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EC number: 209-506-8 | CAS number: 583-52-8
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Ames test (OECD 471): negative in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvrA with and without metabolic activation
(RA from CAS 144-62-7)
Ames test (OECD 471): negative in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 with and without metabolic activation
(RA from CAS 144-62-7)
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- strain with an AT base pair missing
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted 21 July 1997
- Deviations:
- yes
- Remarks:
- strain with an AT base pair missing
- GLP compliance:
- no
- 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
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats or hamsters treated with Aroclor 1254.
- Test concentrations with justification for top dose:
- 100, 333.3, 1000, 3333.3 and 6666.7 µg/plate with and without metabolic activation
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: -S9: 4-Nitro-o-phenylenediamine (5 µg/plate) for TA98, sodium azide (1 µg/pate) for TA100 and TA1535, respectively, 9-aminoacridine (50 µg/plate) for TA1537; +S9: 2-Aminoanthracene (1 or 2.5 µg/plate) for all strains
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: triplicates each in 2 independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: Reduction in numbers of revertant colonies per plate and/or thinning or absence of the bacterial lawn - Evaluation criteria:
- A positive response was indicated by a reproducible, dose-related increase, whether it be twofold over background or not.
- Statistics:
- Mean values and standard deviations were calculated.
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 6666.7 µg/plate with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 6666.7 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 6666.7 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 6666.7 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: The test substance precipitated at 3333.3 µg/plate in all strains with metabolic activation.
RANGE-FINDING/SCREENING STUDIES: The test substance was checked for toxicity in TA100 up to a concentration of 10 mg/plate (data not shown). - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted 21 July 1997
- Deviations:
- yes
- Remarks:
- the batch of S9 was not characterised with a mutagen that requires metabolic activation by microsomal enzymes
- Qualifier:
- according to guideline
- Guideline:
- other: the guideline of the Ministry of Labour, Japan (1988)
- Deviations:
- not specified
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his operon; trp operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Species / strain / cell type:
- S. typhimurium TA 102
- Species / strain / cell type:
- E. coli WP2 uvr A pKM 101
- Species / strain / cell type:
- other: S. typhimurium TA 104
- Metabolic activation:
- with and without
- Metabolic activation system:
- Cofactor supplemented post-mitochondrial factor (S9 mix), prepared from the livers of rats treated with sodium phenobarbital and 5,6-benzoflavone.
- Test concentrations with justification for top dose:
- First experiment (TA 100, TA 1535, WP2uvrA, TA 98, TA 1537): 0.0763, 0.305, 1.22, 4.88, 19.5, 78.1, 313, 1250 and 5000 µg/mL with and without metabolic activation
Second experiment (TA 100, TA 1535, WP2uvrA, TA 98, TA 1537): 78.1, 156, 313, 625, 1250, 2500 and 5000 µg/mL with and without metabolic activation
Third experiment (TA 102, TA 104, WP2uvrA/pKM101): 1.22, 4.88, 19.5, 78.1, 313, 1250 and 5000 µg/mL with and without metabolic activation
Fourth experiment (TA 104, WP2uvrA/pKM101): 19.5, 39.1, 78.1, 156, 313, 625, 1250 µg/mL without metabolic activation
Fourth experiment (TA 104, WP2uvrA/pKM101): 78.1, 156, 313, 625, 1250, 2500 and 5000 µg/mL with metabolic activation
Fourth experiment (TA 102): 78.1, 156, 313, 625, 1250, 2500 and 5000 µg/mL with and without metabolic activation - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- sodium azide
- furylfuramide
- other: - S9: bleomycin (1 µg/plate) for TA 102, pyruvic aldehyde (20 µg/plate) for TA 104; + S9: 2-aminoanthracene (0.5, 1, 2 or 10 μg/plate) for all strains
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: duplicates each in 2 independent experiments (test substance and positive control); quadruplicated each in 4 independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: growth inhibition - Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- 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:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 3: at 5000 µg/plate with and without metabolic activation; Exp. 4: at 2500 µg/plate with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- 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:
- cytotoxicity
- Remarks:
- Exp. 3 and 4: at 1250 µg/plate without metabolic activation and at 5000 µg/plate with metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- other: S. typhimurium 104
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 3 and 4: at 1250 µg/plate without metabolic activation and at 5000 µg/plate with metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES: A range-finding study was not performed.
HISTORICAL CONTROL DATA
Please refer to Table 5 under "any other information on results incl. tables". - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Remarks:
- Summary of available data used for the endpoint assessment of the target substance
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Please refer to analogue justification provided in IUCLID section 13
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- 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:
- cytotoxicity
- Remarks:
- Exp. 1: at 5000 µg/mL with and without metabolic activation; Exp. 2: at 2500 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 3: at 5000 µg/plate with and without metabolic activation; Exp. 4: at 2500 µg/plate with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- 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:
- cytotoxicity
- Remarks:
- Exp. 3 and 4: at 1250 µg/plate without metabolic activation and at 5000 µg/plate with metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- other: S. typhimurium 104
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp. 3: at 5000 µg/plate with and without metabolic activation; Exp. 4: at 1250 µg/plate without metabolic activation and at 5000 µg/plate with metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- 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:
- at 6666.7 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 6666.7 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 6666.7 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 6666.7 µg/mL with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- other: Source: JETOC, 1977
- Conclusions:
- There is no indication that the source substance induces genetic toxicity in bacteria. Applying the RA-A approach, similar results are expected for the target substance.
Referenceopen allclose all
Table 1: Summary of Results
| With or without S9-Mix | Test substance concentration [µg/plate] | Mean number of revertant colonies per plate (average of 3 plates ± Standard deviation) |
|||
| Base-pair substitution type | Frameshift type | ||||
| TA 100 | TA1535 | TA98 | TA1537 | ||
| – | 0 | 79 ± 0.6 | 13 ± 0.9 | 15 ± 1.7 | 9 ± 2.3 |
| – | 100 | 95 ± 4.5 | 9 ± 0.6 | 19 ± 1.2 | 11 ± 1.9 |
| – | 333.3 | 86 ± 10.3 | 8 ± 2.0 | 13 ± 2.3 | 7 ± 0.9 |
| – | 1000 | 94 ± 2.0 | 10 ± 1.5 | 14 ± 2.9 | 7 ± 2.4 |
| – | 3333.3 | 80 ± 3.5 | 9 ± 2.0 | 18 ± 1.0 | 6 ± 0.9 |
| 6666.7 | 61 ± 5.2 s | 8 ± 3.5 s | 9 ± 1.2 s | 4 ± 1.5 s | |
| Positive controls, –S9 | Name | SA | SA | NOPD | 9-AA |
| Concentrations (μg/plate) | 1.0 | 1.0 | 5.0 | 50.0 | |
| Mean No. of colonies/plate (average of 3 ± SD) | 458 ± 10.7 | 375 ± 4.9 | 320 ± 18.8 | 63 ± 7.8 | |
| +S9 mix (rat) | 0 | 91 ± 7.0 | 6 ± 0.3 | 18 ± 1.8 | 13 ± 2.6 |
| +S9 mix (rat) | 100 | 107 ± 14.5 | 7 ± 1.0 | 20 ± 4.3 | 15 ± 1.3 |
| +S9 mix (rat) | 333.3 | 88 ± 6.3 | 7 ± 1.3 | 22 ± 2.7 | 12 ± 2.0 |
| +S9 mix (rat) | 1000 | 100 ± 8.4 | 6 ± 0.6 | 18 ± 0.3 | 10 ± 1.2 |
| +S9 mix (rat) | 3333.3 | 76 ± 9.7 P | 6 ± 1.8 P | 17 ± 1.9 P | 8 ± 2.3 P |
| +S9 mix (rat) | 6666.7 | 92 ± 6.2 s | 2 ± 2.0 s | 18 ± 1.5 s | 7 ± 0.9 s |
| Positive controls, +S9 mix (rat) | Name | 2-AA | 2-AA | 2-AA | 2-AA |
| Concentrations (μg/plate) | 1.0 | 2.5 | 1.0 | 2.5 | |
| Mean No. of colonies/plate (average of 3 ± SD) | 553 ± 5.5 | 271 ± 15.5 | 320 ± 18.8 | 311 ± 10.5 | |
| +S9 mix (hamster) | 0 | 134 ± 4.0 | 18 ± 1.0 | 18 ± 3.2 | 9 ± 1.5 |
| +S9 mix (hamster) | 100 | 101 ± 7.1 | 8 ± 0.9 | 22 ± 2.0 | 9 ± 1.8 |
| +S9 mix (hamster) | 333.3 | 91 ± 6.8 | 9 ± 1.5 | 17 ± 0.9 | 8 ± 3.0 |
| +S9 mix (hamster) | 1000 | 93 ± 7.2 | 7 ± 1.2 | 20 ± 3.8 | 8 ± 0.7 |
| +S9 mix (hamster) | 3333.3 | 77 ± 5.9 P | 8 ± 0.7 P | 18 ± 4.4 P | 6 ± 0.7 P |
| +S9 mix (hamster) | 6666.7 | 25 ± 22.2 s | 8 ± 0.9 s | 4 ± 0.0 s | 1 ± 0.7 s |
| +S9 mix (hamster) | Name | 2-AA | 2-AA | 2-AA | 2-AA |
| Concentrations (μg/plate) | 1.0 | 2.5 | 1.0 | 2.5 | |
| Mean No. of colonies/plate (average of 3 ± SD) | 553 ± 5.5 | 375 ± 4.9 | 864 ± 46.7 | 348 ± 4.0 | |
SA: sodium azide
NOPD: 4-nitro-o-phenylenediamin
9-AA: 9 -aminoacridine
2-AA: 2 -aminoanthracene
Table 1: Results of Experiment 1
| With or without S9-Mix | Test substance concentration [µg/plate] | Mean number of revertant colonies per plate | ||||
| Base-pair substitution type | Frameshift type | |||||
| TA 1535 | TA100 | WP2uvrA | TA98 | TA1537 | ||
| – | Solvent control | 9 | 132 | 26 | 14 | 6 |
| – | 0.0763 | 11 | 149 | 27 | 18 | 6 |
| – | 0.305 | 7 | 165 | 23 | 22 | 4 |
| – | 1.22 | 5 | 139 | 28 | 13 | 5 |
| – | 4.88 | 10 | 170 | 23 | 17 | 6 |
| – | 19.5 | 8 | 140 | 27 | 14 | 8 |
| – | 78.1 | 13 | 153 | 28 | 15 | 7 |
| – | 313 | 6 | 154 | 27 | 23 | 8 |
| 1250 | 7 | 140 | 28 | 20 | 5 | |
| – | 5000 | 0* | 0* | 0* | 0* | 0* |
| Positive controls, –S9 | Name | SA | AF-2 | AF-2 | AF-2 | 9-AA |
| Concentrations (μg/plate) | 0.5 | 0.01 | 0.01 | 0.1 | 80 | |
| Mean No. of colonies/plate | 372 | 926 | 409 | 434 | 389 | |
| + | Solvent control | 9 | 135 | 28 | 24 | 11 |
| + | 0.0763 | 9 | 152 | 18 | 24 | 8 |
| + | 0.305 | 7 | 152 | 35 | 20 | 7 |
| + | 1.22 | 14 | 147 | 25 | 25 | 7 |
| + | 4.88 | 8 | 160 | 20 | 28 | 8 |
| + | 19.5 | 7 | 156 | 24 | 28 | 11 |
| + | 78.1 | 13 | 151 | 34 | 23 | 3 |
| + | 313 | 14 | 147 | 27 | 24 | 8 |
| 1250 | 9 | 154 | 28 | 22 | 11 | |
| + | 5000 | 0* | 0* | 0* | 0* | 0* |
| Positive controls, +S9 | Name | 2AA | 2AA | 2AA | 2AA | 2AA |
| Concentrations (μg/plate) | 2 | 1 | 10 | 0.5 | 2 | |
| Mean No. of colonies/plate | 251 | 1458 | 1055 | 440 | 201 | |
SA: sodium azide
AF-2: furfurylamide
9-AA: 9 -aminoacridine
2-AA: 2 -aminoanthracene
* Toxicity observed
Table 2: Results of Experiment 2
| With or without S9-Mix | Test substance concentration [µg/plate] | Mean number of revertant colonies per plate | ||||
| Base-pair substitution type | Frameshift type | |||||
| TA 1535 | TA100 | WP2uvrA | TA98 | TA1537 | ||
| – | Solvent control | 8 | 137 | 30 | 18 | 5 |
| – | 78.1 | 9 | 133 | 35 | 19 | 3 |
| – | 156 | 12 | 135 | 24 | 20 | 7 |
| – | 313 | 9 | 134 | 27 | 22 | 7 |
| – | 625 | 7 | 133 | 27 | 17 | 8 |
| – | 1250 | 10 | 145 | 25 | 25 | 7 |
| – | 2500 | 9* | 106* | 23* | 16* | 6* |
| – | 5000 | 0* | 0* | 27 | 0* | 0* |
| Positive controls, –S9 | Name | SA | AF-2 | AF-2 | AF-2 | 9-AA |
| Concentrations (μg/plate) | 0.5 | 0.01 | 0.01 | 0.1 | 80 | |
| Mean No. of colonies/plate | 329 | 939 | 334 | 354 | 399 | |
| + | Solvent control | 10 | 134 | 26 | 27 | 17 |
| + | 78.1 | 16 | 146 | 33 | 26 | 10 |
| + | 156 | 8 | 118 | 31 | 21 | 11 |
| + | 313 | 12 | 143 | 30 | 35 | 9 |
| + | 625 | 15 | 131 | 30 | 23 | 10 |
| + | 1250 | 15 | 123 | 39 | 20 | 11 |
| + | 2500 | 0* | 0* | 0* | 0* | 0* |
| + | 5000 | 0* | 0* | 0* | 0* | 0* |
| Positive controls, +S9 | Name | 2AA | 2AA | 2AA | 2AA | 2AA |
| Concentrations (μg/plate) | 2 | 1 | 10 | 0.5 | 2 | |
| Mean No. of colonies/plate | 275 | 1410 | 1101 | 389 | 181 | |
SA: sodium azide
AF-2: furfurylamide
9-AA: 9 -aminoacridine
2-AA: 2 -aminoanthracene
* Toxicity observed
Table 3: Results of Experiment 3
| With or without S9-Mix | Test substance concentration [µg/plate] | Mean number of revertant colonies per plate | ||
| Base-pair substitution type | ||||
| TA 102 | TA 104 | WP2uvrA/pKM101 | ||
| – | Solvent control | 242 | 309 | 43 |
| – | 1.22 | 239 | 323 | 53 |
| – | 4.88 | 263 | 338 | 46 |
| – | 19.5 | 264 | 283 | 55 |
| – | 78.1 | 242 | 291 | 48 |
| – | 313 | 246 | 298 | 56 |
| – | 1250 | 254 | 303* | 45* |
| – | 5000 | 0* | 0* | 0* |
| Positive controls, –S9 | Name | BLM | PA | AF-2 |
| Concentrations (μg/plate) | 1 | 20 | 0.05 | |
| Mean No. of colonies/plate | 915 | 2384 | 1288 | |
| + | Solvent control | 354 | 333 | 65 |
| + | 1.22 | 353 | 347 | 66 |
| + | 4.88 | 342 | 347 | 83 |
| + | 19.5 | 338 | 325 | 82 |
| + | 78.1 | 343 | 335 | 85 |
| + | 313 | 358 | 352 | 85 |
| 1250 | 358 | 319 | 75 | |
| + | 5000 | 0* | 0* | 0* |
| Positive controls, +S9 | Name | 2AA | 2AA | 2AA |
| Concentrations (μg/plate) | 2 | 2 | 2 | |
| Mean No. of colonies/plate | 2621 | 1192 | 1088 | |
BLM: bleomycin
PA: pyruvic aldehyde
AF-2: furfurylamide
2-AA: 2 -aminoanthracene
* Toxicity observed
Table 4: Results of Experiment 4
| With or without S9-Mix | Test substance concentration [µg/plate] | Mean number of revertant colonies per plate | ||
| Base-pair substitution type | ||||
| TA 102 | TA 104 | WP2uvrA/pKM101 | ||
| – | Solvent control | 223 | 312 | 44 |
| – | 19.5 | nt | 292 | 44 |
| – | 39.1 | nt | 327 | 37 |
| – | 78.1 | 220 | 327 | 43 |
| – | 156 | 228 | 328 | 35 |
| – | 313 | 243 | 323 | 40 |
| – | 625 | 221 | 327 | 38 |
| – | 1250 | 234 | 337* | 39* |
| 2500 | 224* | nt | nt | |
| – | 5000 | 0* | nt | nt |
| Positive controls, –S9 | Name | BLM | PA | AF-2 |
| Concentrations (μg/plate) | 1 | 20 | 0.05 | |
| Mean No. of colonies/plate | 942 | 1322 | 1097 | |
| + | Solvent control | 313 | 337 | 56 |
| + | 78.1 | 295 | 332 | 58 |
| + | 156 | 329 | 357 | 54 |
| + | 313 | 298 | 350 | 55 |
| + | 625 | 338 | 348 | 59 |
| + | 1250 | 320 | 361 | 57 |
| 2500 | 0* | 365 | 54 | |
| + | 5000 | 0* | 0* | 0* |
| Positive controls, +S9 | Name | 2AA | 2AA | 2AA |
| Concentrations (μg/plate) | 2 | 2 | 2 | |
| Mean No. of colonies/plate | 251 | 1458 | 1055 | |
BLM: bleomycin
PA: pyruvic aldehyde
AF-2: furfurylamide
2-AA: 2 -aminoanthracene
nt: not tested
* Toxicity observed
Table 5: Historical control data
| Solvent control (water) | Positive control | |||
| Tester strain | -S9 mix | +S9 mix | -S9 mix | +S9 mix |
| TA100 | 138 ± 13 | 146 ± 14 | 803 ± 96 | 1225 ± 216 |
| TA1535 | 12 ± 4 | 13 ± 4 | 388 ± 57 | 300 ± 52 |
| TA98 | 16 ± 2 | 25 ± 3 | 490 ± 103 | 322 ± 59 |
| TA1537 | 9 ± 4 | 13 ± 4 | 705 ± 366 | 207 ± 57 |
| TA102 | 251 ± 33 | 333 ± 33 | 800 ± 119 | 1901 ± 820 |
| TA104 | 322 ± 43 | 370 ± 50 | 1716 ± 479 | 1181 ± 201 |
| WP2uvrA | 29 ± 6 | 33 ± 7 | 249 ± 74 | 1153 ± 137 |
| WP2uvrA/pKM101 | 54 ± 14 | 84 ± 21 | 1284 ± 298 | 990 ± 152 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for read-across
There are no reliable data available regarding genetic toxicity for either dipotassium oxalate monohydrate (CAS 6487-48-5) or dipotassium oxalate anhydrate (CAS 583-52-8). Read-across from an appropriate substance (oxalic acid (CAS 144-62-7) 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 VII, 8.4. Common functional groups, structural similarities and comparable toxicological properties (according to the joint consideration in Annex VI to CLP) 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).
Genetic toxicity (mutagenicity) in bacterial cells
CAS 144 -62 -7
A bacterial gene mutation assay with the source substance oxalic acid was performed in accordance with OECD Guideline 471 (JETOC, 1977). In this study the test substance was not mutagenic in any of the five strains (TA 1535, TA 1537, TA 98, TA 100 and WP2 uvrA) tested with and without metabolic activation in two independent experiments in concentration ranges from 0.0763 up to 5000 µg/plate and from 78.1 up to 5000 µg/plate, respectively. In addition, the mutagenic properties of the source substance was investigated in two further independent experiments using the tester strains TA 102, TA 104 and WP2uvrA pkM101 in the absence and presence of a metabolic activation system (concentration range 1.22 – 5000 µg/plate and 19.5 – 5000 µg/plate) and revealed negative results (JETOC, 1977).
In a second bacterial gene mutation assay according to a test protocol similar to OECD TG 471 oxalic acid showed no mutagenic properties in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 in the concentration range from 100 up to 6666.7 µg/plate in the absence and presence of two different metabolic activation systems (rat and hamster) (Haworth et al., 1983).
The available information from the registration dossier of the source substance oxalic acid shows that oxalic acid is not mutagenic to bacterial cells and revealed no clastogenic and no mutagenic properties in Chinese hamster lung fibroblasts in vitro (ECHA, n.d.). Therefore, based on the analogue approach, dipotassium oxalate is also considered not to be mutagenic in bacterial and in mammalian cells and not to be clastogenic in vitro, respectively. The available data do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.
Reference: ECHA (n.d.), Oxalic Acid, Available from: https://echa.europa.eu/registration-dossier/-/registered-dossier/14786 [accessed 12-09-17]
Justification for classification or non-classification
According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to dipotassium oxalate, data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.
Based on the available information, there is no indication that the source substance oxalic acid is not mutagenic to bacterial cells and revealed no clastogenic and no mutagenic properties in Chinese hamster lung fibroblasts in vitro. Therefore, based on the analogue approach, dipotassium oxalate is also considered not to be mutagenic in bacterial and in mammalian cells and not to be clastogenic in vitro, respectively. The available data 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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