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EC number: 251-359-7 | CAS number: 33045-53-3
- 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:
- key study
- Study period:
- October 12, 2016 - October 25, 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442B (Skin Sensitization: Local Lymph Node Assay: BrdU-ELISA)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EU Method B.51 (Skin sensitisation. local lymph node assay: BrdU-ELISA)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA): BrdU-ELISA
Test material
- Reference substance name:
- Ethyl 5-sulphamoyl-o-anisate
- EC Number:
- 251-359-7
- EC Name:
- Ethyl 5-sulphamoyl-o-anisate
- Cas Number:
- 33045-53-3
- Molecular formula:
- C10H13NO5S
- IUPAC Name:
- ethyl 2-methoxy-5-sulfamoylbenzoate
- Test material form:
- solid
- Details on test material:
- CAS number: 33045-53-3
EC number: 251-359-7
Other name: Ester Sulpiride
Constituent 1
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: yes
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA:J
- Remarks:
- CBA/JRj
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Elevage Janvier Labs (F-53941Le Genest Saint Isle)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks old.
- Weight at study initiation: average weight 0.20 ± 0.01
- Housing: the animals were housed individually (to avoid any test item absorption by oral route) in a suspended solid-floor polypropylene cages furnished with softwood woodflakes.
- Diet: Tkelad Global 16% Protein Rodent Diet (ENVIGO 2016) ad libitum
- Water: tap water from public distribution system ad libitum. Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas - Eurofins (FRANCE)
- Acclimation period: at least 5 days
- Indication of any skin lesions: no
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19ºC-25ºC
- Humidity (%): 30%-70%. A relative humidity lower than 30% was registered on 22 October 2016. The minimum value measured was 28%. This deviation is considered as without impact on the conclusion of the study.
- Air changes (per hr): 10 changes/hour
- Photoperiod (hrs dark / hrs light): 12 h light (7.00 to 19.00) / 12 h darkness
- IN-LIFE DATES: From: 12 October 2016 To: 25 October 2016
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- 50%, 25% and 10%
- No. of animals per dose:
- 4
- Details on study design:
- PRE-SCREEN TESTS: a preliminary screening test was performed using one mouse. The mouse was treated by daily application of 25 µL of the test item diluted at 50% in dimethylformamide (DMF) to the dorsal surface of each ear for three consecutive days (Days 1,2,3). The mouse was observed daily from day 1. Any signs of toxicity or excessive local irritation noted during this period were recorded. Ear thickness was recorded on day 1, day 3 and on day 6. The bodyweight of the mouse was recorded on Day 1 (prior to dosing) and Day 6.
- Compound solubility: A preliminary solubility test was performed using different vehicles (Table 1) and the formulation of 50% in dimethylformamide (DMF) was the most suitable for the test.
- Irritation: No cutaneous reaction was noted at the tested concentration.
- Systemic toxicity: No mortality and no signs of systemic toxicity were noted.
- Ear thickness measurements: values were within the acceptable range (Table 2)
- Erythema scores: no signs of erithema were observed (Table 2)
MAIN STUDY
Groups of four mice were treated with the test item diluted at 50%, 25% and 10% in dimethylformamide based on the results of the pre-screen tests. The mice 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).
- Clinical observations. all animals were observed daily on Days 1, 2, 3 4, 5 and 6. Any signs of toxicity or signs of ill health during the test were recorded.
- Body weight: the bodyweight of each mouse was recorded on Day 1 (prior to dosing) and Day 6 (prior to termination).
- Ear thickness: On day 1 and on day 3 (before application) as well as on day 6 (after sacrifice) of each experiment, the thickness of the right ear of each animal of the vehicle control and treated groups was measured by a micrometer. Furthermore, on day 6, punch biopsies of 8 mm in diameter of the apical area of both ears were prepared and weighted in order to assess the irritation potential of the test item and the two lymph nodes per mouse were weighted.
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Skin sensitisation. Local Lymph Node Assay:BrdU-ELISA
- Criteria used to consider a positive response: BrdU was measured by ELISA using a commercial kit (Roche Applied Science, Mannheim, Germany, Catalogue Number 11 647 229 001 - Batch No. 11866200). Briefly, 100 µL of the LNC suspension was added to the wells of a flat-bottom microplate at least in triplicate. After fixation and denaturation of the LNC, anti-BrdU antibody was removed by washing and the substrate solution was then added and allowed to produce chromogen. After 5 to 30 min, 30 µL of 1 M H2SO4 was added in each well, then shaken for one minute. Absorbance at 450 nm with a reference wavelength of 690 nm was then measured.
The BrdU labelling index was defined as: BrdU labelling index = (ABSem - ABS blankem) - (ABSref - ABS blankref)
The test item will be regarded as a sensitiser if at least one concentration of the test item results is greater than 1.6 compared to control values.
However, the strength of the dose-response relationship, the statistical significance and the consistency of the solvent/vehicle and positive control responses may also be used when determining whether a borderline result (SI value between 1.6 and 1.9) is declared positive. Any test item failing to produce a SI>1.6 will be classified as a "sensitiser".
The EC1.6 value (theoretical concentration resulting in a SI value of 1.6) was detemined by linear interpolation of points on the dose-response curve, immediately above and below the 1.6 -fold threshold. The equation used for calculation of EC1.6 was:
EC1.6 = c + [(1.6 - d) / (b - d)] x (a - c)
Legend: a = the lowest concentration giving stimulation index > 1.6
b = the actual stimulation index caused by a
c = the highest concentration failing to produce a stimulation index of 1.6
d = the actual stimulation index caused by c
TREATMENT PREPARATION AND ADMINISTRATION:
The test item was freshly prepared in dimethylformamide. The test item was diluted at 50% (maximum concentration available), 25% and 10% in dimethylformamine. The mice were treated by daily application of 25 µL of the appropiate 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. A further group of four mice received the vehicle alone in the same manner.
On day 5 (5 mg/mouse) of BrdU (10 mg/mL) solution was injected by intra-peritoneal route.
The BrdU solution was prepared by weighing 309.5 mg of 5 -bromo-2'-deoxyuridine 8SIGMA - Batch No. HMBD6482V) in a glass sample bottle and adding 30.98 mL of physiological saline. Then, the preparation was stirred magnetically and vortex, just before treatment.
On day 6 (end of the test), the animals were anaesthetised with sodium pentobarbital and adminitration continued to fatal levels. The draining auricular lymph nodes from the four mic were excised.
From each mouse, a single-cell suspension through a disposable plastic pestle to crush the lymph nodes followed by passage through a #70 nylon mesh in 15 mL of PBD (Ca2 +/Mg2+ - free) into a well of multi-well 6. The optimised volume was based on achieving a mean absorbance of the negative control group within 0.1 -0.2. Then, BrdU was determined. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
Results and discussion
- Positive control results:
- EC1.6= 9.48%. The substance has to be classified in category 1 "Skin sensitisation".
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- SI
- Value:
- ca. 1.04
- Test group / Remarks:
- 10%
- Key result
- Parameter:
- SI
- Value:
- ca. 0.91
- Test group / Remarks:
- 25%
- Key result
- Parameter:
- SI
- Value:
- ca. 1.37
- Test group / Remarks:
- 50%
- Parameter:
- other: EC1.6
- Remarks on result:
- not determinable
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
No increase in ear thickness and in ear weight was noted in animals treated at 10%, 25% and 50% (Tables 7 and 8).
DETAILS ON STIMULATION INDEX CALCULATION
No stimulation index of more than 1.6 was recorded whatever the tested concentration. the Stimulation Index (SI) calculated by individual approach was 1.04, 0.91 and 1.37 for the treated groups at 10%, 25% and 50%, respectively (Tables 5 and 6).
EC3 CALCULATION
The EC1.6 cannot be determined in this study.
CLINICAL OBSERVATIONS:
No mortality and no signs of systemic toxicity were noted in the test and control animals during the test (Table 3).
Slight dryness of the skin was noted in all animals at the tested concentrations of 25% on day 3. No other cutaneous reaction was noted whatever the tested concentration.
Therefore, the test item has to be considered as not excessively irritant at these concentrations.
BODY WEIGHTS
Bodyweight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period (Table 2).
Any other information on results incl. tables
Table 1. Vehicle determination record
Vehicle |
Concentration |
Method of preparation |
Description of formulation |
Suitability* |
AOO |
50% |
0.1 g test item + 0.1 g vehicle |
Non homogenous suspension |
No |
DMF |
75% |
1.5 g test item + 0.5 g vehicle |
Non homogenous whitish paste |
No |
DMF |
50% |
0.1 g test item + 0.1 g vehicle |
Colorless solution |
Yes |
DMF |
10% |
0.2 g test item + 0.18 g vehicle |
Colorless solution |
Yes |
MEK |
50% |
0.2 g test item + 0.2 g vehicle |
Non homogenous suspension |
No |
PG |
50% |
0.2 g test item + 0.2 g vehicle |
Non homogenous suspension |
No |
DMO |
50% |
0.5 g test item + 0.5 g vehicle |
Non homogenous suspension |
No |
Pluronic®1% acid |
50% |
0.2 g test item + 0.2 g vehicle |
Non homogenous suspension |
No |
Table 2. Clinical observation, bodyweight and mortality data
Concentration % |
Animal |
Bodyweight (g) |
DAY |
||||||
Day 1 |
Day 6 |
1 |
2 |
3 |
4 |
5 |
6 |
||
50% |
Sf8719 |
19.0 |
19.4 |
0 |
0 |
0o |
0 |
0 |
0 |
0: No sign of systemic toxicity and no sign of erythema
o: residue of the test item
|
Ear thickness (mm) on day 1 |
Ear thickness (mm) on day 3 |
Ear thickness (mm) on day 6 |
Ear weight (mg) on day 6 |
Weight Lymph nodes (mg) |
Sf8719 |
0.19 |
0.20 |
0.20 |
25.4 |
5.2 |
Main test:
Table 3. Individual clinical observation and mortality data
Groups |
Test item |
Amimals |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
1 |
DMF |
Nº Sf 8743 |
0 |
0 |
0 |
0 |
0 |
0 |
Nº Sf 8744 |
0 |
0 |
0 |
0 |
0 |
0 |
||
Nº Sf 8745 |
0 |
0 |
0 |
0 |
0 |
0 |
||
Nº Sf 8746 |
0 |
0 |
0 |
0 |
0 |
0 |
||
2 |
10% |
Nº Sf 8748 |
0 |
0 |
0 |
0 |
0 |
0 |
Nº Sf 8752 |
0 |
0 |
0 |
0 |
0 |
0 |
||
Nº Sf 8750 |
0 |
0 |
0 |
0 |
0 |
0 |
||
Nº Sf 8751 |
0 |
0 |
0 |
0 |
0 |
0 |
||
3 |
25% |
Nº Sf 8753 |
0 |
0 |
0o* |
0o |
0o |
0o |
Nº Sf 8754 |
0 |
0 |
0o* |
0o |
0o |
0o |
||
Nº Sf 8757 |
0 |
0 |
0o* |
0o |
0o |
0o |
||
Nº Sf 8756 |
0 |
0 |
0o* |
0o |
0o |
0o |
||
4 |
50% |
Nº Sf 8758 |
0 |
0o |
0o |
0o |
0o |
0o |
Nº Sf 8759 |
0 |
0o |
0o |
0o |
0o |
0o |
||
Nº Sf 8760 |
0 |
0o |
0o |
0o |
0o |
0o |
||
Nº Sf 8761 |
0 |
0o |
0o |
0o |
0o |
0o |
0: No sign of systemic toxicity and no sign of erythema
DMF. dimethylformamide
o: residue of the test item
*: slight dryness
Table 4. Individual body weight and body weight gain
Groups |
Test item |
Amimals |
Body weight (g) |
Body weight gain (g) |
|
Day 1 |
Day 6 |
||||
1 |
DMF |
Nº Sf 8743 |
20.8 |
22.2 |
1.4 |
Nº Sf 8744 |
21.3 |
23.7 |
2.4 |
||
Nº Sf 8745 |
20.6 |
21.4 |
0.8 |
||
Nº Sf 8746 |
21.3 |
23.1 |
1.8 |
||
MEAN |
21.0 |
22.6 |
1.6 |
||
Standard-deviation |
0.4 |
1.0 |
0.7 |
||
2 |
10% |
Nº Sf 8748 |
21.0 |
21.8 |
0.8 |
Nº Sf 8752 |
18.4 |
20.6 |
2.2 |
||
Nº Sf 8750 |
21.6 |
22.3 |
0.7 |
||
Nº Sf 8751 |
22.1 |
22.9 |
0.8 |
||
MEAN |
20.8 |
21.9 |
1.1 |
||
Standard-deviation |
1.6 |
1.0 |
0.7 |
||
3 |
25% |
Nº Sf 8753 |
21.1 |
21.0 |
-0.1 |
Nº Sf 8754 |
19.2 |
20.7 |
1.5 |
||
Nº Sf 8757 |
18.4 |
19.0 |
0.6 |
||
Nº Sf 8756 |
20.8 |
22.1 |
1.3 |
||
MEAN |
19.9 |
20.7 |
0.8 |
||
Standard-deviation |
1.3 |
1.3 |
0.7 |
||
4 |
50% |
Nº Sf 8758 |
20.6 |
22.7 |
2.1 |
Nº Sf 8759 |
20.9 |
21.3 |
0.4 |
||
Nº Sf 8760 |
19.1 |
19.2 |
0.1 |
||
Nº Sf 8761 |
19.3 |
19.9 |
0.6 |
||
MEAN |
20.0 |
20.8 |
0.8 |
||
Standard-deviation |
0.9 |
1.6 |
0.9 |
DMF. dimethylformamide
Table 5. BrdU index & Stimulation index per group and calculation of EC1.6
Groups |
Test item |
BrdU-index (mean*) |
Stimulation Index SI (mean + standard deviation) |
Result |
EC1.6 value |
1 |
DMF |
0.655 |
n.a. |
n.a. |
n.a. |
2 |
10% |
0.681 |
1.04±0.28 |
negative |
n.a. |
3 |
25% |
0.596 |
0.91±0.37 |
negative |
|
4 |
50% |
0.894 |
1.37±0.09 |
negative |
Table 6.BrdU index & Stimulation index (individual data)
Groups |
Test item |
Amimal |
BrdU-Index (DO Indiv) |
BrdU-Index (DO mean) |
BrdU-Index mean* |
Stimulation Index S.I. (indiv±Standard deviation |
1 |
DMF |
Sf 8743 |
0.988 |
0.923 |
0.655 |
n.a |
0.937 |
||||||
0.844 |
||||||
Sf 8744 |
0.626 |
0.602 |
n.a |
|||
0.569 |
||||||
0.611 |
||||||
Sf 8745 |
0.537 |
0.538 |
n.a |
|||
0.506 |
||||||
0.571 |
||||||
Sf 8746 |
0.604 |
0.555 |
n.a |
|||
0.613 |
||||||
0.446 |
||||||
2 |
10% |
Sf 8748 |
0.891 |
0.880 |
0.681 |
1.34±0.09 |
0.933 |
||||||
0.816 |
||||||
Sf 8752 |
0.823 |
0.797 |
1.22±0.04 |
|||
0.778 |
||||||
0.790 |
||||||
Sf 8750 |
0.518 |
0.515 |
0.79±0.06 |
|||
0.474 |
||||||
0.553 |
||||||
Sf 8751 |
0.594 |
0.531 |
0.81±0.09 |
|||
0.521 |
||||||
0.477 |
||||||
3 |
25% |
Sf 8753 |
0.945 |
0.956 |
0.596 |
1.46±0.02 |
0.953 |
||||||
0.968 |
||||||
Sf 8754 |
0.515 |
0.509 |
0.78±0.03 |
|||
0.484 |
||||||
0.526 |
||||||
Sf 8757 |
0.469 |
0.489 |
0.75±0.05 |
|||
0.472 |
||||||
0.525 |
||||||
Sf 8756 |
0.570 |
0.431 |
0.66±0.19 |
|||
0.323 |
||||||
0.399 |
||||||
4 |
50% |
Sf 8758 |
0.930 |
0.926 |
0.894 |
1.41±0.02 |
0.934 |
||||||
0.913 |
||||||
Sf 8759 |
0.785 |
0.811 |
1.24±0.03 |
|||
0.820 |
||||||
0.826 |
||||||
Sf 8760 |
0.841 |
0.905 |
1.38±0.09 |
|||
0.911 |
||||||
0.963 |
||||||
Sf 8761 |
0.931 |
0.932 |
1.42±0.16 |
|||
1.033 |
||||||
0.830 |
*: mean:Σindividual value / 4
DMF: dimethylformamide
Table 7. Individual Ear thickness and irritation level.
Groups |
Test item |
Amimals |
Day 1 Ear thickness (mm) |
Day 3 Ear thickness (mm) |
Day 6 Ear thickness (mm) |
Ear thickness increase D3/D1 (%) |
Ear thickness increase D6/D1 (%) |
1 |
DMF |
Nº Sf 8743 |
0.19 |
0.21 |
0.21 |
10.5 |
10.5 |
Nº Sf 8744 |
0.21 |
0.21 |
0.21 |
0.0 |
0.0 |
||
Nº Sf 8745 |
0.19 |
0.19 |
0.20 |
0.0 |
5.3 |
||
Nº Sf 8746 |
0.19 |
0.19 |
0.21 |
0.0 |
10.5 |
||
MEAN |
0.20 |
0.20 |
0.21 |
2.6 |
6.6 |
||
Standard-deviation |
0.01 |
0.01 |
0.00 |
5.3 |
5.0 |
||
2 |
10% |
Nº Sf 8748 |
0.19 |
0.19 |
0.19 |
0.0 |
0.0 |
Nº Sf 8752 |
0.19 |
0.19 |
0.21 |
0.0 |
10.5 |
||
Nº Sf 8750 |
0.20 |
0.20 |
0.21 |
0.0 |
5.0 |
||
Nº Sf 8751 |
0.19 |
0.19 |
0.20 |
0.0 |
5.3 |
||
MEAN |
0.19 |
0.19 |
0.20 |
0.0 |
5.2 |
||
Standard-deviation |
0.01 |
0.01 |
0.01 |
0.0 |
4.3 |
||
3 |
25% |
Nº Sf 8753 |
0.20 |
0.20 |
0.21 |
0.0 |
5.0 |
Nº Sf 8754 |
0.19 |
0.19 |
0.20 |
0.0 |
5.3 |
||
Nº Sf 8757 |
0.19 |
0.20 |
0.20 |
5.3 |
5.3 |
||
Nº Sf 8756 |
0.19 |
0.19 |
0.19 |
0.0 |
0.0 |
||
MEAN |
0.19 |
0.20 |
0.20 |
1.3 |
3.9 |
||
Standard-deviation |
0.01 |
0.01 |
0.01 |
2.6 |
2.6 |
||
4 |
50% |
Nº Sf 8758 |
0.20 |
0.21 |
0.21 |
5.0 |
5.0 |
Nº Sf 8759 |
0.19 |
0.21 |
0.21 |
10.5 |
10.5 |
||
Nº Sf 8760 |
0.19 |
0.21 |
0.21 |
10.5 |
10.5 |
||
Nº Sf 8761 |
0.19 |
0.19 |
0.20 |
0.0 |
5.3 |
||
MEAN |
0.19 |
0.21 |
0.21 |
6.5 |
7.8 |
||
Standard-deviation |
0.01 |
0.01 |
0.00 |
5.1 |
3.1 |
DMF: dimethylformamide
Table 8. Individual Ear biopsy weight and lymph node weight.
Groups |
Test item |
Amimals |
Ear weight Day 6 (mg) |
% of ear weight increased/group1 |
Lymph nodes (mg) |
1 |
DMF |
Nº Sf 8743 |
25.3 |
|
6.7 |
Nº Sf 8744 |
24.5 |
4.4 |
|||
Nº Sf 8745 |
23.9 |
5.2 |
|||
Nº Sf 8746 |
25.9 |
4.1 |
|||
MEAN |
24.9 |
5.1 |
|||
Standard-deviation |
0.9 |
1.2 |
|||
2 |
10% |
Nº Sf 8748 |
23.5 |
-2.8 |
4.9 |
Nº Sf 8752 |
23.4 |
4.8 |
|||
Nº Sf 8750 |
25.8 |
5.8 |
|||
Nº Sf 8751 |
24.1 |
5.1 |
|||
MEAN |
24.2 |
5.2 |
|||
Standard-deviation |
1.1 |
0.5 |
|||
3 |
25% |
Nº Sf 8753 |
23.4 |
-3.3 |
4.6 |
Nº Sf 8754 |
24.8 |
5.5 |
|||
Nº Sf 8757 |
24.1 |
6.3 |
|||
Nº Sf 8756 |
24.0 |
6.0 |
|||
MEAN |
24.1 |
5.6 |
|||
Standard-deviation |
0.6 |
0.7 |
|||
4 |
50% |
Nº Sf 8758 |
23.5 |
-0.6 |
6.2 |
Nº Sf 8759 |
26.3 |
8.2 |
|||
Nº Sf 8760 |
23.8 |
6.3 |
|||
Nº Sf 8761 |
25.4 |
6.7 |
|||
MEAN |
24.8 |
6.9 |
|||
Standard-deviation |
1.3 |
0.9 |
DMF: dimethylformamide
Table 9. Summary of result – skin irritation
Groups |
Test item |
Ear thickness increase D6/D1 (%) |
Biopsy ear weight Increase (%) |
Excessive irritation# |
1 |
DMF |
6.6 |
n.a |
No |
2 |
10% |
5.2 |
-2.8 |
No |
3 |
25% |
3.9 |
-3.3 |
No |
4 |
50% |
7.8 |
-0.6 |
No |
#: O.E.C.D. criteria: (% increase in ear thickness lower than 25%, score of erythema lower than 3)
DMF: dimethylformamide
Table 10. BrdU index & Stimulation index per group and calculation of EC1.6of the positive control (study performed 29 June 2016 – 5 July 2016)
Groups |
Test item |
BrdU-index (mean*) |
Stimulation Index SI (mean + standard deviation) |
Result |
EC1.6 value |
1 |
AHO |
1.028 |
n.a. |
n.a. |
n.a. |
2 |
5% |
1.379 |
1.34±0.10 |
positive |
9.48% |
3 |
10% |
1.680 |
1.63±0.19 |
positive |
|
4 |
25% |
2.009 |
1.95±0.41 |
positive |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item did not show skin sensitisation potential unter the tested conditions in the LLNA assay (OECD 442B). The stimulation indexes were 1.04, 0.91 and 1.37 at concentrations of test item 10%, 25% and 50%, respectively.
- Executive summary:
The skin sensitisation potential of the test item was tested according OECD 442B and E.U. B.51 method, following GLP. It was tested on three groups of four mouse CBA/J treated for three consecutive days with 50 µL (25 µL per ear) of the test item diluted at concentrations of 10%, 25% and 50% in dimethylformamide. A control group was treated with dimethylformamide. On day 5, 0.5 mL of BrdU solution (10 mg/mL) was injected by the intraperitoneal route. On day 6, the profileration of lymphocytes in the draining auricular lymph nodes was determined by measurement of BrdU content in DNA of lymphocyte using an ELISA kit. No mortality and no signs of systemic toxicity were noted in the test and control animals during the test. No increase in ear thickness and in ear weight was noted in animals treated at 10%, 25% and 50%. Therefore, the test item has to be considered as not excessively irritant at these concentrations. The Stimulation Index (SI) calculated by individual approach was 1.04, 0.91 and 1.37 for the treated groups at 10%, 25% and 50%, respectively. The EC1.6 cannot be determined in this study.
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