Nickel sulphide

Endpoint summary

Description of key information

Value used for CSA:

• NOAEL (oral, systemic, animal): >5,000 mg NiS/kg bw (or >3,650 mg Ni/kg/day) (FDRL, 1983)
• NOAEC (inhalation, systemic, animal, read across from Ni subsulphide): 0.206 mg Ni₃S₂/L air (or ~126 mg Ni/m³ air) (EPSL, 2010)

Additional information

In the only acute oral toxicity study identified with Ni sulphide, Food & Drug Research Laboratories, Inc. (FDRL, 1983) evaluated the acute oral toxicity of Ni sulphide in Sprague-Dawley rats according to GLP and OECD Guidelines for Testing of Chemicals (note: the authors did not state the specific guideline, though the study design appears to be similar to Test # 401 – Acute Oral Toxicity). A range test was conducted prior to the main study in which rats were administered a single oral dose of 100 to 5000 mg NiS/kg (4 rats per dose group). After 8 days , no mortality was observed and no other adverse effects were noted. Based on these findings, ten rats (5 males, 5 females) were exposed to 5000 mg NiS/kg orally. At the conclusion of the 15-day observation period, results indicated the absence of mortality and normal increases in body weight. The authors concluded that based on the data obtained from this study, the acute oral LD₅₀of NiS was considered to be greater than 5000 mg/kg bodyweight.  

A comprehensive read-across assessment for inhalation toxicity was recently completed based on bioaccessibility data in synthetic lung fluids of various nickel compounds combined within vivoverification data for three source nickel substances. The read-across paradigm presented in a summary document in Section 7.2.2 and inAppendix B2to the CSR enables grouping of target Ni substances for classification purposes according to bioaccessibility in interstitial fluid.  The outcome of this assessment indicates that the acute inhalation toxicity of Ni sulphide should be read-across from Ni subsulphide.  Although Ni subsulphide is not currently classified for acute inhalation toxicity, a recently completed OECD-guideline compliant study reported an LC₅₀=1.14 mg/L Ni subsulphide after 4 hours of exposure (EPSL, 2010). This newly generated data demonstrate that Ni subsulphide should be classified as Acute Tox. 4: H332. Therefore, this REACH submission for Ni sulphide reflects self classification as Acute Tox. 4: H332.

An acute intramuscular (i.m.) toxicity study with nickel sulphide in rats was conducted by Novelliet al. (1995). In the Novelliet al. (1995) study, male Wistar rats were administered a single i. m. injection of 7 mg Ni (as Ni sulphide)/kg. After 72 hours, treated rats exhibited significant increases in serum lipoperoxide, amylase, aspartate transaminase, and alkaline phosphatase, as well as a significant decrease in superoxide dismutase (SOD). The authors concluded that the toxicity of nickel compounds involves oxidative reactions such as nickel-induced lipid peroxidation, and that the superoxide radical is an important toxic intermediate in the development of insoluble nickel compound-induced damage.

There are no available data on which to evaluate acute dermal toxicity. However, acute toxicity is expected to be low in view of the poor absorption by this route. 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 sulphide was not acutely toxic at doses up to 5,000 mg NiS/kg in rats (or 3,650 mg Ni/kg bw/day).

INHALATION: Data are read-across from Ni subsulphide. Ni₃S₂can be acutely toxic in rodents following inhalation and intratracheal instillation under laboratory conditions (inhalation LC₅₀= 1.14 mg Ni₃S₂/L; NOAEC=0.206 mg Ni₃S₂/L air (or ~126 mg Ni/m³ air; 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 sulphide is not classified for acute oral toxicity (oral, inhalation, or dermal) according to the 1st ATP to the CLP Regulation. However, a comprehensive read-across assessment was recently completed based on bioaccessibility data in synthetic lung fluids of various nickel compounds combined in vivo verification data for three source nickel substances. The read-across paradigm presented in a summary document in Section 7.2.2 and inAppendix B2to the CSR enables grouping of target Ni substances for classification purposes according to bioaccessibility in interstitial fluid as demonstrated. The outcome of this assessment indicates that Ni sulphide should be read-across from Ni subsulphide. Although Ni subsulphide is not currently classified for acute inhalation toxicity, a recently completed OECD-guideline compliant study reported an LC₅₀=1.14 mg Ni₃S₂/L after 4 hours of exposure. This newly generated data demonstrate that Ni subsulphide should be classified as Acute Tox. 4: H332 (via inhalation). Therefore, this REACH submission for Ni sulphide reflects self-classification for acute toxicity via inhalation as Acute Tox. 4: H332. 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.