Registration Dossier

Administrative data

Description of key information

Value used for CSA:

NOAEL (oral, systemic, animal data):0.011 mg Ni (as soluble ion)/kg bw/day (770 µg Ni/day for 70 kg person or 231 µg Ni/day of absorbed dose based on 30% absorption of Ni from water under fasting conditions)

LOAEC (inhalation, local, animal data): 0.1 mg Ni/m³ air(powder MMAD=1.8μm, GSD=2.4; Oller et al, 2008)

(Oral, local values are not applicable; Inhalation, systemic values are not applicable; Dermal, local or systemic, values are not applicable)

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
LOAEC
0.1 mg/m³

Additional information

A 2 -year inhalation carcinogenicity study with nickel metal provides data on repeated dose toxicity. This study concluded that the LOAEC for respiratory effects associated with long-term inhalation exposure to nickel metal powder (MMAD=1.8 μm, GSD=2.4 ) was 0.1 mg/m3.

Repeated dose toxicity of nickel metal via the oral route of exposure is read-across from Ni sulphate (highest nickel bioavailability). A chronic oral exposure study with Ni sulphate yielded a LOAEL of 6.7 mg Ni/kg bw/day and a NOAEL of 2.2 mg Ni/kg bw/day for body weight effects Heim et al., 2007). However, the oral DNEL for long-term systemic effects of Ni ion released from Ni metal (0.011 mg Ni/kg/day) is based on the Tolerable Daily Intake (TDI) for nickel included in the background document for development of WHO (2007) guidelines for drinking water quality. This TDI derived by WHO (2007) is based on the NOAEL for post-implantation loss/perinatal mortality in the one and two-generation studies in rats exposed orally to Ni sulphate (SLI, 2000a,b), and the application of an AF of 10 for intraspecies variability and an AF of 10 for interspecies variability. This TDI is lower than the one that can be derived based on body weight effects in the Heim et al (2007) study. A summary on this topic is provided in Appendix D5 of the CSR.

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

INHALATION: The LOAEC for respiratory effects associated with inhalation exposure to nickel metal powder (MMAD=1.8 μm, GSD=2.4) was found to be 0.1 mg/m3 in a 2-year bioassay (Oller et al., 2008).

ORAL: Data on lack of chronic oral toxicity are being read-across from Ni sulphate. The oral DNEL for long-term systemic effects of Ni ion (0.011 mg Ni/kg/day) released from nickel metal is based on the TDI for nickel derived by WHO (2007).

DERMAL: Testing by the dermal route has been waived as described above and under Section 7.5.2 of IUCLID.

Justification for classification or non-classification

Ni metal is classified as STOT RE 1; H372 in the 1st ATP to the CLP Regulation. Background information regarding this classification is provided in the discussion section above.