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EC number: 807-645-4 | CAS number: 701920-77-6
- 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
Key in vitro studies were available for undiluted (97,1% pure) bis[2-(2-butoxyethoxy)ethyl]butanedioate for both skin and eye irritation potential. In the EPISKIN-Standard Method, a reconstituted three-dimensional human epidermis model, cytotoxicity was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 15 min exposure and 42 h post incubation period at 37 ± 1°C and compared to those of the concurrent negative controls. The relative mean tissue viability after 15 min of exposure and 42 h post incubation was 104.4% which was > 50%. In the BCOP (bovine corneal opacity and permeability) assay, three isolated corneas per group obtained freshy slaughtered, were evaluated for opacity and permeability after 10 minutes incubation at 32 ± 1°C of 750 µL of test/control substance and washing/2h incubation of the epithelium with RPMI medium at 32 ± 1°C. The Mean in vitro irritation score (IVIS) for the tested group was -1.05, which was <3.
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:
- 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study complies to OECD Test Guidance 439 and GLP, and is considered to be relevant, adequate and reliable.
- 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)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- other: in vitro
- Strain:
- other: human skin model EPISKIN-SM (TM)
- Details on test animals or test system and environmental conditions:
- EPISKIN-SMTM(SkinEthic). This skin model consists of normal (non-cancerous), adult human-derived 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 cultured 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
- Amount / concentration applied:
- The test item was applied undiluted. 10µL (26.3µL/cm2) of the test item were dispensed directly atop the EPISKIN-SMTM tissue.
- Irritation / corrosion parameter:
- other: other: mean relative tissue viability (% versus negative control)
- Value:
- 104.4
- Remarks on result:
- other:
- Remarks:
- Basis: mean. Time point: after 15 min treatment and 42 h postincubation. Max. score: 50.0. Remarks: Test group . (migrated information)
- Irritation / corrosion parameter:
- other: other: relative tissue viability (% versus negative control)
- Value:
- 8.4
- Remarks on result:
- other:
- Remarks:
- Basis: mean. Time point: after 15 min treatment and 42 h postincubation. Max. score: 50.0. Remarks: Positive control group. (migrated information)
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- In this study under the given conditions the test item showed no irritant effects. The test item is therefore classified as “non-irritant” in accordance with UN GHS “No Category”.
- Executive summary:
In the present study the skin irritant potential of bis[2-(2-butoxyethoxy)ethyl]butanedioate was analysed. The EPISKIN-Standard ModelTM(EPISKIN-SMTM), a reconstituted three-dimensional human epidermis model, was used as a replacement for the Draize Skin Irritation Test (OECD TG 404) to distinguish between UN GHS “Category 2” skin irritating test substances and not categorized test substances (“No Category”) which may be considered as non-irritant. Hereby, undiluted (97.1% pure) test item was applied topically. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 15 min exposure and 42 h post incubation period at 37 + 1°C and compared to those of the concurrent negative controls.
In this study under the given conditions the test item showed no irritant effects. The relative mean tissue viability after 15 min of exposure and 42 h post incubation was 104.4% which was > 50%. The test item is therefore not classified by the UN GHS or EU CLP criteria.
Reference
Pre-Experiments:
The mixture of 10 µL test item per 2 mL MTT medium showed no reduction of MTT compared to the solvent. The mixture did not turn blue/purple.
The mixture of 10 µL of the test item per 90 µL aqua dest. showed no colouring detectable by unaided eye-assessment.
Since the test item was not solvable in aqueous solutions, emulsification was observed for both pre-experiments.
Experiment:
Results
Name |
Negative Control |
Positive Control |
Test Item |
||||||
Tissue |
1 |
2 |
3 |
1 |
2 |
3 |
1 |
2 |
3 |
absolute OD550 |
0.937 |
0.923 |
0.934 |
0.116 |
0.129 |
0.115 |
1.098 |
0.966 |
0.906 |
OD550(blank-corrected) |
0.893 |
0.880 |
0.890 |
0.072 |
0.085 |
0.071 |
1.055 |
0.922 |
0.862 |
total mean OD550of 3 replicate tissues (blank-corrected) |
0.890* |
0.075 |
0.929 |
||||||
SD OD550 |
0.009 |
0.007 |
0.098 |
||||||
relative tissue viabilities [%] |
98.9 |
100.9 |
100.2 |
8.3 |
9.3 |
7.7 |
116.9 |
100.6 |
95.8 |
mean relative tissue viability[%] |
100.0 |
8.4** |
104.4 |
||||||
SD tissue viability [%]*** |
1.0 |
0.8 |
11.0 |
||||||
CV [% viability] |
1.0 |
9.9 |
10.6 |
* Corrected mean OD550 of the negative control corresponds to 100% absolute tissue viability.
** Mean relative tissue viability of the three positive control tissues is ≤ 40%.
*** The standard deviation (SD) obtained from the three concurrently tested tissues is < 18%.
Quality Criteria
|
Value |
Cut off |
pass/fail |
Mean OD550nm Blank |
0.044 |
< 0.1 |
pass |
Mean Absolute OD550nmNC |
0.934 |
0.6 ≤ NC ≤ 1.5 |
pass |
Mean Relative Viability [%] PC |
8.4 |
≤ 40% |
pass |
SD of % Viability [%] |
0.8 – 11.0 |
< 18% |
pass |
Historical data
|
OD550Blank |
Mean Absolute OD550 NC |
Relative Viability [%] PC |
SD of Viability [%] |
Mean |
0.043 |
0.869 |
12.50 |
8.01 |
SD |
0.002 |
0.122 |
8.67 |
8.63 |
n |
44 |
44 |
44 |
176 |
The potential of the test item to induce skin irritation was analysed by using the three-dimensional human skin model EPISKIN-SMTM (SkinEthic) comprising a reconstructed epidermis with a functional stratum corneum.
In the present study bis[2-(2-butoxyethoxy)ethyl]butanedioate was applied topically to the EPISKIN-SMTM tissue for 15 min. followed by a 42 h postincubation 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 PBS.
The test item showed no irritant effects. The mean relative tissue viability (% negative control) was > 50% (104.4%) after 15 min. treatment and 42 h post incubation. Furthermore, no effects of any kind were observed for the test item treated tissues.
The controls confirmed the validity of the study. The mean OD550 of the six blank values was < 0.1. The mean absolute OD550 of the three negative control tissues was ≥ 0.6 and ≤ 1.5. The mean relative tissue viability (% negative control) of the positive control was ≤ 40% ( 8.4%) . The maximum standard deviation of viability of replicate tissues of all dose groups was < 18% (0.8% - 11.0%).
The potential of the test item to induce skin irritation was analysed by using the three-dimensional human skin model EPISKIN-SMTM (SkinEthic) comprising a reconstructed epidermis with a functional stratum corneum.
In the
present study bis[2-(2-butoxyethoxy)ethyl]butanedioate was applied
topically to the EPISKIN-SMTM tissue for 15 min. followed by
a 42 h postincubation 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 PBS.
The test item showed no irritant effects. The mean relative tissue viability (% negative control) was > 50% (104.4%) after 15 min. treatment and 42 h post incubation. Furthermore, no effects of any kind were observed for the test item treated tissues. The controls confirmed the validity of the study. The mean OD550 of the six blank values was < 0.1. The mean absolute OD550 of the three negative control tissues was ≥ 0.6 and ≤ 1.5. The mean relative tissue viability (% negative control) of the positive control was ≤ 40% ( 8.4%) . The maximum standard deviation of viability of replicate tissues of all dose groups was < 18% (0.8% - 11.0%).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study complies to OECD Test Guidance 437 and GLP, and is considered to be relevant, adequate and reliable.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- other: ex vivo
- Strain:
- other: Bovine cornea
- Details on test animals or tissues and environmental conditions:
- The assay uses isolated corneas obtained as a by-product from animals freshy slaughtered at the abattoir A. Moksel AG, Buchloe, Germany. On the test day, fresh eyes were collected from the slaughterhouse and were transported in HBSS containing Pen/Strep on ice to the laboratories. Immediately after arrival of the eyes, cornea preparation was initiated.
- Amount / concentration applied:
- The test item was used as provided by the sponsor.
- Irritation parameter:
- other: IVIS
- Basis:
- mean
- Score:
- -1.05
- Max. score:
- 3
- Remarks on result:
- other: Test group
- Irritation parameter:
- other: IVIS
- Basis:
- mean
- Score:
- 2.28
- Max. score:
- 3
- Remarks on result:
- other: Negative control group
- Irritation parameter:
- other: IVIS
- Basis:
- mean
- Score:
- 72.12
- Max. score:
- 55
- Remarks on result:
- other: Positive control group
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- According to the evaluation criteria the test item bis[2-(2-butoxyethoxy)ethyl]butanedioate is classified into UN GHS No Category.
- Executive summary:
The eye irritancy potential of bis[2-(2-butoxyethoxy)ethyl]butanedioate was investigated in the bovine corneal opacity and permeability assay.
Preparation of the test item was tested as provided by the sponsor (undiluted, 97.1% purity).The assay used three isolated corneas per group obtained as a by-product from animals freshy slaughtered, and both opacity and permeability were measured after 10 minutes incubation at 32+1°C of 750 µL of test/control substance and washing/2h incubation of the epithelium with RPMI medium at 32+1°C. The Mean in vitro irritation score (IVIS) for the tested group was -1.05, which was <3.
The in vitro irritation score obtained with the positive control fell within the expected ranges (<3 and >55, respectively).
According to the evaluation criteria the test item bis[2-(2-butoxyethoxy)ethyl]butanedioate is not classified by the UN GHS or EU CLP criteria.
Reference
The
eye irritancy potential of bis[2-(2-butoxyethoxy)ethyl]butanedioate was
investigated in the bovine corneal opacity and permeability assay.
The test item was tested as provided by the sponsor.
The following mean in vitro irritation score was calculated: -1.05.
Therefore
the test item was classified into UN GHS No Category.
The in vitro irritation score obtained with the positive control fell
within the two standard deviations of the current historical mean and
therefore this assay is considered to be valid.
Table 1. Opacity
Cornea |
Test item |
Initial |
Final |
Change of Opacity Value |
Corrected Opacity Value |
1 |
|
4 |
7 |
3 |
|
2 |
4 |
4 |
0 |
|
|
3 |
4 |
5 |
1 |
|
|
MV |
4.00 |
5.33 |
1.33 |
|
|
4 |
|
5 |
58 |
53 |
51.67 |
5 |
5 |
61 |
56 |
54.67 |
|
6 |
5 |
55 |
50 |
48.67 |
|
MV |
5.00 |
58.00 |
53.00 |
51.67 |
|
7 |
|
3 |
4 |
1 |
-0.33 |
8 |
5 |
5 |
0 |
-1.33 |
|
9 |
5 |
5 |
0 |
-1.33 |
|
MV |
4.33 |
4.67 |
0.33 |
-1.00 |
MV = mean value
Table 2. Permeability
Cornea |
Test item |
OD490 |
Corrected |
1 |
|
0.043 |
|
2 |
0.082 |
|
|
3 |
0.065 |
|
|
MV |
0.063 |
|
|
4 |
|
1.778 |
1.715 |
5 |
2.010 |
1.947 |
|
6 |
0.493 |
0.430 |
|
MV |
1.427 |
1.364 |
|
7 |
|
0.083 |
0.020 |
8 |
0.072 |
0.009 |
|
9 |
0.025 |
-0.038 |
|
MV |
0.060 |
-0.003 |
MV = mean value
Table 3. In Vitro Irritation Score
Cornea |
Test item |
Corrected |
Corrected |
IVIS |
1 |
|
3.00 |
0.043 |
2.28 |
2 |
0.00 |
0.082 |
||
3 |
1.00 |
0.065 |
||
MV |
1.33 |
0.063 |
||
4 |
|
51.67 |
1.715 |
72.12 |
5 |
54.67 |
1.947 |
||
6 |
48.67 |
0.430 |
||
MV |
51.67 |
1.364 |
||
7 |
|
-0.33 |
0.020 |
-1.05 |
8 |
-1.33 |
0.009 |
||
9 |
-1.33 |
-0.038 |
||
MV |
-1.00 |
-0.003 |
MV = mean value
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Additional information
A key study for skin irritant potential of bis[2-(2-butoxyethoxy)ethyl]butanedioate was conducted by means of the EPISKIN-Standard ModelTM(EPISKIN-SMTM). Hereby, the undiliuted (97.1% pure) test item was applied to a reconstituted three-dimensional human epidermis model (BioService, 2015a). Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 15 min exposure and 42 h post incubation period at 37 ± 1°C and compared to those of the concurrent negative controls. In this study under the given conditions the test item showed no irritant effects. The relative mean tissue viability after 15 min of exposure and 42 h post incubation was 104.4% which was > 50%. The test item is therefore classified as “non-irritant” in accordance with UN GHS or EC CLP criteria.
The eye irritancy potential of bis[2-(2-butoxyethoxy)ethyl]butanedioate was investigated in the bovine corneal opacity and permeability assay (BioSerivice, 2015b). Preparation of the test item was tested as provided by the sponsor (undiluted, 97.1% purity).The assay used three isolated corneas per group obtained as a by-product from animals freshy slaughtered, and both opacity and permeability were measured after 10 minutes incubation at 32 ± 1°C of 750 µL of test/control substance and washing/2h incubation of the epithelium with RPMI medium at 32 ± 1°C. The Mean in vitro irritation score (IVIS) for the tested group was -1.05, which was <3. The in vitro irritation score obtained with the positive control fell within the expected ranges (<3 and >55, respectively). According to the evaluation criteria the test item bis[2-(2-butoxyethoxy)ethyl]butanedioate is not classified by the UN GHS or EU CLP criteria.
Justification for selection of skin irritation / corrosion endpoint:
Key study
Justification for selection of eye irritation endpoint:
key study
Justification for classification or non-classification
Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC) and CLP regulation (EC No. 1272/2008 of 16 December 2008), bis[2-(2-butoxyethoxy)ethyl]butanedioate does not have to be classified and has no obligatory labelling requirement for skin irritation and eye irritation.
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