2-ethylhexanoic acid, manganese salt

Carcinogenicity

Justification for classification or non-classification

2-ethylhexanoic acid, manganese salt is not expected to be carcinogenic, since the two constituents manganese and 2-ethylhexanoic acid are also not classified as carcinogenic. Thus, 2-ethylhexanoic acid, manganese salt is not classified according to regulation (EC) 1272/2008 as carcinogenic.

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.

 

2-ethylhexanoic, manganese salt is the manganese metal salt of 2-ethylhexanoic acid, which readily dissociates to the corresponding divalent manganese cation and 2-ethylhexanoic acid anions. The manganese cation and the 2-ethylhexanoic acid anion are considered to represent the overall toxicity of 2-ethylhexanoic, manganese salt 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 2-ethylhexanoic acid, manganese salt is available, thus the carcinogenicity will be addressed with existing data on the dissociation products as detailed in the table below.

 

Table: Summary of carcinogenicity data of 2-ethylhexanoic acid, manganese salt and the individual constituents.

	Manganese sulfate (CAS# 7785-87-7)	2-ethylhexanoic acid (CAS# 149-57-5)	2-ethylhexanoic, manganese salt (CAS#15956-58-8)
Carcinogenicity	Negative	Negative	Negative (read-across)

 

Manganese

An extensive review of literature (Assessment of Genotoxicity and Carcinogenicity of inorganic-forms of Manganese, MHRP 2009) concluded through weight-of-evidence that the registered substance, manganese dichloride, is not carcinogenic. This is further supported by the UK HSE report Manganese and its inorganic compounds (EH64 1999), which concludes that there is no evidence linking Manganese and its inorganic compounds to carcinogenicity in humans. The Scientific Committee on Occupational Exposure Limits (SCOEL 2009) states “data on carcinogenicity mutagenicity and genotoxicity are inconclusive and inadequate to establish a definitive position on the carcinogenicity on manganese and its compounds”.

 

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.