Strontium bis(2-ethylhexanoate)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genetic toxicity study with strontium bis(2-ethylhexanoate) is available, thus the genetic toxicity will be addressed with existing data on the individual moieties strontium and 2-ethylhexanoic acid.

Strontium bis(2-ethylhexanoate) is not expected to be genotoxic, since the two moieties strontium and 2-ethylhexanoic acid have not shown gene mutation potential in bacteria and mammalian cells as well as in vivo cytogenicity.

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.

 

Strontium bis(2-ethylhexanoate) is the strontium salt of 2-ethylhexanoic acid, which readily dissociates to the corresponding divalent strontium cation and 2-ethylhexanoic acid anions. The strontium cation and the 2-ethylhexanoic acid anion are considered to represent the overall toxicity of strontium bis(2-ethylhexaate) 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.

 

Genetic toxicity

No genetic toxicity study with strontium bis(2-ethylhexanoate) is available, thus the genetic toxicity will be addressed with existing data on the individual moieties strontium and 2-ethylhexanoic acid as detailed below.

Strontium

The GLP conform bacterial reverse mutation assay performed according to OECD 471, the GLP conform in vitro mammalian cell micronucleus test performed according to OECD 487 and the GLP conform in vitro mammalian cell gene mutation assay performed according to OECD 476 showed that the test item strontium neodecanoate did not induce gene mutations and is not clastogenic and not aneugenic.

Thus, according to Regulation (EC) No 1272/2008 as amended, the test substance strontium neodecanoate is not considered to be genotoxic, and hence no classification or labelling is required. Because of the high solubility of strontium neodecanoate and its complete dissociation in aqueous media, these conclusions are also taken forward for the strontium ion.

 

2-ethylhexanoic acid

in vitro

2-ethylhexanoic acid was negative in the bacterial Ames test with S. typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 and E. coli WP2 uvr A (Jung et al., 1982; Zeiger et al., 1988; Warren et al., 1982), as well as in a HPRT locus assay with mammalian CHO cells (Schulz et al., 2007). In cultured human lymphocytes, 2-ethylhexanoic acid induced a minimal increase in frequency of sister-chromatid exchanges (below 1.5 fold increase at concentrations of the test substance of 0.63 to 2.5 mM; Sipi et al., 1992), which is not considered significant.

in vivo

In an in vivo micronucleus assay with mice, 2-ethylhexanoic acid was administered by gavage up to the maximum tolerated oral dose of 1600 mg/kg/day. No bone marrow toxicity was observed, nor did the test substance induce any bone marrow micronuclei (Holstrom et al., 1994).

 

Strontium bis(2-ethylhexanoate)

Strontium bis(2-ethylhexanoate) is not expected to be genotoxic, since the two moieties strontium and 2-ethylhexanoic acid have not shown gene mutation potential in bacteria and mammalian cells as well as in vivo cytogenicity. 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.

Justification for classification or non-classification

Strontium bis(2-ethylhexanoate) is not expected to be genotoxic, since the two moieties strontium and 2-ethylhexanoic acid have not shown gene mutation potential in bacteria and mammalian cells as well as in vivo cytogenicity.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, strontium bis(2-ethylhexanoate) does not have to be classified and has no obligatory labelling requirement for germ cell mutagenicity.