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EC number: 234-829-6 | CAS number: 12035-72-2
- 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
Acute Toxicity: other routes
Administrative data
- Endpoint:
- acute toxicity: other routes
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Meets generally accepted scientific standards, well documented and acceptable for publication.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- Relative susceptibilities of C57BL/6, (C57BL/6 x C3H/He)F1, and C3H/He mice to acute toxicity and carcinogenicity of nickel subsulfide
- Author:
- Rodriguez RE, Misra M, Diwan BA, Riggs CW, and Kasprzak KS
- Year:
- 1 996
- Bibliographic source:
- Toxicology. 107: 131-140
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Intramuscular injection of 0.5, 1.0, 2.5, 5.0, and 10 mg of Ni3S2/site into the thigh musculature of each of the two hind legs of 3 mouse strains, and observed for up to 78 weeks. The susceptibility of three strains of mice [C57BL/6 (C57BL), (C57BL/6 X C3H/He)F1 (B6C3Fl), and C3H/He (C3H)] to the toxicity and carcinogenicity of nickel subsulfide (Ni3S2) was assessed.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Trinickel disulphide
- EC Number:
- 234-829-6
- EC Name:
- Trinickel disulphide
- Cas Number:
- 12035-72-2
- Molecular formula:
- Ni3S2
- IUPAC Name:
- (trinickel-1-ylidene)-1λ⁴-disulfene
- Details on test material:
- - Name of test material (as cited in study report): nickel subsulfide (Ni3S2)
- Physical state: particulate
- Other: <= 30 um; originated from INCO, Ltd. (Toronto, Canada)
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: C57BL/6, (C57BL/6 x C3H/He)F1, and C3H/He
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: NCE-FCRDC, Animal Production Area (Frederick, MD)
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 23-29 g
- Housing: polycarbonate cages on a hardwood chip bedding
- Diet (e.g. ad libitum): ad libitum NIH-31 open formula 6% Modified (Zeigler Brothers, Gardners, PA)
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- intramuscular
- Vehicle:
- other: 50% glycerol/water
- Details on exposure:
- Animals received injections of single doses of Ni3S2 suspension in 0.05 ml of 50% glycerol/water into the thigh musculature of both hind legs.
- Doses:
- 0, 0,5, 1.0, 2.5, 5.0, and 10.0 mg Ni3S2/ injection site.
- No. of animals per sex per dose:
- 30 mice per group per strain
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: up to 78 months
- Frequency of observations and weighing: every 2 weeks
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, histopathology - Statistics:
- The different effects of Ni3S2 doses on body weight gains among the three mouse strains were analyzed using a one-way analysis of variance, ANOVA. When statistically significant differences were indicated, Duncan's multiple range test was used to determine how the treatments differed from each other.
Results and discussion
Effect levelsopen allclose all
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 5 other: mg/injection in C57BL mice
- Remarks on result:
- other: after 1 week
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- > 5 - < 10 other: mg/injection site in C3H mice
- Remarks on result:
- other: after 1 week
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- > 5 - < 10 other: mg/injection site in B6C3F1 mice
- Remarks on result:
- other: after 1 week
- Mortality:
- 10 mg Ni3S2 dose: C3H mice > 50%, B6C3F1 > 80%, and C57BL > 90% lethality 1 week after exposure.
5 mg Ni3S2 dose: C3H mice < 5%, B6C3F1 > 30%, and C57BL > 50% lethality 1 week after exposure.
2.5 mg Ni3S2 dose: C3H mice 0%, B6C3F1 0%, and C57BL > 25% lethality 1 week after exposure.
1 mg Ni3S2 dose: C3H mice 0%, B6C3F1 0%, and C57BL < 5% lethality 1 week after exposure.
0.5 mg Ni3S2 dose: C3H mice 0%, B6C3F1 0%, and C57BL < 5% lethality 1 week after exposure. - Clinical signs:
- Not applicable
- Body weight:
- The C3H and B6C3Fl mice given 5- and 10-mg Ni3S2 doses tended to gain less weight (P < 0.05 by Duncan's test) than mice given lower doses, or the control mice. This trend apparently reflected the chronic systemic toxicity of Ni3S2 and the morbidity due to tumors after 25 weeks of experiment. No such trend could be confirmed for C57BL mice, for whom statistical analysis was hampered by high mortality.
- Gross pathology:
- Examination of mice dying 1 to 7 days after i.m. Ni3S2 injection revealed morphologic changes only in the kidney and the injected muscles. In kidney, the microscopic lesions included necrosis and inflammation that were particularly severe in the C57BL strain. Nephritis and renal cortex regenerative hyperplasia were found frequently in mice of all three strains which received higher Ni3S2 doses (~2.5 mg) and died 6 and 7 days after the injection, with no apparent difference among the strains.
- Other findings:
- - Histopathology: Histological examination of the injected muscles of the control mice of all three strains from 1 to 14 days post-injection revealed inflammation with moderate hyperplasia, subsiding gradually with time. In the Ni3S2-treated mice, moderate necrotic, inflammatory, and moderate to severe hyperplastic changes were observed over the 14 day period around the injected Ni3S2 particles without any apparent strain-dependent difference in the severity or persistence of those changes.
Any other information on results incl. tables
The present study demonstrates strain-dependent susceptibility of mice to the acute Ni3S2 toxicity: C57BL > B6C3FI > C3H.
Applicant's summary and conclusion
- Conclusions:
- Strain-dependent susceptibility was observed in mice intramuscularly injected with high doses of Ni3S2, where the rank order of susceptibilty was C57BL > B6C3FI > C3H, for mortality 1 week after exposure. The C3H and B6C3F1 mice administered 5 and 10 mg Ni3S2 gained less weight than the lower dose or control groups. High dose exposure also induced renal necrosis and inflammation in C57BL mice, and nephritis and renal cortex hyperplasia in all mice that died 6 and 7 days after exposure. The authors suggest that the acute toxicity of nickel in mice is partly associated with higher antioxidant capacity of target organs (based on the results of a side study in which the muscular GSH levels and LPO levels were studied in mice exposed to Ni(II) acetate). However, the GSH and LPO levels in the most susceptible mouse strains (C57BL and B6C3F1) were not affected by Ni(II) acetate exposure, and the strain least susceptible to acute toxicity (C3H) showed only a transient and modest elevation in antioxidant response after exposure. This hypothesis, therefore, seems at odds with the data presented.
- Executive summary:
Rodriguez et al. (1996) studied the susceptibility of three strains of mice [C57BL/6 (C57BL), (C57BL/6 X C3H/He)F1 (B6C3Fl), and C3H/He (C3H)] to the toxicity and carcinogenicity of nickel subsulfide (Ni3S2). Groups of 30 male mice of each strain were injected with single doses of 0.5, 1.0, 2.5, 5.0, and 10 mg of Ni3S2 /site into the thigh musculature of each of the two hind legs and observed for up to 78 weeks. Strain-dependent susceptibility was observed in mice intramuscularly injected with high doses of Ni3S2 , where the rank order of susceptibility based on mortality 1 week after exposure was C57BL > B6C3FI > C3H. The highest Ni3S2 dose was lethal within 1 week, with mortality rates of C57BL (93%), B6C3Fl (80%), and C3H (53%). The C57BL and B6C3F1 mouse strains also showed significant mortality 1 week after exposure to the next highest Ni3S2 dose (>50% and >30%, respectively). Even at 2.5 mg Ni3S2 , C57BL mice still demonstrated considerable morality (>25%).
The most susceptible C57BL mice also had the most severe necrotic/inflammatory kidney damage, compared with that in the other mice, while all the mice that died 6 and 7 days after exposure demonstrated nephritis and renal cortex hyperplasia regardless of strain. Ni3S2 deposited in the muscle appears to be a source of soluble nickel that can reach and damage the kidneys, although it is unclear why other organs failed to demonstrate similar damage. The C3H and B6C3F1 mice administered 5 and 10 mg Ni3S2 gained less weight than the lower dose or control groups, while the high mortality rates among C57BL mice prevented the authors from drawing any conclusions about high dose Ni3S2 exposure affecting the weight of these mice. The authors suggested that the acute toxicity of nickel in mice was partly associated with higher antioxidant capacity of target organs. This assertion was based on data collected in the current investigation, which indicated that the muscular GSH levels and lipid peroxidation (LPO) levels were studied in mice exposed to Ni(II) acetate). However, the GSH and LPO levels in the most susceptible mouse strains (C57BL and B6C3F1) were not affected by Ni(II) acetate exposure, and the strain least susceptible to acute toxicity (C3H) showed only a transient and modest elevation in antioxidant response (GSH levels) after exposure. The authors suggested that organs with greater antioxidant capacity are more prone to nickel toxicity; however, this seems at odds with the data presented. Collectively, these data indicated that intramuscular injection of Ni3S2 induced both local and distal tissue pathologies, including tumorigenesis, depending on the mouse strain under observation. It was not clear if such strain susceptibilities were associated with each of the strain’s muscle antioxidant capacity. STUDY RATED BY AN INDEPENDENT REVIEWER
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