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EC number: 213-607-2 | CAS number: 993-13-5
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Data from two valid in vitro genotoxicity studies (bacterial mutagenicity and chromosomal aberration) are available conducted with the item MPA and three valid tests conducted with the RA-substance MPAAU (bacterial mutagenicity, mouse lymphoma assay and micronucleus test) are available. In the context of in vitro genotoxicity studies, the chromosomal aberration study is considered to be as the most significant. In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce structural chromosomal aberrations in human lymphocytes in vitro. Therefore, methylphosphonic acid 70 % is considered to be non-clastogenic in this chromosome aberration test, when tested up to the highest required concentration. Likewise, the bacterial and mammalian cell mutagenicity studies revealed negative results. Hence, both MPA and read across substance MPAAU were considered to be not genotoxic. Further in vivo testing for genotoxicity therefore is not necessary.
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2013-01-21 to 2013-02-25
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- The following alteration from the guidelines was performed:
The treatment of lymphocytes was started approx. 72 hours after mitogenic stimulation. - Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- lymphocytes: human
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Dulbeccos's modified Eagle's medium/Ham's F12 medium
- Properly maintained: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9
- Test concentrations with justification for top dose:
- With metabolic activation:
Experiment I: 8.9, 15.6, 27.3, 47.8, 83.6, 146.3, 256.0, 448.0, 784.0, 1372.0 µg/mL
Experiment II: 83.6, 146.3, 256.0, 448.0, 784.0, 1372.0 µg/mL
Without metabolic activation:
Experiment I: 8.9, 15.6, 27.3, 47.8, 83.6, 146.3, 256.0, 448.0, 784.0, 1372.0 µg/mL
Experiment II: 8.9, 15.6, 27.3, 47.8, 83.6, 146.3, 256.0, 448.0, 784.0, 1372.0 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Deionised water
- Justification for choice of solvent/vehicle: solubility and relatively low cytotoxicity in accordance to the OECD Guideline 473 - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Details on test system and experimental conditions:
- Two independent experiments were performed. In Experiment I the exposure period was 4 hours with and without metabolic activation. In Experiment II the exposure period was 4 hours with S9 mix and 22 hours without S9 mix. The chromosomes were prepared 22 hours after start of treatment with the test item. Evaluation of two cultures per dose group.
METHOD OF APPLICATION: in culture medium
DURATION
- Exposure duration: 4 hours (+/- S9 mix) and 22 hours (- S9 mix)
- Fixation time (start of exposure up to fixation or harvest of cells): 22 hours
SPINDLE INHIBITOR (cytogenetic assays): Colcemid
STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: about 1.5
NUMBER OF CELLS EVALUATED: 100 per culture, except for the positive control in Experiment I in the presence of S9 mix, where only 50 metaphases were evaluated.
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index - Evaluation criteria:
- Evaluation of the cultures was performed (according to standard protocol of the "Arbeitsgruppe der Industrie, Cytogenetik") using NIKON microscopes with 100x oil immersion objectives. Breaks, fragments, deletions, exchanges, and chromosome disintegrations were recorded as structural chromosome aberrations. Gaps were recorded as well but not included in the calculation of the aberration rates. 100 well spread metaphases per culture were scored for cytogenetic damage on coded slides, except for the positive control in Experiment I in the presence of S9 mix, where only 50 metaphases were evaluated.
Only metaphases with characteristic chromosome numbers of 46 ± 1 were included in the analysis. To describe a cytotoxic effect the mitotic index (% cells in mitosis) was determined. - Statistics:
- Statistical significance was confirmed by means of the Fisher´s exact test (p <0.05).
- Species / strain:
- lymphocytes:
- Metabolic activation:
- with and without
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- The test item methylphosphonic acid , dissolved in deionised water, was assessed for its potential to induce chromosomal aberrations in human lymphocytes in vitro in the absence and presence of metabolic activation by S9 mix. Two independent experiments were performed. In Experiment I the exposure period was 4 hours with and without S9 mix. In Experiment II the exposure period was 4 hours with S9 mix and 22 hours without S9 mix. The chromosomes were prepared 22 hours after start of treatment with the test item. In each experimental group two parallel cultures were analysed. 100 metaphases per culture were scored for structural chromosomal aberrations, except for the positive control in Experiment I in the presence of S9 mix, where only 50 metaphases were evaluated. 1000 cells were counted per culture for determination of the mitotic index. The highest treatment concentration in this study, 1372.0 µg/mL (approx. 10 mM) was chosen with regard to the molecular weight and the purity (70 % in water) of the test item and with respect to the OECD Guideline for in vitro mammalian cytogenetic tests. No visible precipitation of the test item in the culture medium was observed. No relevant influence on osmolarity or pH value was observed. In this study, in the absence as well as in the presence of S9 mix, no biologically relevant cytotoxicity indicated by clearly reduced mitotic indices could be observed. In both experiments, in the absence and presence of S9 mix, no biologically relevant increase in the number of cells carrying structural chromosome aberrations was observed. The aberration rates of the cells after treatment with the test item (0.5 – 1.5 % aberrant cells, excluding gaps) were similar to the range of the solvent control values (0.5 – 1.5 % aberrant cells, excluding gaps) and within the range of the laboratory historical solvent control data. No evidence of an increase in polyploid metaphases was noticed after treatment with the test item as compared to the control cultures. In both experiments, either EMS (550.0 or 770.0 µg/mL) or CPA (15.0 or 20.0 µg/mL) were used as positive controls and showed distinct increases in cells with structural chromosome aberrations.
- Remarks on result:
- other: strain/cell type: human lymphocytes
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Methylphosphonic acid 70 % is considered to be non-clastogenic in this chromosome aberration test, when tested up to the highest required concentration.
- Executive summary:
The test item methylphosphonic acid 70%, dissolved in deionised water, was assessed for its potential to induce structural chromosomal aberrations in human lymphocytes in vitro in two independent experiments. The following study design was followed:
Without S9 mix
With S9 mix
Exp. I
Exp. II
Exp. I & II
Exposure period
4 hrs
22 hrs
4 hrs
Recovery
18 hrs
-
18 hrs
Preparation interval
22 hrs
22 hrs
22 hrs
In each experimental group two parallel cultures were analysed. Per culture 100 metaphases were evaluated for structural chromosomal aberrations, except for the positive control in Experiment I in the presence of S9 mix, where only 50 metaphases were evaluated. The highest applied concentration in this study (1372.0 µg/mL of the test item, approx. 10 mM) was chosen with regard to the molecular weight and the purity (70 % in water) of the test item and with respect to the current OECD Guideline 473. Dose selection of the cytogenetic experiment was performed considering the toxicity data in accordance with OECD Guideline 473. In the absence and presence of S9 mix, no cytotoxicity was observed up to the highest applied concentration. In both independent experiments, neither a statistically significant nor a biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item. No evidence of an increase in polyploid metaphases was noticed after treatment with the test item as compared to the control cultures. Appropriate mutagens were used as positive controls. They induced statistically significant increases in cells with structural chromosome aberrations.
Reference
Summary of results of the chromosomal aberration study with Methyl phosphonic acid 70%
Exp. | Preparation | Test item | Mitotic indices | Aberrant cells |
| |||||||
| interval | concentration | in % | in % |
| |||||||
|
| in µg/mL | of control | incl. gaps* | excl. gaps* | carrying exchanges |
| |||||
| Exposure period 4 hrs without S9 mix |
| ||||||||||
I | 22 hrs | Solvent control1 | 100.0 | 1.0 | 0.5 | 0.0 |
| |||||
|
| Positive control2 | 51.6 | 24.5 | 24.0S | 11.5 |
| |||||
|
| 448.0 | 91.3 | 0.5 | 0.5 | 0.0 |
| |||||
|
| 784.0 | 74.6 | 1.0 | 0.5 | 0.0 |
| |||||
|
| 1372.0 | 95.6 | 2.0 | 1.5 | 0.0 |
| |||||
| Exposure period 22 hrs without S9 mix |
| ||||||||||
II | 22 hrs | Solvent control1 | 100.0 | 0.5 | 0.5 | 0.0 |
| |||||
|
| Positive control3 | 46.6 | 20.5 | 20.0S | 4.5 |
| |||||
|
| 448.0 | 82.5 | 1.0 | 1.0 | 0.0 |
| |||||
|
| 784.0 | 107.7 | 1.5 | 1.5 | 0.0 |
| |||||
|
| 1372.0 | 112.3 | 1.0 | 1.0 | 0.0 |
| |||||
| Exposure period 4 hrs with S9 mix | |||||||||||
I | 22 hrs | Solvent control1 | 100.0 | 1.5 | 1.5 | 0.0 |
| |||||
|
| Positive control4# | 49.9 | 18.0 | 18.0S | 1.0 |
| |||||
|
| 448.0 | 93.4 | 1.0 | 1.0 | 0.0 |
| |||||
|
| 784.0 | 96.7 | 0.5 | 0.5 | 0.0 |
| |||||
|
| 1372.0 | 94.5 | 1.5 | 1.5 | 0.0 |
| |||||
II | 22 hrs | Solvent control1 | 100.0 | 1.5 | 1.0 | 0.0 |
| |||||
|
| Positive control5 | 49.6 | 14.5 | 13.5S | 2.5 |
| |||||
|
| 448.0 | 85.4 | 1.0 | 1.0 | 0.0 |
| |||||
|
| 784.0 | 115.4 | 2.5 | 1.5 | 0.0 |
| |||||
|
| 1372.0 | 90.0 | 1.5 | 1.5 | 0.0 |
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* Including cells carrying exchanges
# Evaluation of 50 metaphases per culture due to strong clastogenic effects
S Aberration frequency statistically significant higher than corresponding control values
1 Deionised water 10.0 % (v/v)
2 EMS 550.0 µg/mL
3 770.0 µg/mL
4 CPA 20.0 µg/mL
5 CPA 15.0 µg/mL
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Currently no tests are available assessing genotoxic effects in vivo.
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
MPA does not needs to be classified for genetic toxicity based on the available data.
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