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EC number: 876-151-9 | CAS number: 2292123-68-1
- 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)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Part of weight-of-evidence approach adapting the information requirements of Annex VII 8.3.1 and 8.3.2. under REACH in accordance with Annex XI Section 1.2. A sequential series of skin sensitisation tests were performed which collectively provide all the information required to satisfy the information endpoint for Annex VII 8.3.1. and 8.3.2 under REACH. Therefore in accordance with Annex XI, 1.2 of the REACH Regulation is no additional testing is scientifically necessary based on a weight-of evidence approach.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442B (Skin sensitisation: Local Lymph Node Assay: BrdU-ELISA or –FCM)
- Version / remarks:
- Appendix IA, June 25 2018
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA): BrdU-ELISA
Test material
- Reference substance name:
- N,N’-di[3-(p-toluene sulfonyl)oxy]phenyl urea
- EC Number:
- 876-151-9
- Cas Number:
- 2292123-68-1
- Molecular formula:
- C27H24N2O7S2
- IUPAC Name:
- N,N’-di[3-(p-toluene sulfonyl)oxy]phenyl urea
- Test material form:
- solid: particulate/powder
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA:J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Japan
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: 8 weeks for pre-screen, 9 weeks for main study
- Weight at study initiation: See Main study Day 1 - Table 3 in results sections
- Housing: polycarbonate cages with wood chips and environmental enrichment
- Diet (e.g. ad libitum): pelleted diet, ad libitum
- Water (e.g. ad libitum): chlorinated water, ad libitum
- Acclimation period: 7 days for pre-screen, 14 days for main study
- Indication of any skin lesions: all animals in good health condition
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- 10%, 25% and 50%
- No. of animals per dose:
- 4 animals per test item concentration
4 animals for vehicle control
4 animals for positive control - Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: Vehicle solubility trials were performed. Recommended vehicles in the OECD 442, acetone: olive oil (4:1 v/v/ AOO), DMF, methyl ethyl ketone (MEK) and dimethylsulfoxide (DMSO) were selected for solubility trials. The test item dissolved in DMF and DMSO at 50% (v/v), however, after 5 hours test item crystallised in the DMSO. The test item was not soluble on MEK or AOO. and therefore DMF selected as the vehicle for the pre-screen and main study.
- Irritation: none
- Systemic toxicity: none (no abnormalities reported)
- Ear thickness measurements: yes (see Table 2 in the results section)
- Erythema scores: no erythema so not scored
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: The test item was regarded as a "sensitiser" when the SI of the test item was 2.0 or more and was regarded as "non-sensitiser" when the SI of the test item group was less than 1.6. When the SI was between 1.6 and 1.9, dose-response relationship and statistical significance would be considered.
TREATMENT PREPARATION AND ADMINISTRATION:
The test solution was prepared on each sensitisation day. 0.5 was dissolved in DMF and filled up to make 1mL of 50 w/v% solution. The 50 w/v% solution was serially diluted to prepare the test solutions at 25 and 10 w/v%.
25µL of each formulation was applied to the dorsum of each ear of the animals using a micropipette once per day for 3 consecutive days.
Approx. 48 hours after the final application of the formulations, 0.5 mL of BrdU solution was administrated intraperitoneally to each animal using a syringe and a needle. Approx. 24 hours after the BrdU administration, animals were humanely killed and each auricular lymph node was taken. The lymph nodes were carefully dissected and trimmed of surrounding tissue and fat, weighed both sides together. The mean values and standard deviations of the local lymph node weights were calculated for each group. The lymph nodes were stored individually in a biomedical freezer. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- No statistic performed as SI values all <1.6.
Results and discussion
- Positive control results:
- SI = 2.93 +/-0.24.
The SI value was >2 and therefore indicates that the test system was functioning as intended.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 1.08
- Variability:
- S.E. +/- 0.12
- Test group / Remarks:
- 10%
- Remarks on result:
- other: Mean SI value
- Parameter:
- SI
- Value:
- 1.18
- Variability:
- S.E. +/- 0.15
- Test group / Remarks:
- 25%
- Remarks on result:
- other: Mean SI value
- Parameter:
- SI
- Value:
- 1.48
- Variability:
- S.E. +/- 0.21
- Test group / Remarks:
- 50%
- Remarks on result:
- other: Mean SI value
- Parameter:
- SI
- Value:
- 2.93
- Variability:
- S.E. +/- 0.24
- Test group / Remarks:
- Positive control
- Remarks on result:
- other: Mean SI value
- Parameter:
- SI
- Value:
- 1
- Variability:
- S.E. +/- 0.04
- Test group / Remarks:
- Vehicle control
- Remarks on result:
- other: Mean SI value
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
Lymph node weight - see Table 5
DETAILS ON STIMULATION INDEX CALCULATION
EC3 CALCULATION: not calculated
CLINICAL OBSERVATIONS:
See Table 4
BODY WEIGHTS
See Table 3
SIGNS OF TOXICITY (including dermal irritation at the site of administration, if any, e.g. increased ear thickness). None.
Any other information on results incl. tables
Table 1: Body weights in the pre-screen test
Exp. group |
| Animal No. | Body weights (g) | |
Group | Concentration (w/v%) | Day 1 | Day 6a) | |
Test item | 10.0 | 1 | 22.1 | 22.2 (100.5) |
25.0 | 2 | 22.4 | 23.3 (104.0) | |
50.0 | 3 | 22.4 | 23.1 (103.1) |
Figures in parentheses indicate percentages compared to the initial body weight (Day 1)
Table 2: Thicknesses of auricle in the pre-screen test
Exp. Group | Animal No. | Thickness of auricle (mm) | ||||||
Group | Concentration (w/v%) | Day 1 | Day 3 a) | Day 6 a) | ||||
Test item | Left | Right | Left | Right | Left | Right | ||
| 10.0 | 1 | 0.185 | 0.190 | 0.205 (110.8) | 0.210 (110.8) | 0.190 (102.7) | 0.205 (107.9) |
| 25.0 | 2 | 0.205 | 0.195 | 0.195 (95.1) | 0.210 (107.7) | 0.210 (102.4) | 0.210 (107.7) |
| 50.0 | 3 | 0.180 | 0.190 | 0.200 (111.1) | 0.210 (110.5) | 0.200 (111.1) | 0.195 (102.6) |
Figures in parentheses indicate percentages compared to the initial thicknesses (Day 1)
Table 3: Body weights in the main study
Exp Group | Animal No. | Body weights (g) | ||||
Group | Concentration (w/v%) | Day 1 | Day 6 | |||
Individual | Mean ± S.D. | Individual | Mean ± S.D. | |||
Vehicle Control (DMF) | - | 1 | 22.3 | 22.43 ±1.80 | 22.8 | 23.15 ± 1.88 |
2 | 25.0 | 25.9 | ||||
3 | 21.4 | 21.8 | ||||
4 | 21.0 | 22.1 | ||||
Positive Control (HCA) | 25.0 | 5 | 24.7 | 23.45 ± 2.43 | 24.4 | 23.35 ± 1.92 |
6 | 26.2 | 25.4 | ||||
7 | 20.9 | 21.1 | ||||
8 | 22.0 | 22.5 | ||||
Test item | 10.0 | 9 | 24.5 | 22.90 ± 1.49 | 23.9 | 22.50 ± 1.27 |
10 | 23.8 | 23.0 | ||||
11 | 21.9 | 20.9 | ||||
12 | 21.4 | 22.2 | ||||
25.0 | 13 | 22.2 | 22.55 ± 1.84 | 23.0 | 22.70 ± 1.22 | |
14 | 25.2 | 24.2 | ||||
15 | 21.0 | 21.3 | ||||
16 | 21.8 | 22.3 | ||||
50.0 | 17 | 22.5 | 22.45 ± 1.40 | 23.7 | 22.80 ± 1.34 | |
18 | 24.0 | 24.1 | ||||
19 | 20.6 | 21.2 | ||||
20 | 22.7 | 22.2 |
S.D: Standard deviation
DMF: N,N-dimethylformamide
HCA: α-hexylcinnamaldehyde
Table 4: Clinical signs in the main study
Exp Group | Animal No. | Observation period | ||||||
Group | Concentration (w/v%) | |||||||
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | |||
Vehicle Control (DMF) | - | 1 | - | - | - | - | - | - |
2 | - | - | - | - | - | - | ||
3 | - | - | - | - | - | - | ||
4 | - | - | - | - | - | - | ||
Positive Control (HCA) | 25.0 | 5 | - | - | - | - | - | - |
6 | - | - | - | - | - | - | ||
7 | - | - | - | - | - | - | ||
8 | - | - | - | - | - | - | ||
Test item | 10.0 | 9 | - | - | - | - | - | - |
10 | - | - | - | - | - | - | ||
11 | - | - | - | - | - | - | ||
12 | - | - | - | - | - | - | ||
25.0 | 13 | -* | -* | -* | - | - | - | |
14 | -* | -* | -* | - | - | - | ||
15 | -* | -* | -* | - | - | - | ||
16 | -* | -* | -* | - | - | - | ||
50.0 | 17 | -* | -* | -* | - | - | - | |
18 | -* | -* | -* | - | - | - | ||
19 | -* | -* | -* | - | - | - | ||
20 | -* | -* | -* | - | - | - |
DMF: N,N-dimethylformamide
HCA: α-hexylcinnamaldehyde
- : no abnormalities detected
*-: test item crystallised on ear (after application)
Table 5: Lymph node weights in the main study
Exp Group | Animal No. | Lymph node weights (g) | ||
Group | Concentration (w/v%) | |||
Individual | Mean ± S.D. | |||
Vehicle Control (DMF) | - | 1 | 4.3 | 4.28 ± 0.21 |
2 | 4.5 | |||
3 | 4.0 | |||
4 | 4.3 | |||
Positive Control (HCA) | 25.0 | 5 | 9.1 | 8.33 ± 0.80 |
6 | 8.5 | |||
7 | 7.2 | |||
8 | 8.5 | |||
Test item | 10.0 | 9 | 4.7 | 4.65 ± 0.34 |
10 | 4.5 | |||
11 | 4.3 | |||
12 | 5.1 | |||
25.0 | 13 | 4.7 | 4.35 ± 0.39 | |
14 | 4.4 | |||
15 | 4.5 | |||
16 | 3.8 | |||
50.0 | 17 | 4.7 | 5.20 ± 0.36 | |
18 | 5.4 | |||
19 | 5.2 | |||
20 | 5.5 |
S.D: Standard deviation
DMF: N,N-dimethylformamide
HCA: α-hexylcinnamaldehyde
Table 6: BrdU labelling indices and stimulation indices in the main study
Exp Group | Animal No. | BrdU labelling index | Stimulation index | |||
Group | Concentration (w/v%) | |||||
Individual | Mean ± S.E. | Individual | Mean ± S.E. | |||
Vehicle Control (DMF) | - | 1 | 0.176 | 0.1560 ± 1.80 | 1.1 | 1.00 ± 0.04 |
2 | 0.153 | 1.0 | ||||
3 | 0.136 | 0.9 | ||||
4 | 0.159 | 1.0 | ||||
Positive Control (HCA) | 25.0 | 5 | 0.568 | 0.4570 ± 0.0395 | 3.6 | 2.93 ± 0.24 |
6 | 0.384 | 2.5 | ||||
7 | 0.426 | 2.7 | ||||
8 | 0.450 | 2.9 | ||||
Test item | 10.0 | 9 | 0.216 | 0.1708 ± 0.0169 | 1.4 | 1.08 ± 0.12 |
10 | 0.143 | 0.9 | ||||
11 | 0.177 | 1.1 | ||||
12 | 0.147 | 0.9 | ||||
25.0 | 13 | 0.233 | 0.1835 ± 0.0215 | 1.5 | 1.18 ± 0.15 | |
14 | 0.185 | 1.2 | ||||
15 | 0.188 | 1.2 | ||||
16 | 0.128 | 0.8 | ||||
50.0 | 17 | 0.169 | 0.2285 ± 0.0322 | 1.1 | 1.48 ± 0.21 | |
18 | 0.243 | 1.6 | ||||
19 | 0.189 | 1.2 | ||||
20 | 0.313 | 2.0 |
S.E: Standard error
DMF: N,N-dimethylformamide
HCA: α-hexylcinnamaldehyde
Applicant's summary and conclusion
- Conclusions:
- The SIs of the 50.0, 25.0 and 10.0 w/v% test item groups were 1.48, 1.18 and 1.08 (all SIs less than the cut-off value of 1.6. Therefore under the condition of the test, the test item was judged to be non-sensitiser.
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