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EC number: 947-851-2 | 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 vitro
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 15 February 2018 to 22 March 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 442E: hCLAT human Cell Line Activation Test
- Version / remarks:
- (2017)
- Deviations:
- yes
- Remarks:
- The cytotoxicity measurement and estimation of the CV75 value of the dose finding assay was performed by XTT test instead of flow cytometry.
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- activation of dendritic cells
- Justification for non-LLNA method:
- The Human Cell Line Activation Test (h-CLAT) was conducted as an alternative to in vivo skin sensitisation tests. The selected in vitro skin sensitisation test was considered scientifically valid for the evaluation of skin sensitisation hazard of chemicals, based on the ECVAM. Information from this test should be used in combination with other information within a weight-of-evidence approach and not as a stand-alone test method.
Test material
- Reference substance name:
- D,L- Menthol / D,L-Isomenthol
- Molecular formula:
- C10H20O
- IUPAC Name:
- D,L- Menthol / D,L-Isomenthol
Constituent 1
In vitro test system
- Details on the study design:
- DETAILS ON TEST SYSTEM
- Species: Human monocytic leukaemia cell line
- Method(s): XTT test and h-CLAT test
- Expiration date: Not specified
- Date of initiation of testing: 09 October 2019
TEMPERATURE USED FOR TEST SYSTEM
Temperature used during treatment/exposure: The assays were incubated at 37°C
Incubation duration: 24 ± 0.5 hours
CONTROL SAMPLES
Controls: A culture medium with no additives was used as the blank and vehicle control; DMSO and DNCB was used as a positive control.
AMOUNT/CONCENTRATION APPLIED
Test items concentrations: 17, 21, 25, 30, 36, 43, 52 and 62 μg/mL
Positive control concentrations: The concentration for the XTT test were 2.0 and 3.0 μg/mL
Replicates: 7 replicates were used for each test item concentration
Results and discussion
- Positive control results:
- The actual RFI values for CD86 were 519.2 %, 674.2%, 725.3% and 652.8% and 230.8 %, 482.7%, 296.9% and 342.0% for CD54. The RFI values of both CD86 and CD54 antibodies fulfilled the positive control criteria (CD86 ≥ 150% and CD54 ≥ 200%).
In vitro / in chemico
Resultsopen allclose all
- Key result
- Run / experiment:
- other: 1/ Experiment 1: CD 54 (17 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 95.7
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 1/ Experiment 1: CD 86 (17 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 98.6
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 2/ Experiment 1: CD 54 (21 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 109.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 2/ Experiment 1: CD86 (21 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 96.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 3/ Experiment 1: CD 54 (25 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 117.4
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 3/ Experiment 1: CD 86 (25 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 87.5
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 4/ Experiment 1: CD 54 (30 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 87
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 4/ Experiment 1: CD 86 (30 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 64.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 5/ Experiment 1: CD 54 (36 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 93.5
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 5/ Experiment 1: CD 86 (36 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 68.7
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 6/ Experiment 1: CD 54 (43 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 63
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 6/ Experiment 1: CD 86 (43 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 64.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 7/ Experiment 1: CD 54 (52 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 90.2
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 7/ Experiment 1: CD 86 (52 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 81.5
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 8/ Experiment 1: CD 54 (62 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 79.3
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 8/ Experiment 1: CD 86 (62 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 75.4
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 1/ Experiment 2: CD 54 (17 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 119.4
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 1/ Experiment 2: CD 86 (17 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 84.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 2/ Experiment 2: CD 54 (21 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 111.3
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 2/ Experiment 2: CD 86 (21 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 105.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 3/ Experiment 2: CD 54 (25 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 101.6
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 3/ Experiment 2: CD 86 (25 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 101.6
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 4/ Experiment 2: CD 54 (30 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 91.1
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 4/ Experiment 2: CD 86 (30 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 70.2
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 5/ Experiment 2: CD 54 (36 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 96
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 5/ Experiment 2: CD 86 (36 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 84.1
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 6/ Experiment 2: CD 54 (43 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 100.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 6/ Experiment 2: CD 86 (43 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 77
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 7/ Experiment 2: CD 54 (52 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 98.4
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 7/ Experiment 2: CD 86 (52 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 80.9
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 8/ Experiment 2: CD 54 (62 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 105.6
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: 8/ Experiment 2: CD 86 (62 μg/mL)
- Parameter:
- other: RFI (%)
- Value:
- 94.2
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Other effects / acceptance of results:
- - Acceptance criteria met for negative control: The negative control was more than 90 % in comparison to the medium control (100 %).
- Acceptance criteria met for positive control: In the positive control DNCB, the RFI values were 230.8%, 482.7%, 296.9% and 342.0% for CD54 and 519.2%, 674.2%, 725.3% and 652.8% for CD86. All values were within the historical laboratory data (CD54 ≥ 200% and CD86 ≥ 150%). The cell viability was also more than 50 % (73.3%, 70.1% 74% and 73.2%). Therefore, the acceptance criteria for the positive control was fulfilled.
- Acceptance criteria met for variability between replicate measurements: Not specified
- Range of historical values if different from the ones specified in the test guideline: No applicable
Any other information on results incl. tables
Table 1- Results from h-CLAT experiment 1
|
Concentration (µg/mL) |
RFI (%) CD 54 Antibody |
RFI (%) CD 86Antibody |
(%) |
|
Medium Control |
- |
100.0 |
100.0 |
100.0 |
|
DMSO control |
- |
100.0 |
100.0 |
100.0 |
|
Positive control (DNCB) |
2.0 |
230.8 |
519.2 |
73.3 |
|
3.0 |
482.7 |
674.2 |
70.1 |
||
Test item |
17 |
95.7 |
98.6 |
93.7 |
|
21 |
109.8 |
96.8 |
94.1 |
||
25 |
117.4 |
87.5 |
94.4 |
||
30 |
87.0 |
64.8 |
92.3 |
||
36 |
93.5 |
68.7 |
90.3 |
||
43 |
63.0 |
64.8 |
95.6 |
||
52 |
90.2 |
81.5 |
92.0 |
||
62 |
79.3 |
75.4 |
86.3 |
Table 2- Results from h-CLAT experiment 2
|
Concentration (µg/mL) |
RFI (%) CD 54 Antibody |
RFI (%) CD 86Antibody |
(%) |
|
Medium Control |
- |
100.0 |
100.0 |
100.0 |
|
DMSO control |
- |
100.0 |
100.0 |
100.0 |
|
Positive control (DNCB) |
2.0 |
296.9 |
725.3 |
74.0 |
|
3.0 |
342.0 |
652.8 |
73.2 |
||
Test item |
17 |
119.4 |
84.8 |
98.1 |
|
21 |
111.3 |
105.8 |
99.5 |
||
25 |
101.6 |
101.6 |
97.2 |
||
30 |
91.1 |
70.2 |
92.6 |
||
36 |
96.0 |
84.1 |
92.0 |
||
43 |
100.8 |
77.0 |
86.6 |
||
52 |
98.4 |
80.9 |
85.1 |
||
62 |
105.6 |
94.2 |
81.7 |
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- The test item with a log Pow of 3.02 and 3.32, did not cause THP-1 cell activation up to the highest tested concentration (62 μg/mL) under test conditions. Therefore, the test item is considered negative for the third key event of skin sensitisation adverse outcome pathway (AOP).
- Executive summary:
The study is assigned a reliability score of 1 (reliable without restrictions) as it followed OECD Guideline 442E: In Vitro Skin Sensitisation: Human cell line activation test (h-CLAT) and is compliant with GLP.
The skin sensitising potential of the test item was determined by the third key event of the skin sensitisation Adverse Outcome Pathway (AOP). The test item concentrations of 17, 21, 25, 30, 36, 43, 52 and 62 μg/mL were used in the definitive study. Two independent runs were conducted for the study.
The negative control was more than 90 % in comparison to the medium control (100 %). In the positive control DNCB, the RFI values were 230.8%, 482.7%, 296.9% and 342.0% for CD54 and 519.2%, 674.2%, 725.3% and 652.8% for CD86. All values were within the historical laboratory data (CD54 ≥ 200% and CD86 ≥ 150%). The cell viability was also more than 50 % (73.3%, 70.1% 74% and 73.2%). Therefore, all validity criteria were met. The cytotoxicity measurement and estimation of the CV75 value of the dose finding assay was performed by XTT test instead of flow cytometry.
The test item with a log Pow of 3.02 and 3.32, did not cause THP-1 cell activation up to the highest tested concentration (62 μg/mL) under test conditions. Therefore, the test item is considered negative for the third key event of skin sensitisation adverse outcome pathway (AOP).
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