Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

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

No animal studies were identified characterizing skin sensitization following exposure to nickel nitrate. Nickel nitrate has been shown to elicit an allergic reaction in nickel sensitive humans (Santucci et al. 1998). The Ni2+ion is considered exclusively responsible for the immunological effects of nickel (Menné 1994).

Copious information on human dermal sensitization to nickel sulphate is documented in theNickel 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/cm2and 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/cm2from the Fischer et al. (2005) study is carried forward as the basis for the derivation of DNELfor dermal elicitation/sensitization for nickel sulphate. This value is also used for nickel nitrate due to results of similar nickel release in synthetic sweat to nickel sulphate in bioaccessibility testing.

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

No animal studies were identified characterizing skin sensitization following exposure to nickel nitrate. Nickel nitrate has been shown to elicit an allergic reaction in nickel sensitive humans (Santucci et al. 1998).

Value used for CSA:sensitising

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 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 inAppendixB5of 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 (AppendixB5), 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.

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Value used for CSA:sensitising

Justification for classification or non-classification

Ni nitrate is classified as Skin Sens. 1;H317 in the 1st ATP to the CLP Regulation. Background information can be found in the discussion section.

Ni nitrate 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" (AppendixB5). In summary, criteria associated with classification of a given compound as a respiratory sensitizer are not yet well defined. However, the peer-reviewed literature generally indicate that soluble nickel compounds meet the common criteria shared between respiratory and contact allergens as these compounds can both act as haptens, gain access to the target tissue, and engage an immune response via cytokines and chemokines. Regarding criteria that set the respiratory and contact sensitization apart, which are generally accepted to be associated with the type of immunological responses that they induce, soluble nickel compounds have been associated with Type I reactions involving IgE in case studies of workers with occupational asthma. This is the response pathway associated with respiratory hypersensitivity.