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EC number: 242-533-3 | CAS number: 18721-51-2
- 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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: comparable to guideline study with acceptable restrictions (limited documentation)
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Lung toxicity after 13-week inhalation exposure to nickel oxide, nickel subsulfide, or nickel sulfate hexahydrate in F344/N rats and B6C3F1 mice.
- Author:
- Dunnik, J. K. et al.
- Year:
- 1 989
- Bibliographic source:
- Fundamental and Applied Toxicology 12, 584-594
- Reference Type:
- secondary source
- Title:
- Nickel Sulphate, CAS-No.: 7786-81-4, EINECS-No.: 232-104-9, RISK ASSESSMENT Final version March 2008, Chapters 0, 1, 2, 4, 5, 6 & 7 – human health only
- Author:
- Danish Environmental Protection Agency
- Year:
- 2 008
- Bibliographic source:
- European Union Risk Assessment Report
Materials and methods
- Principles of method if other than guideline:
- Test animals were exposed for 13 weeks to various concentrations of nickel sulfate hexahydrate. Examinations were performed on various organs and tissues but mainly focused on the respiratory tract.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 10101-97-0
- EC Number:
- 600-152-3
- Cas Number:
- 10101-97-0
- IUPAC Name:
- 10101-97-0
- Reference substance name:
- nickel sulfate hexahydrate
- IUPAC Name:
- nickel sulfate hexahydrate
- Details on test material:
- - Name of test material (as cited in study report): nickel sulfate hexahydrate from Aldrich Chemical Company, Milwaukee
- Molecular formula (if other than submission substance): NiSO4x6H2O
- Molecular weight (if other than submission substance): 262.86
- Analytical purity: > 99%
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: NTP breeding colonies at Frederick Cancer Research Facility, Frederick, Maryland and Simonsen Laboratories, Gilroy, California, USA
- Age at study initiation: 7-8 weeks
- Housing: individually in multitiered inhalation chambers
- Diet (e.g. ad libitum): NIH-07 diet (Zeigler Brothers, Inc., Gardeners, PA); only available druring nonexposure hours
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Humidity (%): 17 - 45
- Air changes (per hr): 12 ± 2
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- not specified
- Vehicle:
- other: air
- Remarks on MMAD:
- MMAD / GSD: MMAD = 2.3 µm / GSD = 2.4 µm
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Multitiered inhalation chambers: H-1000 (1.0 m3) and H-2000 (1.7 m3) (Hazleton Systems, Aberdeen, MD)
- System of generating particulates/aerosols: Nebuliser. The resulting aerosol was passed through a K-85 discharger to neutralise electrical charge and mixed with diluting air to achieve the desired concentrations in the chambers.
- Air change rate: 12 ± 2 h
- Method of particle size determination: cascade impactors
TEST ATMOSPHERE
- Brief description of analytical method used: The concentration in the exposure chambers was monitored by taking three 2 h filter samples during the 6 h exposure day. The mean daily concentration was calculated from the filter samples.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 6 h/day
- Frequency of treatment:
- 5 days/week for 13 weeks
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0.11, 0.24, 0.49, 0.95 and 1.90 mg nickel citrate/m3
Basis:
other: nickel citrate concentration calculated from the concentration of nickel sulfate hexahydrate
- Remarks:
- Doses / Concentrations:
0.12, 0.25, 0.52, 1.0 and 2.01 mg nickel sulfate hexahydrate/m3
Basis:
analytical conc.
- No. of animals per sex per dose:
- 10 + 5 (additional animals)
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: The exposure levels were selected based on a 12-day study. The top exposure level was set 2.0 mg/m3 because of body weight effects and lung lesions that developed in the 12-day exposures at levels of 3.5 mg/m3.
In addition, 5 male rats for each exposure level were sacrificed after 4, 9 and 13 weeks of exposure as well as 5 female rats for each exposure level were sacrificed after 13 weeks for the quantification of Ni in the lung.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: no data
BODY WEIGHT: Yes
- Time schedule for examinations: no data
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Organ weights taken at necropsy were lung, liver, kidneys, testes, brain and thymus. In addition, sperm morphology, sperm number, sperm motility and vaginal cytology were evaluated on selected subgroups of male animals sacrificed at the end of the 13-week exposure period and for females during the last week of exposure.
HISTOPATHOLOGY: Yes
Complete histopathology was performed on high-exposure and control groups and to a no-effect level in target tissues (Lungs were fixed by intratracheal instillation of fixative.). - Other examinations:
- Ni content in the lungs of exposed animals.
- Statistics:
- Multiple comparison procedures with two-tailed tests (Dunn, Shirley and Williams).
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No exposure-related mortality was seen.
BODY WEIGHT AND WEIGHT GAIN
Body weight gain was not affected by exposure.
ORGAN WEIGHTS
There was a significant dose-dependent increase in lung weight in animals of both sexes. There were no exposure-related changes in the weights of the other organs examined.
HISTOPATHOLOGY: NON-NEOPLASTIC
Inflammatory changes were seen in the lung, nasal cavity and bronchial lymph node.
Lung lesions included alveolar macrophage hyperplasia, inflammation and fibrosis. These lesions were present in animals at each dose level. The incidence and severity of chronic, active inflammation in the lung increased with dose. The lesions consisted of a mild thickening of the alveolar septae by a mononucleas inflammatory cell infiltrate. Animals exposed to higher substance levels had atrophy of the olfactory epithelium. This minimal change was characterised by a decreased number of sensory cell nuclei, particularly in the olfactory epithelium of the dorsal meatus. There was no evidence of an inflammatory or regenerative response in the olfactory mucosa.
The change in the bronchial lymph nodes consisted of minimal to mild lymphoid hyperplasia in both sexes at higher exposure levels.
OTHER FINDINGS
No exposure-related effects were seen in sperm number, sperm motility or sperm morphology or in length of the estrous cycle.
Concentrations of Ni in the lungs of rats increased with exposure concentration and were significantly different from controls in animals exposed to 0.1 mg Ni/m3 or more. However, equilibrium levels of nickel were reached by 13 weeks in the lung after exposure.
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Remarks:
- local
- Effect level:
- 0.24 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: alveolar macrophage hyperplasia (not considered adverse) value for nickel citrate was calculated from nickel sulfate hexahydrate
- Dose descriptor:
- NOAEC
- Remarks:
- local
- Effect level:
- 0.25 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: alveolar macrophage hyperplasia (not considered adverse) nickel sulfate hexahydrate
- Dose descriptor:
- LOAEC
- Remarks:
- local
- Effect level:
- 0.49 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: inflammatory effects in the lung value for nickel citrate was calculated from nickel sulfate hexahydrate
- Dose descriptor:
- LOAEC
- Remarks:
- local
- Effect level:
- 0.52 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: inflammatory effects in the lung nickel sulfate hexahydrate
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Based on the outcome of a simultanously performed stady in mice, the autors stated that rats appeared to be more sensitive than the mouse ((B6C3F1) to the development of chronic active inflammation, with inflammation occuring at lower exposure concentrations for rats than for mice.
Applicant's summary and conclusion
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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