Pentanickel octahydroxide carbonate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Additional information:

Due to the structural similarities of Pentanickel Octahydroxide Carbonate and Nickel Hydroxycarbonate, all information in this section is relevant for Pentanickel Octahydroxide Carbonate (see section 13 for full discussion of read-across strategy).

Ni hydroxycarbonate is currently classified as a dermal sensitizer (R43 and Skin Sens. 1;H317) according to the 1st ATP to the CLP Regulation. The results of a comprehensive bioaccessibility testing program evaluating release of Ni ion in synthetic sweat from various Ni compounds indicate that Ni hydroxycarbonatereleases less nickel (II) ion compared to water soluble nickel substances known to be skin sensitizers (including nickel sulphate and nickel chloride), but releases similar amounts of nickel ion to nickel metal, which is also a known skin sensitizer. This suggests that nickelhydroxycarbonateis probably a skin sensitizer but with lesser potency than water soluble nickel compounds like nickel sulphate. Although the bioaccessibility method has not yet been validatedin vivo, the classification for skin sensitization for nickelhydroxycarbonate is appropriate to be read-across from nickel 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 CSR.

In addition to animal data for nickel sulphate, copious information on human dermal sensitization to nickel sulphate is documented in the Nickel and nickel compounds Background Document in support of individual RISK ASSESSMENT REPORTS of nickel compounds prepared in relation to Council Regulation (EEC) 793/9. 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 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 hydroxycarbonate relative to that released from Ni sulphate were used to derive a DNEL for Ni hydroxycarbonate that takes into account its lower Ni ion release in sweat.

Migrated from Short description of key information:
Ni hydroxycarbonate is currently classified as a dermal sensitizer (R43 and Skin Sens. 1;H317) according to the 1st ATP to the CLP Regulation. This is supported by results of recent bioaccessibility testing suggesting that Ni hydroxycarbonate releases less nickel (II) ion compared to water soluble nickel substances known to be skin sensitizers (including nickel sulphate and nickel chloride), but releases similar amounts of nickel ion to nickel metal, which is also a known skin sensitizer. Nickel hydroxycarbonate is probably a skin sensitizer but with lesser potency than water soluble nickel compounds like nickel sulphate. An explanation of the rationale and methodology is provided Section 7.4.1 of IUCLID and as Appendix B3 in the accompanying CSR.

Respiratory sensitisation

Endpoint conclusion

Additional information:

No studies were identified characterizing respiratory sensitization following exposure to nickel hydroxycarbonate. 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 is extensively reviewed in the background document attached in Section 7.4.2 and provided as Appendix B7 to the CSR. In adition, the available bioaccessibility data (summarized in IUCLID Section 7.2.2 and CSR Appendix B2) indicate Ni hydroxycarbonate behaves in lung fluids like Ni subulfide, which is not considered a respiratory sensitizer.

 

Migrated from Short description of key information:
No studies were identified characterizing respiratory sensitization following exposure to nickel hydroxycarbonate. Based on a recent literature review (Appendix B7), the available data for soluble nickel compounds are not considered sufficient for classification as a respiratory sensitizer.
In addition, available bioaccessibility data (Appendix B2) indicate Ni hydroxycarbonate behaves in lung fluids like Ni subulfide, which is not considered a respiratory sensitizer.

Justification for classification or non-classification

Ni hydroxycarbonate is currently classified as a dermal sensitizer (R43 and Skin Sens. 1; H317) according to the 1st ATP to the CLP Regulation. This is supported by results of recent bioaccessibility testing suggesting that Ni hydroxycarbonate releases less nickel (II) ion compared to water soluble nickel substances known to be skin sensitizers (including nickel sulphate and nickel chloride), but releases similar amounts of nickel ion to nickel metal, which is also a known skin sensitizer. An explanation of the rationale and methodology is provided Section 7.4.1 of IUCLID and as Appendix B3 in the accompanying CSR.

Ni hydroxycarbonate is classified as R42 and Resp. Sens. 1:H334 according to the 1st ATP to the CLP Regulation. Although there is some evidence to indicate that very water-soluble nickel compounds may be respiratory sensitiser in humans, the data seems insufficient to warrant classification of nickel hydroxycarbonate (and water soluble nickel compounds) for this endpoint. The existing data are extensively reviewed in the attached background document in Section 7.4.2 of IUCLID and asAppendix B7 to the CSR.