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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No experimental data was identified following an extensive literature review for 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) for genetic toxicity in vitro. Subsequently, three expert assessments were undertaken for gene mutation in bacteria, cytogenicity / chromosome aberration in mammalian cells, and gene mutation in mammalian cells based on available information identified for the parent acid and amine components of the registered substance; 2-ethylhexanoic acid and 2-aminoethanol. Given that 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) will dissociate in the event of exposure, its genotoxicity is anticipated to be driven by any genotoxic properties possessed by 2-ethylhexanoic acid and 2-aminoethanol. The evidence reviewed infers that 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) is not expected to induce gene mutation in bacteria, nor gene mutation and structural chromosomal aberration in mammalian cells, with and without metabolic activation, up to the respective maximum doses tested. 2-Ethylhexanoic acid, compound with 2-aminoethanol (1:1) is not considered to be a mutagen. An experimental study for genetic toxicity in vitro is subsequently not required.

Link to relevant study records

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Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
other: Expert assessment
Adequacy of study:
key study
Study period:
May 25, 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: An assessment was performed for 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) based on experimental data identified for its parent acid and amine components.
Qualifier:
no guideline required
Principles of method if other than guideline:
An assessment was undertaken to determine the capacity of 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) to induce chromosome aberration in mammalian cells by review of reliable experimental data identified in the literature for the parent acid and amine components; 2-ethylhexanoic acid and 2-aminoethanol.
Type of assay:
in vitro mammalian chromosome aberration test
Key result
Species / strain:
other: Rat lymphocyte cells; rat hepatocytes (RL4)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: 2-Ethylhexanoic acid and 2-aminoethanol did not induce gene mutation in bacteria with and without metabolic activation.
Conclusions:
An assessment was undertaken based on experimental data identified for the parent acid and amine components; 2-ethylhexanoic acid and 2-aminoethanol, of 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1). The registered substance is not expected to induce structural chromosomal aberration in mammalian cells and an experimental study is not required.
Executive summary:

To fulfil Annex VIII of REACH Regulation (EC) No. 1907/2007, the capacity of 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) to induce structural chromosomal aberration in mammalian cells was evaluated. No experimental data was identified for 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) for structural chromosomal aberration in mammalian cells following an extensive review. Therefore, experimental data identified for the parent acid and amine components; 2-ethylhexanoic acid and 2-aminoethanol, relating to in vitro structural chromosomal aberration in mammalian cells was reviewed for the purpose of the endpoint assessment. Given that the registered substance will dissociate in the event of exposure and its acid and amine components will behave independently in water, the mutagenicity of 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) is anticipated to be driven by 2-ethylhexanoic acid and 2-aminoethanol. The study results indicated that the components were negative for structural chromosomal aberration in mammalian cells with and without metabolic activation and were regarded as reliable without restriction (Klimisch score = 1) or reliable with restrictions (Klimisch score = 2). According to the activity of the two components, 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) is not expected to induce structural chromosomal aberration in mammalian cells. An experimental study is not required.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
other: Expert assessment
Adequacy of study:
key study
Study period:
May 25, 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: An assessment was performed for 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) based on experimental data identified for its parent acid and amine components.
Qualifier:
no guideline required
Principles of method if other than guideline:
An assessment was undertaken to determine the capacity of 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) to induce gene mutation in bacteria by review of reliable experimental data identified in the literature for the parent acid and amine components; 2-ethylhexanoic acid and 2-aminoethanol.
Type of assay:
bacterial reverse mutation assay
Key result
Species / strain:
other: Salmonella typhimurium and Escherichia coli
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: 2-Ethylhexanoic acid and 2-aminoethanol did not induce gene mutation in bacteria with and without metabolic activation.
Conclusions:
Based on an assessment of experimental data identified for the parent acid and amine components; 2-ethylhexanoic acid and 2-aminoethanol, of 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1), the registered substance is not expected to induce gene mutation in bacteria. An experimental study is subsequently not required.
Executive summary:

An assessment was undertaken in order to determine the capacity of 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) to induce gene mutation in bacteria, as required under Annex VII of REACH Regulation (EC) No. 1907/2007. No available experimental data was identified following an extensive literature review for 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) for this endpoint. As the registered substance will dissociate in the event of exposure, its genotoxicity is expected to be driven by the genotoxicity of its parent acid and amine components; 2-ethylhexanoic acid and 2-aminoethanol. Reliable experimental data (Klimisch score = 1 or 2) was identified for 2-ethylhexanoic acid and 2-aminoethanol and the studies were performed in line with, or were similar / equivalent to, recommended OECD and Japanese guidelines. The results for either component were negative for gene mutation in all tested bacterial strains up to the maximum dose tested and no significant increase in revertant colony frequency was reported in the experimental data with and without metabolic activation. According to the activity of 2-ethylhexanoic acid and 2-aminoethanol, the evidence reviewed in this endpoint assessment infers that 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) is not expected to induce gene mutation in bacteria. An experimental study is subsequently not required.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
other: Expert assessment
Adequacy of study:
key study
Study period:
May 25, 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: An assessment was performed for 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) based on experimental data identified for its parent acid and amine components.
Qualifier:
no guideline required
Principles of method if other than guideline:
An assessment was undertaken to determine the capacity of 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) to induce gene mutation in mammalian cells by review of reliable experimental data identified in the literature for the parent acid and amine components; 2-ethylhexanoic acid and 2-aminoethanol.
Type of assay:
other: In vitro mammalian cell gene mutation test
Key result
Species / strain:
other: Chinese hamster ovary (CHO) cell line (sub-strain K3); mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: 2-Ethylhexanoic acid and 2-aminoethanol did not induce gene mutation in bacteria with and without metabolic activation.
Conclusions:
2-Ethylhexanoic acid, compound with 2-aminoethanol (1:1) is not expected to induce gene mutation in mammalian cells based on an assessment of experimental data identified for the parent acid and amine components; 2-ethylhexanoic acid and 2-aminoethanol. An experimental study does not need to be conducted.
Executive summary:

The capacity of 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) to induce gene mutation in mammalian cells was evaluated to fulfil Annex VIII of REACH Regulation (EC) No. 1907/2007. No experimental data was identified in the literature for the registered substance for gene mutation in mammalian cells. As the registered substance will dissociate in water and its components will behave independently, its genotoxicity is anticipated to be driven by any genotoxic properties possessed by 2-ethylhexanoic acid and 2-aminoethanol. Experimental data was identified for both components, predominantly attained in compliance with GLP and according to OECD Guideline 476 or a method published by Trosko et al., (1984). 2-Ethylhexanoic acid and 2-aminoethanol was determined not to induce significant gene mutation in mammalian cells with and without metabolic activation up to the maximum dose tested. These results were assigned a Klimisch score of 1 (reliable without restriction) or 2 (reliable with restrictions). Based on the activity of its components, it is possible to conclude that 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1) is not likely to induce a gene mutation response in mammalian cells. An experimental study is subsequently not required.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No experimental data was identified for genetic toxicity in vivo following an extensive literature review for 2-ethylhexanoic acid, compound with 2-aminoethanol (1:1).

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification