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Administrative data

Description of key information

Value used for CSA (read-across from Nickel sulphate or Nickel ion):

NOAEL (oral, systemic, animal): 100 mg NiSO4.6H2O/kg bw(22 mg Ni/kg bw/day) (FDRL, 1983)

LOAEL (oral, systemic, human data): 0.012 mg Ni (Ni ion)/kg bw/day released from metallic nickel in water and food contact material (Nielsen et al 1999)

NOAEC (inhalation, systemic, animal): 0.53 mg NiSO4.6H2O/L air (120 mg Ni/m3) (EPSL, 2009a)

LOAEC (inhalation, local, animal data): 0.7 mg Ni/m3(DNEL calculation is based on 16-day repeated dose study-Benson et al, 1988; no acute data was available)

An acute local inhalation DNEL is derived based on the lung effects (e.g. lung inflammation) associated with nickel sulphate inhalation.  The shortest-term study available examining those effects in animals is a 16-day repeated exposure study.  An adjustment factor was derived to extrapolate the results from the repeated exposure study to an equivalent effect concentration in a 4 hr acute exposure.  SeeAppendix C3for more information.

(Oral, local values are not applicable; Dermal, local or systemic, values are not applicable)

 

Key value for chemical safety assessment

Additional information

There is data from one acute LD50oral rat study and three acute oral toxic class method studies on nickel nitrate.The Smyth et al. (1969) study gave an LD50value of 1620 mg Ni-nitrate/kg. The study method deviates from the Annex V method in several important respects. Only one sex was used (males), and the animals were not fasted prior to dosing. Lower LD50values were reported for females than for males for the other soluble nickel compounds, nickel chloride (FDRL 1983a) and nickel sulphate (FDRL 1983b). Therefore, it is possible that a lower LD50value would have been determined for nickel nitrate if the female sex had been included. Furthermore, the uptake following oral exposure is known to depend greatly on the presence of food in the gastrointestinal tract. The uptake in fasting individuals is approximately 30%, while in non-fasting individuals a much smaller fraction is absorbed, estimated as 5% (see section on toxicokinetics for further details). The Smythet al. study, using non-fasted rats, was thus likely to yield a higher LD50value than a study using fasted rats. Inconclusion, the Smyth et al. study is expected to underestimate the toxicity compared to an Annex V test. Theresults of the three formulations tested by the acute toxic class method show a result in the range between 200and 2000 mg/kg. However, an LD50could not be determined with only two doses (including the limit dose).

A GLP, OECD-guideline compliantacute oral toxicity study (EPSL, 2009b) and an FDRL (1983) study will be read-across from nickel sulphate. Effects data from these studies will be read-across to Ni nitrate to complete the DNEL derivation:LD50of 361.9 mg NiSO4/kg/bw (EPSL, 2009a) and NOAEL of 100 mg NiSO4.6H2O/kg (or 22 mg Ni/kg) (FDRL, 1983).A comprehensive read-across assessment was recently completed based on bioaccessibility data in synthetic gastric fluid of various nickel compounds combinedin vivoverification data for three source nickel substances. The read-across paradigm presented in a summary document in IUCLID Section 7.2.1 andAppendix B1of the CSR enables grouping of target Ni substances for classification purposes according to bioaccessibility in gastric fluid. This assessment supports that nickel nitrateshould be read-across from Ni sulphate for acute oral toxicity.

Data regarding the potential acute inhalation toxicity of Ni nitrate are read-across from Ni sulphate. A comprehensive read-across assessment was recently completed based on bioaccessibility data in synthetic lung fluids of various nickel compounds combinedin vivoverification data for three source nickel substances. The read-across paradigm presented in a summary document in Section 7.2.2 and inAppendix B2to the CSR enables grouping of target Ni substances for classification purposes according to bioaccessibility in interstitial fluid as demonstrated.  The outcome of this assessment indicates that soluble nickel compounds, such as nickel nitrate, should be read-across from Ni sulphate.

There are no available data on which to evaluate acute dermal toxicity. However, acute toxicity is expected to be low in view of the poor absorption by this route. As oral and inhalation routes of exposure are more relevant and data for these have been provided, testing for acute dermal toxicity is therefore waived based on this information.

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

ORAL: No reliable standard acute oral toxicity tests are available for nickel dinitrate. Data for acute oral toxcity of Ni nitrate will be read-across from Ni sulphate to fulfill the testing requirement and use in DNEL derivation: LD50of 361.9 mg NiSO4/kg/bwand NOAEL of 100 mg NiSO4.6H2O/kg (or 22 mg Ni/kg)

INHALATION: Animal studies of toxicity via inhalation are lacking, and no human data on the toxicity of nickel nitrate via this route have been found. Data will be read-across from Ni sulphate for acute inhalation toxicity: LC50of 2.48 mg NiSO4/Land a NOAEC of 0.53 mg NiSO4.6H2O/L air (120 mg Ni/m3).

DERMAL: No risk characterisation will be conducted for acute dermal toxicity. Acute systemic effects are not relevant due to the very low dermal absorption of nickel. Acute local effects are covered by the long term DNEL based on prevention of dermal sensitization.

Justification for classification or non-classification

Ni nitrate is classified as Acute Tox. 4; H302 and Acute Tox.4:H332 in the 1st ATP to the CLP Regulation. Background information regarding this classification has been provided in the discussion section above.