Nickel di(acetate)

Endpoint summary

Description of key information

Value used for CSA: sensitizing (skin and respiratory)

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

No information characterizing sensitization in animal models with nickel acetate was identified. Ni acetate was demonstrated to elicit a reaction in a human patch test study (Santucci et al., 1998).  The Ni²⁺ ion is considered exclusively responsible for the immunological effects of nickel (Menné, 1994).  As such, all nickel substances are classified for skin sensitisation since they all are capable of releasing Ni ions.  However, the potency of the different nickel substances depends on the amount of bioaccessible nickel ions. 

 

Although sufficient data is available to determine skin sensitisation classification for nickel acetate, derivation of a DNEL requires consideration of data for other nickel substances.  A comprehensive bioaccessibility testing program evaluating release of Ni ion in synthetic sweat from various Ni compounds indicates nickel sulphate and nickel acetate release similar amounts of nickel ion (see Appendix B3).   Because the nickel ion is the relevant immunological entity for both substances and data DNEL derivation is not available for nickel acetate, the nickel sulphate data is used to derive the skin sensitisation DNEL for nickel acetate. 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 CSR 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 from the Fischer et al. (2005) study is carried forward as the basis for the derivation of DNEL for dermal elicitation/sensitization for nickel sulphate and read-across to nickel acetate based on similar solubilities in bioaccessibility testing in synthetic sweat. A comprehensive summary on this topic is provided in Appendix B3.

 

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

Data on the potential to cause dermal sensitization exist for nickel acetate, which has been shown to be a dermal sensitizer in a human study. The DNEL for dermal sensitization is read across from nickel sulphate.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Data on the potential to cause respiratory sensitization are being read-across from Ni sulphate. A RAAF table has not been included at this time since respiratory sensitization is not a required endpoint. A few case reports in the 1970s and 1980s suggest that nickel sulphate may be a respiratory sensitiser in humans. Considering the number of workers that have been exposed to soluble nickel compounds in the refining and metal finishing industry over the years, the number of reported cases is very small. No data regarding respiratory sensitisation in animals have been located. A recent comprehensive review of the available literature regarding the potential of soluble Ni compounds to induce respiratory sensitization can be found in the attached background document entitled, "Background-Soluble Nickel Respiratory Sensitization" (Section 7.4.2 of IUCLID) and in Appendix B5 of the CSR.

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

Data on the potential to cause respiratory sensitization are being read-across from Ni sulphate. Based on a recent literature review (Appendix B5), the available data for Ni sulphate may not be sufficient for classification of either compound as a respiratory sensitizer but the possibility cannot be ruled out due to association of soluble nickel compounds with type I allergic reactivity and respiratory reactions.

Justification for classification or non-classification

Ni acetate is classified as Skin Sens. 1; H317 in the 1st ATP to the CLP Regulation. Background information regarding this classification in provided in the discussion section above.

Ni acetate is classified as Resp. Sens. 1; H334 in the 1st ATP to the CLP Regulation. A comprehensive review of the available literature regarding the potential of soluble Ni compounds to induce respiratory sensitization can be found in the attached background document entitled, "Background-Soluble Nickel Respiratory Sensitization" (CSR Appendix B5).