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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:

Introductionto 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. 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.

 

Oxygen-free inorganic zirconium(IV) substances (ZrX4) are highly hygroscopic and rapidly decompose in damp atmosphere or water under formation of zirconyl compounds (ZrOX2and ZrO(OH)X). These zirconyl compounds further show an ageing under formation of zirconium dioxide (ZrO2). The zirconium dioxide is an inert metal oxide with a very low water solubility (<55µg/L) and is also the naturally occurring mineral baddeleyite.

The water solubility test (according to OECD 105 and under GLP, as presented under the respective endpoint in this dossier) with zirconium propionate confirmed the above described decomposition of inorganic zirconium salts under formation of insoluble zirconium dioxide. After 24h stirring at a loading of 100mg/L, the zirconium concentration of the samples was at 11.89 µg Zr/L.

It is concluded that localtoxicological effects of inorganic zirconium salts might be exerted solely due to the caustic properties of the concentrated resulting acid in the decomposition reaction (in this case propionic acid). Potential, local effects caused by zirconium propionate are addressed by substance-specific test data, whereas systemic effects are addressed by reading-across to the decomposition products, namely the propionate anion and zirconium dioxide.

 

Based on the above information, unrestricted read-across is considered feasible and justified.

 

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 zirconium propionate 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 zirconium propionate and the individual constituents.

 

Zirconium dioxide
(CAS# 1314-23-4)

Propionic acid

(CAS# 79-09-4)

Zirconium propionate(CAS# 84057-80-7)

Skin sensitisation

not sensitising

not sensitising

not sensitising

(read-across)

 

Zirconium propionate is not expected to show signs of dermal sensitisation, since the two constituents zirconium and propionic acid have not shown any skin sensitisation potential in experimental testing. Thus, zirconium propionate 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:

Zirconium propionate 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:

Zirconium propionate is not expected to show a respiratory sensitising potential.

Justification for classification or non-classification

Zirconium propionate is not expected to show signs of dermal sensitisation, since the two constituents zirconium and propionic acid have not shown any skin sensitisation potential in experimental testing. Thus, zirconium propionate is not to be classified according to regulation (EC) 1272/2008 as skin sensitising. Furthermore, zirconium propionate has not to be classified according toDirective 67/548 EC as skin sensitising.

In long-time industrial experience in the production and handling of substance zirconium propionate no cases of respiratory hypersensitivity have been observed. Classification as respiratory sensitiser is not applicable.

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