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Key value for chemical safety assessment

Additional information

There were no informations available for the assessment of the genotoxic potential of 2-EHAc itself. However, there were reliable data available from the structural analogon and metabolite 2-ethylhexan-1-ol to assess the genotoxic potential of 2-EHAc.

 

In vitro

Gene mutation in bacteria

A GLP conform Ames test was performed with Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 comparable to OECD guideline 471 (TSCATS OTS 0515130, 1987). Doses of up to 5000 µg 2-ethylhexan-1-ol (unknown purity) per plate were dissolved in ethanol and tested with and without S-9 mix as metabolic activation system. 2-ethylhexan-1-ol did not increase the number of revertants in any strain and was therefore not mutagenic in the Ames test. Cytotoxicity and precipitation was observed generally in the highest dose.

 

Gene mutation in mammalian cells

A GLP conform HGPRT test was performed with Chinese hamster ovary cells (CHO) comparable to OECD guideline 476 (CMA, 1985). Doses of up to 300 or 400 nL 2-ethylhexan-1-ol (unknown purity)/ mL were dissolved in acetone and tested with or without S-9 mix, respectively, as metabolic activation system. 2-ethylhexan-1-ol did not increase the mutant frequencies at the HGPRT locus and was therefore considered as inactive in the CHO/HGPRT test. Cytotoxicity was observed at 400 nL/mL.

 

Cytogenicity in mammalian cells

A GLP conform UDS test was performed with rat hepatocytes comparable to OECD guideline 486 (TSCATS OTS 0515130, 1987). Doses of up to 1000 nL 2-ethylhexan-1-ol (unknown purity)/ mL were dissolved in DMSO and tested without metabolic activation system. 2-ethylhexan-1-ol did not increase the levels of unscheduled DNA synthesis in rat hepatocytes in the range of 2.5 to 250 nL/mL and was therefore considered as inactive in the UDS test. Cytotoxicity was observed at >= 500 nL/mL.

 

In vivo

Cytogenicity

A GLP conform micronucleus test was performed in B6C3F1 mice comparable to OECD guideline 474 (CMA, 1982). A dose of 456 mg 2-ethylhexan-1-ol (unknown purity)/ kg bw were dissolved in corn oil and administered i.p. either as single application or as multiple application twice within 24 hours into six animals per sex per treatment. Bone marrow cells were harvested 30 h after the single application or 24 h after the second application. With one exception (multiple treatment males), there was no significant difference in percent micronucleated polychromatic erythrocytes (PCEs) between animals dosed with the test substance and the corresponding negative control. In this treatment, the corresponding negative control in males was very low, and the corresponding negative female control produced comparable percent micronucleated polychromatic erythrocytes (PCEs) as the test substance treated males. Moreover, the percent micronucleated PCEs in the multiple treated males is not very high and in the range of historical control data. Thus, the observed increase was viewed as a statistical artifact with little biological significance. Thus, 2-ethylhexan-1-ol was not considered to be clastogenic under the conditions of this assay.

 

A GLP conform chromosome aberration assay was performed in Fischer 344 rats comparable to OECD guideline 475 (TSCATS OTS 0515130, 1987). Doses of ca. 16.6, 58.1 and 174.3 mg 2-ethylhexan-1-ol (purity 99.7%)/ kg bw were dissolved in corn oil and administered per gavage on five consecutive days to 5 animals per sex per dose. Bone marrow cells were arrested in C-metaphases by administration of colchicina two hours prior to sacrifice. After examination of 50 metaphases per animal, 2-ethylhexan-1-ol did not cause aberrations in rat bone marrow cells and was therefore considered as inactive under the conditions of this assay.

Read across justification to 2-ethylhexan-1-ol for filling data gaps of 2-ethylhexyl acetate:

As indicated by toxicokinetic studies (see chapter on toxicokinetics, metabolism and distribution), 2-ethylhexyl acetate is rapidly hydrolyzed to 2-ethyhexan-1-ol and acetate (acetic acid). Available data on 2-ethyhexan-1-ol is therefore suitable for filling data gaps of 2-ethylhexyl acetate.


Short description of key information:
in vitro
Gen mutation in bacteria
Ames test, S. typhimurium TA 1535, TA 1537, TA 100, TA 98 with and without metabolic activation: negative (GLP, comp. OECD 471; TSCATS OTS 0515130, 1987)
Gene mutation in mammalian cells
HGPRT test, Chinese hamster ovary cells (CHO) with and without metabolic activation: negative (GLP, comp. OECD 476; CMA, 1985)
Cytogenicity in mammalian cells
UDS test, rat hepatocytes without metabolic activation: negative (GLP, comp. OECD 486; TSCATS OTS 0515130, 1987)

in vivo
Cytogenicity
MNT, i.p. B6C3F1 mouse: negative (GLP, comp. OECD 474; CMA, 1982)
CA, oral F344 rat: negative (GLP, comp. OECD 475; TSCATS OTS 0515130, 1987)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to the available test results for the analogous substance 2-ethylhexan-1-ol, 2-EHAc has not to be classified for genetic toxicity following 67/548/EEC and GHS requirements, respectively.