Trinickel disulphide

Endpoint summary

Description of key information

Value used for CSA:sensitising

Value used for CSA: not sensitising

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Ni subsulphide is classified as Skin Sens. 1;H317  in the 1st ATP to the CLP Regulation.  No animal or human studies were identified characterizing skin sensitization following exposure to nickel subsulphide.  The Ni²⁺ ion is considered exclusively responsible for the immunological effects of nickel (Menné 1994). The results of a comprehensive bioaccessibility testing program evaluating release of Ni ion in synthetic sweat from various Ni compounds indicate that Ni subsulphide releases less nickel (II) ion compared to water soluble nickel substances known to be skin sensitizers (including nickel sulphate and nickel chloride), but releases more nickel ions compared to nickel metal, which is also a known skin sensitizer. This suggests that nickel subsulphide is probably a skin sensitizer but with lesser potency than water soluble nickel compounds like nickel sulphate. Although the  bioaccessibility method has not yet been validated in vivo, the classification for skin sensitization for nickel subsulphide is appropriate to be read-across from nickel sulphate as worst case, since it is a skin sensitizer, based on the study in humans by Santucci et al. (1998).  An explanation of the rationale and methodology is provided in Section 7.4.1 of IUCLID and as Appendix B3. New testing for dermal sensitization in animals is therefore waived for Ni subsulphide.

 

Because the Ni²⁺ ion is considered exclusively responsible for the immunological effects of nickel (Menné 1994), the data is read across from nickel sulphate for DNEL derivation for risk characterization. Both animal and human data for nickel sulphate on human dermal sensitization is 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 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. The Ni ion release in synthetic sweat from Ni subsulphide relative to that released from Ni sulphate were used to derive a DNEL for Ni subsulphide that takes into account its lower Ni ion release in sweat. See Appendix B3.

 

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

Ni subsulphide is classified as Skin Sens. 1;H317  in the 1st ATP to the CLP Regulation.  This is supported by results of recent bioaccessibility testing suggesting that Ni subsulphide releases less nickel (II) ion compared to water soluble nickel substances known to be skin sensitizers (including nickel sulphate and nickel chloride), but releases more nickel ions compared to nickel metal, which is also a known skin sensitizer. Although the  bioaccessibility method has not yet been validated in vivo, the classification for skin sensitization for nickel subsulphide is appropriate with read-across from nickel sulphate, since it is a skin sensitizer. An explanation of the rationale and methodology is provided in Section 7.4.1 of IUCLID and as Appendix B3 in the accompanying CSR.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No animal or human studies were identified characterizing respiratory sensitization following exposure to nickel subsulphide. While there is some evidence to indicate that some of the very water-soluble nickel compounds may be respiratory sensitisers in humans, the available data is not considered sufficient for classification of Ni subsulphide.

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

The available data are not considered sufficient for classification of nickel subsulfide as a respiratory sensitizer.

 

Justification for classification or non-classification

Ni subsulphide is classified as Skin Sens. 1;H317  in the 1st ATP to the CLP Regulation. This is supported by results of recent bioaccessibility testing suggesting that Ni subsulphide releases less nickel (II) ion compared to water soluble nickel substances known to be skin sensitizers (including nickel sulphate and nickel chloride), but releases more nickel ions compared to nickel metal, which is also a known skin sensitizer. Although the  bioaccessibility method has not yet been validated in vivo, the classification for skin sensitization for nickel subsulphide is appropriate with read-across from nickel sulphate, since it is a skin sensitizer. An explanation of the rationale and methodology is provided in Section 7.4.1 of IUCLID and as Appendix B3 in the accompanying CSR.