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EC number: 216-706-9 | CAS number: 1646-26-0
- 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/corrosion (OECD 404): not irritating
Eye irritation (OECD 437): not irritating
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 11 - 15 Nov 1996
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Five different test substance concentrations and the vehicle were tested on each animal.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- 1992
- Deviations:
- yes
- Remarks:
- Five different test substance concentrations and the vehicle were tested on each animal.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Version / remarks:
- 29 Dec 1992
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Danish Accreditation Fund (DANAK); National Board of Health, Medicines Division, Denmark
- Species:
- rabbit
- Strain:
- other: Albino Mol:Russian
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: MØllegaard Breeding and Research Centre, Lille Skensved, Denmark
- Weight at study initiation: 2.1 - 2.2 kg
- Housing: individually in PPO/HIPS (Noryl ®) cages (floor area: 2576 cm²) with perforated floor
- Diet: pelleted complete rabbit diet (Altromin 2123), ad libitum
- Water: domestic quality drinking water acidified with hydrochloric acid to pH 2.5, ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ±15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
- Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- other: ethanol 96% and diethyl phthalate (DEP) 1:1
- Controls:
- yes, concurrent vehicle
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentrations: 1, 5, 10, 25 and 100%
VEHICLE
- Amount(s) applied: 0.5 mL
- Concentration: 50% ethanol (96%) and 50% diethyl phthalate (DEP) - Duration of treatment / exposure:
- 4 h
- Observation period:
- 72 h
reading time points: 1, 24, 48 and 72 h - Number of animals:
- 4 females
- Details on study design:
- TEST SITE
- Area of exposure: 10 x 10 cm on the dorsal area of the trunk divided into six test sites: two anterior located test sites, two centrally located test sites and two posterior located test sites
- Type of wrap if used: The gauze patches were secured with 2.5 cm wide adhesive tape and fixed with Scanpor tape (5 cm width). Thereafter Nobifix (6 cm width) was loosely wound round the trunk.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): After removal of the tape and patches, the treated skin was cleaned with lukewarm water.
- Time after start of exposure: 4 hrs
OBSERVATION TIME POINTS
reading time points: 1, 24, 48 and 72 h
SCORING SYSTEM:
- Method of calculation: according to the method described by Draize (Draize et al., 1944) - Irritation parameter:
- erythema score
- Basis:
- animal: #1, #2 and #4
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Remarks on result:
- other: test substance concentrations: 1, 5, 10, 25 and 100%
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Remarks on result:
- other: test substance concentration: 100%
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Remarks on result:
- other: test substance concentrations: 1 and 5%
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Remarks on result:
- other: test substance concentrations: 10 and 25%
- Irritation parameter:
- edema score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Remarks on result:
- other: test substance concentrations: 1, 5, 10, 25 and 100%
- Irritant / corrosive response data:
- Very slight erythema was observed after 24 h in one rabbit at the test sites exposed to the vehicle and the test substance at concentrations of 1, 5, 10 and 25%, and in the same rabbit after 48 h at the test sites exposed to 10% and 25% test substance concentrations. All effects were fully reversible within 72 h after dosing. No effects occurred the test site exposed to 100%.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of the Acute Dermal Irritation/Corrosion Test in rabbits the test substance does not possess any skin irritating potential.
- Executive summary:
The primary skin irritant effect was investigated according to OECD Guideline 404, "Acute Dermal Irritation/Corrosion", 1992 and GLP. The study was extended to investigate five different concentrations of the test article and a vehicle control on
each animal. Four rabbits were exposed to different concentrations of the test article at six skin sites. After 4 hours of exposure the test article was removed and the skin was examined 1, 24, 48 and 72 hours after termination of exposure. Under the experimental conditions described in this report, the mean score for erythema and oedema in the four rabbits used were as follows: 0.0, 0.2, 0.2, 0.1, 0.1, 0.1 (100%, 25%, 10%, 5%, 1% and vehicle) and 0.0, 0.0, 0.0, 0.0, 0.0, 0.0 (100%, 25%, 10%, 5%, 1% and vehicle), respectively.
Reference
Table 1. Results of skin irritation study.
|
|
Erythema Score at hours |
Edema Score |
|||||||||
Rabbit no. |
Test substance concentration [%] |
1 |
24 |
48 |
72 |
mean (24/48/72 h) |
1 |
24 |
48 |
72 |
mean (24/48/72 h) |
|
1 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
25 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
10 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
Vehicle |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
2 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
25 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
10 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
Vehicle |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
3 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
25 |
0 |
1 |
1 |
0 |
0.67 |
0 |
0 |
0 |
0 |
0 |
||
10 |
0 |
1 |
1 |
0 |
0.67 |
0 |
0 |
0 |
0 |
0 |
||
5 |
0 |
1 |
1 |
0 |
0.33 |
0 |
0 |
0 |
0 |
0 |
||
1 |
0 |
1 |
0 |
0 |
0.33 |
0 |
0 |
0 |
0 |
0 |
||
Vehicle |
0 |
1 |
0 |
0 |
0.33 |
0 |
0 |
0 |
0 |
0 |
||
4 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
25 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
10 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
Vehicle |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
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:
- 13 Mar 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:
- (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, Aschaffenburg, Germany
- Characteristics of donor animals: at least 9 month old
- Storage, temperature and transport conditions of ocular tissue: The isolated eyes were stored in Hank's Buffered Salt Solution (HBSS) containing 1% (v/v) Penicillin/Streptomycin (100 units/mL penicillin and 100 μg/mL 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.
- 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.
- Indication of any antibiotics used: yes, 1% (v/v) Penicillin/Streptomycin (100 units/mL penicillin and 100 μg/mL streptomycin) in transport medium - 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 0.9% NaCl in deionised water (saline)
POSITIVE CONTROL
- Amount applied: 0.75 mL
- Concentration: 10% (w/v) benzalkonium in 0.9% NaCl in deionised water (saline)
NEGATIVE CONTROL
- Amount applied: 0.75 mL
- Concentration: 0.9% NaCl in deionised water (saline) - Duration of treatment / exposure:
- 240 min at 32 ± 1 °C
- 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: The passage of sodium fluorescein dye was measured with the aid of a 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/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 corneae
- Run / experiment:
- 240 min
- Value:
- 0.16
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- 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 = 1.28). The positive control (10% (w/v) Benzalkonium chloride in saline) showed clear opacity and distinctive permeability of the corneae (mean IVIS = 116.83) corresponding to a classification as serious eye damaging (CLP/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 postive control: The positive control resulted in an IVIS which was within two standard deviations of the current historical mean. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of the BCOP assay the test substance was not irritating to the eye. Application of the test substance to bovine corneae resulted in a calculated mean IVIS of 0.16.
- Executive summary:
BCOP assay was performed according to OECD 437 and GLP. After a first opacity measurement of the fresh bovine corneae (t0), the 20% (w/v) suspension in saline (0.9% (w/v) NaCl in deionised water) of the test item, the positive and the negative controls were applied to corneae fixed in an incubation chamber in horizontal position and incubated for 240 minutes at 32 ± 1 °C. Relative to the negative control, the test item did not cause an increase of the corneal opacity or permeability. The calculated mean in vitro irritancy score was 0.16. No classification is required according to Regulation (EC) 1272/2008.
Reference
Table 2. Results after 240 min incubation.
Test group |
Opacity value = Difference (t240-t0) of Opacity |
Permeability at 490 nm (OD490) |
IVIS |
Mean IVIS |
||
|
|
Mean |
|
Mean |
||
Negative Control |
0 |
0.33 |
0.048 |
0.063 |
0.72 |
1.28 |
1 |
0.068 |
2.02 |
||||
0 |
0.073 |
1.10 |
||||
Positive Control |
112.67* |
0.080* |
113.87 |
116.83 |
||
117.67* |
0.114* |
119.38 |
||||
115.67* |
0.106* |
117.26 |
||||
Test substance |
-1.33* |
0.003* |
-1.29 |
0.16 |
||
0.67* |
0.040* |
1.27 |
||||
-0.33* |
0.056* |
0.51 |
*corrected values
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 vivo skin irritation test in rabbits according to OECD Guideline 404 and in compliance with GLP (1996). 4 rabbits were each treated with the test substance at concentrations of 1, 5, 10, 25% diluted in DEP/ethanol (1:1) and 100% under semiocclusive dressing for 4 h. The vehicle was applied as control. Treatment with the vehicle and test substance at concentrations of 1, 5, 10 and 25% caused slight skin irritation in one animal (mean erythema values over 24, 48 and 72 h: 0.33, 0.33, 0.67, 0.67, 0.67 and 0.00; edema score: 0.0), which was fully reversible within 72 h. The other three animals did not show any signs of irritation (erythema and edema scores over 24, 48 and 72 h: 0.00).Therefore, the test subsatance 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 0.16. Thus, the test substance is not considered to be irritant to the eye.
Justification for classification or non-classification
The available data on skin and eye irritation do not meet criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.
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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