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EC number: 268-820-3 | CAS number: 68140-98-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
According to the current OECD Guideline No. 439, 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol is considered as non-irritant to skin and is therefore not classified.
The test item 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4- methanol showed no effects on the cornea of the bovine eye.
Under the conditions of the EpiOcularTM Eye Irritation Test, 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol is considered non- eye irritant and is therefore not classified.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 13 December 2017-10 April 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: EpiSkinTMSM, EPISKIN SNC Lyon, France.
- Details on animal used as source of test system:
- Adult human-derived epidermal keratinocytes are seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV
collagen. - Justification for test system used:
- The EPISKIN model has been validated for irritation testing in an international trial. After a review of scientific reports and peer reviewed publications on the EPISKIN method, it showed evidence of being a reliable and relevant stand-alone test for predicting rabbit skin irritation, when the endpoint is evaluated by MTT reduction and for being used as a replacement for the Draize Skin Irritation test (OECD TG 404 and Method B.4 of Annex V to Directive 67/548/EEC) for the purposes of distinguishing between skin irritating and no skin irritating test substances (STATEMENT OF VALIDITY OF IN-VITRO TESTS FOR SKIN IRRITATION; ECVAM; Institute for Health & Consumer Protection; Joint Research Centre; European Commission; Ispra; 27 April 2007).
- Details on test system:
- Disks of epidermal units (three units) were treated with the test item and incubated for 15 minutes at room temperature. Exposure of the test material was terminated by rinsing the epidermal units with 1x PBS solution. Epidermis units were then incubated at 37±1 °C for 42 hours in an incubator with 5±1 % CO2. The viability of each disk was assessed by incubating the tissues for 3 (±5 min) hours with MTT solution at 37±1 °C in 5±1 % CO2 and protected from light. The resulting formazan crystals were extracted with acidified isopropanol and quantified with the optical densities (OD) recorded spectrophotometrically.
SDS 5 % aq. and 1 x PBS treated (three units / positive and negative control) epidermis units were used as positive and negative controls, respectively. For each treated tissue, viability was expressed as a percentage relative to negative control.
The test item has an intrinsic colour (brown), therefore two additional test item treated tissues were used for the non-specific OD evaluation.
The test item is a possible MTT-reducer, therefore additional controls (test item treated killed tissues and negative control treated killed
tissues) were used to detect and correct for test substance interference with the viability measurement.
The test item is a possible MTT-reducer and has an intrinsic colour (brown). To avoid a possible double correction [TODTT (MTT and
NSC)] for colour interference, a third control for non-specific colour in killed tissues (NSCkilled) was performed. Two killed treated tissues were used to avoid a possible double correction for colour interference. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- 10 μL undiluted test item
Application (day 0):
- Test Item
A volume of 10 μL undiluted test item was applied evenly to the epidermal surface of each of the three test skin units.
- Positive and negative control
A volume of 10 μL positive control (SDS 5 % aq.) or negative control (1 x PBS) was applied to the skin surface by using a suitable pipette. - Duration of treatment / exposure:
- Exposure (day 0): The plates with the treated epidermis units were incubated for the exposure time of 15 minutes at room temperature.
- Duration of post-treatment incubation (if applicable):
- Post-incubation (day 0-2):
After rinsing the units were placed into the plate wells filled with fresh pre-warmed “maintenance medium” (2 mL/well)
below them and then incubated for 42 hours at 37±1°C in an incubator with 5±1 % CO2, ≥ 95 % humidified atmosphere. - Number of replicates:
- Number of replicate wells:
- 3 replicates per test item
- 3 replicates negative controls,
- 3 replicates positive controls,
- 2 replicates colour controls and 2 replicates non-specific colour control
- 3 killed treated tissues and 3 killed negative control tissues (for the MTT evaluation) - Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Test item
- Value:
- > 77 - < 93
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The results obtained from this in vitro skin irritation test, using the EPISKIN model, indicated that the test item reveals no skin
irritation potential under the utilized testing conditions. According to the current OECD Guideline No. 439, 4-ethyl-2-(8-
heptadecenyl)-2-oxazoline-4-methanol is considered as non-irritant to skin and is therefore not classified. - Executive summary:
The purpose of this study was to determine the skin irritation potential of the test item 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol on reconstituted human epidermis in the EPISKIN model in vitro.
Disks of epidermal units (three units) were treated with the test item and incubated for 15 minutes at room temperature. Exposure of the test material was terminated by rinsing the epidermal units with 1x PBS solution. Epidermis units were then incubated at 37±1 °C for 42 hours in an incubator with 5±1 % CO2. The viability of each disk was assessed by incubating the tissues for 3 (±5 min) hours with MTT solution at 37±1 °C in 5±1 % CO2 and protected from light. The resulting formazan crystals were extracted with acidified isopropanol and quantified with the optical densities (OD) recorded spectrophotometrically.
SDS 5 % aq. and 1 x PBS treated (three units / positive and negative control) epidermis units were used as positive and negative controls, respectively. For each treated tissue, viability was expressed as a percentage relative to negative control.
The test item has an intrinsic colour (brown), therefore two additional test item treated tissues were used for the non-specific OD evaluation.
The test item is a possible MTT-reducer, therefore additional controls (test item treated killed tissues and negative control treated killed tissues) were used to detect and correct for test substance interference with the viability measurement.
The test item is a possible MTT-reducer and has an intrinsic colour (brown). To avoid a possible double correction [TODTT (MTT and NSC)] for colour interference, a third control for non-specific colour in killed tissues (NSCkilled) was performed. Two killed treated tissues were used to avoid a possible double correction for colour interference.
The test chemical is identified as requiring classification and labelling according to UN GHS (Category 2 or Category 1), if the mean relative viability after 15 minutes exposure and 42 hours post incubation is less or equal (≤) to 50 % when compared to the viability values obtained from the negative control.
In this in vitro skin irritation test using the EPISKIN model, the test item 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol did not show significantly reduced cell viability in comparison to the negative control (mean relative viability: 82 %). All obtained test item viability results were above 50 % when compared to the viability values obtained from the negative control. Therefore the test item was considered to be non-irritant to skin.
Positive and negative controls showed the expected cell viability values within acceptable limits. The experiment was considered to be valid.
Reference
Cell viability
The results of the optical density (OD) measured at 570 nm of each replicate and the calculated % viability of the cells are presented below:
OD values and viability percentages of the controls:
Substance |
Optical Density (OD) |
Viability (%) |
|
Negative Control:1x PBS |
1 |
1.12818 |
98 |
|
2 |
1.26353 |
109 |
|
3 |
1.07298 |
93 |
|
mean |
1.15490 |
100 |
standard deviation (SD) |
8.49 |
||
Positive Control:SDS (5 % aq.) |
1 |
0.09848 |
9 |
|
2 |
0.06408 |
6 |
|
3 |
0.06213 |
5 |
|
mean |
0.07490 |
6 |
|
standard deviation (SD) |
1.77 |
OD values and viability percentages of the test item (including corrected values):
Test Item |
Optical Density (OD) |
TODTT |
Viability (%) |
Relative Viability (%) |
|
4-ethyl-2- (8-heptadecenyl)-2- oxazoline-4- methanol |
1 |
0.90010 |
0.89788 |
78 |
78 |
|
2 |
1.07165 |
1.06943 |
93 |
93 |
|
3 |
0.88670 |
0.88448 |
77 |
77 |
|
mean |
0.952817 |
0.95060 |
83 |
82 |
|
standard deviation (SD) |
|
8.93 |
8.93 |
OD values of additional controls for MTT-interacting test item:
Additional controls |
Optical Density (OD) |
|
Negative control killed tissues:1x PBS |
1 |
0.10193 |
|
2 |
0.05473 |
|
3 |
0.05963 |
|
mean |
0.07210 |
Test item treated killed tissues:4-ethyl-2-(8-heptadecenyl)-2- oxazoline-4-methanol |
1 |
0.05955 |
|
2 |
0.10325 |
|
3 |
0.06015 |
|
mean |
0.07432 |
OD values and NSC % of additional control:
Additional colour control |
Optical Density (OD) |
Non Specific Colour %(NSC %) |
|
4-ethyl-2-(8-heptadecenyl)-2- oxazoline-4-methanol(test item treated tissues without MTT incubation) |
1 |
0.00905 |
2.8 |
|
2 |
0.05575 |
|
|
mean |
0.03240 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Remarks:
- OEDC 437
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- May 2018-November 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- cattle
- Details on test animals or tissues and environmental conditions:
- Fresh bovine eyes were obtained from the slaughterhouse Müller Fleisch GmbH, Enzstr. 2-4, 75217 Birkenfeld, Germany, on the day of the test. The cattle were between 12 and 60 months old. The eyes were transported to the test facility in Hanks’ Balanced Salt Solution with 1% Penicillin-Streptomycin solution (Penicillin 100 U/mL, Streptomycin 100 μg/mL) in a suitable cooled container within 1 hour.
- Vehicle:
- Hank's balanced salt solution
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 μL
- Concentration (if solution): without dilution
NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 μL
- Concentration (if solution): Hank’s Balanced Salt Solution (HBSS) 10-fold concentrated, diluted in demin. water (1:10), batch no.: 20180607
POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 μL
- Concentration (if solution): Dimethylformamide, DMF, CAS-No. 68-12-2, undiluted, batch no.: 475235719 - Duration of treatment / exposure:
- Exposure time of test item on corneas: 10 minutes at 32 ± 1 °C.
- Number of animals or in vitro replicates:
- three replicates
- Details on study design:
- Closed Chamber Method
The respective substance (negative control solution, test item or positive control) was applied by pipetting 750 μL of the appropriate liquid through the refill hole in the holder on the cornea. The test item was given on the epithelium in such a manner that as much as possible of the cornea was covered with the test item.
Exposure time of the test item on the corneas was 10 minutes at 32 ± 1 °C. After thorough rinsing with cMEM with phenol red and final rinsing with cMEM without phenol red, the anterior chamber was filled with cMEM without phenol red, and the corneas were stored for additional 2 hours at 32 ± 1 °C (post-incubation).
After post-incubation time, the cMEM without phenol red was renewed in both chambers. Then, the final opacity value of each cornea was recorded.
Permeability Test
After the recording of the final opacity value, the cMEM without phenol red was removed from the front chamber, and 1 mL sodium fluorescein solution was added to the front chamber for the detection of permeability of the corneas.
For the closed chamber method, a sodium fluorescein solution with a concentration of 4 mg/mL was used.
The chambers were then closed again and incubated for 90 minutes at 32 ± 1 °C.
After incubation, the content of the posterior chamber was thoroughly mixed. Then, its optical density at 492 nm was measured with the microtiter plate photometer.
SELECTION AND PREPARATION OF CORNEAS
- only corneas which were free from damages were used
- corneas were excised with a scalpel and cut from the globe with a 2-3 mm ring of sclera around the outside.
NUMBER OF REPLICATES
- there replicates
NEGATIVE CONTROL USED
yes
POSITIVE CONTROL USED
yes
TREATMENT METHOD: closed chamber
POST-INCUBATION PERIOD: yes, 2 hours at 32 ± 1 °C
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD at 492nm)
SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
VALIDITY: The test is considered as valid if the positive control causes an IVIS that falls within two standard deviations of the current historical mean. The mean IVIS of the negative control has to show an IVIS ≤ 3. - Irritation parameter:
- in vitro irritation score
- Value:
- 0.39
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes: Hank’s Balanced Salt Solution (HBSS): no irritating effect on the cornea, IVIS (In Vitro Irritancy Score) = 1.34.
- Acceptance criteria met for positive control: yes: Dimethylformamide (DMF) undiluted: serious eye damage on the cornea, IVIS = 120.36 (within two standard deviations of the current historical mean) - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol showed no effects on the cornea of the bovine eye. The calculated IVIS (In Vitro Irritancy Score) is 0.39. According to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS ≤ 3 requires no classification for eye irritation or serious eye damage.
- Executive summary:
The test item 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol was brought onto the cornea of a bovine eye which had been previously incubated with cMEM without phenol red at 32 ± 1 °C for 1 hour and whose opacity had been measured. Bovine corneas used in this study were collected from slaughtered cattle that were between 12 and 60 months old.
The test item was incubated on the cornea for 10 minutes at 32 ± 1 °C. After removal of the test item and 2 hours post-incubation, opacity and permeability values were measured. One valid experiment was performed.
Hank’s Balanced Salt Solution (HBSS) was used as negative control. The negative control showed no irritating effect on the cornea and the calculated IVIS (In Vitro Irritancy Score) is 1.34.
Dimethylformamide (DMF) undiluted was used as positive control. The positive control induced serious eye damage on the cornea and was within two standard deviations of the current historical mean. The calculated IVIS is 120.36.
Under the conditions of this study, the test item 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4- methanol showed no effects on the cornea of the bovine eye. The calculated IVIS is 0.39.
According to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS ≤ 3 requires no classification for eye irritation or serious eye damage.
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14. Jun.2018-15. Nov 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- human
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- 50 µL
- Duration of treatment / exposure:
- Pre-Tests
- Assessment of Direct Reduction of MTT by the Test Item: 3 hours
- Assessment of Coloured or Staining Test Items: 3 hours
Main Test: 28 minutes - Duration of post- treatment incubation (in vitro):
- tissues were incubated for 115 minutes (main test)
- Number of animals or in vitro replicates:
- two tissue replicates
- Irritation parameter:
- other: relative tissue viability
- Value:
- 110.3
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- After treatment with the test item, the mean value of relative tissue viability was increased to 110.3%. This value is well above the threshold for eye irritation potential (≤ 60%).
Under the conditions of the test, 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol is considered non-eye irritant in the EpiOcularTM Eye Irritation Test. - Executive summary:
The test item 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol was applied to a threedimensional human cornea tissue model in duplicate for an exposure time of 28 minutes.
50 μL of the liquid test item were applied to two tissue replicates. One valid experiment was performed.
After treatment, the respective substance was rinsed from the tissue; then, cell viability of the tissues was evaluated by addition of MTT, which can be reduced to formazan. The formazan production was evaluated by measuring the optical density (OD) of the resulting solution.
Demineralised water was used as negative control and methyl acetate was used as positive control.
The controls showed the following results: After treatment with the negative control, the absorbance values were within the required acceptability criterion of mean OD > 0.8 and < 2.5, OD was 1.9. The positive control showed clear eye irritating effects, the mean value of the relative tissue viability was 34.7 % (< 50%).
Variation within tissue replicates of the controls and the test item was acceptable (< 20%).
After treatment with the test item, the mean value of relative tissue viability was 110.3 %.
This value is well above the threshold for eye irritation potential (≤ 60%). Test items that induce values above the threshold are considered non-eye irritant.
Under the conditions of the test, 4-ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol is considered non- eye irritant in the EpiOcularTM Eye Irritation Test.
Referenceopen allclose all
In the pre-test, potential MTT reduction by the test item was observed. This is why an additional test was performed to exclude wrong photometrical measurement values due to direct MTT reduction by the test item.
The additional test showed that the MTT reduction by the test item did not influence the result of the main test.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Additional information
Justification for classification or non-classification
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