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EC number: 263-000-1 | CAS number: 61788-71-4
- 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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- chronic toxicity: inhalation
- Remarks:
- combined repeated dose and carcinogenicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study (OECD 453)
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Comparative Carcinogenic Effects of Nickel Subsulfide, Nickel Oxide, or Nickel Sulfate Hexahydrate Chronic Exposures in the Lung
- Author:
- Dunnick JK, Elwell MR, Radovsky AE, Benson JM, Hahn FF, Nikula KJ, Barr EB, Hobbs CH
- Year:
- 1 995
- Bibliographic source:
- CANCER RESEARCH. 55: 5251-5256
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Deviations:
- not specified
- Principles of method if other than guideline:
- not applicable
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Nickel sulphate
- EC Number:
- 232-104-9
- EC Name:
- Nickel sulphate
- Cas Number:
- 7786-81-4
- Molecular formula:
- NiSO4
- IUPAC Name:
- nickel(2+) sulfate
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Simonsen Laboratories, Gilroy, CA
- Housing: Hazleton 1000 whole-body chambers
- Diet (e.g. ad libitum): ad libitum during non-exposure periods
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 hr dark, 12 hr light
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: no data
- Remarks on MMAD:
- MMAD / GSD: MMAD = 2.02-2.53 um
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel multitiered whole exposure chambers (Hazleton, Aberdeen, MD, USA)
- Method of holding animals in test chamber: not reported
- Source and rate of air: High-efficiency particulate air filter (Flanders, Washington, DC)
- Method of conditioning air: not reported
- System of generating particulates/aerosols: The test compound was generated from aqueous solutions (62.1 g/L in distilled and deionized water) and atomized.
- Temperature, humidity, pressure in air chamber: Temp. 17.2-29.6 deg. C; humidity 8-99%
- Air flow rate: The aerosol was mixed with additional dilution air to achieve the proper concentration and flow rate.
- Air change rate: not reported
- Method of particle size determination: cascade impactor, the mass median aerodynamic diameter (MMAD) ranged from 1.8-3.1 um for all exposure concentrations.
- Treatment of exhaust air: not reported
TEST ATMOSPHERE
- Brief description of analytical method used: aerosol concentrations determined gravimetrically
- Samples taken from breathing zone: yes
VEHICLE: water
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Aerosol concentration was determined by taking three 2-h filter samples throughout the exposure day.
Real-time determination of aerosol concentration was made using real time aerosol monitor-model S units. - Duration of treatment / exposure:
- 6 hr/day
- Frequency of treatment:
- 5 d/wk, 2 yr
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 0.25, 0.5, 1 mg/m3 (equivalent to 0, 0.056, 0.11, 0.22 mg Ni/m3)
Basis:
nominal conc.
- No. of animals per sex per dose:
- 80 males, 80 females
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: based on previous 13-week study
- Positive control:
- Not applicable
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: every 4 weeks
BODY WEIGHT: Yes
- Time schedule for examinations: every 4 weeks
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: No data
CLINICAL CHEMISTRY: No data
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data
OTHER: Lung Ni burden - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, organ weights
HISTOPATHOLOGY: Yes. Complete histopathology was performed on high-exposure and control groups and to a no-effect level in target tissues. - Other examinations:
- lung Ni concentration
- Statistics:
- Tests of significance included pairwise comparisons of each exposed group with controls and a test for overall exposure-related trends. Organ and body weight data were analyzed using parametric multiple comparison procedures, and lung burden data were analyzed using nonparametric multiple comparison methods. The reported values were considered significant at the P < 0.05 level.
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 specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- 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 specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY:
Survival rates of exposed mice were similar to controls.
BODY WEIGHT AND WEIGHT GAIN:
Mean body weights of 1 mg/m3 males and of all Ni-exposed females were lower than control animals during year 2 of the study.
ORGAN WEIGHTS
Significant organ weight changes reported: -increased absolute lung weights of 1 mg/m3 males and females at 15-month evaluation.
-increased relative lung weight of 1 mg/m3 females at 15-month evaluation.
HAEMATOLOGY:
There were no substance-related hematology differences or clinical findings reported.
Tissue Ni burden levels were below the level of detection at the 7- and 15-month evaluation periods.
HISTOPATHOLOGY: NON-NEOPLASTIC
Significantly increased incidences of non-neoplastic lung lesions reported for 2-year study:
-chronic active lung inflammation of 0.5 and 1 mg/m3 male mice, and 0.25, 0.5, and 1 mg/m3 female mice.
-macrophage hyperplasia of 0.5 and 1 mg/m3 male mice, and 0.25, 0.5, and 1 mg/m3 female mice.
-bronchialization of 0.5 and 1 mg/mg3 male mice, and 0.25, 0.5, and 1 mg/m3 female mice.
-interstitial infiltration of 1 mg/m3 male mice, and 0.5 and 1 mg/m3 female mice.
-alveolar proteinosis of 1 mg/m3 male mice, and 0.5 and 1 mg/m3 female mice.
-bronchial lymphoid hyperplasia of 1 mg/m3 male and female mice.
-bronchial macrophage hyperplasia of 0.5 and 1 mg/m3 male and female mice.
The incidence of atrophy of the olfactory epithelium at the end of the 2-year study was significantly increased in 0.5 and 1 mg/m3 male mice,
and in 1 mg/m3 female mice.
HISTOPATHOLOGY: NEOPLASTIC
No nickel sulfate hexahydrate-related neoplasms (alveolar/bronchiolar adenoma or carcinoma) were found in male or female mice exposed to the
test substance via whole body inhalation for 2 years.
Effect levels
- Dose descriptor:
- LOAEC
- Effect level:
- 0.056 other: mg Ni/m3 (as Ni sulfate hexahydrate)
- Sex:
- male/female
- Basis for effect level:
- other: chronic active lung inflammation
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
On the basis of chronic active lung inflammation, the LOAEL was determined to be 0.056 mg Ni/m3 (0.25 mg nickel sulfate hexahydate/m3).
No NOAEL could be determined. The authors reported "no evidence of carcinogenic activity of nickel sulfate hexahydrate in male or
female B6C3F1 mice exposed to 0, 0.25, 0.5, or 1 mg/m3" under the conditions of the 2-year inhalation study.
Applicant's summary and conclusion
- Conclusions:
- Noncarcinogenic effects included alveolar/bronchiolar (A/B) hyperplasia, inflammation, fibrosis, and lymphoid hyperplasia of the lung-associated lymph nodes.Qualitatively, the effects were similar across the three nickel compounds, but were generally considered by the authors as more severe for NiO and Ni3S2; however, effects in mice were considered less sensitive than rats.
- Executive summary:
As part of a study on the toxicity and carcinogenicity of NiSO4, Ni3S2 and NiO, Dunnick et al. (1995) described the toxicity of inhaled Ni3S2 in B6C3F1 mice exposed for 6 hr/d, 5 d/wk, for 2 years (0.15, and 1 mg Ni3S2 /m3; 0.11 and 0.73 mg Ni/m3). Chamber concentrations and aerosol size were determined analytically (MMAD: 2.1 μm; GSD 2.0). Noncarcinogenic effects examined included clinical signs, body and organ weights, tissue histopathology, and lung burden (note: carcinogenic effects and lung burden are described in the Carcinogenicity and Basic Toxicokinetics sections, respectively). No significant differences in mortality were observed between control and treated animals. Bodyweights of exposed animals were said to be within 5-10% of control animals and were not considered characterized as adverse effects. Lung weights in exposed animals were greater than controls and were considered to be due to inflammatory responses. By 7 months, lung weight was significantly increased in males at 1.2 mg/m3 and in females at 0.6 mg/m3. At 15 months, the lung weight was about 0.4 g in male mice treated at either dose versus 0.23 g in control males. In female mice, the lung weights were 0.26, 0.39, and 0.5 g in control mice and the mice treated at low and high doses of Ni3S2 . Noncarcinogenic effects included alveolar/bronchiolar (A/B) hyperplasia, inflammation, fibrosis, and lymphoid hyperplasia of the lung-associated lymph nodes. Qualitatively, the effects were similar across the three nickel compounds, but were generally considered by the authors as more severe for NiO and Ni3S2; however, mice were considered less sensitive than rats. This investigation was part of a comprehensive bioassay conducted by the National Toxicology Program (1996). STUDY RATED BY AN INDEPENDENT REVIEWER
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