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EC number: 208-952-0 | CAS number: 548-61-8
- 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
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- yes
- Remarks:
- - modified LLNA (IMDS): Measurement of cell counts instead of radioactive labelling. In addition, measurements of ear swelling and ear weights were done to discriminate the irritating potential from the sensitizing potential of the test substance.
- Principles of method if other than guideline:
- Modified LLNA (IMDS; Integrated Model for the Differentiation of Skin Reactions). Modifications are authorised in the OECD TG 429 and in the Note for Guidance SWP/2145/00 of the CPMP (2001). Information on validation of IMDS and scientific justification is given in: Vohr HW et al., Arch. Toxicol., 73, 501-509 (2000); Ehling G et al., Toxicology 212, 60-68 and 69-79 (2005).
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Nederland, Kreuzelweg 53, 5960 AD Horst, The Netherlands
- Strain: Hsd Win:NMRI
- Age at study initiation: 10 weeks
- Weight at study initiation: 29 - 40 g
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 6 days - Vehicle:
- dimethylformamide
- Remarks:
- The stability and homogeneity of the test item in the vehicle was analytically verified for up to 4 days.
- Concentration:
- 0, 2, 10, 50 %
- No. of animals per dose:
- 6
- Details on study design:
- TREATMENT PREPARATION AND ADMINISTRATION:
The test item in the formulation or the vehicle was applied epicutaneously onto the dorsal part of both ears of the animals. This treatment was repeated on three consecutive days (d1, d2 and d3). The volume administered was 25 µL/ear. The used concentrations were based on the experiences with the test system and the toxic properties of the test substance.
The animals were anaesthetized by inhalation of carbon dioxide and sacrificed one day after the last application (d4). The appropriate organs were removed. Lymphatic organs (the auricular lymph nodes) were transferred into physiological saline (PBS).
Investigations:
- weight of draining lymph nodes (given as weight index compared to vehicle controls)
- cell counts in draining lymph nodes (given as cell count index compared to vehicle controls)
The so-called stimulation (or LLN-) index is calculated by dividing the absolute weight or number of cell counts of the substance treated lymph nodes by the vehicle treated ones. Thus, in case of no stimulating effect the index is always about 1.00 and the indices of vehicle treated animals are set to 1.00.
- ear swelling (given in 0.01 mm and as index)
- ear weight (given in mg/8 mm diameter punch and as index)
- body weights - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- When it was statistically reasonable, the values from treated groups were compared with those from the control group by a one-way analysis of variance (ANOVA) when the variances are considered homogeneous according to a homogeneity testing like Cochran's test. Alternatively, if the variances are considered to be heterogeneous (p<=0.05), a non-parametric Kruskal-Wallis test has been used (Kruskal-Wallis ANOVA) at significance levels of 5 %. Two sided multiple test procedures were done according to Dunnett or Bonferroni-Holm, respectively. Outlying values in the LN weights were eliminated at a probability level of 99 % by Nalimov's method. In addition, for the LLNA/IMDS the smallest significant differences in the means were calculated by Scheffels method, which according to Sachs can be used for both equal and unequal sample sizes.
- Positive control results:
- Alpha hexyl cinnamic aldehyde, checked in regular intervals, shows a clear sensitising potential in the local lymph node assay (IMDS).
- Parameter:
- SI
- Remarks on result:
- other: see Remark
- Remarks:
- Weight index of draining lymph nodes: no substance specific effects were determined. Cell count index in draining lymph nodes: 'positive level' of 1.4 was just exceeded in the high dose group (not statistically significant). Ear swelling: 'positive level' of 2x10E-2 mm increase (i.e. 10 % of control level) was not reached or exceeded in any dose group. Ear weight: no substance specific effects were determined for ear weights.
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: modified LLNA; measurement of cell counts, LLN weight, ear swelling and weight instead of radioactive labelling
- Interpretation of results:
- other: weak skin sensitizer
- Executive summary:
- The test substance was investigated for both its skin sensitizing and irritant potential in the modified Local Lymph Node Assay (LLNA) on female mice, performed according to OECD TG 429. Concentrations of 0 % (vehicle control), 2 %, 10 % and 50 % test substance in DMF were tested. Body weights were not affected by treatment. Compared to vehicle control an increase of cell counts in the draining lymph nodes was noted for the highest test substance concentration, which was not statistically significant, however, slightly exceeded the 'positive-level' index of 1.4 (i.e. 1.42). The other parameters investigated (weight of draining lymph nodes, ear swelling and ear weight) showed no relevant changes. Under the conditions of this test 4,4',4"-methylidynetrianiline should be considered as a weak skin sensitizer. The concentration of 10 % in DMF turned out to be the NOEL for the parameters investigated in this study with respect to skin sensitization.
Reference
Results of LLNA (means for 6 animals per group)
Parameters investigated |
Vehicle |
Low (2 % in DMF) |
Medium (10 % in DMF) |
High (50 % in DMF) |
Stimulation Index: weight of draining lymph nodes |
1.00 |
1.21 |
1.22 |
1.12 |
Stimulation index: cell count in draining lymph nodes | 1.00 | 1.19 | 1.37 | 1.42 |
Ear swelling in 0.01 mm on day 4 (index) | 18.00 (1.00) | 18.25 (1.01) | 18.58 (1.03) | 18.33 (1.02) |
Ear weight in mg/8 mm diameter punch on day 4 (index) | 12.78 (1.00) | 13.42 (1.05) | 12.69 (0.99) | 12.76 (1.00) |
* statistically significant increase (p<= 0.05)
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
- The test substance was investigated for both its skin sensitizing and irritant potential in the modified Local Lymph Node Assay (LLNA) on female mice, performed according to OECD TG 429. Concentrations of 0 % (vehicle control), 2 %, 10 % and 50 % test substance in DMF were tested. Body weights were not affected by treatment. Compared to vehicle control an increase of cell counts in the draining lymph nodes was noted for the highest test substance concentration, which was not statistically significant, however, slightly exceeded the 'positive-level' index of 1.4 (i.e. 1.42). The other parameters investigated (weight of draining lymph nodes, ear swelling and ear weight) showed no relevant changes. Under the conditions of this test 4,4',4"-methylidynetrianiline should be considered as a weak skin sensitizer. The concentration of 10 % in DMF turned out to be the NOEL for the parameters investigated in this study with respect to skin sensitization. According to EU Regulation 1272/2008 the test item should be classified as skin sensitizer Cat 1B.
Migrated from Short description of key information:
skin sensitization: weak (NOEL = 10 % test item in DMF)
Justification for classification or non-classification
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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