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EC number: 248-468-7 | CAS number: 27458-90-8
- 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
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
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- Endpoint summary
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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
The skin sensitisation potential of DI-TERT-DODECYL DISULPHIDE was
evaluated following dermal exposure (Váliczkó, 2016). Based on the
results of the Preliminary Compatibility Test, the test item
characteristics, its usage and on the recommendations of the OECD
Guideline no. 429, the test item was tested for formulation
compatibility in acetone:olive oil 4:1 (v:v) mixture (abbreviated as
AOO). The highest achievable concentration based on the regulatory
requirements of the OECD guideline and the physical characteristics of
the test item was 100 % (undiluted). The Preliminary Irritation/Toxicity
Test was performed in CBA/CaOlaHsd mice using two doses (2
animals/dose): 100 % (undiluted) and 50 % (w/v) in AOO. Based on the
observations recorded in the preliminary test, the 100 % (undiluted) was
selected as top dose for the main test. In the main assay, twenty-eight
female CBA/CaOlaHsd mice were allocated to seven groups of four animals
each:
- five groups received DI-TERT-DODECYL DISULPHIDE (formulated in AOO) at
100 % (undiluted), 50, 25, 10 and 2 % (w/v) concentrations,
- the negative control group received the vehicle (AOO),
- the positive control group received 25 % (w/v) HCA (dissolved in AOO).
The test item solutions were applied on the dorsal surface of ears of
experimental animals (25 µL/ear) for three consecutive days (Days 1, 2
and 3). There was no treatment on Days 4, 5 and 6. The cell
proliferation in the local lymph nodes was measured by incorporation of
tritiated methyl thymidine (3HTdR) and the values obtained were used to
calculate stimulation indices (SI).
No mortality or signs of systemic toxicity were observed during the
study. There were no indications of any irritancy at the site of
application. No marked body weight loss (=5%) was observed on the mean
body weight of the groups in the study. The stimulation index values
were 3.1, 3.2, 1.7, 1.4 and 0.9 at concentrations of 100 % (undiluted),
50, 25, 10 and 2 % (w/v), respectively. The result of the positive
control substance a-Hexylcinnamaldehyde (HCA) dissolved in the same
vehicle was used to demonstrate the appropriate performance of the
assay. A lymphoproliferative response in line with historic positive
control data was noted for the positive control chemical, this result
confirmed the validity of the assay.
In conclusion, under the conditions of the present assay,
DI-TERT-DODECYL DISULPHIDE, tested in a suitable vehicle, was shown to
have a slight sensitisation potential (sensitizer) in the Local Lymph
Node Assay. The calculated EC3 value was 46.7 % (w/v).
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:
- 02 March 2016 to 09 March 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA
- Sex:
- female
- Details on test animals and environmental conditions:
- Species and strain: CBA/CaOlaHsd mice
Source: Envigo (Formerly: Harlan Laboratories S.r.l.), San Pietro al Natisone (UD), Zona Industriale Azzida, 57, 33049 Italy
Hygienic level: SPF at arrival; standard housing conditions during the study
Justification of strain: On the basis of OECD Guideline, mice of CBA/Ca or CBA/J strain can be used. Females are used because the existing database is predominantly based on females.
Number of animals: 4 animals / group
Sex: Female, nulliparous, non pregnant
Age of animals at starting: 10 weeks old (age-matched, within one week)
Body weight range at starting: 19.8 – 22.1 grams (The weight variation in animals in the study did not exceed ± 20 % of the mean weight).
Acclimatization time: 21 days
Note: In the Preliminary Experiment, mice of 10 weeks of age (17.4-18.7 grams) were used.
Husbandry
Animal health: Only healthy animals were used for the study. Health status was certified by the veterinarian.
Housing / Enrichment: Group caging / mice were provided with glass tunnel-tubes
Cage type: Type II. polypropylene / polycarbonate
Bedding: Bedding was available to animals during the study
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 19.4 - 24.3°C
Relative humidity: 22 - 70 %
Ventilation: 15-20 air exchanges/hour
The temperature and relative humidity were recorded twice every day during the acclimatisation and experimental phases.
Food and feeding
Animals received ssniff® SM Rat/Mouse – “Breeding & Maintenance, 15 mm, autoclavable Complete diet for rats/mice” produced by ssniff Spezialdiäten GmbH (Ferdinand-Gabriel-Weg 16, D-59494 Soest, Germany), ad libitum. The food was considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
Water supply
Animals received tap water from the municipal supply from 500 mL bottles, ad libitum. Water quality control analysis was performed once every three months and microbiological assessment was performed monthly by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József Attila u. 36., Hungary).
Bedding
Bedding of certified wood chips especially designed to keep animals in the best natural environment was provided for animals during the study. Lignocel 3/4-S Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH & Co.KG (D-73494 Rosenberg, Germany) was available to animals during the study. Nest building material was also provided for animals (ARBOCEL crinklets natural produced by J. Rettenmaier & Söhne GmbH +Co KG).
Identification and randomisation
A unique number written on the tail with a permanent marker identified each animal. The animal number was assigned on the basis of CiToxLAB Hungary Ltd.’s master file. The cages were marked with identity cards with information including study code, cage number, and dose group, sex and individual animal number. The animals were randomised and allocated to the experimental groups. The randomisation was checked by computer software using the body weight to verify the homogeneity and variability between the groups. - Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- The Preliminary Irritation/Toxicity Test was started according to the Study Plan on CBA/CaOlaHsd mice using two doses (2 animals/dose) at test item concentrations of 100 % (undiluted) and 50 % (w/v) in AOO.
Based on the observations, the 100 % (undiluted) was selected as top dose for the main test. At the request of the Sponsor additional dose groups (a total of 5) were tested in the main experiment to ensure that data allow the determination of the EC3 value of the test item. - No. of animals per dose:
- 4 per dose
- Details on study design:
- Dose Selection and Justification of Dose Selection
The Preliminary Irritation/Toxicity Test was started according to the Study Plan on CBA/CaOlaHsd mice using two doses (2 animals/dose) at test item concentrations of 100 % (undiluted) and 50 % (w/v) in AOO. The preliminary experiment was conducted in a similar experimental manner to the main study, but it was terminated on Day 6 and the radioactive proliferation assay was not performed.
The maximum concentration of test item in an acceptable solvent was established according to OECD guideline 429. Based on the observation of the solubility test, the maximum available concentration was 100 % (undiluted).
In the Preliminary Irritation / Toxicity Test, all mice were observed daily for any clinical signs of systemic toxicity or local irritation at the application site. Both ears of each mouse were observed for erythema and scored. Ear thickness was also measured using a thickness gauge on Day 1 (pre-dose), Day 3 (approximately 48 hours after the first dose) and Day 6. Additional quantification of the ear thickness was performed by ear punch weight determination after the euthanasia of the experimental animals.
During the Preliminary Irritation / Toxicity Test, no mortality was observed. Erythema (erythema score of 1) was observed in the 100 % (undiluted) dose group on Days 2-5 and in the 50 % (w/v) group on Days 3-5. The body weight loss was more than 5% for one animal in the 100 % (undiluted) dose group; however the mean body weight change of both groups was acceptable (less than 5%).
The mean ear thickness values and the ear punch weights were within the acceptable range, however slightly increased ear thickness value was detected for the left ear of one animal in the 100 % (undiluted) dose group.
The draining auricular lymph nodes of the animals were visually examined: they were larger than normal in both dose groups (subjective judgement by analogy with observations of former experiments).
Based on these observations, the 100 % (undiluted) was selected as top dose for the main test. At the request of the Sponsor additional dose groups (a total of 5) were tested in the main experiment to ensure that data allow the determination of the EC3 value of the test item.
Topical application
During the study, animals were topically dosed with 25 µL of the appropriate formulation using a pipette on the dorsal surface of each ear. Each animal was dosed once a day for three consecutive days (Days 1, 2 and 3). There was no treatment on Days 4, 5 and 6.
PROLIFERATION ASSAY
Injection of Tritiated Thymidine (3HTdR)
On Day 6, animals were taken to the radioactive suite and each mouse was intravenously injected via the tail vein with 250 µL of sterile PBS (phosphate buffered saline) containing approximately 20 µCi of 3HTdR using a gauge 25G x 1" hypodermic needle with 1 mL sterile syringe. Once injected, the mice were left for 5 hours (± 30 minutes).
Removal and Preparation of Draining Auricular Lymph Nodes
Five hours (± 30 minutes) after intravenous injection the mice were euthanized by asphyxiation with ascending doses of carbon dioxide (deep anaesthesia was confirmed before making incision, death was confirmed before discarding carcasses).
The draining auricular lymph nodes were excised by making a small incision on the skin between the jaw and sternum, pulling the skin gently back towards the ears and exposing the lymph nodes. The nodes were then removed using forceps. The carcasses were discarded after cervical dislocation or after cutting through major cervical blood vessels.
Once removed, the nodes of mice from each test group were pooled and collected in separate Petri dishes containing a small amount (1-2 mL) of PBS to keep the nodes wet before processing.
Preparation of Single Cell Suspension of Lymph Node Cells
A single cell suspension (SCS) of pooled lymph node cells (LNCs) was prepared and collected in disposable tubes by gentle mechanical disaggregating of the lymph nodes through a cell strainer using the plunger of a disposable syringe. The cell strainer was washed with PBS (up to 10 mL). Pooled LNCs were pelleted with a relative centrifugal force (RCF) of 190 x g (approximately) for 10 minutes at 4 °C. After centrifugation supernatants were discarded. Pellets were gently resuspended and 10 mL of PBS was added to the tubes. The washing step was repeated twice. This procedure was repeated for each group of pooled lymph nodes.
Determination of Incorporated 3HTdR
After the final washing step, supernatants were removed. Pellets were gently agitated resuspended and 3 mL of 5 % (w/v) TCA solution was added to the tubes for precipitation of macromolecules.
After overnight (approximately 18 hours) incubation at 2-8 °C, precipitates were centrifuged (approximately 190 x g for 10 minutes at 4oC), and supernatants were removed. Pellets were resuspended in 1 mL of 5 % (w/v) TCA solution and dispersed by using an ultrasonic bath. Samples were transferred into a suitable sized scintillation vial filled with 10 mL of scintillation liquid and thoroughly mixed. The vials were loaded into a ß-scintillation counter and 3HTdR incorporation was measured (10-minute measurement).
The ß-counter expresses the 3HTdR incorporation as the number of radioactive disintegrations per minute (DPM). Background level was also measured in duplicates by adding 1 mL of 5 % (w/v) TCA solution into a scintillation vial filled with 10 mL of scintillation liquid.
OBSERVATIONS
Clinical Observations
During the study (Day 1 to Day 6) each animal was observed daily for any clinical signs, including local irritation and systemic toxicity. Clinical observations were performed twice a day (before and after treatments) on Days 1, 2 and 3 and once daily on Days 4, 5 and 6. Individual records were maintained.
Measurement of Body Weight
Individual body weights were recorded on Day 1 (beginning of the test) and on Day 6 (prior to 3HTdR injection) with a precision of ± 0.1 g. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- DPM was measured for each pooled group of nodes. The measured DPM values were corrected with the background DPM value (“DPM”). The average of the two measured DPM values of 5 % (w/v) TCA solutions was used as background DPM value. The results were expressed as “DPN” (DPM divided by the number of lymph nodes) following the industry standard for data presentation.
Stimulation index (SI = DPN value of a treated group divided by the DPN value of the negative control group) for each treatment group was also calculated. A stimulation index of 3 or greater is an indication of a positive result.
Since the test item gave a positive response, the EC3 value of the test item (EC3 means the effective chemical concentration required for SI=3) was calculated by linear interpolation according to the equation:
EC3 = c + [(3-d)/(b-d)] x (a-c)
where the data points lying immediately above and below the SI value of 3 on the LLNA dose-response plot have the co-ordinates (a,b) and (c,d) respectively. - Positive control results:
- The result of the positive control substance a-Hexylcinnamaldehyde (HCA) dissolved in the same vehicle was used to demonstrate the appropriate performance of the assay. The positive control substance was examined at a concentration of 25 % in the relevant vehicle (AOO) using CBA/CaOlaHsd mice.
No mortality, cutaneous reactions or signs of toxicity were observed for the positive control substance in the study. A lymphoproliferative response in line with historic positive control data (stimulation index value of 6.6) was noted for HCA in the main experiment. This value was considered to confirm the appropriate performance of the assay. - Key result
- Parameter:
- EC3
- Remarks:
- % (w/v)
- Value:
- 46.7
- Parameter:
- SI
- Value:
- 0.9
- Test group / Remarks:
- test group (2%)
- Parameter:
- SI
- Value:
- 1.4
- Test group / Remarks:
- test group (10%)
- Parameter:
- SI
- Value:
- 1.7
- Test group / Remarks:
- test group (25%)
- Parameter:
- SI
- Value:
- 3.2
- Test group / Remarks:
- test group (50%)
- Parameter:
- SI
- Value:
- 3.1
- Test group / Remarks:
- test group (100%)
- Parameter:
- SI
- Value:
- 6.6
- Test group / Remarks:
- Positive control
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- In conclusion, under the conditions of the present assay, DI-TERT-DODECYL DISULPHIDE, tested in a suitable vehicle, was shown to have a slight sensitisation potential (sensitizer) in the Local Lymph Node Assay. The calculated EC3 value was 46.7 % (w/v).
- Executive summary:
The aim of the study was to determine the skin sensitisation potential of DI-TERT-DODECYL DISULPHIDE following dermal exposure. The study was performed with vertebrate animals as no full regulatory in vitro alternative is available. The minimum number of animals was used, corresponding to the regulatory guidelines being followed. Based on the results of the Preliminary Compatibility Test, the test item characteristics, its usage and on the recommendations of the OECD Guideline no. 429, the test item was tested for formulation compatibility in acetone:olive oil 4:1 (v:v) mixture (abbreviated as AOO). The highest achievable concentration based on the regulatory requirements of the OECD guideline and the physical characteristics of the test item was 100 % (undiluted). The Preliminary Irritation/Toxicity Test was performed in CBA/CaOlaHsd mice using two doses (2 animals/dose): 100 % (undiluted) and 50 % (w/v) in AOO. Based on the observations recorded in the preliminary test, the 100 % (undiluted) was selected as top dose for the main test. In the main assay, twenty-eight female CBA/CaOlaHsd mice were allocated to seven groups of four animals each:
- five groups received DI-TERT-DODECYL DISULPHIDE (formulated in AOO) at 100 % (undiluted), 50, 25, 10 and 2 % (w/v) concentrations,
- the negative control group received the vehicle (AOO),
- the positive control group received 25 % (w/v) HCA (dissolved in AOO).
The test item solutions were applied on the dorsal surface of ears of experimental animals (25 µL/ear) for three consecutive days (Days 1, 2 and 3). There was no treatment on Days 4, 5 and 6. The cell proliferation in the local lymph nodes was measured by incorporation of tritiated methyl thymidine (3HTdR) and the values obtained were used to calculate stimulation indices (SI).
No mortality or signs of systemic toxicity were observed during the study. There were no indications of any irritancy at the site of application. No marked body weight loss (=5%) was observed on the mean body weight of the groups in the study. The stimulation index values were 3.1, 3.2, 1.7, 1.4 and 0.9 at concentrations of 100 % (undiluted), 50, 25, 10 and 2 % (w/v), respectively. The result of the positive control substance a-Hexylcinnamaldehyde (HCA) dissolved in the same vehicle was used to demonstrate the appropriate performance of the assay. A lymphoproliferative response in line with historic positive control data was noted for the positive control chemical, this result confirmed the validity of the assay.
In conclusion, under the conditions of the present assay, DI-TERT-DODECYL DISULPHIDE, tested in a suitable vehicle, was shown to have a slight sensitisation potential (sensitizer) in the Local Lymph Node Assay. The calculated EC3 value was 46.7 % (w/v).
Reference
Individual Body Weights for all Animals with Group Means
Animal Number |
Identity Number |
Test Group Name |
Initial Body weight (g) |
Terminal Body Weight* (g) |
Change # (%) |
1258 1274 1250 1270
|
1 2 3 4 |
Negative (vehicle control) AOO
Mean |
20.1 21.0 21.5 21.3 21.0 |
19.1 21.7 21.5 22.1 21.1 |
-5.0 3.3 0.0 3.9 0.5 |
1252 1232 1253 1267
|
5 6 7 8 |
DI-TERT-DODECYL DISULPHIDE 100% (undiluted)
Mean |
20.2 21.4 21.2 21.5 21.1 |
20.9 21.4 20.1 21.0 20.9 |
3.5 0.0 -5.2 -2.3 -1.0 |
1255 1234 1261 1272
|
9 10 11 12 |
DI-TERT-DODECYL DISULPHIDE 50% (w/v) in AOO
Mean |
19.9 20.6 20.5 21.4 20.6 |
20.2 20.9 20.3 21.0 20.6 |
1.5 1.5 -1.0 -1.9 0.0 |
1248 1257 1271 1266
|
13 14 15 16 |
DI-TERT-DODECYL DISULPHIDE 25% (w/v) in AOO
Mean |
19.9 20.1 21.4 21.4 20.7 |
20.6 19.6 20.4 21.4 20.5 |
3.5 -2.5 -4.7 0.0 -0.9 |
1254 1263 1273 1260
|
17 17 19 20 |
DI-TERT-DODECYL DISULPHIDE 10% (w/v) in AOO
Mean |
19.8 20.0 21.4 21.8 20.8 |
19.7 20.7 21.2 21.3 20.7 |
-0.5 3.5 -0.9 -2.3 -0.1 |
1259 1275 1269 1262
|
21 22 23 24 |
DI-TERT-DODECYL DISULPHIDE 2% (w/v) in AOO
Mean |
19.8 20.7 21.3 21.3 20.8 |
21.0 20.5 21.4 21.1 21.0 |
6.1 -1.0 0.5 -0.9 1.2 |
1279 1264 1277 1268
|
25 26 27 28 |
Positive control 25 (w/v) % HCA in AOO
Mean |
20.0 19.8 20.8 22.1 20.7 |
20.2 20.2 20.2 21.8 20.6 |
1.0 2.0 -2.9 -1.4 -0.3 |
*: Terminal body weights were measured on Day 6.
#: = (Terminal Body Weight – Initial Body Weight) / Initial Body Weight x 100
DPM, DPN and Stimulation Index Values for all Groups
Test Group Name |
Measured DPM / group |
DPM |
Number of lymph nodes |
DPN |
Stimulation Index |
Background (5% (w/v) TCA) |
31 36 |
- |
- |
- |
- |
Negative control (AOO) |
8230 |
8196.5 |
8 |
1024.6 |
1.0 |
DI-TERT-DODECYL DISULPHIDE 100% (undiluted) |
25149 |
25115.5 |
8 |
3139.4 |
3.1 |
DI-TERT-DODECYL DISULPHIDE 50% (w/v) in AOO |
26570 |
26536.5 |
8 |
3317.1 |
3.2 |
DI-TERT-DODECYL DISULPHIDE 25% (w/v) in AOO |
13801 |
13767.5 |
8 |
1720.9 |
1.7 |
DI-TERT-DODECYL DISULPHIDE 10% (w/v) in AOO |
11785 |
11751.5 |
8 |
1468.9 |
1.4 |
DI-TERT-DODECYL DISULPHIDE 2% (w/v) in AOO |
7224 |
7190.5 |
8 |
898.8 |
0.9 |
Positive control (25% (w/v) HCA in AOO) |
53746 |
53712.5 |
8 |
6714.1 |
6.6 |
Results of the Preliminary Irritation / Toxicity Test
Individual Body Weights for all Animals with Group Means
Animal Number |
Identity Number |
Test Group Name |
Initial Body Weight (g) |
Terminal Body Weight* (g) |
Change# (%) |
988 1001 |
1 2 |
100% (undiluted) 100% (undiluted) Mean |
18.1 17.4 17.8 |
16.9 17.0 17.0 |
-6.6 -2.3 -4.5 |
996 991 |
3 4 |
50% (w/v) 50% (w/v) Mean |
18.7 17.6 18.2 |
18.6 17.9 18.3 |
-0.5 1.7 0.6 |
*: Terminal body weights are measured on Day 6.
#: = (Terminal Body Weight – Initial Body Weight) / Initial Body Weight x 100
Individual Ear Thickness for all Animals
Identity Number |
Animal Number |
Test Group Name |
Ear Thickness on Day 1 (mm) |
Ear Thickness on Day 3 (mm) |
Ear Thickness on Day 6 (mm) |
Biopsy weight* on Day 6 (mg) |
|||
Right |
Left |
Right |
Left |
Right |
Left |
||||
988 1001 996 991 |
1 2 3 4 |
100% (undiluted) 100% (undiluted) 50% (w/v) 50% (w/v) |
0.21 0.21 0.20 0.21 |
0.20 0.22 0.20 0.21 |
0.22 0.22 0.23 0.22 |
0.23 0.23 0.23 0.22 |
0.24 0.24 0.24 0.24 |
0.25 0.24 0.24 0.24 |
18.81 21.08 18.32 18.37 |
*: Historical control range: 11.92 – 22.53 mg. Positive response is over 28.16 mg (=25%)
Summarized Clinical Observations
Period |
Group |
Animal No. |
Identity No. |
Clinical observations |
DAY 1 |
100% (undiluted) |
1 |
988 |
Before treatment: symptom free, ES: 0 After treatment: symptom free, ES: 0 |
2 |
1001 |
Before treatment: symptom free, ES: 0 After treatment: symptom free, ES: 0 |
||
50% (w/v) |
3 |
996 |
Before treatment: symptom free, ES: 0 After treatment: symptom free, ES: 0 |
|
4 |
991 |
Before treatment: symptom free, ES: 0 After treatment: symptom free, ES: 0 |
||
DAY 2 |
100% (undiluted) |
1 |
988 |
Before treatment: symptom free, ES: 0 After treatment: ES: 1 |
2 |
1001 |
Before treatment: symptom free, ES: 0 After treatment: ES: 1 |
||
50% (w/v) |
3 |
996 |
Before treatment: symptom free, ES: 0 After treatment: symptom free, ES: 0 |
|
4 |
991 |
Before treatment: symptom free, ES: 0 After treatment: symptom free, ES: 0 |
||
DAY 3 |
100% (undiluted) |
1 |
988 |
Before treatment: symptom free, ES: 0 After treatment: ES: 1 |
2 |
1001 |
Before treatment: symptom free, ES: 0 After treatment: ES: 1 |
||
50% (w/v) |
3 |
996 |
Before treatment: symptom free, ES: 0 After treatment: ES: 1 |
|
4 |
991 |
Before treatment: symptom free, ES: 0 After treatment: ES: 1 |
||
DAY 4 |
100% (undiluted) |
1 |
988 |
ES: 1 |
2 |
1001 |
ES: 1 |
||
50% (w/v) |
3 |
996 |
ES: 1 |
|
4 |
991 |
ES: 1 |
||
DAY 5 |
100% (undiluted) |
1 |
988 |
ES: 1 |
2 |
1001 |
ES: 1 |
||
50% (w/v) |
3 |
996 |
ES: 1 |
|
4 |
991 |
ES: 1 |
||
DAY 6 |
100% (undiluted) |
1 |
988 |
Symptom free, ES: 0 |
2 |
1001 |
Symptom free, ES: 0 |
||
50% (w/v) |
3 |
996 |
Symptom free, ES: 0 |
|
4 |
991 |
Symptom free, ES; 0 |
The clinical observation of animals on the first day was performed simultaneously with the body weight measurements.
ES: Erythema score.
Summarized Clinical Observations – Main Test
Group |
Animal No. |
Identity No. |
CLINICAL OBSERVATIONS |
|||||
DAY 1 |
DAY 2 |
DAY 3 |
DAY 4 |
DAY 5 |
DAY 6 |
|||
Negative control (AOO) |
1
2
3
4 |
1258
1274
1250
1270 |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
DI-TERT-DODECYL DISULPHIDE 100% (undiluted) |
5
6
7
8 |
1252
1232
1253
1267 |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
DI-TERT-DODECYL DISULPHIDE 50% (w/v) in AOO |
9
10
11
12 |
1255
1234
1261
1272 |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
DI-TERT-DODECYL DISULPHIDE 25% (w/v) in AOO |
13
14
15
16 |
1248
1257
1271
1266 |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
DI-TERT-DODECYL DISULPHIDE 10% (w/v) in AOO |
17
18
19
20 |
1254
1263
1273
1260 |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
DI-TERT-DODECYL DISULPHIDE 2% (w/v) in AOO |
21
22
23
24 |
1259
1275
1269
1262 |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Positive control (25% (w/v) HCA in AOO) |
25
26
27
28 |
1279
1264
1277
1268 |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free BT: symptom-free AT: symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
Symptom-free
Symptom-free
Symptom-free
Symptom-free |
BT: before treatment, AT: after treatment
Historical Control Data
Historical Control Data of the Positive and Negative Controls for CBA/CaOlaHsd mice (2014-2015)
CBA/CaOlaHsd mice |
||||||
|
Vehicles |
|||||
Acetone: Olive oil 4:1 (AOO) |
1% Pluronic PE9200 in water (1% Plu) |
|||||
DPN values |
SI value |
DPN values |
SI value |
|||
Control |
HCA 25% |
HCA 25% |
Control |
HCA 25% |
HCA 25% |
|
Average |
415.2 |
2922.6 |
7.5 |
197.7 |
1825.3 |
10.0 |
Range: min max |
111.3 847.8 |
890.3 7674.5 |
3.3 15.5 |
23.0 680.8 |
154.0 6755.8 |
3.0 33.1 |
Number of cases |
32 |
32 |
30 |
134 |
234 |
128 |
|
Vehicles |
|||||
N,N-Dimethylformanmide (DMF) |
Dimethyl sulfoxide (DMSO) |
|||||
DPN values |
SI values |
DPN values |
SI values |
|||
Control |
HCA 25% |
HCA 25% |
Control |
HCA 25% |
HCA 25% |
|
Average |
244.6 |
2522.6 |
10.8 |
488.7 |
3212.1 |
7.8 |
Range: min max |
140.8 505.8 |
1201.3 4804.6 |
6.3 21.3 |
238.5 934.6 |
2017.2 4877.5 |
3.1 14.5 |
Number of cases |
21 |
21 |
21 |
13 |
13 |
12 |
|
Vehicles |
|||||
Propylene glycol (PG) |
Methyl ethyl ketone (MEK) |
|||||
DPN values |
SI value |
DPN values |
SI value |
|||
Control |
HCA 25% |
HCA 25% |
Control |
HCA 25% |
HCA 25% |
|
Average |
235.4 |
2371.8 |
10.0 |
260.2 |
4888.8 |
19.5 |
Range: min max |
63.3 506.0 |
817.3 4978.0 |
6.5 14.4 |
183.5 383.3 |
3465.3 8682.5 |
8.9 36.3 |
Number of cases |
14 |
14 |
14 |
9 |
10 |
10 |
HCA 25% = alpha-Hexylcinnamaldehyde 25% (w/v)
SI (Stimulation Index) = DPN of a treated group divided by DPN of the appropriate control group.
DPN (Disintegrations Per Node) = DPM (Disintegrations Per Minute) divided by the number of lymph nodes.
In case of individual approach, SI values were calculated from the mean DPN values of the group.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The following classification/labelling is triggered:
Regulation (EC) No 1272/2008 (CLP) / GHS (rev. 6) 2015: Category 1 (sub-category 1B).
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