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EC number: 816-845-0 | CAS number: 1818326-42-9
- 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:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: SENS-IS assay
- Version / remarks:
- This study was conducted in compliance with the Study Plan n°DC20922/SI01 and standard operating procedures, with the deviation described below:
- The SDS quality control performed by the provider of the test system used in the two experiments was outside of our acceptance criteria. Nevertheless, the result for the histology scoring was satisfactory and these batches fulfilled our internal criteria for irritation (with SLS), sensitization (with TNBS) and the absence of sensitization (with DMSO). Therefore these batches were accepted.
This deviation was without impact on the validity of the study results. - Deviations:
- yes
- Remarks:
- This deviation was without impact on the validity of the study results.
- Principles of method if other than guideline:
- - Principle of test:
The SENS-IS method for the detection of sensitisers is based on the 3D EpiSkin™ tissue model as a test system and on the analysis of the expression of a large panel of 61 genes relevant during the skin sensitisation process. The modulation of these biomarkers is measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
The expression profile of 61 genes divided in three sets will be analysed: one set of 23 genes related to the irritation process and the two other sets of genes, named “SENS-IS” and “ARE”, with 21 and 17 biomarkers respectively, involved in skin sensitization.
- Short description of test conditions:
30 µL of test item was deposited on the 3 D reconstituted epidermis surface (EpiskinTM) during 15 minutes. After incubation, the epidermis was removed and RNA were extracted, bocked with bromochloropropane, and purified.
- Parameters analysed / observed:
After reverse transcription, quantitative gene expression was measured by qRT-PCR using SYBRGreen® buffer and specific primers defined for the SENS-IS test. The housekeeping genes (glucuronidase β, β2 microglobuline, and nono « non-POU domain containing octamer-binding ») were analyzed in parallel. The overexpresion of genes lead to different conclusion :
- irritant if at least 16/23 genes of the « IRRITATION » group are significantly over expressed
- sensitizer if at least 7/17 genes of the « ARE » groupe or 7/21 genes in the « SENS-IS » group are significantly overexpressed. - GLP compliance:
- yes
- Type of study:
- other: SENS-IS assay
- Justification for non-LLNA method:
- according to the requirement of the Annex VII of REACh regulation, and in order to avoid animal testing this in-viitro method, SENS-IS lead to a skin sensitistaion data
Test material
- Reference substance name:
- Esterification products of 1,4:3,6-dianhydro-D-glucitol with sunflower oil fatty acids
- Cas Number:
- 1818326-42-9
- Molecular formula:
- Not applicable (UVCB)
- IUPAC Name:
- Esterification products of 1,4:3,6-dianhydro-D-glucitol with sunflower oil fatty acids
- Test material form:
- liquid
1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
LAB 4448- dilinoléate d'isosorbide batch number E8057
- Expiration date of the lot/batch:
retest december 2019
- Purity test date: 99.8% - the test item was considered as 100%pure
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, protected from light
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle : the solubility of the test item was assessed in phosphate buffered saline (PBS), olive oil (OO) and dimethylsulfoxide (DMSO) at a concentration of 10% and 50%, at room temperature. The test item “LAB 4448 – Dilinoléate d’isosorbide” was soluble at 10 and 50% (v/v) in olive oil and in DMSO. It was not soluble at 10 and 50% (v/v) in PBS.
FORM AS APPLIED IN THE TEST (if different from that of starting material) : neat (100%), 50% in olive oil, 10% in olive oil, 1% in olive oil, 10% in DMSO
In vitro test system
- Details on the study design:
- Skin sensitisation (In vitro test system) - Details on study design:
The test item (30 µL) was deposited on the epidermis surface and gently spread on the entire surface [3]. After 15 minutes of exposure, the Episkin™ was rinsed with PBS and then incubated at 37°C for 6 hours.
In experiment 1: the test item was tested in solution : 50%, 10%, 1% in olive oil, and 10 % in DMSO
In experiment 2: the test item was tested pure and in a solution : 50% olive oil.
After incubation, reconstructed epidermis was removed from the inserts with forceps and placed in a cryotube for freezing in liquid nitrogen. The epidermis was then transferred in a tube containing 1 mL of Qiazol reagent and 2 steel beads. Epidermis was homogenized using the TissueLyser II. After centrifugation, the supernatant was collected and stored at -20°C until RNA extraction.
After addition of bromochloropropane, total RNA were purified using the miRNeasy extraction Kit according to the manufacturer’s instructions (Qiagen, Courtaboeuf, France). RNA quality was assessed by measuring 260/280 absorbance ratio. The mRNA (14 µL of each sample) was then reversed as cDNA using SuperScript III Reverse Transcriptase kit and RNase inhibitor.
After reverse transcription, quantitative gene expression was measured by qRT-PCR using a SYBRGreen® buffer and specific primers defined for the SENS-IS test. The housekeeping genes (Glucuronidase ß, ß2 microglobuline, and Nono « non-POU domain containing octamer-binding ») were analyzed in parallel. The amplification program consisted of one cycle at 95 °C with a 10 min hold, followed by 45 amplification cycles (95 °C for 10 s, annealing at 60 °C for 10 s, 72°C for 10 s) and completed by three steps for generating a melting curve and a cooling phase.
Data analysis and interpretation
Samples were analyzed by the LightCycler 480 software using the second derivative maximum method. This method allows the calculation of the crossing point (Cp) of each sample defined as the number of cycles from which the fluorescence signal enters the exponential phase of the reaction. This value is dependent of the amount of the mRNA present in the sample.
For each sample, the mRNA content for each gene of interest was normalized to the mean mRNA content of the 3 house-keeping genes. For each gene, the fold increase expression over vehicle controls was calculated as followed:
E = Expression level for the test item / Expression level for the vehicle controls*
* Mean of OO and PBS samples
The endpoint values are the number of positive genes (i.e., genes obtaining a E > 1.25) in each group.
Validation of the experiment
The following criteria must be met for an experiment to be considered valid:
- Negative sensitization control (DMSO): this control should induce the over-expression of 6 genes at most in the SENS-IS and ARE groups of genes.
- Positive irritation control and negative sensitization control (SLS at 5%): this control should induce the over expression of at least 16 genes in the IRRITATION group of genes and 6 genes at most in the SENS-IS and ARE groups of genes.
- Positive sensitization control (TNBS at 1M): this control should induce the over expression of at least 7 genes in the SENS-IS or ARE group of genes.
Validation of the sample
The following criteria must be met for sample result to be considered valid:
- The Cp value of HSP90AA1 gene must be ≤ 21.
- If more than 20 genes are overexpressed in the “IRRITATION” set of genes for a given concentration, the result is classified as false positive to take into account non-specific genes up regulation that could be due to cell stress.
Test item classification
A test item is classified as irritant if at least 16/23 genes of the “IRRITATION” group are significantly overexpressed.
A test item is classified as sensitizer if at least 7/17 genes of the “ARE” group, and/or 7/21 genes in the “SENS-IS” group are significantly overexpressed.
Moreover, the results obtained with the different concentrations allow the classification of the test item according to the lowest concentration that gives a positive result (E > 1.25). Thus, a test item is classified in:
- category 1A: strong to extreme skin sensitizer, when a positive result is obtained at concentrations of 0.1 and/or 1%,
- category 1B: weak to moderate sensitizer, when a positive result is obtained at concentrations of 10 and/or 50%.
A test item is classified as a non-sensitizer when negative results are observed at 100% and at all other analyzed concentrations.
At least two independent experiments (repetitions) are performed in order to obtain two concordant conclusions. If three repetitions should be performed for a given concentration, a majority of positive results (2 out of 3) must be obtained so that the final outcome is positive, otherwise the final outcome is negative.
Results and discussion
- Positive control results:
- see tables in section any other information on tabels and results
In vitro / in chemico
Results
- Key result
- Run / experiment:
- other: number of overexpressed genes
- Parameter:
- other: number of overexpressed genes in the "SENS-IS" and "ARE" when it was tested at 1, 10 and 50% (v/v) in olive oil and at 10% (v/v) in DMSO and at 100%
- Remarks:
- number of overexpressed genes in the "SENS-IS" and "ARE" when it was tested at 1, 10 and 50% (v/v) in olive oil and at 10% (v/v) in DMSO and at 100%
- Value:
- 7
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
Any other information on results incl. tables
Analysis of positive and negative controls
Experiment 1 (2SI19004):
|
Number of overexpressed genes |
||
Gene group |
SLS 5% Positive control for irritation and negative control for sensitization |
TNBS 1M Positive control for sensitization |
DMSO 100% Negative control for irritation & sensitization |
IRRITATION |
21 |
5 |
6 |
SENS-IS |
5 |
4 |
3 |
ARE |
2 |
14 |
0 |
Conclusion |
|||
IRRITATION |
POSITIVE |
NEGATIVE |
NEGATIVE |
SENSITIZATION |
NEGATIVE |
POSITIVE |
NEGATIVE |
Experiment 2 (2SI19005):
|
Number of overexpressed genes |
||
Gene group |
SLS 5% Positive control for irritation and negative control for sensitization |
TNBS 1M Positive control for sensitization |
DMSO 100% Negative control for irritation & sensitization |
IRRITATION |
21 |
4 |
11 |
SENS-IS |
4 |
2 |
3 |
ARE |
4 |
13 |
0 |
Conclusion |
|||
IRRITATION |
POSITIVE |
NEGATIVE |
NEGATIVE |
SENSITIZATION |
NEGATIVE |
POSITIVE |
NEGATIVE |
SLS at 5% was classified as irritant (number of overexpressed irritant genes > 15) and non-sensitizer, the number of overexpressed genes in both the SENS-IS and ARE groups being below 7.
TNBS at 1M was classified as sensitizer since more than 6 genes are overexpressed in at least one of the two groups of genes (SENS-IS or ARE).
DMSO at 100% was classified as a non-sensitizer, the number of overexpressed genes in both the SENS-IS and ARE groups being below 7.
Analysis of test item
Experiment 1 (2SI19004):
|
Number of overexpressed genes |
|||
Gene group |
50% Oliveoil |
10% Oliveoil |
1% Oliveoil |
10% DMSO |
IRRITATION |
2 |
1 |
2 |
5 |
SENS-IS |
3 |
2 |
1 |
0 |
ARE |
2 |
1 |
1 |
1 |
Cp value - HSP90AA1 |
17.5 |
17.5 |
17.7 |
18.1 |
Conclusion |
||||
SENSITIZATION |
NEGATIVE |
NEGATIVE |
NEGATIVE |
NEGATIVE |
Experiment 2 (2SI19005):
|
Number of overexpressed genes |
|
Gene group |
100% |
50% Oliveoil |
IRRITATION |
0 |
1 |
SENS-IS |
3 |
2 |
ARE |
1 |
0 |
Cp value - HSP90AA1 |
17.9 |
17.9 |
Conclusion |
||
SENSITIZATION |
NEGATIVE |
NEGATIVE |
In the first experiment, the test item “LAB 4448 –Dilinoléated’isosorbide” induced less than 7 genes in the “SENS-IS” and “ARE” gene groups when tested at 1, 10 and 50% (v/v) in olive oil and at 10% in DMSO.
In the second experiment, the test item “LAB 4448 –Dilinoléated’isosorbide” induced less than 7 genes in the “SENS-IS” and “ARE” gene groups when tested at 50% (v/v) in olive oil and at 100% (not diluted).
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The results obtained for the positive and negative controls were within acceptance criteria defined in the Study Plan.
Considering the number of over-expressed gene in the “SENS-IS” and “ARE” gene groups, the test item “LAB 4448 – Dilinoléate d’isosorbide” gave negative result (less than 7 genes induced) when it was tested at 1, 10 and 50% (v/v) in olive oil and at 10% (v/v) in DMSO. Moreover, negative results were obtained when the test item was tested at 100% (not diluted).
In conclusion, under the experimental conditions of this SENS-IS assay, the test item “LAB 4448 – Dilinoléate d’isosorbide” can be classified as a non- skin sensitizer under CLP criteria. - Executive summary:
The objective of this study was to evaluate the capacity of the test item “LAB 4448 – Dilinoléate d’isosorbide” to induce the expression of specific irritation and sensitization biomarkers in a 3D-reconstructed epidermis model, according to SENS-IS assay.
The results obtained for the positive and negative controls were within acceptance criteria defined in the Study Plan.
Considering the number of over-expressed gene in the “SENS-IS” and “ARE” gene groups, the test item “LAB 4448 – Dilinoléate d’isosorbide” gave negative result (less than 7 genes induced) when it was tested at 1, 10 and 50% (v/v) in olive oil and at 10% (v/v) in DMSO. Moreover, negative results were obtained when the test item was tested at 100% (not diluted).
In conclusion, under the experimental conditions of this SENS-IS assay, the test item “LAB 4448 – Dilinoléate d’isosorbide” can be classified as a non- skin sensitizer under CLP criteria.
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