Registration Dossier
Registration Dossier
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EC number: 701-340-9 | CAS number: -
Toxicological information
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Key studies:
- Key studies: Two studies on Bacterial reverse mutation assay (Ames test) according to OECD guideline 471. GLP studies.
Results: negative
- Key study: In vitro mammalian chromosome aberration test according to OECD guideline 473. GLP study.
Result: negative
- Key study: In vitro mammalian cell gene mutation test according to OECD guideline 476. GLP study.
Result: negative
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- OECD guideline 471. GLP study.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- -Identity of media: Center of Japanese Baioatsusi
- Species / strain / cell type:
- E. coli WP2 uvr A
- Details on mammalian cell type (if applicable):
- -Identity of media: Center of Japanese Baioatsusi
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from rat liver
- Test concentrations with justification for top dose:
- Test material dose:
0.50 - 1.50 - 5.00 - 15.00 - 50.00 mg/mL (313, 625, 1250, 2500, 5000 µg/plate) - Negative solvent / vehicle controls:
- yes
- Remarks:
- water for injection
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without metabolic activation
- Positive control substance:
- other: 2,2-(2-Furyl)-3-(5-nitro-2fuiyl)acrylamide
- Remarks:
- TA 100, WP2 uvrA- 2,2-(2-Furyl)-3-(5-nitro-2fuiyl)acrylamide: 0.01 µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water for injection
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without metabolic activation
- Positive control substance:
- other: 2,2-(2-Furyl)-3-(5-nitro-2fuiyl)acrylamide
- Remarks:
- TA 98- 2,2-(2-Furyl)-3-(5-nitro-2fuiyl)acrylamide: 0.1 µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water for injection
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without metabolic activation
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535- sodium azide: 0.5µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water for injection
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA 1537- 9-aminoacridine: 80µg/plate Migrated to IUCLID6: without metabolic activation
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water for injection
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- with metabolic activation
- Positive control substance:
- other: 2-Aminoanthracene
- Remarks:
- TA 100 - 2-Aminoanthracene: 1µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water for injection
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- with metabolic activation
- Positive control substance:
- other: 2-Aminoanthracene
- Remarks:
- TA 1535, TA 1537- 2-Aminoanthracene: 2µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water for injection
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- with metabolic activation
- Positive control substance:
- other: 2-Aminoanthracene
- Remarks:
- WP2 uvrA- 2-Aminoanthracene: 10 µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water for injection
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- with metabolic activation
- Positive control substance:
- other: 2-Aminoanthracene
- Remarks:
- TA 98- 2-Aminoanthracene: 0.5 µg/plate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium made of minimal glucose agar
DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 hours - 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
- 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
- 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
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle 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
- Positive controls validity:
- valid
- Conclusions:
- The result was that the test material is not mutagenic (negative).
- Executive summary:
The aim of the test was to assess the potential of test material to induce a point mutation at the histidine-requiring gene locus in strains of Salmonella typhimurium and E.coli.
The test procedure used was the OECD guideline 471.
Test material doses were: 0.50 - 1.50 - 5.00 - 15.00 - 50.00 mg/mL
The result was that the test material is not mutagenic.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- OECD guideline 473. GLP study.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- other: Chinese hamster cells (CHL/IU)
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- With absence of S9 mix: 0.078, 0.016, 0.31 mg/mL
With presence of S9 mix: 1.3, 2.5, 5.0 mg/mL
24 hour of continuous treatment: 0.031, 0.063, 0.13 mg/mL - Vehicle / solvent:
- Carboxymethyl cellulose sodium solution (0.5 w/v %)
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Carboxymethyl cellulose sodium solution (0.5 w/v %)
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- without metabolic activation
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Carboxymethyl cellulose sodium solution (0.5 w/v %)
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- Exposure duration:
-6h without S9 mix
-6h with S9 mix
-24h without S9 mix
NUMBER OF REPLICATIONS: two
NUMBER OF CELLS EVALUATED: 100 cell per replicate - Statistics:
- Fisher's exact method (p < 0.01, one-sided ); Cochrane test (p < 0.01, one-side).
- Species / strain:
- other: Chinese hamster cells (CHL/IU)
- 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
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- The result was negative.
- Executive summary:
The aim of the test was to determine if the test material can causes structural chromosome aberrations in cultured mammalian cells.
The test procedure used was the OECD guideline 473.
Chinese hamster cells (CHL/IU) were used for the test.
The concentrations of the test material were:
-with absence of S9 mix: 0.078, 0.016, 0.31 mg/mL -
-with presence of S9 mix: 1.3, 2.5, 5.0 mg/mL
-24 hour of continuous treatment: 0.031, 0.063, 0.13 mg/mL
The result of the test was negative (not induced structural chromosomal abnormalities in cells).
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 4th May 2004 to 8th September 2004
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: OECD guideline 471 and EU method B.13/B.14. GLP study.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- Obtained from Professor B.N. Ames (University of California, Berkeley.USA).
Kept in the laboratory and preserved in liquid nitrogen - Species / strain / cell type:
- other: E.Coli WP2 pKM 101
- Details on mammalian cell type (if applicable):
- Obtained from CROFTON-SLEIGH (The Institute of Cancer Research:Royal Cancer Hospital, Sutton, Surrey, Great Britain).
Kept in the laboratory and preserved in liquid nitrogen - Species / strain / cell type:
- E. coli WP2 uvr A pKM 101
- Details on mammalian cell type (if applicable):
- Obtained from CROFTON-SLEIGH (The Institute of Cancer Research:Royal Cancer Hospital, Sutton, Surrey, Great Britain).
Kept in the laboratory and preserved in liquid nitrogen - Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix from rat livers
- Test concentrations with justification for top dose:
- 50 - 150 - 500 - 1500 - 5000 µg/plate test material
- Vehicle / solvent:
- Distilled water
- Negative solvent / vehicle controls:
- yes
- Remarks:
- distilled water
- Positive controls:
- yes
- Remarks:
- without metabolic activation
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535 and TA 100-sodium azide: 1µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- distilled water
- Positive controls:
- yes
- Remarks:
- without metabolic activation
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- TA 98-2-nitrofluorene: 2µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- distilled water
- Positive controls:
- yes
- Remarks:
- without metabolic activation
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA1537-9-aminoacridine: 50 µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- distilled water
- Positive controls:
- yes
- Remarks:
- without metabolic activation
- Positive control substance:
- mitomycin C
- Remarks:
- WP2(pkM101)-mitomycin C: 0.125µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- distilled water
- Positive controls:
- yes
- Remarks:
- without metabolic activation
- Positive control substance:
- other: potasium dichromate
- Remarks:
- WP2uvrA(pKM101)-potasium dichromate : 15µg/plate
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Remarks:
- with metabolic activation
- Positive control substance:
- other: 2-anthramine
- Remarks:
- TA 1535, TA 1537, TA 98 and TA 100-2-anthramine: 2µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- distilled water
- Positive controls:
- yes
- Remarks:
- with metabolic activation
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- WP2(pkM101) and WP2uvrA(pLM101)-benzo(a)pyrene:5µg/plate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
Salmonella typhimurium: 0.1 ml of the test substance at the relevant concentration and 0.1 ml of a bacterial suspension from a culture agitated overnight at 37 ºC are successively added to 2 ml of top agar to which 10% of 0.5 mM biotin histidine solution, maintained in a state of superfusion at 45 ºC, has been added. The content of each tube are agitated, then spread out in a Petri plate containing 20 ml of minimum agar. The plates are then incubated at 37 ºC for 48 h approximately.
E. coli: 0.1 ml of the test substance at the relevant concentratiion and 0.1 ml of a bacterial suspension from a culture agitated overnight at 37 ºC are successively added to 2 ml of top agar containing 5% Oxoid No. 2 to which 10% of 0.5 mM tryptophan solution, maintained in a state of superfusion at 45 ºC has been added. The contents of each tube are agitated and then spread out in a Petri plate containing 20 ml of minimum agar. The plates are incubated at 37 ºC for 48 h approximately.
DURATION
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: Three plates per treatment
Two independent assays were carried out. - Evaluation criteria:
- -Criteria based on biological significance:
Strains TA 1535. TA 1537
A product causing a positive response proportional to the dose for at least 3 concentrations with, for the highest increase, a value greater than or equal to 3 times the value for the solvent control, is considered positive in the assay.
Strains TA 98. TA 100. WP2(pKM101) and WP2uvrA
Reproducibility
If a product causes a positive response during a single assay and that result cannot be reproduced in at least 2 independent assays, the initial positive result may be considered as not significant.
All these criteria are not absolute, but they, however, help in coming to a decision that can be conclusive in the majority of the cases (Brusick, 1980). - Statistics:
- -Criteria based on statistical significance
In parallel, data are analysed by means of Dunnetfs method (Mahon et al, 1989) allowing the comparison of the mean value for each dose to the mean value for the corresponding solvent control. - 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
- 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
- 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
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli, other: WP2(pKM101)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A pKM 101
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- With and without metabolic activation, the test substance did not induce any toxicity whatever the strain tested and whatever the dose tested.
Both without and with metabolic activation, in two independetn assays, no biologically significant increase in the number of revertants was noted in the four Salmonella typhimurium and the two Escherichia coli strains tested in the presence of the test substance.
It is to be noted that in the second assay with metabolic activation, a slight but statistically significant increase in the number of revertants was observed in strain TA100 at all the doses tested, except at the minimum dose of 50 µg/plate, with a ratio of 1.5 a the maximum dose tested of 5000 µg/plate. However, this effect was neither biologically significant (ratio < 2) nor dose-related, and was thus not attributed to a mutagenic activity.
Moreover, a statistically significant decrease in the numberr of revertants was observed in the second assay without metabolic activation in strain TA98 at the lowest dose tested of 50 µg/plate. This decrease can be related to the random distribution of revertants colonies and have in any case no meaning in terms of mutagenic hazard. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
In the conditions of the study, the test material induced no mutagenic activity in the four Salmonella typhimurium and the two Escherichia coli strains tested. - Executive summary:
The aim of the test was to detect some potential mutagenic effect on bacterial strains of Salmonella typhimurium and E.coli. The test procedure was the Ames test according to OECD guideline 471. The test material doses were: 50 - 150 - 500 - 1500 - 5000 µg/plate test material. In the conditions of the study, the test material induced no mutagenic activity in the four Salmonella typhimurium and the two Escherichia coli strains tested.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 31st March 2010 to 02nd June 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: OECD guideline 476. GLP study.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Thymidine kinase (TK) locus
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- Obtained from ATCC (American Type Culture Collection -Rockville, MD 20852 - USA). A stock of these cells is maintained and stored frozen in liquid nitrogen in the laboratory.
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from rat liver induced by Aroclor 1254 (S9-mix)
- Test concentrations with justification for top dose:
- Without S9 mix: Assay 1 (3-hour treatment): 5000 – 2500– 1250 – 625 µg/mL
Assay 2 (24-hour treatment): 5000 – 2500– 1250 – 625 µg/mL
With S9 mix: Assay 1 and 2 (3-hour treatment): 5000 – 2500– 1250 – 625 µg/mL - Vehicle / solvent:
- Distilled water
- Negative solvent / vehicle controls:
- yes
- Remarks:
- (distilled water)
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- cyclophosphamide, 2µg/mL
Migrated to IUCLID6: (with metabolic activation) - Negative solvent / vehicle controls:
- yes
- Remarks:
- (distilled water)
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- methylmethanesulfonate 10µg/mL (3-h treatment), 2µg/mL (24-h treatment)
Migrated to IUCLID6: (without metabolic activation) - Details on test system and experimental conditions:
- - Preculture
Before each assay, a sufficient number of cells are thawed from the cryogenic ampoules, and cultured for 2 to 4 days in RPMI 10 medium in order to maintain exponential growth. The cells are then subcultured in 75 cm2 flasks at a determined cell density and incubated for 3 days at 37°C ± 0.5, humidity near 95% and 5% of CO2.
- Number of assays: 2
- Number of replicate cultures: 2 per concentration
- Expression time: 2 days after treatment
- Treatment duration: Without S9-mix: 3 hours and 24 hours
With S9-mix: 3 hours
DETERMINATION OF CYTOTOXICITY
- Method: plating efficiency - Evaluation criteria:
- Criteria for scoring mutation plates
Each well of the mutation plates (in selective medium containing TFT) is scored as containing either a small colony, a large colony or no colony according to the following criteria:
SMALL COLONIES: colonies having a diameter less than 25% of the diameter of the well. A small colony should also have a dense colonal morphology and a clear contour.
LARGE COLONIES: colonies having a diameter greater than 25% of the diameter of the well. A large colony should show less densely packed cells, and blurred contour.
Any well containing one or more small colonies is scored as positive for small colony.
Any well containing one or more large colonies is scored as positive for large colony.
Any well containing a combination of large and small colonies is scored at the same time as large colony and small colony.
An empty well is one which contains no cell growth.
Criteria for a mutagenic activity: biological significance
Under our experimental conditions and when the criteria for validity are fulfilled, a test item is considered as mutagenic in this system if the following conditions are fulfilled:
-The induced mutation frequency for at least one tested concentration is higher than the mutation frequency in the vehicle control cultures by at least the global evaluation factor of 126 x10-6 (Moore et al., 2006).
- A statistical trend test demonstrates a positive dose related increase in the mutation frequency (Moore et al., 2006).
- The results have to be reproducible in an independent study, at least from a qualitative point of view.
If none of the three criteria mentioned above is fulfilled, the tested substance is considered as not mutagenic in this study system.
In all other cases, the results are discussed on a case by case basis, and the results obtained on other study systems are taken into account.
All these criteria are not absolute: however, they give help when a decision has to be taken, making a conclusion possible in the majority. - Statistics:
- Statistical evaluation of data for the total number of mutants and for small colony mutants is performed using the method proposed by Robinson et al. (1990)
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- The plating efficiency of the negative control (mean of the 2 cultures) ranged from 65 to 120 % at T2. The mutation frequency (MF) of the negative control is ranged from 50 to 170 x10-6 mutants and within the range of historical data of the laboratory, except in the first assay both without and with metabolic activation where the values were slightly higher than the highest value already observed in historical data for negative control. Nevertheless, this slight deviation was considered as minor as values were ranged from 50 to 170 x10-6 mutants. The suspension growth value of the negative control ranged from 8 to 32 in the 3-hour treatments, and were above 32 in the 24-hour treatment.
The induced mutation frequencies (IMF) for the positive controls were significantly increased when compared to the MF for the solvent control, and demonstrated an increase above the spontaneous background MF of at least 300 x10-6 mutants. However, in the second assay in absence of metabolic activation, the value for the mutation frequency of the positive control was above the limit previously observed in historical data. Nevertheless, as the positive control was found clearly mutagenic in this condition, the deviation was considered as minor and did not affect the quality or the integrity of the current study. The other observed values were within the limits of historical positive controls of the laboratory. The acceptance criteria for the results were thus fulfilled.
In the second assay using a 3-hour treatment with metabolic activation, a statistically significant increase in the mean number of small colonies and in the mutation frequency of small colony mutants was noted at the highest concentration tested of 5000 μg/mL with a statistically linear trend. However as no statistically significant increase in the mutation frequency of total induced mutants (small and large colonies) was noted at all the concentrations tested and as the effect was not reproducible, indeed no statistically significant increase in the mean number of small colonies was noted in the first assay, this effect was considered as not relevant.
In the first assay with metabolic activation and in two independent assays using 3-hour or 24-hour treatments without metabolic activation, no significant increase in the mutation frequency of total induced mutants (small and large colonies) or in the mean number of small colonies and in the mutation frequency of small colony mutants was noted at any concentrations tested in the presence of the test substance. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
Under the experimental conditions, the test item induced no biologically significant mutagenic activity being demonstrated at the TK locus in L5178Y mouse lymphoma cell culture either with or without metabolic activation, in two independent assays. - Executive summary:
The aim of the test was to investigate a potential mutagenic effect on a model consisting of mammalian cells (L5178Y mouse lymphoma cells) by revealing mutations caused at the thymidine kinase (TK) locus. The test item is studied without and with metabolic activation (using microsomal fractions of liver) in order to demonstrate direct mutagens and promutagens, respectively. The test procedure was according to OECD guideline 476. The test concentration were: 625 -1250 -2500 -5000 µg/mL. Under the experimental conditions, the test item induced no biologically significant mutagenic activity being demonstrated at the TK locus in L5178Y mouse lymphoma cell culture either with or without metabolic activation, in two independent assays.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Key studies:
- Key studies: Two studies on Bacterial reverse mutation assay (Ames test) according to OECD guideline 471.
Results: negative
- Key study: In vitro mammalian chromosome aberration test according to OECD guideline 473.
Result: negative
- Key study: In vitro mammalian cell gene mutation test according to OECD guideline 476.
Result: negative
Justification for selection of genetic toxicity endpoint
No study was selected since the four in-vitro studies were negative.
Justification for classification or non-classification
Based on the available data on genetic toxicity in vitro, the substance is considered as negative and therefore, it is not classified.
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.
