Registration Dossier
Registration Dossier
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EC number: 220-543-9 | CAS number: 2802-68-8
Toxicological information
Genetic toxicity: in vitro
Currently viewing:
Administrative data
- Endpoint:
- genetic toxicity in vitro, other
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Similar to all coordination complexes of boron trifluoride with organic and inorganic species (like alcohols, ethers, amines, sulfuric acid, sulfuric dioxide, etc) the complex of boron trifluoride and methanol is extremely water sensitive and reacts even with moist air. Given the extremely rapid decomposition the rate of hydrolysis cannot be quantitatively derived in a study conducted according to OECD Guideline 111. However sufficient information is available on the identity of hydrolysis products which aquatic organisms may be eposed.
In the instantaneous reaction with water as a first step methanol and boron trifluoride dihydrates are formed.
BF3·CH3OH+ 2 H2O -> BF3· 2 H2O + CH3OH
The hydrolysis of borontrifluoride dihydrate was investigated at pH-values of 1.2; 4.0; 7.0 and 9.0 (BASF SE, Study No. 09S01179, 26.19.2009)
The hydrolysis of the test item is a very fast process (half-life < 30 minutes). Already at room temperature about 30 to 60% of the test item was hydrolyzed within minutes in all tested buffer solutions in the pH range 1.2 to 9.0.
The main reactions of the hydrolysis process are the following:
BF3.2H2O + H2O → B(OH)3+ 3HF
HF + BF3.2H2O → HBF4+ 2H2O
B(OH)3+ 4HF → HBF4+ 3 H2O
HBF4+ H2O ↔ HBF3(OH) + HF
Total hydrolysis of HBF4:
HBF4↔ HBF3(OH) ↔ HBF2(OH)2↔ HBF(OH)3↔ HB(OH)4= B(OH)3+ H2O
Boric acid and tetrafluoroborate are expected to be the main species in the dilute hydrolysis solution (Zhang Weijiang et al.).
In conclusion it is justified to base the assessment of environmental fate and pathways of hydrogen trifluoromethoxyborate (1-), compound with methanol (1.1) on the properties of the breakdown products, which is considered acceptable in accordance with REACH Annex XI, section 1.5.
References:
BASF SE, Boron trifluoride dihydrate: hydrolysis as a function of pH, Study No. 09S01179, 26.10.2009
Wamser C. A. Equilibria in the system boron trifluoride-water at 25 °C,Journal of the American Chemical Society, 1951, 73: 409-416
Zhang Weijiang et al., Equilibrium on the hydrolysis of Boron trifluoride in large amount of water,Transactions of Tianjin University, 2016, 22: 486-491
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
boron trifluoride dihydrate (CAS no. 13319-75-0), methanol (67-56-1). For purity and impurities see study records in IUCLID chapter 7.6.1.
3. ANALOGUE APPROACH JUSTIFICATION
The hydrolysis data in IUCLID chapter 5.1.2 demonstrate the rapidity of the hydrolysis reaction. Exposure will never occur to the complex of boron trifluoride methanol but to its hydrolysis products, BF3 dihydrate and methanol. Therefore, these two substances are the relevant ones for evaluation of potential health effects.
4. DATA MATRIX
A data matrix is not applicable in this case. The present read-across approach is not based on the comparison of experimental data for one or more compounds, but the hydrolysis products of the registered material are considered the relevant toxophors due to the rapid hydrolysis reaction. Reliable data are provided for all hydrolysis products, whereby an evaluation of potential health hazards can be performed.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- genetic toxicity in vitro
- Remarks:
- Type of genotoxicity: genome mutation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
- Principles of method if other than guideline:
- Determination of chromosomal malsegregation in ascomycetes during mitosis induced by test substance application.
- GLP compliance:
- not specified
- Type of assay:
- other: Mitotic recombination in ascomycetes
- Target gene:
- not applicable
- Species / strain / cell type:
- other: Aspergillus nidulans diploid strain P1
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- without
- Test concentrations with justification for top dose:
- 5.2, 5.6, 6.0, 7.0 % (v/v)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: no data
- Species / strain:
- other: Aspergillus nidulans diploid strain P1
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 7.0 % (lowest concentration to arrest conidial germination)
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- not specified
- Conclusions:
- Interpretation of results (migrated information):
positive
There was a concentration-related increase in non-disjunctions (chromosomal malsegregation) with a maximum of about 3 %. No aneuploidies were noted at the lowest test concentration. The result was statistically significant at two concentrations and a dose-response relationship was evident (IPCS/WHO 1997).
No other forms of malsegregation were statistically significant (1/265 cross-over seen at 6.0 %). The survival was reduced in dose-related manner.
Survival and amount of aneuploidy in Aspergillus nidulans after methanol-treatment:
Concentration [%] |
Survival [%] |
Scored colonies |
Aneuploids (yellow segregants) |
|
counts |
[%] |
|||
5.2 |
26 |
268 |
0 |
0 |
5.6 |
19 |
407 |
6 |
1.47* |
6.0 |
10 |
265 |
8 |
3.02** |
7.0 |
5 |
176 |
0 |
0 |
Spontaneous control |
||||
0 |
100 |
2673 |
7 |
0.26 |
* P<0.01; ** P<0.001
Note: Similar results were obtained with ethanol and other primary aliphatic alcohols. The aneuploidy rate of ethanol reached a maximum of about 10 %.
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comprehensive test programme using test procedures in accordance with accepted standard methods, but limited documentation.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- Only strains TA97 and TA102 tested
- Principles of method if other than guideline:
- According to Maron and Ames, 1983.
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His-operon
- Species / strain / cell type:
- S. typhimurium TA 97
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 102
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with
- Metabolic activation system:
- S9 mix from Aroclor-induced SD rat livers
- Test concentrations with justification for top dose:
- <= 7.5 mg/plate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
- Evaluation criteria:
- Positive response: dose response relationship, revertant ratio >=2.
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with
- Genotoxicity:
- ambiguous
- Remarks:
- slightly positive trend
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Conclusions:
- Interpretation of results (migrated information):
negative
In TA102, a slightly positive trend was indicated [(±) ambiguous], reproducible in 5 parallel independent experiments, but never exceeding the revertant ratio of 2: Spontaneous mutation rate 200 - 300/plate, while in the presence of high methanol doses, an increase in the mutation frequency above background of 140 revertants was found.
The methanol-related increase in the mutation frequency in TA102 did not fulfil the accepted criteria for mutagenic activity. Along with the high methanol doses required to induce such a weak effect and the negative results observed in all other Ames tests, the overall evidence clearly demonstrates that methanol is not mutagenic in bacterial reverse-mutation systems.
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comprehensive test programme using test procedures in accordance with accepted standard methods, but limited documentation.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- Salmonella TA102 and/or E.coli WP2 missing
- Principles of method if other than guideline:
- according to Ames et al., 1975.
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His-operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 1538
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix from Aroclor-induced SD rat livers
- Test concentrations with justification for top dose:
- <= 2.5 mg/plate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- non-toxic within the range of testing
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- non-toxic within the range of testing
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Conclusions:
- Interpretation of results (migrated information):
negative
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- in vitro DNA damage and/or repair study
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Meets generally accepted scientific standards, well documented with methodological restrictions.
- Principles of method if other than guideline:
- The endpoint of the test was cytotoxicity due to chromosome damage. The ratio of the minimal inhibitory concentration (MIC) of repair proficient to the MIC of repair-deficient E. coli strains was taken as an indicator for genotoxicity.
- GLP compliance:
- not specified
- Type of assay:
- other: DNA damage and repair assay in bacteria
- Target gene:
- not applicable
- Species / strain / cell type:
- E. coli WP2
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- other: wild-type, repair proficient
- Species / strain / cell type:
- E. coli, other: WP67
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- other: repair deficient: uvrA-, polA-
- Species / strain / cell type:
- E. coli, other: CM871
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- other: repair deficient: uvrA-, recA-, lexA-
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- No details: the initial concentration was governed by the solubility or by the toxicity of the TS as inferred from preliminary testing. Starting from this, eight 2-fold dilution steps followed in general.
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: no data
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium and 2-h preincubation:
Trials were conducted in miniature form (liquid micromethod procedure: 350 μl) using microwell plates that contained nutrient broth, and as 2-h preincubation assay ("treat-and-plate method" on nutrient broth agar).
DURATION
- Preincubation period: 2 h
- Exposure duration: 16 h (liquid micromethod procedure)
DETERMINATION OF CYTOTOXICITY
- Method: other: determination of the Minimal Inhibitory Concentration (MIC): growth retardation - Evaluation criteria:
- For each tester strain, the Minimal Inhibitory Concentration (MIC) was determined. The endpoint was cytotoxicity due to chromosome damage. The ratio of the MIC of the repair proficient to the MIC of the repair deficient strains was taken as indicator for genotoxicity. A ratio of greater than 2 was accepted as significant only if reproducible in 5 parallel independent experiments.
- Species / strain:
- E. coli, other: WP2, WP67, CM871
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 40 mg/well
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: WP67, CM871
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- 20 mg/well
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 40 mg/well
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: not specified
- Metabolic activation:
- with
- Genotoxicity:
- ambiguous
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: not specified
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: other: microwell method
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
ambiguous
The microwell method resulted in a negative result in the presence of S9 and in a positive result in the absence of S9 at 20 mg/well (Flora et al., 1990, 1984). But the preincubation procedure was negative without S9, but ambiguous with S9 (Flora et al. 1984).
Note: The MIC concentrations were very high (40 and 20 mg/well = about 120 g/L and 60 g/l).
Given the high concentrations and the conflicting findings, it is concluded that observations made at the margin of significance (ratio = 2) are of low reliability and biological relevance. The weak relative increase of toxicity in repair-deficient strains may be an increase in unspecific cytotoxicity rather than solely "genotoxicity". (Note: A similar result was obtained with ethanol at somewhat lower concentrations).
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vitro cytogenicity / micronucleus study
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Test procedure in accordance with accepted standard methods, sufficiently documented, acceptable for assessment.
- Principles of method if other than guideline:
- In vitro micronucleus test with V79 cells comparing alcohols, acetone and various alkylating agents.
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian cell micronucleus test
- Target gene:
- not applicable
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- without
- Test concentrations with justification for top dose:
- 50 µL/mL (approx. 40 mg/mL)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: medium (Eagle's MEM + 10 % FCS), acetone for positive controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
- Remarks:
- 0, 0.02, 0.04, 0.08 µg/mL; solvent acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- 0, 0.4, 2, 10, 50, 100 µg/mL; solvent acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- 0, 25, 50, 100 µg/mL; solvent acetone
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 48 h
STAIN (for cytogenetic assays): 4% Giemsa
NUMBER OF REPLICATIONS: not reported
NUMBER OF CELLS EVALUATED: 7000 interphase cells at each concentration used
OTHER
Cells were plated at a density of 13000 cells/cm², incubated for 15-18 h, then treated with the test substance. After treatment, the cells were incubated for 48 h, then collected, subjected to hypotonic treatment with KCl, fixed with acetic acid-methanol, and then stained with 4% Giemsa. - Evaluation criteria:
- Criteria used to score MN: (1) staining intensity equal to that of the nucleus, (2) diameter less than one-fifth that of the nucleus, (3) location in cytoplasm, (4) no contact with nucleus to distinguish from nuclear blebs.
- Statistics:
- The dose response was estimated by linearr regression curves. Difference in the sensitivity of mutagenic compounds was established by comparing the slopes of corresponding dose-response regression curves. For a comparison of mean values, Student's t test was used.
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Conclusions:
- Interpretation of results (migrated information):
negative
No MN increases induced by any alcohol or acetone, whereas the alkylating agents produced significant MN frequencies above medium controls.
|
Max. number of MN/1000 cells [mean±S.E.] |
|
|
Control (solvent dose) |
Chemical (dose) |
Methanol |
4.00±0.71 (50 µL/mL) |
3.50±1.19 (50 µL/mL) |
MNNG |
3.2±0.40 (5 µL/mL) |
8.2±0.83 (0.08 µg/mL) |
MMS |
3.9±0.59 (5 µL/mL) |
16.5±0.50 (100 µg/mL) |
EMS |
2.2±0.40 (5 µL/mL) |
7.0±0.69 (100 µg/mL) |
Solvent for methanol: medium
Solvent for MNNG, MMS, EMS: acetone
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Only abstract, no detailed data.
- Principles of method if other than guideline:
- Optimisation of the amount of S9-mix to be used to obtain maximum yield of mutations. Comparative study including typical mutagens. According to Clive and Spector (1975), Mutat Res 31: 17-29.
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Thymidin-kinase
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with
- Metabolic activation system:
- Aroclor 1254-induced rat liver S9-mix
- Test concentrations with justification for top dose:
- 7.9 mg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: no data
- Details on test system and experimental conditions:
- DURATION
- Exposure duration: at least 4 h
SELECTION AGENT (mutation assays): TFT (trifluorothymidine) - Evaluation criteria:
- Significant increases in mutation frequency with the test substance
- Statistics:
- no data
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
positive
In the presence of 10 - 15 µL/mL S9 and methanol (7.9 mg/mL), there was a significant increase in mutation frequency. No detailed results presented.
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study, also largely meeting current standards, sufficient documentation, acceptable for assessment.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- yes
- Remarks:
- Exposure and expression period combined
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- HPRT
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- no data
- Test concentrations with justification for top dose:
- 15.8, 31.7, 47.4, 63.3 mg/ml
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: culture medium (Eagle's MEM)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-dimethylnitrosamine
- Remarks:
- with S9
Migrated to IUCLID6: 1 and 2 mg/mL - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: MNNG, 0.29 and 0.59 µg/mL
- Remarks:
- without S9
- Details on test system and experimental conditions:
- DURATION
- Exposure duration: 6 days
- Expression time (cells in growth medium): combined with 6 days exposure
- Selection time (if incubation with a selection agent): after 6 days
SELECTION AGENT (mutation assays): 8-Azaguanin, 6-Thioguanin, Ouabain
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency (colony formation) - Evaluation criteria:
- Significant increase in V79 cells resistant to 8-Azaguanine, 6-Thioguanine or Ouabain.
- Statistics:
- Calculation of mean mutation frequency±S.D. per 10e6 surviving cells.
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 63.3 mg/ml (approx. 70 % inhibition of colony formation)
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results (migrated information):
negative
The test substance induced no increases in mutant frequency in gene mutation to drug resistance vs. negative control, whereas the positive control DMN produced increases in dose-related manner in the presence of metabolic activation (S9 mix), and MNNG in the absence of metabolic activation.
Maximum mutation frequency of V79 cells (per 10e6 survival cells, mean±SD) for resistance towards 6-TG, 8-AG and Ouabain after methanol treatment:
|
Control |
Test substance (mg/mL) |
||
Selectant |
-S9 |
+S9 |
-S9 |
+S9 |
6-Thioguanine |
0.70±1.79 |
0.94±2.18 |
1.55±3.08 (47.4 mg/mL) |
0.84±2.21 (31.7 mg/mL) |
8-Azaguanine |
23.42±8.70 |
24.29±7.30 |
22.34±7.39 (31.7 mg/mL) |
20.05±13.01 (31.7 mg/mL) |
Ouabain |
1.23±2.23 |
0 |
2.64±2.79 (47.7 mg/mL) |
0.11±0.36 (47.7 mg/mL) |
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comprehensive test programme using test procedures in accordance with accepted standard methods, sufficiently documented.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His-operon, Trp-operon (E. coli)
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 1538
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- E. coli WP2 uvr A
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Liver S9 fraction of KC500-pretreated rats
- Test concentrations with justification for top dose:
- 5, 10, 50, 100, 500, 1000, 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 0.01 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) without S9, benzo(a)pyrene (B(a)P) with S9
- Remarks:
- TA100
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- both 5.0 µg/plate, respectively
- Positive control substance:
- other: N-ethyl -N'-nitro-N-nitrosoguanidine (ENNG) without S9, 2-aminoanthracene (2AA) with S9
- Remarks:
- TA1535both 5.0 µg/plate, respectively
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 0.05 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) without S9, 2-aminoanthracene (2AA) with S9
- Remarks:
- WP2 uvrA
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 0.05 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) without S9, benzo(a)pyrene (B(a)P) with S9
- Remarks:
- TA98
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 80.0 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 9-aminoacridine (9AC) without S9, benzo(a)pyrene (B(a)P) with S9
- Remarks:
- TA1537
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 0.25 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 4-nitroquinoline-1-oxide (4NQO) without S9, benzo(a)pyrene (B(a)P) with S9
- Remarks:
- TA1538
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: duplicates
DETERMINATION OF CYTOTOXICITY
- Method: other: growth inhibition of revertant clones - Evaluation criteria:
- Doubling of revertant numbers in comparison to control and dose-response correlation.
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Conclusions:
- Interpretation of results (migrated information):
negative
Maximum number of revertants:
|
Control (water) [mean±SD] |
Test substance (µg/plate) |
||
Strain |
-S9 |
+S9 |
-S9 |
+S9 |
TA100 |
149±17.1 |
161±16.2 |
175 (100) |
180 (50) |
TA1535 |
28±6.9 |
15±3.6 |
35 (50) |
17 (5000) |
TA98 |
29±6.2 |
39±8.6 |
42 (50) |
39 (1000) |
TA1537 |
16±6.4 |
21±8.1 |
22 (5000) |
35 (5) |
TA1538 |
21±5.5 |
28±7.0 |
18 (500) |
31 (5) |
E.coli WP2 uvrA |
32±7.3 |
33±10.3 |
36 (5000) |
43 (10) |
The test substance was not mutagenic in the tested strains up to 5000 µg/plate.
Data source
Materials and methods
Test material
- Reference substance name:
- Hydrogen trifluoromethoxyborate(1-), compound with methanol (1:1)
- EC Number:
- 220-543-9
- EC Name:
- Hydrogen trifluoromethoxyborate(1-), compound with methanol (1:1)
- Cas Number:
- 2802-68-8
- Molecular formula:
- CH4O.CH3BF3O.H
- IUPAC Name:
- hydrogen trifluoro(methanolato)borate(1-) methanol (1:1)
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- other: mouse lymphoma cells, E. coli, S. typhimurium, Chinese hamster lung fibroblasts (V79), Aspergillus nidulans diploid strain P1
- Metabolic activation:
- with and without
Results and discussion
Test resultsopen allclose all
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100, TA 1538, and E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other:
- Vehicle controls validity:
- other:
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- other:
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100, TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: WO2, WP67, CM871
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: WP67, CM871
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: not specified
- Metabolic activation:
- with
- Genotoxicity:
- ambiguous
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: not specified
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: Shimizu et al., 1985
Applicant's summary and conclusion
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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