Registration Dossier

Administrative data

Description of key information

Value used for CSA: sensitizing (skin)

Value used for CSA: not sensitizing (respiratory)

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

No animal data on dermal sensitisation with nickel metal have been found. Nickel metal is well known as a skin sensitiser, and is one of the most frequent skin sensitisers in man. The Ni2+ ion is considered exclusively responsible for the immunological effects of nickel (Menné, 1994). Patch testing with nickel metal has demonstrated nickel metal is a skin sensitizer in humans (Uter et al., 1995; Menné et al., 1987). There is also an abundance of reports on human sensitisation with metallic nickel (see Section 7.10.4 of IUCLID). New testing for dermal sensitization in animals is waived based on human data. Sufficient data from human studies exists to warrant classification of Ni metal as a dermal sensitizer.

Because the Ni2+ ion is considered exclusively responsible for the immunological effects of nickel (Menné, 1994), patch test data from nickel sulphate is considered together with relative Ni release in sweat for risk characterization. In addition to animal data for nickel sulphate, additional studies are summarized in the Nickel Sulphate IUCLID dossier Section 7.10.4. One of these studies, a meta-analysis of published patch test studies by Fischer et al. (2005) has been used as the basis for the derivation of a DNEL for dermal elicitation/sensitization with nickel sulphate as described in Section 5.11. The aim of the study by Fischer et al. (2005) was to assess thresholds of response by making a statistical analysis of available dose-response studies with a single occluded exposure and comparing the results to thresholds from other modes of exposure. Eight occluded Ni dose-response studies were selected based on statistical considerations. The statistical analysis showed that 5% of a sensitized population reacts to 0.44 µg Ni/cm2 and 10% react to 1.04 µg Ni/cm2. In another study with a single open application, 7.8% of sensitized persons responded to a dose 6x higher than the dose to which 10% reacted in occluded exposure. The NOAEL of 0.00044 mg Ni/cm2 (as 100% bioaccessible ion) from the Fischer et al. (2005) study is carried forward as the basis for the derivation of DNEL for dermal elicitation/sensitization by Ni metal. The Ni ion release in synthetic sweat from Ni metal relative to that released from Ni sulphate was used to derive a DNEL for Ni metal that takes into account its lower Ni ion release in sweat. The DNEL for Ni metal after adjustment for relative bioaccessibility is 35 µg Ni/cm2 skin. See Appendix B3.

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

Sufficient data from human studies exists to warrant classification of Ni metal as a dermal sensitizer.

Value used for CSA: sensitizing

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No animal data on respiratory sensitisation with nickel metal have been found. While there is some evidence from exposure to indicate that metallic nickel may be a respiratory sensitiser in humans, the available data is not considered sufficient for classification. The classification of nickel metal as a respiratory sensitizer was discussed extensively in 2004 by the EU Classification and Labelling Subcommittee (under EU Existing Substances regulation, 793-93). Only the water soluble nickel salts (but not nickel metal or water insoluble nickel compounds) are classified as respiratory sensitizers. Neither nickel metal nor water insoluble nickel compounds have been classified as respiratory sensitizers under.

While the 60 year old male described by Block & Yeung (1982) had exposures to a nickel containing alloy, the subject also had exposure to soluble nickel compounds and to other metals including Cr (a potential sensitizer). There was positive response to bronchial challenge with nickel sulphate while chromium was not tested. A causal association with nickel metal cannot be established by this case.

The 27 year old female described by Estlander et al. (1993) had similar exposures as the above mentioned 60 year old male, although exposure to soluble nickel compounds was not described. There was a positive response to bronchial challenge with nickel sulphate while chromium was ruled out as a confounder. A causal association with metallic nickel is suggested by this data.

Therefore, these few case reports provide only a hint that exposure to metallic nickel may be causing or eliciting sensitization in susceptible individuals. Given the tens of thousands of exposed workers and the limited quality of the existing data linking nickel metal exposure to hypersensitivity/asthma reactions, the evidence does not comply with the criterion for classification of substances as respiratory sensitizers.

 

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

The available data is not considered sufficient for classification as a respiratory sensitizer.

 

Justification for classification or non-classification

Nickel metal is classified as Skin Sens. 1: H317 in the 1st ATP to the CLP Regulation. Background information regarding this classification is provided in the discussion section.

Nickel metal is not classified for respiratory sensitization in the 1st ATP to the CLP Regulation. Available data are not considered sufficient for classification.