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EC number: 245-423-3 | CAS number: 23089-26-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Different in vitro and in vivo studies on skin sensitisation are available for (-)-α-Bisabolol (CAS 23089 -26 -1, levomenol) and the synthetic racemic (+/-)-α-Bisabolol.
(+/-)-α-Bisabolol (source substance) is considered to be a suitable read across substance for (-)-α-Bisabolol (target substance).
In vitro, conflicting results were obtained with (-)-α-Bisabolol: While the KeratinoSens (Ref. 7.4.1 -4) was negative, a positive result was obtained with the DPRA (Ref. 7.4.1 -3) due to depletion of Cystein peptide despite precipitation. No depletion was observed with the lysine peptide, however, due to technical difficulties (phase separation) this result could not be taken into account. Conducting an h-CLAT is not suitableas a negative result is not accepted for substances with a log Pow> 3.5, what applies to the test item.
In vivo tests are available for the synthetic racemic (+/-)-α-Bisabolol, which is proposed for read across as it contains the test item to 50%:
In a Buehler (Ref. 4.7.1 -1) test according to OECD 406, (+/-)-α-Bisabolol was negative when tested at a concentration of 100% (induction and challenge). In contrast, (+/-)-α-Bisabolol (source substance) was positive when tested in a Guinea Pig Maximisation Test (Ref. 4.7 .1 -2) according to OECD 406 (Induction: 5% intradermal, 100% topic; Challenge: 100% topic).
However, the registered substance is used specifically in cosmetic leave-on formulations up to a concentration of 1% for sensitive skin (CIR Report on Bisabolol, Int. J. Toxicol. 18, Suppl. 3, 33 -40, 1999) . No sensitizing effects are known from the cosmetic use, which has a long history of safe use. Moreover, no sensitizing potential was observed in a clinical sensitization test (Kligman maximisation protocol) in 25 volunteers treated with a cosmetic formulation with 0.1% Bisabolol (CIR, 1999).
Therefore, based on the comprehensive data base available for (-)-α-Bisabolol and the racemic (+/-)-α-Bisabolol (source compound) it is concluded that (-)-α-Bisabolol has no relevant potential for skin sensitization.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The test item (+/-)-α-Bisabolol is a racemic mixture containing the stereoisomers (+)-α-Bisabolol and (-)-α-Bisabolol. Studies on skin sensitisation were not performed for the target substance (-)-α-Bisabolol due to availability of reliable experimental data for (+/-)-α-Bisabolol. (+/-)-α-Bisabolol is considered to be a suitable read across substance.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source substance (+/-)-α-Bisabolol, CAS 515-69-5, which was used in the skin sensitisation study, had a purity of 86.8%. No information on impurities is available. The target substance (-)-α-Bisabolol, CAS 23089-26-1, is one of the two stereoisomers of (+/-)-α-Bisabolol.
3. ANALOGUE APPROACH JUSTIFICATION
Experimental data i.e. a skin sensitisation study was available for (+/-)-α-Bisabolol. (+/-)-α-Bisabolol was tested in a skin sensitisation study according to OECD 406 in guinea pigs. No skins sensitising potential was observed in this study. The information given on (+/-)-α-Bisabolol is considered to be sufficient to cover the required endpoint information for the target substance (-)-α-Bisabolol. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100 %
- No. with + reactions:
- 15
- Total no. in group:
- 20
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100 %
- No. with + reactions:
- 15
- Total no. in group:
- 20
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The test item (+/-)-α-Bisabolol is a racemic mixture containing the stereoisomers (+)-α-Bisabolol and (-)-α-Bisabolol. Studies on skin sensitisation were not performed for the target substance (-)-α-Bisabolol due to availability of reliable experimental data for (+/-)-α-Bisabolol. (+/-)-α-Bisabolol is considered to be a suitable read across substance.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source substance (+/-)-α-Bisabolol, CAS 515-69-5, which was used in the skin sensitisation study, had a purity of 86.8%. No information on impurities is available. The target substance (-)-α-Bisabolol, CAS 23089-26-1, is one of the two stereoisomers of (+/-)-α-Bisabolol.
3. ANALOGUE APPROACH JUSTIFICATION
Experimental data i.e. a skin sensitisation study was available for (+/-)-α-Bisabolol. (+/-)-α-Bisabolol was tested in a skin sensitisation study according to OECD 406 in guinea pigs. No skins sensitising potential was observed in this study. The information given on (+/-)-α-Bisabolol is considered to be sufficient to cover the required endpoint information for the target substance (-)-α-Bisabolol. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Endpoint:
- skin sensitisation: in chemico
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018-09-24 to 2018-12-07
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
- Version / remarks:
- adopted 04 February 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Direct Peptide Reactivity Assay (DPRA) for Skin Sensitization Testing, DB-ALM Protocol n°154
- Version / remarks:
- 12 January 2013
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany
- Type of study:
- direct peptide reactivity assay (DPRA)
- Details on the study design:
- The in chemico direct peptide reactivity assay (DPRA) enables detection of the sensitising potential of a test item by quantifying the reactivity of test chemicals towards synthetic peptides containing either lysine or cysteine. In the present study, the test item was dissolved in acetonitrile, based on the results of the pre-experiments. Based on a molecular weight of 222.37 g/mol a 100 mM stock solution was prepared. The test item solutions were tested by incubating the samples with peptides containing either cysteine or lysine for 24 ± 2 h at 25 ± 2.5 °C. Subsequently, samples were analysed by HPLC.
- Positive control results:
- The 100 mM stock solution of the positive control (cinnamic aldehyde) showed sufficient reactivity towards the synthetic peptides. The mean depletion of both peptides was 65.64%.
- Key result
- Run / experiment:
- other: cysteine run
- Parameter:
- other: mean peptide depletion [%]
- Value:
- 36.14
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Run / experiment:
- other: lysine run
- Parameter:
- other: mean peptide depletion [%]
- Value:
- 0
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable because of methodological limitations
- Other effects / acceptance of results:
- Acceptance Criteria
The run meets the acceptance criteria if:
- the standard calibration curve has a r² > 0.99,
- the mean percent peptide depletion (PPD) value of the three replicates for the positive control is between 60.8% and 100% for the cysteine peptide and the maximum standard deviation (SD) for the positive control replicates is < 14.9%,
- the mean percent peptide depletion (PPD) value of the three replicates for the positive control is between 40.2% and 69.0% for the lysine peptide and the maximum SD for the positive control replicates is < 11.6%,
- the mean peptide concentration of the three reference controls A replicates is 0.50 ± 0.05 mM,
- the coefficient of variation (CV) of peptide peak areas for the six reference control B replicates and three reference control C replicates in acetonitrile is < 15.0%.
The results of the test item meet the acceptance criteria if:
- the maximum standard deviation (SD) for the test chemical replicates is < 14.9% for the cysteine percent depletion (PPD),
- the maximum standard deviation (SD) for the test chemical replicates is < 11.6% for the lysine percent depletion (PPD),
- the mean peptide concentration of the three reference controls C replicates in the appropriate solvent is 0.50 ± 0.05 mM.
Both peptide runs and the test item results met the acceptance criteria of the test. - Interpretation of results:
- other: should be considered in the context of integrated approached such as IATA
- Conclusions:
- In this study under the given conditions the test item showed moderate reactivity towards the cysteine peptide. The test item is considered as positive in this in chemico assay for skin sensitisation.
The data generated with this test should be considered in the context of integrated approaches such as IATA, combining the result with other complementary information, e.g. derived from in vitro assays addressing other key events of the skin sensitisation AOP. - Executive summary:
In the present study the test item was dissolved in acetonitrile, based on the results of the pre-experiments. Based on a molecular weight of 222.37 g/mol a 100 mM stock solution was prepared. The test item solutions were tested by incubating the samples with the peptides containing either cysteine or lysine for 24 ± 2 h at 25 ± 2.5 °C. Subsequently, samples were analysed by HPLC.
All test item solutions were freshly prepared immediately prior to use.
For the 100 mM stock solution of the test item turbidity was observed when diluted with the cysteine peptide solution. After the 24 h ± 2 h incubation period but prior to the HPLC analysis samples were inspected for precipitation, turbidity or phase separation. Precipitation was observed for the samples of the test item (excluding the co-elution control). Samples were centrifuged prior to the HPLC analysis.
For the 100 mM stock solution of the test item turbidity was observed when diluted with the lysine peptide solution. After the 24 h ± 2 h incubation period but prior to the HPLC analysis samples were inspected for precipitation, turbidity or phase separation. Slight phase separation was observed for the samples of the test item and the positive control (small droplets) including the co-elution control. Samples were not centrifuged prior to the HPLC analysis.
Since the acceptance criteria for the depletion range of the positive control were fulfilled, the observed phase separation was regarded as not relevant.
Precipitation of the test item with the cysteine peptide peak and phase separation with the lysine peptide peak was observed. Therefore, the given peak areas and corresponding peptide values can only be considered as an estimation of the peptide depletion.
The 100 mM stock solution of the test item showed moderate reactivity towards the synthetic cysteine peptide and no reactivity towards the synthetic lysine peptide. The peptide depletion of the cysteine peptides was > 13.89% (36.14%). Even though precipitates with the cysteine peptide and phase separation with the lysine peptide were observed, a positive result can still be used. Based on the prediction model 2 the test item can be considered as positive in this in chemico assay for skin sensitisation.
The 100 mM stock solution of the positive control (cinnamic aldehyde) showed sufficient reactivity towards the synthetic peptides. The mean depletion of both peptides was 65.64%.
The controls confirmed the validity of the study for both, the cysteine and lysine run.
- Endpoint:
- skin sensitisation: in vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018-10-08 to 2018-10-29
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
- Qualifier:
- according to guideline
- Guideline:
- other: KeratinoSens™, EURL ECVAM DB-ALM Protocol No. 155, July 1st, 2015
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany
- Type of study:
- activation of keratinocytes
- Details on the study design:
- The in vitro KeratinoSens™ assay enables detection of the sensitising potential of a test item by addressing the second molecular key event of the adverse outcome pathway (AOP), namely activation of keratinocytes, by quantifying the luciferase activity in the transgenic cell line KeratinoSens™. The luciferase activity, assessed by luminescence measurement, compared to the respective solvent controls is used to support discrimination between skin sensitisers and non-sensitisers.
- Positive control results:
- The luciferase activity induced by the positive control at a concentration of 64 µM was between 2 and 8 (7.72 (experiment 1); 4.70 (experiment 2)).
- Key result
- Run / experiment:
- other: 1
- Parameter:
- other: luciferase activity
- Value:
- 1.08
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Concentration: 31.25 µM
- Remarks:
- Cell viability was 0.2% at 62.5 µM
- Key result
- Run / experiment:
- other: 1
- Parameter:
- other: cell viability [%]
- Value:
- 88
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Concentration: 31.25 µM
- Key result
- Run / experiment:
- other: 1
- Parameter:
- other: EC1.5 [µM]
- Value:
- 0
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: No significant luciferase induction > 1.5 was found. Therefore, no EC1.5 value could be calculated.
- Key result
- Run / experiment:
- other: 2
- Parameter:
- other: luciferase activity
- Value:
- 1.03
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Concentration: 31.25 µM
- Remarks:
- Cell viability was 0% at 62.5 µM
- Key result
- Run / experiment:
- other: 2
- Parameter:
- other: cell viability [%]
- Value:
- 85.6
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Run / experiment:
- other: 2
- Parameter:
- other: EC1.5 [µM]
- Value:
- 0
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: No significant luciferase induction > 1.5 was found. Therefore, no EC1.5 value could be calculated.
- Other effects / acceptance of results:
- Acceptance Criteria
The test meets acceptance criteria if:
- the luciferase activity induction of the positive control is statistically significant above the threshold of 1.5 (using a t-test) in at least one of the tested concentrations
- the average induction in the three technical replicates for the positive control at a concentration of 64 µM is between 2 and 8
- the EC1.5 value of the positive control is within two standard deviations of the historical mean
- the average coefficient of variation (CV; consisting of 6 wells) of the luminescence reading for the negative (solvent) control DMSO is <20% in each repetition.
The controls fullfilled the validity criteria of the test. - Interpretation of results:
- other: should be considered in the context of integrated approached such as IATA
- Conclusions:
- In this study under the given conditions the test item did not induce the luciferase activity in the transgenic KeratinoSens™ cell line in at least two independent experiment runs. Therefore, the test item can be considered as non sensitiser.
The data generated with this method may be not sufficient to conclude on the absence of skin sensitisation potential of chemicals and should be considered in the context of integrated approach such as IATA. - Executive summary:
In the present study the test material was dissolved in DMSO.
Based on a molecular weight of 268.5 g/mol a stock solution of 200 mM was prepared.
Based on the stock solution a set of twelve master solutions in 100% solvent was prepared by serial dilution using a constant dilution factor of 1:2. These master solutions were diluted 1:100 in cell culture medium. The following concentration range was tested in the assay:
2000, 1000, 500, 250, 125, 62.5, 31.25, 15.63, 7.81, 3.91, 1.95, 0.98 µM
Cells were incubated with the test item for 48 h at 37°C. After exposure cells were lysed and luciferase activity was assessed by luminescence measurement.
In the first and second experiment, no significant luciferase induction > 1.5 was found in the tested concentration range. Therefore, no EC1.5 value could be calculated.
No dose response for luciferase activity induction was observed for each individual run as well as for an overall luciferase activity induction.
Under the condition of this study the test item is therefore considered as non sensitiser.
Referenceopen allclose all
Cysteine and Lysine Values of the Calibration Curve
Sample |
Cysteine Peptide |
Lysine Peptide |
||
Peak Area |
Peptide Concentration [mM] |
Peak Area |
Peptide Concentration [mM] |
|
STD1 |
17.4320 |
0.5340 |
17.6620 |
0.5340 |
STD2 |
8.7580 |
0.2670 |
8.8410 |
0.2670 |
STD3 |
4.3320 |
0.1335 |
4.4020 |
0.1335 |
STD4 |
2.1060 |
0.0667 |
2.1750 |
0.0667 |
STD5 |
1.0150 |
0.0334 |
1.0680 |
0.0334 |
STD6 |
0.4700 |
0.0167 |
0.5310 |
0.0167 |
STD7 |
0.0000 |
0.0000 |
0.0000 |
0.0000 |
Depletion of the Cysteine Peptide
Cysteine Peptide |
||||||
Sample |
Peak Area |
Peptide Conc. [mM] |
Peptide Depletion [%] |
Mean Peptide Depletion [%] |
SD of Peptide Depletion [%] |
CV of Peptide Depletion [%] |
Positive Control |
5.0850 |
0.1566 |
69.79 |
69.97 |
0.22 |
0.31 |
5.0140 |
0.1545 |
70.21 |
||||
5.0620 |
0.1559 |
69.92 |
||||
Test Item |
10.8320 |
0.3320 |
35.64 |
36.14 |
0.91 |
2.51 |
10.8380 |
0.3321 |
35.60 |
||||
10.5710 |
0.3240 |
37.19 |
Depletion of the Lysine Peptide
Lysine Peptide |
||||||
Sample |
Peak Area |
Peptide Conc. [mM] |
Peptide Depletion [%] |
Mean Peptide Depletion [%] |
SD of Peptide Depletion [%] |
CV of Peptide Depletion [%] |
Positive Control |
6.3980 |
0.1938 |
61.65 |
61.30 |
0.42 |
0.69 |
6.4360 |
0.1949 |
61.42 |
||||
6.5340 |
0.1979 |
60.83 |
||||
Test Item |
16.8800 |
0.5102 |
0.00 |
0.00 |
0.00 |
n.a. |
16.8690 |
0.5099 |
0.00 |
||||
16.8540 |
0.5094 |
0.00 |
Prediction Model 1
Cysteine 1:10/ Lysine 1:50 Prediction Model 1
Mean Cysteine andLysine PPD |
Reactivity Class |
DPRA Prediction² |
0.00% ≤ PPD ≤ 6.38% |
No or Minimal Reactivity |
Negative |
6.38% < PPD ≤ 22.62% |
Low Reactivity |
Positive |
22.62% < PPD ≤ 42.47% |
Moderate Reactivity |
|
42.47% < PPD ≤ 100% |
High Reactivity |
1 The numbers refer to statistically generated threshold values and are not related to the precision of the measurement.
2 DPRA predictions should be considered in the framework of an IATA.
Prediction Model 2
Cysteine 1:10 Prediction Model
Cysteine PPD |
ReactivityClass |
DPRA Prediction² |
0.00% ≤ PPD ≤ 13.89% |
No or Minimal Reactivity |
Negative |
13.89% < PPD ≤ 23.09% |
Low Reactivity |
Positive |
23.09% < PPD ≤ 98.24% |
Moderate Reactivity |
|
98.24% < PPD ≤ 100% |
High Reactivity |
Categorization of the Test Item
Prediction Model |
Prediction Model 1 |
Prediction Model 2 |
||||
Test Substance |
Mean Peptide Depletion [%] |
Reactivity Category |
Prediction |
Mean Peptide Depletion [%] |
Reactivity Category |
Prediction |
Test Item |
18.07 |
-- |
-- |
36.14 |
Moderate Reactivity |
positive |
Positive Control |
65.38 |
High Reactivity |
positive |
69.97 |
Moderate Reactivity |
positive |
Results of the Cytotoxicity Measurement
|
Concentration [µM] |
Cell Viability [%] |
|||
Experiment 1 |
Experiment 2 |
Mean |
SD |
||
Solvent Control |
- |
100 |
100 |
100 |
0.0 |
Positive Control |
4.00 |
95.5 |
102.3 |
98.9 |
4.8 |
8.00 |
98.2 |
107.3 |
102.7 |
6.4 |
|
16.00 |
102.6 |
104.8 |
103.7 |
1.5 |
|
32.00 |
104.3 |
109.2 |
106.7 |
3.5 |
|
64.00 |
97.1 |
105.8 |
101.4 |
6.2 |
|
Test Item |
0.98 |
92.1 |
99.9 |
96.0 |
5.5 |
1.95 |
98.0 |
96.5 |
97.2 |
1.0 |
|
3.91 |
96.3 |
96.3 |
96.3 |
0.0 |
|
7.81 |
95.2 |
99.6 |
97.4 |
3.1 |
|
15.63 |
91.1 |
90.5 |
90.8 |
0.4 |
|
31.25 |
88.0 |
85.6 |
86.8 |
1.7 |
|
62.50 |
0.2 |
0.0 |
0.1 |
0.1 |
|
125.00 |
0.1 |
0.0 |
0.0 |
0.1 |
|
250.00 |
0.1 |
0.1 |
0.1 |
0.0 |
|
500.00 |
0.1 |
0.1 |
0.1 |
0.0 |
|
1000.00 |
0.1 |
0.1 |
0.1 |
0.0 |
|
2000.00 |
0.1 |
0.1 |
0.1 |
0.0 |
Induction of Luciferase Activity Experiment 1
Experiment 1 |
Concentration [µM] |
Fold Induction |
Significance |
||||
Rep. 1 |
Rep. 2 |
Rep. 3 |
Mean |
SD |
|||
Solvent Control |
- |
1.00 |
1.00 |
1.00 |
1.00 |
0.00 |
|
Positive Control |
4.00 |
1.24 |
1.14 |
1.04 |
1.14 |
0.10 |
|
8.00 |
1.09 |
1.18 |
1.16 |
1.15 |
0.05 |
|
|
16.00 |
1.21 |
1.34 |
1.39 |
1.31 |
0.09 |
||
32.00 |
1.41 |
1.75 |
1.48 |
1.55 |
0.18 |
* |
|
64.00 |
2.70 |
2.77 |
2.77 |
2.75 |
0.04 |
* |
|
Test Item |
0.98 |
1.27 |
1.10 |
1.29 |
1.22 |
0.10 |
|
1.95 |
1.09 |
1.01 |
1.08 |
1.06 |
0.04 |
|
|
3.91 |
1.01 |
1.03 |
1.04 |
1.03 |
0.01 |
|
|
7.81 |
1.02 |
0.99 |
1.20 |
1.07 |
0.11 |
|
|
15.63 |
0.97 |
1.04 |
0.99 |
1.00 |
0.03 |
|
|
31.25 |
1.07 |
1.04 |
1.13 |
1.08 |
0.04 |
|
|
62.50 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
125.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
250.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
500.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
1000.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
||
2000.00 |
0.00 |
0.01 |
0.00 |
0.00 |
0.00 |
* = significant induction according to Student’s t-test, p < 0.05
Induction of Luciferase Activity Experiment 2
Experiment 2 |
Concentration [µM] |
Fold Induction |
Significance |
||||
Rep. 1 |
Rep. 2 |
Rep. 3 |
Mean |
SD |
|||
Solvent Control |
- |
1.00 |
1.00 |
1.00 |
1.00 |
0.00 |
|
Positive Control |
4.00 |
1.11 |
1.09 |
1.02 |
1.08 |
0.05 |
|
8.00 |
1.21 |
1.30 |
1.21 |
1.24 |
0.06 |
|
|
16.00 |
1.20 |
1.23 |
1.37 |
1.27 |
0.09 |
||
32.00 |
1.54 |
1.58 |
1.59 |
1.57 |
0.02 |
* |
|
64.00 |
2.45 |
2.25 |
1.84 |
2.18 |
0.31 |
* |
|
Test Item |
0.98 |
1.02 |
1.04 |
1.05 |
1.04 |
0.01 |
|
1.95 |
0.95 |
1.01 |
0.94 |
0.97 |
0.04 |
|
|
3.91 |
1.33 |
1.12 |
0.99 |
1.15 |
0.17 |
|
|
7.81 |
1.06 |
0.94 |
1.03 |
1.01 |
0.06 |
|
|
15.63 |
1.05 |
0.93 |
1.05 |
1.01 |
0.07 |
|
|
31.25 |
1.14 |
0.97 |
0.97 |
1.03 |
0.10 |
|
|
62.50 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
125.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
250.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
500.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
1000.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
||
2000.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
* = significant induction according to Student’s t-test, p < 0.05
Induction of Luciferase Activity – Overall Induction
|
Concentration [µM] |
Fold Induction |
Significance |
|||
Experiment 1 |
Experiment 2 |
Mean |
SD |
|||
Solvent Control |
- |
1.00 |
1.00 |
1.00 |
0.00 |
|
Positive Control |
4.00 |
1.14 |
1.08 |
1.11 |
0.04 |
|
8.00 |
1.15 |
1.24 |
1.19 |
0.07 |
|
|
16.00 |
1.31 |
1.27 |
1.29 |
0.03 |
||
32.00 |
1.55 |
1.57 |
1.56 |
0.02 |
* |
|
64.00 |
2.75 |
2.18 |
2.46 |
30.4 |
* |
|
Test Item |
0.98 |
1.22 |
1.04 |
1.13 |
0.13 |
|
1.95 |
1.06 |
0.97 |
1.02 |
0.07 |
|
|
3.91 |
1.03 |
1.15 |
1.09 |
0.08 |
|
|
7.81 |
1.07 |
1.01 |
1.04 |
0.04 |
|
|
15.63 |
1.00 |
1.01 |
1.00 |
0.01 |
|
|
31.25 |
1.08 |
1.03 |
1.05 |
0.04 |
|
|
62.50 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
125.00 |
0.00 |
0.00 |
0.00 |
0.02 |
|
|
250.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
500.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
1000.00 |
0.00 |
0.00 |
0.00 |
0.00 |
|
|
2000.00 |
29.270.00 |
0.00 |
0.00 |
0.00 |
|
* = significant induction according to Student’s t-test, p < 0.05
Additional Parameters
Parameter |
Experiment 1 |
Experiment 2 |
Mean |
SD |
EC1.5[µM] |
n.a. |
n.a |
n.a. |
n.a. |
Imax |
1.22 |
1.15 |
1.18 |
0.05 |
IC30[µM] |
37.65 |
36.94 |
37.30 |
0.51 |
IC50[µM] |
44.77 |
44.24 |
44.51 |
0.38 |
Acceptance Criteria
Criterion |
Range |
Experiment 1 |
pass/fail |
Experiment 2 |
pass/fail |
CV Solvent Control |
< 20% |
10.8 |
pass |
10.8 |
pass |
No. of positive control concentration steps with significant luciferase activity induction >1.5 |
≥ 1 |
2.0 |
pass |
2.0 |
pass |
EC1.5 PC |
± 2 x SD of historical mean |
28.87 |
pass |
28.26 |
pass |
Induction PC at 64 µM |
2.00 < x < 8.00 |
2.75 |
pass |
2.18 |
pass |
Historical Data
Acceptance Criterion |
Range |
Mean |
SD |
N |
CV Solvent Control |
< 20% |
11.6 |
3.5 |
96 |
No. of positive control concentration steps with significant luciferase activity induction >1.5 |
≥ 1 |
2.4 |
0.6 |
96 |
EC1.5 PC |
7 < x < 34 µM |
18.5 |
6.0 |
96 |
Induction PC at 64 µM |
2.00 < x < 8.00 |
3.8 |
1.5 |
96 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No 1272/2008
The available data are considered sufficient to conclude on skin sensitisation potential of the test item under Regulation 1272/2008.
Based on the data available, the substance is not classified for skin sensitisation under Regulation (EC) No 1272/2008.
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