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Diss Factsheets

Toxicological information

Carcinogenicity

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Administrative data

Description of key information

Key value for chemical safety assessment

Justification for classification or non-classification

Nickel 2-ethylhexanoate is legally classified as Carc. Category 1A; H350 in the 1st ATP of the CLP regulation.

Additional information

Read-across approach


Selected endpoints for the human health hazard assessment are addressed by read-across, using a combination of data on the metal cation and the organic acid anion. This way forward is acceptable, since metal carboxylates are shown to dissociate to the organic anion and the metal cation upon dissolution in aqueous media. No indications of complexation or masking of the metal ion through the organic acid were apparent during the water solubility and dissociation tests (please refer to the water solubility and dissociation in sections 4.8 and 4.21 of IUCLID). Once the individual transformation products of the metal carboxylate become bioavailable (i.e., in the acidic environment in the gastric passage or after phagocytosis by pulmonary macrophages), the “overall” toxicity of the dissociated metal carboxylate can be described by a combination of the toxicity of these transformation products, i.e., the metal cation and carboxylate anion according to an additivity approach.


 


Nickel bis(2-ethylhexanoate) is the nickel salt of 2-ethylhexanoic acid, which readily dissociates to the corresponding divalent nickel cation and monovalent 2-ethylhexanoate anions. The nickel cation and the 2-ethylhexanoate anion are considered to represent the overall toxicity of nickel bis(2-ethylhexanoate) in a manner proportionate to the free acid and the metal (represented by one of its readily soluble salts). 


 


A detailed justification for the read-across approach is added as a separate document in section 13 of IUCLID.


 


Carcinogenicity


No carcinogenicity study with nickel bis(2-ethylhexanoate) is available, thus the carcinogenicity will be addressed with existing data on the dissociation products as detailed in the table below. 


 


Table: Summary of carcinogencicity data of nickel bis(2 -ethylhexanoate) and the individual constituents.


















 



nickel ion



2-ethylhexanoic acid


(CAS# 149-57-5)



nickel bis(2 -ethylhexanoate)


(CAS# 4454-16-4)



Carcinogenicity



Carc. Cat. 1A



Negative



Carc. Cat. 1A



 


Nickel


Data on respiratory carcinogenicity associated with inhalation exposure to nickel chloride and/or Ni sulphate (in mixed nickel exposures) from multiple human studies are considered (e.g., Oller et al., 2014; Grimsrud et al., 2002). Ni sulphate has been classified as Carc. 1A; H350i in the 1st ATP to the CLP Regulation.


A well-conducted OECD 451 study in rats did not show any carcinogenic potential of nickel sulphate following oral administration. The available data concerning dermal exposure are too limited for an evaluation of the carcinogenic potential in experimental animals following dermal contact to nickel sulphate. However, as oral exposure to nickel sulphate does not show any carcinogenic potential, there are good reasons to assume that cancer is not a relevant end-point with respect to dermal exposure either. Studies via other routes of exposure and promoter studies provide at most limited evidence of carcinogenicity of nickel sulphate in animals.


 


2-ethylhexanoic acid


2-ethylhexanoic acid is not mutagenic in the Ames test or in mammalian cell systems both in the absence and presence of metabolic activation. 2-ethylhexanoic acid did not induce micronuclei in bone marrow of mice. Taking into account the lack of genotoxic effects, it is concluded that carcinogenicity should not be an endpoint of concern.


 


Nickel bis(2-ethylhexanoate)


Nickel bis(2-ethylhexanoate) is legally classified as Carc. Category 1A; H350 in the 1st ATP of the CLP regulation. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.