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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Introduction to read-across matrix

A comprehensive data gap analysis was conducted for the entire substance portfolio of the REACH Metal Carboxylates Consortium (RMC), covering 10 metal carboxylates in total back in 2013. This literature screening effort included:

 

  • all available proprietary studies from the REACH Metal Carboxylates Consortium (RMC)
  • detailed literature searches in online databases
  • screening of human health review articles
  • rigorous quality and reliability screening according to Klimisch criteria, where those criteria apply

 

During the literature search and data gap analysis it became obvious that the overall database on substance-specific human health hazard data for the metal carboxylates is too scant to cover all REACH endpoints. Therefore, the remaining data gaps had to be covered by either experimental testing or read-across from similar substances.

 

Selected endpoints for the human health hazard assessment are addressed by read-across, using a combination of data on the organic acid counterion and the metal (or one of its readily soluble salts). This way forward is acceptable, since metal carboxylates 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 tests (please refer to the water solubility data in section of the IUCLID and chapter of the CSR). Once the individual constituents 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 the toxicity of the “individual” constituents. Since synergistic effects are not expected for this group of metal carboxylates, the human health hazard assessment consists of an individual assessment of the metal cation and the organic anion.

 

The hazard information of the individual constituents was obtained from existing REACH registration dossiers via a license-to-use obtained by the lead registrant. These registration dossiers were submitted to ECHA in 2010 as full registration dossiers, and are thus considered to contain relevant and reliable information for all human health endpoints. All lead-registrant dossiers were checked for completeness and accepted by ECHA, i.e. a registration number was assigned.

 

 

In order to check whether read-across from 2-ethylhexanoic acid, molybdenum salt to sodium molybdate is justified, a combined water solubility and UV spectral analysis was conducted.

 

The water solubility study with 2-ethylhexanoic acid, molybdenum salt was conducted in accordance with OECD 105 and under GLP. The test was conducted in triplicate vessels over 16 days and the solubility of the substance was determined by measuring dissolved Mo by ICP-OES after 1, 2, 3, 14,15 and 16 days. A constant concentration of dissolved Mo was achieved, at ca. 13 mg Mo/L. Throughout the experiment, the pH of the solutions was in the range 3.8 - 4. In order to assess the species of the dissolved molybdenum, UV spectra were taken during each day of sampling.

 

A read-across approach for inorganic molybdenum substances and molybdenum metal was developed by the Molybdenum Consortium, which reports as follows:“The species in solutions of sodium molybdate at concentrations 1–10 mg/L and pH ca 7 is the the molybdate ion, [MoO4]2−with a UV absorption maximum (peak) at 207–208 nm (48000 cm-1). As the pH is lowered the [MoO4]2−ion becomes protonated giving [HMoO4]and [H2MoO4] species, the peaks in the UV spectra shifting to lower energies (longer wavelengths). From our UV spectra we shall see that the predominant (>90%) species from our compounds in solution or in contact with water are the [MoO4]2−and [HMoO4]ions. The UV spectral analysis has enabled us to describe the speciation in water solutions of soluble molybdates (sodium and ammonium molybdates) and in supernatant solutions of suspensions of poorly soluble molybdenum substances (calcium molybdate, molybdenum metal, ferromolybdenum, molybdenum dioxide, molybdenum trioxide, roasted molybdenum concentrate and molybdenum disulfide). The solutions and supernatant liquids contain the molybdate ion and, in addition at lower pHs, protonated molybdate. At biological concentrations and pH the only molybdenum species produced from the molybdenum substances studied is the molybdate, [MoO4]2-, ion. Read across from sodium molybdate is therefore justified.”(International Molybdenum Association (2009) Speciation of molybdenum compounds in water - Ultraviolet spectra and REACH read across - Report for the International Molybdenum Association REACH Molybdenum Consortium, unpublished report).

 

The UV spectral analysis of the samples taken during water solubility testing of 2-ethylhexanoic acid, molybdenum salt show that [MoO4]2−and [HMoO4]ions are formed upon dissolution of 2-ethylhexanoic acid, molybdenum salt in aqueous media. The presence of the molybdate and the protonated molybdate anion represent the dominant species at the pH of 3.8-4 being observed in the water solubility test. Under physiological conditions the molybdate anion will be the relevant molybdenum species liberated form 2-ethylhexanoic acid, molybdenum salt.

 

2-ethylhexanoic acid, molybdenum salt is the molybdenum metal salt of 2-ethylhexanoic acid, which readily dissociates to the corresponding molybdate anion and 2-ethylhexanoic acid anions. The molybdate anion and the 2-ethylhexanoic acid anion are considered to represent the overall toxicity of the 2-ethylhexanoic acid, molybdenum salt in a manner proportionate to the free acid and the metal (represented by the readily soluble disodium molybdate, as detailed above).

 

Although the term „constituent“ within the REACH context is defined as substance (also being part of a mixture), the term constituent within this hazard assessment is meant to describe either part of the metal carboxylate salt, i.e. anion or cation.

Sensitisation

No skin sensitisation study with 2-ethylhexanoic acid, molybdenum salt 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 2-ethylhexanoic acid, molybdenum salt and the individual constituents.

 

Disodium molybdate

(CAS# 7631-95-0)

2-ethylhexanoic acid

(CAS# 149-57-5)

2-ethylhexanoic acid, molybdenum salt
(CAS# 34041-09-3)

Skin sensitisation

not sensitising

not sensitising

not sensitising

(read-across)

 

2-ethylhexanoic acid, molybdenum salt is not expected to show signs of dermal sensitisation, since the two constituents molybdate and 2-ethylhexanoic acid have not shown any skin sensitisation potential in experimental testing. Thus, 2-ethylhexanoic acid, molybdenum salt 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.


Migrated from Short description of key information:
2-ethylhexanoic acid, molybdenum salt is not expected to show signs of dermal sensitisation.

Justification for selection of skin sensitisation endpoint:
Read-across information.

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:

a)           clinical history and data from appropriate lung function tests related to exposure to the substance, confirmed by other supportive evidence which may include:

i.             in vivo immunological test (e.g. skin prick test);

ii.            in vitro immunological test (e.g. serological analysis);

iii.           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;

iv.          a chemical structure related to substances known to cause respiratory hypersensitivity;

b)           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.


Migrated from Short description of key information:
2-ethylhexanoic acid, molybdenum salt is not expected to show a respiratory sensitising potential.

Justification for classification or non-classification

2-ethylhexanoic acid, molybdenum salt is not expected to show signs of dermal sensitisation, since the two constituents molybdate and 2-ethylhexanoic acid have not shown any skin sensitisation potential in experimental testing. Thus, 2-ethylhexanoic acid, molybdenum salt is not to be classified according to regulation (EC) 1272/2008 as skin sensitising.

In long-time industrial experience in the production and handling of substance 2-ethylhexanoic acid, molybdenum salt, no cases of respiratory hypersensitivity have been observed.Classification as respiratory sensitiser is not applicable.

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