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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 225-193-0 | CAS number: 4707-47-5
- 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 sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Remarks:
- LLNA was performed in 2004
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08 April, 2003 - 15 April, 2003
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- information is sufficiently adequate
- Justification for type of information:
- LLNA was performed before 2016
Data source
Reference
- Title:
- Unnamed
- Year:
- 2 004
- Report date:
- 2004
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2002
- Deviations:
- yes
- Remarks:
- No details on test material, no details on clinical signs or local irritation at application site, positive control study performed 9 month before main study instead of 6 months, no dose relationship in response was observed in the positive control test.
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Methyl 2,4-dihydroxy-3,6-dimethylbenzoate
- EC Number:
- 225-193-0
- EC Name:
- Methyl 2,4-dihydroxy-3,6-dimethylbenzoate
- Cas Number:
- 4707-47-5
- Molecular formula:
- C10H12O4
- IUPAC Name:
- methyl 2,4-dihydroxy-3,6-dimethylbenzoate
- Test material form:
- other: solid
1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/Ca/Ola/Hsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Interfauna UK Limited, Blackthorne, Bicester, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: Young adults
- Weight at study initiation: 14.4 - 19.6 g
- Housing: A maximum of 4 mice was housed per cage, in cages suitable for animals of this strain and weight range.
- Diet: Free access to RM1 diet (supplied by Special Diets Services Limited, Witham, Essex, UK
- Water: Free access to mains water
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS set to maintain
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): A minimum of 15
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (LLNA)
- Vehicle:
- other: 25% ethanol/ 75% diethyl phthalate
- Concentration:
- Undiluted test item or the test item at concentrations of 1%, 2.5%, 5%, 10% or 25% w/v in vehicle.
- No. of animals per dose:
- Groups of four mice were treated.
- Details on study design:
- TREATMENT PROCEDURES:
TOPICAL APPLICATION:
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with different test item concentrations of 1 %, 2.5%, 5%, 10 %, 25% and 100 % (undiluted) in 25% ethanol/ 75% diethyl phthalate (w/v). The application volume, 25 μL, was spread over the entire dorsal surface of each ear lobe once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).
ADMINISTRATION OF 3H-METHYL THYMIDINE:
Three days after the third application, all mice were administered with approximately 250 μL of phosphate buffered saline (PBS) containing approximately 20 μCi of a 2.0 Ci/mmol specific activity 3H-methyl thymidine (3HTdR) by intravenous injection via the tail vein.
DETERMINATION OF INCORPORATED 3HTdR:
Approximately five hours after treatment with 3HTdR all mice were euthanized by inhalation of halothane vapour followed by cervical dislocation. The draining auricular lymph nodes were removed from each animal and, together with the nodes from the other animals in the group, were placed in a container of PBS.
A single cell suspension was prepared by mechanical disaggregation of lymph nodes through stainless steel gauze (200 μm mesh size). After washing three times with phosphate buffered saline (approx. 10 mL) the lymph node cells were resuspended in 5% trichloroacetic acid (approx. 3 mL) and incubated at approximately +4 °C overnight, the samples were pelleted by centrifugation and the supernatant was discarded. for precipitation of macromolecules. The precipitates were then resuspended in 5% trichloroacetic acid (1 mL) and transferred to glass scintillation vials with 10 mL of scintillation liquid (Optiphase) and thoroughly mixed.
The level of 3HTdR incorporation was then measured on a β-scintillation counter (Packard Tri-Carb 2500TR Liquid Scintillation Counter).
OBSERVATIONS:
Body weights: The bodyweight of each animal was recorded prior to dosing on day 1 and prior to injection of 3HTdR on day 6.
Clinical signs (local / systemic): Animals were checked at least once daily for signs of systemic toxicity. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Not performed.
Results and discussion
- Positive control results:
- The application of hexylcinnamaldehyde at concentrations of 2.5%, 5% or 10% w/v in acetone resulted in a greater than 3-fold increase in isotope incorporation at all three concentrations (no dose relationship in response was observed). Therefore, hexylcinnamaldehyde was shown to be a skin sensitiser, confirming the validity of this study. See section "Any other information on results incl. tables".
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- EC3
- Remarks:
- % w/v
- Value:
- 19
- Key result
- Parameter:
- other: NOEC %
- Value:
- 10
- Parameter:
- SI
- Value:
- 1.59
- Remarks on result:
- other: 1%
- Parameter:
- SI
- Value:
- 2.25
- Remarks on result:
- other: 2.5%
- Parameter:
- SI
- Value:
- 1.99
- Remarks on result:
- other: 5%
- Parameter:
- SI
- Value:
- 1.41
- Remarks on result:
- other: 10%
- Parameter:
- SI
- Value:
- 3.94
- Remarks on result:
- other: 25%
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
See section "Any other information on results incl. tables"
DETAILS ON STIMULATION INDEX CALCULATION
See section "Any other information on results incl. tables"
EC3 CALCULATION
See section "Any other information on results incl. tables"
CLINICAL OBSERVATIONS: No data on results.
BODY WEIGHTS:
The body weight of the animals, recorded at the start of application and on day 6, was within the range commonly recorded for animals of this strain and age.
Any other information on results incl. tables
Skin sensitisation potential of Methyl atrarate:
Concentration of test substance (% w/v) | Number of lymph nodes assayed | Disintegration per minute (dpm) | dpm per lymph node | Test control ratio |
0 (vehicle only) | 8 | 3050 | 381 | N/A |
1 | 8 | 4846 | 606 | 1.59 |
2.5 | 8 | 6866 | 858 | 2.25 |
5 | 8 | 6052 | 757 | 1.99 |
10 | 8 | 4314 | 539 | 1.41 |
25 | 8 | 12008 | 1501 | 3.94 |
EC3 | 19% w/v |
N/A: not applicable
Skin sensitisation potential of the positive control substance hexylcinnamaldehyde:
Concentration of hexylcinnamaldehyde (% w/v) |
Number of lymph nodes assayed | Disintegration per minute (dpm) | dpm per lymph node | Test control ratio |
0 (vehicle only) | 8 | 2570 | 321 | N/A |
2.5 | 8 | 16088 | 2011 | 6.26 |
5 | 8 | 15659 | 1957 | 6.10 |
10 | 8 | 15611 | 1951 | 6.08 |
N/A: not applicable
Applicant's summary and conclusion
- Interpretation of results:
- other: Sensitiser 1B
- Remarks:
- According to EU CLP (EC No. 1272/2008 and its amendments).
- Conclusions:
- The SI values calculated for the substance concentrations 1, 2.5, 5, 10 and 25 % were 1.59, 2.25, 1.99, 1.41 and 3.94, respectively. These results show that the test substance could elicit a SI ≥ 3. An EC3 value of 19% w/v was calculated. A NOEC of 10% is derived. The test isubstance was considered to be a sensitiser under the conditions of the test.
- Executive summary:
The skin sensitisation potential of the substance has been tested according to OECD TG 429 test guideline and GLP principles. At 1, 2.5, 5, 10 and 25% the substance showed SI values of 1.59, 2.25, 1.99, 1.41 and 3.94, respectively. Reliable negative and positive controls were included. These results show that the test substance could elicit a SI ≥ 3. An EC3 value of 19% w/v was calculated. A NOEC of 10% is derived. Based on the results, the substance was considered to be a sensitiser and should be classified as skin sensitizer (Category 1B) and labeled as H317: May cause an allergic skin reaction according to Regulation (EC) No. 1272/2008 and GHS.
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.