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EC number: 222-883-3 | CAS number: 3648-18-8
- 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
Warren (2013a) OECD 431, EU Method B.40, Not corrosive (in vitro, Reconstructed Human Epidermis (RHE) model).
Warren (2013b), OECD 439, EU Method B.46, Not irritating (in vitro, Reconstructed Human Epidermis (RHE) model).
EYE
Sanders (2013) OECD 405, EU Method B.5, Non-irritant (Rabbit, male).
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:
- 02 October 2012 to 08 October 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to valid guidelines and the study was conducted under GLP conditions.
- 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)
- Amount / concentration applied:
- 10 µL of test material was applied topically.
- Duration of treatment / exposure:
- 15 minutes.
- Irritation / corrosion parameter:
- other: other: Relative viability (%)
- Value:
- 101.8
- Remarks on result:
- other:
- Remarks:
- Basis: mean. Time point: 15 minutes. Max. score: 100.0. (migrated information)
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the test, the test material was considered to be a non-irritant.
- Executive summary:
The skin irritation potential of the test material was determined in vitro, in accordance with standardised guidelines OECD 439 and EU Method B.46 using the EPISKIN™ Reconstructed Human Epidermis (RHE) Model.
During the study triplicate tissues were treated with the test material 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-labelled 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 labelled 96 well plate. The optical density (OD) was measured at 540 nm (OD540).
Under the conditions of the study, the relative mean viability of the test material treated tissues was 101.8 % after the 15 minute exposure period. The quality control criteria required for acceptance of results were satisfied and the test material was concluded to be a non-irritant to the skin.
Reference
Direct MTT Reduction
The MTT solution containing the test material did not turn blue which indicated that the test material did not directly reduce MTT.
Main Test - Results
The relative mean viability of the test material treated tissues was 101.8 % after a 15 minute exposure period.
Table 1: Results
Item |
OD540 of tissues |
Mean OD540 of triplicate tissues |
± SD of OD540 (%) |
Relative individual tissue viability (%) |
Relative mean viability (%) |
± SD of Relaive mean viability (%) |
|
Negative control item |
0.727 |
0.725 |
0.044 |
100.3 |
100* |
6.1 |
|
0.680 |
93.8 |
||||||
0.768 |
105.9 |
||||||
Positive control item |
0.070 |
0.053 |
0.015 |
9.7 |
7.3 |
2.1 |
|
0.046 |
6.3 |
||||||
0.043 |
5.9 |
||||||
Test material |
0.785 |
0.738 |
0.110 |
108.3 |
101.8 |
15.2 |
|
0.612 |
84.4 |
||||||
0.816 |
112.6 |
SD = standard deviation
* = the mean viability of the negative control tissues is set at 100 %
Quality Criteria
The relative mean tissue viability for the positive control treated tissues was 7.3 % relative to the negative control treated tissues and the standard deviation value of the percentage viability was 2.1 %. The positive control criterion was therefore satisfied.
The mean OD540 for the negative control treated tissues was 0.725 and the standard deviation value of the percentage viability was 6.1 %. The negative control acceptance criterion was therefore satisfied.
The standard deviation calculated from individual percentage tissue viabilities of the three identically treated tissues was 15.2 %. The test material acceptance criterion was therefore satisfied.
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:
- 12 November 2012 to 22 November 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to valid guidelines and the study was conducted under GLP conditions.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- 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
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.53 - 2.59 kg
- Housing: individually in suspended cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light.
IN-LIFE DATES: From 12 November 2012 - 22 November 2012 - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL - Duration of treatment / exposure:
- - Dose administration: 0.1 mL of the test material was placed into the conjunctival sac of the right eye of one rabbit by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were then held together for about 1 second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. After consideration of the initial pain reaction (see Table 2) in the first treated animal, a second animal was treated.
- Observation period (in vivo):
- Animals were observed up to 72 hours post administration.
- Number of animals or in vitro replicates:
- One male initially, followed by a further male once the irritation potential was fully assessed in the first animal.
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
Washing: Irrigation was not performed.
SCORING SYSTEM:
The reactions observed were scored in accordance with the criteria of Draize (1977).
TOOL USED TO ASSESS SCORE:
Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope. - Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- other: 24, 48 and 72 hours
- Score:
- 1.67
- Max. score:
- 110
- Reversibility:
- fully reversible within: 72 hours
- Irritation parameter:
- cornea opacity score
- Remarks:
- (opacity)
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Remarks on result:
- other: Mean at 24, 48 and 72 hours
- Irritation parameter:
- cornea opacity score
- Remarks:
- (opacity)
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Remarks on result:
- other: Mean at 24, 48 and 72 hours
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Remarks on result:
- other: Mean at 24, 48 and 72 hours
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Remarks on result:
- other: Mean at 24, 48 and 72 hours
- Irritation parameter:
- conjunctivae score
- Remarks:
- (redness)
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.66
- Max. score:
- 3
- Reversibility:
- fully reversible within: 72 hours
- Remarks on result:
- other: Mean at 24, 48 and 72 hours
- Irritation parameter:
- conjunctivae score
- Remarks:
- (redness)
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 3
- Reversibility:
- fully reversible within: 24 hours
- Remarks on result:
- other: Mean at 24, 48 and 72 hours
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 24 hours
- Remarks on result:
- other: Mean at 24, 48 and 72 hours
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 24 hours
- Remarks on result:
- other: Mean at 24, 48 and 72 hours
- Irritant / corrosive response data:
- No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Minimal conjunctival irritation was noted in both treated eyes at the 24 hour observation and persisted in one treated eye at the 48 hour observation. One treated eye appeared normal at the 48 hour observation and the other treated eye appeared normal at the 72 hour observation.
- Other effects:
- Both animals showed expected gain in bodyweight during the study.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the test, the test material only elicited slight reactions in any of the animals during the course of the study that meant the test material does not require classification as an eye irritant.
- Executive summary:
The eye irritation potential of the test material was determined in accordance with standardised guidelines OECD 405 and EU Method B.5, in vivo. During the study, 0.1 mL of test material was placed into one eye of each of two rabbits and assessed for up to 72 hours to determine the grade of ocular reaction. No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Minimal conjunctival irritation was noted in both treated eyes at the 24 hour observation and persisted in one treated eye at the 48 hour observation. One treated eye appeared normal at the 48 hour observation and the other treated eye appeared normal at the 72 hour observation. Under the conditions of the test, the test material only elicited slight reactions in any of the animals during the course of the study that meant the test material does not require classification as an eye irritant.
Reference
Table 3: Results
Animal |
No. 1 |
No. 2 |
||||||
Time after treatment |
1 h |
24 h |
48 h |
72 h |
1 h |
24 h |
48 h |
72 h |
Cornea |
||||||||
Degree of opacity |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Area of cornea involved |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Iris |
||||||||
Iris |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Conjunctivae |
||||||||
Redness |
2 |
1 |
1 |
0 |
2 |
1 |
0 |
0 |
Chemosis |
2 |
1 |
0 |
0 |
2 |
1 |
0 |
0 |
Discharge |
1 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
Individual total scores |
10 |
4 |
2 |
0 |
10 |
4 |
0 |
0 |
Initial pain reaction: When the test material was instilled in the eye, the animals were observed to blink a few times within one or two minutes. The initial pain reaction of 1 was given to each animal tested.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin
A two tiered in vitro testing strategy was adopted to investigate skin irritation and corrosion, both of which are key to addressing this endpoint.
Warren (2013a) determined the potential for the test material to cause skin corrosion using the EPISKIN™ Reconstructed Human Epidermis (RHE) Model. Under the conditions of the test the relative mean viability of treated tissues after exposure for 240, 60 and 3 minutes were, 83.5%, 87.1% and 97.1, respectively. Since all values were ≥ 35% relative to the negative control the test material can be predicted to be non-corrosive.
Similarly, Warren (2013b) determined the potential for the test material to cause skin irritation using the EPISKIN™ Reconstructed Human Epidermis (RHE) Model. Under the conditions of the test, the relative mean viability of the treated tissue was 101.8 % after a 15 minute exposure period. Since the cell viability was > 50% relative to the negative control the test material can be predicted to be non-irritating to the skin.
Both studies were performed under GLP conditions and in line with standardise guidelines. Accordingly they have both been assigned a reliability score of 1 in accordance with the principles for assessing data quality as defined by Klimisch (1997).
Based on these results, it can be concluded that the test material does not cause corrosion or irritation when exposed to the skin. The data is sufficient in addressing this endpoint, negating the need for further in vivo testing.
Eye
The key study (Sanders, 2013) determined the potential for the test material to cause eye irritation in vivo in accordance with GLP and standardised guidelines. The study was assigned a reliability score of 1 in line with the principles for assessing data quality as defined in Klimisch (1997). Under the conditions of the test, the test material only elicited slight reactions in any of the animals during the course of the study, meaning the test material does not require classification as an eye irritant.
The supporting study (Warren, 2013c) determined the eye irritation potential of the test material in vitro, using the SkinEthic Reconstituted Human Corneal model. The study was assigned a reliability score of 2 in line with the principles for assessing data quality as defined in Klimisch (1997). Under the conditions of the study the relative mean viability of the test material treated tissues, after a 10 minute exposure period, was 86.8 %. In accordance with the criteria defined in the study the test material was considered to be a "non-irritant". The result was in good agreement with the findings of the key study and is sufficient to act as supporting data.
Justification for selection of skin irritation / corrosion endpoint:
A two tiered testing strategy was adopted to address this endpoint. Both the corrosivity and irritation studies are important in addressing this endpoint, however, skin irritation potential cannot be assessed on the basis of the information provided in the corrosion study alone. Therefore the skin irritation has been selected to represent this endpoint. Warren (2013b) was performed according to standardised guidelines and under GLP conditions, being assigned a reliability score of 1 in line with Klimisch (1997).
Justification for selection of eye irritation endpoint:
The key study (Sanders, 2013) was performed in vivo, according to standardised guidelines and under GLP conditions. It was assigned a reliability score of 1 in accordance with the criteria outlined in Klimisch (1997), and is considered suitable to be the key study for this endpoint.
Justification for classification or non-classification
Skin
In accordance with with criteria for classification and labelling as defined in Regulation (EC) No. 1272/2008 (CLP) and Directive 67/548/EEC (DSD), the test material does not require classification for skin irritation or corrosion.
Eye
In accordance with the criteria for classification and labelling as defined in Regulation (EC) No. 1272/2008 and Directive 67/548/EEC (DSD), the test material does not require classification for eye irritation.
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