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EC number: 229-146-5 | CAS number: 6419-19-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 07 November 2017 to 23 November 2017
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Only one test strain of E. coli was used to detect mutations via cross-linking.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- yes
- Remarks:
- Only one test strain of E. coli was used to detect mutations via cross-linking.
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- [nitrilotris(methylene)]trisphosphonic acid, sodium salt
- EC Number:
- 243-900-0
- EC Name:
- [nitrilotris(methylene)]trisphosphonic acid, sodium salt
- Cas Number:
- 20592-85-2
- Molecular formula:
- General formula C3H12NO9P3.xNa where x=3-5 ATMP-3Na C3H9NNa3O9P3 ATMP-4Na C3H8NNa4O9P3 ATMP-5Na C3H7NNa5O9P3
- IUPAC Name:
- Sodium salt of [nitrilotris(methylene)]trisphosphonic acid (3-5Na:1)
- Test material form:
- liquid
1
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/vehicle: On the day of the experiment, ATMP-H was dissolved in deionised water to form the sodium salt. The solvent was chosen because of its solubility properties and its relative non-toxicity to the bacteria.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: Not applicable
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: All formulations were prepared freshly before treatment and used within two hours of preparation. The formulation was assumed to be stable for this period unless specified otherwise by the Sponsor.
- Preliminary purification step: The dose selection was adjusted to the purity of 33%.
- Final dilution of a dissolved solid, stock liquid or gel: Not applicable
- Final preparation of a solid: Not applicable
Method
Species / strain
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/β-naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- To evaluate the toxicity of the test item, a pre-experiment was performed. Eight concentrations were tested for toxicity and mutation induction with each 3 plates. The experimental conditions in this pre-experiment were the same as described for the experiment I below (plate incorporation test). In the pre-experiment, the concentration range of the test item was 3 – 5000 µg/plate. Since no relevant toxic effects were observed, 5000 µg/plate were selected as the maximal concentration.
Pre-Experiment/Experiment I: 3; 10; 33; 100; 333; 1000; 2500; and 5000 µg/plate
Experiment II: 33; 100; 333; 1000; 2500; and 5000 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: deionised water
- Justification for choice of solvent/vehicle: The solvent was selected because of its solubility properties and its relative nontoxicity to the bacteria.
Controls
- Untreated negative controls:
- yes
- Remarks:
- no treatment
- Negative solvent / vehicle controls:
- yes
- Remarks:
- deionised water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- other: 2-aminoanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: In agar (plate incorporation); preincubation
ACTIVATION: An appropriate quantity of S9 supernatant was thawed and mixed with S9 cofactor solution, to result in a final concentration of approximately 10 % (v/v) in the S9 mix. Cofactors were added to the S9 mix to reach the following concentrations in the S9 mix: 8 mM MgCl2, 33 mM KCl, 5 mM glucose-6-phosphate, 4 mM NADP in 100 mM sodium-ortho-phosphate-buffer, pH 7.4.
DURATION
- Preincubation period: 60 minutes at 37°C
- Exposure duration: 48 hours at 37°C in the dark
SELECTION AGENT (mutation assays): Selective agar
NUMBER OF REPLICATIONS: Triplicate cultures
DETERMINATION OF CYTOTOXICITY
- Method: Number of revertants
- Any supplementary information relevant to cytotoxicity: Not specified - Rationale for test conditions:
- To evaluate the toxicity of the test item a pre-experiment was performed. Eight concentrations were tested for toxicity and mutation induction with each 3 plates. The experimental conditions in this pre-experiment were the same as described for the experiment I below (plate incorporation test). In the pre-experiment, the concentration range of the test item was 3 – 5000 µg/plate. Since no relevant toxic effects were observed, 5000 µg/plate were selected as the maximal concentration.
- Evaluation criteria:
- A test item is considered as a mutagen if a biologically relevant increase in the number of revertants exceeding the threshold of twice the colony count of the corresponding solvent control is observed.
A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration.
An increase exceeding the threshold at only one concentration is judged as biologically relevant if reproduced in an independent second experiment.
A dose dependent increase in the number of revertant colonies below the threshold is regarded as an indication of a mutagenic potential if reproduced in an independent second experiment. However, whenever the colony counts remain within the historical range of negative and solvent controls such an increase is not considered biologically relevant. - Statistics:
- According to the OECD guideline 471, a statistical analysis of the data is not mandatory.
Results and discussion
Test results
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Not specified
- Effects of osmolality: Not specified
- Evaporation from medium: Not specified
- Water solubility: Not specified
- Precipitation: Not observed
RANGE-FINDING/SCREENING STUDIES: In the pre-experiment, the concentration range of the test item was 3 – 5000 µg/plate. The pre-experiment is reported as experiment I. Since no relevant toxic effects were observed, 5000 µg/plate were chosen as maximal concentration. The concentration range included two logarithmic decades.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: Within the range of positive historical control data
- Negative (solvent/vehicle) historical control data: Within the range of negative historical control data
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: Number of revertants
Any other information on results incl. tables
Table 1: Summary of experiment 1
Test Group |
Dose Level (per plate) |
Revertant Colony Counts (Mean ± SD) |
|
|
|
Without Activation |
|
WP2 uvrA |
|
|
|
Deionised water |
|
48 ± 8 |
Untreated |
|
48 ± 4 |
ATMP-H |
3 µg |
43 ± 5 |
|
10 µg |
48 ± 8 |
|
33 µg |
44 ± 8 |
|
100 µg |
48 ± 10 |
|
333 µg |
43 ± 9 |
|
1000 µg |
47 ± 11 |
|
2500 µg |
40 ± 7 |
|
5000 µg |
36 ± 5 |
MMS |
2.0 µL |
953 ± 87 |
|
|
|
With Activation |
|
|
Deionised water |
|
55 ± 3 |
Untreated |
|
56 ± 11 |
ATMP-H |
3 µg |
51 ± 8 |
|
10 µg |
57 ± 8 |
|
33 µg |
51 ± 13 |
|
100 µg |
49 ± 15 |
|
333 µg |
51 ± 7 |
|
1000 µg |
55 ± 7 |
|
2500 µg |
39 ± 9 |
|
5000 µg |
47 ± 13 |
2-AA |
10.0 µg |
534 ± 112 |
|
|
|
Table 2: Summary of experiment 2
Test Group |
Dose Level (per plate) |
|
Revertant Colony Counts (Mean ± SD) |
Without Activation |
|
|
WP2 uvrA |
Deionised water |
|
|
32 ± 5 |
Untreated |
|
|
34 ± 4 |
ATMP-H |
33 µg |
|
36 ± 5 |
|
100 µg |
|
35 ± 5 |
|
333 µg |
|
32 ± 6 |
|
1000 µg |
|
31 ± 2 |
|
2500 µg |
|
33 ± 4 |
|
5000 µg |
|
19 ± 2 |
MMS |
2.0 µL |
|
945 ± 40 |
|
|
|
|
With Activation |
|
|
|
Deionised water |
|
|
42 ± 2 |
Untreated |
|
|
49 ± 12 |
ATMP-H |
33 µg |
|
34 ± 3 |
|
100 µg |
|
43 ± 2 |
|
333 µg |
|
37 ± 4 |
|
1000 µg |
|
36 ± 4 |
|
2500 µg |
|
35 ± 5 |
|
5000 µg |
|
28 ± 3 |
2-AA |
10.0 µg |
|
495 ± 16 |
|
|
|
|
MMS: methyl methane sulfonate
2-AA: 2-aminoanthracene
Applicant's summary and conclusion
- Conclusions:
- In a valid bacterial reverse mutation assay (reliability 2), conducted according to OECD Test Guideline 471 and in compliance with GLP, ATMP-xNa has been tested using E. coli WP2 uvr A. No increase in the number of revertants was observed in any test strain, with or without metabolic activation when tested up to limit concentration. Appropriate positive, negative and solvent controls were added and gave expected results. It is concluded that ATMP-xNa is negative for mutagenicity to bacteria under the conditions of the test.
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