Nickel sulphide

Carcinogenicity

Description of key information

ORAL: Data are read-across from Ni sulfate.  A well-conducted OECD 451 study in rats did not show any carcinogenic potential of nickel sulphate following oral administration. A summary document on this topic can be found in the attached document entitled, "Background-Oral Carcinogenicity for all Nickel Compounds" (Section 7.7 of IUCLID) and in Appendix B6 of the CSR.
INHALATION: Data are read-across from Ni subsulfide.  The most robust and environmentally relevant carcinogenicity study for Ni3S2 was conducted as part of a National Toxicology Program study on the toxicity and carcinogenicity of NiSO4, Ni3S2 and NiO (Dunnick et al. 1995). Following inhalation of Ni3S2 for up to two years (6 hr/d, 5 d/wk, two exposure levels), a dose-dependent incidence of lung tumors (combined adenomas and carcinomas) was observed in F344/N rats. 
DERMAL: Read-across from Ni sulfate.  As oral exposure to nickel sulphate does not show any carcinogenic potential, there are good reasons to assume that cancer is not a relevant end-point with respect to dermal exposure either.

Justification for classification or non-classification

Ni sulphide is classified as Carc. 1A; H350i via inhalation route of exposure according to the 1st ATP to the CLP Regulation. Background information can be found in the discussion section.

In addition, a background document that includes a summary of the potential of Ni compounds to cause cancer via the oral route of exposure can be found in Appendix B1 of the CSR. In summary, absence of oral carcinogenicity of the nickel (II) ion demonstrates that the possible carcinogenic effects of nickel-containing substances in humans are limited to the inhalation route of exposure and the associated organ of entry (i. e., the respiratory tract). After inhalation, respiratory toxicity limits the systemic absorption of Ni (II) ion to levels below those that can be achieved via oral exposure. 

Additional information

Data on the oral carcinogenicity of Ni sulphide are read-across from Ni sulphate as Ni sulphate represents a worst-case scenario for oral absorption of nickel. Nickel sulphate hexahydrate represents a worst-case scenario for systemic absorption of nickel since nickel sulphate hexahydrate is significantly more readily solubilized in gastrointestinal fluid than Ni subsulphide and results in the highest systemic absorption of Ni (II) ions (Ishimatsu et al., 1995). A 2-year carcinogenicity study with rats performed according to OECD 451 did not show any carcinogenic potential of exposure to nickel sulphate following oral (gavage) administration. There is sufficient oral carcinogenicity data to show that nickel sulphate does not show any carcinogenic potential in experimental animals following oral administration. Likewise, less bioavailable Ni compounds (like Ni subsulphide) are also not expected to have any oral carcinogenic potential.A document containing a summary on this topic is provided as a background document in section 7.5.1 of IUCLID and inAppendix B1of the CSR.

Inhalation carcinogenicity information can be derived from epidemiological data (e.g. ICNCM, 1990). These studies demonstrated that exposures to for sulphidic nickel compounds, such as nickel sulphide, are associated with carcinogenicity of the respiratory tract. Available carcinogenicity animal data from Ni sulphate (oral) and human data from epidemiological studies (inhalation) indicate that nickel sulphide does not cause carcinogenicity afteroral exposure but does have the potential to cause respiratory tract carcinogenicity after inhalation exposure.

Data on the dermal carcinogenicity of Ni sulphide are read-across from Ni sulphate. As oral exposure to nickel sulphate does not show any carcinogenic potential, there are good reasons to assume that cancer is not a relevant end-point with respect to dermal exposure either.

The following information is taken into account for any hazard / risk assessment:

ORAL: Data are read-across from Ni sulphate. A well-conducted OECD 451 study in rats did not show any carcinogenic potential of nickel sulphate following oral administration. A document containing a summary on this topic can be found in Section 7.7 of IUCLID and inAppendix B1of the CSR.

INHALATION: Data are read-across from Ni subsulphide. The most robust and environmentally relevant carcinogenicity study for Ni₃S₂was conducted as part of a National Toxicology Program study on the toxicity and carcinogenicity of NiSO₄, Ni₃S₂and NiO (Dunnicket al. 1995). Following inhalation of Ni₃S₂for up to two years (6 hr/d, 5 d/wk, two exposure levels), a dose-dependent incidence of lung tumors (combined adenomas and carcinomas) was observed in F344/N rats.

DERMAL: Read-across from Ni sulphate. As oral exposure to nickel sulphate does not show any carcinogenic potential, there are good reasons to assume that cancer is not a relevant end-point with respect to dermal exposure either.

Value used for CSA (route: oral):

NOAEL: 11 mg Ni/kg bw/dayas nickel sulphate hexahydrate

Value used for CSA (route: inhalation):

LOAEC: 0.11 mg Ni/m³ as nickel subsulphide