and Chronic
Category 1 (4)
Notes:
1. Following the Einecs rules, an entry for an inorganic salt covers both the anhydrous compound as well as all
hydrates unless hydrates are mentioned specifically in a separate entry.
2. Taken from Danish EPA (2007) and Milieu (2005b).
3. As the LD50 for female rats is 275 mg/kg, the classification for acute toxicity is more stringent in GHS
classification system than in the EU.
4. In the GHS system separate classifications are given for both Acute and Chronic effects..
5. There is agreement that metallic nickel should not be classified for hazards to the aquatic environment.
However, nickel metal products with diameter less than 1 mm should be classified as R52-53.
6. There is agreement that metallic nickel should not be classified for hazards to the aquatic environment.
However, nickel metal products with average specific surface area ≥ 0.1 m2/g should be classified as Acute and
Chronic Category 3.
7. Estimated on the basis of the LC50 values of 67 – 1900 mg/m3 (30 minute exposure), UK HSE (1987)
46.
As the available data for metallic nickel for a key endpoint, carcinogenicity, is not adequate to
assess the effects of the metal, it was recognised that the Annex I classification might need further revision
when the results of the current inhalational carcinogenicity study become available.
47.
The extent of the available data varies for the different endpoints discussed above. Whilst for some
endpoints the conclusions are based on human or experimental data for most of the individual compounds
discussed, these decisions in themselves are based, to a varying extent, on read-across.
16
In some cases, like skin sensitisation, the evidence for an effect is extensive. In other cases, such as
respiratory sensitisation, the database is limited to data on a few cases seen with nickel sulfate, nickel metal
and anecdotal evidence for nickel matte.
In some cases, such as skin sensitisation, carcinogenicity and repeated inhalational toxicity, there is clear
evidence that the effect occurs over the whole of the solubility range considered. This does not necessarily
mean that the mechanism of action is identical across the solubility spectrum, and Industry has argued that the
mechanisms of carcinogenicity may be different in the soluble nickel compounds and the less soluble sulfidic
and oxidic compounds. The evidence for the sparingly soluble compounds (nickel carbonate and nickel
dihydroxide) is particularly limited, and the classification for there two compounds is based on a higher
degree of read-across than has been necessary for the other compounds considered.
48.
The recognition that read-across is appropriate within this partial category of nickel compounds
considered specifically is an important consideration in extending the same considerations to a larger group of
comparable compounds.
THE NEED FOR FURTHER TESTING.
49.
Additional testing is currently underway to evaluate metallic nickel following inhalational
administration.
50.
Industry has initiated a research programme concerning the influence of abiotic factors on the
(chronic) ecotoxicological effects of nickel using the BLM theory 26 .
51.
Apart from the inhalational carcinogenicity study and the BLM studies, the Danish EPA is not
aware of any plans at the present time for specific testing aimed at providing additional data that would be
expected to modify the classification agreed for any of the substances discussed above.
52.
With the exception of the availability studies that have been carried out on the spinels and rutiles
(see discussion below), no further testing on compounds in the additional extended category is envisaged.
53.
NiPERA have argued that a minimum of test data is required for any individual substance to be
included in the category. Information such as basic toxicokinetic data and/or acute and irritation studies
would provide a minimum of scientifically supportable criteria for the inclusion of individual chemical
compounds into a group (NiPERA, 2006).
54.
Provision of additional information was not considered to be necessary by the EU TC C&L, and the
Danish proposal was agreed without provision of further data. An external assessment of the category was not
considered necessary for agreement on this approach.
55.
Since the potential candidates for a read-across approach are listed individually, the potential
eligibility of individual compounds has been evaluated on a case-by-case approach. This is described below.
FILL DATA GAPS BY READ-ACROSS, EXTRAPOLATION, INTERPOLATION ETC.
56.
The use of read-across for specific endpoints within the limited group of substances for which data
is available is clearly acceptable. This being the case, it seems reasonable to consider to what extent the same
approach can be applied to the much larger group of “nickel and nickel compounds”.
26
Biotic Ligand Model
17
57.
In cases where there are clear similarities to the compounds considered above, the use of readacross to evaluate the hazards of these compounds would seem justified. For example, soluble nickel(II) salts
would be expected to show the same effects as the other soluble nickel(II) salts evaluated on the basis of their
measured data.
58.
For the purposes of this evaluation, nickel compounds are placed in one of eight sub-categories:
a)
nickel sulfate, nickel dichloride, nickel dinitrate and other soluble compounds with a watersolubility greater than 10-2 mol/L (corresponding to the groups of “soluble” and “very soluble”
compounds in the Table in paragraph 20 above).
b)
nickel carbonate, nickel dihydroxide and other sparingly soluble compounds with a water-solubility
in the range 10-4 - 10-2 mol/L, (corresponding to the group of “slightly soluble” compounds in the
Table in paragraph 20 above), but excluding nickel carbonyl (group (f) below).
c)
nickel sulfide, nickel subsulfide and other ‘insoluble’ compounds with a water solubility less than
10-4 mol/L (corresponding to the group of “insoluble” compounds in the Table in paragraph 20
above) but excluding the oxides and metallic compounds (groups (d) and (e) below).
d)
nickel oxide and mixed nickel oxides
e)
metallic nickel and metallic nickel compounds
f)
nickel carbonyl
g)
nickel compounds specifically excluded from the category
h)
nickel compounds not included in the category
59.
The distinction between groups (g) and (h) reflects the fact that in group (g) compounds have been
considered individually and excluded from the category for specific reasons. In additional there are a number
of compounds in group (h) that, whilst they form part of the initial category, are not considered relevant for
inclusion for a specific classification proposal. It is possible that for some compounds in this sub-category,
additional data would indicate whether or not they should be included.
REFINEMENT OF THE CATEGORY.
60.
Read-across is used for inorganic compounds, some organic compounds and for relevant complex
substances where possible. This approach has been carried out following a process of refinement of the initial
list of nickel compounds in order to ensure that compounds for which read-across is not relevant are excluded
from the category.
61.
Whilst it is not always easy to distinguish between nickel(I) and nickel (II) compounds 27 ,
compounds known to be nickel(I) compounds have been excluded.
62.
Nickelates have also been systematically excluded, as there is no data on which to assess the
validity of a read-across from the other nickel compounds for which data is available.
63.
Tetraammine and hexaammine compounds have also been excluded as the read-across from the
hexaammine nickel complex to a hydrated nickel ion is not necessarily appropriate.
64.
Following additional information provided by Industry, a number of complex nickel oxide
compounds have been deleted from the category.
27
An example is nickel(II)chloride which is often described as nickel chloride and not by its more correct name nickel
dichloride. There is however a nickel(I)chloride that has not been included in the proposal.
18
Industry has argued that the nickel availability from these compounds, which are complex nickel-containing
oxides with either a rutile or a spinel structure, is significantly different from that of nickel oxide.
One nickel-containing mixed oxide has been studied in the OECD SIDS programme (UNEP, 2005). The
compound, C.I.Pigment Yellow 53 is a rutile pigment. Based on a nickel category approach, the main
potential hazards would be expected to be a) carcinogenicity, b) repeated dose inhalational toxicity and c)
sensitisation. Carcinogenicity was not studied in the SIDS evaluation. Repeated dose inhalational toxicity was
studied in a rat inhalation study with exposure to 60 mg/m3 for 6 hr/day for 5 days. The study produced no
clinical signs of toxicity. However, the absence of histological examination prevented identification of a
reliable NOAEC. No data are available on sensitisation. However, the substance was not considered likely to
produce this effect as the nickel has been shown to be not biologically available following repeated inhalation
and oral exposure in rats.
Following discussions with Industry, it was agreed that the concerns for carcinogenicity, repeated dose
toxicity or skin sensitisation could not be dismissed on the basis of lack of systemic absorption following oral
or repeated inhalational exposure alone. Nickel is a potent skin sensitiser and the rate set for the maximum
acceptable release from metallic nickel or nickel alloys in products intended to come into direct and
prolonged contact with the skin in the so-called Nickel Directive (EC, 1994) is 0.5 μg/cm²/week as measured
by EN 1811 (CEN, 1998).
Industry has measured the nickel release from some spinels and rutiles and compared this with the release
from bunsenite. Studies have been performed using the CEN assay used to assess the nickel release from
nickel-containing alloys for conformity with the Nickel Directive dealing with skin sensitisation as well as the
OECD 29 test method (Eurocolour, 2006). These studies have shown a different pattern of nickel release from
the spinels and rutiles compared to nickel oxide, and this justifies the exclusion of these compounds from the
category.
The Eurocolour comments (Eurocolour, 2005) suggested that in addition to the substances discussed above
cobalt nickel grey periclase should also be excluded from the proposal. Industry has subsequently shown that
the similarity of the X-ray diffraction spectrum of the periclase to bunsenite, the naturally occurring form of
nickel oxide, and the ready solubility of the periclase in concentrated hydrochloric acid indicates that it
should not be excluded from the category.
Finally, it is possible that there are other nickel-containing mixed oxides that could also be removed from this
proposal. These include a number of pigments which are no longer on the market. In the absence of further
information suggesting that these entries should be excluded, the EU TC C&L group decided that it is most
appropriate to keep these entries in the proposal.
The following spinel and rutile compounds have been excluded from the category:
CAS No.
Substance name
Crystal type
68187-10-0
Nickel-ferrite-brown-spinel; CI Pigment Brown 34
spinel
12168-54-6
Iron nickel oxide (Fe2-NiO4)
spinel (1)
71631-15-7
Nickel-iron-chromite-black-spinel; CI Pigment Black 30
spinel
68611-43-8
Nickel-niobium-titanium-yellow-rutile; CI Pigment Yellow 161
rutile
69011-05-8
Nickel titanium oxide tungstate (NiTi20-O35-(WO6)2)
rutile
68186-85-6
CI Pigment Green 50
spinel
8007-18-9
Antimony-nickel-titanium-oxide-yellow-; C.I. Pigment Yellow 53
rutile
73892-02-1
Antimony oxide (Sb203), solid soln. with nickel oxide (NiO) and titanium oxide
rutile
54576-53-3
Antimony-nickel-titanium-oxide
rutile
19
71077-18-4
Rutile, antimony nickel yellow
rutile
12018-18-7
Chromium nickel oxide (Cr2-NiO4)
spinel
97435-21-7
Iron nickel zinc oxide (Fe2-NiZnO4)
spinel
99749-23-2
Cassiterite, cobalt manganese nickel grey
cassiterite
12645-50-0
Iron-nickel-zinc-oxide-
spinel
95046-47-2
Spinels, cobalt nickel zinc grey
spinel
Notes:
1. According to Eurocolour, this compound is identical with CI Pigment Brown 34 (Eurocolour, 2002). Iron
nickel oxide with CAS No. 12168-54-6 is placed on the market separately, and one supplier has given this a
provisional classification with R49-43 (Alfa Aesar, 2005). In this case, the provisional classification applied by
the supplier is more stringent than the result of the category approach.
2. See also UNEP, 2005.
65.
Nickel forms metal-metal compounds with a number of elements. These compounds are substances
and not alloys, and the compounds with aluminium, niobium, lanthanum, dysprosium and bismuth are known
to be on the market. The classification of metallic metal has been based on data for the compound and not on
read-across from any of the other nickel compounds under review. In particular, the classification for cancer
has been based on the limited data available rather than on read-across. Studies on the inhalational
carcinogenicity of metallic nickel are currently in progress, and the relevance of including these metal-metal
compounds can be considered when the results of this study have been evaluated.
The following metal-metal compounds have therefore been provisionally excluded from the category:
EC No.
CAS No.
Substance name
234-827-5
12035-52-8
Antimony, compd. with nickel (1:1)
235-676-8
12503-49-0
Antimony, compd. with nickel (1:3)
234-439-6
12003-78-0
Aluminum, compd. with nickel (1:1)
235-261-1
12142-92-6
Nickel, compd. with zirconium (1:2)
234-807-6
12034-55-8
Nickel, compd. with niobium (1:1)
235-034-7
12059-23-3
Nickel, compd. with tin (3:1)
235-372-5
12196-72-4
Lanthanum, compd. with nickel (1:5)
235-341-6
12175-27-8
Dysprosium, compd. with nickel (1:2)
235-773-5
12688-64-1
Bismuth, compd. with nickel (1:1)
257-510-3
51912-52-8
Copper, compd. with lanthanum and nickel (4:1:1)
66.
There are a number of nickel containing compounds on the market listed as high production volume
chemicals or, in some cases, as low production volume chemicals, which are not considered as relevant for
consideration in a category approach, as their effects are not considered to be adequately described by their
nickel content.
Asphalt (EC No: 232-490-9, CAS No. 8052-42-4) is obtained as the non-volatile residue from distillation of
crude oil or by separation as the raffinate from a residual oil in a deasphalting or decarbonisation process.
Asphalt is a very complex combination of high molecular weight organic compounds containing a relatively
high proportion of hydrocarbons having carbon numbers predominantly greater than C25 with high carbon-tohydrogen ratios. Asphalt also contains small amounts of various metals such as nickel, iron or vanadium
(European Commission, 1990).
The Einecs entries for “Glass, oxide” (EC No: 266-046-0, CAS No: 65997-17-3) and “Ceramic materials and
wares” (EC No: 266-340-9, CAS No: 66402-68-4) list the various chemicals manufactured in the production
of inorganic glasses and in the production of ceramics. The elements listed in these Einecs entries are
principally present as components of oxide systems, but some may be present in other forms (European
Commission, 1990).
20
The Einecs entries for “Frits, chemicals” (EC No.: 266-047-6, CAS No.: 65997-18-4), describes the
production of frits as a mixture of chemicals substances produced by rapidly quenching a molten, complex
combination of materials, confining the chemical substances thus manufactured as non-migratory components
of glassy solid flakes or granules. This category includes all of the chemical substances specified in the entry
(Einecs includes a list of 35 elements, including nickel) when they are intentionally manufactured in the
production of frit. The primary members of this category are oxides of some or all the listed elements.
Fluorides of these elements may also be included in combination with these primary substances (European
Commission, 1990). Eurocolour, an umbrella organisation under CEFIC, has described the production of
nickel-containing frits from nickel oxide and nickel hydroxide. The group of “frits” as such is considered to
be too poorly defined in terms of the content of nickel oxide to justify a classification proposal based on the
effects of nickel and its compounds. The IUCLID file recognises that the classification will depend on the
composition of the individual product. Whilst frits with concentrations of nickel oxide above 0.1% should be
classified as Category 1 carcinogens according to EU legislation, not all frits will contain nickel oxide.
Copper matte (EC No.: 266-967-8, CAS No.: 67711-91-5) is defined in Einecs as the product of smelting
roaster calcines concentrates or cement copper with flux in reverberatory or electric furnaces. The matte is
composed primarily of copper and copper, iron and lead sulphides with minor sulphides of other metals
(European Commission, 1990). Copper matte produced from nickel-containing copper ores can contain some
nickel sulphide. Whilst copper mattes with concentrations of nickel sulphide or subsulfide above 0.1% should
be classified as Category 1 carcinogens according to EU legislation, not all copper mattes will contain nickel
sulphide at these concentrations.
Copper smelting slags (EC No.: 266-968-3, CAS No.: 67711-92-6) are slags resulting from the smelting of a
heterogeneous mixture of copper and precious metals from primary and secondary sources and plant reverts.
Major constituents are iron-calcium-aluminium silicates, with minor amounts of copper, lead, nickel and
various non-ferrous metals and oxides (European Commission, 1990). Whilst slags with concentrations of
nickel oxide above 0.1% should be classified as Category 1 carcinogens according to EU legislation, not all
slags will contain nickel oxide at these concentrations.
Ashes (residues) (EC No.: 268-627-4, CAS No.: 68131-74-8) are the residues from the burning of a
combination of carbonaceous materials. The following elements may be present as oxides: aluminium,
calcium, iron, magnesium, nickel, phosphorous, potassium, silicon, sulfur, titanium and vanadium (European
Commission, 1990). A similar compound, Ashes (residues), heavy fuel oil fly (EC No.: 297-402-3, CAS No.:
93571-76-7) is a LPVC. Whilst ashes with concentrations of nickel oxide above 0.1% should be classified as
Category 1 carcinogens, not all ashes will contain nickel oxide.
Lead alloy, base, Pb, Sn, dross (EC No.: 273-701-4, CAS No.: 69011-60-5) are the oxides formed during
melting, refining, and casting of solders. Major constituents are oxides of tin, lead and antimony; minor
constituents are iron, nickel, sulfur, arsenic, copper and silver (European Commission, 1990). A similar
compound, Lead alloy, base, dross (EC No.: 273-700-9, CAS No.: 69011-59-2) is a LPVC. Whilst drosses
with concentrations of nickel oxide above 0.1% should be classified as Category 1 carcinogens, not all
drosses will contain nickel oxide. The high concentration of lead oxide (included in Annex I No. 082-001-006) in the dross could provide a basis for the evaluation of this compound.
Waste solids, copper electrolyte purifn. cathodes (EC No.: 273-720-8, CAS No.: 69012-20-0) are impure
copper cathodes formed during the electrolytic demetallizing of spent copper refining electrolyte. They
consist primarily of copper with varying levels of antimony, arsenic, bismuth, lead and nickel (European
Commission, 1990). The Einecs description suggests the nickel is present in metallic form, but does not
indicate the concentration. Whilst cathodes with concentrations of nickel above 1% should be classified as
Category 3 carcinogens, it is not clear that all cathodes will contain nickel at this concentration. Classification
should also reflect the presence of other metals such as antimony and lead.
Leach residues, zinc ore-calcine, cadmium-copper ppt. (EC No.: 293-311-8, CAS No.: 91053-46-2) is an
insoluble material precipitated by hydrolysis during hydrometallurgical treatment of crude zinc sulfate
21
solution. It consists primarily of cadmium, cobalt, copper, lead, manganese, nickel, thallium, tin and zinc
(European Commission, 1990). The Einecs description does not make clear the form of the nickel in the
compound or indicate the concentration. Classification should also reflect the presence of other metals such as
cadmium, thallium and lead.
Leach residues, zinc ore-calcine, iron-contg. (EC No.: 293-312-3, CAS No.: 91053-47-3) is an insoluble
material precipitated by hydrolysis during hydrometallurgical treatment of crude zinc sulfate solution. It
consists primarily of ferric oxide and, as impurities, arsenic, cadmium, cobalt, copper, lead, nickel, thallium,
tin and zinc (European Commission, 1990). The Einecs description does not make clear the form of the nickel
in the compound or indicate the concentration. Classification should also reflect the presence of other metals
such as arsenic, cadmium, thallium and lead.
The production of ferro-nickel slags (EC No.: 273-729-7, CAS No.: 69012-29-9) is described in the risk
assessment report for nickel metal. According to EU waste legislation (EC, 2001a) nickel slag from primary
production is classified as non-hazardous waste (10 08 09). 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. Whilst slags with concentrations of nickel oxide above 0.1% should be classified as
Category 1 carcinogens, the composition data indicates that not all slags will contain concentrations of nickel
oxide above this limit. NiPERA (2005) has stressed that all ferro-nickel slags contain a negligible
concentration of nickel oxide.
It should be noted that ferronickel and slags from nickel matte production are not included in Einecs, and so
are not included in the category, even though the quantities involved are also likely to qualify them as
HPVCs.
67.
Read-across is also used for certain organic nickel compounds in cases where these are expected to
behave similarly to soluble inorganic compounds. Organic compounds (largely soluble compounds) have
been included on the basis of an evaluation of the solubility and the association constants. Organic nickel
compounds where the nickel is sufficiently soluble and sufficiently dissociated from the organic moiety are
considered as being comparable to inorganic nickel compounds of similar water solubility. This selection was
made on the basis of expert judgement.
68.
The UK has pointed out that for the following compounds initially included in the category (Danish
EPA, 2005), the presence of a double bond makes the molecule more likely to be biologically active (Danish
EPA, 2006a):
CAS No
60700-37-0
Chemical Name
2-Propenoic acid, nickel(2+) salt
51222-18-5
13001-15-5
2-Propenoic acid, nickel salt
9-Octadecenoic acid (Z)-, nickel(2+) salt
6283-67-6
2-Butenedioic acid (E)-, nickel(2+) salt (1:1)
52496-91-0
2-Propenoic acid, 2-methyl-, nickel(2+) salt
94275-78-2
2-Propenoic acid, 2-methyl-, nickel salt
67952-41-4
Butanedioic acid, 2,3-dihydroxy- [R-(R*,R*)]-, nickel(2+) salt (2:1)
Deletion of the tartrate (CAS number 67952-41-4) has also led to deletion of the other two entries for tartrates
shown in the proposal (CAS Nos. 52022-10-3 and 10471-42-8).
In addition, for the following compounds, the UK considers that the contribution of the organic moiety to the
overall hazard profile should be considered (Danish EPA, 2006a):
22
CAS No
14100-15-3
Chemical Name
Nickel, bis(8-quinolinolato-N(1)-,O(8))-
71767-12-9
Uranate(2-), tetrakis(acetato-O)dioxo-, nickel(2+) (1:1), (OC-6-11)-
68958-89-4
Nickel(2+), bis(1,2-ethanediamine-N,N’)-, bis[bis(cyano-C)aurate(1-)]
12794-26-2
Nickel, bis(1-nitroso-2-naphthalenolato)-
14406-66-7
Nickel, bis(1-nitroso-2-naphthalenolato-N(1)-,O(2))-, (T-4)-
Whilst it is possible that for some endpoints, a category approach for these compounds might be appropriate,
these compounds have been deleted from the category.
69.
There is uncertainty about the identity of nickel metaborate shown in ECICS (Table 1.4). The CAS
number does not correspond to this compound. Given the uncertainty concerning the identity of this
compound, this has not been included in the category.
70.
The compounds described in paragraphs 61 – 69 above have been excluded from the category.
71.
Organonickel compounds that are likely to behave as largely or entirely organonickel complexes
were not included in the category.
72.
Among the organonickel compounds not included in the category are a number that are listed as
LPVCs. These include substances used as nickel colorants, as well as other compounds where the use is not
clear from the information in IUCLID.
CAS No
Chemical Name
70833-37-3
Nickel, bis(3-amino-4,5,6,7-tetrachloro-1H-isoindol-1-one oximato-N(2)-,O(1))-
13927-77-0
Nickel, bis(dibutylcarbamodithioato-S,S')-, (SP-4-1)-
29204-84-0
Nickel, bis[2,3-bis(hydroxyimino)-N-phenylbutanamidato-N(2)-,N(3)-]-
42739-61-7
Nickel, bis[2,3-bis(hydroxyimino)-N-(2-methoxyphenyl)butanamidato]-
14055-02-8
Nickel, [29H,31H-phthalocyaninato(2-)-N(29)-,N(30)-,N(31)-,N(32)-]-, (SP-4-1)-
14516-71-3
Nickel, (1-butanamine)[[2,2'-thiobis[4-(1,1,3,3-tetramethylbutyl)phenolato]](2-)-O,O',S]-
68511-62-6
Nickel, 5,5'-azobis-2,4,6(1H,3H,5H)-pyrimidinetrione complexes
90459-30-6
Nickel, acetate carbonate C8-C10-branched fatty acids C9-C11-neofatty acids complexes
Some of these compounds have provisional classifications in the HEDSET files included in IUCLID. As
these compounds fall outside the category, this category approach is not appropriate to evaluate the potential
hazards of these compounds. ETAD has offered its cooperation to assess the proper classification of nickel
based organic pigments and dyes (ETAD, 2005).
REFINEMENT OF THE READ-ACROSS.
73.
In the read-across shown below, the read-across has been based on the classifications agreed for the
individual nickel compounds shown in the Table in paragraph 45 above. The read-across is shown using the
EU classifications agreed by the TC C&L. The GHS equivalents are shown in the Table in paragraph 45.
a) Soluble nickel(II) compounds, with a water-solubility greater than 10-2 mol/L (corresponding to the
groups of “soluble” and “very soluble” compounds in the Table shown in paragraph 20 above) are
23
classified based on the classification for nickel sulfate shown in paragraph 45 above: Carc. Cat. 2 28 ;
R49; Repr. Cat. 2; R61; Muta. Cat. 3; R68; T; R48/23; R42/43 and N; R50-53, with specific
concentration limits for R43 of 0.01% and for T; R48/23 of 1%. Read-across has not been used for
the classification for acute toxicity or for irritation.
b) Sparingly soluble nickel(II) compounds, with a water-solubility in the range 10-4 - 10-2 mol/L
(corresponding to the group of “slightly soluble” compounds in the Table shown in paragraph 20
above) are classified based on the classification for nickel carbonate shown in paragraph 45 above:
Carc. Cat. 2; R49; Repr. Cat. 2; R61; Muta. Cat. 3; R68; T; R48/23; R42/43 and N; R50-53. Unlike
the soluble compounds, no specific concentration limits are included. Read-across has not been used
for the classification for acute toxicity or for irritation. The Commission has subsequently suggested
that the classification for the systemic effects reproductive toxicity (Repr. Cat. 2; R61) and
mutagenicity (Muta. Cat. 3; R68) should not be applied to this group of compounds.
c) Insoluble nickel compounds, with a water-solubility less than 10-4 mol/L but excluding nickel oxides
and metallic metal compounds (corresponding to the group of “insoluble” compounds in the Table
shown in paragraph 20 above) are classified based on the classification for nickel sulfide: Carc. Cat.
2; R49; T; R48/23; R43 and N; R50-53. No specific concentration limits are included. Read-across
has not been used for mutagenicity.
d) Mixed nickel oxides are classified based on the classification for nickel oxide: Carc. Cat. 2; R49; T;
R48/23 and R43 and R53. Read-across has not been used for classification for environmental hazards.
e) Read-across for nickel metal compounds has not been carried out. This is discussed in paragraph 65
above.
f) Nickel tetracarbonyl is included in the Table shown in paragraph 20 above by Carlsen (2001),
although this is not a typical inorganic nickel compound. Its low solubility is caused by its
hydrophobic character, rather than by a low dissociation constant. Whilst the environmental effects
appear to be consistent with the results expected from its water solubility, apart from its effects on
reproductive toxicity, its effects on human health are not immediately comparable to any of the other
nickel compounds studied. The data from this compound has not been used as the basis for any readacross.
74.
In cases where other metals or anions are present that have known significant toxic effects as shown
by other Annex I group entries for these metals or anions, these effects are included in the classification using
the Guidance under Note A in the Foreword to Annex I in Directive 67/548/EEC.
“For substances belonging to more than one group of substances included in Annex I, the symbols, indications of danger, R- and S-phrases
to be used for each substance shall be those shown in both the appropriate entries given in Annex I. In cases where two different
classifications are given in the two entries for the same hazard, the classification reflecting the more severe hazard classification is used.
Example:
for substance AB - no individual entry in Annex I:
Annex I group entry for compounds of A:
Repr. Cat. 1; R61 Repr. Cat. 3; R62 Xn; R20/22
R33
N; R50-53
Annex I group entry for compounds of B:
Carc. Cat.1; R45 T; R23/25 N; R51-53
Classification of substance AB thus becomes:
Carc. Cat. 1; R45 Repr. Cat. 1; R61 Repr. Cat. 3; R62
28
T; R23/25
R33
N; R50-53”
For discussion of classification as category 1 or 2 carcinogens, see paragraph 80.
24
This guidance assumes an additive effect of the different effects due to the different components of the
compound.
75.
Acute toxicity
This endpoint was discussed at some length, both under the discussion of the individual compounds reviewed
initially and in the subsequent discussion of the category approach. In the initial Danish proposals for
classification of the three soluble ESR nickel compounds, nickel sulfate, nickel dichloride and nickel
dinitrate, the possibility was raised of a common classification for all three compounds, rather than basing the
classification on the specific LD50 data for each. This suggestion was based on the assumption that the
measured LD50 values for these compounds could be seen as different point estimates of the acute oral
toxicity of the Ni2+ ion. This approach found some sympathy with some members of the EU TC C&L, but
was finally not accepted. Nickel dichloride was classified as T; R25 29 , whilst the sulfate 30 and dinitrate were
classified as Xn; R22. Whilst the LD50 data for nickel acetate is very similar to that of nickel sulfate, nickel
dinitrate has an LD50 substantially higher than either of the other two compounds. Whilst nickel dinitrate is
the most water soluble of the individual nickel compounds studied, the LD50 is closer to that of the slightly
soluble compounds, nickel carbonate and nickel dihydroxide, which have LD50 values around 840 – 1700
mg/kg.
NiPERA (2005) recognised that even though the proposal to classify all the soluble nickel compounds as Xn;
R20/22 may prove to be acceptable at this time, there are too many unknowns for this approach to be
considered valid.
The uncertainties reflected in the discussion led to the Danish EPA deleting proposals for acute toxicity based
on read-across 31 from the proposals. Note H was added instead 32 .
There was however agreement that where acute oral toxicity is identified as a hazard, in the absence of further
information, acute inhalational toxicity should also be identified as a hazard at the same level of concern as
the acute oral toxicity.
76.
Irritation/ corrosivity
This endpoint was also discussed at some length. The available data that indicates that soluble nickel
compounds can cause on skin irritation is derived from humans, whilst the available animal data does not
support classification for this effect. Unlike the results for eye irritation of nickel sulfate, nickel dinitrate
showed severe eye irritation. It was suggested that the greater severity with this compound was due to its
oxidising properties. This suggests that this local property is more dependent on the counterion than other
systemic effects. NiPERA (2005) pointed out that this endpoint not only depends on the water solubility of
the nickel compound, but on the nature of the anion, and that the read-across for nickel salts must include an
evaluation of not just nickel ion availability, but also the irritancy of the anions. NiPERA (2005) also pointed
out that, since the water soluble nickel salts are not irritating at concentrations below 20% it will be
impossible to consider a direct extrapolation of irritancy data without some knowledge of the bioavailable
fraction of nickel released by a particular compound and the potential irritancy of the molecule to which it is
bound.
29
Although not included as a specific entry in either the UN Recommendations on the Transport of Dangerous Goods
(UN, 2001) ADN (UN ECE 2001a) or in the ADR (UN ECE, 2001b), both solid and liquid nickel chloride meet the
criteria under ADR/RID/IMDG for Class 6.1 “Toxic Substances”. The agreed classification for nickel dichloride reflects
this UN Transport classification.
30
As noted above, under the GHS criteria, nickel sulfate is classified for acute toxicity in the same category as nickel
dichloride, based on the LD50 value of 275 mg/kg.
31
Classification for acute toxicity is included where data is available.
32
Note H is described in more detail in paragraph 83 below. This is a Note that indicates that the classification agreed is
a partial classification, and that other hazards not included in the harmonised classification need to be addressed by the
supplier of the chemical.
25
The uncertainties reflected in the discussion led to the Danish EPA deleting proposals for irritation /
corrosivity based on read-across 33 from the proposals. Note H was added instead.
77.
Skin Sensitisation
Nickel skin sensitisation has been evaluated almost entirely on the basis of human studies with very watersoluble nickel compounds, and studies on release rates with nickel metal. Animal studies have contributed
little to the understanding of this effect. There is limited data on skin sensitisation or nickel release from
compounds with lower water-solubility. There is however agreement that this effect also occurs with
compounds with very low water solubility such as nickel oxide. The studies carried out by Industry with the
nickel-containing spinels are interesting in that they demonstrate that there is in fact an additional group of
compounds where the nickel availability is even less than that seen with the nickel oxides. These studies have
identified nickel compounds which show the same, very limited, nickel release that that has previously been
demonstrated for certain nickel-containing alloys such as certain stainless steels, and which does not give rise
to concern for skin sensitisation.
NiPERA (2005) have expressed concerns about read-across for this effect, particularly for the organonickel
compounds, where the possibility of lipophilicity of insoluble compounds creates the possibility that some
insoluble organonickel compounds could penetrate the skin and be metabolised in the basal layer to release
nickel. However, it is just as likely that the nickel ion may not be released from water-soluble organonickel
compounds, raising the possibility that they may not be sensitising at any concentration. Once again, some
determination of the bioavailability (not just water solubility) of the nickel ion from the compound is required
for an accurate read-across.
This argument was not supported by the EU TC C&L, and it was agreed to read-across this classification for
all the nickel compounds finally included in the category. The specific concentration limits for this effect
agreed for nickel sulfate were also applied to the other soluble nickel compounds considered.
78.
Respiratory sensitisation.
Respiratory sensitisation is recognised as an effect with the soluble and sparingly water-soluble nickel
compounds, although this conclusion is based on a limited number of cases with nickel sulfate. The TC C&L
has agreed that R42 is not appropriate for nickel sulphide, nickel subsulphide or metallic nickel, although
there is limited evidence from people exposed to metallic nickel, and some suggestion that this effect can also
be seen with other compounds, as is shown by the anecdotal evidence from the IUCLID file that nickel matte
also shows this effect.
NiPERA (2005) commented that although the mechanisms are different, the issue of bioavailability of nickel
ion from the compound will be the determinant in the read-across of the respiratory sensitisation of soluble
inorganic nickel salts to other nickel containing compounds.
The EU TC C&L agreed to read-across this classification for all the soluble and sparingly soluble nickel
compounds. It is possible that further studies may show that this effect occurs across a wider spectrum of
water-solubility than is currently recognised.
79.
Repeated dose toxicity
Repeated dose toxicity following inhalation is an effect that leads to classification in both soluble (nickel
sulfate) and insoluble nickel compounds (nickel subsulfide and nickel oxide). The effects are seen at
substantially lower levels with nickel sulfate than with the insoluble compounds.
NiPERA (2005) commented that, as already noted the issue of ion availability from the water-soluble
organometallic compounds further complicates the read-across on the basis of water solubility alone.
Consequently, even though the proposal to classify all the nickel compounds as T; R48/23 may prove to be
acceptable at this time there are too many unknowns for this approach to be considered as validated.
33
Classification for corrosivity/irritation is included where data is available.
26
The EU TC C&L agreed to read-across this classification for all the soluble and sparingly soluble nickel
compounds.
The use of the approach given in Note A in the Foreword to Annex I means that R33 needs to be assigned for
some entries. In the EU classification and labelling system, R33 is used to identify concerns due to
bioaccumulation, but where the concerns are less than those covered by classification with R48. This Rphrase is now largely redundant, following development of the improved criteria for R48, and within GHS
cumulative effects are clearly covered by the criteria for STOST – repeat exposure (Milieu, 2005a). Since the
concern that gave rise to the application of R33 may be covered by other possible classifications, R33 has not
been included and is covered by Note H.
80.
Germ cell mutagenicity
Agreement on the use of read-across for this endpoint was only obtained after much discussion. In their
comments to the proposal, Belgium (2005) questioned whether it was necessary to include the Muta. Cat. 3;
R68 classification given that the compounds are already classified Carc. Cat. 1; R49. They also took into
account the fact that the evidence for mutagenicity is conflicting, and that the Specialized Experts concluded
that there was insufficient evidence for the classification of nickel carbonate, a sparingly soluble compound.
In these circumstances, Belgium did not consider that performing a read-across classification for such a
conflicting endpoint seems justified. NiPERA (2005) has also expressed concern about the use of read-across
for this endpoint, in particular with respect to the organic compounds included in the proposal.
In their evaluation, the Specialised Experts concluded that concluded nickel sulfate, nickel chloride and nickel
nitrate should be classified as Muta. Cat. 3; R68. This conclusion is based on evidence of in vivo genotoxicity
in somatic cells, after systemic exposure, and, hence the possibility that the germ cells are affected cannot be
excluded. The Specialised Experts also concluded that further testing of effects on germ cells was not
considered practicable. This conclusion is reflected in the agreement to classify nickel sulfate, nickel
dichloride and nickel dinitrate as Muta. Cat. 3; R68 and the “conclusion (i) on hold” 34 for this endpoint for
these three compounds under the Existing Substances Regulation (Danish EPA, 2005b, 2005e, 2005f). In
reaching their conclusion concerning nickel carbonate, the Specialised Experts did so based on the data for
this substance alone, and were not asked to look at the data for the less soluble nickel sulphide. The TC C&L
subsequently accepted classification as Muta. Cat. 3; R68 (in the 30th. ATP) on the basis of a derogation
request from Industry made in the context of the risk assessment evaluation. The EU TC C&L subsequently
agreed to classify both the sulphide and the subsulphide as Muta. Cat. 3; R68 on the basis of data.
In the following discussions, a distinction was made between possible effects on the germ cells and other
genotoxic effects. Consideration was also given to the fact that for soluble nickel compounds, further testing
was not considered practicable. The EU TC C&L agreed that read-across for classification as Muta. Cat. 3;
R68 for germ cell mutagenicity was reasonable for the soluble compounds, but was not appropriate for the
non-soluble nickel compounds. Note H was added to cover this effect for the less water-soluble compounds.
The conclusions of the discussions in the EU TC C&L for the sparingly soluble compounds have been
discussed further within the Commission. The discussion at the March 2006 distinguished between “soluble”
nickel compounds for which read-across was agreed and “non-soluble” nickel compounds for which readacross was not considered appropriate. It is unclear whether "non-soluble" nickel compounds include the
sparingly soluble nickel compounds. The Commission has concluded on the basis of their understanding of
the discussion and having in mind the last Danish proposal (ECBI/96/04 Add. 2 Rev 1) that "non-soluble"
should include the "sparingly soluble".
Whilst there is evidence of systemic availability of the nickel ion for nickel carbonate and nickel hydroxide as
shown by the acute toxicity of these compounds, and hence, effects on germ cells cannot be excluded, for the
other semi-soluble compounds included in the proposal, information demonstrating systemic availability is
34
Whilst conclusion (i) under the Existing Substances Regulation means that further data is required, a conclusion (i) on
hold means that whilst there is agreement that additional data is needed, there is also an agreement that no further testing
should actually be carried out.
27
not available. Given the differences in water-solubility between the slightly soluble compounds (with water
solubility in the range 10-4 - 10-2 mol/L) and the soluble compounds (from 10-2 to over 5·10-1 mol/L), the
assumption that the nickel ion is systemically available for the slightly soluble compounds is not necessarily
justified, and the read-across for this systemic effect is not used, and Note H can be used to cover this
endpoint for the slightly-soluble compounds.
81.
Carcinogenicity
There is epidemiological evidence for carcinogenicity of soluble nickel compounds as well as for nickel
sulfide, nickel subsulfide and nickel oxides (Danish EPA 2005a, 2005b, 2005c, 2005d, 2005e, 2005f). IARC
(1990) concluded that “nickel compounds are carcinogenic to humans (Group 1)”. Chronic animal studies
have shown carcinogenicity for the poorly water-soluble nickel compounds tested, but the NTP studies with
nickel sulfate failed to show a positive result.
NiPERA (2005) has argued that while it would appear that the carcinogen classification of nickel sulfate,
nickel subsulfide, and nickel monoxide can be read-across to all the inorganic and organic compounds in the
Danish proposal, the very fact that all these compounds are classified as Carc. Cat. 1; R49 demonstrates a
fallacy in the use of water solubility for extrapolation. Since all these compounds have different water
solubilities, but have each been deemed to be Category 1 carcinogens it is obvious that the determinant of
carcinogenic potential has nothing to do with water solubility. In fact, it appears that there are two separate
modes of action by which exposure to nickel substances may increase the appearance of tumors. For water
insoluble nickel compounds the likely determinant of carcinogenicity is the bioavailability of the nickel ion
released from these compounds to the critical site in the target cells in the lung. Nickel substances with very
low bioavailability may not cause tumors at all. For inorganic water soluble salts of nickel, the mode of action
may be secondary to localized toxicity. In this case, the solubility is high but the bioavailability is low due to
poor uptake of the nickel ion into the cells. This is demonstrated in the fact that there is no evidence of
systemic carcinogenicity at the oral MTD which occurs at exposures that are higher than can be achieved
through inhalation (hence the R49 classification for nickel compounds). Since it is clear that simple water
solubility is not the determining factor in the carcinogenicity of these compounds it is not possible to predict
how all of the compounds proposed by the Danes for classification will behave biologically. This is
particularly true of the organic compounds where it is not certain how they will be metabolized or whether
“nickel” will be bioavailable at all.
The EU TC C&L agreed that read-across for classification for carcinogenicity was reasonable for all the
compounds in the revised category. However, following a lengthy discussion, a majority of Member States
agreed that the classification should be in Category 2 rather than in Category 1, as the classification was
based on read-across. This view was not supported by a number of Member States that argued that Category 1
classification was appropriate since it was the nickel ion that was the basis for the classification. The
conclusions of the discussions in the EU TC C&L have been discussed further within the Commission, who
have proposed classification in Category 1, with reference to the SCHER opinion on the risk assessment of
the nickel compounds in which the classification is based on the effects of the nickel ion (SCHER, 2006),
adopted subsequent to the discussions in the EU TC C&L.
82.
Reproductive toxicity
Reproductive toxicity is identified as a hazard with the soluble and sparingly water-soluble nickel compounds
evaluated as reference compounds.
NiPERA (2005) commented that reproductive toxicity is a threshold based toxicity. Therefore, the nickel ion
will have to be made bioavailable to the target organs in sufficient concentration to cause the effect. This
requires the reproductive toxicity threshold to be reached before the Maximum Tolerated Dose of the
maternal animal prevents higher exposure. In the case of water soluble nickel salts this scenario can occur. It
is unclear if it can occur with the sparingly soluble compounds and it is unlikely to occur with the insoluble
compounds. In addition, the systemic bioavailability of the nickel ion would have to be ascertained for all the
organonickel compounds in order to ascertain whether the reproductive toxicity hazard could exists from
exposure to these compounds. Consequently, NiPERA did not agree on relying on solubility as the sole
28
decision criteria and considered that some toxicokinetic data on the absorption, bioavailability, and
metabolism of each compound must be included to make an informed extrapolation.
The EU TC C&L agreed to read-across classification as Repr. Cat. 2; R61 for all the soluble and sparingly
soluble nickel compounds.
The conclusions of the discussions in the EU TC C&L for the sparingly soluble compounds have been the
discussed further within the Commission. As for mutagenicity, there is evidence of systemic availability of
the nickel ion for nickel carbonate and nickel hydroxide as shown by the acute toxicity of these compounds,
and hence, effects on reproductive toxicity cannot be excluded. For the other semi-soluble compounds
included in the proposal, information demonstrating systemic availability is not available. Given the
differences in water-solubility between the slightly soluble compounds (with water solubility in the range 10-4
- 10-2 mol/L) and the soluble compounds (from 10-2 to over 5·10-1 mol/L), the assumption that the nickel ion is
systemically available for the slightly soluble compounds is not necessarily justified, and the read-across for
this systemic effect is not used, and Note H is used to cover this endpoint for the slightly-soluble compounds.
83.
Hazards to the aquatic environment.
The TC C&L Environment group has agreed that the appropriate L(E)C50 value for the evaluation of these
compounds is 0.068 mg/L. The TC C&L Environment group has agreed that all the nickel compounds with
the exception of the nickel oxides and metallic nickel should be classified as N; R50-53. Since the
classification is based on the toxicity of the nickel ion, the molecular weights of the different compounds have
been checked to see whether this classification requires modification (to e.g. N; R51-53). No correction for
molecular weight is necessary.
In accordance with the metal classification strategy agreed by the TC C&L Environment group, nickel
monoxide was originally classified as R53 by default because of lack of data. According to data subsequently
provided by Industry, the greatest Ni2+ ion concentration achieved in dissolution testing of nickel oxide is
4µg/L and the average value was 2 µg/L (NiPERA, 2006). NiPERA (2006) argued that since no significant
amounts of nickel ion were released, the R53 value is not merited and should not be used for any substances
analogous to nickel oxide. The Danish EPA (2006b) pointed out in reply that since the chronic toxicity EC10
value is less than 4 µg/l, the classification should remain as R53. This was agreed by the EU TC C&L
Environment group at the meeting in April 2006.
Where there is a clear analogy to nickel oxide, these compounds are classified as R53. In other cases, where
there is uncertainty about the contribution of other metal constituents to the environmental classification, no
environmental classification has been given and Note H has been added for this effect.
ADVICE WHEN READ-ACROSS IS NOT NECESSARILY APPLICABLE.
84.
In cases where read-across has not been applied, the classification for certain endpoints is covered
by Note H.
The wording of Note H in the Foreword to Annex I is shown in the 28th ATP (EC 2001b).
“Note H:
The classification and label shown for this substance applies to the dangerous property(ies) indicated by the risk
phrase(s) in combination with the category(ies) of danger shown. The requirements of Article 6 of this Directive
on manufacturers, distributors and importers of this substance apply to all other aspects of classification and
labelling. The final label shall follow the requirements of section 7 of Annex VI of this Directive.
This note applies to certain coal- and oil-derived substances and to certain entries for groups of substances in
Annex I.”
29
Whilst this category approach for the nickel compounds could be considered as a group entry, as the nickel
compounds covered by the Danish proposal are shown individually, the EU TC C&L has agreed to delete the
last sentence in Note H in the 31st ATP currently in preparation in order to avoid any ambiguity.
85.
Inclusion of Note H imposes a duty on the manufacturers, distributors and importers of a substance
where this label is included to evaluate the hazards not specifically addressed in the harmonised classification
shown in Annex I. The following paragraphs indicate possible ways to do this for the hazards that have not
been specifically covered on the basis of read-across.
86.
Acute toxicity
NiPERA (2006) has suggested that the biological information already available in the scientific literature can
be combined with in vitro test data to provide an empirical means of future extrapolation of the acute toxicity
potential by untested nickel containing materials. Specifically, in vivo determination of the LD50 values for
multiple nickel compounds has been published in the scientific literature. Determination of nickel release
rates for each of the tested compounds in in vitro gastric and lung fluid dissolution tests will establish a range
of nickel concentrations in these tests for nickel ion induced LD50 values from < 200 mg/kg bw to > 5000
mg/kg bw. Comparison of the equivalent dissolution test nickel ion concentration of a nickel compound for
which the LD50 is unknown to the known values will permit an estimation of the in vivo LD50 value for both
oral and inhalation exposure. A final evaluation of the potential impact of the counter-ion will have to be
made for the material with an “unknown” LD50 (NiPERA, 2006).
For acute toxicity, most of the available data for both soluble and slightly soluble compounds is in the range
of oral toxicity currently covered by the criteria for “Harmful” (200 mg/kg bw < LD50 < 2000 mg/kg bw). As
a default position, soluble and sparingly soluble nickel compounds included in this category should be
classified as Xn; R20/22. However, counter-ions and the presence of other metal ions may lead to increased
toxicity, and it is likely that there are additional soluble nickel compounds that, like nickel chloride, show an
LD50 < 200 mg/kg (e.g. nickel cyanide). Use of the additivity formula given in Note A can be used. In vivo
testing should only be considered as a last resort.
It should also be noted that the data on inhalational toxicity is very limited, and consideration should be given
to this endpoint in evaluating the substance.
87.
Irritation/ corrosivity
The evidence for skin irritation for nickel sulfate and nickel chloride comes from human experience, and the
results of the available animal studies are negative. There is evidence that the effect is more severe in the case
of some counter-ions, e.g. the oxidising counter-ions nitrate and chlorate. It would probably be difficult to
prove convincingly that a soluble nickel salt was not skin irritating, as a negative animal study would be
consistent with the effects seen with nickel sulfate. This would appear to be supported by the fact that
Material Safety data sheets for a number of nickel compounds already include skin and eye irritation as
potential health hazards, without any apparent data to support this.
As a default position, soluble and sparingly soluble nickel compounds included in this category should be
classified as Xi; R38. If there is reason to believe that the counter-ion would lead to a greater effect, a more
stringent classification for skin and eye should also be considered. If necessary, this can be supplemented by
relevant in vitro tests. In vivo testing should only be considered as a last resort.
88.
Mutagenicity
For the compounds for which Note H has been recommended, there is very little data for this effect. The
group of “sulfidic compounds” are a fairly limited group of compounds with very similar water solubility
(e.g. borides, phosphides, selenides, arsenides). The data on which the classification for mutagenicity is based
(Comet assay) reflects concerns for genotoxicity rather than for germ cell mutagenicity.
Since the Comet assay is a non-standard test, it is difficult to recommend this as a basis for further testing.
The evaluation of this group of compounds for this effect is unlikely to be easy, and is probably best
approached by systematic development of relevant data for this effect for this group of compounds.
30
89.
Hazards to the aquatic environment.
For nickel oxides where no environmental classification is shown, either a screening or a full 28-day
transformation/dissolution protocol test should be carried out. For Ni2+ concentrations exceeding 0.068 (EC50)
mg/L, classification with N; R50-53 is appropriate. For Ni2+ concentrations between 0.068 mg/L and 0.0024
mg/L classification with R53 is appropriate. For Ni2+ concentrations below 0.0024 mg/L derived from a full
28-day transformation/dissolution protocol test, no hazard classification for this effect is required.
CONCLUSIONS.
90.
The discussions reported above describe the arguments used in
a) initiating a discussion for a category approach (Danish EPA, 2005a), including a rationale for the
proposed classification for each entry
b) refining the approach (Danish EPA 2006a) including a revised rationale for the proposed
classification for each entry and finally
c) agreeing a category approach.
These discussions resulted in the two relevant EU Working groups, the TC C&L for Human Health and for
Environmental Effects agreeing to the Danish proposal, as modified as a result of the discussions in these
Technical Committees.
Following the discussions in the Technical Committees, a modified version of these proposals (including the
use of Note H to cover mutagenicity and reproductive toxicity for the group of semi-soluble nickel
compounds and classification as a Category 1 carcinogen) has been circulated by the Commission DG ENV
for comments. A draft of the classification proposals for including classifications for 117 compounds has
been posted by the ECB on its website (ECB, 2007).
31
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http://ecb.jrc.it/classlab/9604a2_DK_ nickel
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final written approval of JuneNovember 2005, Chapters 0, 1, 2, 4, 5, 6 & 7 – human health only.
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Draft for final written approval of JuneNovember 2005, Chapters 0, 1, 2, 4, 5, 6 & 7 – human health only.
R420_1105_hh_chapter0124567
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Draft for final written approval of JuneNovember 2005, Chapters 0, 1, 2, 4, 5, 6 & 7 – human health only.
R424_1105_hh_chapter0124567
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nickel compounds. 6. February, 2006. ECBI/96/04 – Add 2 – Rev. 1. Document available on the ECB website
as: http://ecb.jrc.it/classlab/9604a2r1_DK_%20nickel.doc.
35
This draft reports is available on request from the Danish EPA
36
This draft reports is available on request from the Danish EPA.
32
Danish EPA (2006b): Danish comments on the comments of the nickel producers February 27, 2006:
“Comments on Toxicity Categories Regarding the “Classification of Nickel Compounds: Revised Danish
Proposal for Classification of Nickel Compounds””, environmental classification. March 7 2006. ECBI/26/95
– Add. 84. Document available on the ECB website as: http://ecb.jrc.it/classlab/2695a84_DK_nickel.doc
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03/2006. 27. March, 2006. ECBI/96/04 – Add. 25. Document available on the ECB website as:
http://ecb.jrc.it/classlab/9604a25_draft%20Annex%20I%20entries.doc.
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assessment reports of nickel compounds prepared in relation to Council Regulation (EEC) 793/93: Draft for
final written approval of November 2006, Chapters 0, 1, 2, 4, 5, 6 & 7 – human health only.
R_NickelBackground_1105_hh_chapter0124567
Danish EPA (2007): Danish proposal for classification of 5 nickel compounds in preparation for the
workshop on experience in applying the GHS criteria for classification and labelling using SIDS documents.
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Directive 76/769/EEC on the approximation of the laws, regulations and administrative provisions relating to
the marketing and use of certain dangerous substances and preparations. OJ. L188, 22.7.1994, p. 1-2.
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homepage: http://ecb.jrc.it/classification-labelling/.
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Chemical Substances – A guide to the classification of chemicals in the Combined Nomenclature. Volume 1
– Alphabetical list of chemical products. Volume 2 – Numerical list (by CUS-Number) Correlation between
CAS- and CUS-Numbers. Office for Official Publications of the European Communities. ISBN 92-828-06375. Also available online at: http://europa.eu.int/comm./taxation_customs/dds/en/ecicau.databases/ecis_en.htm.
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twelfth time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative
33
provisions relating to the classification, packaging and labelling of dangerous substances. OJ L180 & OL
L180A, 8.07.1991, p. 1.
Environment Canada and Health Canada (1994): PSL1 Report on Nickel and its Compounds. Cat. No.: En 40215/43E
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Danish EPA, 2006d.
Eurocolour (2005): Comments on Danish Proposal for Classification of Inorganic Poigments containing
Nickel. ECBI/96/04 – Add. 17
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Add. 10. Detailed study results are shown in documents ECBI/42/06 Add. 11 parts I- XVII which are
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34
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Compounds and Complex Materials: DEPA Proposal for an approach to group classification”. Comments of
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revised Danish Proposal for Classification of Nickel compounds”. Comments of the Nickel Producers
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53. http://www.chem.unep.ch/irptc/sids/OECDSIDS/8007189.pdf
35
TABLE 1: INVENTORY OF NICKEL COMPOUNDS
In the following inventory, compounds reviewed by the Danish EPA review of HPV chemicals under the EU
Existing Chemicals Regulation are shown with green shading. The classification for these entries is included
in the 30th ATP.
Other nickel compounds already in Annex I with Annex I numbers starting with 028 (nickel) are also shown
with green shading. Where relevant, revisions to the classification of these entries has been agreed for
inclusion in the draft 31st. ATP (ECB, 2007b).
Compounds for which classification proposals based on a group approach have been agreed for inclusion in
the draft 31st ATP are shaded in yellow.
Compounds explicitly excluded from the category approach using read-across are shaded in red.
Unshaded nickel containing compounds were not included in the category approach using read-across for a
variety of reasons and are not considered further in this review. It should be noted that further analysis might
show that some of these compounds may in fact be suitable for this approach.
TABLE 1.1: Nickel and Nickel Compounds in Einecs.
The nickel compounds in Einces are divided into four groups in this Table: nickel and compounds with nickel
metals; inorganic nickel compounds, organic nickel compounds and diverse nickel-containing compounds.
Nickel and compounds with nickel metal.
EC Number CAS
Number
Annex I No.
Chemical Name
HPVC /
LPVC
CUS 37
Number
231-111-4 7440-02-0
028-002-00-7
Nickel
HPVC
11024
234-439-6 12003-78-0
Aluminum, compd. with nickel (1:1)
235-261-1 12142-92-6
Nickel, compd. with zirconium (1:2)
234-807-6 12034-55-8
Nickel, compd. with niobium (1:1)
235-034-7 12059-23-3
Nickel, compd. with tin (3:1)
234-827-5 12035-52-8 [051-003-00-9] Antimony, compd. with nickel (1:1)
235-676-8 12503-49-0 [051-003-00-9] Antimony, compd. with nickel (1:3)
235-372-5 12196-72-4
Lanthanum, compd. with nickel (1:5)
235-341-6 12175-27-8
Dysprosium, compd. with nickel (1:2)
235-773-5 12688-64-1
Bismuth, compd. with nickel (1:1)
257-510-3 51912-52-8
Copper, compd. with lanthanum and nickel (4:1:1)
37
The EU CUS number is a five-digit number in the European Customs Inventory of Chemical Substances (ECICS).
The list shows the correlation between the CUS number and the CAS number
36
Inorganic nickel compounds.
EC Number CAS
Number
Annex I No.
Chemical Name
HPVC /
LPVC
CUS
Number
215-215-7 1313-99-1
028-003-00-2
Nickel monooxide (NiO)
HPVC
20749
215-217-8 1314-06-3
028-005-00-3
Nickel trioxide (Ni2O3)
20765
234-323-5 11099-02-8 (028-003-00-2) Nickel oxide
234-823-3 12035-36-8 028-004-00-6
Nickel dioxide (NiO2)
234-454-8 12004-35-2
Aluminum nickel oxide (Al2-NiO4)
234-825-4 12035-39-1
Nickel titanium oxide (NiTiO3)
235-752-0 12653-76-8
Nickel-titanium-oxide-
257-970-5 52502-12-2
Nickel vanadium oxide (NiV2-O6)
234-636-7 12018-18-7
Chromium nickel oxide (Cr2-NiO4)
235-335-3 12168-54-6
Iron nickel oxide (Fe2-NiO4)
306-902-3 97435-21-7
Iron nickel zinc oxide (Fe2-NiZnO4)
261-346-8 58591-45-0
Cobalt nickel oxide (CoNiO2)
269-051-6 68186-89-0
Cobalt-nickel-gray-periclase-
268-169-5 68016-03-5
Cobalt molybdenum nickel oxide (CoMo2-NiO8)
274-755-1 70692-93-2
Nickel zirconium oxide (NiZrO3)
305-835-7 95046-47-2
Spinels, cobalt nickel zinc grey
238-034-5 14177-55-0
Molybdenum nickel oxide (MoNiO4)
234-824-9 12035-38-0
Nickel tin oxide (NiSnO3)
238-032-4 14177-51-6
Nickel tungsten oxide (NiWO4)
LPVC
20760
239-876-6 15780-33-3 [092-002-00-3] Nickel uranium oxide (NiU3-O10)
277-627-3 73892-02-1 [051-003-00-9] Antimony oxide (Sb2-O3), solid soln. with nickel oxide
(NiO) and titanium oxide (TiO2)
232-353-3 8007-18-9
[051-003-00-9] Antimony-nickel-titanium-oxide-yellow-
269-071-5 68187-10-0
Nickel-ferrite-brown-spinel-
271-112-7 68515-84-4
Olivine, nickel green
LPVC
LPVC
271-853-6 68610-24-2 [056-002-00-7] Nickel-barium-titanium-primrose-priderite-; C.I.
Pigment Yellow 157
271-892-9 68611-43-8
Nickel-niobium-titanium-yellow-rutile-
275-738-1 71631-15-7
Nickel-iron-chromite-black-spinel-
309-018-6 99749-23-2
Cassiterite, cobalt manganese nickel grey
273-686-4 69011-05-8
Nickel titanium oxide tungstate (NiTi20-O35-(WO6)2)
269-047-4 68186-85-6
C.I.Pigment Green 50
234-348-1 11113-74-9 028-008-00-X
Nickel hydroxide
235-008-5 12054-48-7 028-008-00-X
Nickel dihydroxide (Ni(OH)2)
234-493-0 12007-00-0
Nickel boride (NiB)
234-494-6 12007-01-1
Nickel boride (Ni2-B)
234-495-1 12007-02-2
Nickel boride (Ni3-B)
235-723-2 12619-90-8
Nickel-boride-
37
LPVC
LPVC
20745
Inorganic nickel compounds (continued).
235-033-1 12059-14-2
Nickel silicide (Ni2-Si)
235-379-3 12201-89-7
Nickel silicide (NiSi2)
234-828-0 12035-64-2
Nickel phosphide (Ni2-P)
234-349-7 11113-75-0 028-006-00-9
Nickel sulphide
234-829-6 12035-72-2 028-007-00-4
Nickel subsulphide (Ni3S2)
240-841-2 16812-54-7 028-006-00-9
Nickel sulphide (NiS)
25517
LPVC 25516
235-103-1 12068-61-0 [033-002-00-5] Nickel arsenide (NiAs2)
248-169-1 27016-75-7 [033-002-00-5] Nickel arsenide (NiAs)
215-216-2 1314-05-2
[034-002-00-8] Nickel selenide (NiSe)
233-263-7 10101-96-9 [034-002-00-8] Selenious acid, nickel(2+) salt (1:1)
239-125-2 15060-62-5 [034-002-00-8] Selenic acid, nickel(2+) salt (1:1)
20757
235-260-6 12142-88-0
Nickel telluride (NiTe)
20758
271-512-1 68583-44-8
Cadmium sulfide (CdS), solid soln. With zinc sulfide,
nickel and silver-doped
271-539-9 68584-42-9
Cadmium sulfide (CdS), solid soln. With zinc sulfide,
copper and nickel-doped
270-961-0 68512-22-1
Zinc sulfide (ZnS), nickel and silver-doped
271-601-5 68585-93-3
Zinc sulfide (ZnS), copper and nickel-doped
272-277-8 68784-84-9
Zinc sulfide (ZnS), copper and nickel and silver-doped
236-669-2 13463-39-3 028-001-00-1
Nickel carbonyl (Ni(CO)4), (T-4)-
209-160-8 557-19-7
[006-007-00-5] Nickel cyanide (Ni(CN)2)
254-261-2 39049-81-5
Nickelate(2-), tris(cyano-C)-, dipotassium
238-082-7 14220-17-8
Nickelate(2-), tetrakis(cyano-C)-, dipotassium, (SP-4-1)-
238-946-3 14874-78-3
Ferrate(4-), hexakis(cyano-C)-, nickel(2+) (1:2), (OC-611)-
222-068-2 3333-67-3
028-010-00-0
Carbonic acid, nickel(2+) salt
20730
20734
20738
HPVC 20729
240-408-8 16337-84-1 028-010-00-0
Carbonic acid, nickel salt
235-715-9 12607-70-4 028-010-00-0
[carbonato(2-)]tetrahydroxytrinickel
265-748-4 65405-96-1 028-010-00-0
[μ-[carbonato(2-)-O:O’]]dihydroxy trinickel
233-071-3 10028-18-9
Nickel fluoride (NiF2)
LPVC 20739
Nickel dichloride (NiCl2)
HPVC 20731 39
231-743-0 7718-54-9
028-012-00-1
253-399-0 37211-05-5
Nickel-chloride- {a nickel[1] compound}
267-897-0 67952-43-6
Chloric acid, nickel(2+) salt
237-124-1 13637-71-3
Perchloric acid, nickel(2+) salt
236-665-0 13462-88-9
Nickel bromide (NiBr2)
238-596-1 14550-87-9
Bromic acid, nickel(2+) salt
236-666-6 13462-90-3
Nickel iodide (NiI2)
38
The CUS Number shown is for the tetrahydrate, CAS No. 39430-27-8.
39
Also nickel (II) chloride hexahydrate, CAS No.: 7791-20-0, CUS No.: 39096
38
LPVC (25626) 38
20754
LPVC 20728
20747
Inorganic nickel compounds (continued).
231-827-7 7757-95-1
232-104-9 7786-81-4
Sulfurous acid, nickel(2+) salt (1:1)
028-009-00-5
Nickel sulphate
HPVC 20762
237-563-9 13842-46-1
Sulfuric acid, nickel(2+) potassium salt (2:1:2)
20756
239-793-5 15699-18-0
Sulfuric acid, ammonium nickel(2+) salt (2:2:1)
11026
275-897-7 71720-48-4
Sulfuric acid, monoethyl ester, nickel(2+) salt
237-396-1 13770-89-3
Sulfamic acid, nickel(2+) salt (2:1)
239-967-0 15851-52-2
Telluric acid (H2-TeO3), nickel(2+) salt (1:1)
239-974-9 15852-21-8
Telluric acid (H2-TeO4), nickel(2+) salt (1:1)
236-068-5 13138-45-9 028-013-00-7
Nickel dinitrate
238-076-4 14216-75-2 028-013-00-7
Nitric acid, nickel salt
238-278-2 14332-34-4
Phosphoric acid, nickel(2+) salt (1:1)
242-522-3 18718-11-1
Phosphoric acid, nickel(2+) salt (2:1)
233-844-5 10381-36-9
Phosphoric acid, nickel(2+) salt (2:3)
268-585-7 68130-36-9
Molybdenum-nickel-hydroxide-oxide-phosphate-
238-426-6 14448-18-1
Diphosphoric acid, nickel(2+) salt (1:2)
238-511-8 14507-36-9
Phosphinic acid, nickel(2+) salt
252-840-4 36026-88-7
Phosphinic acid, nickel salt
236-771-7 13477-70-8 [033-005-00-1] Arsenic acid (H3-AsO4), nickel(2+) salt (2:3)
244-578-4 21784-78-1
Silicic acid (H2-SiO3), nickel(2+) salt (1:1)
237-411-1 13775-54-7
Silicic acid (H4-SiO4), nickel(2+) salt (1:2)
250-788-7 31748-25-1
Silicic acid (H2-SiO3), nickel(2+) salt (4:3)
253-461-7 37321-15-6
Silicic acid, nickel salt
235-688-3 12519-85-6
Nickel hydroxide silicate (Ni3-(OH)4-(Si2-O5))
238-766-5 14721-18-7 [024-017-00-8] Chromic acid (H2-CrO4), nickel(2+) salt (1:1)
LPVC 20761
HPVC 20750 40
20751
20746
20724
20759
20732
239-646-5 15586-38-6 [024-017-00-8] Dichromic acid (H2-Cr2-O7), nickel(2+) salt (1:1)
237-595-3 13859-60-4
Nickelate(2-), tetrafluoro-, dipotassium, (T-4)-
308-989-3 99587-11-8
Nickelate(2-), tetrachloro-, diammonium, (T-4)-
246-378-2 24640-21-9
Nickelate(1-), trichloro-, ammonium
237-597-4 13859-65-9
Nickel, tetrakis(phosphorous trifluoride)-, (T-4)-
238-753-4 14708-14-6
Borate(1-), tetrafluoro-, nickel(2+) (2:1)
237-638-6 13877-20-8
Nickel(2+), hexaammine-, (OC-6-11)-,
bis[tetrafluoroborate(1-)]
247-430-7 26043-11-8 [009-013-00-6] Silicate(2-), hexafluoro-, nickel(2+) (1:1)
250-370-4 30868-55-4
Zirconate(2-), hexafluoro-, nickel(2+) (1:1), (OC-6-11)-
235-531-9 12263-13-7
Molybdate(3-), tetracosa-mu-oxododecaoxo[mu12[phosphato(3-)O:O:O:O':O':O':O'':O'':O'':O''':O''':O''']]dodeca-, nickel(2+)
(2:3)
40
Also nickel(II) nitrate hexahydrate, CAS No.: 13478-00-7, CUS No. 39097.
39
11021
20740
20741
Organic nickel compounds (listed in order of increasing carbon number).
EC Number CAS
Number
Chemical Name
222-101-0 3349-06-2
Formic acid, nickel(2+) salt
239-946-6 15843-02-4
Formic acid, nickel salt
268-755-0 68134-59-8
Formic acid, copper nickel salt
272-149-1 68758-60-1
Nickel(2+), hexaammine-, (OC-6-11)-, diformate
237-205-1 13689-92-4 [615-032-00-6]
Thiocyanic acid, nickel(2+) salt
208-933-7 547-67-1
Ethanedioic acid, nickel(2+) salt (1:1)
[607-007-00-3]
HPVC /
LPVC
20742
20752
243-867-2 20543-06-0 [607-007-00-3]
Ethanedioic acid, nickel salt
206-761-7 373-02-4
Acetic acid, nickel(2+) salt
LPVC
239-086-1 14998-37-9
Acetic acid, nickel salt
LPVC
240-235-8 16083-14-0
Acetic acid, trifluoro-, nickel(2+) salt
262-383-2 60700-37-0
2-Propenoic acid, nickel(2+) salt
257-066-0 51222-18-5
2-Propenoic acid, nickel salt
267-961-8 67968-22-3
Nickelate(4-),
[[[nitrilotris(methylene)]tris[phosphonato]](6-)]-,
triammonium hydrogen, (T-4)-
264-338-2 63588-33-0
Nickelate(4-),
[[[nitrilotris(methylene)]tris[phosphonato]](6-)]-,
tetrapotassium, (T-4)-
268-296-6 68052-00-6
Nickelate(4-),
[[[nitrilotris(methylene)]tris[phosphonato]](6-)N,O,O'',O''']-, tetrasodium, (T-4)-
222-102-6 3349-08-4
Propanoic acid, nickel(2+) salt
267-923-0 67952-69-6
1,2,3-Propanetriol, mono(dihydrogen phosphate),
nickel(2+) salt (1:1)
269-946-1 68391-37-7
1,2,3-Propanetriol, 1-(dihydrogen phosphate), nickel(2+)
salt (1:1)
264-136-4 63427-32-7 [006-007-00-5]
Copper(2+), bis(1,2-ethanediamine-N,N’)-, (SP-4-1)tetrakis(cyano-C)nickelate(2-) (1:1)
273-379-5 68958-89-4 [006-007-00-5]
Nickel(2+), bis(1,2-ethanediamine-N,N’)-, bis[bis(cyanoC)aurate(1-)]
244-300-1 21264-77-7
Nickel(2+), bis(ethylenediamine)-, sulfate (1:1)
287-849-2 85586-46-5
Nickel, bis(1H-1,2,4-triazole-3-sulfonato-N(2)-,O(3))-
228-501-1 6283-67-6
2-Butenedioic acid (E)-, nickel(2+) salt (1:1)
237-618-7 13869-33-5
Nickel, [N-(carboxymethyl)glycinato(2-)-N,O,O(N)-]-
268-711-0 68133-84-6
Nickel, [(2-amino-2-oxoethoxy)acetato(2-)]-
268-195-7 68025-40-1
Nickelate(3-), [N,N-bis(phosphonomethyl)glycinato(5-)], triammonium, (T-4)-
264-360-2 63597-34-2
Nickelate(3-), [N,N-bis(phosphonomethyl)glycinato(5-)], tripotassium, (T-4)-
268-196-2 68025-41-2
Nickelate(3-), [N,N-bis(phosphonomethyl)glycinato(5-)], trisodium, (T-4)-
41
Also nickel(II) acetate tetrahydrate, CAS No.: 6018-89-9, CUS No. 39093.
40
20723 41
Organic nickel compounds (continued).
257-963-7 52496-91-0
2-Propenoic acid, 2-methyl-, nickel(2+) salt
304-466-9 94275-78-2
2-Propenoic acid, 2-methyl-, nickel salt
267-894-4 67952-41-4
Butanedioic acid, 2,3-dihydroxy- [R-(R*,R*)]-,
nickel(2+) salt (2:1)
257-610-7 52022-10-3
Butanedioic acid, 2,3-dihydroxy- [R-(R*,R*)]-, nickel
salt
237-877-6 14038-85-8 [006-007-00-5]
Nickelate(2-), tetrakis(cyano-C)-, disodium, (SP-4-1)-
273-375-3 68958-86-1
Nickelate(6-), [[[1,2ethanediylbis[nitrilobis(methylene)]]tetrakis[phosphonat
o]](8-)]-, pentaammonium hydrogen, (OC-6-21)-
273-376-9 68958-87-2
Nickelate(6-), [[[1,2ethanediylbis[nitrilobis(methylene)]]tetrakis[phosphonat
o]](8-)]-, pentapotassium hydrogen, (OC-6-21)-
273-377-4 68958-88-3
Nickelate(6-), [[[1,2ethanediylbis[nitrilobis(methylene)]]tetrakis[phosphonat
o]](8-)]-, pentasodium hydrogen, (OC-6-21)-
257-953-2 52486-98-3
Nickel, bis[(2-hydroxyethyl)carbamodithioato-S,S’]-,
(SP-4-1)-
239-560-8 15521-65-0
Nickel, bis(dimethylcarbamodithioato-S,S’)-, (SP-4-1)-
252-235-5 34831-03-3
Nickelate(1-), [N,N-bis(carboxymethyl)glycinato(3-)N,O,O’,O’’]-, hydrogen, (T-4)-
264-377-5 63640-18-6
Nickelate(1-), [N,N-bis(carboxymethyl)glycinato(3-)N,O,O’,O’’]-, potassium, (T-4)-
254-642-3 39819-65-3
Benzenesulfonic acid, nickel(2+) salt
303-972-7 94232-44-7
1,2,3-Propanetricarboxylic acid, 2-hydroxy-, cobalt(2+)
nickel(2+) salt (2:1:2)
227-873-2 6018-92-4
1,2,3-Propanetricarboxylic acid, 2-hydroxy-, nickel(2+)
salt (2:3)
304-013-5 94232-84-5
1,2,3-Propanetricarboxylic acid, 2-hydroxy-, cobalt(2+)
nickel(2+) salt (2:2:1)
268-176-3 68025-13-8
1,2,3-Propanetricarboxylic acid, 2-hydroxy-, ammonium
nickel(2+) salt (2:2:1)
242-533-3 18721-51-2
Citric acid, nickel(2+) salt (1:1)
242-161-1 18283-82-4
Citric acid, ammonium nickel salt
245-119-0 22605-92-1
1,2,3-Propanetricarboxylic acid, 2-hydroxy-, nickel salt
209-046-8 553-71-9
Benzoic acid, nickel(2+) salt
254-210-4 38951-94-9
Nickel, bis[2-butene-2,3-dithiolato(2-)-S,S’]-, (SP-4-1)-
275-994-4 71767-12-9 [092-002-00-3]
Uranate(2-), tetrakis(acetato-O)dioxo-, nickel(2+) (1:1),
(OC-6-11)-
20766
236-782-7 13478-93-8
Nickel, bis[(2,3-butanedione dioximato)(1-)-N,N’]-, (SP4-1)-
16135
224-699-9 4454-16-4
Hexanoic acid, 2-ethyl-, nickel(2+) salt
231-480-1 7580-31-6
Hexanoic acid, 2-ethyl-, nickel salt
301-323-2 93983-68-7
Hexanoic acid, dimethyl-, nickel salt
225-656-7 4995-91-9
Octanoic acid, nickel(2+) salt
249-555-2 29317-63-3
Isooctanoic acid, nickel(2+) salt
248-585-3 27637-46-3
Isooctanoic acid, nickel salt
41
20737
20733
20726
LPVC
Organic nickel compounds (continued).
284-349-6 84852-37-9
Isononanoic acid, nickel(2+) salt
300-094-6 93920-10-6
Neononanoic acid, nickel(2+) salt
215-039-0 1271-28-9
Nickelocene-
274-912-4 70824-02-1
Nickel, bis(5-oxo-L-prolinato-N(1)-,O(2))-
285-069-7 85026-81-9
Nickel, bis(5-oxo-DL-prolinto-N(1)-,O(2))-
247-019-2 25481-21-4
Nickelate(2-), [[N,N'-1,2-ethanediylbis[N(carboxymethyl)glycinato]](4-)-N,N',O,O',O(N)-,O(N')]-, dihydrogen, (OC-6-21)-
267-686-3 67906-12-1
Nickelate(1-), [[N,N'-1,2-ethanediylbis[N(carboxymethyl)glycinato]](4-)-N,N',O,O',O(N)-,O(N')]-, potassium, (OC-6-21)-
221-875-7 3264-82-2
Nickel, bis(2,4-pentanedionato-O,O')-, (SP-4-1)-
223-463-2 3906-55-6
Cyclohexanebutanoic acid, nickel(2+) salt
257-954-8 52486-99-4
Nickel, bis[bis(2-hydroxyethyl)carbamodithioato-S,S']-,
(SP-4-1)-
278-504-7 76625-10-0
Nickel, bis[N-(2-hydroxyethyl)-N-methylglycinatoN,O,O(N)-]-
238-157-4 14267-17-5
Nickel, bis(diethylcarbamodithioato-S,S')-, (SP-4-1)-
258-044-3 52610-81-8
Nickel, bis(diethylcarbamodithioato-S,S')-
287-468-1 85508-43-6
Isodecanoic acid, nickel(2+) salt
287-469-7 85508-44-7
Neodecanoic acid, nickel(2+) salt
257-447-1 51818-56-5
Neodecanoic acid, nickel salt
239-028-5 14949-69-0
Nickel, bis(1,1,1,5,5,5-hexafluoro-2,4-pentanedionatoO,O')-, (SP-4-1)-
300-093-0 93920-09-3
Neoundecanoic acid, nickel(2+) salt
235-339-5 12170-92-2
Nickel, di-mu-carbonylbis(eta(5)-2,4-cyclopentadien-1yl)di-, (Ni-Ni)
255-387-0 41476-75-9
Nickel, bis(1-piperidinecarbodithioato-S,S')-
276-205-6 71957-07-8
Nickel, bis(D-gluconato-O(1)-,O(2))-
258-051-1 52625-25-9
Benzoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-,
nickel(2+) salt (2:1)
215-072-0 1295-35-8
Nickel, bis[(1,2,5,6-eta)-1,5-cyclooctadiene]-
238-536-4 14522-99-7
Nickel, bis(6-methyl-2,4-heptanedionato-O,O')-
284-350-1 84852-38-0
Nickel, (2-ethylhexanoato-O)(isooctanoato-O)-
237-138-8 13654-40-5
Hexadecanoic acid, nickel(2+) salt
274-916-6 70833-37-3
Nickel, bis(3-amino-4,5,6,7-tetrachloro-1H-isoindol-1one oximato-N(2)-,O(1))-
250-401-1 30947-30-9
Phosphonic acid, [[3,5-bis(1,1-dimethylethyl)-4hydroxyphenyl]methyl]-, monoethyl ester, nickel(2+) salt
(2:1)
287-470-2 85508-45-8
Nickel, (2-ethylhexanoato-O)(isononanoato-O)-
287-471-8 85508-46-9
Nickel, (isononanoato-O)(isooctanoato-O)-
265-022-7 64696-98-6
Nickel, [2,3'-bis[[(2-hydroxyphenyl)methylene]amino]2-butenedinitrilato(2-)-N(2)-,N(3)-,O(2)-,O(3)-]-, (SP-42)-
42
20735
20753
32526
LPVC
Organic nickel compounds (continued).
237-950-2 14100-15-3
Nickel, bis(8-quinolinolato-N(1)-,O(8))-
239-841-5 15751-00-5
Nickel(2+), hexakis(1H-imidazole-N(3))-, dichloride,
(OC-6-11)-
284-347-5 84852-35-7
Nickel, (isooctanoato-O)(neodecanoato-O)-
284-351-7 84852-39-1
Nickel, (2-ethylhexanoato-O)(isodecanoato-O)-
285-698-7 85135-77-9
Nickel, (2-ethylhexanoato-O)(neodecanoato-O)-
285-909-2 85166-19-4
Nickel, (isodecanoato-O)(isooctanoato-O)-
235-832-5 13001-15-5
9-Octadecenoic acid (Z)-, nickel(2+) salt
237-696-2 13927-77-0
Nickel, bis(dibutylcarbamodithioato-S,S')-, (SP-4-1)-
239-354-8 15317-78-9
Nickel, bis[bis(2-methylpropyl)carbamodithioato-S,S']-,
(SP-4-1)-
218-744-1 2223-95-2
Octadecanoic acid, nickel(2+) salt
288-967-7 85958-80-1
Nickel, [2-hydroxybenzoic acid [3-[1-cyano-2(methylamino)-2-oxoethylidene]-2,3-dihydro-1Hisoindol-1-ylidene]hydrazidato(2-)]-
284-348-0 84852-36-8
Nickel, (isodecanoato-O)(isononanoato-O)-
287-592-6 85551-28-6
Nickel, (isononanoato-O)(neodecanoato-O)-
235-829-9 12794-26-2
Nickel, bis(1-nitroso-2-naphthalenolato)-
238-380-7 14406-66-7
Nickel, bis(1-nitroso-2-naphthalenolato-N(1)-,O(2))-, (T4)-
249-503-9 29204-84-0
Nickel, bis[2,3-bis(hydroxyimino)-Nphenylbutanamidato-N(2)-,N(3)-]-
287-467-6 85508-42-5
Nickel, (isodecanoato-O)(neodecanoato-O)-
300-092-5 93920-08-2
Nickel, (neononanoato-O)(neoundecanoato-O)-
256-331-8 47726-62-5
Nickel, [[2,2'-(4,8-dichlorobenzo[1,2-d:4,5d']bisoxazole-2,6-diyl)bis[4,6-dichlorophenolato]](2-)]-
255-924-9 42739-61-7
Nickel, bis[2,3-bis(hydroxyimino)-N-(2methoxyphenyl)butanamidato]-
252-937-1 36259-37-7
Nickel, bis(dipentylcarbamodithioato-S,S')-, (SP-4-1)-
286-563-5 85269-39-2
Nickel, bis[N-(2,4-dimethoxyphenyl)-2,3bis(hydroxyimino)butanamidato-N(2)-,N(3)-]-, (SP-4-1)-
279-314-7 79817-91-7
Nickelate(3-), [5-[(4,5-dihydro-3-methyl-5-oxo-1phenyl-1H-pyrazol-4-yl)azo]-4-hydroxy-3-[(2-hydroxy3-nitro-5-sulfophenyl)azo]-2,7-naphthalenedisulfonato(5)]-, trisodium
243-820-6 20437-10-9
Nickel, [[1,1'-[1,2phenylenebis(nitrilomethylidyne)]bis[2naphthalenolato]](2-)-N,N',O,O']-
249-353-4 28984-20-5
Nickel, bis[1,2-diphenyl-1,2-ethenedithiolato(2-)-S,S']-,
(SP-4-1)-
248-536-6 27574-34-1
Nickel, [[2,2'-thiobis[4-(1,1,3,3tetramethylbutyl)phenolato]](2-)-O,O',S]-
251-715-1 33882-09-6
Nickel, [[2,2'-thiobis[3-octylphenolato]](2-)-O,O',S]-
240-485-8 16432-37-4
Nickel, [[2,2'-sulfonylbis[4-(1,1,3,3tetramethylbutyl)phenolato]](2-)-O(1)-,O(1')-,O(2)-]-
262-703-0 61300-98-9
Nickelate(1-), [3,4-bis[[(2-hydroxy-1naphthalenyl)methylene]amino]benzoato(3-)-N(3)-,N(4),O(3)-,O(4)-]-, hydrogen
43
LPVC
20736
27634
LPVC
LPVC
Organic nickel compounds (continued).
255-965-2 42844-93-9
Nickel, [1,3-dihydro-5,6-bis[[(2-hydroxy-1naphthalenyl)methylene]amino]-2H-benzimidazol-2onato(2-)-N(5)-,N(6)-,O(5)-,O(6)-]-, (SP-4-2)-
257-521-3 51931-46-5
Nickel, bis[3-[(4-chlorophenyl)azo]-2,4(1H,3H)quinolinedionato]-
267-045-8 67763-27-3
Nickel, (2-propanol)[[2,2'-thiobis[4-(1,1,3,3tetramethylbutyl)phenolato]](2-)-O,O',S]-
249-155-8 28680-76-4
Nickel, [29H,31H-phthalocyaninetetrasulfonyl
tetrachloridato(2)-N(29)-,N(30)-,N(31)-,N(32)-]-
237-893-3 14055-02-8
Nickel, [29H,31H-phthalocyaninato(2-)-N(29)-,N(30),N(31)-,N(32)-]-, (SP-4-1)-
254-212-5 38951-97-2
Nickel, bis[1,2-bis(4-methoxyphenyl)-1,2ethenedithiolato(2-)-S,S']-, (SP-4-1)-
253-958-9 38465-55-3
Nickel, bis[1-[4-(dimethylamino)phenyl]-2-phenyl-1,2ethenedithiolato(2-)-S,S']-
238-523-3 14516-71-3
Nickel, (1-butanamine)[[2,2'-thiobis[4-(1,1,3,3tetramethylbutyl)phenolato]](2-)-O,O',S]-
276-364-1 72139-08-3
Nickelate(8-), bis[3-[(2-amino-8-hydroxy-6-sulfo-1naphthalenyl)azo]-2-hydroxy-5-sulfobenzoato(5-)]-,
hexasodium dihydrogen
281-282-4 83898-70-8
Nickel, dimethoxy[29H,31H-phthalocyaninato(2-)N(29)-,N(30)-,N(31)-,N(32)-]-, (OC-6-12)-
274-027-3 69524-96-5
Nickel, bis(4-benzoyl-2,4-dihydro-5-methyl-2-phenyl3H-pyrazol-3-onato-O,O')-
238-400-4 14428-08-1
Nickel, bis[bis(2-ethylhexyl)carbamodithioato-S,S']-
238-154-8 14264-16-5
Nickel, dichlorobis(triphenylphosphine)-
279-060-7 79102-62-8
Nickelate(4-), [[[(3-amino-4sulfophenyl)amino]sulfonyl]-29H,31Hphthalocyaninetrisulfonato(6-)-N(29)-,N(30)-,N(31),N(32)-]-, tetrahydrogen
300-365-9 93939-76-5
Nickelate(4-), [[[(3-amino-4sulfophenyl)amino]sulfonyl]-29H,31Hphthalocyaninetrisulfonato(6-)-N(29)-,N(30)-,N(31),N(32)-]-, tetrasodium
235-851-9 13007-90-4
Nickel, dicarbonylbis(triphenylphosphine)-, (T-4)-
283-380-2 84604-95-5
Nickel, bis[bis(3,5,5-trimethylhexyl)carbamodithioatoS,S’]-
260-258-7 56557-00-7
Nickel, bis[2,4-dihydro-5-methyl-4-(1-oxodecyl)-2phenyl-3H-pyrazol-3-onato-O,O’]-
276-491-2 72229-81-3
Nickelate(3-), [[[[3-[(4-amino-6-chloro-1,3,5-triazin-2yl)amino]phenyl]amino]sulfonyl]tris(aminosulfonyl)29H,31H-phthalocyaninetrisulfonato(5-)-N(29)-,N(30),N(31)-,N(32)-]-, trisodium
275-295-4 71243-96-4
Nickelate(3-), [22-[[[3-[(5-chloro-2,6-difluoro-4pyrimidinyl)amino]phenyl]amino]sulfonyl]-29H,31Hphthalocyanine-1,8,15-trisulfonato(5-)-N(29)-,N(30),N(31)-,N(32)-]-, trisodium, (SP-4-2)-
276-168-6 71889-22-0
Nickel, [mu-(piperazine-N(1)-:N(4))]bis[3-[1-[(4,5,6,7tetrachloro-1-oxo-1H-isoindol-3-yl)hydrazono]ethyl]2,4(1H,3H)-quinolinedionato(2-)]di-
239-949-2 15843-91-1
Nickel, bis[[2-hydroxy-4(octyloxy)phenyl]phenylmethanonato]-
44
LPVC
LPVC
32583
32582
Organic nickel compounds (continued).
306-462-2 97280-68-7
Nickelate(4-), [bis[[[4-[[2(sulfooxy)ethyl]sulfonyl]phenyl]amino]sulfonyl]29H,31H-phthalocyaninedisulfonato(6)-N(29)-,N(30),N(31)-,N(32)-]-, tetrasodium
245-028-6 22484-07-7
Nickel, [mu-[[1,1’,1’’,1’’’-[1,2,4,5benzenetetrayltetrakis(nitrilomethylidyne)]tetrakis[2naphthalenolato]](4-)]]di-
272-095-9 68698-80-6
Nickelate(6-), [4-[[5-[[(3,6-dichloro-4pyridazinyl)carbonyl]amino]-2-sulfophenyl]azo]-4,5dihydro-5-oxo-1-[5-[[(trisulfo-29H,31Hphthalocyaninyl)sulfonyl]amino]-2-sulfophenyl]-1Hpyrazole-3-carboxyla
299-467-3 93891-86-2
Nickelate(6-), [4-[[5-[[(3,6-dichloro-4pyridazinyl)carbonyl]amino]-2-sulfophenyl]azo]-4,5dihydro-5-oxo-1-[2-sulfo-5-[[(trisulfo-29H,31Hphthalocyaninyl)sulfonyl]amino]phenyl]-1H-pyrazole-3carboxyla
272-799-6 68912-08-3
Nickel, bis(2-heptadecyl-1H-imidazoleN(3))bis(octanoato-O)-
279-067-5 79121-51-0
Nickel, bis(4-benzoyl-2,4-dihydro-5-methyl-2-phenyl3H-pyrazol-3-onato-O,O’)(2,2,4,4-tetramethyl-7-oxa3,20-diazadispiro[5.1.11.2]heneicosan-21-one-O(21))-
276-399-2 72152-45-5
Nickelate(6-), [22-[[[3-[[4,5-dihydro-3-methyl-5-oxo-1[3-sulfo-4-[2-[2-sulfo-4-[(2,5,6-trichloro-4pyrimidinyl)amino]phenyl]ethenyl]phenyl]-1H-pyrazol4-yl]azo]-4-sulfophenyl]amino]sulfonyl]-29H,31H-
306-784-3 97404-21-2
Nickel, [[N,N’,N’’-[29H,31Hphthalocyaninetriyltris(sulfonylimino-3,1phenylene)]tris[3-oxobutanamidato]](2-)-N(29)-,N(30),N(31)-,N(32)-]-
269-684-8 68309-97-7
Nickel(2+), tris(4,7-diphenyl-1,10-phenanthroline-N(1),N(10))-, (OC-6-11)-, bis[tetrafluoroborate(1-)]
254-127-3 38780-90-4
Nickel(2+), tris(4,7-diphenyl-1,10-phenanthroline-N(1),N(10))-, (OC-6-11)-, dinitrate
277-174-1 72986-45-9
Nickel, [N,N’,N’’,N’’’-tetrakis[4-(4,5-dihydro-3-methyl5-oxo-1H-pyrazol-1-yl)phenyl]-29H,31Hphthalocyaninetetrasulfonamidato(2-)-N(29)-,N(30),N(31)-,N(32)-]-
306-785-9 97404-22-3
Nickel, [[N,N’,N’’,N’’’-[29H,31Hphthalocyaninetetrayltetrakis(sulfonylimino-3,1phenylene)]tetrakis[3-oxobutanamidato]](2-)-N(29),N(30)-,N(31)-,N(32)-]-
252-777-2 35884-66-3
Nickel, tetrakis[tris(methylphenyl) phosphite-P]-
262-934-7 61725-51-7
Nickel, 3-[(4-chlorophenyl)azo]-4-hydroxy-2(1H)quinolinone complex
263-000-1 61788-71-4
Naphthenic acids, nickel salts
269-826-9 68334-36-1
Resin acids and Rosin acids, nickel salts
271-764-2 68607-31-8
Resin acids and Rosin acids, calcium nickel salts
270-174-2 68412-18-0
Nickel, [29H,31H-phthalocyaninato(2-)-N(29)-,N(30),N(31)-,N(32)-]-, sulfo [[4-[[2(sulfooxy)ethyl]sulfonyl]phenyl]amino]sulfonyl derivs.
270-944-8 68511-62-6
Nickel, 5,5'-azobis-2,4,6(1H,3H,5H)-pyrimidinetrione
complexes
45
LPVC
Organic nickel compounds (continued).
276-877-0 72828-53-6
Nickel, [29H,31H-phthalocyaninato(2-)-N(29)-,N(30),N(31)-,N(32)-]-, [[3-[(1,3dioxobutyl)amino]phenyl]amino]sulfonyl derivs.
294-302-1 91697-41-5
Fatty acids, C6-C19-branched, nickel salts
283-972-0 84776-45-4
Fatty acids, C8-C18 and C18-unsatd., nickel salts
287-356-2 85480-75-7
Nickel, 2,2'-thiobis[4-nonylphenol] complexes
291-676-8 90459-33-9
Nickel, isooctanoate naphthenate complexes
287-801-0 85585-98-4
Nickel, isononanoate naphthenate complexes
287-800-5 85585-97-3
Nickel, isodecanoate naphthenate complexes
287-802-6 85585-99-5
Nickel, naphthenate neodecanoate complexes
291-673-1 90459-30-6
Nickel, acetate carbonate C8-C10-branched fatty acids
C9-C11-neofatty acids complexes
291-674-7 90459-31-7
Nickel, borate C8-C10-branched carboxylate complexes
291-675-2 90459-32-8
Nickel, C5-C23-branched carboxylate octanoate
complexes
291-677-3 90459-34-0
Nickel, acetylacetone 6-methyl-2,4-heptanedione
complexes
291-678-9 90459-35-1
Nickel, [29H,31H-phthalocyaninato(2-)-N(29)-,N(30),N(31)-,N(32)-]-, [[3-[(5-chloro-2,6-difluoro-4pyrimidinyl)amino]phenyl]amino]sulfonyl sulfo derivs.,
sodium salts
291-679-4 90459-36-2
Nickelate(4-), [bis[[[3-[[4,5-dihydro-3-methyl-5-oxo-1[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]-1H-pyrazol-4yl]azo]phenyl]amino]sulfonyl]-29H,31Hphthalocyaninedisulfonato(6-)-N(29)-,N(30)-,N(31)-,N(3
295-925-1 92200-98-1
Nickel, C5-C23-branched carboxylate naphthenate
complexes
295-926-7 92200-99-2
Nickel, C5-C25-branched carboxylate naphthenate
octanoate complexes
296-343-0 92502-55-1
Nickel, borate neodecanoate complexes
297-548-8 93573-14-9
Nickel, C5-C23-branched carboxylate C4-C10-fatty
acids naphthenate complexes
297-549-3 93573-15-0
Nickel, C4-C10 fatty acids naphthenate complexes
297-550-9 93573-16-1
Nickel, C4-C10 fatty acids octanoate complexes
297-774-7 93762-59-5
Nickel, C5-C23-branched carboxylate C4-C10 fatty acids
complexes
297-551-4 93573-17-2
Nickel, [29H,31H-phthalocyaninato(2-)-N(29)-,N(30),N(31)-,N(32)-]-, chlorosulfonyl derivs., reaction
products with 2-[(4-aminophenyl)sulfonyl]ethyl
hydrogen sulfate monosodium salt, potassium sodium
305-643-3 94891-42-6
Nickel, [29H,31H-phthalocyaninato(2-)-N(29)-,N(30),N(31)-,N(32)-]-, chlorosulfonyl derivs., reaction
products with 2-[(4-aminophenyl)sulfonyl]ethyl
hydrogen sulfate monosodium salt, potassium salts
305-644-9 94891-43-7
Nickel, [29H,31H-phthalocyaninato(2-)-N(29)-,N(30),N(31)-,N(32)-]-, chlorosulfonyl derivs., reaction
products with 2-[(4-aminophenyl)sulfonyl]ethyl
hydrogen sulfate monosodium salt, sodium salts
46
LPVC
Diverse Nickel compounds.
EC Number CAS
Number
Annex I No.
Chemical Name
HPVC /
LPVC
307-554-5 97660-42-9
Copper, bis(8-quinolinolato-N(1)-,O(8))-, reaction
products with C8-C10-branched fatty acids, tert-decanoic
acid, nickel(2+) diacetate, nickel(2+) carbonate (1:1) and
nickel hydroxide (Ni(OH)2)
283-945-3 84776-20-5
Bentonite, nickeloan
232-490-9 8052-42-4
Asphalt
HPVC
266-046-0 65997-17-3
Glass, oxide, chemicals
HPVC
266-047-6 65997-18-4
Frits, chemicals
HPVC
266-048-1 65997-19-5
Steel manufacture, chemical
266-340-9 66402-68-4
Ceramic materials and wares, chemicals
266-965-7 67711-89-1
Calcines, copper roasting
266-967-8 67711-91-5
Matte, copper
HPVC
266-968-3 67711-92-6
Slags, copper smelting
HPVC
268-627-4 68131-74-8
Ashes, residues
HPVC
273-700-9 69011-59-2
Lead alloy, base, dross
LPVC
273-701-4 69011-60-5
Lead alloy, base, Pb,Sn, dross
HPVC
273-704-0 69011-64-9
Babbitt, dross
273-720-8 69012-20-0
Waste solids, copper electrolyte purifn. cathodes
HPVC
273-729-7 69012-29-9
Slags, ferronickel-manufg.
HPVC
273-749-6 69012-50-6
Matte, nickel
HPVC
273-795-7 69029-51-2
Lead, antimonial, dross
282-214-6 84144-92-3
Leach residues, nickel-vanadium ore
293-311-8 91053-46-2
Leach residues, zinc ore-calcine, cadmium-copper ppt.
HPVC
293-312-3 91053-47-3
Leach residues, zinc ore-calcine, iron contg.
HPVC
293-796-6 91082-81-4
Waste solids, chromium-nickel steel manuf.
293-799-2 91082-84-7
Waste solids, nickel-manuf.
295-859-3 92129-57-2
Slimes and Sludges, copper electrolyte refining,
decopperised, Ni sulfate
HPVC
297-402-3 93571-76-7
Ashes (residues), heavy fuel oil fly
LPVC
305-433-1 94551-87-8
Slimes and Sludges, copper electrolyte refining,
decopperised
LPVC
CUS
Number
HPVC
308-765-5 98246-91-4 [082-001-00-6] Speiss, lead, nickel-contg.
310-050-8 102110-49-6 [082-001-00-6] Residues, copper-iron-lead-nickel matte, sulfuric acidinsol.
Note: Einecs entries that include a reference to nickel as e.g. a catalyst rather than as a constituent have not
been included.
47
TABLE 1.2: Nickel compounds included in Elincs.
EC Number CAS
Number
Annex I No.
Chemical Name
410-160-7 148732-74-5 607-288-00-2
Tetrasodium (c-(3-(1-(3-(e-6-dichloro-5-cyanopyrimidinf-yl(methyl)amino)propyl)-1,6-dihydro-2-hydroxy-4methyl-6-oxo-3-pyridylazo)-4sulfonatophenylsulfamoyl) phtalocyanine-a,b,dtrisulfonato(6-))nickelato II, where a 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 f together are 2 and 4 or 4
and 2 respectively
407-110-1 -
611-103-00-0
Trisodium (1-(3-carboxylato-2-oxido-5sulfonatophenylazo)-5-hydroxy-7-sulfonatophthalen-2amido)nickel(II)
417-250-5 151436-99-6 611-122-00-2
Hexasodium (di(N-(3-(4-[5-(5-amino-3-methyl-1phenylpyrazol-4-yl-azo)-2,4-disulfo-anilino]-6-chloro1,3,5-triazin-2-ylamino)phenyl)-sulfamoyl](disulfo)phthalocyaninato)nickel
48
HPVC /
LPVC
CUS
Number
TABLE 1.3: Additional Nickel compounds, and complex substances containing nickel included in
TSCA (through 08/2000) but not included in Einecs.
EC No.
CAS Number Annex I No.
Chemical Name
12031-65-1
Lithium nickel oxide (LiNiO2)
12645-50-0
Iron-nickel-zinc-oxide-
12673-58-4
Molybdenum-nickel-oxide-
12737-30-3
Cobalt-nickel-oxide-
14221-00-2
Nickel, tetrakis(triphenyl phosphite-kappaP)-, (T-4)-
14406-71-4
Nickel, [[2,2'-[1,2-phenylenebis[(nitrilokappaN)methylidyne]]bis[phenolato-kappaO]](2-)]-
14434-67-4
Nickel, bis(hexahydro-1H-azepine-1-carbodithioatokappaS,kappaS')-, (SP-4-1)-
17169-61-8
Phosphoric acid, calcium nickel salt
18824-79-8
1,2-Benzenedicarboxylic acid, 3,4,5,6-tetrabromo-,
nickel(2+) salt (1:1)
18972-69-5
[006-007-00-5]
Nickel(2+), bis(1,2-propanediaminekappaN,kappaN')-, bis[bis(cyano-kappaC)aurate(1-)]
19372-20-4
Diphosphoric acid, nickel(2+) salt
34109-80-3
Titanate(2-), hexafluoro-, nickel(2+), (1:1), (OC-611)-
36545-21-8
Nickel, bis[(phenyldiazenecarbothioic acid-kappaS)
2-phenylhydrazidato-kappaN2]-
51449-18-4
Nickel, bis[1-[4-(diethylamino)phenyl]-2-phenyl1,2-ethenedithiolato(2-)-kappaS,kappaS']-
53199-85-2
Nickel(1+), [1-[2-amino-4-(imino-kappaN)-5(4H)thiazolylidene]-N-[1-[2-amino-4-(imino-kappaN)5(4H)-thiazolylidene]-1H-isoindol-3-yl-kappaN]1H-isoindol-3-aminato-kappaN2]-, chloride
54576-53-3
[051-003-00-9]
Antimony-nickel-titanium-oxide-
55868-93-4
Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)4-hydroxy-, nickel(2+) salt (2:1)
65229-23-4
Nickel-boron-phosphide-
68189-15-1
Nickel, bis[[2-(hydroxy-kappaO)-4octylphenyl]phenylmethanonato-kappaO]-
68412-19-1
Nickel, [29H,31H-phthalocyaninato(2-)N29,N30,N31,N32]-, [(3aminophenyl)amino]sulfonyl sulfo derivs.
68412-20-4
Nickel, dextrin complexes
68585-48-8
Sulfuric acid, nickel(2+) salt (1:1), reaction products
with nickel and nickel oxide (NiO)
69012-51-7
Copper cake, zinc-refining
70776-98-6
Nickel, (2-ethylhexanoato-kappaO)(trifluoroacetatokappaO)-
71050-57-2
Acetic acid, nickel(2+) salt, polymer with
formaldehyde and 4-(1,1,3,3-tetramethylbutyl)phenol
49
HPVC/
LPVC
CUS
Number
Additional Nickel compounds in TSCA (continued)
71215-73-1
Nickel, [[2,2'-[methylenebis(thiokappaS)]bis[acetato-kappaO]](2-)]-
71215-97-9
Nickel(2+), tris(1,2-ethanediaminekappaN,kappaN')-, (OC-6-11)-, salt with
dimethylbenzenesulfonic acid (1:2)
71215-98-0
Nickel(2+), bis(1,2-ethanediaminekappaN,kappaN')-, salt with
dimethylbenzenesulfonic acid (1:2)
71605-83-9
Nickel, bis[N-hydroxy-3-(hydroxyimino-kappaN)N'-(2-methoxyphenyl)butanimidamidato-kappaN']-
71889-20-8
Nickel, [N-(4-chlorophenyl)-3-[[[1-(4chlorophenyl)-4,5-dihydro-3-methyl-5-(oxokappaO)-1H-pyrazol-4-yl]methylene]hydrazinokappaN2]-alpha-cyano-1H-isoindole-3acetamidato(2-)-kappaN2,kappaO3]-
72162-32-4
Sulfuric acid, nickel salt, reaction products with
sulfurized calcium phenolate
72252-57-4
Nickel, [N,N',N''-tris[4-(4,5-dihydro-3-methyl-5oxo-1H-pyrazol-1-yl)phenyl]-29H,31Hphthalocyanine-C,C,C-trisulfonamidato(2-)kappaN29,kappaN30,kappaN31,kappaN32]-
72319-19-8
2,7-Naphthalenedisulfonic acid, nickel(2+) salt (1:1)
79357-65-6
Aluminum, triethyl-, reaction products with
nickel(2+) bis(2-ethylhexanoate)
83864-02-2
Nickel, bis[(cyano-C)triphenylborato(1-)N]bis(hexanedinitrile-N,N')-
91845-72-6
Fatty acids, C3-22, nickel salts, basic
106316-556
Nickel, aqua[2-[[4,5-dihydro-3-methyl-5-(oxokappaO)-1H-pyrazol-4-yl]azo-kappaN1]benzoato(2)-kappaO]-
108818-899
Nickel(2+), hexakis(1H-imidazole-kappaN3)-, (OC6-11)-, 1,2-benzenedicarboxylate (1:1)
113894-885
Nickel, [29H,31H-phthalocyaninato(2-)N29,N30,N31,N32]-, sulfo [[4-[[2(sulfooxy)ethyl]sulfonyl]phenyl]amino]sulfonyl
derivs., potassium sodium salts
131866-994
Nickel, [29H,31H-phthalocyaninato(2-)N29,N30,N31,N32]-, sulfo [[4-[[2(sulfooxy)ethyl]sulfonyl]phenyl]amino]sulfonyl
derivs., sodium salts
50
TABLE 1.4: Additional Nickel compounds listed in ECICS (European Customs Inventory of chemical
substances), but not included in Einecs or the TSCA Inventory.
EC No.
CAS No.
Annex I No.
Name
HPVC/
LPVC
CUS
Number
10471-42-8
Nickel tartrate
20764
10534-88-0
Hexaamminenickel dichloride
18196
12137-12-1
Trinickel tetrasulfide
20763
42
12758-25-7
Nickel metaborate
13601-55-3
Hexaamminenickel dibromide
11020
15651-35-1
Tetraamminenickel dinitrate
11025
16039-61-5
Nickel dilactate
20748
74195-78-1
Diammonium nickel hexacyanoferrate
11023
Trinickel bis(arsenite)
20725
74646-29-0
033-002-00-5
20727
TABLE 1.5: Additional Nickel compounds in Annex I to Directive 67/548/EEC but not in Einecs or
TSCA.
EC No.
CAS No.
Annex I No.
Name
HPVC/
LPVC
12256-33-6 033-002-00-5
nickel arsenide, Ni11As8
12255-80-0 033-002-00-5
nickel arsenide, Ni5As2
12255-10-6 033-002-00-5
nickel arsenide sulfide, NiAsS
12137-13-2 033-002-00-5
nickel selenide, Ni3Se2
71077-18-4 051-003-00-9
Rutile, antimony nickel yellow
68130-19-8 082-001-00-6
Silicic acid, lead nickel salt
CUS
Number
TABLE 1.6: Additional nickel compound found in the course of compiling the inventory of nickel
compounds.
EC No.
CAS No.
Annex I No.
Name
HPVC/
LPVC
11132-10-8
nickel potassium fluoride
391864-36-1
nickel potassium cyanide (NiK2(CN)4)
55465-44-6
potassium nickel cyanide
nickel calcium cyanide 43
131344-56-4
cobalt lithium nickel oxide
162004-08-2
cobalt lithium nickel oxide (Co,Li,Ni)O2
510727-46-5
cobalt lithium nickel oxide (Co,Li)NiO2
42
The CAS number shown corresponds to boron nickel oxide and not to “nickel metaborate”.
43
Marketed without CAS No.
51
CUS
Number
TABLE 1.7: Additional nickel hydroxycarbonate compounds not included in the lists above.
EC No.
CAS No.
Annex I No.
Name, formula
152008-07-6
4NiCO3.Ni(OH)2
128024-15-7
3NiCO3.Ni(OH)2
342774-56-5
Ni(CO3)0-1.5(OH)0-3
148522-90-1
3NiCO3.4Ni(OH)2
12122-15-5
pentanickel dicarbonate hexahydroxide,
2NiCO3.3Ni(OH)2
12274-86-1
NiCO3.3Ni(OH)2
404866-99-5
NiCO3.13Ni(OH)2
HPVC/
LPVC
CUS
Number
TABLE 1.8: Nickel containing minerals (from IARC, 1990 and NiPERA, 1996).
CAS Number
Name
Chemical composition
Pentlandite
(Fe,Ni)9S8
1314-04-1
Millerite
NiS
12035-71-1
Heazlewoodite
Ni3S2
Polydymite
Ni3S4
Siegenite
(Co,Ni)3S4
Violarite
Ni2FeS4
Vaesite
NiS2 2
Pyrrhotite, nickeliferous
(Fe,Ni)1-xS
1303-13-5
Niccolite, nickeline
NiAs
12044-65-4
Maucherite
Ni11As8
Rammelsbergite
NiAs2
12255-11-7
Gersdorffite
NiAsS
12201-85-3
Makinenite, Maekinenite
NiSe
12125-61-0
Breithauptite
NiSb
24270-51-7
Imgreite
NiTe
Garnierite
(Ni, Mg)SiO3.nH2O
Nickeliferous limonite
(Fe,Ni)O(OH).nH2O
34492-97-2
Bunsenite
NiO
39430-27-8
Zaratite (basic nickel carbonate, tetrahydrate)
NiCO3.2Ni(OH)2.4H2O
Morenosite (nickel sulphate heptahydrate)
NiSO4.7H2O
53809-86-2, 12174-14-0
12035-50-6
1
1
Notes:
1)
CAS No. 53809-86-2 corresponds to Fe9Ni9S16; CAS No. 12174-14-0 corresponds to (Fe0.4-0.6Ni0.4-0.6)9S8 (NiPERA,
1996).
2)
IARC also lists pure nickel sulphide (NiS2), CAS No. 12035-51-7. Both compounds are in the +4 oxidation state.
Minerals are exempted from registration under REACH. However, minerals should be classified if they fulfill
the classification criteria. The chemical composition of some of these compounds could justify the use of
read-across for relevant endpoints.
52