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EC number: - | 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
- 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 (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08 MAR 2021 - 27 OCT 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
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 406 (Skin Sensitisation)
- Version / remarks:
- adopted July 17, 1992
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- Although the murine Local Lymph Node Assay (LLNA) is currently the preferred assay for chemicals under EU REACH regulation, guinea pig assays are equally acceptable under other regulations.
The guinea pig has been found informative for predictive sensitisation tests and is used as animal model since several decades. The Buehler test is able to detect substances with moderate to strong sensitisation potential, including those with relatively weak sensitisation potential.
Test material
- Reference substance name:
- bis(2,2,6,6-tetramethyl-1-(1,3-benzothiazol-2-ylsulfanyl)piperidin-4-yl)carbonate
- Cas Number:
- 2311845-49-3
- Molecular formula:
- C33H42N4O3S4
- IUPAC Name:
- bis(2,2,6,6-tetramethyl-1-(1,3-benzothiazol-2-ylsulfanyl)piperidin-4-yl)carbonate
- Test material form:
- solid: particulate/powder
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Remarks:
- healthy Crl: HA albino guinea pigs
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 6–7 weeks old
- Weight at study initiation: 337–430 g
- Housing: Semi barrier in an air-conditioned room, animals were kept in groups in Terluran cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): Free access to autoclaved hay and to Altromin 3122 maintenance diet for guinea pigs, rich in crude fibre
- Water (e.g. ad libitum): Free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: Adequate acclimatisation period (at least 5 days)
- Indication of any skin lesions: none
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark
Study design: in vivo (non-LLNA)
Induction
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: undiluted, moistened with cottonseed oil
- Concentration / amount:
- Undiluted (100 %). A gauze patch was loaded with 0.1 g of the prepared test substance, which was the maximum technically applicable amount.
- Day(s)/duration:
- gauze patch was applied for 6 hours and repeated at weekly intervals
- Adequacy of induction:
- highest technically applicable concentration used
Challengeopen allclose all
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: undiluted, moistened with cottonseed oil
- Remarks:
- undiluted, moistened with cottonseed oil
- Concentration / amount:
- Undiluted (100 %). A gauze patch was loaded with 0.1 g of the prepared test substance, which was the maximum technically applicable amount.
- Day(s)/duration:
- gauze patch was applied for 6 hours
- Adequacy of challenge:
- other: expected to be the highest non-irritant concentration, please refer to any other information on results for further information.
- No.:
- #2
- Route:
- epicutaneous, occlusive
- Vehicle:
- cotton seed oil
- Concentration / amount:
- The test substance was applied at a concentration of 50%
- Day(s)/duration:
- gauze patch was applied for 6 hours
- Adequacy of challenge:
- other: The concentration was lowered to 50% in order to eliminate irritant reactions, in line with the technical report no. 78 by the ECETOC. It was considered still to be high enough to evoke potential allergic reactions.
- No. of animals per dose:
- 10 animals in control group and 20 animals in the test group
- Details on study design:
- RANGE FINDING TESTS:
For the justification of dose levels a preliminary test was performed. The concentration for each induction exposure should be the highest to cause mild irritation and the concentration used for the challenge exposure will be the highest non-irritating dose.
A gauze patch was loaded with 0.1 g of the prepared test substance, which was the maximum technically applicable amount. The patch was applied to the test area of approximately 2.5 x 2.5 cm on the closed-clipped flank of the animals. Thus, an adequate dermal exposure of the test substance was ensured.
2 animals were treated topically with concentrations of 100 % (undiluted test item) for 6 hours.
The test item was moistened with cottonseed oil before application.
Based on the results of this preliminary test the following concentrations were chosen for the main test:
a concentration of 100 % for the dermal inductions
a concentration of 100 % for the challenge application
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: once a week for 6 hours
- Test groups: Test group and negative control group
- Site: The left flank was cleared of hair (close-clipped) prior to the first application and again prior to further applications. The patch was applied to the test area of approximately 2.5 x 2.5 cm and was held in contact with the help of an occlusive dressing.
- Frequency of applications: weekly
- Duration: 6 hours
- Concentrations: Test group: 100 %. A gauze patch was loaded with 0.1 g of the test substance moistened with cottonseed oil and applied to the test area; negative control group: 0%. A gauze patch moistened with cottonseed oil was applied to the test area.
B. CHALLENGE EXPOSURE
- No. of exposures: 1x challenge and 1x rechallenge
- Day(s) of challenge: 14 days after the last induction application (challenge), 14 days after challenge (rechallenge)
- Exposure period: once for 6 hours
- Test groups: Test group and original negative control group (challenge and rechallenge)
- Site: Both flanks were cleared of hair (close-clipped) prior to the challenge/rechallenge application.
Challenge: Test group and control animals: Test item application: right flank; intraspecific control: left flank
Rechallenge: Test group and control animals: Test item application: left flank; intraspecific control right flank
- Concentrations:
Challenge: 100%. 0.1 g of the test substance moistened with cottonseed oil was loaded on a patch and applied to the test area on the right flank. A patch only moistened with cottonseed oil was applied on the left flank at an untreated site (intraspecific control).
Rechallenge: Test substance was applied at a concentration of 50%, suspended with cottonseed oil to the test area on the left flank. A patch moistened with cottonseed oil was applied on the right flank (intraspecific control).
- Evaluation (hr after challenge or rechallenge): 24 and 48 hours
- Observations: approximately 24 and 48 hours after removing the patch the skin reaction was observed and recorded
OTHER:
The animals were weighed prior to the administration, after the challenge (48 hours after removing the patch) and at the end of the observation period (rechallenge: 48 hours after removing the patch). - Challenge controls:
- After challenge, weak skin reactions were noted in test and control animals. A lower concentration was used in the rechallenge in order to clarify the nature of the skin reactions.
The rechallenge was performed using the test item at a concentration of 50%, in line with the technical report no. 78 by the ECETOC. The concentration was lowered to 50% in order to eliminate irritant reactions and was considered still to be high enough to evoke potential allergic reactions.
The rechallenge was performed with same negative control group.
After rechallenge, no positive reactions were observed in any of the test or control animals. Therefore, the effects observed after challenge were considered as irritant in their nature. In contrast, positive rechallenge data, regardless of the used concentration, would have rendered the study positive. - Positive control substance(s):
- yes
Results and discussion
- Positive control results:
- The recent reliability check was performed during the period from 22 Feb to 25 Mar 2021. The sensitisation rate after application of the positive-control substance 2-mercaptobenzothiazole (50 % (in vaseline) inductions I, II and III and 25 % (in vaseline) challenge) was 70 %, confirming the reliability of the test system.
20 animals used for positive-control group.
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- test substance was applied at a concentration of 50%, suspended with cottonseed oil
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- At the clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- test substance was applied at a concentration of 50%, suspended with cottonseed oil
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- At the clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- test substance was applied at a concentration of 50%, suspended with cottonseed oil
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- At the clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- test substance was applied at a concentration of 50%, suspended with cottonseed oil
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- At the clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100 % undiluted (0.1 g of the test substance moistened with cottonseed oil)
- No. with + reactions:
- 6
- Total no. in group:
- 20
- Clinical observations:
- At the clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.
- Remarks on result:
- other: erythema grade 1 in 6/20 test animals at the test site
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100 % undiluted (0.1 g of the test substance moistened with cottonseed oil)
- No. with + reactions:
- 8
- Total no. in group:
- 20
- Clinical observations:
- At the clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.
- Remarks on result:
- other: erythema grade 1 in 8/20 test animals at the test site
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 100 % undiluted (0.1 g of the test substance moistened with cottonseed oil)
- No. with + reactions:
- 2
- Total no. in group:
- 10
- Clinical observations:
- At the clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.
- Remarks on result:
- other: erythema grade 1 in 2/10 negative-control animals
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 100 % undiluted (0.1 g of the test substance moistened with cottonseed oil)
- No. with + reactions:
- 4
- Total no. in group:
- 10
- Clinical observations:
- At the clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.
- Remarks on result:
- other: erythema grade 1 in 4/10 negative-control animals
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 25 % in vaseline
- No. with + reactions:
- 13
- Total no. in group:
- 20
- Clinical observations:
- not specified
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 25 % in vaseline
- No. with + reactions:
- 14
- Total no. in group:
- 20
- Clinical observations:
- not specified
- Remarks on result:
- positive indication of skin sensitisation
Any other information on results incl. tables
Table a. Summary: Frequency of Positive Skin Reactions after Challenge in Comparison to Control Animals
E0 | E1 | E2 | E3 | O0 | O1 | O2 | O3 | Skin Reaction Positive* Animals (%) | |
T24 | 14 | 6 | -- | -- | 20 | -- | -- | -- | 30 |
T48 | 12 | 8 | -- | -- | 20 | -- | -- | -- | 40 |
C24 | 8 | 2 | -- | -- | 10 | -- | -- | -- | 20 |
C48 | 6 | 4 | -- | -- | 10 | -- | -- | -- | 40 |
E= erythema; O = oedema; T = test group; C = control group; 0 – 3 = grade; 24/48 = 24/48 hours after end of challenge treatment; * = skin reactions were not considered to be allergenic
Table b. Summary: Frequency of Sensitisation after Rechallenge in Comparison to Control Animals
E0 | E1 | E2 | E3 | O0 | O1 | O2 | O3 | Sensitised Animals (%) | |
T24 | 20 | -- | -- | -- | 20 | -- | -- | -- | 0 |
T48 | 20 | -- | -- | -- | 20 | -- | -- | -- | 0 |
C24 | 10 | -- | -- | -- | 10 | -- | -- | -- | 0 |
C48 | 10 | -- | -- | -- | 10 | -- | -- | -- | 0 |
E= erythema; O = oedema; T = test group; C = control group; 0 – 3 = grade; 24/48 = 24/48 hours after end of rechallenge treatment
Table c. Frequency of Sensitisation in Positive-Control Animals
Group / Hours after Challenge Treatment | Number of Sensitised Animals | Persentage of Sensitised Animals | |||||||
E0 | E1 | E2 | E3 | O0 | O1 | O2 | O3 | ||
T24 | 7 | 12 | 1 | 0 | 20 | 0 | 0 | 0 | 65 |
T48 | 6 | 11 | 3 | 0 | 20 | 0 | 0 | 0 | 70 |
C24 | 10 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 |
C48 | 10 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 |
T = test group (positive control); C = negative control group; 24/48 = 24/48 hours after end of rechallenge treatment; E0/1/2/3 = erythema grade 0/1/2/3; O0/1/2/3 = oedema grade 0/1/2/3
Applicant's summary and conclusion
- Interpretation of results:
- other: EU GHS criteria not met
- Conclusions:
- Under the conditions of the present study the test item Carbonic acid bis-[1-(benzothiazol-2-ylsufanyl)-2,2,6,6-tetramethyl-piperidin-4-yl] ester was considered not to cause reactions identified as sensitisation.
- Executive summary:
The study was performed in order to assess the potential of the test item to induce delayed contact hypersensitivity when applied topically to albino guinea pigs, according to OECD 406 (Buehler test) under GLP compliance.
Based on the results of the preliminary test, for the first, second, third induction and challenge, the test item was used as provided (powder), i.e. at a 100% concentration. The test item was moistened with cottonseed oil before application.
At the clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.
Induction I, II and III (6-hour exposure, occlusive):
Immediately and 24 hours after removing the patch neither erythema nor oedema was observed in any animal at any time of observation.
Challenge Exposure (6-hour exposure, occlusive):
24 hours after removing the patch: erythema grade 1 in 2/10 control and 6/20 test animals
48 hours after removing the patch: erythema grade 1 in 4/10 control and 8/20 test animals
Neither control nor test animal showed oedema at any observation time.
There was evidence of positive skin reactions in the challenge in test as well as in control animals.In order to clarify the results of the challenge, a rechallenge (second challenge) using the same negative control group was performed with the test item at the concentration of 50%.
Rechallenge Exposure (6-hour exposure, occlusive):
24 hours after removing the patch: neither erythema nor oedema was observed in any animal at any time of observation
48 hours after removing the patch: neither erythema nor oedema was observed in any animal at any time of observationThere was no evidence of sensitisation at the rechallenge and the percentage of sensitised animals was 0%.
After challenge, weak skin reactions were noted in test and control animals. A lower concentration was used in the rechallenge in order to clarify the nature of the skin reactions.
After rechallenge, no positive reactions were observed in any of the test or control animals. Therefore, the effects observed after challenge were considered as irritant in their nature. In contrast, positive rechallenge data, regardless of the used concentration, would have rendered the study positive.Therefore, under the conditions of the present study the test item Carbonic acid bis-[1-(benzothiazol-2-ylsufanyl)-2,2,6,6-tetramethyl-piperidin-4-yl] ester was considered not to cause reactions identified as sensitisation.
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