Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Values used for CSA:

  • NOAEL (oral, systemic, animal data): > 9000 mg Ni/kg bw (FDRL, 1983)
  • NOAEL (oral, systemic, human data): 0.012 mg Ni (Ni ion)/kg bw/day released from metallic nickel in water and food contact material (Nielsen et al 1999)
  • NOAEC (inhalation, systemic, animal data): ≥10200 mg Ni/m3 air (FDRL, 1985). - An acute systemic inhalation DNEL is not derived for nickel metal since acute systemic toxicity is so low that the substance does not merit classification for this health endpoint.
  • LOAEC (inhalation, local, animal data): 4 mg Ni/m3 (MMAD = 1.5 µm) (DNEL calculation is based on 28-day repeated dose study-WIL Research Laboratories, 2002; no acute data available) - An acute local inhalation DNEL is derived based on the lung effects (e.g. lung inflammation) associated with nickel metal inhalation. The shortest-term study available examining those effects in animals is a 28-day repeated exposure study. An adjustment factor was derived to extrapolate the results from the repeated exposure study to an equivalent effect concentration in a 4 hr acute exposure. See Appendix C3 for more information.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

The acute oral toxicity of nickel metal has been determined in a well-performed animal study, showing that nickel metal has low toxicity via the oral route. The acute oral LD50 was greater than 9000 mg/kg bw. In some instances, people are exposed orally to nickel ions released into food and/or water from food contact materials, heating elements of kettles, or pipes and fittings, all of which contain metallic nickel. For acute toxicity risk characterization for Man via the Environment (MvE), an oral DNEL for acute systemic effects (0.37 mg Ni/kg/day) for the Ni ion released from Ni metal is based on acute oral toxicity studies in rats conducted with the most bioavailable of the Ni compounds (e.g., Ni sulphate hexahydrate). A comparable DNEL range based on observations of acute oral toxicity in humans (Sunderman et al., 1988) was derived as 0.24 - 0.47 mg Ni/kg. This comparison shows that the derivation of the acute oral DNEL from acute toxicity studies in rats is within the range of one derived from humans and will be protective of acute effects in the general population. The DNEL of 0.37 mg Ni (for the soluble Ni ion)/kg will be protective for acute effects in the general population, but does not cover acute-sensitive subpopulations (e.g. for the sensitive endpoint of oral exacerbation of existing dermatitis) (see MvE Appendix D5 for more information).

Data from an acute inhalation animal study indicated no toxicity. However, the exposure duration was one hour, whereas a four-hour exposure is the typical criteria for classification of acute inhalation toxicity[1]. Further, as no toxicity was observed in the acute inhalation study, the acute inhalation LC50 was estimated to be > 10 mg/L for 1 hour. There is also a case report of a worker exposed to 380 mg Ni/m3 for 1.5 hours who subsequently died (Rendall et al., 1994; Phillips et al., 2010). However, in this case the particle size of the aerosol was in the nanoscale range (50 nm). Due to the expected poor absorption of nickel via inhalation of nickel metal, further testing is not considered critical for the risk assessment of metallic nickel.

Data on acute toxicity in animals via dermal exposure have not been found. Dermal acute toxicity is expected to be low in view of the low oral toxicity and the negligible absorption via the skin. Therefore, testing for acute dermal toxicity is waived.

No classification for acute oral, inhalation, or dermal toxicity is suggested.

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

ORAL: The acute oral systemic toxicity of nickel metal has been determined in a well-performed animal study which concluded the acute oral LD50 was > 9000 mg/kg bw.

INHALATION: The acute inhalation systemic toxicity animal study indicated no toxicity for nickel metal. A NOAEC of > 10 mg/L was determined or >2.5 mg/L if extrapolated to 4 hours. However, due to the expected poor absorption of nickel via inhalation of nickel metal, further testing is not considered relevant.

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.

[1]According to ECHA Guidance on Information Requirements and Chemical Safety Assessment; Chapter R.7a: Endpoint specific guidance, “…For the inhalation route, standard protocols involve a 4-hour exposure. If data for other time periods are available (e.g. for 0.5 to 8 hours), extrapolation to a 4-hour exposure period can be achieved using a modification of Haber’s Law (Cn.t = k)....”

Justification for classification or non-classification

  • Ni metal is not classified for acute toxicity endpoints in the 1st ATP to the CLP Regulation. Background information is provided in the discussion section above.