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EC number: 209-099-7 | CAS number: 555-45-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
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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
Skin sensitisation (QSAR, LLNA, Buehler): not sensitising
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation, other
- Remarks:
- QSAR
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
The OECD QSAR Toolbox v3.4 is a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry (http://toolbox.oasis-lmc.org).
2. MODEL (incl. version number)
OECD QSAR Toolbox version 3.4
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
The SMILES code for the test substance was used.
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: The model was used to predict the in vivo skin sensitisation potential of the test substance using the option 'Skin sensitisation (Danish EPA database)'. The results from this model are based on the Danish (Q)SAR Database, developed by the Danish Environmental Protection Agency (EPA). The (Q)SAR database comprises predictions made by some 70 models for about 166,000 organic chemicals for a wide range of different endpoints. In 2004, a collaborative project was set up between the Danish EPA and the ECB to develop an internet-accessible version of the database, which was also incorporated in the OECD QSAR Toolbox. This version of the Danish (Q)SAR Database was constructed to enable different types of searching, including structure (substructure/exact match) searching, ID (CAS number, name) searching and parameter (endpoint) searching, specifically for skin sensitisation potential. See report attached under 'Attached background material'.
- Short description of test conditions: The SMILES code of the test substance is compared with substances in the database, for which the (lack of) skin sensitising potential is known.
- Parameters analysed / observed: A QSAR prediction of the skin sensitisation potential of the main constituents of the test substance was performed by comparing them with the substances in the 'Skin sensitisation (Danish EPA database)'.
- Unambiguous algorithm: Prediction approach: prediction from existing (Q)SAR model; calculation approach: SAR/(Q)SAR prediction; model name: Skin sensitisation (Danish EPA DB); predicted value: negative.
- Defined domain of applicability: Predictions and domain results are pre-calculated and stored in the database.
5. APPLICABILITY DOMAIN
- Descriptor domain: The target chemical falls within the applicability domain of the prediction. Predictions and domain results are pre-calculated and stored in the database.
6. ADEQUACY OF THE RESULT
The results may be used in a weight-of-evidence approach together with other information to reach a conclusion regarding the skin sensitising potential of the test substance. - Principles of method if other than guideline:
- - Principle of test: The OECD QSAR Toolbox v3.4 is a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry (http://toolbox.oasis-lmc.org). It contains several different databases with data on chemicals. The model was used to predict the skin sensitisation potential of the main constituents of the test substance using the option 'Skin sensitisation (Danish EPA database)'. The results from this model are based on the Danish (Q)SAR Database, developed by the Danish Environmental Protection Agency (EPA). The (Q)SAR database comprises predictions made by some 70 models for about 166,000 organic chemicals for a wide range of different endpoints. In 2004, a collaborative project was set up between the Danish EPA and the ECB to develop an internet-accessible version of the database, which was also incorporated in the OECD QSAR Toolbox. This version of the Danish (Q)SAR Database was constructed to enable different types of searching, including structure (substructure/exact match) searching, ID (CAS number, name) searching and parameter (endpoint) searching, specifically for skin sensitisation potential.
- Short description of test conditions: The SMILES code of the main constituents of the test substance is compared with substances in the database, for which the (lack of) skin sensitising potential is known.
- Parameters analysed / observed: A QSAR prediction of the skin sensitisation potential of the main constituents of the test substance was performed by comparing them with the substances in the 'Skin sensitisation (Danish EPA database)'. - GLP compliance:
- no
- Remarks on result:
- not measured/tested
- Remarks on result:
- not measured/tested
- Remarks on result:
- not measured/tested
- Interpretation of results:
- other: The prediction results was negative for skin sensitising potential, based on QSAR prediction (OECD QSAR Toolbox v3.4, Danish EPA database). The results may only be used for classification purposes together with other data in a weight-of-evidence approach.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 11 May - 10 Sep 1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- adopted in 1992
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Version / remarks:
- adopted in 1996
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- The study was performed according to OECD guideline 406 (Buehler method) prior to the requirement stipulated in Regulation (EC) No 1907/2006, Annex VII, Column 2, that the Local Lymph Node Assay (LLNA) is the first-choice method for in vivo testing. As the available data is sufficient to meet the requirements, no addiitonal testing was performed.
- Species:
- guinea pig
- Strain:
- other: Dunkin-Hartley, Pirbright White Hsd/Poc:DH
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany.
- Age at study initiation: young adults
- Weight at study initiation: < 500 g
- Housing: maximum 5 animals per cage in Type IV Makrolon cages.
- Diet: Ssniff G 4 diet in pellet form (laboratory standard guinea pig dietdiet, Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70 (temporary deviations were caused by cleaning the animal room)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- epicutaneous, occlusive
- Vehicle:
- petrolatum
- Concentration / amount:
- Induction: 50%
Challenge: 50% - Route:
- epicutaneous, occlusive
- Vehicle:
- petrolatum
- Concentration / amount:
- Induction: 50%
Challenge: 50% - No. of animals per dose:
- 10 (controls), 20 (in test groups)
- Details on study design:
- RANGE FINDING TESTS:
In a preliminary miscibility test, a test substance concentration of 50% (w/w) was determined as the highest concentration which was easily miscible and well applicable.
In a preliminary skin irritation test with 3 female animals, test substance formulations of 10, 20, 30 and 50% were topically applied to the flank under occlusive conditions for 6 h. The maximum non-irritant concentration of 50% was used for challenge.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in vehicle
- Control group: vehicle
- Site: left flank
- Frequency of applications: every 7 days
- Duration: Days 0-14
- Concentrations: 50% test substance in vaseline
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: test substance in vehicle and vehicle only
- Control group: test substance in vehicle and vehicle only
- Site: posterior right flank (test substance) and anterior right flank (vehicle)
- Concentrations: 50% test substance in vaseline
- Evaluation (hr after challenge): 24 and 48 h after test substance removal with corn oil. - Challenge controls:
- In the 4th week of the test, 3 additional animals (accompanying group), kept under the same conditions, but without treatment, were used to re-determine the maximum non-irritant concentration for the challenge treatment.
This additional determination of the challenge concentration was carried out because it was suspected that the sensitivity of the skin changed as the weight of the animals increased. This ensured that the challenge concentration was determined on animals which had approximately the same weight as the 30 animals in the challenge phase. In this test, the concentrations administered and the experimental conditions corresponded to those of the preliminary test.
The determination of the challenge concentration in the 4th week of the test on 3 untreated animals of the same age led to no signs of dermal irritation in any animal 24 and 48 h post-application of formulations containing 10, 20, 30 and 50% test substance in vehicle.
On the basis of these results and the results of the induction period, the 50% test substance in vehicle was administered for the challenge treatment in the main test.
Since this test was conducted with untreated animals approximately at the same time as the challenge application, it can be considered as a challenge control test. - Positive control substance(s):
- yes
- Remarks:
- α-hexylcinnamaldehyde
- Positive control results:
- The positive control substance α-hexylcinnamaldehyde (100% induction, 50% challenge concentration) induced positive reactions in 10/20 and 9/20 animals at 24 and 48 h after challenge, respectively. Thus, the reliability criteria for the Buehler test (≥ 15% positive response) were met.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 10.0.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 20.0.
- Key result
- 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:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 10.0.
- 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:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 20.0.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 19 Nov - 22 Nov 2007
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Modified Local Lymph Node Assay (Integrated Model for the Differentiation of Skin Reactions, IMDS) accordimng to Vohr, H.-W. et al. (Arch Toxicol 73:501-509, 2000) and Ehling, G. et al. (Toxicology 212: 60-68 and 89-79, 2005).
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- yes
- Remarks:
- Modified Local Lymph Node Assay (Integrated Model for the Differentiation of Skin Reactions, IMDS) accordimng to Vohr, H.-W. et al. (Arch Toxicol 73:501-509, 2000) and Ehling, G. et al. (Toxicology 212: 60-68 and 89-79, 2005).
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- other: Hsd Win:NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: 23-29 g
- Housing: during the adaptation period, up to 8 mice were housed together in conventional Makrolon type III cages, while during the study period the animals were single-housed in type II cages. During adaptation period, the cages were changed at least twice a week. Low-dust wood shavings were used as bedding.
- Diet: PROVIMI KLIBA SA 3883 maintenance diet for rats and mice (Provimi Kliba SA, Kaiseraugst, Switzerland), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 40-70
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 2, 10 and 50%
- No. of animals per dose:
- 6
- Details on study design:
- RANGE FINDING TESTS:
A range finding test was not conducted. According to the author, based on in-house experience with the test system and the available information on the properties of the test item, the following concentrations were used: 0 (vehicle control), 2, 10 and 50%."
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local lymph node weight and cell count determinations
- Criteria used to consider a positive response:
Cell count index: The "positive level" for the cell count index was stated to be 1.4.
Ear swelling: The "positive level" of ear swelling was stated to be a 2E-02 mm increase (about 10% of the control values)
The author explicitly stated that the cut-off values for "positive levels" mentioned above are exclusively defined for the NMRI outbred mice used for this study (Homey, B. et al. [1998] Toxicol. and Appl. Pharmacol. 153:83-94; Vohr, H.-W. et al. [2000] Arch. Toxicol. 73:501-509). Further, the author noted that such positive limits have to be calculated for each strain of mice individually (Ehling, G. et al. [2005] Toxicology 212:60-68; Ehling, G. et al. [2005] Toxicology 212:69-79).
TREATMENT PREPARATION AND ADMINISTRATION:
The test item in the formulation or the vehicle was applied epicutaneously onto the dorsal part of both ears of the animals. This treatment was repeated on three consecutive days (d1, d2 and d3). The volume administered was 25 µL/ear.
INVESTIGATIONS
-Autopsies:
The animals were anaesthetized by inhalation of carbon dioxide and sacrificed one day after the last application (Day 4). The appropriate organs were then removed. Lymphatic organs (the auricular lymph nodes) were transferred into physiological saline (PBS).
- LLN Weight and cell count determinations:
The weight of the lymph nodes was determined on a semiautomatic balance and stored electronically. After crushing the lymph nodes through a sieve in a 12-well plate and dispersion in 2 mL PBS, the cell counts per mL were determined using an electronic cell counter. These data were also directly collected and processed by a computer. Mean values, indices and standard deviations were calculated by a spreadsheet software.
A special software was used to calculate mean values and standard deviations of lymph node weights. Indices were calculated manually.
The so-called stimulation (or LLN-) index is calculated by dividing the absolute number of weight or cell counts of the substance-treated lymph nodes by the vehicle-treated ones. Thus, in case of no stimulating effect, the index is always about 1.00 (± standard deviation), and the indices of vehicle-treated animals are set to 1.00 (± standard deviation).
- Ear swelling:
Before the first treatment and before sacrifice, the thickness of both auricles of the animals was measured using a spring-loaded micrometer. Mean values, indices and standard deviations of the ear swelling were calculated by a spreadsheet software.
- Ear weight:
On Day 4 of the study, the ear weight of the sacrificed animals was measured using a punch to take a piece of every ear with a diameter of 8 mm. The weights were determined on a semiautomatic balance. Mean values, indices and standard deviations of the ear weights were calculated by a spreadsheet software.
- Body weight:
The body weights of the animals were recorded at the start and at the end of the study (Day 1 and Day 4). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- When it was statistically reasonable, the values from the treated groups were compared with those from the control group(s; vehicle) by a one-way analysis of variance (ANOVA) when the variances were considered homogeneous according to a homogeneity testing like Cochran's test. Alternatively, if the variances were considered heterogeneous (p ≤ 0.05), a non-parametric Kruskal-Wallis test has been used (Kruskal-Wallis ANOVA) at significance levels of 5%. Two-sided multiple test procedures were done according to Dunnett or Bonferroni-Holm, respectively. Outlying values in the LN weights were eliminated at a probability level of 99% by Nalimov's method. In addition, for the LLNA/IMDS the smallest significant differences in the means were calculated by Scheffe'S method, which can be used for both equal and unequal sample sizes.
In this method of statistical processing of measurements a large number of comparisons is made, and as a result of the multiple tests the overall probability of error is considerably greater than the p values suggest (increased number of false-positive results). On the other hand, the known methods of adjusting p values lead to an excessive increase in the number of false negatives. In view of these problems, the biological and toxicological relevance was also taken into consideration in the evaluation of statistical significance.
For this reason, in the case of indices only the standard deviations between groups and difference analysis of the mean values were used in the evaluation of the biological relevance. - Key result
- Parameter:
- SI
- Remarks on result:
- other: see Remark
- Remarks:
- Cell count index (± standard deviation in %): Vehicle control: 1.00 ± 27.43 2%: 0.84 ± 32.82 10%: 0.95 ± 20.12 50%: 0.97 ± 20.22 Ear swelling index on Day 4: Vehicle control: 1.00 2%: 1.04 10%: 1.00 50%: 1.02 Ear weight index: Vehicle control: 1.00 2%: 0.99 10%: 1.00 50%: 1.06
- Key result
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: see Remark
- Remarks:
- No significant changes were observed in the absolute number of lymph node cell counts per mL (see Table 2 for details) Group mean cell counts (1000 cells/mL lymph node suspension ± standard deviation): Vehicle control: 10961,50 ± 3006.68 2%: 9169.42 ± 3009.43 10%: 10421.25 ± 2096.75 50%: 10629.50 ± 2149.53 No significant changes were observed in ear thickness between Day 1 and Day 4 as well as between animals treated with the test item and with the vehicle (see Table 3 for details). Group mean ear swelling (Day 1 / Day 4; in 0.01 mm ± standard deviation in %): Vehicle control: 17.83 ± 3.24 / 17.25 ± 2.62 2%: 17.67 ± 3.69 / 17.92 ± 2.87 10%: 17.08 ± 3.01 / 17.17 ± 4.86 50% 17.33 ± 5.12 / 17.67 ± 4.41
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Referenceopen allclose all
The predicted skin sensitisation potential of Glycerol trimyristate was modelled in the OECD QSAR Toolbox v3.4. The test substance falls within the model applicability domain for the database 'Skin sensitisation (Danish EPA DB)'. The result of the prediction was negative.
Therefore, Glycerol trimyristate is not expected to have a skin sensitising potential.
Table 2. Individual cell counts
Cell count (1000 cells/mL lymph node suspension) | ||||||
Treatment group | Animal No. | Arithmetic mean (n = 2) | Group mean | SD | SD (%) | Cell count index |
Vehicle | 1 | 10541.5 | 10961.50 | 3006.68 | 27.43 | 1.00 |
2 | 13500.5 | |||||
3 | 11383 | |||||
4 | 11254.5 | |||||
5 | 13686 | |||||
6 | 5403.5 | |||||
2% | 7 | 7443 | 9169.42 | 3009.43 | 32.82 | 0.84 |
8 | 9853.5 | |||||
9 | 9090.5 | |||||
10 | 6253.5 | |||||
11 | 14736 | |||||
12 | 7640 | |||||
10% | 13 | 10796.5 | 10421.25 | 2096.75 | 20.12 | 0.95 |
14 | 9343 | |||||
15 | 7629.5 | |||||
16 | 14002 | |||||
17 | 10206.5 | |||||
18 | 10550 | |||||
50% | 19 | 7714.5 | 10629.50 | 2149.53 | 20.22 | 0.97 |
20 | 8873.5 | |||||
21 | 12331.5 | |||||
22 | 11729.5 | |||||
23 | 13247.5 | |||||
24 | 9880.5 |
Table 3. Ear swelling (6 animals per group, in 0.01 mm).
Dose (%) | Day 1 (mean ± SD in %) | Day 4 (mean ± SD in %) | Index Day 4 |
0 (vehicle) | 17.83 ± 3.24 | 17.25 ± 2.62 | 1.00 |
2 | 17.67 ± 3.69 | 17.92 ± 2.87 | 1.04 |
10 | 17.08 ± 3.01 | 17.17 ± 4.86 | 1.00 |
50 | 17.33 ± 5.12 | 17.67 ± 4.41 | 1.02 |
Table 4. Ear and lymph node weight.
Ear weight (6 animals per group, in mg per 8 mm punch) | Lymph node weight (6 animals per group) | ||
Dose (%) | Day 4 (mean ± SD in %) | Index Day 4 | Weight index (index of mean ± SD in %) |
0 (vehicle) | 11.44 ± 6.52 | 1.00 | 1.00 ± 20.70 |
2 | 11.28 ± 4.64 | 0.99 | 0.99 ± 28.19 |
10 | 11.43 ± 9.14 | 1.00 | 1.00 ± 23.44 |
50 | 12.18 ± 7.94 | 1.06 | 1.02 ± 20.02 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Analogue justification
There are no available data on the skin sensitisation potential of Glycerol trimyristate (CAS 555-45-3). The assessment was therefore based on QSAR modelling and studies conducted with analogue (source) substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).
Skin sensitisation
QSAR predictions
CAS 555-45-3
The potential for Glycerol trimyristate to be a skin sensitiser was predicted in the QSAR OECD Toolbox (WoE, 2017). There was no alert for skin sensitisation potential in the Danish EPA DB.
Animal data
CAS 97593-30-1
The skin sensitising potential of Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates was investigated in a modified Local Lymph Node Assay (LLNA) in mice performed according to OECD guideline 429 and in compliance with GLP (WoE, 2008). In this study, 6 female Hsd Win:NMRI mice per test group were treated with test substance at concentrations of 2, 10 and 50% in acetone/olive oil (4:1 v/v) or with the vehicle alone. The test substance formulations or the vehicle were applied epicutaneously onto the dorsal part of each ear (25 µL/ear) for three consecutive days. In order to assess skin irritation, the thickness of both auricles of the animals was measured before the first treatment and prior to sacrifice. In addition, ear weights were determined at necropsy. On Day 4, animals were sacrificed and weight of the lymph nodes was determined. The cell proliferation of pooled lymph nodes from individual animals was measured by counting the cells in suspension using an electronic cell counter. The mean cell count (1000 cells/mL lymph node suspension) for each test group was 9169, 10421 and 10630 at concentrations of 2, 10 and 50% of the test substance, respectively. Treatment with the test substance did not result in a significant increase of absolute number of lymph node cell counts per mL compared with the control group. Based on these results, cell count indices of 0.84, 0.95 and 0.97 were calculated for treatment concentrations of 2, 10 and 50%, respectively. A positive result in this strain of mice was obtained if the cell count index was ≥ 1.4. No local or systemic toxicity and no effects on body weights were observed. No effects on ear weights and ear swelling were observed in the treated animals compared to controls. The historical positive control alpha hexyl cinnamic aldehyde at concentrations of 3, 10 and 30% confirmed the validity of the method. Under the conditions of this study, the test substance was not found to be a sensitiser in the modified LLNA.
CAS 555-43-1
The skin sensitising potential of Glycerol tristearate was investigated in male and female guinea pigs in a Buehler test according to OECD 406 and under GLP conditions (WoE, 1998). A test substance concentration of 50% (w/w) was determined as the highest concentration which was easily miscible and well applicable. In a preliminary skin irritation test with 3 female animals, test substance formulations of 10, 20, 30 and 50% in petrolatum were topically applied to the flank under occlusive conditions for 6 h in order to establish a non-irritant concentration for induction. The concentration for challenge exposure was determined in a further 4-week test on 3 animals using the same concentrations. The maximum non-irritant concentration of 50% was used for topical application in the induction and challenge phase of the main assay. In the induction phase, the test substance at concentrations of 50% in petrolatum was applied to the clipped skin of the left flank of 20 animals under occlusive conditions. Three consecutive topical induction applications for a period of 6 h each were performed at intervals of 7 days. A control group of 10 animals was treated with the vehicle. For challenge exposure on Day 28, the test substance at 50% concentration in petrolatum and the vehicle only was applied for 6 h to the clipped skin of the posterior and anterior right flank of all animals, respectively. Skin reactions were evaluated 24 and 48 after application. None of the treated animals of the test and control group showed symptoms of dermal irritation after challenge treatment. No test substance-related systemic effects and no effects on body weights were observed in the test or control animals. The positive control substance α-hexyl cinnamic aldehyde showed the expected results thereby confirming the reliability of the study. Based on these results and the experimental conditions chosen, the test substance had no skin sensitising effect in guinea pigs.
Overall conclusion for skin sensitisation
A weight-of-evidence approach was applied to assess the skin sensitising potential of the target substance Glycerol trimyristate. The OECD QSAR Toolbox did not predict skin sensitising properties for the target substance. The in vivo studies (LLNA and Buehler) performed with two source substances were negative. Taking into account the available information, Glycerol trimyristate is not expected to be skin sensitising.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". As the analogue concept is applied to Glycerol trimyristate, data will be generated from reference source substance(s) and QSAR predictions to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.
Therefore, based on the analogue read-across approach combined with QSAR analyses performed with the main component, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.
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