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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 204-317-7 | CAS number: 119-36-8
- 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
For skin irritation, the key study is an unpublished GLP-compliant report (Schreiter, 1999), Rel 1, indicating that MeS is not irritating to skin.
For eye irritation, the key study is an unpublished GLP-compliant study following the OECD 491 guideline (2019, Rel. 1). This study indicates that MeS induces a decrease of the cell viability below 70%, so that MeS causes serious eye damage.
Key value for chemical safety assessment
Skin irritation / corrosion
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 03 April 2019 to 11 June 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 491 (Short Time Exposure In Vitro 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:
- 25 June 2018
- Deviations:
- yes
- Remarks:
- MTT solution prepared in Eagle’s MEM without supplements. During the establishment of the STE test, more stable and comparable results were obtained using the medium without supplements. STE test proficiency study was conducted under the same conditions.
- GLP compliance:
- yes (incl. QA statement)
- Species:
- other: rabbit corneal cell line SIRC (Statens Seruminstitut Rabbit Cornea)
- Details on test animals or tissues and environmental conditions:
- - Justification of the test method and considerations regarding applicability:
The cytotoxic effect of test items on corneal epithelia cells is an important mode of action leading to corneal epithelium damage and eye irritation. Cell viability in the STE test method is assessed by the quantitative measurement, after extraction from cells, of blue formazan salt produced by the living cells by enzymatic conversion of the vital dye MTT [(3-4,5-dimethyl thiazole 2-yl) 2,5-diphenyl-tetrazoliumbromide], also known as Thiazolyl Blue Tetrazolium Bromide. It was verified that the test substance falls into the applicability domain of the guideline method.
- Description of the cell system used, incl. certificate of authenticity and the mycoplasma status of the cell live:
The rabbit corneal cell line SIRC (Statens Seruminstitut Rabbit Cornea) is the cell line that is recommended in the OECD test guideline No 491 and was used for performing the STE test method. SIRCs are growing as confluent monolayers. - Vehicle:
- physiological saline
- Controls:
- yes, concurrent vehicle
- yes, concurrent positive control
- yes, concurrent negative control
- other: Medium Control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not applicable
- Concentration (if solution): 0.5% (v/v) and 0.05% (v/v)
VEHICLE
- Amount(s) applied (volume or weight with unit): the test item was prepared in physiological saline (0.9% (w/v) NaCl in deionised water) to reach a final concentration of 5% (w/w). Following, this solution was diluted by serial 10-fold dilution with the respective solvent to reach final concentrations of 0.5% (v/v) and 0.05% (v/v).
- Concentration (if solution): /
- Lot/batch no. (if required): /
- Purity: / - Duration of treatment / exposure:
- 5 minutes at room temperature.
- Observation period (in vivo):
- not applicable (in vitro).
- Duration of post- treatment incubation (in vitro):
- Immediately after exposure, cells were washed and MTT cell viability measurement was performed.
- Number of animals or in vitro replicates:
- All dose groups were tested in three replicate wells.
- Details on study design:
- - Cell line used, its source, passage number and confluence of cells used for testing
:
Cell line: The rabbit corneal cell line SIRC (Statens Seruminstitut Rabbit Cornea)
Source: ATCC
Passage number: The cells were sub-cultured twice weekly. The cell cultures were incubated at 37 ± 1.5 °C and 5.0 ± 0.5% carbon dioxide atmosphere. Cells were propagated 2 to 3 passages in a culture flask before being employed for testing and did not exceed 25 passages from thawing. The cells used for the first experiment were seeded in the first passage after thawing instead of second or third passage.
Seeding of the culture and confluence: exponentially growing stock cultures more than 50% confluent were rinsed with PBS and treated with Trypsin at 37 ± 1.5 °C for 5 minutes. Then the enzymatic digestion was stopped by adding complete medium and a single cell suspension was prepared.
Individual wells of a 96-well tissue-culture microtiter plate were inoculated with 0.2 mL complete medium containing approximately 3 x 104 cells/mL (6000 cells per well) in case that the cells were seeded four days prior to the treatment and 1.5 x 104 cells/mL (3000 cells per well) in case that the cells were seeded 5 days prior to the treatment. The seeding day and the day of treatment are included in the calculation of the days for the cell cultivation: e.g. seeding on Friday of 6000 cells/well and treatment on Monday (four days) or seeding on Friday of 3000 cells/well and treatment on Tuesday (five days). The plates were incubated at 37 ± 1.5 °C and 5.0 ± 0.5% carbon dioxide atmosphere. Cells reached a confluence of more than 80% at the time of testing.
- Number of repetitions and replicates used : 1 repetition and 3 replicates
- Test chemical concentrations used (if different than the ones recommended) : not applicable
- Justification for choice of solvent for each test chemical : solvent recommended in the guideline.
- Duration of exposure to the test chemical (if different than the one recommended) : not applicable
- Description of any modifications of the test procedure : The MTT solution is prepared in Eagle’s minimum essential medium (MEM) without supplements. During the establishment of the STE test at Envigo CRS GmbH, more stable and comparable results between the three independent experiments were obtained using the medium without supplements. The STE test proficiency study was conducted under the same conditions.
- Description of evaluation and decision criteria used :
The optical density (OD) value obtained from the test item, medium and positive control were used to calculate cell viability relative to the solvent control, which is set at 100%. The relative cell viability is expressed as a percentage and obtained by dividing the OD of the test groups (test item, medium or positive controls) by the OD of the respective solvent control after subtracting the OD of blank from both values. For the cell viability calculation of the medium control physiological saline was used as solvent control.
Cell viability [%] = (mean OD test group - mean OD blank) / (mean OD solvent control - mean OD blank) x 100
Similarly, the relative cell viability of each solvent control is expressed as a percentage and obtained by dividing the OD of each solvent control by the OD of the medium control after subtracting the OD of blank from both values. The arithmetic mean of the three wells of the test item, positive and solvent control in each independent experiment was used to calculate the final arithmetic mean of relative cell viability, respectively.
- Reference to historical positive control mean and Standard Deviation (SD) : not reported
- Demonstration of proficiency of the laboratory in performing the test method (e.g. by testing of proficiency substances) or demonstration of reproducible performance of the test method over time: not reported - Irritation parameter:
- other: cell viability (%)
- Remarks:
- Test Item at 0.05%
- Run / experiment:
- 1
- Value:
- 11.6
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: cell viability ≤ 70 %
- Irritation parameter:
- other: cell viability (%)
- Remarks:
- Test Item at 5%
- Run / experiment:
- 1
- Value:
- 25.5
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: cell Viability ≤ 70 %
- Irritation parameter:
- other: cell viability (%)
- Remarks:
- Test Item 0.05%
- Run / experiment:
- 2
- Value:
- 3.9
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: cell viability ≤ 70 %
- Irritation parameter:
- other: cell viability (%)
- Remarks:
- Test Item at 5%
- Run / experiment:
- 2
- Value:
- 26.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: cell viability ≤ 70 %
- Irritation parameter:
- other: cell viability (%)
- Remarks:
- Test Item at 0.05%
- Run / experiment:
- 3
- Value:
- 19.9
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: cell viability ≤ 70 %
- Irritation parameter:
- other: cell viability (%)
- Remarks:
- Test Item at 5%
- Run / experiment:
- 3
- Value:
- 31
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: cell viability ≤ 70 %
- Irritation parameter:
- other: mean cell viability (%)
- Remarks:
- Test Item at 0.05%
- Run / experiment:
- Mean of 3 runs
- Value:
- 11.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: cell viability ≤ 70 %
- Irritation parameter:
- other: mean cell viability (%)
- Remarks:
- Test Item at 5%
- Run / experiment:
- Mean of 3 runs
- Value:
- 27.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: cell viability ≤ 70 %
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: microtiter well surfaces were observed in the wells of the 5% test item treated cells (possibly reactivity of the test item with plastic of the microtiter plate). This could have led to a higher absorption for the 5% test item treated cells.
ACCEPTANCE OF RESULTS: The acceptance criteria were met in all three independent tests of the test item. - Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Conclusions:
- Under the experimental conditions of this study, the test item Methyl Salicylate induced a decrease of the cell viability below 70%. Thus, the test item is classified as “Category 1” for eye irritation or serious eye damage according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.
- Executive summary:
This GLP compliant study was performed to assess the eye irritation potential of the test item Methyl Salicylate in vitro vivo using the rabbit corneal cell line SIRC. This test was performed according to the OECD Test Guideline No. 491 (25 June 2018).
Material and methods
Solutions of the test item with concentrations of 0.05 and 5% were prepared using physiological saline. Both concentrations (0.05 and 5%) of the test item were tested three times with three replicates per test. The cells were incubated for 5 minutes at room temperature.
Furthermore, complete medium was used as medium control. The solvent control for the test item was physiological saline. A 0.01% solution of SLS in physiological saline was used as positive control.
Results
Complete medium did not induce cytotoxic effects in all the tests. The positive control induced an expected distinct reduction in cell viability in all tests within the range of the acceptance criteria.
The medium control showed an OD of ≥ 0.3 after subtraction of blank OD in all tests.
The acceptance criteria were met in all three independent tests of the test item.
Toxic effects were observed following incubation with the two tested concentrations of 0.05% and 5% in all of the runs. The cell viabilities were reduced below 70% for the 0.05% test item treated cells in the range between 3.9% and 19.9% and for the 5% test item treated cells in the range between 25.5% and 31.0%. The slightly higher measured cell viability of the 5% test item treated cells in comparison to the cell viability of the 0.05% treated cells was possibly due to changes of the microtiter well surfaces only observed in the wells of the 5% test item treated cells (possibly reactivity of the test item with plastic of the microtiter plate). This could have led to a higher absorption for the 5% test item treated cells. However, since both test item concentrations induced a decrease of the cell viability below 70%, the test item Methyl Salicylate is classified as “Category 1” for eye irritation or serious eye damage according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.
Conclusion
Under the experimental conditions of this study, the test item Methyl Salicylate induced a decrease of the cell viability below 70%. Thus, the test item is classified as “Category 1” for eye irritation or serious eye damage according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.
Reference
Tables 1. Summary of Results of METHYL SALICYLATE and the controls
Test Group |
Cell Viability [%] per Test |
Mean Cell Viability [%] |
Standard Deviation [%]
|
Predicted Eye Irritation Potential |
||
Test 1 |
Test 2 |
Test 3 |
||||
Medium Control |
109.8 |
97.7 |
115.2 |
107.6
|
9.0
|
|
Solvent Control (0.9% NaCl) |
100.0 |
100.0 |
100.0 |
100.0
|
0.0
|
|
Positive Control |
34.9 |
19.6 |
13.7 |
22.7
|
10.9
|
|
Test Item 0.05% |
11.6 |
3.9 |
19.9 |
11.8
|
8.0
|
Category1 |
Test Item 5% |
25.5 |
26.8 |
31.0 |
27.8
|
2.9
|
|
Solvent control (0.9% NaCl) compared to medium control |
91.1 |
102.4 |
86.8 |
|
|
|
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irreversible damage)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Additional information
Skin irritation
The primary skin irritation of MeS was investigated in a GLP-compliant study according to OECD Guideline 404 (Schreiter, 1999). Four female albino rabbits were exposed to the test article and the vehicle at two skin sites on the back. After 4 hours of exposure the test article was removed and the skin was examined at 1, 24, 48 and 72 hours, as well as 7 and 14 days after the termination of exposure. Slight to well-defined skin reactions were observed. The mean scores reported were: undiluted MeS: 1.3 for erythema and 0.6 for oedema; 25% solution: 0.2 for erythema and 0.0 for oedema. No reactions were reported for 1, 5 or 10% solutions. According to Directive 93/21/, the test substance should not be classified as irritating to the skin.
Eye irritation
Contradictory eye irritation results were found in-vivo with methyl salicylate but none of the existing available study was considered as fully acceptable. In one eye irritation study (unpublished report, 2001), chemosis, discharge and redness of the conjunctiva (score of 1) were only observed at 1 hour, but not thereafter. Since this result was not confirmed in 2 additional animals as recommended in the OECD TG 405, no final conclusion can be made from this study. In contrast, additional data report ocular irritation but were assigned with a reliability of 3 or 4 due to very low level of details and/or major deficiencies in the experimental design. Contradictory results were also reported for methyl salicylate in the Cosmetic Ingredient Review (Cir, 2003).
As no clear conclusion was possible based on the existing in-vivo data, a new test was performed in 2019 and is considered as the key study.
This GLP compliant study was performed to assess the eye irritation potential of the test item Methyl Salicylate in vitro using the rabbit corneal cell line SIRC. This test was performed according to the OECD Test Guideline No. 491.
Solutions of the test item with concentrations of 0.05 and 5% were prepared using physiological saline. Both concentrations (0.05 and 5%) of the test item were tested three times with three replicates per test. The cells were incubated for 5 minutes at room temperature.
Furthermore, complete medium was used as medium control. The solvent control for the test item was physiological saline. A 0.01% solution of SLS in physiological saline was used as positive control.
Toxic effects were observed following incubation with the two tested concentrations of 0.05% and 5% in all of the runs. The cell viabilities were reduced below 70% for the 0.05% test item treated cells in the range between 3.9% and 19.9% and for the 5% test item treated cells in the range between 25.5% and 31.0%. Since both test item concentrations induced a decrease of the cell viability below 70%, the test item Methyl Salicylate is considered as a severe eye irritant.
Respiratory irritation
No specific study has been carried out on respiratory irritation, howeverThe absence of any adverse effects from repeated exposure to MeS vapour at 0.7 mg/l (almost saturated atmosphere) for 7 hours per day 5 days per week for 4 weeks supports a conclusion that MeS is not irritating to the respiratory system.
Justification for classification or non-classification
Skin:
The threshold for classification of a substance as irritating to the skin according to the criteria ofAnnex VI Directive 67/748/EEC(R38) is overall mean score for erythema or oedema at 24/48/72 hours ≥ 2 or mean score for 2/3 animals for 24/48/72 hours ≥ 2. According to the criteria ofEU/GHS the threshold for Irritant Cat. 2 is mean score for 2/3 animals for 24/48/72 hours ≥ 2.3.
According to the GLP-compliant study (Symrise) MeS was not irritating to skin (overall mean score, erythema 1.33, oedema 0.67). MeS therefore does not fulfill the criteria for classification as irritant.
MeS is therefore not classified for skin irritation according to the criteria of Annex VI Directive 67/748/EECor EU GHS.
Eye:
Methyl Salicylate induced a decrease of the cell viability below 70% in a test performed according to OECD guideline 491. Thus, it is classified as “Category 1” for eye irritation or serious eye damage according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.
Respiratory:
There are no data to indicate that MeS should be considered a respiratory irritant.
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.