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EC number: 816-312-2 | CAS number: 92343-70-9
- 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
Irritation corrosion was studied in vitro in GLP compliant OECD 439 and OECD 492 assays. Both assays were negative.
In addition skin irritation was studied in vivo according to OECD 404 to support registration in China. In this assay the dermal exposure to the test substances resulted in severe skin effects which did not resolve
within the 14 day observation period. Therefore, the test item is considered to be a skin irritant. An in vivo eye irritation study was thus not performed due to animal welfare reasons.
According to the Regulation (EC) No 1272/2008, a skin irritant substance may be considered as leading to eye irritation. As worst case approach, the test item was therefore considered to be irritating to eye despite the negative result from the in vitro eye irritation study.
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:
- weight of evidence
- Study period:
- December 5, 2017 - May 4, 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- Commission Regulation (EU) No. 640/2012 amending, for the purpose of its adaption to technical progress, Regulations (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and the council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- July 28, 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Skinethic skin irritation test -42bis Standard operating procedure (SOP) 2009
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Before application, the test item was pre-warmed to 37°C to get a liquid, which was applied neat to the tissues. - Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- foreskin from a single donor
- Justification for test system used:
- standard model
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- No vehicle used in this study; The test item was applied neat to the tissues.
- Details on test system:
- CELL CULTURE
- Supplier: EpiSkin/SkinEthic Laboratories, Lyon, France)
- Source: human keratinocytes cultured on a polycarbonate filter in conditions which permit their terminal differentiation
- Format: 24 well plate
- Batch: 18-RHE-037
- Expires: April 16, 2018
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment: room temperature
- Temperature of post-treatment incubation: 37°C
REMOVAL OF THE TEST MATERIAL AND CONTROL
After the end of the treatment interval, the residual test item was removed immediately by gently rinsing with a minimum volume of 25 mL DPBS using a pipette. Excess DPBS was removed by gently shaking the inserts and blotting the bottom with blotting paper.
DYE BINDING METHOD
- Dye used in the dye-binding assay: MTT
- Spectrophotometer:ELx800, BioTek Instruments GmbH, Bad Friedrichshall, Germany at 570 nm - Control samples:
- yes, concurrent negative control
- Amount/concentration applied:
- TEST MATERIAL: 16 µL
NEGATIVE CONTROL: 16 µL (Dulbecco`s Phosphate-Buffered Saline)
POSITIVE CONTROL: 16 µL (5% aqueous solution of sodium dodecyl sulfate in deionised water) - Duration of treatment / exposure:
- 42 min (± 1 minute)
- Duration of post-treatment incubation (if applicable):
- 42 hours (± 1 hour)
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Experiment 1 / Run 1
- Value:
- 55.9
- Vehicle controls validity:
- not applicable
- Remarks:
- The test item was applied neat to the tissues
- 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: none
- Direct-MTT reduction: none
- Colour interference with MTT: none
ACCEPTANCE OF RESULTS:
Acceptability of the Quality Control Data of the Skin Model with Reference to Historical Batch Data:
Acceptance Criterion Result
Negative control OD ≥ 0.8 and ≤ 3.0 1.507 to 1.756
Acceptability of the Positive and Negative Control stated by Episkin/SkinEthic Laboratories:
Acceptance Criterion Result
Mean OD negative control ≥ 1.2 1.660
Mean viability positive control < 40% 1.3%
SD of group-mean value ≤ 18% 15.4% (positive control)
8.1% (negative control)
Acceptability of the Positive and Negative Control based on Historical Data of the Testing Laboratory:
Acceptance Criterion Result
Mean OD negative control ≥ 1.455 1.660
Mean viability positive control ≤ 2.97% 1.3%
Test Item Data Acceptance Criteria:
Acceptance Criterion Result
SD of group-mean value ≤ 18% 8.4%
The study met all acceptance criteria. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- This study was performed according to GLP and the methods applied are fully compliant with OECD TG 439. Under the conditions of the present study, the test item is not considered to possess an irritant potential to skin (UN GHS: No Category).
- Executive summary:
Objective
The objective of the present study was to investigate the potential of the test item to induce skin irritation in an in vitro human skin model.
Study Design
The test item was applied topically to a human reconstructed skin model followed by determination of the cell viability. Cell viability was determined by enzymatic conversion of vital dye MTT into a blue formazan salt and measurement of the formazan salt after extraction from tissues. The percent reduction of cell viability in comparison to untreated negative controls was used to predict the skin irritation potential.
Triplicates of the human skin RHE-model were treated with the test item, the negative or the positive control for 42 minutes (± 1 minute). 16 µL of either the test item, the negative control (DPBS-buffer) or the positive control (5% aqueous solution of sodium dodecyl sulfate) were applied to the tissues.
Results
All acceptability criteria after treatment with the negative control (DPBS-buffer) and the positive control (5% aqueous solution of sodium dodecyl sulfate) were met.
Following treatment with the test item, the tissue viability was 55.9% and, thus, higher than 50%,i.e.according to OECD 439 the test item is considered as non-irritant to skin (UN GHS: No Category).
Conclusion
Under the conditions of the present study, the test item is not considered to possess an irritant potential to skin (UN GHS: No Category).
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 01 Feb 2019 - 25 Apr 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Species: Rabbit
Strain: New Zealand White
Condition: SPF-Quality
Source: Charles River France, L’Arbresle, France
Number of Animals: 1 Female.
Age at the Initiation of Dosing: A young adult animal (approximately 27 weeks old) was selected.
Weight at the Initiation of Dosing: 4210 g.
Acclimatisation: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C
- Humidity (%): 57 to 58%.
- Air changes (per hr): 10 or greater
- Photoperiod (hrs dark / hrs light): 12/12 hours
- Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- 0.5 g
- Duration of treatment / exposure:
- 4 h
- Observation period:
- 14 days
- Number of animals:
- 1 female
- Details on study design:
- TEST SITE
Approximately 24 hours before dosing, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring,
the treated skin area was re-clipped at least 3 hours before the observations.
The animal was treated by dermal application of 0.5 grams of the test item. The test item was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test item using tap water.
SCORING SYSTEM:
- Method of calculation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 and 14 days after the removal of the dressings and test item. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of the animal served as control.
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:
Erythema and eschar formation:
No erythema .............................................................................................................................................................. 0
Very slight erythema (barely perceptible) ................................................................................................................. 1
Well-defined erythema ............................................................................................................................................... 2
Moderate to severe erythema..................................................................................................................................... 3
Severe erythema (beef redness) * ............................................................................................................................ 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.
Oedema formation:
No oedema.................................................................................................................................................................. 0
Very slight oedema (barely perceptible)..................................................................................................................... 1
Slight oedema (edges of area well-defined by definite raising)................................................................................. 2
Moderate oedema (raised approximately 1 millimeter)................................................................................................ 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) ................................. 4 - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 days
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 3.3
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 days
- Irritant / corrosive response data:
- Four hours exposure to 0.5 g of the test item resulted in severe erythema and severe oedema in the treated skin area of the rabbit. Gray necrosis of the edges of the application area were noted from 24 hours after application until 72 hours after application. Furthermore, reduced flexibility of the skin, scabs, scaliness, superficial fissures and bald skin were noted during the observation period.
The skin irritation did not completely resolve within the 14 days observation period.
Based on these severe irritation results, no further animals were treated. - Other effects:
- No signs of systemic toxicity were observed in the animal during the test period and no mortality occurred.
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of the test material to the intact rabbit skin. However, the test item is considered to be irritating to skin.
- Executive summary:
The objective of this primary skin irritation study was to assess the possible irritation or corrosion potential of a single dose of the test material when administered to the intact skin of rabbits.
The study was carried out in compliance with the guidelines described in:
• OECD No. 404 (2015) "Acute Dermal Irritation / Corrosion".
• EC No 440/2008, part B: "Acute Toxicity: Dermal Irritation/Corrosion".
• EPA, OPPTS 870.2500 (1998), "Acute Dermal Irritation".
• JMAFF Guidelines (2000), including the most recent revisions.
One rabbit was exposed to 0.5 grams of the test material, by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours and 7 and 14 days after exposure.
Exposure to the test material resulted in severe skin effects which did not resolve within the 14 day observation period. Severe erythema and severe oedema were seen in the treated skin area of the rabbit.
Gray discoloration (signs of necrosis) at the edges of the application area were noted from 24 hours after application until 72 hours after application.
Furthermore, reduced flexibility of the skin, scabs, scaliness, superficial fissures and bald skin were noted during the observation period. The skin irritation did not completely resolve within the 14 days observation period.
No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of the test material to the intact rabbit skin.
Based on these results, the test item is considered to be irritating to skin.
Referenceopen allclose all
Group | Time / [min] | Mean OD | Mean Relative viability / [%] |
Negative Control | 42 | 1.660 | 100 |
Positive Control | 42 | 0.022 |
1.3 |
Test Material |
42 |
0.928 |
55.9 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (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:
- January 29, 2018 - June 19, 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
- Version / remarks:
- October 9, 2017
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: DB-ALM Protocol No. 164: Ocular Irritation Assay for Chemicals using EpiOcular™ EIT,
- Version / remarks:
- September 14, 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EpiOcular Eye Irritation Test (OCL-200-EIT) for the prediction of acute ocular irritation of chemicals; For use with MatTek Corporation`s Reconstructed Human EpiOcular Model; MatTek Corporation
- Version / remarks:
- June 29, 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Before application, the test item was pre-warmed to 37°C to get a liquid, which was applied neat to the tissues.. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL: 50 µL per tissue
NEGATIVE / VEHICLE CONTROL: 50 µL per tissue
Sterile deionized water was used as negative control.
POSITIVE CONTROL: 50 µL per tissue
Designation: Methyl acetate
Supplier: MatTek In Vitro Life Science Laboratories
Lot-No.: 022118ISA
Catalog #: TC-MA
Purity (GC): 99.7%
Appearance: Colorless liquid
Expiration date: February 21, 2019
Storage: 15 to 30°C - Duration of treatment / exposure:
- 30 ± 2 minutes
- Number of animals or in vitro replicates:
- in vitro: duplicate design
- Irritation parameter:
- other: Viability %
- Run / experiment:
- Run 1 / Experiment 1
- Value:
- 100.5
- 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 observations
ACCEPTANCE OF RESULTS:
1. The negative control OD is >0.8 and <2.5 (2.199 and 2.202).
2. The mean relative viability of the positive control is below 50% of the negative control viability (48.9%).
3. The difference of viability between the two relating tissues of a single chemical is <20% (values between 0.1% to 7.2%) in the same run (for positive and negative control tissues and tissues of single chemicals).
The study met all acceptance criteria - Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of the present study, the test item did not show an eye hazard potential. The test item is identified as not requiring classification and labeling according to UN GHS (No Category).
- Executive summary:
Objective
The objective of the present study was to investigate the potential of the test item to induce eye irritation in an in vitro human cornea model.
Study Design
The test item was applied topically to a reconstructed human cornea-like epithelium model (EpiOcularä) followed by determination of the cell viability. Cell viability was determined by enzymatic conversion of vital dye MTT into a blue formazan salt and measurement of the formazan salt after extraction from tissues. The percent reduction of cell viability in comparison to untreated negative controls was used to predict the eye irritation potential.
Duplicates of the EpiOcularä-model were treated with the test item, the negative or the positive control for30 ± 2 minutes. 50 µL of either the test item, the negative control (sterile deionized water) or the positive control (methyl acetate) were applied to the tissues.
Results
After treatment with the negative control (sterile deionized water) the mean OD was 2.201 (study acceptance criterion: >0.8 and <2.5). Treatment with the positive control (methyl acetate) revealed a mean viability value of 48.9% (study acceptance criterion: <50%). Thus, the acceptance criteria were met.
Following treatment with the test item, the tissue viability was 100.5% and, thus, higher than 60%,i.e.according to OECD 492 the test item is identified as not requiring classification and labeling according to UN GHS (No Category).
Conclusion
Under the conditions of the present study, the test item did not show an eye hazard potential. The test item is identified as not requiring classification and labeling according to UN GHS (No Category).
Reference
Mean OD | Mean Viability | |
Negative Control | 2.201 | 100.0% |
Positive Control | 1.077 | 48.9% |
Test Item | 2.211 | 100.5% |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), the test substance should be classified as: skin and eye irritant (Category 2).
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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