Nickel di(acetate)

Endpoint summary

Description of key information

NOAEL (oral, systemic, animal): 175 mg/kg bw (42 mg Ni/kg bw/day) (EPSL, 2008)

LOAEL (oral, systemic, human data; read-across): 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; read-across): 0.53 mg NiSO₄.6H₂O/L air (120 mg Ni/m³) (EPSL, 2009)

LOAEC (inhalation, local, animal; read-across): 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.  See Appendix C3 for more information.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

550 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2.48 mg/m³ air

Additional information

One available study sufficiently characterizes lethality following oral exposure in rats (EPSL, 2008). An LD₅₀ value of 550 mg/kg (with a 95% confidence interval of 191.7-1,680 mg/kg) was reported as a result of a guideline-based, GLP study that implemented the up and down procedure in rats. The result was based on a series of exposures in female rats to doses ranging from 175 mg/kg to 2,000 mg/kg.

Data on acute inhalation toxicity of Ni acetate are read-across from Ni sulphate (see read-across framework justification table above).Both inorganic nickel compounds are very similar in chemical structure and upon inhalation both transform (to similar extents) into a common soluble Ni²⁺ ion, the toxic moiety responsible for the acute toxicity of nickel compounds.A comprehensive read-across assessment was completed based on bioaccessibility data in synthetic lung fluids of various nickel compounds combined with in vivo verification data for three source nickel substances (Henderson et al., 2012a,b; 2014). The read-across paradigm presented in a summary document in Section 7.2.2 of IUCLID and in Appendix B2 of 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 Ni acetate should be read-across from Ni sulphate for acute inhalation toxicity. Ni sulphate hexahydrate has been shown to have an acute inhalation LC₅₀ of 2.48 mg NiSO₄/L and a NOAEC of 0.53 mg NiSO₄.6H₂O/L air (120 mg Ni/m³) (EPSL, 2009). Therefore, application of this read-across confirms that Ni acetate should be classified as Acute Tox 4; H332.

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, 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: In a GLP, guideline-based study, the acute oral LD₅₀ of Ni acetate was determined in female rats using the up and down procedure. Statistical evaluation of mortality data resulting from exposures ranging from 175 to 2000 mg/kg indicated an oral LD₅₀ of 550 mg/kg body weight and a NOAEL of 175 mg/kg bw (or 42 mg Ni/kg bw/day).

INHALATION: Data are read-across from Ni sulphate. The outcome of a recently completed read-across assessment based on bioaccessibility and in vivo animal data for various nickel compounds indicates that Ni acetate should be read-across from Ni sulphate for acute inhalation toxicity. Ni sulphate hexahydrate has been shown to have an acute inhalation LC₅₀ of 2.48 mg NiSO₄/L and 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

A recent in vivo study confirms Ni acetate should be classified for acute oral toxicity as Acute Tox. 4: H302 (LD₅₀=550 mg/kg).

Ni acetate is classified as Acute Tox. 4: H332 for acute inhalation toxicity according to the CLP. Background information regarding this classification has been provided in the discussion section above.