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EC number: 220-621-2 | CAS number: 2835-99-6
- 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
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 7 September 2016 to 12 September 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 4-amino-m-cresol
- EC Number:
- 220-621-2
- EC Name:
- 4-amino-m-cresol
- Cas Number:
- 2835-99-6
- Molecular formula:
- C7H9NO
- IUPAC Name:
- 4-amino-m-cresol
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: supplied by HFC Prestige Service, batch No. DRDGAMC110703W
- Expiration date of the lot/batch: 30 June 2018
- Purity test date: 13 May 2016
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient temperature
- Stability under test conditions: not specified
- Solubility and stability of the test substance in the solvent/vehicle: test item used as supplied
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: test item used as supplied
- Preliminary purification step (if any): no purification made
- Final dilution of a dissolved solid, stock liquid or gel: no dilution performed
- Final preparation of a solid: used as supplied
FORM AS APPLIED IN THE TEST (if different from that of starting material)
OTHER SPECIFICS:
In vitro test system
- Test system:
- artificial membrane barrier model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: reconstructed human derived epidermis model of adult human epidermal keratinocytes
- Source strain:
- not specified
- Justification for test system used:
- Following a full validation study the EpiSkinTM reconstructed human epidermis model showed evidence of being a reliable and relevant stand-alone test for predicting rabbit skin irritation when the endpoint is measured by MTT reduction and for being used as a replacement for the Draize Skin Irritation Test for the purpose of distinguishing between Irritating and Non-Irritating test items.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiSkinTM
- Tissue batch number(s): 16-EKIN-036
- Production date: not specified
- Shipping date: not specified
- Delivery date:06 September 2016
- Date of initiation of testing: 07 September 2016
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: approximately at 37 deg Celsius
- Temperature of post-treatment incubation (if applicable):at 37 deg Celsius
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: At the end of the exposure period, each tissue was removed from the well using forceps and rinsed using a wash bottle containing DPBS with Ca++ and Mg++. Rinsing was achieved by
filling and emptying each tissue insert for approximately 40 seconds using a constant soft stream of DPBS to gently remove any residual test item.
- Observable damage in the tissue due to washing: Not specified
- Modifications to validated SOP: No modifications
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 0.3 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: Anthos 2001 microplate reader
- Wavelength: 562 nm (without a reference filter)
- Filter: No reference filter was used
- Filter bandwidth: No reference filter was used
- Linear OD range of spectrophotometer: not specified
NUMBER OF REPLICATE TISSUES: triplicate for each conditions
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- Killed tissues
- Procedure used to prepare the killed tissues (if applicable):Water-killed tissues were prepared by placing untreated EPISKINTM tissues in a 12-well plate containing 2.0 mL of sterile distilled water in each well. The tissues were incubated at 37 °C, 5% CO2 in air for 48 ± 1 hours. At the end of the incubation the water was discarded. Once killed the tissues were stored in a freezer (-14 to -30 °C) for up to 6 months. Before use each tissue was thawed by placing in 2.0 mL of maintenance medium for approximately 1 hour at room temperature.
- N. of replicates : 3
- Method of calculation used: Relative mean viability (%) = (mean Optical Density at 562 nm of test item / mean Optical Density at 562 nm of negative control) x 100
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 2 test sequences (pre-test and main test)
PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if [complete, e.g. the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.]
- The test substance is considered to be non-corrosive to skin if [complete, e.g. the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.] - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mg (26.3 mg/cm2)
- Concentration (if solution): pure
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 10µL of DPBS
- Concentration (if solution): used as supplied (pure)
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 10 µL
- Concentration (if solution): 5% w/v aqueous solution - Duration of treatment / exposure:
- 15 minutes
- Duration of post-treatment incubation (if applicable):
- 42 hours
- Number of replicates:
- 3 per conditions
Results and discussion
In vitro
Resultsopen allclose all
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Main test (test item)
- Value:
- 63.4
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Main test (positive control)
- Value:
- 5.6
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Main test (negative control)
- Value:
- 100
- 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: Not specified
- Direct-MTT reduction: Yes
- Colour interference with MTT: No
DEMONSTRATION OF TECHNICAL PROFICIENCY: SDS used as positive control
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
- Range of historical values if different from the ones specified in the test guideline: Not specifies
Any other information on results incl. tables
Table1 :Mean OD562Values and Viabilities for the Negative Control Item, Positive Control Item and Test Item
Item |
OD562 of tissuestvt |
Mean of OD562 |
OD562 of tissues corrected fortkt-ukt (0.104) |
± SD ofOD562 |
Relative individual tissue viability (%) |
Relative mean viability (%) |
± SD of Relative meanviability(%) |
Negative Control |
1.133 |
1.234 |
|
0.099 |
91.8 |
100* |
8.1 |
1.331 |
107.9 |
||||||
1.237 |
100.2 |
||||||
Positive Control |
0.082 |
0.069 |
|
0.020 |
6.6 |
5.6 |
1.6 |
0.079 |
6.4 |
||||||
0.046 |
3.7 |
||||||
Test Item |
0.898 |
0.885 |
0.781 |
0.017 |
64.4 |
63.4 |
1.3 |
0.892 |
63.9 |
||||||
0.866 |
61.8 |
Corrected viability of treatedkilledtissues = 0.216 (tkt)-0.112 (ukt) =0.104
* = mean viability of the negative control tissues is set at 100%
OD562 = Optical Oensity
SD = Standard Deviation
tvt = treated viable tissues
tkt = treated killed tissues
ukt = untreated killed tissues
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the experimental conditions of the study, incubation of the registered substance 4-amino-m-cresol induced a relative mean viability at 63.3% compared to negative control. Hence, the registered substance was classified as Non-irritant for the skin (EU CLP Not classified for Irritation).
- Executive summary:
The purpose of this GLP compliant test was to evaluate the skin irritation potential of the test item using the EPISKINTM reconstructed human epidermis model after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours according to the OECD guideline 439 method.
Triplicate tissues were treated with the test item for an exposure period of 15 minutes. The test item was found to directly reduce MTT and therefore additional non-viable tissues were incorporated into the testing for correction purposes. 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-labeled 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.
The relative mean viability of the test item treated tissues was 63.3% after the 15-Minute exposure period and 42-Hours post-exposure incubation period.
Under the experimental conditions of the study, incubation of the registered substance 4-amino-m-cresol induced a relative mean viability at 63.3% compared to negative control. Hence, the registered substance was classified as Non-irritant for the skin (EU CLP Not classified for Irritation).
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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