Registration Dossier
Registration Dossier
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EC number: 701-396-4 | CAS number: -
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
- Genetic toxicity in bacteria (according to OECD 471, RL1), Ames: negative
- Genetic toxicity (cytogenicity) in mammalian cells (according to OECD 476, RL1), HPRT with RA substance: negative
- Genetic toxicity (mutagenicity) in mammalian cells (according to OECD 473, RL1), CA with RA-substance: negative
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:
- 1 Mar - 24 Mar 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 21 July 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Version / remarks:
- August 1998
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- 30 May 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- OGYÉI National Institute of Pharmacy and Nutrition, Budapest, Hungary
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature (15-25°C, below 70 RH%), protected from light and humidity - Target gene:
- his operon, tryp operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactor-supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of male rats, treated with phenobarbital and β-naphthoflavone
- Test concentrations with justification for top dose:
- Based on a range-finding study (performed in tester strains TA 98 and TA 100; doses applied 10 - 5000 µg/mL), the following concentrations were used in the main experiments:
First experiment (all strains): 5, 15.81, 50, 158.1, 500, 1581, 5000 μg/plate with and without metabolic activation (tested up to the limit concentration)
Second experiment (all strains): 1.581 5, 15.81, 50, 158.1, 500, 1581, 5000 μg/plate with and without metabolic activation (tested up to the limit concentration) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMF (N,N-Dimethylformamide)
- Justification for choice of solvent/vehicle: Due to the limited solubility of the test substance in water and DMSO, DMF was selected as the vehicle. - Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMF (test substance), DMSO or distilled water for positive control substances
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- sodium azide
- methylmethanesulfonate
- other: 4-nitro-1,2-phenylene-diamine (NPD), 2-aminoanthracene (2AA)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation) (first experiment); preincubation (second experiment)
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 ±1 h
NUMBER OF REPLICATIONS: triplicates each in two independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: revertant colony number and inspection of the bacterial background lawn ? - Evaluation criteria:
- Acceptance criteria
The study was considered valid if:
- the number of revertant colonies of the negative (solvent) and positive controls were in the historical control range in all strains of the main tests
- at least five analyzable concentrations were presented in all strains of the main tests
Evaluation criteria
When the test substance shows a biologically relevant and dose-related increase in the number of revertant colonies of more than two times (TA 98, TA 100, and WP2 uvrA) or three times (TA 1535 and TA 1537) compared to that of the solvent control, the response is judged to be positive. Additionally, the positive response should be reproducible for at least one of the dose groups and should occur in at least one strain with or without metabolic activation. A statistical method may be used as an aid in evaluating the test results but should not be the only determining factor for a positive response.
The test item was considered to have shown no mutagenic activity in this study if it produces neither a dose-related increase in the number of revertants nor a reproducible biologically relevant positive response at any of the dose groups, with or without metabolic activation. - Statistics:
- Mean values and standard deviations were calculated.
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- 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:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative 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
- Remarks:
- number of revertant colonies decreased to less than half compared to solvent control in exp. 2 at 5000 μg/ plate with S9 mix (53%)
- 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:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Precipitate/slight precipitate was detected on the plates in all examined strains with and without metabolic activation at least at the highest concentration tested - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from similar mixture/product
- Adequacy of study:
- key study
- Study period:
- 09 May 2012 - 12 Mar 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- 29 July 2016
- Deviations:
- yes
- Remarks:
- 200 metaphases scored; mitotic index used as parameter for cytotoxicity (no RPD or RICC values given), no C-charts or X-bar charts provided
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
- Version / remarks:
- 1998
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Bayrisches Landesamt für Gesundheit und Lebensmittelsicherheit, Erlangen, Germany
- Type of assay:
- other: in vitro mammalian chromosome aberration test
- Target gene:
- not applicable
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: V79 cells (ATCC, CCL-93)
- Suitability of cells: yes
- Proliferation rate: 12 - 14 h:
- Modal number of chromosomes: diploid number, 2n = 22
MEDIA USED
- Type and identity of media: MEM medium supplemented with 10% fetale bovine serum, 100 U/100 µg/mL penicilline/streptomycin solution, 2 mM L-glutamine, 2.5 µg/mL amphotericin, 25 µM HEPES. - Metabolic activation:
- with and without
- Metabolic activation system:
- Co-factor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbital/β-naphthoflavone
- Test concentrations with justification for top dose:
- Pre-experiment for Toxicity:
with and without metabolic activation: 7.8, 15.6, 31.3, 62.5, 125, 250, 500, 1000, 2500 and 5000 µg/mL
Experiment I:
4 h treatment with and without metabolic activation: 3.16, 10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/mL
Experiment II:
20 h treatment without metabolic activation: 10.0, 30.0, 100, 250, 500, 1000, 2500 and 5000 µg/mL
4 h treatment with metabolic activation: 100, 316, 1000, 3000, 4000 and 5000 µg/mL
The following concentrations were selected in the main experiments for the microscopic analyses:
Experiment I:
with and without metabolic activation: 1000, 2500 and 5000 µg/mL
Experiment II:
without metabolic activation: 500, 1000 and 5000 µg/mL
with metabolic activation: 1000, 3000 and 5000 µg/mL - Vehicle / solvent:
- No vehicle was used.
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- no
- Remarks:
- not applicable
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
- Cell density at seeding: 1E+04 - 5E+04 cells depending on preparation time
DURATION
- Exposure duration: 4 and 20 h
- Fixation time (start of exposure up to fixation or harvest of cells): 4 h treatment: 20 h; 20 h treatment: 20 h
SPINDLE INHIBITOR: 0.2 µg/mL Colcemid in medium
STAIN: Giemsa
NUMBER OF REPLICATIONS: duplicates each in 2 independent experiments
METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED:
Colcemid was added to the cultures 17.5 h after the start of each treatment. 2.5 h later, the cells were treated on the slides in the chambers with hypotonic solution (0.4% KCl) for 20 min at 37 °C. After incubation in the hypotonic solution the cells were fixed with methanol/glacial acetic acid (3:1 v/v). All the steps were carried out on precision hot plates at 37 °C. After fixation the slides were air dried and stained.
All slides were independently coded before microscopic analysis.
NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells): 200. Parallel cultures were treated at each concentration. 100 metaphases per culture were scored
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; relative cell density
OTHER EXAMINATIONS:
- Determination of polyploidy: Yes
If observed, structural chromosomal aberrations, including breaks, fragments, deletions, exchanges and chromosomal disintegration were recorded. Gaps were recorded but not included in the calculation of the aberration rates. - Evaluation criteria:
- A test substance was considered positive (clastogenic) in the chromosome aberration test if:
- a clear and dose-related increase in the number of cells with aberrations,
- a biologically relevant response for at least one of the dose groups, which is higher than the laboratory negative control range (0.0% - 4.0% aberrant cells (with and without metabolic activation)) was observed.
A test item is considered to be negative if there is no biologically relevant increase in the percentage of aberrant cells above concurrent control levels, at any dose group. Although most experiments will give clearly positive or negative results, in some cases the data set will preclude making a definitive judgement about the activity of the test substance. - Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- In experiment II without metabolic activation, a biologically relevant decrease of the relative mitotic index and the relative cell density was noted at 5000 µg/mL (54% relative mitotic index and 56% relative cell density)
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: The test item could be suspended in cell culture medium at a concentration of 5000 µg/mL.
- Precipitation: Precipitation of the test substance was observed in following experiments:
Experiment I without metabolic activation: starting at 1000 µg/mL
Experiment II without metabolic activation: starting at 500 µg/mL
Experiment II with metabolix activation: starting at 1000 µg/mL
RANGE-FINDING/SCREENING STUDIES: The highest concentration analysed in the pre-experiment for toxicity was 5000 µg/mL. The relative mitotic index was used as the parameter for evaluating toxicity. The concentrations evaluated in the main experiments were based on the results of the pre-experiment. - Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- read-across from similar mixture/product
- Adequacy of study:
- key study
- Study period:
- 21 May - 02 Aug 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- 29 July 2016
- Deviations:
- yes
- Remarks:
- no C-charts or X-bar charts provided; no statistical analysis performed; evaluation criteria differ from the current criteria
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.5300 (Detection of Gene Mutations in Somatic Cells in Culture)
- Version / remarks:
- 1998
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Bayrisches Landesamt für Gesundheit und Lebensmittelsicherheit, Landesinstitut für Arbeitsschutz und Produktsicherheit, München, Germany
- Type of assay:
- other: in vitro mammalian cell gene mutation test
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Expiration date of the lot/batch: Jun 2013
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was suspended in cell culture medium and diluted prior to treatment. - Target gene:
- HPRT locus
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- - Source of cells: V79 cells (ATCC, CCL-93)
- Type and identity of media: MEM medium supplemented with 10% fetal bovine serum, 100 U/100 µg/mL penicillin/streptomycin, 2 mM L-glutamine, 25 mM HEPES, 2.5 µg/mL amphotericin B
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically 'cleansed' against high spontaneous background: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- Cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbital (80 mg/kg bw/day) and β-naphthoflavone (100 mg/kg bw/day) for three consecutive days by oral route.
- Test concentrations with justification for top dose:
- Pre-test for toxicity
4 h treatment with and without metabolic activation: 0.316, 1.00, 3.16, 10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/mL
Experiment I
4 h treatment with and without metabolic activation: 0.316, 1.00, 3.16, 10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/mL
Experiment II
20 h treatment without metabolic activation: 0.316, 1.00, 3.16, 10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/mL
4 h treatment with metabolic activation: 25, 50, 100, 250, 500, 750, 1250, 2000, 3000 and 5000 µg/mL - Vehicle / solvent:
- No vehicle was used.
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- no
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
- Cell density at seeding: 1.0 - 1.5E+06 cells in 30 mL medium/175 cm² plastic flask.
DURATION
1st experiment: 4 h exposure with and without metabolic activation.
2nd experiment: 4 h exposure with metabolic activation and 20 h exposure without metabolic activation.
- Expression time (cells in growth medium): During the following expression period the cells of the logarithmic growing culture were subcultured 48 to 72 h after treatment.
- Selection time (if incubation with a selection agent): At the end of the expression period for selection the mutants, cells from each treatment group were seeded in cell culture petri dishes (diameter 90 mm) with selection medium containing 6-thioguanine for further incubation (about one week). At the end of the selection period, colonies were fixed and stained for counting.
SELECTION AGENT (mutation assays): 11 µg/mL 6-thioguanine
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency; relative total growth - Evaluation criteria:
- A test is considered to be negative if there is no biological relevant increase in the number of mutants. There are several criteria for determining a positive result:
- a repdoucible three times higher mutation frequency than the solvent control for at least one of the concentrations;
- a concentration related increase of the mutation frequency; such an evaluation may be considered also in the case that a three-fold increase of the mutant frequency is not observed;
- if there is by chance a low spontaneous mutation rate in the corresponding negative and solvent controls a concentration related increase of the mutations within their range has to be discussed.
According to the OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the results is not regarded as necessary. - Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. I: starting at 2500 µg/mL +S9 (relative growth: 65.3 and 68.4% at 2500 and 5000 µg/mL); Exp. II: at 5000 µg/mL -S9 (relative growth: 54.7%)
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: The pH-value detected with the test item was within the physiological range.
- Precipitation: Precipitation of the test item (oily droplets) was noted starting at concentrations of 1000 µg/mL in both experiments with and without S9 mix. In the 2nd experiment without metabolic activation precipitation was observed at concentrations of 1000 µg/mL and higher, with metabolic activation at concentrations of 1250 µg/mL and higher.
RANGE-FINDING/SCREENING STUDIES:
No biologically relevant growth inhibition was observed in the pre-test with and without metabolic activation.
Referenceopen allclose all
Table 1: Summary of test results (experiment 1; Initial Mutation Test, Plate Incorporation Method)
With or without S9-Mix |
Test substance concentration (μg/plate) |
Mean number of revertant colonies per plate (average of 3 plates) |
|||||
Frameshift type |
Base-pair substitution type |
||||||
TA1537 |
TA98 |
TA100 |
TA1535 |
WP2 uvrA |
|||
– |
Solvent control (distilled water) |
- |
- |
89.3 ± 15.04 |
7.7 ± 0.58 |
29.3 ± 3.21 |
|
Solvent control (DMSO) |
7.7 ± 2.52 |
21.3 ± 2.52 |
96.3 ± 8.33 |
11.3 ± 2.08 |
28.0 ± 2.65 |
||
Solvent control (DMF, 100µL) |
8.0 ± 1.73 |
17.7 ± 3.79 |
86.7 ± 14.50 |
12.7 ± 1.15 |
31.3 ± 2.08 |
||
Untreated control |
6.7 ± 3.21 |
18.7 ± 1.53 |
94.0 ± 8.66 |
13.7 ± 1.53 |
27.3 ± 3.06 |
||
5 |
5.3 ± 3.21 |
16.7 ± 3.79 |
88.3 ± 9.02 |
11.3 ± 2.89 |
25.3 ± 2.89 |
||
15.81 |
6.3 ± 3.06 |
21.0 ± 7.94 |
97.0 ± 2.65 |
14.3 ± 6.11 |
26.7 ± 4.73 |
||
50 |
8.0 ± 2.00 |
17.0 ± 2.0 |
103.7 ± 2.89 |
9.0 ± 4.36 |
27.0 ± 6.56 |
||
158.1 |
10.3 ± 0.58 |
22.0 ± 2.65 |
95.7 ± 18.01 |
11.7 ± 1.15 |
29.7 ± 8.02 |
||
500 |
8.3 ± 3.79 |
17.0 ± 2.0 |
89.0 ± 13.53 |
13.0 ± 3.61 |
32.3 ± 0.58 |
||
1581 |
7.0 ± 1.00 |
19.3 ± 1.53 |
83.3 ± 7.23 |
12.3 ± 2.31 |
29.7 ± 2.89 |
||
5000 |
8.3 ± 1.53 P |
24.3 ± 4.62 P |
76.7 ± 12.50 P |
13.3 ± 3.21 P |
24.7 ± 4.04 P |
||
Positive controls (unit/plate) |
9AA |
4-NPD |
SAZ |
SAZ |
MMS |
||
Mean No. of colonies/plate (average of 3 plates) |
407.3 ± 5.03 |
375.3 ± 16.04 |
1125.3 ± 137.95 |
1052.0 ± 68.23 |
893.3 ± 28.10 |
||
+ |
Solvent control (distilled water) |
- |
- |
91.0 ± 9.54 |
11.7 ± 2.31 |
30.3 ± 2.52 |
|
Solvent control (DMSO) |
10.0 ± 2.00 |
21.7 ± 3.79 |
79.0 ± 4.58 |
9.3 ± 3.06 |
33.3 ± 1.15 |
||
Solvent control (DMF, 100µL) |
9.3 ± 1.15 |
21.3 ± 3.51 |
87.0 ± 11.27 |
9.0 ± 2.65 |
26.7 ± 1.53 |
||
Untreated control |
6.7 ± 2.08 |
29.0 ± 3.0 |
91.3 ± 2.52 |
11.0 ± 1.00 |
31.7 ± 1.53 |
||
5 |
7.3 ± 1.15 |
24.3 ± 0.58 |
98.0 ± 10.54 |
12.0 ± 3.46 |
35.0 ± 7.94 |
||
15.81 |
6.3 ± 2.89 |
23.3 ± 4.04 |
92.0 ± 4.36 |
11.3 ± 3.06 |
32.3 ± 7.77 |
||
50 |
8.0 ± 2.65 |
20.7 ± 2.89 |
84.0 ± 1.73 |
10.3 ± 5.86 |
39.0 ± 1.73 |
||
158.1 |
9.7 ± 3.51 |
25.7 ± 1.53 |
88.7 ± 1.53 |
9.3 ± 1.53 |
36.7 ± 2.31 |
||
500 |
9.7 ± 6.43 |
22.3 ± 5.69 |
83.7 ± 12.50 |
6.3 ± 2.31 |
28.0 ± 1.73 |
||
1581 |
6.3 ± 2.08 |
29.0 ± 4.36 |
75.7 ± 12.34 |
10.0 ± 3.61 |
33.0 ± 2.65 |
||
5000 |
7.3 ± 2.31 P |
22.3 ± 1.53 P |
70.0 ± 9.54 P |
8.7 ± 2.31 P |
28.7 ± 4.93 P |
||
Positive controls (µg/plate) |
2AA |
2AA |
2AA |
2AA |
2AA |
||
Mean No. of colonies/plate (average of 3 plates) |
187.3 ± 5.03 |
2272.0 ± 104.92 |
2160.0 ± 84.66 |
213.3 ± 10.07 |
184.0 ± 8.00 |
||
9AA = 9-aminoacridine
4-NPD = 4-nitro-1,2-phenylene-diamine
SAZ = sodium azide
MMS = methyl-methanesulfonate
2AA = 2-aminoanthracene
P = precipitate
Table 2:Summary of test results (experiment 2; Confirmatory Mutation Test, Pre-Incubation Method)
With or without S9-Mix |
Test substance (μg/plate) |
Mean number of revertant colonies per plate (average of 3 plates) |
|||||
Frameshift type |
Base-pair substitution type |
||||||
TA1537 |
TA98 |
TA100 |
TA1535 |
WP2 uvrA |
|||
– |
Solvent control (distilled water) |
- |
- |
114.3 ± 8.14 |
12.0 ± 2.65 |
20.0 ± 4.36 |
|
Solvent control (DMSO) |
5.0 ± 2.65 |
19.7 ± 1.53 |
107.3 ± 13.80 |
13.0 ± 3.61 |
21.0 ± 1.00 |
||
Solvent control (DMF, 100µL) |
4.3 ± 1.53 |
16.3 ± 1.15 |
84.3 ± 2.08 |
11.0 ± 3.61 |
18.7 ± 2.52 |
||
Untreated control |
8.0 ± 2.65 |
13.3 ± 2.08 |
112.7 ± 13.58 |
12.7 ± 3.79 |
20.0 ± 2.65 |
||
1.581 |
4.7 ± 2.08 |
19.3 ± 2.52 |
80.0 ± 3.61 |
9.7 ± 2.08 |
16.7 ± 3.06 |
||
5 |
5.7 ± 3.79 |
19.7 ± 1.15 |
84.3 ± 5.13 |
13.0 ± 1.73 |
16.0 ± 4.58 |
||
15.81 |
5.0 ± 2.00 |
20.3 ± 5.51 |
68.7 ± 9.50 |
12.3 ± 1.15 |
16.7 ± 1.53 |
||
50 |
5.3 ± 0.58 |
19.3 ± 6.81 |
62.0 ± 7.55 |
12.7 ± 1.53 |
16.0 ± 4.36 |
||
158.1 |
6.0 ± 1.00 |
20.7 ± 6.43 |
57.3 ± 2.52 |
9.7 ± 2.08 |
15.0 ± 3.46 |
||
500 |
5.0 ± 1.73 |
19.0 ± 3.00 |
63.3 ± 8.50 |
11.0 ± 1.73 |
19.3 ± 2.52 |
||
1581 |
8.0 ± 1.00 SP |
20.3 ± 4.93 SP |
51.3 ± 3.51 |
11.0 ± 3.61 SP |
19.0 ± 3.61 |
||
5000 |
3.7 ± 2.08 P |
19.0 ± 1.00 SP |
64.7 ± 2.31 SP |
8.3 ± 3.06 SP |
23.7 ± 5.86 SP |
||
Positive controls (unit/plate) |
9AA |
4-NPD |
SAZ |
SAZ |
MMS |
||
Mean No. of colonies/plate (average of 3 plates) |
394.7 ± 14.47 |
362.0 ± 13.11 |
1009.3 ± 96.44 |
1109.3 ± 48.88 |
898.7 ± 25.32 |
||
Solvent control (distilled water) |
- |
- |
106.7 ± 11.93 |
10.3 ± 2.08 |
19.3 ± 8.50 |
||
+ |
Solvent control (DMSO) |
5.0 ± 2.00 |
29.0 ± 4.36 |
115.0 ± 10.54 |
8.7 ± 1.53 |
19.3 ± 3.79 |
|
Solvent control (DMF, 100µL) |
5.3 ± 3.21 |
19.3 ± 3.51 |
91.3 ± 7.57 |
10.0 ± 1. 00 |
18.7 ± 0.58 |
||
Untreated control |
4.3 ± 1.15 |
26.0 ± 3.46 |
123.7 ± 10.07 |
9.0 ± 1.73 |
24.3 ± 6.03 |
||
1.581 |
7.3 ± 1.15 |
23.7 ± 0.58 |
103.0 ± 6.24 |
9.0 ± 1.00 |
22.0 ± 3.00 |
||
5 |
6.7 ± 0.58 |
25.3 ± 5.03 |
80.3 ± 5.51 |
9.7 ± 4.51 |
29.0 ± 3.00 |
||
15.81 |
4.3 ± 0.58 |
22.0 ± 2.00 |
76.0 ± 4.58 |
10.7 ± 2.52 |
19.0 ± 3.00 |
||
50 |
6.7 ± 0.58 |
25.3 ± 1.53 |
98.7 ± 10.21 |
12.7 ± 1.53 |
25.0 ± 5.57 |
||
158.1 |
9.7 ± 3.21 |
20.3 ± 1.15 |
80.0 ± 3.61 |
9.7 ± 3.79 |
26.7 ± 5.03 |
||
500 |
6.7 ± 2.52 |
24.3 ± 5.03 |
76.3 ± 8.50 |
12.0 ± 1.00 |
27.7 ± 6.03 |
||
1581 |
6.0 ± 1.73 SP |
23.7 ± 3.51 |
71.0 ± 7.00 |
10.0 ± 1.00 |
29.0 ± 3.46 |
||
5000 |
6.3 ± 2.31 SP |
23.7 ± 0.58 SP |
74.3 ± 10.60 SP |
4.7 ± 0.58 P |
25.0 ± 5.57 SP |
||
Positive controls (µg/plate) |
2AA |
2AA |
2AA |
2AA |
2AA |
||
Mean No. of colonies/plate (average of 3 plates) |
204.7 ± 12.06 |
2224.0 ± 48.00 |
2229.3 ± 92.98 |
206.0 ± 9.17 |
181.3 ± 8.33 |
||
9AA = 9-aminoacridine
4-NPD = 4-nitro-1,2-phenylene-diamine
SAZ = sodium azide
MMS = methyl-methanesulfonate
2AA = 2-aminoanthracene
SP = slight precipitate
P = precipitate
Table 1: Results of the pre-experiment
| Concentration in µg/mL | Mitotic Index in % | Cell Density in % | ||
| relative | relative | |||
| without S9 mix | ||||
| Control | 72 | 100 | 67 | 100 |
| 7.8 | 72 | 100 | 90 | 135 |
| 15.6 | 68 | 94 | 73 | 109 |
| 31.3 | 68 | 92 | 62 | 93 |
| 62.5 | 67 | 93 | 39 | 59 |
| 125 | 76 | 106 | 77 | 115 |
| 250 | 55 | 76 | 70 | 105 |
| 500 | 53 | 74 | 69 | 100 |
| 1000 | 52 | 72 | 49 | 73 |
| 2500 | 64 | 89 | 72 | 108 |
| 5000 | 52 | 72 | 59 | 88 |
| with S9 mix | ||||
| Control | 94 | 100 | 68 | 100 |
| 7.8 | 74 | 79 | 65 | 95 |
| 15.6 | 75 | 80 | 76 | 112 |
| 31.3 | 96 | 102 | 87 | 129 |
| 62.5 | 84 | 89 | 76 | 113 |
| 125 | 99 | 105 | 73 | 109 |
| 250 | 82 | 87 | 66 | 96 |
| 500 | 83 | 88 | 77 | 114 |
| 1000 | 80 | 85 | 59 | 87 |
| 2500 | 84 | 89 | 69 | 102 |
| 5000 | 88 | 94 | 63 | 93 |
The mitotic index was determined in 1000 cells per culture of each test group.
The relative values of the mitotic index are related to the negative control.
The cell density was determined in 20 cell counts for each test group.
Table 2. Test results of experiment I and II
| Test item | Concentration | Mitotic Index | Aberrant cells in % | ||
| in µg/mL | in % | with gaps | without gaps | ||
| Exp. I, Exposure period 4 h, fixation time 20 h, without S9 mix | |||||
| Control | medium | 100 | 3.5 | 2.0 | |
| EMS | 900 | 92 | 12.5 | 8.5 | |
| Test substance | 1000 P | 101 | 4.0 | 2.0 | |
| 2500 P | 81 | 3.5 | 2.0 | ||
| 5000 P | 77 | 1.0 | 0 | ||
| Exp. I, Exposure period 4 h, fixation time 20 h, with S9 mix | |||||
| Control | medium | 100 | 2.5 | 2.0 | |
| CPA | 0.83 | 115 | 11.5 | 9.5 | |
| Test substance | 1000 | 107 | 2.0 | 0.5 | |
| 2500 | 115 | 5.0 | 2.5 | ||
| 5000 | 94 | 4.0 | 2.0 | ||
| Exp. II, Exposure period 20 h, fixation time 20 h, without S9 mix | |||||
| Control | medium | 100 | 3.0 | 1.5 | |
| EMS | 400 | 96 | 11.0 | 9.5 | |
| Test substance | 500 P | 70 | 2.5 | 1.0 | |
| 1000 P | 54 | 4.0 | 2.0 | ||
| 5000 P | 64 | 1.5 | 0.5 | ||
| Exp. II, Exposure period 20 h, fixation time 20 h, withS9 mix | |||||
| Control | medium | 100 | 6.0 | 3.5 | |
| CPA | 0.83 | 112 | 15.0 | 14.0 | |
| Test substance | 1000 P | 94 | 5.0 | 4.0 | |
| 3000 P* | 104 | 3.5 | 2.5 | ||
| 5000 P | 65 | 4.5 | 2.5 | ||
EMS: Ethylmethanesulfonate; CP: Cyclophosphamide (positive controls)
The mitotic index was determined in 1000 cells per culture of each test group.
For evaluation of aberrant cells, 100 cells per culture of each test group were scored (in total 200 cells)
* For evaluation of aberrant cells, 400 cells were scored.
Table 3: Historical Laboratory Control Data
| Number of aberrant cells | ||||
| with S9 mix | without S9 mix | |||
| Negative control | + gaps | - gaps | + gaps | - gaps |
| mean in % | 4.3 | 2.0 | 3.6 | 1.5 |
| SD | 1.43 | 0.81 | 1.55 | 0.82 |
| RSD in % | 33.5 | 41.4 | 42.4 | 56.6 |
| min in % | 1.0 | 0.0 | 0.5 | 0.0 |
| max in % | 8.5 | 4.0 | 9.0 | 4.0 |
| n | 244 | 244 | 244 | 244 |
| Positive control | ||||
| mean in % | 13.1 | 9.7 | 13.1 | 9.7 |
| SD | 2.29 | 1.66 | 2.70 | 1.96 |
| RSD in % | 17.4 | 17.1 | 20.7 | 20.3 |
| min in % | 8.5 | 8.0 | 8.5 | 8.0 |
| max in % | 23.0 | 16.0 | 26.5 | 20.5 |
| n | 235 | 235 | 235 | 235 |
mean = mean number of aberrant cells
SD = Standard Deviation
RSD = relative Standard Deviation
min = minimum number of aberrant cells
max = maximum number of aberrant cells
n = Number of assays
Remarks on results and discussion: Genotoxicity
Due to a missing dose response, the increased mutation rates exceeding the respective negative controls and the historical control data observed in the 1st and 2nd experiment at 2500 (1st experiment, -S9), 31.6 and 2500 µg/mL (1st experiment, +S9), 0.316 and 1000 (2nd experiment, -S9) are considered as incidental and not test item related.
Table 1: Experiment I - 4 h exposure - Without Metabolic Activation
| Concentration | Cloning efficiency [%] | Relative Total Growth [%] | Mutants per 1E+06 surviving cells | Mutation factor |
| [µg/mL] | ||||
| NC1 (0) | 68 | 100 | 20.66 | |
| NC2 (0) | 63 | 100 | 31.20 | |
| 0.316 | 64 | 100.7 | 21.01 | 0.81 |
| 1.00 | 64 | 97.2 | 18.90 | 0.73 |
| 3.16 | 59 | 114.5 | 24.58 | 0.95 |
| 10.0 | 67 | 114.5 | 20.90 | 0.81 |
| 31.6 | 66 | 109.6 | 25.95 | 1.00 |
| 100 | 60 | 111.5 | 21.58 | 0.83 |
| 316 | 61 | 96.8 | 24.49 | 0.94 |
| 1000 P | 62 | 97.6 | 23.58 | 0.91 |
| 2500 P | 57 | 100.7 | 48.67 | 1.88 |
| 5000 P | 57 | 115.5 | 20.09 | 0.77 |
| EMS (300) | 53 | 85.6 | 211.32 | 8.15 |
EMS = Ethyl methane sulphonate
NC = Negative control
P = Precipitate (oily droplets)
Table 2: Experiment I - 4 h exposure - With Metabolic Activation
| Concentration | Cloning efficiency [%] | Relative Total Growth [%] | Mutants per 1E+06 surviving cells | Mutation factor |
| [µg/mL] | ||||
| NC1 (0) | 63 | 100 | 26.40 | |
| NC2 (0) | 63 | 100 | 16.73 | |
| 0.316 | 70 | 89.6 | 13.67 | 0.63 |
| 1.00 | 68 | 101.9 | 21.48 | 1.00 |
| 3.16 | 69 | 118.1 | 10.11 | 0.47 |
| 10.0 | 64 | 101.9 | 13.28 | 0.62 |
| 31.6 | 54 | 120.5 | 40.00 | 1.85 |
| 100 | 67 | 111.2 | 25.56 | 1.19 |
| 316 | 70 | 116.6 | 12.19 | 0.57 |
| 1000 P | 63 | 98.1 | 33.60 | 1.56 |
| 2500 P | 60 | 65.3 | 59.75 | 2.77 |
| 5000 P | 69 | 68.4 | 26.28 | 1.22 |
| DMBA (1.0) | 62 | 67.2 | 475.81 | 22.06 |
| DMBA (1.5) | 51 | 45.0 | 770.44 | 35.72 |
DMBA = 7,12 -Dimethylbenz(a)anthracene
NC = Negative control
P = Precipitate (oily droplets)
Table 3: Experiment II - 20 h Exposure - Without Metabolic Activation
| Concentration | Cloning efficiency [%] | Relative Total Growth [%] | Mutants per 1E+06 surviving cells | Mutation factor |
| [µg/mL] | ||||
| NC1 (0) | 67 | 100 | 43.12 | |
| NC2 (0) | 61 | 100 | 37.19 | |
| 0.316 | 69 | 100.9 | 44.20 | 1.10 |
| 1.00 | 67 | 106.8 | 20.07 | 0.50 |
| 3.16 | 69 | 100.3 | 40.88 | 1.02 |
| 10.0 | 62 | 98.5 | 48.39 | 1.20 |
| 31.6 | 65 | 100.9 | 33.98 | 0.85 |
| 100 | 75 | 100.9 | 22.15 | 0.55 |
| 316 | 66 | 102.7 | 28.68 | 0.71 |
| 1000 P | 71 | 89.6 | 45.77 | 1.14 |
| 2500 P | 73 | 73.0 | 22.07 | 0.55 |
| 5000 P | 80 | 54.7 | 20.75 | 0.52 |
| EMS (300) | 72 | 70.6 | 554.17 | 13.80 |
EMS = Ethyl methane sulphonate
NC = Negative control
P = Precipitate (oily droplets)
Table 4: Experiment II - 4 h Exposure - With Metabolic Activation
| Concentration | Cloning efficiency [%] | Relative Total Growth [%] | Mutants per 1E+06 surviving cells | Mutation factor |
| [µg/mL] | ||||
| NC1 (0) | 70 | 98.7 | 30.11 | |
| NC2 (0) | 71 | 101.3 | 44.37 | |
| 25 | 63 | 101.3 | 27.89 | 0.75 |
| 50 | 65 | 103.0 | 37.21 | 1.00 |
| 100 | 80 | 101.3 | 25.00 | 0.67 |
| 250 | 70 | 107.2 | 23.74 | 0.64 |
| 500 | 64 | 114.0 | 14.96 | 0.40 |
| 750 | 66 | 112.3 | 22.14 | 0.59 |
| 1250 P | 68 | 101.3 | 31.85 | 0.86 |
| 2000 P | 70 | 88.5 | 42.29 | 1.14 |
| 3000 P | 70 | 86.8 | 23.57 | 0.63 |
| 5000 P | 71 | 83.6 | 25.53 | 0.69 |
| DMBA (1.0) | 57 | 67.2 | 186.90 | 5.02 |
| DMBA (1.5) | 53 | 58.4 | 275.47 | 7.40 |
DMBA = 7,12 -Dimethylbenz(a)anthracene
NC = Negative control
P = Precipitate (oily droplets)
Mean = Mean of mutants/106cells
Min = Minimum of mutants/106cells
Max = Maximum of mutants/106cells
SD = Standard deviation
RSD = Relative standard deviation
n = Number of control values
Table 5: Historical laboratory control data
| Negative control | Positive control | |||
| -S9mix | +S9mix | EMS | DMBA | |
| Mean | 15 | 13 | 296 | 362 |
| SD | 9.9 | 8.8 | 163 | 256 |
| RSD [%] | 68 | 66 | 55 | 71 |
| Min | 1 | 2 | 89 | 69 |
| Max | 39 | 39 | 670 | 895 |
| n | 52 | 51 | 50 | 54 |
Mean = Mean of mutants/106 cells
Min = Minimum of mutants/106 cells
Max = Maximum of mutants/106 cells
SD = Standard deviation
RSD = Relative standard deviation
n = Number of control values
EMS = Ethyl methane sulphonate
DMBA = 7,12 -Dimethylbenzo(a)anthracene
Validity of controls
The mean of mutants observed in experiment I and experiment II are within or close to the range of the historical control data. However, as the "outliers" are near to the outer boarder of the historical control range, the assay is considered as acceptible.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Genetic toxicity
Justification for read-across
There are data available regarding genetic toxicity in bacteria for Polyaldo 2-1-IS (CAS 73296-86-3). In addition, read-across from an appropriate substance is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.4. 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).
As only data on genetic toxicity in bacteria is available for Polyaldo 2-1-IS (CAS 73296-86-3), information available for the analogue substance Di(isooctadecanoic) acid, diester with oxydi(propanediol) (CAS 67938-21-0) are taken into account to fulfill the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.4.
Genetic toxicity in bacteria (Ames)
CAS 73296-86-3
The test item was investigated for mutagenicity to bacteria (Ames test) according to OECD guideline 471 and in compliance with GLP (Orovecz, 2016). The Salmonella typhimurium strains TA 1535, TA 1537, TA 100, TA 98 and E. coli WP2 were exposed to concentrations ranging from 5 - 5000 µg/plate in DMF (N,N-Dimethylformamide) with and without the addition of a metabolic activation system (cofactor-supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of male rats, treated with phenobarbital and β-naphthoflavone) in two independent assays with triplicates each. The experiments were conducted according to the plate incorporation (1stexperiment) and preincubation (2ndexperiment) methodology. Cytotoxicity was observed in tester strain TA 1535 in the presence of S9-mix, where the number of revertant colonies decreased to less than half compared to solvent control (53%) in the 2ndexperiment at 5000 μg/plate. None of the observed revertant colony numbers were above the respective biological threshold value. There were no dose-related trends and no indication of any treatment effect. Precipitate/slight precipitate was detected on the plates in all examined strains with and without metabolic activation at least at the highest concentration tested. The reference mutagens showed the expected increase in the number of revertant colonies. Based on these results, the test item was considered to be not mutagenic to bacteria under the conditions of the test.
CAS 67938-21-0
Supportive information is available from the RA substance Di(isooctadecanoic) acid, diester with oxydi(propanediol) (CAS 67938-21-0). The mutagenic potential was tested in a Salmonella typhimurium reverse mutation assay equivalent to OECD guideline 471 and GLP (Müller, 1994). The following strains were used: TA 1535, TA 1537, TA 98 and TA 100. Tester strains were incubated with test material concentrations of 4 - 5000 µg/plate in acetone with and without the addition of a 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)). Two independent experiments were performed with triplicates each according to the plate incorporation methodology. No toxicity of the test substance was observed. Visible precipitation of the test compound on the plates has been observed at 2500 µg/plate and above. Positive control materials induced significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent negative controls was observed in all strains tested, neither in the presence nor in the absence of metabolic activation. Thus, the test substance was considered to be not mutagenic to bacteria under the conditions of the test.
Genetic toxicity (cytogenicity) in mammalian cells in-vitro
CAS 67938-21-0
An in vitro mammalian chromosome aberration test was performed with the test substance in Chinese hamster lung fibroblasts (V79) according to OECD guideline 473 and GLP (Zeller, 2013). Duplicate cultures of human lymphocytes were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix). In the first experiment cells were exposed for 4 h to test substance concentrations of 3.16, 10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/mL without metabolic activation and to test substance concentrations of 100, 316, 1000, 3000, 4000 and 5000 µg/mL with metabolic activation (cofactor-supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of male rats, treated with phenobarbital and β-naphthoflavone). In the second experiment cells were exposed for 20 hours to 10.0, 30.0, 100, 250, 500, 1000, 2500 and 5000 µg/mL without metabolic activation and to 100, 316, 1000, 3000, 4000 and 5000 µg/mL for 4 h with metabolic activation. Ethylmethanesulphonate and cyclophosphamide were used as positive control substances. Positive control materials induced statistically significant increases in aberration frequencies indicating the validity of the test and of the activity of the metabolizing system. Evaluation of 200 well-spread metaphase cells per concentration for structural chromosomal aberrations revealed no increase in the frequency of chromosome aberrations and polyploid cells at any dose level in comparison to the negative controls. The test material only demonstrated cytotoxicity in experiment II without metabolic activation at 5000 µg/mL. The test material was therefore considered to be non-clastogenic to Chinese hamster lung fibroblasts in vitro.
Genetic toxicity (mutagenicity) in mammalian cells in-vitro
CAS 67938-21-0
An in vitro mammalian cell gene mutation assay according to OECD guideline 476 and GLP was performed with the test substance in Chinese hamster lung fibroblasts (V79) (Wallner, 2012). The cells were treated for 4 and 20 hours with and without metabolic activation (cofactor-supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of male rats, treated with phenobarbital and β-naphthoflavone). The test substance was tested up to precipitation, the following concentrations were tested: 0.316, 1.00, 3.16, 10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/mL (1stexperiment with and without metabolic activation, 4 h exposure; 2ndexperiment without metabolic activation, 20 h exposure) and 25, 50, 100, 250, 500, 750, 1250, 2000, 3000 and 5000 µg/mL (2ndexperiment with metabolic activation, 4 h exposure). 7,12-dimethylbenzanthracene and ethylmethanesulphonate were used as positive controls with and without S9 mix, respectively. Reduced cloning efficiency was observed in the 1stexperiment starting at 2500 µg/mL in the presence of S9 and in the 2ndexperiment at 5000 µg/mL without S9 (relative growth: 54.7%). Positive and negative controls were valid and within or close to the range of historical control data. No biological significant increase in the mutation frequency at the HPRT locus was observed after treatment either in the absence or in the presence of S9-mix. Due to a missing dose response, the increased mutation rates exceeding the respective negative controls and the historical control data observed in the 1stand 2ndexperiment at 2500 (1stexperiment, -S9), 31.6 and 2500 µg/mL (1stexperiment, +S9), 0.316 and 1000 (2ndexperiment, -S9) are considered as incidental and not test item related. Thus, it was concluded that the test substance is not mutagenic in Chinese hamster lung fibroblasts (V79) under the experimental conditions described.
Conclusion for genetic toxicity
The available data show that Polyaldo 2-1-IS (CAS 73296-86-3) is not mutagenic to bacteria. In addition, the available data of the analogue substance Di(isooctadecanoic) acid, diester with oxydi(propanediol) (CAS 67938-21-0) show that the analogue substance is neither clastogenic nor mutagenic in Chinese hamster lung fibroblasts in vitro. Therefore, based on common functional groups and structural similarities, Polyaldo 2-1-IS (CAS 73296-86-3) is also considered not to be clastogenic or mutagenic in vitro.
Justification for classification or non-classification
The available data on genetic toxicity with Polyaldo 2-1-IS (CAS 73296-86-3) and the appropriate read-across substance Di(isooctadecanoic) acid, diester with oxydi(propanediol) (CAS 67938-21-0) do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.
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.
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