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EC number: 206-169-9 | CAS number: 305-84-0
- 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
Skin irritation (OECD 439): not irritating
Eye irritation / Serious eye damage (OECD 437): not irritating
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:
- 11 Apr - 5 May 2017
- 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)
- Version / remarks:
- adopted 28 Jul 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- Commission Regulation (EC) No 440/2008 of 30 May 2008, 1st ATP 2009
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: EpiDerm™ (EPI-200-SIT)
- Source strain:
- other: 00267
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm™ (EPI-200-SIT) (MatTek Corporation, Bratislava, Slovakia)
- Tissue batch number(s): 25810
- Shipping date: 3 May 2017
- Delivery date: 3 May 2017
- Date of initiation of testing: 3 May 2017
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 1.5 °C for 35 min in the incubator; thereafter at room temperature for 25 min in a sterile bench
- Temperature of post-treatment incubation: Tissues were incubated for 24.7 hours at 37 ± 1.5 °C. After change of medium, tissues were again incubated for another 17.5 hours at 37 ± 1.5 °C
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: Inserts were removed from the 6-well plate and tissues were gently rinsed with DPBS at least 15 times in order to remove any residual test material. After rinsing, the Inserts were submerged in DPBS at least three times. Afterwards the inserts were once again rinsed with sterile DPBS from the inside and the outside.
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 h
- Spectrophotometer: microplate reader (Versamax, Molecular Devices, Softmax Pro v.4.7.1)
- Wavelength: 570 nm
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: The quality of the EpiDerm tissue was assessed by undertaking an MTT cell viability test. The determined OD (540 - 570 nm) was 1.556 ± 0.088 (acceptance criteria: 1.0 - 3.0).
- Barrier function: The barrier function was assessed by determination of the exposure time required to reduce tissue viability by 50% (ET-50) upon application of 100 µL of 1% Triton X-100. The ET-50 value was determined to be 5.23 h (acceptance criteria: 4.77-8.72 h).
- Contamination: The cells used to produce the EpiDerm tissue were screened for the presence of viruses, bacteria, yeast and other fungi.
- Reproducibility: Absorbance of positive and negative control were within the range of historical controls.
NUMBER OF REPLICATE TISSUES: 3
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- Since the test substance did not directly reduce MTT in a pre-test, an additional test with freeze-killed tissues was not performed.
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:
- single experiment
PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritant to skin if the viability after 1 hour exposure is ≤ 50%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount applied: 25 mg ± 2 mg (~ 39 mg/cm2) of the test item, wetted with 25 μL DPBS
NEGATIVE CONTROL
- Amount applied: 30 μL
POSITIVE CONTROL
- Amount applied: 30 μL
- Concentration: 5% - Duration of treatment / exposure:
- 35 min at 37 ± 1.5 °C and 25 min at RT
- Duration of post-treatment incubation (if applicable):
- 42.2 h
- Number of replicates:
- triplicates
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 60 min
- Value:
- 102.9
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- - OTHER EFFECTS:
- Direct-MTT reduction: The test substance did not interfere with the MTT assay (no reducing capacity).
- Colour interference with MTT: The test substance did not change colour when mixed with deionised water. Also its intrinsic colour was not intensive.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Absorbance values were well within the required acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for the 60 minutes treatment interval, thus assuring the quality of the tissues.
- Acceptance criteria met for positive control: Treatment with the positive control induced a decrease in the relative absorbance as compared to the negative control to 4.5% thus ensuring the validity of the test system.
- Acceptance criteria met for variability between replicate measurements: The relative standard deviations between the % variability values in the main test were below 11% (threshold of the "OECD Guideline for the Testing of Chemicals 439: In vitro Skin Irritation: Reconstructed Human Epidermis Test Method”: ≤18%), thus ensuring the validity of the study.
- Range of historical values if different from the ones specified in the test guideline: The relative standard deviations of historical positive controls were with 20.12% higher than standard deviations ≤ 18% in the test guideline. In the study, the relative standard deviations of the positive control were 5.1% and therefore ≤ 18%. - Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
- Conclusions:
- Under the conditions of the reconstructed human epidermis test the test substance does not possess any skin irritating potential.
- Executive summary:
The skin irritation potential of the test substance was determined by an in vitro skin irritation test using a reconstructed human skin model according to OECD Guideline 439 and in compliance with GLP (2016). After treatment with the test substance for 60 min the tissue viability was 102.9% compared to the negative control (threshold for irritancy ≤ 50%). Therefore, the test substance is not considered to be irritating to the skin.
Reference
Table 2. Results after treatment with the test substance and controls
Test group |
Mean absorbance at 570 nm* |
Rel. absorbance (%)** |
SD (%) |
Rel. absorbance (% of negative control)*** |
||||
Tissue 1 |
Tissue 2 |
Tissue 3 |
Tissue 1 |
Tissue 2 |
Tissue 3 |
|||
Negative control |
1.504 |
1.372 |
1.266 |
108.9 |
99.4 |
91.7 |
8.6 |
100.0 |
Positive control |
0.062 |
0.059 |
0.065 |
4.5 |
4.3 |
4.7 |
5.1 |
4.5 |
Test substance |
1.281 |
1.401 |
1.578 |
92.8 |
101.5 |
114.3 |
10.8 |
102.9 |
* Mean of three replicate wells after blank correction (blank = 0.037)
** Relative absorbance per tissue (rounded values): 100 × (absorbance tissue) / (mean absorbance negative control)
*** Relative absorbance per treatment group (rounded values): 100 × (mean absorbance test substance/positive control) / (mean absorbance negative control)
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:
- 18 April 2017
- 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)
- Version / remarks:
- adopted July 2013
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
- Version / remarks:
- Commission Regulation (EU) No 1152/2010
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Species:
- cattle
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: Schlachthof Aschaffenburg, Germany
- Characteristics of donor animals: at least 9 month old
- Storage, temperature and transport conditions of ocular tissue: The freshly isolated eyes were stored in Hank's Buffered Salt Solution (HBSS) containing 1% (v/v) Penicillin/Streptomycin in the cooled slaughter-house until transportation on the same morning to the laboratory using a Styrofoam box.
- Time interval prior to initiating testing: The corneae were isolated on the same day after delivery of the eyes and directly used in the BCOP test.
- Indication of any existing defects or lesions in ocular tissue samples: All eyes were carefully examined macroscopically for defects. Those presenting defects such as vascularization, pigmentation, opacity and scratches were discarded. - Vehicle:
- physiological saline
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 0.75 mL
- Concentration: 20% (w/v) in saline
VEHICLE / NEGATIVE CONTROL
- Amount applied: 0.75 mL
- Concentration: 0.9% NaCl (w/v) in deionised water (saline)
POSITIVE CONTROL
- Amount applied: 0.75 mL
- Concentration: 10 % (w/v) in 0.9% NaCl in deionised water - Duration of treatment / exposure:
- 240 min
- Number of animals or in vitro replicates:
- triplicates for each treatment and control group
- Details on study design:
- SELECTION AND PREPARATION OF CORNEAS:
The cornea was carefully removed from the eye using scalpel and rounded scissors. A rim of about 2 mm of tissue (sclera) was left for stability and handling of the isolated cornea. Each cornea was mounted in a specially designed cornea holder.
QUALITY CHECK OF THE ISOLATED CORNEAS:
At the end of the equilibration period, the basal opacity was determined (t0). Each cornea with a value of the basal opacity >7 was discarded.
TREATMENT METHOD:
The cornea holder consists of anterior and posterior compartments, which interface with the epithelial and endothelial sides of the cornea, respectively. The endothelial side of the cornea was positioned against the sealing ring (O-ring) of the posterior part of the holder. The cornea was gently flattened over the O-ring but stretching was avoided. The anterior part of the holder was positioned on the top of the cornea and fixed in place with screws. Both compartments of the holder were filled with incubation medium. The posterior compartment was filled first to return the cornea to its natural convex position. After equilibration for about 1 hour, the anterior compartment received the test substance or the controls on the surface of the corneae. The corneae were incubated in a horizontal position at 32 ± 1 °C in the water-bath for 240 minutes.
NUMBER OF REPLICATES: 3 corneae per test group
REMOVAL OF TEST SUBSTANCE:
The test substance was rinsed off from the application side with saline.
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: Corneal opacity was determined by the amount of light transmission through the cornea via an opacitometer (OP_KiT opacitometer, Electro Design, France).
- Corneal permeability: After incubation with fluorescein dye at 32 ± 1 °C in the water-bath for 90 min in a horizontal position, passage of sodium fluorescein dye was measured using microplate reader (Versamax Molecular Devices) at 490 nm (OD490).
SCORING SYSTEM: In Vitro Irritancy Score (IVIS), IVIS = opacity value + (15x OD490 value)
DECISION CRITERIA:
Test substance with an IVIS > 55 was regarded as serious eye damage and labelled Category 1 according to CLP/EPS/GHS.
Test substance with an IVIS ≤ 3 was regarded as non-irritant and labelled in no category.
Test substance with an IVIS > 3; ≤ 55 no prediction can be made. - Irritation parameter:
- in vitro irritation score
- Remarks:
- mean value of 3 corneas
- Run / experiment:
- 240 min
- Value:
- 0
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- With the negative control (saline) neither an increase of opacity nor permeability of the corneae could be observed (mean IVIS = 1.01). The positive control (10% (w/v) Benzalkonium chloride in saline) showed clear opacity and distinctive permeability of the corneae (mean IVIS =102.27) corresponding to a classification as serious eye damaging (CLP/EPA/GHS (Cat 1)).
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The negative control resulted in opacity and permeability values that were less than the established upper limits for background opacity and permeability values for bovine corneae treated with the respective negative control.
- Acceptance criteria met for positive control: The positive control resulted in an IVIS which was within two standard deviations of the current historical mean. - Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
- Conclusions:
- Under the conditions of the Bovine Corneal Opacity and Permeability Test (BCOP) the test substance was not irritating to the eye. Application of the test substance to bovine corneae resulted in a calculated mean IVIS of 0.00.
- Executive summary:
The eye irritation potential of the test substance was determined by a bovine corneal opacity and permeability (BCOP) test according to OECD Guideline 437 and in compliance with GLP (2017). Application of the test substance to bovine corneae resulted in a calculated mean IVIS of 0.00. Thus, the test substance is not considered to be irritating to the eye.
Reference
Table 2. Results after 240 min incubation time.
Test group |
Opacity value = Difference (t240-t0) of Opacity |
Permeability at 490 nm (OD490) |
IVIS |
Mean IVIS |
||
|
|
Mean |
|
Mean |
||
Vehicle Control |
0 |
0.00 |
0.061 |
0.067 |
0.92 |
1.01 |
0 |
0.080 |
1.20 |
||||
0 |
0.061 |
0.92 |
||||
Positive Control |
115.0* |
0.014* |
115.21 |
102.27 |
||
82.00* |
0.040* |
82.60 |
||||
109.00* |
0.001* |
109.01 |
||||
Test substance |
-1.00* |
0.029* |
0.00** |
0.00 |
||
0.00* |
0.010* |
0.15* |
||||
0.00* |
0.002* |
0.03* |
*corrected values
**negative values are set to zero
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin
The skin irritation potential of the test substance was determined by an in vitro skin irritation test using a reconstructed human skin model according to OECD Guideline 439 and in compliance with GLP (2016). After treatment with the test substance for 60 min the tissue viability was 102.9% compared to the negative control (threshold for irritancy ≤ 50%). Therefore, the test substance is not considered to be irritating to the skin.
Eye
The eye irritation potential of the test substance was determined by a bovine corneal opacity and permeability (BCOP) test according to OECD Guideline 437 and in compliance with GLP (2017). Application of the test substance to bovine corneae resulted in a calculated mean IVIS of 0.00. Thus, the test substance is not considered to be irritating to the eye.
Justification for classification or non-classification
The available data on skin and eye irritation are conclusive but not sufficient for classification.
The data do not meet the criteria for classification according to Regulation (EC) 1272/2008.
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.
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