Registration Dossier
Registration Dossier
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EC number: 204-640-3 | CAS number: 123-66-0
Endpoint summary
Administrative data
Description of key information
As a weight of evidence approach, three in vitro assays were carried out, namely DPRA, LuSens and h-CLAT for a linear ethyl ester. The DPRA study was negative as the test substance showed no chemical reactivity under the current conditions. The LuSens assay showed a negative result regarding sensitization as the test substance did not have a keratinocyte activation potential. The h-CLAT assay was positive regarding sensitization as the substance activated dendritic cells.
Based on a weight of evidence approach according to Bauch et al 2012 two negative results drive the prediction of a test substance to be a non-sensitizer.
Bauch C. et al, (2012), Regul Toxicol Pharmacol, 63(3), 489 -504
Key value for chemical safety assessment
Skin sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
To evaluate the skin sensitisation effects of ethyl hexanoate a combination of 3 in vitro methods addressing the key events of the adverse outcome pathway (AOP) for skin sensitization were performed. The tests are the Direct Peptide Reactivity Assay (DPRA), the ARE Reporter Assay (LuSens) and the Dendritic Cell Line Activation Assay (h-CLAT).
DPRA test
In the DPRA test (OECD 442C) the reactivity of ethyl hexanoate towards synthetic cysteine (C)- or lysine (K)- containing peptides was evaluated. Incubation of the synthetic peptides with ethyl hexanoate was done for 24 hours and the remaining concentrations of cysteine- or lysine-containing peptides were determined.
The mean C-peptide depletion, caused by the test substance was determined to be -0.52%.
The mean K-peptide depletion, caused by the test substance was determined to be -0.04%.
Based on the observed results and applying the prediction model proposed in Gerberick et. al (2007) it is concluded that ethyl hexanoate shows no chemical reactivity in the DPRA test under the current conditions.
LuSens test
In the LuSens assay (OECD 442D) the keratinocyte activating potential of ethyl hexanoate was evaluated. Ethyl hexanoate was incubated with a luciferase reporter cell line (LuSens cells) for 48 hours and the antioxidant response element (ARE) dependent luciferase activity was measured, in parallel to a MTT assay to assess the cytotoxicity. No precipitates were noticed in any preparations. The acceptance criteria were met. After exposure to ethyl hexanoate, activity in LuSens cells was not induced significantly in at least two consecutive concentrations affording at least 70% viability in at least two independent experiments. It has to be concluded that test substance ethyl hexanoate does not have a keratinocyte activating potential.
h-CLAT test
In the third in vitro study (OECD 442E) the potential of ethyl hexanoate to induce the expression of the cell membrane markers CD86 and CD54 in the human Cell Line Test (h-CLAT) was evaluated. In the human pro-monocytic cell line THP-1 the change in the expression of the cell membrane markers is measured by flow cytometry after 24 hours of test substance exposure through staining with FITC labeled anti-human-CD86/anti human CD54 antibody and propidium iodide.
No precipitates were noticed at any concentration.Calculation of an EC150 (the concentration resulting in a RFI of 150) for CD86 and an EC200 (the concentration resulting in a RFI of 200) for CD54 was not applicable.
In summary, after 24 hours of exposure to test substance ethyl hexanoate CD54 expression was induced in THP-1 cells affording at least 50% viability in at least two independent experiments. From this it has to be concluded that test substance ethyl hexanoate induces dendritic cell activation.
The test battery evaluation uses the results of the three individual assays reflecting three key events along the adverse outcome pathway leading to skin sensitization. In the test battery a weight of evidence approach is made in such a way that any 2 out of 3 tests determine the overall result (2 positive test results drive the prediction of a sensitizer, while 2 negative test results drive the prediction of a non-sensitizer). In the case of ethyl hexanoate 2 of the tests are negative and 1 is positive. Applying the evaluation criteria ethyl hexanoate is predicted not to be a skin sensitizer.
Conclusion
Ethyl hexanoate is not considered to be a skin sensitizer.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the available in chemico and in vitro results, the substance is not classified as sensitising according to Regulation (EC) No 1272/2008.
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