Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 211-750-5 | CAS number: 693-36-7
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 16-Feb-2022 to 24-May-2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 022
- Report date:
- 2022
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)
- Version / remarks:
- 29 July 2016
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian cell gene mutation tests using the thymidine kinase gene
Test material
- Reference substance name:
- Dioctadecyl 3,3'-thiodipropionate
- EC Number:
- 211-750-5
- EC Name:
- Dioctadecyl 3,3'-thiodipropionate
- Cas Number:
- 693-36-7
- Molecular formula:
- C42H82O4S
- IUPAC Name:
- dioctadecyl 3,3'-thiodipropionate
- Test material form:
- solid: flakes
Constituent 1
Method
- Target gene:
- thymidine kinase (TK) locus
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- CELLS USED
- Type and source of cells: L5178Y/TK+/--3.7.2C mouse lymphoma cells obtained from American Type Culture Collection (ATCC, Manassas, USA) in 2011
- Suitability of cells: Recommended test system in international guidelines (e.g. OECD)
- Normal cell cycle time (negative control): n.a.
For cell lines:
- Absence of Mycoplasma contamination: yes
- Number of passages if applicable: -
- Methods for maintenance in cell culture: Cell density was kept below 1x10^6 cells/mL.
- Cell cycle length, doubling time or proliferation index: -
- Modal number of chromosomes: -
- Periodically checked for karyotype stability: -
- Periodically ‘cleansed’ of spontaneous mutants: yes
MEDIA USED
- Type and composition of media, CO2 concentration, humidity level, temperature, if applicable:
Basic medium was made of RPMI 1640 HEPES buffered medium or RPMI 1640 HEPES buffered medium containing penicillin/streptomycin (50 U/mL and 50 μg/mL, respectively), 1 mM sodium pyruvate and 2 mM L-glutamin. Growth medium consisted of basic medium, supplemented with 10% (v/v) heat-inactivated horse serum.
Environmental conditions: All incubations were carried out in a humid atmosphere (80 - 100%, actual range 31.5 - 103.0%, lowest and highest mean values ranging from 84.8% to 99.0%) containing 5.0 ± 0.5% CO2 in air in the dark at 37.0 ± 1.0°C (actual range 34.1 - 37.6°C, lowest and highest mean values ranging from 34.5°C to 37.4°C). Temperature and humidity were continuously monitored throughout the experiment. The CO2 percentage was monitored once on each working day. Temporary deviations from the temperature, humidity and CO2 percentage may occur due to opening and closing of the incubator door. Any variation to these conditions were evaluated.
- Cytokinesis block (if used):
- -
- Metabolic activation:
- with and without
- Metabolic activation system:
- Type and composition of metabolic activation system:
- source of S9: Rat liver microsomal enzymes (S9 homogenate) were obtained from Trinova Biochem GmbH, Giessen, Germany and was prepared from male Sprague Dawley rats that have been dosed orally with a suspension of phenobarbital (80 mg/kg body weight) and ß-naphthoflavone (100 mg/kg body weight).
- method of preparation of S9 mix: S9-mix was prepared immediately before use and kept refrigerated. S9-mix components contained per mL physiological saline: 1.63 mg MgCl2x6H2O; 2.46 mg KCl; 1.7 mg glucose-6-phosphate; 3.4 mg NADP; 4 μmol HEPES. The solution was filter-sterilized (0.22 μm). To 0.5 mL S9-mix components 0.5 mL S9-fraction was added (50% (v/v) S9-fraction) to complete the S9-mix.
- concentration or volume of S9 mix and S9 in the final culture medium: 4% (v/v)
- quality controls of S9 (e.g., enzymatic activity, sterility, metabolic capability): - - Test concentrations with justification for top dose:
- First mutagenicity test:
A dose-range finding test with concentration levels between 16-250 µg/ml was performed. Since the test material was only soluble in THF at 100 mg/mL, this resulted in a maximum feasible concentration of 250 μg/mL in the exposure medium. After 3 and 24 hours, the test material precipitated in the exposure medium at concentrations of 16 μg/mL and above. Both in the absence and presence of S9-mix, no toxicity in the relative suspension growth was observed up to and including the highest test material concentration of 250 μg/mL compared to the solvent control after 3 hours of treatment with 24 and 48 hours of subculture. No toxicity in the relative suspension growth was observed up to test material concentrations of 125 μg/mL compared to the solvent control after 24 hours of treatment with 24 hours of subculture in the absence of S9 mix.
Mutagenicity Test:
Based on the dose-range finding test, the following concentration levels were used.
First mutagenicity test and 1st repeat test: 0.05. 0.1, 0.2, 0.5, 1, 2, 4, 8, 16 and 32 μg/mL with and without S9-mix
Since no precipitation and no toxicity at any of the concentrations were observed, the following concentration levels were used.
2nd repeat test: 0.08, 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, 25, 50 and 100 μg/mL with and without S9-mix
Second mutagenicity test:
Based on the results of the dose-range finding test and experiment 1, the following concentration levels were selected for the second mutagenicity testing.
Second mutagenicity test: 0.15, 0.3, 0.6, 1.3, 2.5, 5, 10, 20, 50 and 100 μg/mL exposure medium without S9 mix
Since the acceptability criteria for the solvent controls were not met, the following concentration levels were used in the repeat experiment.
1st repeat test: 0.15, 0.3, 0.6, 1.3, 2.5, 5, 10, 20, 50 and 100 μg/mL exposure medium - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: tetrahydrofuran (THF)
- Justification for choice of solvent/vehicle: A solubility test was performed based on visual assessment. The test material formed a clear colourless solution in THF.
- Justification for percentage of solvent in the final culture medium: 0.25% (v/v)
Controls
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- methylmethanesulfonate
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: test item and positive control were tested in single, solvent was tested in duplicate
- Number of independent experiments: 2
METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding (if applicable): per culture 8 x 10^6 cells (10^6 cells/mL for 3- hour treatment) or 6 x 10^6 cells (1.25 x 10^5 cells/mL for 24- hour treatment) were used
- Test substance added in medium
TREATMENT AND HARVEST SCHEDULE:
- Exposure duration/duration of treatment: test item was tested in the presence of S9-mix with a 3- hour treatment period and in the absence of S9-mix with 3- and 24- hour treatment periods
- Harvest time after the end of treatment (sampling/recovery times): cells were cultured for 2 days after the treatment period (during this culture period at least 4 x 10^6 cells (where possible) were subcultured every day in order to maintain log phase growth)
FOR GENE MUTATION:
- Expression time (cells in growth medium between treatment and selection): 2 days
- Selection time (if incubation with a selective agent): selection using trifluorothymidine (TFT; 5 µg/mL), incubated for 11 or 12 days
- Fixation time (start of exposure up to fixation or harvest of cells): none, but staining with MTT for 1.5-2 hours
- Method used: microwell plates
- Number of cells seeded and method to enumerate numbers of viable and mutants cells: For determination of the cloning efficacy at day2 (CEday2), the cell suspensions were diluted and seeded in wells of a 96-well dish. One cell was added per well (2 x 96-well microtiter plates/concentration) in non-selective medium.
- For determination of the mutant frequency (MF) a total number of 9.6 x 10^5 cells per concentration were plated in five 96-well microtiter plates, each well containing 2000 cells in selective medium (TFT-selection), with the exception of the positive control groups where a total number of 9.6 x 10^5 cells/concentration were plated in ten 96-well microtiter plates, each well containing 1000 cells in selective medium (TFT-selection).
The plates for the CEday2 and MF were incubated for 11 or 12 days. After the incubation period, the plates for the TFT-selection were stained for 1.5-2 hours by adding MTT to aid distinguishing between small and large colonies. The plates were scored with the naked eye or with the microscope.
- Criteria for small (slow growing) and large (fast growing) colonies: The small colonies are morphologically dense colonies with a sharp contour and with a diameter less than a quarter of a well. The large colonies are morphologically less dense colonies with a hazy contour and with a diameter larger than a quarter of a well. A well containing more than one small colony is classified as one small colony. A well containing more than one large colony is classified as one large colony. A well containing one small and one large colony is classified as one large colony.
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method:
The suspension growth (SG) for the 3- hour treatment = [Day 1 cell count/1.6 x 10^5] x [Day 2 cell count/1.25 x 10^5]
The suspension growth (SG) for the 24- hour treatment = [Day 0 cell count/1.25 x 10^5] x [Day 1 cell count/1.25 x 10^5] x [Day 2 cell count/1.25 x 10^5]
Relative Suspension Growth (RSG) = SG (test) / SG (controls) x 100
The cloning efficiency was determined by dividing the number of empty wells by the total number of wells. The value obtained is the P(0), the zero term of the Poisson distribution:
P(0) = number of empty wells/total number of wells
The cloning efficiency (CE) was then calculated as follows:
CE = -ln P(0)/number of cells plated per well
The relative cloning efficiency (RCE) at the time of mutant selection = CE (test) / CE (controls) x 100
The Relative Total Growth (RTG) was also calculated as the product of the cumulative relative suspension growth (RSG) and the relative survival for each culture:
RTG = RSG x RCE/100
METHODS FOR MEASUREMENTS OF GENOTOXICIY
The mutant frequency was expressed as the number of mutants per 10^6 viable cells. The plating efficiencies of both mutant and viable cells (CEday2) in the same culture were determined and the mutant frequency (MF) was calculated as follows:
MF = {-ln P(0)/number of cells plated per well}/ CEday2 x 10^6
Small and large colony mutation frequencies were calculated in an identical manner. - Evaluation criteria:
- Evaluation criteria:
The global evaluation factor (GEF) has been defined by the IWGT as the mean of the negative/solvent mutation frequency (MF) distribution plus one standard deviation. For the micro well version of the assay the GEF is 126 x 10^-6.
A test material is considered positive in the mutation assay if it induces a MF of more than MF(controls) + 126 in a dose-dependent manner. An observed increase should be biologically relevant and will be compared with the historical control data range.
A test material is considered equivocal in the mutation assay if no clear conclusion for positive or negative result can be made after an additional confirmation study.
A test material is considered negative (not mutagenic) in the mutation assay if none of the tested concentrations reaches a mutant frequency of MF(controls) + 126.
Acceptability criteria:
A mutation assay was considered acceptable if it met the following criteria:
a) The absolute cloning efficiency of the solvent controls (CEday2) is between 65 and 120% in order to have an acceptable number of surviving cells analyzed for expression of the TK mutation.
b) The spontaneous mutant frequency in the solvent control is ≥ 50 per 10^6 survivors and ≤ 170 per 10^6 survivors.
c) The suspension growth (SG) over the 2-day expression period for the solvent controls should be between 8 and 32 for the 3-hour treatment, and between 32 and 180 for the 24-hour treatment.
d) The positive control should demonstrate an absolute increase in the total mutant frequency, that is, an increase above the spontaneous background MF (an induced MF (IMF)) of at least 300 x 10^-6. At least 40% of the IMF should be reflected in the small colony MF. And/or, the positive control has an increase in the small colony MF of at least 150 x 10^-6 above that seen in the concurrent solvent control (a small colony IMF of 150 x 10^-6). - Statistics:
- not applicable
Results and discussion
Test results
- 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:
- not applicable
- True negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- Additional info on results
TEST-SPECIFIC CONFOUNDING FACTORS
The pH and osmolarity of the culture medium containing the highest tested concentration (if not precipitating) will be recorded as part of the solubility test or as part of this study.
- Data on pH: no effect (pH 7.2 at 16 µg/ml test substance vs. pH 7.2 in control)
- Data on osmolality: no effect (0.327 Osm/kg test substance vs. 0.328 Osm/kg in control)
- Possibility of evaporation from medium: not expected based on vapor pressure of the material
- Water solubility: The test item was dissolved in tetrahydrofuran. The highest concentration (250 µg/mL) in the mutagenicity test was determined based on the solubility of the test material in the culture medium.
- Precipitation and time of the determination: In the dose range finding test, the test material precipitated in the exposure medium at concentrations of 16 μg/mL and above after 3 and 24 hours. In the first mutagenicity test with 3 hours of treatment, precipitation was observed at and above 2.5 μg/mL. In the second mutagenicity test with 24 hours of treatment, precipitation was observed at and above 20 μg/mL.
- Definition of acceptable cells for analysis: -
- Other confounding effects: -
RANGE-FINDING/SCREENING STUDIES (if applicable):
Cells were treated with a test material concentration range of 16 to 250 μg/mL in the absence of S9-mix with 3- and 24- hour treatment periods and in the presence of S9-mix with a 3- hour treatment period. After 3 and 24 hours, the test material precipitated in the exposure medium at concentrations of 16 μg/mL and above. The pH and osmolarity at a concentration of 16 μg/mL were 7.2 and 0.327 Osm/kg respectively (compared to 7.2 and 0.328 Osm/kg in the solvent control). As this concentration (the lowest tested) showed already precipitation but showed no significant difference when compared to the vehicle control, pH and osmolarity were considered sufficiently investigated in the presence of precipitation.
Both in the absence and presence of S9-mix, no toxicity in the relative suspension growth was observed up to and including the highest test material concentration of 250 μg/mL compared to the solvent control after 3 hours of treatment and 24 and/or 48 hours of subculture.
No toxicity in the relative suspension growth was observed up to test material concentrations of 125 μg/mL compared to the solvent control after 24 hours of treatment and 24 hours of subculture.
Results are detailed in Table 1 and 2 in the section “Any other information on results incl. tables”
STUDY RESULTS
The mutant frequency found in the solvent control cultures was within the acceptability criteria of this assay and within the 95% control limits of the distribution of the historical negative control database.
Positive control chemicals, methyl methanesulfonate and cyclophosphamide, both produced significant increases in the mutant frequency. In addition, the mutant frequency found in the positive control cultures was within the 95% control limits of the distribution of the historical positive control database. It was therefore concluded that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly.
- Results from cytotoxicity measurements:
In Experiment 1 using 3 hours of treatment with/without S9 mix, there were no signs of toxicity up to the highest concentration tested. Precipitation was observed at and above 2.5 μg/mL.
In Experiment 2 using 24 hours of treatment without S9 mix, there were no signs of toxicity up to the highest concentration tested. Precipitation was observed at and above 20 μg/mL.
- Genotoxicity results:
Both in the First and in the Second Mutagenicity Test, no biologically relevant increase in the mutant frequency at the TK locus was observed after treatment with the test material either in the absence or in the presence of S9-mix. The numbers of small and large colonies in the test material treated cultures were comparable to the numbers of small and large colonies of the solvent controls.
The results of the First and Second Mutagenicity Test are detailed in Table 3 and 4 in the section “Any other information on results incl. tables”.
HISTORICAL CONTROL DATA: results were compare the available historical control data; please see table 5 and 6 in the section “Any other information on results incl. tables” - Remarks on result:
- other: no mutagenic potential with and without metabolic activation
Any other information on results incl. tables
Table 1: Dose-range Finding Test: Cytotoxicity (3 Hour Treatment)
dose (μg/mL) | cell count after 24 hours of subculture (10^5 cells/mL) | cell count after 48 hours of subculture (10^5 cells/mL) | SG | RSG (%) |
without metabolic acitvation | ||||
SC | 3.0 | 5.2 | 8 | 100 |
16 (1) | 4.6 | 5.4 | 12 | 159 |
31 (1) | 4.3 | 5.6 | 12 | 154 |
63 (1) | 3.9 | 5.5 | 11 | 138 |
125 (1) | 3.3 | 6.1 | 10 | 129 |
250 (1) | 4.9 | 5.8 | 14 | 182 |
with metabolic activation | ||||
SC | 2.1 | 4.6 | 5 | 100 |
16 (1) | 2.2 | 6.4 | 7 | 146 |
31 (1) | 2.5 | 5.4 | 7 | 140 |
63 (1) | 2.4 | 5.2 | 6 | 129 |
125 (1) | 3.3 | 5.0 | 8 | 171 |
250 (1) | 3.8 | 5.0 | 10 | 197 |
All calculations were made without rounding off.
SC = solvent control = THF
SG = suspension growth
RSG = relative suspension growth
(1) = the test material precipitated in the exposure medium
SG = Suspension growth = [Cell count after 24 hour of subculture (Day 1) /1.6 x 10^5] x [Cell count after 48 hours of subculture (Day 2) /1.25 x 10^5]
RSG = [SG(test)/SG(control)] x 100
Table 2: Dose-range Finding Test: Cytotoxicity (24 Hour Treatment)
dose (μg/mL) | cell count after 24 hours of subculture (10^5 cells/mL) | cell count after 48 hours of subculture (10^5 cells/mL) | SG | RSG (%) |
without metabolic acitvation | ||||
SC | 10.8 | 4.7 | 32 | 100 |
16 (1) | 10.4 | 3.8 | 25 | 78 |
31 (1) | 10.7 | 4.7 | 32 | 99 |
63 (1) | 10.1 | 4.3 | 28 | 86 |
125 (1) | 10.8 | 4.7 | 32 | 100 |
250 (1) | 0.0 (2) | 0.0 | 0 | 0 |
All calculations were made without rounding off.
SC = solvent control = THF
SG = suspension growth
RSG = relative suspension growth
(1) = the test material precipitated in the exposure medium
(2) = no subculture performed (less than 1.25 x 10^5 cells/mL)
SG = Suspension growth = [Cell count after 24 hour of subculture (Day 1) /1.6 x 10^5] x [Cell count after 48 hours of subculture (Day 2) /1.25 x 10^5]
RSG = [SG(test)/SG(control)] x 100
Table 3: Experiment 1: Cytotoxic and Mutagenic Response in the Mouse Lymphoma L5178Y Test System
dose (μg/mL) | RSG (%) | CE day2 (%) | RCE (%) | RTG (%) | mutant frequency per 10^6 survivors | ||
total | ( small | large ) | |||||
without metabolic activation | |||||||
3 hour treatment | |||||||
SC | 100 | 97 | 100 | 100 | 72 | ( 30 | 39 ) |
SC | 83 | 68 | ( 18 | 49 ) | |||
0.08 | 103 | 93 | 103 | 106 | 67 | ( 35 | 30 ) |
0.16 | 103 | 97 | 108 | 111 | 73 | ( 22 | 49 ) |
0.31 | 116 | 98 | 109 | 127 | 72 | ( 30 | 40 ) |
0.63 | 111 | 97 | 108 | 120 | 72 | ( 37 | 32 ) |
1.25 | 101 | 102 | 114 | 115 | 57 | ( 17 | 39 ) |
2.5 (1) | 108 | 77 | 86 | 93 | 95 | ( 36 | 55 ) |
MMS | 77 | 60 | 67 | 52 | 701 | ( 204 | 431 ) |
with metabolic activation | |||||||
3 hour treatment | |||||||
SC | 100 | 86 | 100 | 100 | 64 | ( 23 | 39 ) |
SC | 94 | 68 | ( 23 | 44 ) | |||
0.08 | 78 | 80 | 89 | 70 | 68 | ( 31 | 36 ) |
0.16 | 91 | 84 | 93 | 84 | 64 | ( 37 | 25 ) |
0.31 | 76 | 95 | 106 | 81 | 50 | ( 10 | 40 ) |
0.63 | 96 | 83 | 92 | 88 | 72 | ( 21 | 50 ) |
1.25 | 94 | 81 | 90 | 85 | 73 | ( 30 | 41 ) |
2.5 (1) | 94 | 76 | 84 | 79 | 65 | ( 28 | 35 ) |
CP | 28 | 75 | 83 | 23 | 334 | ( 123 | 192 ) |
Note: all calculations were made without rounding off
RSG = Relative Suspension Growth; CE = Cloning Efficiency; RCE = Relative Cloning Efficiency; RTG = Relative Total Growth; SC = Solvent control = THF; MMS = Methylmethanesulfonate; CP = Cyclophosphamide
(1) = the test item precipitated in the exposure medium
Table 4: Experiment 2: Cytotoxic and Mutagenic Response in the Mouse Lymphoma L5178Y Test System
dose (μg/mL) | RSG (%) | CE day2 (%) | RCE (%) | RTG (%) | mutant frequency per 10^6 survivors | ||
total | ( small | large ) | |||||
without metabolic activation | |||||||
24 hour treatment | |||||||
SC | 100 | 90 | 100 | 100 | 131 | ( 24 | 103 ) |
SC | 104 | 83 | ( 13 | 68 ) | |||
0.15 | 91 | 98 | 101 | 93 | 71 | ( 22 | 47 ) |
0.3 | 121 | 99 | 103 | 124 | 102 | ( 30 | 67 ) |
0.6 | 117 | 91 | 94 | 110 | 98 | ( 35 | 59 ) |
1.3 | 103 | 145 | 150 | 155 | 73 | ( 15 | 55 ) |
2.5 | 120 | 110 | 113 | 136 | 88 | ( 11 | 75 ) |
5 | 103 | 94 | 97 | 99 | 90 | ( 20 | 67 ) |
10 | 108 | 90 | 93 | 100 | 120 | ( 31 | 83 ) |
20 (1) | 130 | 107 | 110 | 143 | 111 | ( 21 | 85 ) |
MMS | 107 | 88 | 90 | 96 | 465 | ( 79 | 356 ) |
Note: all calculations were made without rounding off
RSG = Relative Suspension Growth; CE = Cloning Efficiency; RCE = Relative Cloning Efficiency; RTG = Relative Total Growth; SC = Solvent control = THF; MMS = Methylmethanesulfonate; CP = Cyclophosphamide
(1) = the test item precipitated in the exposure medium
Table 5: Historical Control Data of the Spontaneous Mutant Frequencies of the Solvent Controls for the Mouse Lymphoma Assay
Mutant frequency per 10^6 survivors | |||
-S9 mix | + S9 mix | ||
3-hour treatment | 24-hour treatment | 3-hour treatment | |
Mean | 101 | 98 | 101 |
SD | 28 | 25 | 28 |
n | 82 | 77 | 82 |
Lower Control Limit (95% Control Limits) | 46 | 48 | 47 |
Upper Control Limit (95% Control Limits) | 156 | 148 | 156 |
SD = Standard deviation
n = Number of observations
Distribution historical negative control data from experiments performed between December 2018 and December 2021.
Table 6: Historical Control Data of the Mutant Frequencies of the Positive Controls for the Mouse Lymphoma Assay
Mutant frequency per 10^6 survivors | |||
-S9 mix | + S9 mix | ||
3-hour treatment | 24-hour treatment | 3-hour treatment | |
Mean | 1021 | 795 | 1425 |
SD | 405 | 235 | 740 |
n | 79 | 78 | 80 |
Lower Control Limit (95% Control Limits) | 227 | 334 | -25 |
Upper Control Limit (95% Control Limits) | 1816 | 1255 | 2876 |
SD = Standard deviation
n = Number of observations
Distribution historical negative control data from experiments performed between December 2018 and December 2021.
Applicant's summary and conclusion
- Conclusions:
- In conclusion, the test stubstance is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions chosen.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.