Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
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
Endpoint summary
Administrative data
Description of key information
Value used for CSA:
NOAEL (oral, systemic, animal): >11,000 mg Ni3S2/kg bw/day (or >8,000 mg Ni/kg bw/day) (EPSL, 2008)
NOAEC (inhalation, systemic, animal): 0.206 mg Ni3S2/L air (or ~126 mg Ni/m³ air) (EPSL, 2010)
Key value for chemical safety assessment
Acute toxicity: via oral route
Endpoint conclusion
- Dose descriptor:
- LD50
Acute toxicity: via inhalation route
Endpoint conclusion
- Dose descriptor:
- LC50
- Value:
- 1 140 mg/m³ air
Additional information
Two background documents describing the use of Ni subsulphide as a source substance for read-across of oral and inhalation toxicity to other nickel compounds has been attached to Sections 7.2.1 and 7.2.2 of IUCLID and included in the CSR as Appendices B1and B2.
Many studies were identified characterizing the acute toxicity of Ni3S2 in rodents following oral or intratracheal instillation. In addition, one acute inhalation toxicity study was recently completed, and no studies characterizing acute toxicity following dermal contact were identified. The most well-characterized endpoint associated with rodent exposures to Ni3S2 was mortality; GLP guideline-based studies were available for both oral and inhalation exposures.
A robust GLP, guideline-based study was conducted by Eurofins Product Safety Laboratory (EPSL, 2008) and reported the findings of the acute oral toxicity of Ni3S2 as determined by the acute toxicity up and down procedure in female rats. Following a single oral exposure to 11,000 mg/kg Ni3S2, all animals survived, gained body weight, and appeared healthy and active during the study. No signs of gross toxicity, adverse pharmacologic effects, abnormal behavior, or gross abnormalities were observed. Based on these findings, the acute oral LD50 of Ni3S2 was estimated to be greater than 11,000 mg/kg b. w. in female rats.
Eurofins Product Safety Lab (EPSL, 2010) characterized lethality associated with acute inhalation. This GLP, guideline-based study exposed rats (nose-only) for four hours to nickel subsulphide (3 dose groups) and monitored survivial, body weight, and a number of clinical endpoints. Under the conditions of this study, the acute inhalation defined LC50 of nickel subsulphide was 1.352 mg/L (95% CI of 0.3371 to 5.422 mg/L) in male rats and 0.9237 mg/L (95% CI of 0.5215 to 1.6359 mg/L) in female rats. The average inhalation LC50 is calculated to be 1.14 mg/L (MMAD =3 µm).
Lower LD50 estimates were reported in an intratracheal instillation study conducted by Fisher et al. (1984).The findings demonstrated the importance of physical form in the evaluation of pulmonary toxicity and lethality ofNi3S2 particles of different size. Fine particles (1.8 μm) were clearly more toxic and lethal than the coarse particles (13.3 μm), with reported LD50 values of 4 and 50 mg/kg, respectively; lethality was associated with pulmonary hemorrhage and possible congestion and edema.
Several studies also evaluated cellular, biochemical, and histological endpoints following intratracheal exposures. Benson et al. (1984) exposed F344 rats to 0.01 to 1.0 μmol Ni3S2 and reported moderate multifocal alveolotis and dose-dependent increases in a number of biochemical parameters. In a 1986 study, this group of authors evaluated similar endpoints and correlated findings with the concentration of nickel in lung tissues following a similar exposure paradigm (0.01 to 1.0 μmol). Levels of Ni in the lung were virtually identical after 1 and 7 days of exposure to Ni3S2 (1 μmol Ni), but elevated relative to untreated animals. No significant biochemical, cytological, or histopathological changes were detected in nickel-exposed animals 1 day following administration. However, dose-related responses were observed following 7 days of exposure, indicating acute toxicity associated with exposure to Ni3S2. Acute toxicity following intratracheal exposure in mice (0.5 mg/kg Ni3S2 in 20 μL PBS) was also reported by Finch et al. (1987). Observations of lethargy, pulmonary hemmorraging, increased bodyweights and lung weight, and increased cell yields and polymorphonuclear (PMN) cells in lung lavage fluid led the authors to conclude that Ni3S2 was acutely toxic in mice. Collectively, these data are indicative of acute toxicity following intratracheal exposure to Ni3S2 in rodents.
Though not studied using a relevant route of exposure, strain susceptibilities associated with Ni3S2 were also reported by Rodriguez et al. (1996). Male mice injected with single doses (0.5 to 10 mg/site) resulted in strain-dependent susceptibility in mortality, necrotic/inflammatory kidney damage, and changes in bodyweight, indicating Ni3S2 induced both local and distal tissue pathologies.
Taken together, the available data indicate that Ni3S2 can be acutely toxic in rodents following inhalation and intratracheal instillation under laboratory conditions (inhalation LC50= 0.9237mg/L for most sensitive gender). However, following oral exposure, Ni3S2 was not acutely toxic at doses up to 11,000 mg/kg in rats (8,000 mg Ni/kg). Thus, the data clearly indicate the importance of accounting for strain susceptibilities, exposure route, dose, and particle size when evaluating acute toxicity.
As oral and inhalation routes of exposure are more relevant and data for these have been provided, testing for acute dermal toxicity is therefore waived based on this information.
The following information is taken into account for any hazard / risk assessment:
ORAL: Ni subsulphide was not acutely toxic at doses up to 11,000 mg Ni3S2/kg in rats (8,000 mg Ni/kg/day).
INHALATION: Ni3S2 can be acutely toxic in rodents following inhalation and intratracheal instillation under laboratory conditions (inhalation LC50= 0.9237 mg Ni3S2/L for most sensitive gender; NOAEC=126 mg Ni/m3, MMAD=3.0 µm).
DERMAL: No risk characterisation will be conducted for acute dermal toxicity. Acute systemic effects are not relevant due to the very low dermal absorption of nickel. Acute local effects are covered by the long term DNEL based on prevention of dermal sensitization.
Justification for classification or non-classification
Ni subsulphide does not have a harmonized classification for oral or dermal acute toxicity, according to the CLP regulation. However in 2021, a new harmonized inhalation classification of Acute Tox. 3: H331 was published in the 17th ATP to the CLP Regulation. Therefore, this REACH submission reflects a harmonized classification for acute toxicity via inhalation as Acute Tox. 3: H331. Acute toxicity via the oral and dermal routes of exposure will remain unclassified. Supporting information can be found in the discussion section for this endpoint.
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.