Nickel bis(dihydrogen phosphate)

Endpoint summary

Description of key information

Values 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 associated with nickel bis(dihydrogen phosphate) was identified. The Ni²⁺ ion is considered exclusively responsible for the immunological effects of nickel (Menné, 1994). Data on the potential to cause dermal sensitization are being read-across from Ni sulphate since nickel sulphate and nickel bis(dihydrogen phosphate) have similar solubility in water. Nickel sulphate has been shown to be a dermal sensitizer in human studies (Santucci et al., 1998; Fischer et al., 2005).  A comprehensive summary on this topic is provided in Appendix B3. New testing for dermal sensitization in animals is therefore waived for Ni bis(dihydrogen phosphate).

 

Information on human dermal sensitization to nickel sulphate is summarized in the Nickel Sulphate IUCLID dossier Section 7.10.4.  One of these studies, is a study by Santucci et al. (1998) where 151 patients were patch tested using nickel sulphate using a standardized patch testing protocol. Briefly, nickel sulfate solution was applied in Finn Chambers on Scanpore for patch testing and were read at 48 and 96 h (visual scoring according to international guidelines at 48 h). A comprehensive summary on this topic is provided in Appendix B3. 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 for nickel sulphate and read-across to nickel bis(dihydrogen phosphate) based on similar solubilities in bioaccessibility testing in synthetic sweat.

 

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

Ni bis(dihydrogen phosphate) is classified as Skin Sens. 1:H317 in the 1st ATP to the CLP Regulation. Data on the potential to cause and DNEL for dermal sensitization are being read-across from Ni sulfate, since nickel sulphate and nickel bis(dihydrogen phosphate) have similar solubility in water, and solubility is expected to be similar in synthetic sweat. Nickel sulphate has been shown to be a dermal sensitizer in human studies. A comprehensive summary on this topic is provided in Section 7.4.1 of IUCLID and as Appendix B3.

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 few case reports in 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 bis(dihydrogen phosphate) is classified as Skin Sens. 1;H317 in the 1st ATP to the CLP Regulation. Data on the potential to cause dermal sensitization are being read-across from Ni sulfate, since nickel sulphate and nickel bis(dihydrogen phosphate) have similar solubility in water, and solubility is expected to be similar in synthetic sweat. A comprehensive summary on this topic is provided in Section 7.4.1 of IUCLID and as Appendix B3.

 

Ni bis(dihydrogen phosphate) 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).