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EC number: 232-104-9 | CAS number: 7786-81-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.05 mg/m³
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other:
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 104 mg/m³
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
- Overall assessment factor (AF):
- 7.5
- Modified dose descriptor starting point:
- other: HEC-NOAEC
- Value:
- 783 mg/m³
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.05 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- other:
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.6 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 4.3
- Dose descriptor starting point:
- other: HEC-LOAEC
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.44 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- Overall assessment factor (AF):
- 1
- Dose descriptor:
- other: NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Note 1. Exposures are always given in terms of mg nickel and NOT as mg substance
Note 2. All the values (including the dermal one) are provided in the table below.
Note 3. In cases where existing standards (OELs in case of workers, ambient air standards in case of general public) are used instead of DNEL/DMEL, the fields for Assessment factors and Dose descriptor Starting Points were left blank. Further information on the Standard derivation is contained in the documents referenced in the Table below.
Nickel sulphate hexahydrate DN(M)ELs for workers
Exposure pattern | Route | Descriptor | DNEL / DMELa | AF | Corrected Dose descriptor | Most sensitive endpoint | Justification |
Acute - systemic effects | Dermal |
|
|
|
|
| Not relevant, negligible absorption |
Acute - systemic effects | Inhalation | DNEL (Derived No Effect Level) | 104 mg Ni/m³ Inhalable Fractionb | 7.5c | HEC-NOAEC: 783 mg Ni/m3 Inhalable Fractiond | acute toxicity (mortality) | See footnotes |
Acute - local effects | Dermal | DNEL (Derived No Effect Level) | 20% |
|
|
|
|
Acute - local effects | Inhalation | DNEL (Derived No Effect Level) | 1.6 mg Ni/m³ Inhalable Fractionb | 4.3e | HEC-LOAEC: 6.9 mg Ni/m3 Inhalable Fractionf | repeated dose toxicity (lung inflammation) | See footnotes |
Long-term - systemic effects | Dermal |
|
|
|
|
| Not relevant, negligible absorption |
Long-term - systemic effects | Inhalation | DNEL (Derived No Effect Level) | 0.05 mg Ni/m³ Inhalable fractiong |
|
| developmental toxicity | See footnotes |
Long-term - local effects | Dermal | DNEL (Derived No Effect Level) | 0.00044 mg Ni/cm²h | 1i | NOAEL:0.00044 mg Ni/cm2 | sensitisation (skin) | See footnotes |
Long-term - local effects | Inhalation | DNEL (Derived No Effect Level) | 0.05 mg Ni/m³ Inhalable fractiong |
|
| carcinogenicity and repeated toxicity (respiratory tract- inhalation) | See footnotes |
Long-term - local effects | Inhalation | DNEL (Derived No Effect Level) | 0.05 mg Ni/m³ Inhalable fractiong |
|
| carcinogenicity and repeated toxicity (respiratory tract- inhalation) | See footnotes |
a. The approaches used in the derivation of DNELs are described in a report prepared by VITO Consultancy (Belgium)(Appendix C1), and in Appendices C2 (long-term DNELs),C3(acute DNELs), and C4 (Summary DNEL table).
b. The derivation of the acute inhalation DNELs is described in detail in Appendix C3. Dosimetric modeling was used to calculate human equivalent air concentrations (HECs) for the points of departures based on effects associated with pulmonary deposited (systemic effects) or retained (local effects) nickel doses in rats. This modeling accounts for differences in pulmonary deposition of different particle sizes between rats and humans, and also allowed the incorporation of inhalable workplace particle size ranges in the calculations.
c. Assessment Factor (AF) = 7.5. [AF interspecies differences in susceptibility (AS) = 1 for exposures expressed as concentrations mg/m3, and for lethal effects; AF interspecies remaining differences in susceptibility for respiratory tract = 2.5; AF intraspecies differences in susceptibility = 3 for substances that do not undergo metabolism, see Appendix C3 section C3.6 for more detailed justification; Overall AF = 2.5 x 3 =7.5].
d. The HEC-NOAEC of 783 mg Ni/m3 (inhalable fraction) was derived from the NOAEC of 120 mg Ni/m3 (MMAD=3µm) by applying a dosimetry adjustment as described in Appendix C3.
e. AF = 4.3. [AF interspecies difference (AS) = 1 local respiratory effects. AF interspecies difference in susceptibility = 1 (for respiratory toxicity effects after inhalation of particles of nickel or most metal-containing substances in the respirable range, rats seem to be more susceptible to toxicity effects than mice, primates or humans; AF intraspecies differences in susceptibility=3 for substances that do not undergo metabolism. AF for conversion of LOAEC to NAEC=3 based on steep dose-response for nickel toxicity. An AF for exposure duration = 1/2.1 was applied to extrapolate from 16 day repeated exposures to a single exposure. Overall AF= 1 X 3 X 3 X 1/2.1 = 4.3]. See Appendix C3 section C3.6.2 for more detailed justification of AF selection.
f. The HEC-LOAEC of 6.9 mg Ni/m3 (inhalable fraction) was derived from the LOAEC of 0.7 mg Ni/m3 (MMAD<4µm) by applying a dosimetry adjustment as described in Appendix C3.
g. The justification for the use of an inhalable OEL of 0.05 mg Ni/m3 is provided in Appendix C2. This value is based on the SCOEL proposed inhalable OEL for nickel compounds of 0.01 mg Ni/m3 (June 2011) with further adjustments for differences in particle size distributions between animal experiments and workplace exposures and differences in sampling efficiency between workplace 37-mm and inhalable samplers. The SCOEL value was based on epidemiological data on cancer effects. The registrant-derived inhalable value of 0.05 mg Ni/m3 is based on carcinogenicity effects in the respiratory tract observed in human studies, as well as toxicity local effects observed in the lungs of rats after inhalation. Both registrant and SCOEL consider nickel compounds to be genotoxic carcinogens with a practical threshold. These values are also protective against possible reproductive effects. For detailed description of the DNEL derivation and selection of AF, see Appendices C1and C2.
h. The DNEL for dermal sensitization/elicitation is based on a patch test study with Ni sulphate where exposure lasted for 48 h under occlusion. This value is likely to overestimate risk compared to workplace 8 h exposure without occlusion. This DNEL is protective of both acute and long-term dermal exposures. See Appendix B3.
i. AF =1. Study done in humans, 48 hours under occlusion. Study was done with a susceptible population.
Appendix C1= Derivation of DNELs for 4 Reference Ni substances
Appendix C2= Background Document in Support of Long-term Inhalable DNELs for Nickel Metal and Nickel Compounds
Appendix C3 = Background Document in Support of Acute DNELs and Guidance Values for Nickel Metal and Nickel Compounds
Appendix C4 = Excel table of DNEL derivations –nickel sulphate
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 60 ng/m³
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other:
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.8 mg/m³
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- other: HEC-NOAEC
- Value:
- 109.6 mg/m³
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 60 ng/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- other:
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.1 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 7.1
- Dose descriptor starting point:
- other: HEC-LOAEC
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.013 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- BMDL10
- Value:
- 1.3 mg/kg bw/day
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.37 mg/kg bw/day
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 36.6 mg/kg bw/day
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Note 1. Exposures are always given in terms of mg nickel and NOT as mg substance
Note 2. All the values (including the inhalation one) are provided in the table below:
Note 3. In cases where existing standards (OELs in case of workers, ambient air standards in case of general public) are used instead of DNEL/DMEL, the fields for Assessment factors and Dose descriptor Starting Points were left blank. Further information on the Standard derivation is contained in the documents referenced in the Table below.
Nickel sulphate hexahydrate DN(M)ELs for general population (MvE)
Exposure pattern | Route | Descriptor | DNEL / DMELa | AF | Corrected Dose descriptor | Most sensitive endpoint | Justification |
Acute - systemic effects | Dermal |
|
|
|
|
| Not relevant, negligible absorption |
| Inhalation | DNEL (Derived No Effect Level) | 8.8 mg Ni/m³b | 12.5c | HEC-NOAEC: 109.6 mg Ni/m3 d | acute toxicity (mortality) | See footnotes |
| Oral | DNEL (Derived No Effect Level) | 0.37 mg Ni/kg/day | 100e | NOAEL= 36.6 mg Ni/kg/day | acute toxicity (mortality) | See footnotes |
Acute - local effects | Dermal |
|
|
|
|
| Not relevant, negligible dermal exposure |
| Inhalation | DNEL (Derived No Effect Level) | 0.1 mg Ni/m³b | 7.1f | HEC-LOAEC: 0.8 mg Ni/m3 g | repeated dose toxicity (lung inflammation) | See footnotes |
Long-term - systemic effects | Dermal |
|
|
|
|
| Not relevant, negligible absorption |
| Inhalation | DNEL (Derived No Effect Level) | 0.00006mg Ni/m3h |
| Calculated NAEC 0.11 mg Ni/m3 | reproductive developmental toxicity | See footnotes |
| Oral |
| 0.013 mg Ni/kg/dayi | 100j | BMDL10: 1.3 mg Ni/kg/day | reproductive developmental toxicity | See footnotes |
Long-term - local effects | Dermal |
|
|
|
|
| Not relevant, negligible exposure |
| Inhalation | DNEL (Derived No Effect Level) | 0.00006mg Ni/m3h |
| Calculated NAEC 0.11 mg Ni/m3 | repeated dose toxicity (lung inflammation) carcinogenicity
| See footnotes |
a. The approaches used in the derivation of DNELs are described in a report prepared by VITO Consultancy (Belgium) (Appendix C1), and in AppendicesC2 (long-term DNELs),C3 (acute DNELs), andC4 (Summary DNEL table).
b. The derivation of the acute inhalation DNELs is described inAppendix C3. Dosimetric modeling was used to calculate human equivalent air concentrations (HECs) for the points of departures based on effects associated with pulmonary deposited (systemic effects) or retained (local effects) nickel doses in rats. This modeling accounts for differences in pulmonary deposition of different particle sizes between rats and humans. HECs were calculated using particle size of animal aerosol that reasonably correspond to the PM10aerosol fraction of ambient air.
c. Assessment Factor (AF) = 12.5. [AF interspecies differences in susceptibility (AS) = 1 for exposures expressed as concentrations mg/m3, and for lethal effects; AF interspecies remaining differences in susceptibility for respiratory tract = 2.5; AF intraspecies differences in susceptibility =5 for substances that do not undergo metabolism, seeAppendix C3section C3.6 for more detailed justification; Overall AF = 1 x 2.5 x 5 =12.5].
d. The HEC-NOAEC of 109.6 mg Ni/m3(ambient air) was derived from the NOAEC of 120 mg Ni/m3(MMAD=3µm) by applying a dosimetry adjustment as described inAppendix C3.
e. AF= 100 [AF interspecies difference other =2.5; AF interspecies AS =4 (rat-human); AF intraspecies differences in susceptibility=10 for the general population according to ECHA Guidance Table R. 8-6 Default assessment factor;s AF to account for differences in exposure duration=1; Overall AF = 2.5 x 4 x 10 = 100.
f. AF = 7.1 [AF interspecies difference (AS) = 1 local respiratory effects. AF interspecies difference in susceptibility = 1 (for respiratory toxicity effects after inhalation of particles of nickel or most metal-containing substances in the respirable range, rats seem to be more susceptible to toxicity effects than mice, primates or humans. AF intraspecies differences in susceptibility=5for substances that do not undergo metabolism. AF for conversion of LOAEC to NAEC=3, based on steep dose-response for nickel toxicity. An AF for exposure duration= 1/2.1 was applied to extrapolate from 16 day repeated exposures to a single exposure.SeeAppendix C3section C3.6.2 for more detailed justification of AF. Overall AF= 1 X 5 X 3 X 1/2.1 = 7.1].
g. The HEC-LOAEC of 0.8 mg Ni/m3(ambient air) was derived from the LOAEC of 0.7 mg Ni/m3(MMAD<4µm) by applying a dosimetry adjustment as described inAppendix C3.
h. An ambient air PM10 DNEL of 60 ng/m3was derived based on the dose descriptors reported by Oller et al., (2014) and the subsequent application of assessment factors described in Buekers et al. (2015) and described inAppendix C1andAppendix D5. The DNEL value is applied to ‘total nickel’ (including all chemical forms of nickel) because information on the speciation of emitted Ni substances is not always available. The value is applicable to typical mixtures of Ni prevailing in ambient air, at the regional and local scale. This DNEL protects from possible respiratory toxicity and reproductive effects, as well as carcinogenicity by considering nickel compounds to be indirect genotoxic carcinogens with a practical threshold similar to the approach taken by SCOEL (2011) when deriving OELs for nickel compounds (seeAppendix C1andAppendix D5).
i. The oral DNEL for long-term systemic effects (0.013 mg Ni/kg/day) is based the tolerable daily intake (TDI) for nickel derived by EFSA (2020). An increased incidence of post-implantation loss in rats in SLI (2000) was identified as the critical effect for the risk characterisation of chronic oral exposure and a BMDL10 of 1.3 mg Ni/kg body weight (bw) per day was selected as the reference point for the establishment of a TDI. The application of an uncertainty factor of 100 (10 to account for interspecies variation and 10 to account for intraspecies variation) gives a TDI of 13 µg/kg of body weight.
j. AF= 100 [AF interspecies difference other =2.5; AF interspecies AS =4 (rat-human); AF intraspecies differences in susceptibility=10 for the general population according to ECHA Guidance Table R. 8-6 Default assessment factor;s AF to account for differences in exposure duration=1; Overall AF = 2.5 x 4 x 10 = 100.; the inclusion of a factor of 2-3 for severity of effects is not justified since an exposure level corresponding to 2-fold the NOAEL in the second generation study with nickel sulphate was considered by some experts as the NOAEL for the observed effects.
Sensitive subpopulations. Sensitive subpopulations are not separately addressed as the oral DNEL values used for long term oral systemic exposure correspond to the TDI calculated by WHO for the general public. Although soluble nickel compounds carry a CLP classification as Resp. Sens. 1; H334, the occurrence of nickel-induced asthma among exposed workers is rare and there are only a few cases pointing to a workplace-related asthmatic disease. For this reason, deriving DNELs that protect workers or the general population from respiratory toxicity are considered to be protective of any possible sensitization effects as well.
Appendix C1= VITO report: Derivation of DNELs for 4 Ni substances
Appendix C2= Background Document in Support of Long-term Inhalable DNELs for Nickel Metal and Nickel
Compounds
Appendix C3= Background Document in Support of Acute DNELs and Guidance Values for Nickel Metal and
Nickel Compounds
Appendix C4= Excel table of DNEL derivations –nickel sulphate
Appendix D5= Man Via the Environment Risk Assessment
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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