Registration Dossier

Administrative data

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:

Ni dihydroxide is currently classified as a dermal sensitizer 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 dihydroxide releases significantly less nickel (II) ion compared to nickel substances known to be skin sensitizers, including nickel sulphate and nickel metal. This suggests that nickel dihydroxide may not be a skin sensitizer. However, the bioaccessibility method has not yet been validated in vivo so the classification for skin sensitization can be conservatively read-across from nickel sulphate, since it is classified as a skin sensitizer with positive animal and human skin sensitisation data. A comprehensive summary on this topic is provided in Section 7.4.1 of IUCLID and as Appendix B3 in the accompanying CSR. Data for nickel sulphate has been provided for extrapolation purposes.

Because the Ni2+ ion is considered exclusively responsible for the immunological effects of nickel (Menné 1994), data is read across from nickel sulphate for risk characterization. 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 dihydroxide relative to that released from Ni sulphate were used to derive a DNEL for Ni dihydroxide 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 dihydroxide is currently classified as a dermal sensitizer 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 dihydroxide releases significantly less nickel (II) ion compared to nickel substances known to be skin sensitizers, including nickel sulphate and nickel metal. This suggests that nickel dihydroxide may not be a skin sensitizer. However, the bioaccessibility method has not yet been validated in vivo so the classification for skin sensitization can be conservatively read-across from nickel sulphate, since it is classified as a skin sensitizer with positive animal and human skin sensitisation data. A comprehensive summary on this topic is provided in Section 7.4.1 of IUCLID and as Appendix B3 in this CSR.

Respiratory sensitisation

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

No studies were identified characterizing respiratory sensitization following exposure to nickel dihydroxide. A few case reports in 1970’s and 1980’s 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 B5 to the CSR. The available bioaccessibility data (summarized in IUCLID Section 7.2.2 and CSR Appendix B2) indicate Ni dihydroxide behaves most like Ni oxide, which is not considered to be a respiratory sensitizer. However, there is insufficient in vivo data to override the current respiratory sensitisation classification currently assigned by the CLP.

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

 

No studies were identified characterizing respiratory sensitization following exposure to nickel dihydroxide. Based on a recent literature review (Appendix B5), the available data for soluble nickel compounds may not be considered sufficient for classification as a respiratory sensitizer. In addition, the available bioaccessibility data (summarized in IUCLID Section 7.2.2 and CSR Appendix B2) indicate Ni dihydroxide behaves most like Ni oxide, which is not considered to be a respiratory sensitizer. However, the CLP currently classifies nickel dihydroxide as a respiratory sensitizer.

 

Value used for CSA:sensitizing (respiratory)

Justification for classification or non-classification

Ni dihydroxide is currently classified as a dermal sensitizer (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 dihydroxide releases significantly less nickel (II) ion compared to nickel substances known to be skin sensitizers, including nickel sulphate and nickel metal. This suggests that nickel dihydroxide may not be a skin sensitizer. However, the bioaccessibility method has not yet been validatedin vivoso the classification for skin sensitization can be conservatively read-across from nickel sulphate, since it is classified as a skin sensitizer with positive human and animal skin sensitisation data. A comprehensive summary on this topic is provided in Section 7.4.1 of IUCLID and asAppendix B3in the accompanying CSR.

 

Ni dihydroxide is classified as Resp. Sens. 1:H334 according to the 1st ATP to the CLP Regulation. However, the available bioaccessibility data in synthetic lung fluids (summarized in IUCLID Section 7.2.2 and Appendix B2) indicate Ni dihydroxide behaves most like Ni oxide. As Ni oxide is not considered a respiratory sensitizer, these data suggest the classification of Ni dihydroxide as a respiratory sensitizer requires further scrutiny.