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EC number: 231-388-1 | CAS number: 7526-26-3
- 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
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- 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
Gene mutation in mammalian cells (Mouse Lymphoma Assay), OECD 476 (now OECD 490), mouse Lymphoma L5178Y cells, +/-S9, negative
Gene mutation in bacteria, S. typhimurium, QSAR, +/-S9, negative
Chromosome aberration, CHO cells, QSAR, +/-S9, negative
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Study period:
- 23 MAY 2022
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
OECD QSAR Toolbox v4.5, Danish QSAR database
2. MODEL (incl. version number)
SciQSAR version 3.1.00
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CP(=O)(Oc1ccccc1)Oc1ccccc1
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please refer to attached QMRF
5. APPLICABILITY DOMAIN
Please refer to attached QPRF - Guideline:
- other: ECHA Guidance R.6
- Version / remarks:
- May 2008
- Principles of method if other than guideline:
- - Software tool(s) used including version: OECD QSAR Toolbox v4.5, Danish QSAR database
- Model(s) used: SciQSAR version 3.1.00
- Model description: see field 'Justification for non-standard information' and 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information' and 'Attached justification' - Type of assay:
- in vitro mammalian chromosome aberration test
- Specific details on test material used for the study:
- CP(=O)(Oc1ccccc1)Oc1ccccc1
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: not applicable
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- not applicable
- True negative controls validity:
- not applicable
- Positive controls validity:
- not applicable
- Remarks on result:
- no mutagenic potential (based on QSAR/QSPR prediction)
- Conclusions:
- Test item was predicted negative for Chromosome aberration in CHO cells by SciQSAR model (Danish QSAR database).
- Executive summary:
Test item was predicted negative for Chromosome aberration in CHO cells by SciQSAR model (Danish QSAR datatbase), which is implemented in OECD QSAR toolbox v4.5. The prediction falls into the applicability domain of this model.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Study period:
- 23 MAY 2022
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
OECD QSAR Toolbox v4.5, Danish QSAR database
2. MODEL (incl. version number)
Battery model (v1.0) in Danish QSAR database
This model gives an average value from 3 different models; SciQSAR v3.1.00, Leadscope v3.1.1‐10, and Caseultra v1.4.6.6
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CP(=O)(Oc1ccccc1)Oc1ccccc1
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please refer to attached QMRF
5. APPLICABILITY DOMAIN
Please refer to attached QPRF - Guideline:
- other: ECHA Guidance R.6
- Version / remarks:
- May 2008
- Principles of method if other than guideline:
- - Software tool(s) used including version: OECD QSAR Toolbox v4.5, Danish QSAR database
- Model(s) used: Battery model v1.0 (this model gives an average value from 3 different models; SciQSAR v3.1.00, Leadscope v3.1.1‐10, and Caseultra v1.4.6.6)
- Model description: see field 'Justification for non-standard information' and 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information' and 'Attached justification' - Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- CP(=O)(Oc1ccccc1)Oc1ccccc1
- Species / strain / cell type:
- S. typhimurium, other: multiple strains
- Metabolic activation:
- with and without
- Species / strain:
- S. typhimurium, other: multiple strains
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: not applicable
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- not applicable
- True negative controls validity:
- not applicable
- Positive controls validity:
- not applicable
- Remarks on result:
- no mutagenic potential (based on QSAR/QSPR prediction)
- Conclusions:
- Ames mutagenicity was predicted by the battery model (Danish QSAR database). The substance was predicted to be negative. The prediction falls into the applicability domain of this model.
- Executive summary:
Ames mutagenicity was predicted by the battery model (Danish QSAR database). This model gives an average value from 3 different models; SciQSAR, Leadscope, and Caseultra model. The substance was predicted to be negative. The prediction falls into the applicability domain of this model.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2012-07-02 to 2012-08-20
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- new OECD Guideline for this test: OECD Guideline 490 (issued in 2015)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- thymidine kinase (TK) locus
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI 1640 complete
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes - Additional strain / cell type characteristics:
- other: high proliferation rate (doubling time 10 - 12 h in stock cultures) and cloning efficiencies of untreated cells of usually more than 50 %; a stable karyotype with a near diploid (40 ± 2) chromosome number
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/β-naphthoflavone induced Wistar rat liver microsome preparations (S9 mix)
- Test concentrations with justification for top dose:
- Pre-experiment: 19.4, 38.8, 77.5, 155, 310, 620, 1240 and 2480 µg/mL
Main Experiment I: 9.7, 19.4, 38.8, 77.5, 155 and 310 mg/mL (without S9 mix); 19.4, 38.8, 77.5, 155, 310, 465 and 620 µg/mL (with S9 mix);
Main Experiment II: 9.7, 19.4, 38.8, 77.5, 116.3 and 155 mg/mL (without S9 mix); 19.4, 38.8, 77.5, 155, 310, 387.5 and 465 µg/mL (with S9 mix); - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: [DMSO]. The final concentration of DMSO in the culture medium will be 0.5 % (v/v).
- Justification for choice of solvent/vehicle: the substance is well soluble in DMSO. - Untreated negative controls:
- yes
- Remarks:
- solvent control
- Negative solvent / vehicle controls:
- yes
- Remarks:
- negative control
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- methylmethanesulfonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Preincubation period: thawed stock cultures were propagated in RPMI 1640 complete culture medium and the cells were subcultured two times prior to treatment (until density of 1x10E7 and 3x10E6 during 4h and 24 h exposure, respectively);
- Exposure duration: 4 and 24 hours in the experiments I and II, respectively;
- Expression time (cells in growth medium): 48 hours;
- Selection time (if incubation with a selection agent): not reported
SELECTION AGENT (mutation assays): TFT (Trifluorothymidine).
NUMBER OF REPLICATIONS: The cell density was determined each day and adjusted to 3x10E5 cells/mL, if necessary.
NUMBER OF CELLS EVALUATED: 3x10E5 cells/mL for relative suspension growth; 4x10E3 cells in selective medium; 2 cells per well into microtiter plate for cloning efficiency.
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency was determined by seeding about 2 cells per well into microtiter plates (same medium without TFT). The plates were incubated at 37 °C ± 1.5 °C in 4.5 % CO2/95.5 % water saturated air for 10 - 15 days. Then the plates were evaluated. The relative total growth (RTG) is calculated by the RSG multiplied by the viability.
- relative suspension growth (RSG) of the treated cell cultures was calculated at the end of the growth period by the day 1 fold-increase in cell number multiplied by the day 2 fold-increase in cell number according to the method of Clive and Spector:
D. Clive, J.F.S. Spector
Laboratory procedure for assessing specific locus mutation at the TK locus in cultured L5178Y mouse lymphoma cells
Mutation Research 31, 17-29, 1975. - Evaluation criteria:
- A test item is classified as mutagenic if the induced mutation frequency reproducibly exceeds a threshold of 126 colonies per 10E6 cells above the corresponding solvent control.
A relevant increase of the mutation frequency should be dose-dependent.
A mutagenic response is considered to be reproducible if it occurs in both parallel cultures.
However, in the evaluation of the test results the historical variability of the mutation rates in the solvent con¬trols of this study are taken into consideration.
Results of test groups are generally rejected if the relative total growth is less than 10 % of the vehicle control unless the exception criteria specified by the IWGT recommendations are met.
Whenever a test item is considered mutagenic according to the above mentioned criteria, the ratio of small versus large colonies is used to differentiate point mutations from clastogenic effects. If the increase of the mutation frequency is accompanied by a reproducible and dose dependent shift in the ratio of small versus large colonies clastogenic effects are indicated.
A test item is classified as non-mutagenic if the induced mutation frequency does not reproducibly exceed a threshold of 126 colonies per 106 cells above the corresponding solvent control.
A test item not meeting the conditions for a classification as mutagenic or non-mutagenic will be considered equivocal in this assay and may be considered for further investigation - Statistics:
- A linear regression (least squares) was performed to assess a possible dose dependent increase of mutant frequencies using SYSTAT11 (SYSTAT Software, Inc., 501, Canal Boulevard, Suite C, Richmond, CA 94804, USA) statistics software. The number of mutant colonies obtained for the groups treated with the test item was compared to the solvent control groups. A trend is judged as significant whenever the p-value (probability value) is below 0.05. However, both, biological relevance and statistical significance were considered together.
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at the two highest concentrations in experiment I (465 and 620 µg/L) and II (387.5 and 465 µg/L) with metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no effects
- Effects of osmolality: no effects
- Precipitation: The test medium (main experiments) was checked for precipitation or phase separation visible to the naked eye at the end of the 4 hours treatment just before the test item was removed. Neither phase separation nor precipitation occurred up to the maximum concentration with and without metabolic activation.
- Other confounding effects: no
RANGE-FINDING/SCREENING STUDIES: The pre-experiment was performed in the presence (4 h treatment) and absence (4 h and 24 h treatment) of metabolic activation. Test item concentrations between 19.4 µg/mL and 2480 µg/mL (equal to a molar concentration of approximately 10 mM) were used. The highest concentration in the pre-experiment was chosen with regard to the purity (99.88%) and the molecular weight (248 g/mol) of the test item.
Toxic effects leading to RSG values below 50 % were observed following 4 hours treatment at 310.0 µg/mL and above with and without metabolic activation. After 24 hour treatment without metabolic activation toxic effects were noted at 155.0 µg/mL and above.
The test medium was checked for precipitation or phase separation at the end of the treatment period (4 and 24 hours) just before the test item was removed. Phase separation was observed following 4 hour treatment at 310.0 µg/mL and above without metabolic activation and at 620 µg/mL and above with metabolic activation.
Both, pH value and osmolarity was determined in the pre-experiment at the highest concentration of the test item and in the solvent control without metabolic activation. There was no relevant shift of both parameters. To overcome problems with possible deviations in toxicity and solubility the main experiments were started with more than four concentrations (see above).
COMPARISON WITH HISTORICAL CONTROL DATA: yes
ADDITIONAL INFORMATION ON CYTOTOXICITY: Relevant cytotoxic effect indicated by a relative total growth of less than 50 % of survival was observed in the first experiment at 155.0 µg/mL without metabolic activation (both cultures) and at 465.0 µg/mL with metabolic activation (culture II only, culture I was not analysable due to exceedingly severe cytotoxic effects). In the second experiment cytotoxic effects as described above occurred at 116.3 µg/mL and above without metabolic activation and at 310.0 µg/mL and above with metabolic activation. The recommended cytotoxic range of approximately 10-20 % RTG was covered with and without metabolic activation. The data generated in experiment I at 310 µg/mL without metabolic activation (both cultures) are not considered valid since the Relative Total Growth (RTG) remained far below the threshold of 10 % in both parallel cultures. - Conclusions:
- In conclusion it can be stated that during the mutagenicity test described and under the experimental conditions reported the test item did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation. Therefore, Diphenyl methylphosphonate is considered to be non-mutagenic in this mouse lymphoma assay.
- Executive summary:
The study was performed to investigate the potential of Diphenyl methylphosphonate to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y.
The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The second experiment was performed with a treatment period of 24 hours in the absence of metabolic activation and 4 hours in the presence of metabolic activation.
The highest concentration (2480 µg/mL) applied in the pre-experiment was chosen with regard to the molecular weight of the test item corresponding to a molar concentration of about 10 mM. The concentration range of the main experiments was limited by cytotoxic effects of the test item. The concentrations which have been evaluated were between 19.4 µg/mL and 310 µg/mL (experiment I, with and without metabolic activation and experiment II with metabolic activation) and between 19.4 and 155 µg/mL (experiment II without metabolic activation).
No substantial and reproducible dose dependent increase in mutant colony numbers was observed in both main experiments. No relevant shift of the ratio of small versus large colonies was observed up to the maximal concentration of the test item.
Appropriate reference mutagens were used as positive controls and showed a distinct increase in induced mutant colonies, indicating that the tests were sensitive and valid.
Conclusion
In conclusion it can be stated that during the mutagenicity test described and under the experimental conditions reported the test item did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation.
Therefore, Diphenyl methylphosphonate is considered to be non-mutagenic in this mouse lymphoma assay.
Referenceopen allclose all
Pre-experiment
The osmolarity and the pH-value were determined in culture medium of the solvent control and of the maximum concentration in the pre-experiment without metabolic activation:
|
Solvent control |
Diphenyl methylphosphonate |
Osmolarity mOsm |
369 |
340 |
pH-value |
7.50 |
7.52 |
Main experiment
The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The second experiment was solely performed in the absence of metabolic activation with a treatment period of 24 hours. According to the results of the pre-test at least four adequate concentrations were chosen for the mutation experiment. However, to overcome problems with possible deviations in toxicity and solubility the main experiments were started with more than four concentrations (see above).
Following the expression phase of 48 hours the cultures at the lowest concentration in experiment I and II without metabolic activation were not continued since a minimum of only four analysable concentrations is required by the guidelines. The cultures at the two highest concentrations in experiment I and II with metabolic activation were not continued due to exceedingly strong toxic effects.
Therefore, the main experiments were evaluated at the following concentrations:
Experiment I:
without S9
mix: 19.4; 38.8; 77.5; 155.0; and 310.0
µg/mL
with S9 mix: 19.4; 38.8; 77.5;
155.0; and 310.0 µg/mL
Experiment II:
without S9
mix: 19.4; 38.8; 77.5; 116.3; and 155.0
µg/mL
with S9 mix: 19.4; 38.8; 77.5;
155.0; and 310.0 µg/mL
No substantial and reproducible dose dependent increase of the mutation frequency was observed with and without metabolic activation. The mutation frequency did not reach or exceed the threshold of 126 above the corresponding solvent control.
A linear regression analysis (least squares) was performed to assess a possible dose dependent increase of mutant frequencies using SYSTATâ11 statistics software. No significant dose dependent trend of the mutation frequency indicated by a probability value of <0.05 was determined in any of the experimental groups.
In this study the range of the solvent controls was from 48 up to 78 mutant colonies per 106cells; the range of the groups treated with the test item was from 25 up to 86 mutant colonies per 106cells. The lowest solvent control value (48 colonies per 106cells) fell just short of the recommended 50 – 170 x 106control range as stated under paragraph 8.12,acceptability of the assay of this report. The data are acceptable however, as the mutant frequency in the parallel culture (55 colonies per 106cells) and the mean of both parallel cultures (51.5 colonies per 106cells) is fully acceptable.
MMS (19.5 µg/mL in experiment I and 13.0 µg/mL in experiment II) and CPA (3.0 µg/mL and 4.5 µg/mL in both main experiments) were used as positive controls and showed a distinct increase in induced total mutant colonies at acceptable levels of toxicity with at least one of the concentrations of the controls. Table 1: p-valuesexperimental group |
p-value |
experiment I, culture I without S9 mix |
0.735 |
experiment I, culture II without S9 mix |
0.069 |
experiment I, culture I with S9 mix |
0.597 |
experiment I, culture II with S9 mix |
0.391 |
experiment II, culture I without S9 mix |
0.372 |
experiment II, culture II without S9 mix |
0.801 |
experiment II, culture I with S9 mix |
0.276 |
experiment II, culture II with S9 mix |
0.993 |
Table 2: Summary of results
|
Conc |
S9 mix |
Relative total growth |
Mutant colonies/106cells |
Threshold |
Relative total growth |
Mutant colonies/106cells |
Threshold |
Experiment I (4h treatment) |
|
|
Culture I |
Culture II |
||||
DMSO |
|
- |
100.0 |
63 |
189 |
100.0 |
78 |
204 |
Positive control (MMS) |
19.5 |
- |
34.0 |
275 |
189 |
40.5 |
291 |
204 |
Test item |
9.7 |
- |
Culture was not continued# |
Culture was not continued# |
||||
19.4 |
- |
139.9 |
25 |
189 |
133.3 |
45 |
204 |
|
38.8 |
- |
103.7 |
41 |
189 |
130.2 |
52 |
204 |
|
77.5 |
- |
109.3 |
39 |
189 |
103.5 |
42 |
204 |
|
155.0 |
- |
25.1 |
41 |
189 |
19.7 |
26 |
204 |
|
310.0 |
- |
0.4 |
71 |
189 |
0.1 |
0 |
204 |
|
Experiment I (4h treatment) |
|
|
Culture I |
Culture II |
||||
DMSO |
|
+ |
100.0 |
52 |
178 |
100.0 |
51 |
177 |
Positive control (CPA) |
3.0 |
+ |
92.6 |
107 |
178 |
95.8 |
75 |
177 |
Positive control (CPA) |
4.5 |
+ |
31.7 |
367 |
178 |
27.5 |
289 |
177 |
Test item |
19.4 |
+ |
136.6 |
59 |
178 |
Culture was not continued# |
||
38.8 |
+ |
116.7 |
81 |
178 |
79.3 |
51 |
177 |
|
77.5 |
+ |
99.6 |
54 |
178 |
115.8 |
42 |
177 |
|
155.0 |
+ |
79.6 |
86 |
178 |
89.9 |
33 |
177 |
|
310.0 |
+ |
67.3 |
41 |
178 |
81.7 |
31 |
177 |
|
465.0 |
+ |
Culture was not continued## |
10.6 |
80 |
177 |
|||
620.0 |
+ |
Culture was not continued## |
Culture was not continued## |
|||||
Experiment II |
|
|
Culture I |
Culture II |
||||
DMSO |
|
- |
100.0 |
68 |
194 |
100.0 |
64 |
190 |
Positive control (MMS) |
13.0 |
- |
34.3 |
260 |
194 |
29.0 |
311 |
190 |
Test item |
9.7 |
- |
Culture was not continued# |
Culture was not continued# |
||||
19.4 |
- |
75.8 |
45 |
194 |
95.0 |
46 |
190 |
|
38.8 |
- |
66.6 |
46 |
194 |
94.2 |
42 |
190 |
|
77.5 |
- |
63.3 |
55 |
194 |
75.4 |
55 |
190 |
|
116.3 |
- |
15.8 |
60 |
194 |
28.0 |
48 |
190 |
|
155.0 |
- |
18.8 |
36 |
194 |
13.0 |
53 |
190 |
|
Experiment II |
|
|
Culture I |
Culture II |
||||
DMSO |
|
+ |
100.0 |
55 |
181 |
100.0 |
48 |
174 |
Positive control (CPA) |
3.0 |
+ |
40.2 |
271 |
181 |
49.8 |
198 |
174 |
Positive control (CPA) |
4.5 |
+ |
25.4 |
523 |
181 |
53.0 |
310 |
174 |
Test item |
19.4 |
+ |
82.5 |
52 |
181 |
59.5 |
46 |
174 |
38.8 |
+ |
49.0 |
77 |
181 |
90.8 |
40 |
174 |
|
77.5 |
+ |
130.4 |
47 |
181 |
98.8 |
55 |
174 |
|
155.0 |
+ |
71.2 |
56 |
181 |
87.8 |
54 |
174 |
|
310.0 |
+ |
11.3 |
41 |
181 |
7.3 |
44 |
174 |
|
387.5 |
+ |
Culture was not continued## |
Culture was not continued## |
|||||
465.0 |
+ |
Culture was not continued## |
Culture was not continued## |
threshold = number of mutant colonies per 106cells of each solvent control plus 126
# culture was not continued since a minimum of only four analysable concentrations is required
## culture was not continued due to exceedingly severe cytotoxic effects
The values printed in bold are judged as invalid, since the acceptance criteria are not met (RTG < 10 % in both parallel cultures).Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
A Bacterial Reverse Mutation Test (AMES Test; according to OECD 471 / OPPTS 870.5100 / EC B.13/14 / GLP) and an in vitro mammalian cell micronucleus assay (L5178Y mouse lymphoma cell line, according to OECD 487 / GLP) have been ordered in a CRO to improve the dataset for this endpoint.
Gene mutation in mammalian cells (Mouse Lymphoma Assay), OECD 476 (now OECD 490), GLP
A study was performed to investigate the potential of Diphenyl methylphosphonate to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y (Wollny, 2012; Report No. 1477102).
The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The second experiment was performed with a treatment period of 24 hours in the absence of metabolic activation and 4 hours in the presence of metabolic activation.
The highest concentration (2480 µg/mL) applied in the pre-experiment was chosen with regard to the molecular weight of the test item corresponding to a molar concentration of about 10 mM. The concentration range of the main experiments was limited by cytotoxic effects of the test item. The concentrations which have been evaluated were
No substantial and reproducible dose dependent increase in mutant colony numbers was observed in both main experiments. No relevant shift of the ratio of small versus large colonies was observed up to the maximal concentration of the test item.
Appropriate reference mutagens were used as positive controls and showed a distinct increase in induced mutant colonies, indicating that the tests were sensitive and valid. In conclusion, diphenyl methylphosphonate did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation.
Gene mutation in bacteria
Ames mutagenicity in S. typhimurium was predicted by the battery model (Danish QSAR database). This model gives an average value from 3 different models; SciQSAR, Leadscope, and Caseultra model. The substance was predicted to be negative. The prediction falls into the applicability domain of this model.
Chromosome aberration in mammalian cells
The substance was predicted negative for Chromosome aberration in CHO cells by SciQSAR model (Danish QSAR datatbase), which is implemented in OECD QSAR toolbox v4.5. The prediction falls into the applicability domain of this model.
Justification for classification or non-classification
Based on the presented results, the registered substance is not subject to classification and labelling according to Regulation (EC) No 1272/2008.
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