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EC number: 211-055-7 | CAS number: 628-81-9
- 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
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- Nanomaterial pour density
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- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
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- 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
The skin irritant potential of butyl ethyl ether (98.4 % purity) was analysed according to OECD 439 using the EPISKIN-Standard Model™ (EPISKIN-SMTM). Based on the results the target substance can be considered as non-irritant to the skin.
The eye irritation potential of butyl ethyl ether (98.4% purity) was examined in an in vivo study according to OECD 405. Only a slight irritant effect (grade 1) which was fully reversible within 6 days could be observed. Based on these results butyl ethyl ether can be considered as non-irritant to the eye.
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:
- 2016-11-10 to 2016-12-22
- 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
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- skin obtained from plastic surgery from multiple donors
- Justification for test system used:
- This test uses the EPISKIN-SM™ reconstructed human epidermis model (SkinEthic) which consists of normal human epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely mimics the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis. This test method is able to detect chemicals that cause skin irritation, i.e. produce reversible damage to the skin and allows for hazard identification in accordance with UN GHS "Category 2". Depending on the regulatory framework it can also be used to identify non-classified chemicals.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used:
The test was carried out with the reconstituted three-dimensional human skin model EPISKIN-SM™ (SkinEthic). This skin model consists of normal human epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis. The NHEK are cultured on chemically modified, collagen-coated cell culture inserts. A highly differentiated and stratified epidermis model is obtained after 13-day culture period comprising the main basal, supra basal, spinous and granular layers and a functional stratum corneum.
- Tissue batch number(s): 16-EKIN-046
- Expiration date: November 21, 2016
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: Room temperature
- Temperature of post-treatment incubation (if applicable):
a) 37 ± 1 °C (5.0% CO2 for 42 ± 1 h) in 2 mL pre-warmed fresh maintenance medium
b) 37 ± 1 °C (5.0% CO2 for 3 h ± 5 min) in 2 mL pre-warmed MTT medium
REMOVAL OF TEST MATERIAL AND CONTROLS
- Volume and number of washing steps:
* washed with DPBS; excess DPBS was removed by blotting bottom with blotting paper;
* after post-incubation: excess medium was removed by blotting bottom on absorbent paper
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 0.3 mg/mL
- Incubation time: 3 h ± 5 min at 37 ± 1 °C, 5.0% CO2.
- Spectrophotometer: plate spectrophotometer
- Wavelength: 570 nm
- Filter bandwidth: ± 30 nm
NUMBER OF REPLICATE TISSUES: 3 tissues per dose group
PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered irritant to the skin if the viability after 15 minutes exposure and 42 h of post-incubation is less or equal to 50%. Further testing is required to resolve between UN GHS categories 1 and 2 and decide on the final classification of the test substance
- The test substance is considered to be non-corrosive to skin if the viability after 15 minutes exposure and 42 h is greater than 50%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 µL (26.3 µL/cm²) of the test item was dispensed directly atop the EPISKIN-SM tissue using a positive displacement pipette. The test item was spread to match size of the tissue.
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 10 µL DPBS (Gibco, Cat. No. 14040-091, Lot No.: 1737107)
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 10 µL 5% sodium dodecyl sulfate (SDS; AppliChem, Art.-No. A1112,0500, CAS No.: 151-21-3, Lot No.: 40015277) in aqua dest. - Duration of treatment / exposure:
- 15 ± 0.5 min
- Duration of post-treatment incubation (if applicable):
- 42 ± 1 h
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean of three tissues
- Value:
- 73.5
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- For detailed results see box "Any other information on results".
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item showed no irritant effects in an in vitro skin irritation study conducted according to OECD 439.
- Executive summary:
In an in vitro skin irritation study according to OECD Guideline 439 (Reconstructed Human Epidermis Test), the potential of buthl ethyl ether (98.4% purity) to induce skin irritation was analysed by using the three-dimensional human skin model EPISKIN-SM™ (SkinEthic) comprising a reconstructed epidermis with a functional stratum corneum. In the present study the test item was applied topically to the EPISKIN-SM™ tissue for 15 min followed by a 42 h post-incubation period and immediate determination of cytotoxic effects via MTT reduction assay. Irritant potential of the test item was predicted from the relative mean tissue viabilities obtained compared to the corresponding negative control tissues concurrently treated with DPBS. The test item showed no irritant effects and is therefore considered to be non-irritating to the skin.
Reference
Results of the Pre-Experiments
The mixture of 10 µL test item per 2 mL MTT medium showed no reduction of MTT as compared to the solvent. The mixture did not turn blue/purple. Therefore, NSMTT equalled 0%.
The mixtures of 10 µL of the test item per 90 µL aqua dest. and per 90 µL isopropanol showed no colouring detectable by unaided eye-assessment. Therefore, NSCliving equalled 0%.
Table 1: Results of the test item butyl ethyl ether
Name | Negative Control | Positive Control | Test Item | ||||||
Tissue | 1 | 2 | 3 | 1 | 2 | 3 | 1 | 2 | 3 |
Absolute OD570 | 0.760 0.824 |
0.715 0.735 |
0.741 0.795 |
0.235 0.182 |
0.176 0.180 |
0.185 0.153 |
0.573 0.573 |
0.532 0.523 |
0.607 0.618 |
OD570 (Blank corrected | 0.717 0.781 |
0.672 0.693 |
0.698 0.752 |
0.192 0.139 |
0.133 0.137 |
0.142 0.110 |
0.531 0.530 |
0.489 0.480 |
0.565 0.575 |
Mean OD570 of the Duplicates (Blank corrected) | 0.749 | 0.683 | 0.725 | 0.166 | 0.135 | 0.126 | 0.530 | 0.485 | 0.570 |
Total Mean OD570 of 3 Replicate Tissues (Blank corrected) | 0.719* | 0.142 | 0.528 | ||||||
SD OD570 | 0.034 | 0.021 | 0.043 | ||||||
Relative Tissue Viabilities [%] | 104.2 | 94.9 | 100.9 | 23.0 | 18.8 | 17.6 | 73.7 | 67.4 | 79.3 |
Mean Relative Tissue Viabilities [%] | 100.0 | 19.8** | 73.5 | ||||||
SD Tissue Viabilities [%]*** | 4.7 | 2.9 | 5.9 | ||||||
CV [% Viability] | 4.7 | 14.5 | 8.1 |
* Corrected mean OD570 of the negative control corresponds to 100% absolute tissue viability.
** Mean relative tissue viability of the three positive control tissues is ≤ 40%.
*** Standard deviation (SD) obtained from the three concurrently tested tissues is ≤ 18%.
Table 2: Test Acceptance Criteria
|
Value |
Cut off |
pass/fail |
Mean OD570Blank |
0.043 |
< 0.1 |
pass |
Mean Absolute OD570NK |
0.762 |
0.6 ≤ NK ≤ 1.5 |
pass |
Mean Relative Viability PC [%] |
19.8 |
≤ 40% |
pass |
Max. SD of % Viability |
5.9 |
≤ 18% |
pass |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2017-01-17 to 2017-04-10
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- adopted 02 October 2012
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: animal 1: approx. 44 weeks old; animal 2: approx. 41 weeks old
- Weight at study initiation: > 2 kg
- Housing: ABS-plastic or Noryl rabbit cages, floor 4200 cm², in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum - Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits, rich in crude fibre
- Water (e.g. ad libitum): ad libitum - Free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days under laboratory conditions
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test item was applied to the test site - Duration of treatment / exposure:
- single treatment
- Observation period (in vivo):
- The animals were observed for 72 hours after dosing. To determine the reversibility of the observed effects in animal no. 2, the observation period was extended up to 6 days after dosing.
- Number of animals or in vitro replicates:
- 2 rabbits
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye was not rinsed after application.
SCORING SYSTEM: Grading system for ocular lesions according to OECD 405
TOOL USED TO ASSESS SCORE: At the end of the observation period the treated eyes were examined with the aid of a fluorescein solution. The eyes were rinsed with physiological saline 0.9% NaCl after the examination.
TEST PROCEDURE:
Initial test: The in vivo test was performed initially using one animal.
Confirmatory test: The results of the initial test did not indicate the test item to be corrosive or a severe irritant to the eye using the procedure described. In order to confirm the response, one additional animal was treated in the same manner. According to OECD 405, section 23, treatment of a third animal was omitted as results from the second animal were sufficient to allow for hazard classification determination. - Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- fully reversible within: 72 hours
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 6 days
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritant / corrosive response data:
- After the application into the eyes of two male NZW rabbits the test item produced slight irritant but not corrosive effects in both animals, which were fully reversible within 72 hours in animal no. 1 and within 6 days in animal no. 2. Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal. Conjunctival redness, chemosis and hypersecretion were observed in both animals.
- Other effects:
- Neither mortality nor significant clinical signs of toxicity but local effects were observed. Moreover, the body weight development of all animals was within the expected range.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In an in vivo acute eye irritation/corrosion study in rabbits, butyl ethyl ether was tested negative regarding irritation to the eye.
- Executive summary:
In a primary eye irritation study 0.1 mL of butyl ethyl ether (98.4 % purity) was applied into the conjunctival sac of one eye of two male New Zealand White Rabbits, Crl: KBL (NZW). The treated eye was not rinsed after the application. The untreated eye served as control. Control and treated animals were observed for a period of 72 hours.
Under the conditions of the present study, a single ocular application of the test item to rabbits at a dose of 0.1 mL produced slight irritant but not corrosive effects in both animals, which were fully reversible within 72 hours in animal no. 1 and within 6 days in animal no. 2. Neither mortalities nor significant clinical signs of toxicity were observed. Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal.
On the basis of the test results and in conformity with the criteria given in Annex I of Regulation (EC) 1272/2008, the substance should be not classified.
Reference
Table 1: Eye Irritation Scores - Animal No. 1 | ||||||||||
Observation | Animal No. 1, Eye Irritation Scores Post-Application After | Average Score (24, 48 and 72 hours) | ||||||||
1 hour | 24 hours | 48 hours | 72 hours | |||||||
Test item | Control | Test item | Control | Test item | Control | Test item | Control | |||
Redness | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0.67 | |
Chemosis | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Iris | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Cornea | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Table 2: Eye Irritation Scores - Animal No. 2 | ||||||||||
Observation | Animal No. 2, Eye Irritation Scores Post-Application After | Average Score (24, 48 and 72 hours) | ||||||||
1 hour | 24 hours | 48 hours | 72 hours | |||||||
Test item | Control | Test item | Control | Test item | Control | Test item | Control | |||
Redness | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | |
Chemosis | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Iris | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Cornea | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Butyl ethyl ether (98.4 % purity) was tested negative for acute dermal irritating properties in a study conducted according to OECD 439. In a screening study for identifying ocular corrosives and severe irritants (BCOP, OECD 437) no prediction could be made regarding the classification of butyl ethyl ether and further testing was required. Thus, an acute eye irritation/corrosion study in vivo (OECD 405) was conducted in rabbits. Only slight irritating effects (grade 1) were observed in both animals. These effects were fully reversible within 72 hours to 6 days. Based on the results, butyl etyhyl ether is considered to be not irritating to the skin and/or eye.
Justification for classification or non-classification
Butyl ethyl ether (98.4 % purity) was tested negative for acute dermal irritating and eye irritating/corrosive properties in studies conducted according to OECD 439 and OECD 405. Therefore, butyl ethyl ether does not warrant classification for skin and/or eye irritation.
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