Calcium 3,5,5-trimethylhexanoate

Endpoint summary

Description of key information

Calcium 3,5,5-trimethylhexanoate is not expected to show signs of dermal sensitisation, because the two dissociation products, calcium cations and 3,5,5-trimethylhexanoate anions, have not shown any skin sensitisation potential in experimental testing.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

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.

 

Calcium 3,5,5-trimethylhexanoate is the calcium salt of 3,5,5-trimethylhexanoic acid and readily dissociates to the corresponding divalent calcium cation and monovalent 3,5,5-trimethylhexanoate anions. The calcium cation and the 3,5,5-trimethylhexanoate anion are considered to represent the overall toxicity of calcium 3,5,5-trimethylhexanoate 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.

 

Sensitisation

No skin sensitisation study with Calcium 3,5,5-trimethylhexanoate is available, thus the skin sensitisation potential will be addressed with existing data on the dissociation products as detailed in the table below. Further details on the skin sensitisation potential of the individual constituents within the framework of regulation (EC) 1907/2006 are given below.

 

Table: Summary of skin sensitisation data of calcium isononanoate and the individual constituents.

	calcium substances	3,5,5 -trimethylhexanoic acid (CAS# 3302-10-1)	Calcium 3,5,5-trimethylhexanoate(CAS# 64216-15-5)
Skin sensitisation	not sensitising	not sensitising	not sensitising (read-across)

 

Calcium 3,5,5-trimethylhexanoate is not expected to show signs of dermal sensitisation, since the two constituents calcium and 3,5,5-trimethylhexanoic acid have not shown any skin sensitisation potential in experimental testing. Thus, calcium 3,5,5-trimethxlhexanoate is not to be classified according to regulation (EC) 1272/2008 as skin sensitising. Further testing is not required. For further information on the toxicity of the individual constituents, please refer to the relevant sections in the IUCLID and CSR.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

According to the CLP regulation the hazard identification and subsequently a proposal for classification as “Respiratory sensitiser” will normally be based on human experience. In this context, hypersensitivity is normally seen as asthma, but other hypersensitivity reactions such as rhinitis/conjunctivitis and alveolitis are also considered. The condition will have the clinical character of an allergic reaction. However, immunological mechanisms do not have to be demonstrated.

The evidence could be:

1. clinical history and data from appropriate lung function tests related to exposure to the substance, confirmed by other supportive evidence which may include:
   
   
   
   • in vivo immunological test (e.g. skin prick test);
   
   
   • in vitro immunological test (e.g. serological analysis);
   
   
   • studies that indicate other specific hypersensitivity reactions where immunological mechanisms of action have not been proven, e.g. repeated low-level irritation, pharmacologically mediated effects;
   
   
   • a chemical structure related to substances known to cause respiratory hypersensitivity
   
   
   
   


2. data from one or more positive bronchial challenge tests with the substance conducted according to accepted guidelines for the determination of a specific hypersensitivity reaction.

Calcium 3,5,5-trimethylhexanoate is not expected to show a respiratory sensitising potential.

Justification for classification or non-classification

Calcium 3,5,5-trimethylhexanoate is not expected to show signs of dermal sensitisation, since the two constituents calcium and 3,5,5-trimethylhexanoic acid have not shown any skin sensitisation potential in experimental testing. Thus, calcium 3,5,5-trimethylhexanoate is not to be classified according to regulation (EC) 1272/2008.