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EC number: 607-233-2 | CAS number: 2343-89-7
- 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
The substance was tested in a reliable in vitro skin corrosion assay and then in a reliable in vitro skin irritation assay. It gave negative results in both in vitro studies. The substance was also tested in a reliable in vitro eye irritation assay (BCOP) where it gave inconclusive results. Because the results were inconclusive an additional eye irritation study was performed in vivo. This study was reliable and gave negative results.
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:
- 9/6/15 to 15/6/15
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Recently conducted study performed to OECD guideline and under GLP
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- GLP compliance:
- yes (incl. QA statement)
- Species:
- other: EpiSkin Reconstructure Human Epidermis Model Kit
- Strain:
- not specified
- Details on test animals or test system and environmental conditions:
- Test System: EPISKIN Reconstructed Human Epidermis Model Kit
Supplier: SkinEthic Laboratories, Lyon, France
Date Received: 9th June 2015
EpiSkin Tissues (0.38cm^2) lot number: 15-EKIN-023
Maintenance Medium lot number: 15-MAIN3-023
Assay Medium lot number: 15-ESSC-023 - Type of coverage:
- not specified
- Preparation of test site:
- not specified
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Duration of treatment / exposure:
- 15 minutes
- Observation period:
- 42 hours
- Number of animals:
- Not applicable
- Irritation / corrosion parameter:
- other: other: Relative mean tissue viability
- Value:
- 102.8
- Remarks on result:
- other:
- Remarks:
- Basis: other: Prediction. Time point: 42 hours. Reversibility: no data. (migrated information)
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The substance was non-irritant to the skin in an in vitro assay
- Executive summary:
Introduction
The purpose of this test was to evaluate the skin irritation potential of the test item using the EPISKINTM reconstructed human epidermis model after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours. The principle of the assay was based on the measurement of cytotoxicity in reconstructed human epidermal cultures following topical exposure to the test item by means of the colorimetric MTT reduction assay. Cell viability is measured by enzymatic reduction of the yellow MTT tetrazolium salt (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) to a blue formazan salt (within the mitochondria of viable cells) in the test item treated tissues relative to the negative controls.
Method
Triplicate tissues were treated with the test item for an exposure period of 15 minutes. At the end of the exposure period each tissue was rinsed before incubating for 42 hours. At the end of the post-exposure incubation period each tissue was taken for MTT-loading. The maintenance medium from beneath each tissue was transferred to pre-labeled micro tubes and stored in a freezer for possible inflammatory mediator determination. After MTT-loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues.
At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 μL samples were transferred to the appropriate wells of a pre-labeled 96-well plate. The optical density was measured at 562 nm.
Data are presented in the form of percentage viability (MTT reduction in the test item treated tissues relative to negative control tissues).
Results
The relative mean viability of the test item treated tissues was 102.8% after the 15-Minute exposure period and 42-Hours post-exposure incubation period.
Quality criteria: The quality criteria required for acceptance of results in the test were satisfied.
Conclusion
The test item was classified as non-irritant. The following classification criteria apply:
EU DSD and CLP: Not classified for Irritation.
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 29/4/15 to 1/5/15
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Species:
- other: EpiDermn Reconstructed Human Epidermis Model Kit
- Strain:
- not specified
- Details on test animals or test system and environmental conditions:
- Test System: EpiDerm Reconstructed Human Epidermis Model Kit
Supplier: MatTek
Date Received: 28 April 2015
EpiDerm Tissues (0.5 cm^2) lot number: 21663/D
Assay Medium lot number: 0923152SC
Upon receipt of the EpiDerm tissues, the sealed 24-well plate was placed into a refrigerator. - Type of coverage:
- not specified
- Preparation of test site:
- not specified
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Duration of treatment / exposure:
- 3 minutes and 60 minutes
- Observation period:
- None
- Number of animals:
- Not applicable
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 minutes
- Value:
- 113.6
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 60 minutes
- Value:
- 21.3
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The substance was non-corrosive to the skin in an in vitro assay
- Executive summary:
In an in vitro skin corrosion study human skin tissue (eipdermis keratinocytes) was exposed to undiluted substance for 3-minutes or 1-hour. There was 113.6% and 21.3% tissue viability following the 3-minutes and 1-hour exposure points, respectively. Resultantly, the test material is considered to be non-corrosive to skin.
Referenceopen allclose all
TABLE 1 - Mean OD562 Values and Viabilities for the Negative Control Item, Positive Control Item and Test Item
Item | Exposure Time | Mean OD562 | Percentage Viability |
Negative Control | 3 minutes | 1.852 | 100 |
Negative Control | 60 minutes | 2.335 | 100 |
Positive Control | 3 minutes | 0.191 | 10.3 |
Positive Control | 60 minutes | 0.066 | 2.8 |
Test Item | 3 minutes | 2.103 | 113.6 |
Test Item | 60 minutes | 0.497 | 21.3 |
The mean viability of the negative control tissues is set at 100%
The mean OD562 values is based on the mean of EpiDermTM tissues tested in duplicate
Viability is expressed as a percentage of the 3 and 60 minute negative control tissues
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:
- key study
- Study period:
- 18/5/15 to 4/6/15
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories UK Ltd.
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 2.6 to 2.8 kg
- Housing: Individual suspended cages
- Diet (e.g. ad libitum): ad libitum, 2930C Teklad Global Rabbit diet
- Water (e.g. ad libitum): ad libitum, mains drinking water
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours darkness, 12 hours light - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: Tested animals were also used as control - test item was adminstered to only one eye, with the other left untreated for control purposes.
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml - Duration of treatment / exposure:
- Eight hours
- Observation period (in vivo):
- 72 hours
- Number of animals or in vitro replicates:
- Three
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- iris score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 0.7
- Max. score:
- 1
- Reversibility:
- fully reversible within: 72 hours
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 0.17
- Max. score:
- 1
- Reversibility:
- fully reversible within: 48 hours
- Irritant / corrosive response data:
- No corneal or iridial effects were noted in any animal during the study. Moderate conjunctival irritation was seen in two animals at one hour and minimal conjunctival irritation was seen in one animal at one hour. Minimal conjuctival irritation was seen at 24 hours and 48 hours. No effects were seen at 72 hours in the surviving animals.
- Other effects:
- The first treated animal was found dead three days after test substance application and the third animal was found dead two days after application.
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The substance is not classified as corrosive or irritant based on the results of this study. It is not clear whether the mortalities noted on the study were test substance related.
- Executive summary:
A study has been undertaken according to OECD method 405 and EU method B5 to determine the eye irritancy of 2 -Propenoic acid, 2 -fluoro-, methyl ester. The study shows that the test item does not meet the criteria for classification according to Regulation (EC) No. 1272/2008. It is not clear whether the observed mortalities within the study are test substance related.
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 8/5/15 to 8/5/15
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Recently conducted study performed to OECD guideline and under GLP
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- GLP compliance:
- yes (incl. QA statement)
- Species:
- other: Cow
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Local abattoir
- Age at study initiation: 12 to 60 months - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 ml - Duration of treatment / exposure:
- 10 minutes
- Observation period (in vivo):
- 120 minutes
- Number of animals or in vitro replicates:
- 9 corneas used
- Irritation parameter:
- in vitro irritation score
- Value:
- ca. 10.3 - < 10.7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- The test item had an in vitro irritancy score of 10.3. This is in the range of 3 to 55, and within this range no predicition of eye irritation can be made.
- Executive summary:
SUMMARY
Introduction
The purpose of this test was to identify test items that can induce serious eye damage and to identify test items not requiring classification for eye irritation or serious eye damage. The Bovine Corneal Opacity and Permeability (BCOP) test method is an organotypic model that provides short-term maintenance of normal physiological and biochemical function of the bovine cornea in vitro. In this test method, damage by the test item is assessed by quantitative measurements of changes in corneal opacity and permeability. The test method can correctly identify test items (both chemicals and mixtures) inducing serious eye damage as well as those not requiring classification for eye irritation or serious eye damage, as defined by the United Nations (UN) Globally Harmonized System of Classification and Labelling of Items (GHS) and EU Classification, Labelling and Packaging (CLP) of chemicals (Regulation (EC) No 1272/2008), and it was therefore endorsed as scientifically valid for both purposes. Test items inducing serious eye damage are classified as UN GHS and EU CLP Category 1. Items not classified for eye irritation or serious eye damage are defined as those that do not meet the requirements for classification as UN GHS/ EU CLP Category 1 or 2 (2A or 2B), i.e. they are referred to as UN GHS/EU CLP No Category.
Method
The undiluted test item was applied for 10 minutes followed by an incubation period of 120 minutes. Negative and positive control items were tested concurrently. The two endpoints, decreased light transmission through the cornea (opacity) and increased passage of sodium fluorescein dye through the cornea (permeability) were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS).
Interpretation
The test item is classified according to the prediction model below:
IVIS Classification ≤ 3
No category. Not requiring classification to UN GHS or EU CLP
> 3; ≤55
No prediction of eye irritation can be made
> 55 Category 1. UN GHS or EU CLP Causes serious eye damage
Results
The In Vitro irritancy scores are summarized as follows:
Treatment In Vitro Irritancy Scor Test Item 10.3 Negative Control 2.7 Positive Control 35.9 Conclusion
No prediction of eye irritation can be made.
Referenceopen allclose all
Individual scores for Ocular Irritation
Rabbit name and sex | 75066 Male | 75073 Male | 75083 Male | ||||||||
IPR | 0 | 0 | 0 | ||||||||
Time after treatment | 1 hour | 24 hours | 48 hours | 72 hours | 1 hour | 24 hours | 48 hours | 72 hours | 1 hour | 24 hours | 48 hours |
Cornea | |||||||||||
Degree of Opacity | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | - |
Area of Cornea Involved | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | - |
Iris | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | - |
Conjunctivae | |||||||||||
Redness | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 2 | 1 | - |
Chemosis | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | - |
Discharge | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | - |
Individual and Mean Corneal Opacity and Permeability Measurements
Opacity | Permeability | ||||||||
Treatment | Cornea Number | Pre-treatment | Post-treatment | Post-incubation | Post-incubation - Pre-treatment | Corrected Value | Corrected Value | In Vitro Irritancy Score | |
Negative Control | 1 | 4 | 5 | 5 | 1 | 0.001 | |||
Negative Control | 5 | 4 | 4 | 5 | 1 | 0.002 | |||
Negative Control | 12 | 4 | 5 | 6 | 2 | 0.278 | |||
Negative Control | 1.3 | 0.094 | 2.7 | ||||||
Positive Control | 3 | 5 | 35 | 32 | 27 | 25.7 | 1.004 | 0.910 | |
Positive Control | 16 | 2 | 31 | 28 | 26 | 24.7 | 0.894 | 0.800 | |
Positive Control | 19 | 4 | 35 | 28 | 24 | 22.7 | 0.697 | 0.603 | |
Positive Control | 24.3 | 0.771 | 35.9 | ||||||
Test Item | 14 | 4 | 17 | 16 | 12 | 10.7 | 0.020 | 0.000 | |
Test Item | 18 | 6 | 21 | 17 | 11 | 9.7 | 0.025 | 0.000 | |
Test Item | 20 | 4 | 14 | 16 | 12 | 10.7 | 0.009 | 0.000 | |
Test Item | 10.3 | 0.000 | 10.3 |
Corneal Epithelium Condition Post-reatment and Post-incubation
Observation | |||
Treatment | Cornea Number | Post-treatment | Post-incubation |
Negative Control | 1 | Clear | Clear |
Negative Control | 5 | Clear | Clear |
Negative Control | 12 | Clear | Clear |
Positive Control | 3 | Cloudy | Cloudy |
Positive Control | 16 | Cloudy | Cloudy |
Positive Control | 19 | Cloudy | Cloudy |
Test Item | 14 | Partly cloudy | Partly cloudy |
Test Item | 18 | Partly cloudy | Partly cloudy |
Test Item | 20 | Partly cloudy | Partly cloudy |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
The substance gave negative results in skin corrosion and skin irritantancy assays conducted in vitro. It gave an inconclusive result in an in vitro eye irritation study and only minimal irritation effects in an in vivo eye study. Therefore classification for corrosion/irritancy effects is not justified.
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