Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 600-896-9 | CAS number: 109089-77-2
- 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 in vitro: Key study. Method according to OECD 439, GLP study. The mean corrected percent viability of the treated tissues was 93.2 %, versus 1.3% in the positive control (5% SDS). Therefore, the test item is not irritant to the skin.
Eye irritation in vitro: Key study. Method according to OECD 437, GLP study. According to the overall in vitro classification, no prediction can be made since the combination of the 3 endpoints for the test item was 1 x III, 2 x II.
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:
- From June 6th, 2018 to June 14th, 2018
- 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)
- 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)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- other: normal human keratinocytes.
- Cell source:
- other: human adult donor, not specified.
- Source strain:
- not specified
- Details on animal used as source of test system:
- The SkinEthic™ RHE model has been validated for irritation testing (Validation study based on the original ECVAM Performance Standards (21) in 2008) and its use is recommended by the relevant OECD guideline for irritation testing (OECD No. 439); therefore, it was considered to be suitable for this study.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: SkinEthic RHE® model
- Tissue batch number(s): 18-RHE-064
- Delivery date: 12/06/2018
- Expiration date: 18/06/2018
- Date of initiation of testing: 06/06/2018
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature
- Temperature of post-treatment incubation (if applicable): 37ºC
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 25 x 1 mL of DPBS
- Observable damage in the tissue due to washing: no
- Modifications to validated SOP: no
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 300 µL of a MTT solution at 1.0 mg/mL
- Incubation time: 3 hours at 36.2 - 38.0°C, 5% CO2
- Spectrophotometer: ELx800 absorbance microplate reader (BioTek)
- Wavelength: 570 nm
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: O.D. = 1.1 (CV 2.7%)
- Barrier function: n/a
- Contamination: no
NUMBER OF REPLICATE TISSUES: 3
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE: no interference.
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritant to skin if the viability after 42 minutes exposure is less than or equal to 50%.
- The test substance is considered to be non-irritant to skin if the viability after 42 minutes exposure is greater than 50%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 16 mg (32mg/cm2)
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 16 µL
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 16 µL
- Concentration (if solution): 5% SDS - Duration of treatment / exposure:
- 42 minutes
- Duration of post-treatment incubation (if applicable):
- 42 hours
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean
- Value:
- 93.2
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Remarks:
- (DPBS)
- Positive controls validity:
- valid
- Remarks:
- 1.3% viability (5% SDS)
- Other effects / acceptance of results:
- - OTHER EFFECTS:
- Visible damage on test system: no
- Direct-MTT reduction: no
- Colour interference with MTT: no
DEMONSTRATION OF TECHNICAL PROFICIENCY: yes. A full demonstration of proficiency was performed for the EpiSkin-SM model, plus a reduced validation with the SkinEthic RHE model. Adequate results were obtained for the evaluated chemicals.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes.
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes - Interpretation of results:
- GHS criteria not met
- Remarks:
- (EU criteria)
- Conclusions:
- The mean corrected percent viability of the treated tissues was 93.2 %, versus 1.3% in the positive control (5% Sodium Dodecyl Sulfate). Therefore, the test item is not irritant to the skin.
- Executive summary:
An in vitro skin irritation test of the test item was performed in a reconstructed human SkinEthic™ RHE epidermis model, according to OECD TG 439 (GLP study). Three epidermis units were treated with 16 mg test item for 42 minutes at room temperature. Exposure of the test item was terminated by rinsing with 25 x 1 mL of DPBS. The epidermis units were then incubated at 37°C for 42 hours in an incubator with 5% CO2. The viability of each disk was assessed by incubating the tissues with MTT, extracting the precipitated formazan crystals using isopropanol during 2 hours under gentle agitation in the dark, and measuring the concentration of formazan by determining the OD at 570 nm, just after dilution of the extracts 1:2 in isopropanol. Under test conditions, the mean corrected percent viability of the treated tissues was 93.2%, versus 1.3% in the positive control (5% Sodium Dodecyl Sulfate). Therefore, the test item is not irritant to the skin.
Reference
Table 1. Summary of results (12/06/2018).
|
Skin |
OD |
Mean OD/ |
Mean OD/ |
Viability |
Mean |
SD |
Conclusion |
Negative |
1 |
0.936 |
0.999 |
0.923 |
108.3 |
100.0 |
7.9 |
- |
2 |
0.852 |
0.853 |
92.4 |
|||||
3 |
0.914 |
0.916 |
99.3 |
|||||
Positive |
4 |
0.011 |
0.013 |
0.012 |
1.4 |
1.3 |
0.1 |
Irritant |
5 |
0.012 |
0.012 |
1.3 |
|||||
6 |
0.012 |
0.012 |
1.3 |
|||||
Test ítem PH-16/0272 |
13 |
0.836 |
0.892 |
0.860 |
96.7 |
93.2 |
3.4 |
Non irritant |
14 |
0.823 |
0.830 |
90.0 |
|||||
15 |
0.856 |
0.859 |
93.1 |
# mean of 3 values (triplicate of the same extract).
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:
- From May 25th, 2018 to May 28th, 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU method B.48 (Isolated chicken eye test method for identifying occular corrosives and severe irritants)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- chicken
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: eyes collected from chickens obtained from a slaughterhouse (Etablissement Brun, 33820 Etauliers, France) where they are killed for human consumption.
- Characteristics of donor animals (e.g. age, sex, weight): 7 weeks old. 1.5 - 2.5 kg.
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): Because eyes were dissected in the laboratory, the intact heads were transported from the slaughterhouse at ambient temperature in plastic boxes humidified with towels moistened with physiological saline.
- Time interval prior to initiating testing: The heads were collected on 28 May 2018 at 8:30 am. The eyes were enucleated at Phycher on 28 May 2018 at 10:05 am.
- indication of any existing defects or lesions in ocular tissue samples: no.
- Indication of any antibiotics used: no. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 mg - Duration of treatment / exposure:
- 10 seconds
- Number of animals or in vitro replicates:
- 3 replicates per group (test item, positive control, negative control)
- Details on study design:
- SELECTION AND PREPARATION OF ISOLATED EYES: In order to control the quality of the procedure, the eyeballs used for the purpose of the experiment were assessed for potential damage. After being placed in the superfusion apparatus, the eyes were examined with a slit-lamp microscope to ensure that they have not been damaged during the dissection procedure. Corneal thickness was also measured at this time at the corneal apex using the depth measuring device on the slit-lamp microscope. Eyes with; (i), a fluorescein retention score of > 0.5; (ii) corneal opacity > 0.5; or, (iii), any additional signs of damage were replaced. For eyes that are not rejected based on any of these criteria, individual eyes with a corneal thickness deviating more than 10% from the mean value for all eyes are to be rejected.
EQUILIBRATION AND BASELINE RECORDINGS: Once all eyes had been examined and approved, the eyes were incubated between 45 and 64 minutes to equilibrate them to the test system prior to dosing. Following the equilibration period, a zero reference measurement was recorded for corneal thickness and opacity to serve as a baseline (i.e., time = 0). The fluorescein score determined at dissection was used as the baseline measurement for that endpoint.
NUMBER OF REPLICATES: 3
NEGATIVE CONTROL USED: 30 µL physiological saline
SOLVENT CONTROL USED: not applicable.
POSITIVE CONTROL USED: 30 mg sodium hydroxide
APPLICATION DOSE AND EXPOSURE TIME: 30 mg test item, exposure 10 seconds.
OBSERVATION PERIOD: Treated corneas were evaluated pretreatment and starting at 30, 75, 120, 180, and 240 minutes (± 5 minutes) after the post-treatment rinse.
REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: the test item was rinsed from the eye with 20 mL of physiological saline at ambient temperature (2 rinses with 10 mL each).
- Indicate any deviation from test procedure in the Guideline: no.
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: corneal opacity was calculated by using the area of the cornea that was most densely opacified for scoring. The mean corneal opacity value for all test eyes was calculated for all observation time points. Based on the highest mean score for corneal opacity, as observed at any time point, an overall category score was then given for each test or control item.
- Damage to epithelium based on fluorescein retention: The mean fluorescein retention value for all test eyes was calculated for the 30-minute observation
time point only, which was used for the overall category score given for each test or control item.
- Swelling: measured with optical pachymeter on a slit-lamp microscope (HaagStreit BP900 slit-lamp microscope with depth-measuring device no. I); slit-width setting: the slit-width was set at 9½, equalling 0.095 mm. The mean percentage of corneal swelling for all test eyes was calculated for all observation time points. The value was determined from corneal thickness measurements. Based on the highest mean score for corneal swelling, as observed at any time point, an overall category score was then given for each test item.
- Macroscopic morphological damage to the surface: qualitative assessment. The aim of this evaluation was to determine whether any “pitting” of corneal epithelial cells, “loosening” of epithelium, “roughening” of the corneal surface and “sticking” of the test item to the cornea were visible.
- Others (e.g, histopathology): no.
SCORING SYSTEM:
- Mean corneal swelling (%) was calculated as follows: [(corneal thickness at time t - corneal thickness at time 0)/corneal thickness at time 0] x 100.
- Mean maximum opacity score:
0 No opacity
0.5 Very faint opacity
1 Scattered or diffuse areas; details of the iris clearly visible
2 Easily discernible translucent area; details of the iris are slightly obscured
3 Severe corneal opacity; no specific details of the iris are visible; size of the pupil is barely discernible
4 Complete corneal opacity; iris invisible
- Mean fluorescein retention score at 30 minutes post-treatment:
0 No fluorescein retention
0.5 Very minor single cell staining
1 Single cell staining scattered throughout the treated area of the cornea
2 Focal or confluent dense single cell staining
3 Confluent large areas of the cornea retaining fluorescein
DECISION CRITERIA: as indicated in the TG. - Irritation parameter:
- fluorescein retention score
- Run / experiment:
- mean
- Value:
- 2.3
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE class III
- Irritation parameter:
- cornea opacity score
- Run / experiment:
- mean
- Value:
- 1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE class II
- Irritation parameter:
- percent corneal swelling
- Run / experiment:
- mean
- Value:
- 7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: ICE class II
- Irritation parameter:
- morphological effects
- Run / experiment:
- mean
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: no. No morphological effects were noted, whatever the examination time.
- Other observations: the test item required additional rinsing to be removed from the cornea.
DEMONSTRATION OF TECHNICAL PROFICIENCY: yes.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes.
- Acceptance criteria met for positive control: yes.
- Range of historical values if different from the ones specified in the test guideline: no. - Interpretation of results:
- study cannot be used for classification
- Remarks:
- (EU criteria)
- Conclusions:
- The combinations of the 3 endpoints for the test item were 1 x III, 2 x II. Therefore, no prediction can be made.
- Executive summary:
An in vitro (ex vivo) study was conducted in order to determine the potential severe eye damaging effects of the test item according to the OECD guideline 438 under GLP conditions. Eyeballs were isolated from chickens killed for human consumption and after the appropriate preparation were exposed to either 30 mg of the test item, 30 mg of sodium hydroxide (positive control) or 30 µL of physiological saline (negative control). Three eyeballs were used in each group. Fluorescein retention, corneal opacity and corneal swelling were evaluated, then the results of each endpoint were assigned to ICE classes according to OECD guideline 438. According to the overall in vitro classification (CLP Regulation), no prediction can be made since the combinations of the 3 endpoints for the test item were 1 x III, 2 x II.
Reference
Table 1. Test item results (30 mg), 28/05/2018.
Endpoint measured |
Eye No. |
0 |
30 |
75 |
120 |
180 |
240 |
Corneal opacity |
13 |
0 |
1 |
1 |
1 |
1 |
1 |
14 |
0 |
1 |
1 |
1 |
1 |
1 |
|
15 |
0 |
1 |
1 |
1 |
1 |
1 |
|
Mean |
0.0 |
1.0 |
1.0 |
1.0 |
1.0 |
1.0 |
|
ICE class |
II |
||||||
Fluorescein retention |
13 |
0.5 |
3 |
- |
- |
- |
- |
14 |
0.5 |
2 |
- |
- |
- |
- |
|
15 |
0.5 |
2 |
- |
- |
- |
- |
|
Mean |
0.5 |
2.3 |
- |
- |
- |
- |
|
ICE class |
III |
||||||
Corneal thickness |
13 |
0.59 |
0.59 |
0.61 |
0.63 |
0.63 |
0.63 |
14 |
0.64 |
0.64 |
0.66 |
0.66 |
0.66 |
0.66 |
|
15 |
0.59 |
0.60 |
0.64 |
0.64 |
0.65 |
0.65 |
|
Corneal swelling (%) |
13 |
- |
0 |
3 |
7 |
7 |
7 |
14 |
- |
0 |
3 |
3 |
3 |
3 |
|
15 |
- |
2 |
8 |
8 |
10 |
10 |
|
Mean |
- |
1 |
5 |
6 |
7 |
7 |
|
ICE class |
II |
||||||
Combination of the 3 endpoints |
1 x III, 2 x II |
||||||
Classification |
No prediction can be made |
No morphological effects were noted, whatever the examination time.
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
Based on the available information, the substance is not classified for irritation/corrosion in accordance with CLP, Regulation (EC) No. 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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.