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EC number: 204-653-4 | CAS number: 123-81-9
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
GDMA is considered non-genotoxic in vitro based on experimental results as well as read-across from NaTG.
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Justification for type of information:
- This scenario covers the analogue approach for which the read-across hypothesis is based on (bio) transformation to common compound(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst-case approach
The hypothesis corresponds to Scenario 1 of the RAAF. The source substance NaTG will be used to read-across two endpoints, e.g. repeated dose toxicity and toxicity to reproduction, of the target substance GDMA. Source and target substance are expected to share common metabolites. GDMA is rapidly hydrolysed after absorption into TGA and ethylene glycol, while NaTG will dissociate into TGA and sodium ion. By now, no experimental toxicokinetic data is available for GDMA. Therefore, simulated gastric acid hydrolysis as well as in vitro metabolic studies are planned to strengthen the hypothesis.
For detailed information, please refer to section 13.2. - Reason / purpose for cross-reference:
- read-across: supporting information
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: With S9 : 1000 µg/ml. Without S9 : 300 µg/ml
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Conclusions:
- Based on the read-across hypothesis, GDMA is expected to show similar effects as TGA. Therefore, GDMA is considered not to induce chromosomal abberation.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From May 23, 2022 to July 05, 2022
- Reliability:
- 1 (reliable without restriction)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test using the Hprt and xprt genes)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian cell gene mutation test using the Hprt and xprt genes
- Target gene:
- Hprt gene
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Remarks:
- CHO-K1
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- -tested up to the precipitation-free concentration (500 µg/mL) without and with metabolic activation system over a 5-hour treatment period:
+/-S9-mix: 62.5, 125, 250, 500 and 1000* µg/mL (*: precipitation was observed) - Vehicle / solvent:
- -Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle:
This solvent is compatible with the survival of the V79 cells and the S9 activity and was chosen based on the results of the preliminary solubility test, and its suitability was confirmed with the available laboratory’s historical database. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS: 2
DURATION:
- Exposure duration: 5-hour treatment
- Phenotypic expression time: 8 days
- Mutant selection time (selection medium): 8 days
SELECTION MEDIUM: (F12*-SEL) for 6-TG resistant mutants contained 3.4 µg/mL 6-thioguanine (6-TG) (EX-CELL® CD CHO Serum-Free Medium for CHO Cells-SEL)
METHODS FOR MEASUREMENT OF CYTOTOXICITY
Cytotoxicity was determined by relative survival (RS), where the cloning efficiency (CE) of cells plated immediately after treatment adjusted by any loss of cells during treatment as compared with adjusted cloning efficiency in negative controls (assigned a survival of 100%). - Evaluation criteria:
- Evaluation of Results:
Providing that all acceptability criteria are fulfilled, a test item is considered to be clearly positive if, in any of the experimental conditions examined:
• at least one of the test concentrations exhibits a statistically significant increase compared with the concurrent negative control,
• any of the results are outside the distribution of the laboratory historical negative control data (based 95% control limit),
• the increase of mutant frequency is concentration-related when evaluated with an appropriate trend test.
Providing that all acceptability criteria are fulfilled, a test item is considered clearly negative if, in all experimental conditions examined:
• none of the test concentrations exhibits a statistically significant increase compared with the concurrent negative control,
• there is no concentration-related increase when evaluated with an appropriate trend test, all results are inside the distribution of the historical negative control data (based 95% control limit - Statistics:
- -Linear trend analysis in mutant frequency
-Bartlett's homogeneity of variance test for variance between groups
-Duncan's Multiple Range test for intergroup-differences
-Kolmogorov-Smirnov test when significant heterogenety was found
-Kruskal-Wallis one-way analysis of variance in case of a none-normal distribution
-Mann-Whitney U-test if positive result was found - Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Remarks:
- concentration of 62.5, 125, 250, 500 and 1000*µg/mL (*precipitation was observed)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
-No biologically relevant changes in osmolality of the test system were noted at the different dose levels tested.
-The pH values showed a slight dose-dependent decrease. These changes were in the physiological range.
HISTORICAL CONTROL DATA:
- Positive historical control data:
The concurrent positive controls Ethyl methanesulfonate (1.0 µL/mL) and 7, 12-Dimethyl benz[a]anthracene (20 µg/mL) caused the expected biologically relevant increase of cells with mutation frequency as compared to solvent controls and were compatible with the historical positive control data.
- Negative (solvent/vehicle) historical control data:
The mutation frequency found in the negative controls (-S9: 5.94-6.00 and +S9: 6.00-6.93) were within the 95% control limits of historical laboratory control data (-S9: 5.77–8.15 and +S9: 5.73-8.54). - Conclusions:
- Under the applied test conditions, GDMA was not mutagenic to Chinese hamster ovary cells. The conclusion for gene mutation in mammalian cells is negative.
- Executive summary:
In conclusion, GDMA tested up to the precipitation-free concentration (500 µg/mL) without and with metabolic activation system over a 5-hour treatment period did not induce statistically and biologically significant increases in mutant frequency compared to the solvent control. All values were within the range of the laboratory historical control data and no dose-response relationships were noted.
Thus, it is concluded that the test item, GDMA, was not mutagenic in this In Vitro Mammalian Cell Gene Mutation Test performed with Chinese hamster ovary cells.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 05.10.2021 - 05.11.2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix
- Test concentrations with justification for top dose:
- Incorporation method:
- 1. experiment: 5, 1.5, 0.5, 0.15 and 0.05 µL/plate
- 2. experiment: 5, 3.3, 2.2, 1.5, 1.0, 0.7 µL/plate
Pre-incubation method
5, 1.67, 0.56, 0.19, 0.06, 0.021 µL/plate
5µL was chosen as the maximum recommended concentration according to the guideline - Vehicle / solvent:
- DMSO
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- benzo(a)pyrene
- mitomycin C
- other: 2-amino anthracene and 4-Nitro-1,2-phenylene diamine
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration (single, duplicate, triplicate): triplicate
- Number of independent experiments: 3
METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding (if applicable): 10^9 cells/mL
- Test substance added in agar (plate incorporation); preincubation; in suspension;
TREATMENT AND HARVEST SCHEDULE:
- Preincubation period, if applicable: 20min for pre-incubation method
- Exposure duration/duration of treatment: 48h
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method, e.g.: background growth inhibition;
METHODS FOR MEASUREMENTS OF GENOTOXICIY
- number of revertant colonies - Rationale for test conditions:
- - precipitation: No precipitation was found up to the highest test substance concentration
- Cytotoxicity: ≥1 µl/plate (plate incorporation method) and ≥ 1.67 µl/plate (pre-incubation method)
- concentration selection for the 2. plate incorporation method: concentrations of 3.3, 2.2, 1.5µl/plate were chosen to exclude possible mutagenicity in the upper concentration range - Evaluation criteria:
- Five different analysable concentrations were used for the evaluation of the mutagenic potential of the test item.
A result is considered as clearly positive if all following criteria are fulfilled:
• A concentration-related increase, in revertants
• a clear biologically relevant increase in at least one concentration compared to the concurrent solvent control
• at least one concentration with an increase above the distribution of historical solvent control data (mean ± 3 SD).
A biologically relevant increase is described as follows:
• if in the bacteria strains TA98, TA100, TA102 the number of revertants is at least twice as high than the reversion rate of the negative controls (increase factor of at least 2.0)
• if in the bacteria strains TA1535 and TA1537 the number of revertants is at least three times higher than the reversion rate of the negative controls (increase factor of at least 3.0).
A test result is considered as clearly negative, if it does not meet the criteria above. - Statistics:
- The mean values and standard deviations of each threefold determination were calculated as well as the increase factor of revertant induction (mean revertants divided by mean spontaneous revertants) of the test item solutions and the positive controls. Additionally, the absolute number of revertants (mean revertants minus mean spontaneous revertants) is given.
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle 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
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle 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
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Based on the results of this study it is concluded that Thiocure® 120 is not mutagenic in the Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 in the presence and absence of metabolic activation under the experimental conditions in this study.
- Executive summary:
This study was performed in order to evaluate the mutagenic potential of Thiocure® 120 in the Bacterial Reverse Mutation Test using five strains of Salmonella typhimurium (TA98, TA100, TA102, TA1535 and TA1537) based on the most recent Guidelines OECD 471 (2020) and EU Method B.13/14 (2008). The test substance was tested with concentrations of 5, 1.5, 0.5, 0.15, 0.05 µL/plate and 5, 3.3, 2.2, 1.5, 1.0, 0.7 µL/plate in two independent experiments using plate incorporation method as well as 5, 1.67, 0.56, 0.19, 0.06, 0.021 µL/plate in one experiment using the pre-incubation method. No precipitation was observed, however, the substance showed cytotoxicity at concentrations ≥ 1µl/plate. After 48h of exposure no significant increase in the number of revertant colonies could be observed. Therefore it is concluded, that Thiocure® 120 is not mutagenic in bacteria.
Referenceopen allclose all
Main Mutation Assay
Day 1 and Day 8 cloning efficiencies:
In the absence and in the presence of metabolic activation, at concentrations of 62.5, 125, 250 and 500 µg/mL a minimal cytotoxic effect (2 and 9%) were observed. At concentration of 1000 µg/mL precipitation was observed, confirming the response seen in the preliminary cytotoxicity assays.
The Day 8 cloning efficiency data indicate that at concentrations of 62.5, 125, 250,
500 µg/mL the cells had recovered during the expression period. The observed cloning
efficiency was in the range of 99-101%.
The mutation data:
There were no biologically or statistically significant increases in mutation frequency at any concentration tested, either in the absence or in the presence of metabolic activation. There were no significant differences between treatment and control groups and no dose-response relationships were noted. All values were within the range of the laboratory historical negative control data and no dose-related increase was observed in any of the cultures. The sensitivity of the tests and the efficacy of the S9 mix were demonstrated by large and statistically significant (p < 0.01) increases in mutation frequency in the positive control cultures with Ethyl methanesulfonate (1.0 µL/mL) and 7,12-Dimethyl benz[a]anthracene (20 µg/mL). The mutation frequencies of the positive control cultures were consistent with the historical control data.
The mutation frequency found in the negative controls (-S9:5.94-6.00 and + S9:6.00-6.93) were within the 95% control limits of historical laboratory control data (-S9:5.77 – 8.15 and + S9:5.73 - 8.54). No biologically relevant changes in osmolality of the test system were noted at the different dose levels tested. The pH values showed a slight dose-dependent decrease. These changes were in the physiological range.
TABLE 2: CHO/HPRT MUTAGENESIS ASSAY RESULTS MAIN MUTATION ASSAY/a, and b (5-HOUR TREATMENT WITHOUT S9-MIX) Replicate 1
TEST CONDITION | SURVIVAL TO TREATMENT | Relative- Population Growth (%) of Control | MUTANT COLONIES DISH NUMBER | TOTAL MUTANT COLONIES | CE | Absolute CE % | MUTANT FREQ. X 10-6 | |||||||
Mean Colony Number | CE | Adjusted CE | RS % | 1 | 2 | 3 | 4 | 5 | ||||||
Solvent control a | 203.7 | 1.02 | 0.98 | 100 | 100 | 1 | 1 | 1 | 1 | 2 | 6 | 1.00 | 100 | 6.00 |
Pos. control (EMS 1.0 µL/mL) a | 49.0 | 0.25 | 0.22 | 23 | 62 | 190 | 205 | 187 | 193 | 201 | 976 | 0.63 | 63 | 1549.21** |
TEST ITEM |
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62.5 µg/mL a | 202.7 | 1.01 | 0.93 | 95 | 100 | 2 | 2 | 2 | 0 | 0 | 6 | 1.00 | 100 | 6.00 |
125 µg/mL a | 201.7 | 1.01 | 0.89 | 91 | 101 | 1 | 1 | 0 | 3 | 0 | 5 | 1.01 | 101 | 4.95 |
250 µg/mL a | 201.3 | 1.01 | 0.91 | 93 | 99 | 1 | 1 | 0 | 1 | 3 | 6 | 1.00 | 100 | 6.00 |
500 µg/mL a | 203.3 | 1.02 | 0.90 | 92 | 100 | 1 | 0 | 0 | 1 | 4 | 6 | 1.01 | 101 | 5.94 |
1000 µg/mL a* | 190.7 | 0.95 | 0.84 | 86 | 98 | 1 | 0 | 2 | 0 | 3 | 6 | 0.98 | 98 | 6.12 |
Results
Plate incorporation method - 1. experiment
Strain | TA98 | TA100 | TA102 | TA1535 | TA1537 | ||||||
Induction | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | |
Demin. water | Mean | 15 | 17 | 64 | 63 | 168 | 149 | 7 | 7 | 5 | 5 |
sd | 2.3 | 1.0 | 4.4 | 1.5 | 6.9 | 12.2 | 0.0 | 1.2 | 1.2 | 1.0 | |
DMSO | Mean | 14 | 16 | 60 | 59 | 167 | 167 | 7 | 7 | 4 | 4 |
sd | 1.5 | 1.0 | 1.0 | 3.2 | 10.1 | 10.1 | 0.6 | 1.2 | 1.2 | 1.0 | |
Positive | Mean | 515 | 148 | 595 | 1480 | 653 | 885 | 408 | 119 | 113 | 124 |
sd | 39.5 | 27.7 | 25.7 | 21.2 | 48.2 | 44.1 | 13.9 | 4.6 | 4.6 | 8.0 | |
f(I) | 36.79 | 9.25 | 9.30 | 25.08 | 3.89 | 5.30 | 58.29 | 17.00 | 28.25 | 31.00 | |
5 µL/plate | Mean | 0 | 4 | 0 | 0 | 0 | 26 | 0 | 1 | 0 | 0 |
sd | 0.0 | 1.5 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.6 | 0.0 | 0.6 | |
f(I) | 0.00 | 0.25 | 0.00 | 0.00 | 0.00 | 0.16 | 0.00 | 0.14 | 0.00 | 0.00 | |
1.5 µL/plate | Mean | 10 | 13 | 0 | 30 | 41 | 169 | 2 | 6 | 0 | 4 |
sd | 2.0 | 1.5 | 0.0 | 1.2 | 5.0 | 10.1 | 1.0 | 1.0 | 0.0 | 1.0 | |
f(I) | 0.71 | 0.81 | 0.00 | 0.51 | 0.25 | 1.01 | 0.29 | 0.86 | 0.00 | 1.00 | |
0.5 µL/plate | Mean | 15 | 19 | 46 | 45 | 167 | 163 | 5 | 6 | 5 | 4 |
sd | 4.0 | 3.1 | 1.2 | 4.6 | 16.7 | 8.3 | 0.6 | 0.6 | 0.6 | 0.6 | |
f(I) | 1.07 | 1.19 | 0.77 | 0.76 | 1.00 | 0.98 | 0.71 | 0.86 | 1.25 | 1.00 | |
0.15 µL/plate | Mean | 17 | 24 | 60 | 46 | 172 | 159 | 6 | 5 | 4 | 5 |
sd | 1.5 | 1.5 | 2.0 | 5.5 | 4.0 | 6.1 | 1.0 | 0.6 | 0.0 | 0.6 | |
f(I) | 1.21 | 1.50 | 1.00 | 0.78 | 1.03 | 0.95 | 0.86 | 0.71 | 1.00 | 1.25 | |
0.05 µL/plate | Mean | 16 | 21 | 61 | 52 | 156 | 159 | 6 | 6 | 4 | 4 |
sd | 3.2 | 1.5 | 2.1 | 4.6 | 8.0 | 10.1 | 1.0 | 0.6 | 1.0 | 0.6 | |
f(I) | 1.14 | 1.31 | 1.02 | 0.88 | 0.93 | 0.95 | 0.86 | 0.86 | 1.00 | 1.00 |
f(I) = increase factor
bold marked values = relevant increase in the number of revertants
italic marked values = cytotoxicity
Plate incorporation method - 2. experiment
Strain | TA98 | TA100 | TA102 | TA1535 | TA1537 | ||||||
Induction | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | |
Demin. water | Mean | 11 | 16 | 60 | 62 | 161 | 140 | 7 | 7 | 4 | 5 |
sd | 1.2 | 1.0 | 4.5 | 5.5 | 8.3 | 6.9 | 1.5 | 2.1 | 1.2 | 1.5 | |
DMSO | Mean | 11 | 16 | 50 | 49 | 160 | 165 | 8 | 8 | 4 | 3 |
sd | 2.0 | 3.0 | 4.9 | 3.2 | 10.6 | 10.1 | 1.0 | 1.2 | 0.6 | 0.6 | |
Positive | Mean | 368 | 71 | 275 | 1384 | 392 | 424 | 188 | 136 | 135 | 120 |
sd | 44.5 | 8.3 | 39.5 | 112.9 | 22.3 | 25.0 | 16.0 | 10.6 | 6.1 | 10.6 | |
f(I) | 33.45 | 4.44 | 4.58 | 28.24 | 2.43 | 2.57 | 26.86 | 17.00 | 33.75 | 40.00 | |
5 µL/plate | Mean | 0 | 0 | 0 | 0 | 0 | 40 | 0 | 0 | 0 | 0 |
sd | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.5 | 0.0 | 0.0 | 0.0 | 0.0 | |
f(I) | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.24 | 0.00 | 0.00 | 0.00 | 0.00 | |
3.3 µL/plate | Mean | 0 | 3 | 0 | 0 | 0 | 153 | 0 | 4 | 0 | 1 |
sd | 0.0 | 1.0 | 0.0 | 0.0 | 0.0 | 9.2 | 0.0 | 1.2 | 0.0 | 0.6 | |
f(I) | 0.00 | 0.19 | 0.00 | 0.00 | 0.00 | 0.93 | 0.00 | 0.50 | 0.00 | 0.33 | |
2.2 µL/plate | Mean | 0 | 11 | 0 | 44 | 0 | 152 | 0 | 3 | 0 | 3 |
sd | 0.0 | 2.0 | 0.0 | 2.5 | 0.0 | 8.0 | 0.6 | 0.6 | 0.0 | 0.6 | |
f(I) | 0.00 | 0.69 | 0.00 | 0.90 | 0.00 | 0.92 | 0.00 | 0.38 | 0.00 | 1.00 | |
1.5 µL/plate | Mean | 1 | 10 | 0 | 42 | 168 | 151 | 2 | 3 | 0 | 5 |
sd | 1.7 | 1.5 | 0.0 | 1.2 | 16.0 | 8.3 | 0.0 | 1.5 | 0.0 | 1.5 | |
f(I) | 0.09 | 0.63 | 0.00 | 0.86 | 1.05 | 0.92 | 0.25 | 0.38 | 0.00 | 1.67 | |
1.0 µL/plate | Mean | 4 | 9 | 44 | 45 | 173 | 173 | 2 | 9 | 2 | 3 |
sd | 1.0 | 0.6 | 2.0 | 3.8 | 4.6 | 6.1 | 0.6 | 1.2 | 1.2 | 0.6 | |
f(I) | 0.36 | 0.56 | 0.88 | 0.92 | 1.08 | 1.05 | 0.25 | 1.13 | 0.50 | 1.00 | |
0.7 µL/plate | Mean | 6 | 12 | 45 | 50 | 161 | 155 | 8 | 6 | 4 | 4 |
sd | 1.2 | 1.0 | 1.7 | 5.8 | 8.3 | 16.2 | 1.5 | 1.5 | 1.2 | 0.0 | |
f(I) | 0.55 | 0.75 | 0.90 | 1.02 | 1.01 | 0.94 | 1.00 | 0.75 | 1.00 | 1.33 |
f(I) = increase factor
bold marked values = relevant increase in the number of revertants
italic marked values = cytotoxicity
Pre- incubation method
Strain | TA98 | TA100 | TA102 | TA1535 | TA1537 | ||||||
Induction | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | |
Demin. water | Mean | 11 | 14 | 53 | 52 | 153 | 147 | 8 | 7 | 4 | 5 |
sd | 2.1 | 2.1 | 4.0 | 4.0 | 4.6 | 4.6 | 1.5 | 2.1 | 1.5 | 1.0 | |
DMSO | Mean | 12 | 16 | 51 | 53 | 147 | 153 | 8 | 7 | 3 | 4 |
sd | 0.6 | 2.3 | 2.1 | 1.0 | 6.1 | 6.1 | 2.1 | 1.7 | 0.6 | 0.6 | |
Positive | Mean | 416 | 116 | 225 | 1280 | 739 | 619 | 269 | 88 | 62 | 141 |
sd | 28.8 | 18.3 | 26.0 | 76.3 | 37.8 | 28.1 | 24.4 | 6.9 | 6.0 | 18.0 | |
f(I) | 34.67 | 7.25 | 4.25 | 24.15 | 4.83 | 4.05 | 33.63 | 12.57 | 20.67 | 35.25 | |
5 µL/plate | Mean | 0 | 6 | 0 | 0 | 0 | 44 | 0 | 0 | 0 | 0 |
sd | 0.0 | 1.2 | 0.0 | 0.0 | 0.0 | 6.0 | 0.0 | 0.0 | 0.0 | 0.0 | |
f(I) | 0.00 | 0.38 | 0.00 | 0.00 | 0.00 | 0.29 | 0.00 | 0.00 | 0.00 | 0.00 | |
1.67 µL/plate | Mean | 1 | 11 | 0 | 19 | 86 | 160 | 3 | 5 | 0 | 4 |
sd | 1.2 | 1.5 | 0.0 | 6.2 | 4.0 | 6.9 | 1.2 | 2.1 | 0.0 | 0.6 | |
f(I) | 0.08 | 0.69 | 0.00 | 0.36 | 0.59 | 1.05 | 0.38 | 0.71 | 0.00 | 1.00 | |
0.56 µL/plate | Mean | 9 | 12 | 43 | 50 | 163 | 156 | 6 | 6 | 3 | 4 |
sd | 0.6 | 2.1 | 1.7 | 2.5 | 12.2 | 4.0 | 2.3 | 1.2 | 1.5 | 0.6 | |
f(I) | 0.75 | 0.75 | 0.84 | 0.94 | 1.11 | 1.02 | 0.75 | 0.86 | 1.00 | 1.00 | |
0.19 µL/plate | Mean | 12 | 15 | 52 | 50 | 144 | 152 | 5 | 6 | 3 | 5 |
sd | 1.5 | 0.6 | 3.2 | 3.5 | 4.0 | 4.0 | 0.6 | 0.6 | 0.6 | 1.5 | |
f(I) | 1.00 | 0.94 | 1.02 | 0.94 | 0.98 | 0.99 | 0.63 | 0.86 | 1.00 | 1.25 | |
0.06 µL/plate | Mean | 11 | 15 | 50 | 51 | 152 | 155 | 6 | 8 | 4 | 4 |
sd | 1.0 | 1.0 | 1.0 | 3.0 | 10.6 | 6.1 | 1.2 | 2.5 | 0.6 | 0.6 | |
f(I) | 0.92 | 0.94 | 0.98 | 0.96 | 1.03 | 1.01 | 0.75 | 1.14 | 1.33 | 1.00 | |
0.021 µL/plate | Mean | 11 | 16 | 52 | 47 | 149 | 147 | 7 | 6 | 3 | 5 |
sd | 1.5 | 2.5 | 2.5 | 3.0 | 2.3 | 8.3 | 1.5 | 0.6 | 0.6 | 1.5 | |
f(I) | 0.92 | 1.00 | 1.02 | 0.89 | 1.01 | 0.96 | 0.88 | 0.86 | 1.00 | 1.25 |
f(I) = increase factor
bold marked values = relevant increase in the number of revertants
italic marked values = cytotoxicity
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
GDMA is considered non-genotoxic in vivo based on read-across from structurally related compounds.
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
Gene mutation in bacteria:
Studies according to OECD 471 are available for target and source substance. Both substances show no potency to induce gene mutation in bacteria.
Chromosomal aberration:
An in vitro study according to EOCD 473 is available for TGA, the common metabolite of GDMA and TGA. No structural chromosome aberrations were observed in the tested cells, therefore it is concluded that TGA does not induce chromosomal aberration. Based on the read-across hypothesis, GDMA is rapidly hydrolysed to TGA and ethylene glycol. Therefore, GDMA is expected to show similar effects as TGA and can be considered as negative in chromosomal aberration assay.
Gene mutation in mammalian cells:
An in vitro study according to OECD 476 is available for GDMA and for ATG, a surrogate of NaTG, but not for NaTG itself. No potential for gene mutation in mammalian cells was observed for both substances. Same metabolism is predicted for ATG as for NaTG, however, it is not determined in this justification whether data on ATG can be used to predict toxic properties of GDMA. Therefore these data cannot be used to support the read-across hypothesis.
To support the read-across hypothesis, in vitro toxicokinetic studies (simulated gastric acid hydrolysis and in vitro metabolism using human liver microsomes) will be conducted.
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