Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-382-9 | CAS number: 106-30-9
Endpoint summary
Administrative data
Description of key information
The test item is not skin sensitising.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vitro
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study using a read-across test substance
- Justification for type of information:
- Read-across from ethyl hexanoate to ethyl heptanoate is considered justified based on strong similarities with regard to chemical structure and metabolic pathways. A full read-across justification including comparison of toxicological profiles is included in section 13 of the IUCLID dossier.
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Parameter:
- other: Luciferase activity
- Remarks on result:
- no indication of skin sensitisation
- Other effects / acceptance of results:
- After 48h of exposure to the source substance ethyl hexanote, luciferase activity in LuSens cells was not induced in at least two consecutive concentrations with statistical significance affording at least 70% viability in at least two independent experiments. It is hence not expected that the target substance ethyl heptanoate will have keratinocyte activating potential.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Read-across was done from ethyl hexanoate. Based on the result, and on the structural, chemical and toxicological similarities between ethyl hexanoate and ethyl heptanoate, ethyl heptanoate is not a sensitiser.
- Executive summary:
Read-across was done from ethyl hexanoate. In the current study the skin sensitising potential of ethyl hexanoate was assessed according to OECD 442D and GLP.
The keratinocyte activating potential of ethyl hexanoate was evaluated in the LuSens assay. Ethyl hexanoate was incubated with a luciferase reporter cell line (LuSens cells) for 48 hours at 37°C and the antioxidant response element (ARE) dependent luciferase activity was measured.
In order to determine the concentrations suitable for the main experiment a pre-test was performed in which cells were exposed to 9 concentrations and the cytotoxicity was determined by MTT assay. The CV75 value (=estimated concentration that affords 75% cell viability) was determined by linear regression from the concentration response curve.
In the main test the luciferase activity was measured and in parallel a MTT assay was performed to assess the cytotoxicity of ethyl hexanoate. The experiment was done in triplicate. Ethyl hexanoate was dissolved in 4% DMSO and in the end 1% DMSO was present in culture at all concentrations. No precipitates were noticed in any preparations. The acceptance criteria were met.
Exposure to ethyl hexanoate did not induce a statistical significant 1.5 fold increase in luciferase activity in LuSens cells while 70% viability was reached. In other words, ethyl hexanoate did not show any keratinocyte activating potential.
Based on the result, and on the structural, chemical and toxicological similarities between ethyl hexanoate and ethyl heptanoate, ethyl heptanoate is expected to not have a keratinocyte activating potential.
- Endpoint:
- skin sensitisation: in chemico
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study using a read-across test substance
- Justification for type of information:
- Read-across from ethyl hexanoate to ethyl heptanoate is considered justified based on strong similarities with regard to chemical structure and metabolic pathways. A full read-across justification including comparison of toxicological profiles is included in section 13 of the IUCLID dossier.
- Reason / purpose for cross-reference:
- read-across source
- Run / experiment:
- other: C-containing peptide (mM)
- Parameter:
- other: Peptide depletion
- Value:
- -0.52
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Run / experiment:
- other: K-containing peptide (mM)
- Parameter:
- other: Peptide depletion
- Value:
- -0.04
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Parameter:
- other: Mean peptide depletion
- Value:
- 0
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Other effects / acceptance of results:
- The mean peptide depletion of the positive control was 34.77%.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Read-across was done from ethyl hexanoate. Based on the result, and on the structural, chemical and toxicological similarities between ethyl hexanoate and ethyl heptanoate, ethyl heptanoate is not a sensitiser.
- Executive summary:
Read-across was done from ethyl hexanoate. The skin sensitisation effect of ethyl hexanoate was assessed in an in chemico assay according to OECD 442C.
This method quantifies the remaining concentrations of cysteine- or lysine-containing peptides after 24 hours incubation with ethyl hexanoate at 25 +/-2.5 °C. The percentage of depletion of cysteine- and lysine-peptides is calculated and used in a prediction model to assign ethyl hexanoate to one of four reactivity classes and in this way discriminate between sensitisers and non-sensitisers.
Ethyl hexanoate was dissolved at a 100 mM concentration in acetonitrile (ACN) and 3 samples were incubated with a typical concentration of 0.667 mM of cysteine in a pH 7.5 phosphate buffer or 0.667 mM of lysine in a pH 10.2 ammonium acetate buffer. Incubation was done for 24 hours in the dark at 25 +/- 2.5°C. The remaining non-depleted concentrations were determined by HPLC with gradient elution and UV-detector at 220 nm.
The mean C-peptide depletion, caused by ethyl hexanoate was determined to be -0.52%.
The mean K-peptide depletin, caused by ethyl hexanoate was determined to be -0.04%.
Negative depletions are considered to be "zero" for the calculation of the mean peptide depletion, resulting in 0.0% for the RA susbstance. Based on the results and the prediction model, it is concluded that ethyl hexanoate shows no chemical reactivity in the DPRA test under the current conditions.
Based on the result, and on the structural, chemical and toxicological similarities between ethyl hexanoate and ethyl heptanoate, ethyl heptanoate is not expected to show chemical reactivity in the DPRA test.
- Endpoint:
- skin sensitisation: in vitro
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study using a read-across test substance
- Justification for type of information:
- Read-across from ethyl hexanoate to ethyl heptanoate is considered justified based on strong similarities with regard to chemical structure and metabolic pathways. A full read-across justification including comparison of toxicological profiles is included in section 13 of the IUCLID dossier.
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Parameter:
- other: dendritic cell activation
- Remarks on result:
- positive indication of skin sensitisation
- Other effects / acceptance of results:
- After 24 hours of exposure to test substance, 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 induces dendritic cell activation. For a full overview of the experimental results, please see below
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- Read-across was done from ethyl hexanoate. Based on the result, and on the structural, chemical and toxicological similarities between ethyl hexanoate and ethyl heptanoate, ethyl heptanoate induces dendritic cell activation.
- Executive summary:
Read-across was done from ethyl hexanoate. The skin sensitisation potential of ethyl hexanoate was assessed according to the new OECD 442E TG.
The potential of ethyl hexanoate to induce the cell membrane markers CD86 and CD54 expression was evaluated in the human Cell Line Test (h-CLAT). Ethyl hexanoate was incubated with the human pro-monocytic cell line THP-1 for 24 hours at 37°C and the membrane markers expression was measured by flow cytometry through staining with FITC labeled anti-human-CD86/anti human CD54 antibody and propidium iodide.
In order to determine the concentration suitable for the main test a pre-test was performed.
The CV75 value (= estimated concentration that affords 75% cell viability) was determined by linear regression from the concentration response curve.
In the main experiment ethyl hexanoate was tested at concentrations of 566 μg/mL onwards. No precipitates were noticed in any concentration after 24 hours.
Relative fluorescence intensity and concurrent relative viability were determined in 2 main experiments. 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.
After 24 hours of exposure, ethyl hexanoate induced CD54 expression in THP-1 cells with 83% viability in two independent experiments. Therefore, it was concluded that ethyl hexanoate induces dendritic cell activation.
Based on the result, and on the structural, chemical and toxicological similarities between ethyl hexanoate and ethyl heptanoate, ethyl heptanoate is expected to induce dendritic cell activation.
Referenceopen allclose all
Mean value and standard deviation for 1st experiment:
| Concentration (test substance) µg/mL | RFI CD86 | RFI CD54 | Rel. Viability (%) | SD of viability | ||
| mean | SD | mean | SD | |||
| 515.82 | 169.9 | 20.3 | 320.5 | 6.8 | 89.0 | 2.8 |
| 618.80 | 180.6 | 29.0 | 288.5 | 62.3 | 75.4 | 1.3 |
| 742.74 | 160.8 | 13.2 | 395.5 | 16.5 | 67.6 | 4.8 |
| 890.38 | 150.9 | 0.8 | 333.3 | 22.8 | 14.6 | 1.4 |
| 1069.00 | 221.5 | 1.8 | 418.7 | 106.4 | 53.0 | 23.8 |
| 1283.16 | 198.4 | 28.8 | 582.5 | 72.4 | 63.7 | 9.8 |
| 1539.25 | 218.4 | 19.5 | 607.1 | 78.6 | 53.0 | 3.3 |
| 1847.28 | 78.0 | 114.5 | 506.4 | 38.1 | 39.3 | 2.4 |
| VC | 100.0 | - | 100.0 | - | 100.0 | 0.2 |
| LA 1000 µg/mL | 79.5 | 10.7 | 124.1 | 25.5 | 99.6 | 0.2 |
| DNCB 4µg/mL | 311.9 | 88.5 | 368.1 | 70.2 | 82.1 | 3.7 |
Mean value and standard deviations fo 2nd experiment:
| Concentration (test substance) µg/mL | RFI CD86 | RFI CD54 | Rel. Viability (%) | SD of viability | ||
| mean | SD | mean | SD | |||
| 298.01 | 102.1 | 4.6 | 240.7 | 15.3 | 100.4 | 0.3 |
| 358.16 | 96.1 | 0.1 | 236.4 | 41.8 | 100.3 | 0.3 |
| 429.24 | 106.3 | 3.4 | 382.3 | 47.8 | 100.0 | 0.1 |
| 515.82 | 100.2 | 1.3 | 364.9 | 189.4 | 99.7 | 0.1 |
| 618.80 | 107.2 | 4.7 | 422.1 | 66.3 | 98.3 | 0.8 |
| 742.74 | 127.0 | 9.8 | 557.8 | 89.0 | 78.5 | 3.9 |
| 890.38 | 130.0 | 12.2 | 737.3 | 65.9 | 71.0 | 0.9 |
| 1069.00 | 129.1 | 5.7 | 592.7 | 150.1 | 56.2 | 1.7 |
| VC | 100.0 | - | 100.0 | - | 100.0 | 100.0 |
| LA 1000 µg/mL | 66.9 | 1.4 | 104.9 | 14.2 | 100.3 | 0.2 |
| DNCB 4µg/mL | 300.0 | 19.7 | 392.6 | 0.9 | 84.4 | 1.1 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
For this endpoint a human maximization study on ethyl heptanoate is available as well as in vitro skin sensitization tests (in chemico DPRA, in vitro LuSens and in vitro h-CLAT test) on ethyl hexanoate. Therefore, read-across (RA) was done from ethyl hexanoate and the results on ethyl hexanoate are used for the classification of ethyl heptanoate taking into account the human maximization study on ethyl heptanoate.
DPRA:
The reactivity of ethyl hexanoate towards synthetic cysteine or lysine containing peptides was evaluated in the DPRA test according to OECD 442C. The percentage of depletion of cysteine- and lysine-peptides is calculated and used in a prediction model to assign the test item to one of four reactivity classes and discriminate between sensitisers and non-sensitisers.
The mean C- and K-peptide depletion was below 0.0%. Negative depletions are considered to be "zero" for the calculation of the mean peptide depletion. Ethyl hexanoate shows no chemical reactivity in the DPRA under the current test conditions.
Based on the result, and on the structural, chemical and toxicological similarities to ethyl hexanoate, ethyl heptanoate is not expected to show chemical reactivity in the DPRA test.
LuSens:
The keratinocyte activating potential of ethyl hexanoate was evaluated in the LuSens assay according to OECD 442D. Ethyl hexanoate was incubated with a luciferase reporter cell line (LuSens cells) for 48 hours at 37°C and the antioxidant response element (ARE) dependent luciferase activity was measured.
Ethyl hexanoate did not precipitate in the experiment and the acceptance criteria were met. Ethyl hexanoate did not induce a statistical significant increase in luciferase activity in LuSens cells in two consecutive concentrations, while the 70% viability was reached. From this it is concluded that ethyl hexanoate does not have keratinocyte activating potential.
Based on the result, and on the structural, chemical and toxicological similarities between ethyl hexanoate and ethyl heptanoate, ethyl heptanoate is not expected to have keratinocyte activating potential.
h-CLAT:
The potential of ethyl hexanoate to induce cell membrane markers CD86 and CD54 expression was evaluated in the human cell line activation test according to the new OECD 442E TG. Ethyl hexanoate was incubated with the human pro-monocytic cell line THP-1 for 24 hours at 37°C and the membrane markers expression was measured by flow cytometry through staining with FITC labeled anti-human-CD86/anti human CD54 antibody and propidium iodide.
Ethyl hexanoate was tested at concentrations of 566 μg/mL onwards and no precipitates were noticed in any concentration. Relative fluorescence intensity and concurrent relative viability were determined. Ethyl hexanoate induced CD54 expression in THP-1 cells with 83% viability. Therefore, it was concluded that ethyl hexanoate induces dendritic cell activation.
Based on the result, and on the structural, chemical and toxicological similarities between ethyl hexanoate and ethyl heptanoate, ethyl heptanoate induces dendritic cell activation.
Maximisation test:
A human maximisation test, with 25 healthy male and female volunteers between 18 and 47 years old, was performed with a dose of 8% of ethyl heptanoate. No sensitization reactions were observed in any of the volunteers, indicating that the substance is not a sensitiser.
Conclusion:
To come to a conclusion the results of the 3 individual in vitro assays need to be taken together as they reflect the 3 key events in the adverse outcome pathway (AOP) leading to skin sensitisation. For this reason, a weight of evidence approach is applied for the test battery stating that: 'any two of the three tests determine the overall results, i.e. any two positive results drive the prediction of a sensitizer, while any two negative results drive the prediction of a test substance to be a non-sensitizer'.
Ethyl hexanoate is not peptide reactive, does not activate keratinocytes, however activates dendritic cells. Taking together and applying the evaluation criteria described above, ethyl hexanoate is predicted not to be a skin sensitizer. Due to the read-across strategy it can be concluded that ethyl heptanoate is also not a sensitiser. The supporting human maximisation study confirms the conclusion that ethyl heptanoate is not a skin sensitiser.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Regarding the classification of the substance for skin sensitisation the results of the three individual assays of the in vitro skin sensitisation test battery need to be taken together as they reflect three key events in the adverse outcome pathway leading to skin sensitisation. For this reason, a weight of evidence approach is applied for the test battery stating that: 'any two of the three tests determine the overall restuls, i.e. any two positive results drive the prediction of a sensitizer, while any two negative results drive the prediction of a test substance to be a non-sensitizer'.
Due to the RA strategy it can be stated that ethyl heptanoate is not peptide reactive, does not activate keratinocytes, however activates dendritic cells. Taking together the results and applying the evaluation criteria described above, the test substance is predicted not to be a skin sensitizer.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
