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EC number: 947-854-9 | 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
An in vitro bacterial mutagenicity test is available for the target substance:
Ames test (OECD 471): negative with S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 with and without metabolic activation
In the absence of data on gene mutation in mammalian cells for Fatty acids C16 -18 (even numbered), mono and diesters with sucrose (no CAS) read-across approach was conducted on source substance
Fatty acids C16 -18 (even numbered), mono, di and triesters with sucrose (no CAS) and Sucrose laurate as explained in the analogue justification (chapter 13):
Gene mutation in mammalian cells (OECD 490): negative in mouse lymphoma L5178Y cells with and without metabolic activation
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 16 - 25 April
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- missing 5th strain (TA 102 or E. coli WP2)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted May 26, 1983
- Deviations:
- yes
- Remarks:
- missing 5th strain (TA 102 or E. coli WP2)
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
- Version / remarks:
- Sep 1985
- Deviations:
- not specified
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of male rats treated with Aroclor 1254 (500 mg/kg bw)
- Test concentrations with justification for top dose:
- 4, 20, 100, 500, 2500 and 5000 µg/plate with and without metabolic activation
- Vehicle / solvent:
- - Vehicle/solvent used: DMSO
- Justification for choice of solvent/vehicle: Test substance is well soluble in DMSO at approx. 48 °C and is stabil for 4 h. - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- other: 2-Aminoanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: triplicates in 2 different experiments
DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of colonies or a thinning of the bacterial background lawn - Evaluation criteria:
- A test compound is classified as mutagenic if it has either of the following effects:
a) a test compound produces at least a 2-fold increase in the mean number of revertants per plate of at least one of the tester strains over the mean number of
revertants per plate of the appropriate vehicle control at complete bacterial background lawn
b) a test compound induces a dose-related increase in the mean number of revertants per plate of at least one of the tester strains over the mean number of
revertants per plate of the appropriate vehicle control in at least two to three concentrations of the test compound at complete bacterial background lawn.
lf the test substance does not produce reproducible increases of at least 2 times the concurrent solvent controls, at any dose level with any bacterial strain, it is considered to show no evidence of mutagenic activity in this system.
The test results must be reproducible. - Statistics:
- Mean values and standard deviations were calculated.
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp 1: +S9: at and above 2500 µg/plate; -S9: at and above 500 µg/plate Exp 2: +S9: at and above 500 µg/plate; -S9: at and above 100 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp 1: +S9: at and above 2500 µg/plate; -S9: at and above 100 µg/plate Exp 2: +/- S9: at and above 500 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp 1 and 2: +S9: at and above 2500 µg/plate; -S9: at and above 500 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp 1: +S9: at and above 5000 µg/plate; -S9: at and above 500 µg/plate Exp 2: +/- S9: at and above 2500 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Visible precipitation of the test substance was observed at 2500 µg/plate and above in both experiments.
RANGE-FINDING/SCREENING STUDIES: In a toxicity test with a dilution of tester strain TA 100, which was performed in parallel with the second experiment, toxicity was found at a concentration of 2500 μg/plate in the presence of metabolic activation and 100 μg/plate in the absence of metabolic activation.
ADDITIONAL INFORMATION ON CYTOTOXICITY: In both mutagenicity experiments strain dependent cytotoxicity was observed in a dose range of 100 to 2500 μg/plate and above without metabolic activation and in a dose range of 500 to 5000 μg/plate withmetabolic activation. Thinning of bacterial
lawn and in most cases also a reduction in the number of colonies were observed at these doses. - Conclusions:
- Under the test conditions used, the substance was not mutagenic in any of the four strains of Salmonella typhimurium (TA 1535, TA 1537, TA 98 and TA 100) tested with and without metabolic activation.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- refer to analogue justification provided in IUCLID section 13
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other:
- Remarks:
- growth inhibition was seen at all concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Source: Fatty acids, C16-18 (even numbered), mono di and triesters with sucrose (no CAS), Schreib, 2017
- Conclusions:
- Based on the results of the mouse lymphoma assay in L5178Y cells, both source substances were non-mutagenic in mammalian cells with or without metabolic activation. Therefore and by analogy, the target substance is expected to be non-mutagenic in mammalian cells.
Referenceopen allclose all
Table 1: Results of Experiment 1
|
Number of revertant colonies (mean of 3 plates±SD) |
|||||
With S9 |
||||||
Test substance (µg/plate) |
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
||
Solvent control |
10.7±1.2 |
14.7±1.2 |
26.7±5.5 |
115.3±5.0 |
||
Negative control (untreated) |
10.3±1.5 |
17.0±4.6 |
22.3±1.5 |
148.3±4.0 |
||
0 |
10.7±1.2 |
14.7±1.2 |
26.7±5.5 |
115.3±5.0 |
||
4 |
13.3±1.5 |
14.3±2.5 |
26.7±4.7 |
123.7±6.7 |
||
20 |
11.7±3.5 |
14.3±1.5 |
21.0±1.7 |
132.7±8.0 |
||
100 |
9.3±2.3 |
13.0± 1.0 |
22.7±2.1 |
126.0±2.6 |
||
500 |
9.7±0.6 |
14.7±3.5 |
19.7±2.5 |
121.7±3.2 |
||
2500 |
7.0±1.7 r |
2.7±1.2 r |
16.3±6.7 r |
93.3±10.1 |
||
500 |
3.0±2.0 r |
1.0±0.0 c |
8.3±2.5 r |
102.0±15.6 r |
||
Positive Control |
2-AA |
2-AA |
2-AA |
2-AA |
||
Dose (µg/plate) |
1.0 µg/plate |
1.0 µg/plate |
0.5 µg/plate |
0.5 µg/plate |
||
Number of revertant colonies/plate |
194.3±9.3 |
288.7±33.2 |
2211.7±0.5 |
1757.7±69.6 |
||
Without S9 |
||||||
Test substance (µg/plate) |
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
||
Solvent control |
8.3±0.6 |
12.0±2.0 |
19.7±3.2 |
116.3±15.3 |
||
Negative control (untreated) |
11.7±0.6 |
12.7±1.2 |
25.0±3.6 |
119.3±15.2 |
||
0 |
8.3±0.6 |
12.0±2.0 |
19.7±3.2 |
116.3±15.3 |
||
4 |
12.7±0.6 |
8.3±3.1 |
22.7±2.9 |
107.7±11.9 |
||
20 |
10.3±2.9 |
8.0±3.0 |
19.3±2.5 |
129.0±17.6 |
||
100 |
9.7±2.1 |
5.0±3.6 r |
21.3±2.9 |
117.0±5.3 |
||
500 |
10.0±2.0 r |
5.0±1.7 r |
12.7±2.1 r |
83.7±7.6 |
||
2500 |
1.7±0.6 r |
2.7±1.2c |
6.3±0.6 r |
93.0±9.5 |
||
5000 |
1.3±0.6 r |
1.0±0.0 c |
6.7± 3.1 c |
83.3±14.4 r |
||
Positive Control |
NaN3 |
9-AA |
2-NF |
NaN3 |
||
Dose (µg/plate) |
2.5 |
2.5 |
2.5 |
2.5 |
||
Number of revertant colonies/plate |
461.3±2.3 |
150.7±43.1 |
564.3±67.5 |
636.3±10.1 |
||
2AA: 2-Aminoanthracene 9-AA: 9-Aminoacridine 2-NF: 2-Nitrofluorene NaN3: sodium azide |
r: reduced background growth c: clearing of background growth |
Table 2. Results of Experiment 2
|
Number of revertant colonies (mean of 3 plates±SD) |
|||
With S9 |
||||
Test substance (µg/plate) |
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
Solvent control |
12.3±1.2 |
9.7±2.5 |
31.3±5.1 |
130.3±0.6 |
Negative control (untreated) |
12.3±1.5 |
10.3±0.6 |
26.0±2.6 |
163.3±13.3 |
0 |
12.3±1.2 |
9.7±2.5 |
31.3±5.1 |
130.3±0.6 |
4 |
9.3±7.6 |
9.0±1.0 |
32.7±6.5 |
137.7±12.4 |
20 |
8.3±5.5 |
8.3±1.2 |
23.7±2.1 |
139.0±11.5 |
100 |
10.7±3.1 |
10.3±3.2 |
28.0±3.0 |
149.3±5.1 |
500 |
12.3±2.9 r |
4.3±2.5 r |
30.3±12.1 |
143.7±10.1 |
2500 |
6.3±2.9 r |
3.0±1.7 r |
12.3±2.1 r |
129.7±0.6 r |
500 |
6.3± 6.7 r |
2.0±1.0 c |
10.3±1.2 r |
135.3±14.2 r |
Positive Control |
2-AA |
2-AA |
2-AA |
2-AA |
Dose (µg/plate) |
1.0 µg/plate |
1.0 µg/plate |
0.5 µg/plate |
0.5 µg/plate |
Number of revertant colonies/plate |
172.7±13.1 |
272.3±13.8 |
2199.7±150.5 |
1897.7±114.2 |
Without S9 |
||||
Test substance (µg/plate) |
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
Solvent control |
13.7±0.6 |
8.0±0.0 |
20.3±1.2 |
130.3±0.6 |
Negative control (untreated) |
13.7±2.1 |
7.3±1.2 |
26.0±4.4 |
163.3±13.3 |
0 |
13.7±0.6 |
8.0±0.0 |
20.3±1.2 |
125.3±15.9 |
4 |
11.0±2.6 |
7.0±1.0 |
24.0±1.7 |
129.3±7.0 |
20 |
9.0±1.7 |
8.3±1.2 |
24.3±1.2 |
124.0±8.2 |
100 |
11.3±3.1 r |
7.0±1.0 |
26.7±3.8 |
123.7±23.6 |
500 |
11.3±2.5 r |
2.3±0.6 r |
13.0±2.6 r |
105.3±19.5 |
2500 |
1.7±1.5 r |
1.3±0.6 c |
6.7±0.6 r |
95.0±3.6 r |
5000 |
0.3±0.6 r |
1.0±0.0 c |
5.0±1.0 r |
83.0±7.9 r |
Positive Control |
NaN3 |
9-AA |
2-NF |
NaN3 |
Dose (µg/plate) |
2.5 |
2.5 |
2.5 |
2.5 |
Number of revertant colonies/plate |
431.3±55.0 |
215.3±33.1 |
520.3±89.2 |
1897.7±114.2 |
2AA: 2-Aminoanthracene 9-AA: 9-Aminoacridine 2-NF: 2-Nitrofluorene NaN3: sodium azide |
r: reduced background growth c: clearing of background growth |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
In the absence of data on gene mutation in mammalian cells in vivo for Fatty acids C16 -18 (even numbered), mono and diesters with sucrose (no CAS) read-across approach was conducted on source substance
Fatty acids C16 -18 (even numbered), mono, di and triesters with sucrose (no CAS) as explained in the analogue justification (chapter 13):
Micronucleus test (OECD 474): negative in mouse erythrocytes
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- October 27 - November 9, 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian germ cell cytogenetic assay
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, protected from light
- Stability under test conditions: Expected to be stable.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance was ground until it passed through a 425 micron sieve.
- Final dilution of a dissolved solid, stock liquid or gel: The test substance was dissolved in distilled water. A separate dilution was prepared for each dose level in order to maintain a constant dose volume.
FORM AS APPLIED IN THE TEST (if different from that of starting material): Solution - Species:
- mouse
- Strain:
- ICR
- Details on species / strain selection:
- Mice were selected as micronucleated erythrocytes are not readily removed from the blood.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Envigo Laboratories, Inc.
- Age at study initiation: 8 weeks (preliminary test), 7 weeks (main test)
- Weight at study initiation: Preliminary test - 31-39.7 g males, 24.8-28.5 g females; Main test - 36-39 g males, 23-27 g females
- Assigned to test groups randomly: yes
- Fasting period before study: No
- Housing: Plastic solid bottom cages
- Diet: Harlan Teklad Global 16% Protein Rodent Diet #2016, ad libitum
- Water: Filtered tap water ad libitum
- Acclimation period: 5-18 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 42-55
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: October 27, 2015 To: November 19, 2015 - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: distilled water
- Concentration of test material in vehicle: Preliminary test - 500 and 2000 mg/kg bw, Main test - 2000 mg/kg bw
- Amount of vehicle (if gavage or dermal): Enough vehicle for constant volume dose of 5 ml. - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Prepared on day of dosing. The test substance was ground until it passed through a 425 micron sieve. The test substance was dissolved in distilled water. A separate dilution was prepared for each dose level in order to maintain a constant dose volume.
- Duration of treatment / exposure:
- Preliminary test: two doses administered at a 24 hr interval
Main test: two doses administered at a 24 hr interval, positive control single dose on Day 2 - Frequency of treatment:
- Once daily
- Post exposure period:
- 2 days
- Dose / conc.:
- 500 mg/kg bw/day
- Remarks:
- Preliminary test only
- Dose / conc.:
- 2 000 mg/kg bw/day
- Remarks:
- Preliminary and main test
- No. of animals per sex per dose:
- Preliminary test: 3 animals per group per sex
Main test: 5 animals per group per sex - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide monohydrate
- Route of administration: oral gavage
- Doses / concentrations: 40 mg/kg bw/day - Tissues and cell types examined:
- Blood, erythrocytes
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Based on preliminary test.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Sampling performed 44-48 hrs after final treatment.
DETAILS OF SLIDE PREPARATION: Duplicate samples of 60-120 microliters of blood per sample were collected. The blood was fixed by rapid pipetting in chilled methanol, and stored for at least three days. The samples were centrifuged, the methanol removed, and the cells suspended in shipping buffer. One set of samples was sent to Litron Laboratories, 3500 Winton PI, Rochester, New York 14623, United Sates of America, for analysis. Cells were stained with fluorescent labeled anti-CD71, fluorescent labeled anit-CD61 antibody, and propidium iodide following RNAse treatment.
METHOD OF ANALYSIS: The cells were analyzed by flow cytometry for a minimum of 4000 immature erythrocytes per animals, and DNA content in both immature and mature erythrocytes.
- Evaluation criteria:
- Micronucleated immature erythrocytes (MIE) values within expected range based on published values and laboratory control values for negative controls. Clear increase in MIE values outside historical control range for negative control animals in the positive controls. A statistically significant dose-related increase in MIE values as compared to the negative control group with at least two individual animals outside the laboratory control range was considered a positive result.
- Statistics:
- Analysis of variance followed by Bonferroni-corrected multiple comparison test.
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 500-2000 mg/kg bw/day
- Clinical signs of toxicity in test animals: No
- Evidence of cytotoxicity in tissue analyzed: No
- Harvest times: 44-48 hrs after final exposure
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): No significant difference from negative controls.
- Appropriateness of dose levels and route: The route chosen (oral gavage) is the recommended route. The dose levels were chosen based on the preliminary test. The highest dose in the preliminary test (2000 mg/kg bw/day) was chosen based on the lack of toxicity and cytotoxocity.
- Statistical evaluation: No test substance related change in reticulocyte fraction (% RET) was observed. No statistically significant increase in micronucleus frequency (% MN-NCE) was observed. - Conclusions:
- The test substance is not genotoxic with respect to micronucleus induction.
- Executive summary:
An In Vivo Mouse Erythrocyte Micronucleus Test (Flow Cytometry) was performed using the test substance Sucrose Palmitate Stearate MDT. A dose of 2000 mg/kg bw was administered to 5 female and 5 male mice on two consecutive days. The mice were sacrificed two days later, and blood samples drawn for analysis of micronuclei. Other groups of mice were used as negative and positive controls. The test substance Sucrose Palmitate Stearate MDT Grade is not genotoxic with respect to micronucleus induction.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Only data on the gene mutation in bacteria of Fatty acids, C16-18 (even numbered), mono and diesters with sucrose are available. The assessment was therefore additionally based on QSAR modelling and studies conducted with an analogue substance 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 due 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).
In vitro gene mutation in bacteria
Fatty acids, C16-18 (even numbered), mono and diesters with sucrose (target)
A bacterial gene mutation assay with the target substance was performed in accordance with OECD Guideline 471 and in compliance with GLP (Müller, 1996). In two independent experiments, the Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 were exposed to test substance concentrations of 4, 20, 100, 500, 2500 and 5000 µg/plate in DMSO with and without metabolic activation using the plate incorporation method. A toxicity experiment using histidine enriched agar plates and a dilution of the tester strain TA 100 was performed in parallel with the second experiment. Precipitation of the test substance was observed at 2500 µg/plate and above in both experiments. The test substance was bacteriotoxic towards all tester strains in a dose range of 500 to 5000 µg/plate with metabolic activation and 100 to 2500 µg/plate and above without metabolic activation. In the absence and presence of metabolic activation the test substance did not result in relevant increases in the number of revertants in any of the bacterial strains. The revertant frequencies of the vehicle and negative control were within the expected range and the positive control chemicals induced marked increases in revertant colonies, demonstrating the effective performance of the experiments. Under the conditions of this experiment, the test substance did not show mutagenicity in the selected S. typhimurium strains in the presence and absence of metabolic activation.
Genetic toxicity (mutagenicity) in bacteria profiling in silico
Fatty acids, C16-18 (even numbered), mono and diesters with sucrose
As only four Salmonella strains were tested for bacterial mutagenicity, the target substance Fatty acids, C16-18 (even numbered), mono and diesters with sucrose (no CAS) was further assessed for its mutagenicity potential by QSAR modelling (OECD Toolbox, 2018 and VEGA, 2018). Four constituents of the UVCB substance, which were considered representative for the UVCB substance, were selected for evaluation by means of (Q)SAR models included in the free available OECD QSAR Toolbox v4.1 and VEGA software v1.1.4. The models or profilers included in VEGA and the OECD QSAR Toolbox did not provide any results indicative for mutagenic potential of evaluated components of the target substance. Only two alerts (“H-acceptor-path3-H-acceptor” and “Oxolane”) were identified as possibly related to micronucleus mutagenicity. H-acceptor-path3-H-acceptor is triggered by a multitude of different substances, and was therefore considered as negligible. The alert “Oxolane” resulted from the sucrose moiety of the target substance. Experimental data available in the data base of OECD QSAR Toolbox for sucrose showed no mutagenicity. Therefore this alert was also considered negligible for the target substance. Absence of mutagenic potential was also supported by the findings of the VEGA software. The four evaluated constituents were consistently predicted as “Non-Mutagenic” by the VEGA models for Mutagenicity (Ames test). Therefore following a weight of evidence approach and in good congruence with the experimental results of the Ames test, Fatty acids, C16-18 (even numbered), mono and diesters with sucrose is considered as not mutagenic in bacteria.
Gene mutation in mammalian cells
Fatty acids, C16-18 (even numbered), mono, di and triester with sucrose
An in vitro mammalian cell gene mutation assay was performed with source substance Fatty acids, C16-18 (even numbered), mono di and triesters with sucrose according to OECD guideline 490 and under GLP conditions (Schreib, 2017). Based on a pre-experiment, mouse lymphoma L5178Y cells were exposed for 4 h to test substance concentrations of 10, 20, 50, 100, 200, and 300 µg/mL, both with and without metabolic activation. Tetrahydrofuran (THF) was used as a solvent. Negative, solvent, and positive controls were used. Precipitation was seen at the highest test concentration of 300 µg/mL. The test substance was not cytotoxic, nor mutagenic. In conclusion, the test substance did not induce gene mutation in mouse lymphoma cells.
Sucrose laurate
An in vitro mammalian cell gene mutation assay was performed with source substance Sucrose laurate to OECD guideline 490 and under GLP conditions (Schreib, 2016). Based on a pre-experiment, mouse lymphoma L5178Y cells were exposed for 4 h to test substance concentration of 0.005, 0.010, 0.025, 0.050, 0.075, 0.100, 0.125 and 0.150 mg/mL without metabolic activation, and 0.075, 0.100, 0.125, 0.150, 0.175, 0.200, 0.225, 0.250 mg/mL with metabolic activation. Growth inhibition was seen at all concentrations with and without metabolic activity. No biologically relevant increase in mutants was seen after exposure to the test substance. No dose-response relationship was observed. In conclusion, the test substance did not induce mutations in mouse-lymphoma L5178Y cells, neither in the presence nor in the absence of a metabolic activation system, under the experimental conditions used.
In vivo
Cytogenicity in mammalian cells
Fatty acids, C16-18 (even numbered), mono, di and triesters with sucrose
A micronucleus assay in bone marrow cells of ICR mice was performed with source substance Fatty acids, C16-18 (even numbered), mono di and triesters with sucrose according to OECD Guideline 474 and in compliance with GLP (Koetzner, 2016). In an preliminary test 3 animals each received 500 and 2000 mg/kg bw/day test substance oral by gavage, respectively. Since no systemic toxicity or cytogenicity was observed, in the main test 5 male and 5 female mice received 2000 mg/kg bw/day test substance oral by gavage on two consecutive days. 44 – 48 h after final exposure animals were killed, blood was collected and erythrocytes were isolated. Cells were stained with fluorescent labeled anti-CD71 antibody and propidium iodide. At least 4000 immature cells per animal were analysed by flow cytometry. No clinical signs of toxicity were observed in the animals during the study period. No test substance related change in reticulocyte fraction (% RET) and micronucleus frequency (% MN-NCE) was observed. The data indicate that the test substance is not genotoxic in mammalian bone marrow cells with respect to micronucleus induction under in vivo test conditions.
Overall conclusion for genetic toxicity
Data from a gene mutation study in bacteria (Ames) for Fatty acids, C16-18 (even numbered), mono and diesters with sucrose (no CAS) are available. The OECD QSAR toolbox did not predict bacterial mutagenicity of the target substance and therefore confirms the results of the Ames test. In the absence of in vitro mammalian cell data, read-across from the analogue substances Fatty acids, C16-18 (even numbered), mono, di and triesters with sucrose and Sucrose laurate was applied. Infact, both substances were tested for in vitro mammalian cell gene mutation according to OECD 490; results of both read-across substances were negative.
Similarly, in the absence of in vivo genotoxicity data, read-across from the analogue substance Fatty acids, C16-18 (even numbered), mono, di and triesters with sucrose was applied. In fact, Fatty acids, C16-18 (even numbered), mono, di and triesters with sucrose was tested negative in the in vivo MNT according to OECD 474.
Based on the available data and following the analogue approach, Fatty acids, C16-18 (even numbered), mono and diesters with sucrose is not expected to be mutagenic and/or clastogenic.
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". Since the analogue concept is applied to Fatty acids C16 -18 (even numbered), mono and diesters with sucrose (no CAS), data will be generated from data available for reference source substance(s) to avoid unnecessary 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, the available data on genetic toxicity 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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