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EC number: 948-040-6 | CAS number: -
- 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
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
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- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
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- Endpoint summary
- Stability
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- 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
Skin sensitisation: Category 1B; OECD 429; A Sanders., 2018
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
- Study period:
- 09 February 2018 - 29 May 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- Study conducted in accordance with international guidelines and in accordance with GLP. All guideline validity criteria were met.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Specific details on test material used for the study:
- RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity:
N/A
- Specific activity:
N/A
- Locations of the label:
N/A
- Expiration date of radiochemical substance:
N/A
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 2-8 ºC, protected from light
- Stability under test conditions: Assumed stable
- Solubility and stability of the test substance in the solvent/vehicle: Soluble in acetone: olive oil, 4:1 v/v
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dissolved in acetone: olive oil, 4:1 v/v
- Preliminary purification step (if any): N/A
- Final dilution of a dissolved solid, stock liquid or gel: Test item dose solutions prepared at 50, 25, 10 % in acetone: olive oil, 4:1 v/v
- Final preparation of a solid: N/A
FORM AS APPLIED IN THE TEST (if different from that of starting material): Applied as a liquid
TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable): N/A
OTHER SPECIFICS: N/A - Species:
- mouse
- Strain:
- CBA/Ca
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Envigo RMS B.V., Inc., Horst, The Netherlands
- Females (if applicable) nulliparous and non-pregnant: Yes
- Microbiological status of animals, when known: Not reported
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15-23 g
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with softwood wood flakes
- Diet (e.g. ad libitum): Free access to food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains tap water) was allowed throughout the study.
- Acclimation period: ≥ 5 days
- Indication of any skin lesions: No
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): ≥15
- Photoperiod (hrs dark / hrs light): 12:12
- IN-LIFE DATES: From: 22 February 2018 To: 29 March 2018 - Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- Prelim test: Undiluted, 50, 25 % v/v
Main test: 50, 25, 10 % v/v - No. of animals per dose:
- 5
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility:
Soluble in vehicle at 50 %
- Irritation:
No signs of irritation observed in any of the test groups.
- Systemic toxicity:
Animal in the undiluted test item group showed severe signs of systemic toxicity and was humanely killed 1-hour post dose on Day 1. No other animals showed signs of sstemic toxicity.
- Ear thickness measurements: The thickness of each ear was measured using a Mitutoyo 547-300S gauge (Mitutoyo Corporation), pre and post dose on Day 1, post dose on Days 2 and 3 and on Days 4, 5 and 6. Any changes in the ear thickness were noted. Mean ear thickness changes were calculated between time periods Days 1 and 3 and Days 1 and 6. A mean ear thickness increase of equal to or greater than 25% was considered to indicate excessive irritation and limited biological relevance to the endpoint of sensitisation.
No abnormal ear thickness measurements were recorded in any of the test groups.
- Erythema scores:
No sign of erythema obsered in any of thes test groups (all values = 0)
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Mouse Local Lymph Node Assay (individual test method)
- Criteria used to consider a positive response:
The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per animal and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).
The test item will be regarded as a sensitizer if at least one concentration of the test item results in a threefold or greater increase in 3HTdR incorporation compared to control values. Any test item failing to produce a threefold or greater increase in 3HTdR incorporation will be classified as a "non sensitizer".
- Irritation: Local skin irritation was scored daily. The thickness of each ear was measured and recorded pre and post dose on Day 1, post dose on Days 2 and 3 and on Days 4, 5 and 6.
TREATMENT PREPARATION AND ADMINISTRATION:
For the purpose of the study, the test item was used undiluted and freshly prepared as a solution in acetone/olive oil 4:1. This vehicle was chosen as it produced the highest concentration that was suitable for dosing.
The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
The mice were treated by daily application of 25 µL of the appropriate concentration of the test item to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The test item formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Data was processed to give group mean values for disintegrations per minute and standard deviations where appropriate. Individual and group mean disintegrations per minute values were assessed for dose response relationships. Data was first assessed for suitability by analysis of normality and homogeneity of variance. If the assumptions that the data are both normally distributed and has homogeneity of variances, then parametric one way analysis of variance (ANOVA) and Dunnett’s multiple comparison procedure were used to determine statistical significance. If the assumptions were not met, non parametric Kruskal Wallis Rank Sum and Mann Whitney U test procedures were used.
- Positive control results:
- The positive control article produced a Stimulation Index of 4.59 (positive indication)
- Key result
- Parameter:
- EC3
- Value:
- 10.7
- Key result
- Parameter:
- SI
- Value:
- 2.6
- Variability:
- SD: ±1620
- Test group / Remarks:
- 10 % v/v
- Key result
- Parameter:
- SI
- Value:
- 11.61
- Variability:
- SD: ±4145
- Test group / Remarks:
- 25 % v/v
- Key result
- Parameter:
- SI
- Value:
- 17.2
- Variability:
- SD: ±4728
- Test group / Remarks:
- 50 % v/v
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
Not reported
DETAILS ON STIMULATION INDEX CALCULATION
The scintillation counter provided data including the DPM value (disintegrations per minute during a ten minute period) for each individual animal. The mean DPM value for each test group was divided by the mean DPM for the control group to provide the Stimulation Index (SI) value for each test group.
EC3 CALCULATION
The EC3 value is the concentration of test item expected to cause a 3 fold increase in 3HTdR incorporation. The equation used for the calculation of EC3 is:
EC3 = c + [[(3-d) / (b-d)] x (a-c)]
where;
a = lowest concentration giving stimulation index >3
b = actual stimulation index caused by 'a'
c = highest concentration failing to produce stimulation index of 3
d = actual stimulation index caused by 'c'
in this test;
a = 25
b = 11.61
c = 10
d = 2.60
therefore;
EC3 = 10.7 %
The concentration of test item expected to cause a 3 fold increase in 3HTdR incorporation (EC3 value) was calculated to be 10.7 %.
CLINICAL OBSERVATIONS:
There were no clinical signs indicative of a systemic effect of treatment among mice treated with the vehicle or with 10, 25 or 50 % v/v formulations of the test article. No irritation was noted in any of the test groups.
BODY WEIGHTS
There was no indication of a treatment related effect on body weight. - Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- Based on the condition of this study, the test item was classified as a Category 1B sensitiser in accordance with Regulation (EC) No 1272/2008.
- Executive summary:
OECD 429 (2018) - In a dermal sensitization study with Reaction mass of N,N,N’,N’-tetrabutylmethylenediamine and dibutylamine in acetone: olive oil (4:1 v/v) young female adult mice (CBA/CaCrl) were tested using the Local Lymph Node Assay (LLNA).
Following a preliminary screening test in which no clinical signs of toxicity were noted at a concentration of 50 %, this concentration was selected as the highest dose investigated in the main test. Three groups, each of five animals, were treated with 25 μL of the test item in solution in the vehicle at concentrations of 50, 25 and 10 % v/v. A further group of five animals was treated with the vehicle alone. A concurrent positive control test, using a group of five animals, was also performed with the known sensitiser, α-Hexylcinnamaldehyde at a concentration of 25 % v/v in the vehicle.
There were no signs of systemic toxicity or skin irritation through the test period. Ear thickness were also within the normal range. There were no clinical abnormalities or macroscopic abnormalities of the surrounding area were noted for any of the animals and no mortality reported during the study. The Stimulation Index, expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group, was determined for each treatment group.
The test item did elicit a Stimulation Index ≥ 3 when tested at ≥ 25 % v/v with SI values of 2.60, 11.61 and 17.20 in the 10, 25 and 50 % w/v test groups, respectively. The test item was therefore considered to be a sensitiser under the conditions of the test. The EC3value, the concentration of test item expected to cause a three-fold increase in3HTdR incorporation (EC3value) was calculated to be 10.7 %.
In this study, the test item was a dermal sensitiser.
Based on the condition of this study, the test item was classified as a Category 1B sensitiser in accordance with Regulation (EC) No 1272/2008.
Reference
Table 1 Clinical Observations, Body Weight and Mortality Data – Preliminary Screening Test
Concentration | Animal Number | Body Weight (g) | Day | |||||||||
1 | 2 | 3 | 4 | 5 | 6 | |||||||
Day 1 | Day 6 | Pre-Dose | Post Dose | Pre-Dose | Post Dose | Pre-Dose | Post Dose | |||||
100 | S-1 | 19.6 | - | PrPt | - | - | - | - | - | - | - | |
25 | S-2 | 18.1 | 18.5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
50 | S-3 | 19.1 | 19.4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Table 2 Local Skin Irritation – Preliminary Screening Test
Concentration | Animal Number | Local Skin Irritation | |||||||||||
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||||
left | right | left | right | left | right | left | right | left | right | left | right | ||
100 | S-1 | 0 | 0 | - | - | - | - | - | - | - | - | - | - |
25 | S-2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
50 | S-3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Table 3 Measurement of Ear Thickness and Mean Ear Thickness Changes – Preliminary Screening Test
Concentration | Animal Number | Ear Thickness Measurement (mm) | |||||||||||||
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||||||
pre‑dose | 1 Hour | 1 Hour | 1 Hour | ||||||||||||
left | right | left | right | left | right | left | right | left | right | left | right | left | right | ||
100% | S-1 | 0.22 | 0.21 | - | - | - | - | - | - | - | - | - | - | - | - |
overall mean (mm) | 0.215 | - | - | - | - | - | - | ||||||||
overall mean ear thickness change (%) | - | - | - | - | - |
Concentration (% v/v) in | Animal Number | Ear Thickness Measurement (mm) | |||||||||||||
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||||||
pre‑dose | 1 Hour | 1 Hour | 1 Hour | ||||||||||||
left | right | left | right | left | right | left | right | left | right | left | right | left | right | ||
25% | S-2 | 0.22 | 0.21 | 0.22 | 0.22 | 0.22 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | 0.20 | 0.21 | 0.22 | 0.21 |
overall mean (mm) | 0.215 | 0.215 | 0.210 | 0.210 | 0.205 | 0.215 | |||||||||
overall mean ear thickness change (%) | na | 0.000 | -2.326 | -2.326 | -4.651 | 0.000 |
Table 3 (Continued) Measurement of Ear Thickness and Mean Ear Thickness Changes – Preliminary Screening Test
Concentration (% v/v) in | Animal Number | Ear Thickness Measurement (mm) | |||||||||||||
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||||||
pre‑dose | 1 Hour | 1 Hour | 1 Hour | ||||||||||||
left | right | left | right | left | right | left | right | left | right | left | right | left | right | ||
50% | S-3 | 0.20 | 0.21 | 0.20 | 0.21 | 0.21 | 0.22 | 0.21 | 0.21 | 0.21 | 0.21 | 0.22 | 0.21 | 0.22 | 0.21 |
overall mean (mm) | 0.205 | 0.215 | 0.210 | 0.210 | 0.215 | 0.215 | |||||||||
overall mean ear thickness change (%) | 4.878 | 2.439 | 2.439 | 4.878 | 4.878 |
Table 4 Individual Disintegrations per Minute and Stimulation Index – Main Test
Treatment Group | Animal Number | Mean dpm/Animal | Stimulation Index b | Result | |
Vehicle | 1-1 | 781.37 | 1250.67 | na | |
1-2 | 1255.20 | ||||
1-3 | 1631.04 | ||||
1-4 | 1247.48 | ||||
1-5 | 1338.26 | ||||
Test Item | 2-1 | 3853.82 | 3257.11 | 2.60 | Negative |
2-2 | 5239.57 | ||||
2-3 | 2204.47 | ||||
2-4 | 1090.55 | ||||
2-5 | 3897.13 | ||||
Test Item | 3-1 | 18597.07 | 14522.23** | 11.61 | Positive |
3-2 | 14353.77 | ||||
3-3 | 14063.90 | ||||
3-4 | 17590.18 | ||||
3-5 | 8006.25 | ||||
Test Item | 4-1 | 24202.56 | 21510.59** | 17.20 | Positive |
4-2 | 21990.93 | ||||
4-3 | 26536.65 | ||||
4-4 | 14016.35 | ||||
4-5 | 20806.45 | ||||
Positive Control Item | 5-1 | 7916.88 | 5745.41** | 4.59 | Positive |
5-2 | 6709.41 | ||||
5-3 | 6290.52 | ||||
5-4 | 3062.95 | ||||
5-5 | 4747.28 |
Table 5 Individual Clinical Observations and Mortality Data – Main Test
Treatment Group | Animal Number | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | |||
Pre-Dose | Post Dose | Pre-Dose | Post Dose | Pre-Dose | Post Dose | |||||
Vehicle | 1-1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
1-2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
1-3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
1-4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
1-5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Test Item | 2-1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
2-2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
2-3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
2-4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
2-5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Test Item | 3-1 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
3-2 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
3-3 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
3-4 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
3-5 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Test Item | 4-1 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
4-2 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
4-3 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
4-4 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
4-5 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Positive Control Item | 5-1 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
5-2 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
5-3 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
5-4 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
5-5 | 0 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Table 6 Measurement of Ear Thickness and Mean Ear Thickness Changes – Main Test
Treatment Group | Animal Number | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||
pre‑dose | post‑dose | post dose | |||||||||||
left | right | left | right | left | right | left | right | left | right | left | right | ||
Vehicle | 1-1 | 0.21 | 0.21 | 0.21 | 0.20 | 0.21 | 0.20 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 |
1-2 | 0.20 | 0.20 | 0.21 | 0.20 | 0.21 | 0.21 | 0.22 | 0.21 | 0.22 | 0.21 | 0.22 | 0.21 | |
1-3 | 0.20 | 0.21 | 0.21 | 0.21 | 0.21 | 0.20 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | |
1-4 | 0.22 | 0.21 | 0.22 | 0.21 | 0.22 | 0.20 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | |
1-5 | 0.20 | 0.20 | 0.21 | 0.20 | 0.22 | 0.20 | 0.22 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | |
overall mean (mm) | 0.206 | 0.208 | 0.208 | 0.212 | 0.211 | 0.211 | |||||||
overall mean ear thickness change (%) | Not applicable | 0.971 | 0.971 | 2.913 | 2.427 | 2.427 |
Treatment Group | Animal Number | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||
pre‑dose | post‑dose | post dose | |||||||||||
left | right | left | right | left | right | left | right | left | right | left | right | ||
Vehicle | 2-1 | 0.21 | 0.20 | 0.21 | 0.21 | 0.20 | 0.21 | 0.20 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 |
2-2 | 0.20 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | 0.21 | 0.22 | 0.22 | 0.22 | 0.22 | |
2-3 | 0.22 | 0.21 | 0.21 | 0.20 | 0.23 | 0.22 | 0.23 | 0.21 | 0.23 | 0.21 | 0.23 | 0.21 | |
2-4 | 0.21 | 0.20 | 0.22 | 0.21 | 0.22 | 0.21 | 0.23 | 0.21 | 0.23 | 0.22 | 0.23 | 0.22 | |
2-5 | 0.20 | 0.20 | 0.21 | 0.20 | 0.21 | 0.21 | 0.22 | 0.22 | 0.22 | 0.21 | 0.22 | 0.21 | |
overall mean (mm) | 0.206 | 0.209 | 0.213 | 0.215 | 0.218 | 0.218 | |||||||
overall mean ear thickness change (%) | Not applicable | 1.456 | 3.398 | 4.369 | 5.825 | 5.825 |
Table 6 (continued) Measurement of Ear Thickness and Mean Ear Thickness Changes – Main Test
Treatment Group | Animal Number | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||
pre‑dose | post‑dose | post dose | |||||||||||
left | right | left | right | left | right | left | right | left | right | left | right | ||
Vehicle | 3-1 | 0.21 | 0.20 | 0.20 | 0.20 | 0.21 | 0.21 | 0.21 | 0.21 | 0.20 | 0.20 | 0.21 | 0.21 |
3-2 | 0.22 | 0.21 | 0.21 | 0.21 | 0.22 | 0.22 | 0.22 | 0.23 | 0.22 | 0.23 | 0.22 | 0.23 | |
3-3 | 0.22 | 0.22 | 0.22 | 0.22 | 0.22 | 0.22 | 0.21 | 0.21 | 0.22 | 0.21 | 0.22 | 0.22 | |
3-4 | 0.22 | 0.21 | 0.21 | 0.22 | 0.22 | 0.21 | 0.22 | 0.22 | 0.21 | 0.22 | 0.21 | 0.22 | |
3-5 | 0.22 | 0.22 | 0.22 | 0.23 | 0.21 | 0.23 | 0.22 | 0.22 | 0.22 | 0.21 | 0.22 | 0.21 | |
overall mean (mm) | 0.215 | 0.214 | 0.217 | 0.217 | 0.214 | 0.217 | |||||||
overall mean ear thickness change (%) | Not applicable | -0.465 | 0.930 | 0.930 | -0.465 | 0.930 |
Treatment Group | Animal Number | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||
pre‑dose | post‑dose | post dose | |||||||||||
left | right | left | right | left | right | left | right | left | right | left | right | ||
Vehicle | 4-1 | 0.22 | 0.21 | 0.22 | 0.21 | 0.22 | 0.21 | 0.22 | 0.22 | 0.21 | 0.21 | 0.21 | 0.21 |
4-2 | 0.21 | 0.20 | 0.21 | 0.21 | 0.22 | 0.22 | 0.22 | 0.23 | 0.22 | 0.22 | 0.22 | 0.22 | |
4-3 | 0.22 | 0.21 | 0.21 | 0.22 | 0.21 | 0.23 | 0.22 | 0.23 | 0.21 | 0.21 | 0.21 | 0.21 | |
4-4 | 0.22 | 0.22 | 0.22 | 0.22 | 0.22 | 0.24 | 0.23 | 0.23 | 0.23 | 0.24 | 0.23 | 0.24 | |
4-5 | 0.22 | 0.22 | 0.22 | 0.22 | 0.21 | 0.22 | 0.22 | 0.22 | 0.23 | 0.22 | 0.23 | 0.22 | |
overall mean (mm) | 0.215 | 0.216 | 0.220 | 0.224 | 0.220 | 0.221 | |||||||
overall mean ear thickness change (%) | Not applicable | 0.465 | 2.326 | 4.186 | 2.326 | 2.791 |
Table 6 (continued) Measurement of Ear Thickness and Mean Ear Thickness Changes – Main Test
Treatment Group | Animal Number | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||
pre‑dose | post‑dose | post dose | |||||||||||
left | right | left | right | left | right | left | right | left | right | left | right | ||
Vehicle | 5-1 | 0.21 | 0.21 | 0.21 | 0.21 | 0.22 | 0.22 | 0.22 | 0.22 | 0.23 | 0.22 | 0.22 | 0.22 |
5-2 | 0.20 | 0.21 | 0.21 | 0.22 | 0.22 | 0.22 | 0.23 | 0.22 | 0.23 | 0.22 | 0.23 | 0.22 | |
5-3 | 0.21 | 0.20 | 0.20 | 0.20 | 0.21 | 0.22 | 0.21 | 0.22 | 0.22 | 0.21 | 0.22 | 0.21 | |
5-4 | 0.22 | 0.20 | 0.21 | 0.21 | 0.21 | 0.21 | 0.22 | 0.22 | 0.22 | 0.23 | 0.22 | 0.23 | |
5-5 | 0.21 | 0.21 | 0.20 | 0.21 | 0.22 | 0.21 | 0.22 | 0.22 | 0.21 | 0.21 | 0.21 | 0.21 | |
overall mean (mm) | 0.208 | 0.208 | 0.216 | 0.220 | 0.220 | 0.219 | |||||||
overall mean ear thickness change (%) | Not applicable | 0.000 | 3.846 | 5.769 | 5.769 | 5.288 |
Table 7 Individual Body Weights and Body Weight Change – Main Test
Treatment Group | Animal Number | Body Weight (g) | Body Weight Change (g) | |
Day 1 | Day 6 | |||
Vehicle | 1-1 | 20.1 | 21.2 | 1.1 |
1-2 | 20.0 | 19.6 | -0.4 | |
1-3 | 20.9 | 20.8 | -0.1 | |
1-4 | 19.8 | 20.0 | 0.2 | |
1-5 | 19.6 | 19.1 | -0.5 | |
Test Item | 2-1 | 18.9 | 19.8 | 0.9 |
2-2 | 18.9 | 20.6 | 1.7 | |
2-3 | 19.7 | 20.0 | 0.3 | |
2-4 | 21.2 | 21.6 | 0.4 | |
2-5 | 20.4 | 21.1 | 0.7 | |
Test Item | 3-1 | 18.9 | 19.0 | 0.1 |
3-2 | 21.4 | 21.6 | 0.2 | |
3-3 | 20.7 | 21.2 | 0.5 | |
3-4 | 20.6 | 20.3 | -0.3 | |
3-5 | 20.3 | 19.8 | -0.5 | |
Test Item | 4-1 | 21.3 | 21.2 | -0.1 |
4-2 | 19.9 | 18.8 | -1.1 | |
4-3 | 20.3 | 20.5 | 0.2 | |
4-4 | 20.2 | 20.1 | -0.1 | |
4-5 | 20.7 | 19.4 | -1.3 | |
Positive Control Item | 5-1 | 20.1 | 21.1 | 1.0 |
5-2 | 19.3 | 19.7 | 0.4 | |
5-3 | 20.0 | 20.4 | 0.4 | |
5-4 | 19.9 | 20.9 | 1.0 | |
5-5 | 19.6 | 20.5 | 0.9 |
0 = No signs of systemic toxicity
Pr = Prostration
Pt = Ptosis
Rd = Decreased respiratory rate
Rl = Labored respiration
K = Animal humanely killed due to the occurrence of clinical signs of toxicity that approached the moderate severity limit set forth in the UK Home Office Project Licence. Body weight at termination was 18.9g.
- = No data, animal dead
- = No data, animal dead
na = Not applicable
- = No data, animal dead
na = Not applicable
dpm = Disintegrations per minute
a = Total number of lymph nodes per animal is 2
b = Stimulation Index of 3.0 or greater indicates a positive result
na = Not applicable
** = Significantly different from control group p<0.01
0 = No signs of systemic toxicity
- = Observations not recorded due to a technician error
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
OECD 429 (2018) - In a dermal sensitization study with Reaction mass of N,N,N’,N’-tetrabutylmethylenediamine and dibutyylamine in acetone: olive oil (4:1 v/v) young female adult mice (CBA/CaCrl) were tested using the Local Lymph Node Assay (LLNA).
Following a preliminary screening test in which no clinical signs of toxicity were noted at a concentration of 50 %, this concentration was selected as the highest dose investigated in the main test. Three groups, each of five animals, were treated with 25 μL of the test item in solution in the vehicle at concentrations of 50, 25 and 10 % v/v. A further group of five animals was treated with the vehicle alone. A concurrent positive control test, using a group of five animals, was also performed with the known sensitiser, α-Hexylcinnamaldehyde at a concentration of 25 % v/v in the vehicle.
There were no signs of systemic toxicity or skin irritation through the test period. Ear thickness were also within the normal range. There were no clinical abnormalities or macroscopic abnormalities of the surrounding area were noted for any of the animals and no mortality reported during the study. The Stimulation Index, expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group, was determined for each treatment group.
The test item did elicit a Stimulation Index ≥ 3 when tested at ≥ 25 % v/v with SI values of 2.60, 11.61 and 17.20 in the 10, 25 and 50 % w/v test groups, respectively. The test item was therefore considered to be a sensitiser under the conditions of the test. The EC3value, the concentration of test item expected to cause a three-fold increase in 3HTdR incorporation (EC3value) was calculated to be 10.7 %.
In this study, the substance was a dermal sensitiser.
Based on the condition of this study, the test item was classified as a Category 1B sensitiser in accordance with Regulation (EC) No 1272/2008.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Harmonised classification:
The substance has no harmonised classification for skin sensitisation according to the Regulation (EC) No. 1272/2008 (CLP).
Self classification:
The substance meets the criteria for classification as a skin sensitiser (category 1B) in accordance with Regulation (EC) No 1272/2008 (CLP).
No information is available regarding respiratory sensitisation.
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