Registration Dossier
Registration Dossier
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EC number: 231-835-0 | CAS number: 7758-16-9
- 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
A weight of evidence approach is used on the test substance and analagous substances to fulfil the Annex VII, Section 8.4.1 endpoint: in vitro gene mutation study in bacteria.
A key study performed on an analogous substance is available for the Annex VIII Section 8.4.2 in vitro cytogenicity in mammalian cells and Section 8.4.3 in vitro gene mutation study in mammalian cells endpoint.
A range of supporting studies are available for all endpoints, including the Annex VIII Section 8.4.2 in vitro cytogenicity study in mammalian cells or in vitro micronucleus study.
None of the studies suggest the substance is mutagenic.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- no data
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category
(1) The source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table, sodium or potassium, and pyrophosphoric/phosphoric acid. Thus, they all share the Na+ or K+ cation and the P2O74-/PO34- anion as common functional groups.
(2) All members of the group will ultimately dissociate into the common breakdown products of the Na+ or K+ cations and the P2O74-/PO34- anion. In biological systems pyrophosphates will be metabolised by intestinal alkaline phosphatase and it is assumed that the majority of diphosphate is absorbed as orthophosphate and thus both the target and source substances contain the same breakdown products.
(3) Potassium and sodium cations and phosphate anions are essential micronutrients and as such, their uptake is tightly regulated and is therefore not considered to pose a risk for genotoxicity.
It is therefore deemed scientifically justified to avoid any further testing and use the data from a study conducted on an orthophosphate (with either a potassium or sodium cation) for hazard assessment purposes.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.
3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.
4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’. - Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- AMES study conducted using 3 strains of S. typhimurium only, positive control substances differ from those recommended in the guideline, only one dose level investigated
- GLP compliance:
- no
- Remarks:
- Study predates GLP
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- not applicable
- Species / strain / cell type:
- S. typhimurium, other: TA 1535, TA 1537, TA 1538
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not specified
- Species / strain / cell type:
- yeast, other: Saccharomyces cerevisiae D4
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- Metabolic activation preparations derived from the tissues of ICR random bred male mice, Sprague-Dawley adult male rats and Macaca mulatta adult male primates
- Test concentrations with justification for top dose:
- Plate test (S. typhimurium): 0.1%
Suspension tests (S. typhimurium): 1.13, 2,25%
Suspension tests (S. cerevisiae): 0.05, 0.1% - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: no data
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- Used in non-activation assays with tester strains TA 1535 and S. cerevisiae D4
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: quinacrine mustard
- Remarks:
- Used in a non-activation assay with tester strain TA 1537
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- Used in a non-activation assay with tester strain TA 1538
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: dimethylnitrosamine
- Remarks:
- Used in an activation assay with tester strain TA 1535 and S. cerevisiae D4
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- Used in an activation assay with tester strains TA 1537 and TA 1538
- Details on test system and experimental conditions:
- Two types of assay were conducted; plate tests and suspension tests.
1. PLATE TESTS (bacteria only):
METHOD OF APPLICATION:
Nonactivation studies: plate incorporation
Activation studies: in suspension
DURATION
- Exposure duration: 4 days at 37°C
2. SUSPENSION TESTS (bacteria and yeast):
METHOD OF APPLICATION: in suspension
Nonactivation tests:
DURATION
- Exposure duration: 4 hours at 30°C (yeast assays), 1 hour at 37°C (bacterial assay)
- Selection time (if incubation with a selection agent): 48 hours at 37°C (bacterial assay), 3-5 days at 30°C
Activation tests:
DURATION
- Exposure duration: 4 hours at 30°C (yeast assays), 1 hour at 37°C (bacterial assay)
DETERMINATION OF CYTOTOXICITY
- Method: Each chemical was tested for survival against the specific indicator strains over a range of doses to determine 50% survival dose. - Evaluation criteria:
- no data
- Statistics:
- No data
- Species / strain:
- S. typhimurium, other: TA 1353, TA 1357, TA 1358
- 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:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- yeast, other: Saccharomyces cerevisiae D4
- 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:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: test substance was soluble at the treatment concentration employed in this study. All tests were conducted in an aqueous environment.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Test date for toxicity determinations: September 15, 1974
The 50% survival level was determined for bacterial and yeast indicator organisms by conducting survival curves with the test compound at the following concentrations (w/w or v/v): For D4: 1, 2, 3, 4, 5. For S. typhimurium: 0.001, 0.005, 0.01, 0.05, 0.1%
-Concentrations of the test compound used in mutagenicity tests:
BACTERIA:
- Plate tests: 0.1%
-1/4 50% survival: 0.05%
-1/2 50% survival: 0.1%
YEAST:
- Plate tests: --
-1/4 50% survival: 1.13%
-1/2 50% survival: 2.25% - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Tetrasodium pyrophosphate did not exhibit genetic activity in any of the assays employed and is considered to be non-mutagenic under the conditions of this study.
This data is submitted to provide a weight of evidence to support the conclusion that disodium dihydrogenpyrophosphate is unlikely to produce a positive genotoxic response. - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Remarks:
- .
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category
(1) The source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table, sodium or potassium, and pyrophosphoric/phosphoric acid. Thus, they all share the Na+ or K+ cation and the P2O74-/PO34- anion as common functional groups.
(2) All members of the group will ultimately dissociate into the common breakdown products of the Na+ or K+ cations and the P2O74-/PO34- anion. In biological systems pyrophosphates will be metabolised by intestinal alkaline phosphatase and it is assumed that the majority of diphosphate is absorbed as orthophosphate and thus both the target and source substances contain the same breakdown products.
(3) Potassium and sodium cations and phosphate anions are essential micronutrients and as such, their uptake is tightly regulated and is therefore not considered to pose a risk for genotoxicity.
It is therefore deemed scientifically justified to avoid any further testing and use the data from a study conducted on an orthophosphate (with either a potassium or sodium cation) for hazard assessment purposes.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.
3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.
4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’. - Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The mutation test was carried out in accordance with the preincubation procedure described by Ames et al.
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Not applicable
- Species / strain / cell type:
- S. typhimurium, other: TA 97 and TA 102
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- 0.1, 0.5, 1, 5, 10 mg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: distilled water
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- Used with tester strain TA 97 without S9 mix Migrated to IUCLID6: (50 µg)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 mins
- Exposure duration: no data
DETERMINATION OF CYTOTOXICITY
No data - Evaluation criteria:
- No data
- Statistics:
- Kruskal-Wallis test and regression analysis
- Species / strain:
- S. typhimurium, other: TA 97 and TA 102
- 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:
- valid
- Additional information on results:
- No data
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- The authors conclude that sodium pyrophosphate is non-mutagenic under the conditions of this study.
This data is submitted to provide a weight of evidence to support the conclusion that disodium dihydrogenpyrophosphate is unlikely to produce a positive genotoxic response. - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- No postive control data
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- not specified
- Remarks:
- Study pre-dates GLP
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Not applicable
- Species / strain / cell type:
- S. typhimurium, other: TA 92, TA 1535, TA 100, TA 1537, TA 94 and TA 98
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with
- Metabolic activation system:
- Rat liver S-9
- Test concentrations with justification for top dose:
- Maximum dose: 10.0 mg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Phosphate buffer
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- Remarks:
- exposed to appropriate solvent or untreated
- True negative controls:
- not specified
- Positive controls:
- no
- Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 minutes at 37°C
- Exposure duration: 2 days at 37 °C- Evaluation criteria:
The result was considered positive if the number of colonies found was twice the number in the control (exposed to the appropriate solvent or untreated). A negative result indicates that no significant increases in the numbers of revertant colonies were detected in any S. typhimurium strains at the maximum dose.- Statistics:
- No data
- Species / strain:
- S. typhimurium, other: TA 92, TA 1535, TA 100, TA 1537, TA 94 and TA 98
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not examined
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- not applicable
- Additional information on results:
- No data
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Disodium dihydrogen phosphate is considered to be non-mutagenic in strains of S.typhimurium, under the conditions of this assay.
This data is submitted to provide a weight of evidence to support the conclusion that disodium dihydrogenpyrophosphate is unlikely to produce a positive genotoxic response. - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category
(1) The source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table, sodium or potassium, and pyrophosphoric/phosphoric acid. Thus, they all share the Na+ or K+ cation and the P2O74-/PO34- anion as common functional groups.
(2) All members of the group will ultimately dissociate into the common breakdown products of the Na+ or K+ cations and the P2O74-/PO34- anion. In biological systems pyrophosphates will be metabolised by intestinal alkaline phosphatase and it is assumed that the majority of diphosphate is absorbed as orthophosphate and thus both the target and source substances contain the same breakdown products.
(3) Potassium and sodium cations and phosphate anions are essential micronutrients and as such, their uptake is tightly regulated and is therefore not considered to pose a risk for genotoxicity.
It is therefore deemed scientifically justified to avoid any further testing and use the data from a study conducted on an orthophosphate (with either a potassium or sodium cation) for hazard assessment purposes.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.
3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.
4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’. - Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- Study does not cover all tester strains recommended in the guideline. Positive control substances differ from those recommended in the guideline
- Principles of method if other than guideline:
- In addition to the bacterial studies, the same assay was also performed on Saccharomyces cerevisiae, strain: D4.
- GLP compliance:
- not specified
- Remarks:
- Stduy predates GLP
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Not applicable
- Species / strain / cell type:
- S. typhimurium, other: TA 1535, TA 1537, TA 1538 TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not specified
- Species / strain / cell type:
- yeast, other: Saccharomyces cerevisiae, D4
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S-9 homogenate prepared from Sprague-Dawley adult male rat liver induced by Aroclor 1254 5-days prior to kill.
- Test concentrations with justification for top dose:
- 0.001, 0.01, 0.1, 1.0 and 5 μL per plate
- Vehicle / solvent:
- - Vehicle/solvent used: distilled water
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: methylnitrosoguanidine (10 µg/plate)
- Remarks:
- Used with tester strains TA 1535, TA 100 and S. cerevisiae; D4, in assays without metabolic activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: quinacrine mustard (10 µg/plate)
- Remarks:
- Used with tester strains TA 1537, in assays without metabolic activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- Used with tester strains TA 1538 and TA 98, in assays without metabolic activation Migrated to IUCLID6: 100 µg/plate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: 2-anthramine (100 µg/plate)
- Remarks:
- Used with tester strains TA 1535 and TA 100, in assays with metabolic activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: 8-aminoquinoline (100 µg/plate)
- Remarks:
- Used with tester strains TA 1537, in assays with metabolic activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 2-acetylaminofluorene
- Remarks:
- Used with tester strains TA 1538 and TA 98, in assays with metabolic activation Migrated to IUCLID6: 100 µg/plate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: DMNA (100 µMol/plate)
- Remarks:
- Used with tester strains S. cerevisiae; D4, in assays with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: plate incorporation
DURATION
- Exposure duration: 48 hr at 37°C
- Expression time (cells in growth medium): overnight - Evaluation criteria:
- The criteria used to determine positive effects are inherently subjective and are based on historical data. Most data sets were evaluated using the following criteria:
- STRAINS TA 1353, TA-1357 and TA 1358
If the solvent control value is within the normal range, a chemical that produces a positive dose response over 3 concentrations with the lowest increase equal to 2x the solvent control value is considered to be mutagenic (positive result).
- STRAINS TA 98, TA 100 AND D4:
If the solvent control value is within the normal range, a chemical that produces a positive response of 3 concentrations with the highest increase equal to 2x the solvent value (TA 100) and 2-3x the solvent control value (TA 98 and D4) is considered to be mutagenic (positive result). The dose-response increase should start at approximately the solvent control value. - Statistics:
- no data
- Species / strain:
- S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- The compound was tested over a series of concentrations such that there was either quantitative or qualitative evidence of some chemically-induced physiological effects at the high dose level.
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- yeast, other: Saccharomyces cerevisiae, D4
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- The compound was tested over a series of concentrations such that there was either quantitative or qualitative evidence of some chemically-induced physiological effects at the high dose level.
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- ADDITIONAL INFORMATION ON CYTOTOXICITY: The substance was tested over a series of concentrations. The dose range employed in the study was below a concentration that demonstrated any toxic effect.
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- The test compound MCTR-257 did not demonstrate mutagenic activity in any of the assays conducted in this evaluation and was considered not-mutagenic under these test conditions.
This data is submitted to provide a weight of evidence to support the conclusion that disodium dihydrogenpyrophosphate is unlikely to produce a positive genotoxic response. - 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 with acceptable restrictions
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category
(1) The source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table, sodium or potassium, and pyrophosphoric/phosphoric acid. Thus, they all share the Na+ or K+ cation and the P2O74-/PO34- anion as common functional groups.
(2) All members of the group will ultimately dissociate into the common breakdown products of the Na+ or K+ cations and the P2O74-/PO34- anion. In biological systems pyrophosphates will be metabolised by intestinal alkaline phosphatase and it is assumed that the majority of diphosphate is absorbed as orthophosphate and thus both the target and source substances contain the same breakdown products.
(3) Potassium and sodium cations and phosphate anions are essential micronutrients and as such, their uptake is tightly regulated and is therefore not considered to pose a risk for genotoxicity.
It is therefore deemed scientifically justified to avoid any further testing and use the data from a study conducted on an orthophosphate (with either a potassium or sodium cation) for hazard assessment purposes.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.
3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.
4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’. - Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- not specified
- Remarks:
- Study published in the literature and therefore GLP compliance not specified.
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- Not applicable
- Species / strain / cell type:
- E. coli WP2 uvr A
- Details on mammalian cell type (if applicable):
- Not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9: induced with Aroclor 1254 or a combination of phenobarbitone and β-naphthoflavone.
- Test concentrations with justification for top dose:
- 0, 301.25, 602.5, 1,205, 2,410, 4,820 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: No data - Untreated negative controls:
- yes
- Remarks:
- 0 µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Untreated negative controls:
- yes
- Remarks:
- 0 µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Untreated negative controls:
- yes
- Remarks:
- 0 µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (2-AF)
- Untreated negative controls:
- yes
- Remarks:
- 0 µg/plate
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 2-acetylaminofluorene
- Remarks:
- Migrated to IUCLID6: (2-AA)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); without metabolic activation
preincubation; with metabolic activation
DURATION
- Preincubation period: 20 minutes or more
- Exposure duration: 48-72 hrs at 37°C
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: Cytotoxicity detected by a reduction in the number of reverting colonies, a clearing or diminution of the background lawn, or the degree of survival of treated cultures. - Evaluation criteria:
- Number of revertant colonies per plate were counted. The mutant frequency was expressed as the quotient of the number of revertant colonies over the number of colonies in the negative control. A mutagenic potential of a test item was assumed if the mutant frequency is 2.0 or higher.
- Statistics:
- No data
- 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- 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:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Tetrasodium pyrophosphate was found to be non-genotoxic in an AMES test both with and without metabolic activation.
Referenceopen allclose all
PLATE TESTS:
Table 2: Results of plate tests
TEST |
SPECIES |
TISSUE |
REVERTANTS/PLATES |
|||||
TA 1535 |
TA 1537 |
TA 1538 |
||||||
1 |
2 |
1 |
2 |
1 |
2 |
|||
1. Nonactivation |
||||||||
Positive control –(0.5 mL) |
- |
- |
>103 |
>103 |
|
|
|
|
Positive control – QM (0.25 mg) |
- |
- |
|
|
>102 |
>102 |
|
|
Positive control – NF (0.25 mg) |
- |
- |
|
|
|
|
>102 |
>102 |
Solvent control - saline |
|
|
2 |
1 |
2 |
4 |
|
|
Solvent control – DMSO (<10%) |
|
|
|
|
|
|
5 |
1 |
Test compound – 1 (0.1%) |
- |
- |
2 |
2 |
6 |
8 |
1 |
3 |
2. Activation |
||||||||
Positive control - DMNA |
Mouse |
Liver |
>103 |
>103 |
|
|
|
|
Positive control – AAF |
Liver |
|
|
44 |
43 |
>102 |
>102 |
|
Positive control – DMNA |
Lung |
2 |
4 |
|
|
|
|
|
Positive control – AAF |
Lung |
|
|
9 |
3 |
13 |
8 |
|
Positive control – DMNA |
Testes |
1 |
5 |
|
|
|
|
|
Positive control – AAF |
Testes |
|
|
6 |
10 |
3 |
3 |
|
Solvent control –DMNA |
- |
3 |
0 |
|
|
|
|
|
Solvent control – AAF |
- |
|
|
10 |
5 |
1 |
0 |
|
Solvent control – saline |
- |
1 |
1 |
|
|
|
|
|
Solvent control –DMSO (<10%) |
- |
|
|
12 |
10 |
6 |
7 |
|
Test compound (0.1%) |
Liver |
2 |
0 |
7 |
9 |
17 |
12 |
|
Test compound (0.1%) |
Lung |
1 |
2 |
8 |
5 |
8 |
7 |
|
Test compound (0.1%) |
Testes |
0 |
0 |
9 |
4 |
12 |
15 |
|
Positive control – DMNA (25 µmoles) |
Rat |
Liver |
>102 |
>102 |
|
|
|
|
Positive control – AAF (1.25 mg) |
Liver |
|
|
41 |
30 |
>102 |
>102 |
|
Positive control – DMNA (25 µmoles) |
Lung |
1 |
0 |
|
|
|
|
|
Positive control – AAF (1.25 mg) |
Lung |
|
|
7 |
10 |
5 |
0 |
|
Positive control – DMNA (25 µmoles) |
Testes |
3 |
0 |
|
|
|
|
|
Positive control – AAF (1.25 mg) |
Testes |
|
|
14 |
17 |
10 |
3 |
|
Positive control – DMNA (25 µmoles) |
- |
3 |
0 |
|
|
|
|
|
Positive control – AAF (1.25 mg) |
- |
|
|
10 |
5 |
1 |
0 |
|
Solvent control – saline |
- |
1 |
1 |
|
|
|
|
|
Solvent control –DMSO (<10%) |
- |
|
|
12 |
10 |
6 |
7 |
|
Test compound (0.1%) |
Liver |
1 |
0 |
9 |
4 |
18 |
5 |
|
Test compound (0.1%) |
Lung |
1 |
0 |
7 |
9 |
3 |
2 |
|
Test compound (0.1%) |
Testes |
0 |
2 |
4 |
11 |
5 |
6 |
|
Positive control – DMNA (25 µmoles) |
Monkey |
Liver |
>102 |
>102 |
|
|
|
|
Positive control – AAF (1.25 mg) |
Liver |
|
|
32 |
46 |
>102 |
>102 |
|
Positive control – DMNA (25 µmoles) |
Lung |
0 |
4 |
|
|
|
|
|
Positive control – AAF (1.25 mg) |
Lung |
|
|
20 |
13 |
2 |
4 |
|
Positive control – DMNA (25 µmoles) |
Testes |
1 |
1 |
|
|
|
|
|
Positive control – AAF (1.25 mg) |
Testes |
|
|
10 |
11 |
3 |
7 |
|
Positive control – DMNA (25 µmoles) |
- |
3 |
0 |
|
|
|
|
|
Positive control – AAF (1.25 mg) |
- |
|
|
10 |
5 |
1 |
0 |
|
Solvent control – saline |
- |
1 |
1 |
|
|
|
|
|
Solvent control –DMSO (<10%) |
- |
|
|
12 |
10 |
6 |
7 |
|
Test compound |
Liver |
2 |
1 |
12 |
8 |
5 |
8 |
|
Test compound |
Lung |
1 |
0 |
7 |
7 |
8 |
5 |
|
Test compound |
Testes |
0 |
0 |
5 |
5 |
7 |
8 |
SUSPENSION TESTS:
Table 3. Results of suspension tests with and without activation
Test |
Species |
Organ |
Salmonella reversion frequencies |
D4 conversion frequencies (x 10-5) |
|||
TA 1535 |
TA 1537 |
TA 1538 |
Ade+ |
Trp+ |
|||
Nonactivation |
|||||||
Positive control |
- |
- |
1104.27 |
115.80 |
48.98 |
89.60 |
112.73 |
Negative control |
- |
- |
1.46 |
11.81 |
10.61 |
6.55 |
4.37 |
High dose |
- |
- |
2.12 |
10.29 |
7.39 |
6.44 |
4.93 |
Low dose |
- |
- |
1.26 |
9.11 |
10.11 |
5.86 |
3.86 |
Activation |
|||||||
Solvent control |
- |
- |
2.42 |
6.62 |
5.82 |
5.54 |
4.62 |
Chemical control |
- |
- |
2.22 |
8.49 |
7.07 |
6.16 |
3.54 |
Positive control |
Mouse |
Liver |
731.67 |
15.10 |
29.84 |
8.20 |
8.83 |
Positive control |
Mouse |
Lung |
6.59 |
4.95 |
7.11 |
6.20 |
4.57 |
Positive control |
Mouse |
Testes |
5.62 |
2.17 |
8.59 |
6.09 |
5.41 |
High dose |
Mouse |
Liver |
0.97 |
11.07 |
7.29 |
7.17 |
6.05 |
Low dose |
Liver |
2.94 |
6.79 |
8.74 |
6.24 |
6.86 |
|
High dose |
Lung |
1.70 |
6.12 |
4.72 |
6.11 |
5.65 |
|
Low dose |
Lung |
1.00 |
4.82 |
8.00 |
7.71 |
7.13 |
|
High dose |
Testes |
0.69 |
3.07 |
5.78 |
7.19 |
4.04 |
|
Low dose |
Testes |
0.49 |
3.02 |
2.54 |
6.70 |
3.87 |
|
Solvent control |
- |
- |
2.67 |
7.52 |
9.55 |
3.40 |
2.92 |
Chemical control |
- |
- |
3.33 |
17.09 |
3.88 |
2.71 |
2.50 |
Positive control |
Rat |
Liver |
245.70 |
29.39 |
42.80 |
9.42 |
10.27 |
Positive control |
Rat |
Lung |
0.97 |
10.17 |
5.90 |
3.91 |
3.55 |
Positive control |
Rat |
Testes |
1.68 |
8.83 |
6.08 |
0.23 |
2.02 |
High dose |
Rat |
Liver |
1.33 |
9.83 |
6.91 |
-- |
3.01 |
Low dose |
Liver |
2.05 |
8.14 |
5.73 |
3.78 |
2.81 |
|
High dose |
Lung |
1.23 |
6.89 |
5.69 |
6.52 |
3.42 |
|
Low dose |
Lung |
0.71 |
6.94 |
7.69 |
5.72 |
2.63 |
|
High dose |
Testes |
1.49 |
6.94 |
1.80 |
6.68 |
4.20 |
|
Low dose |
Testes |
0.55 |
2.32* |
3.47 |
4.40 |
2.45 |
|
Solvent control |
- |
- |
2.49 |
16.19 |
13.85 |
2.86 |
1.33 |
Chemical control |
- |
- |
4.27 |
18.27 |
9.18 |
4.06 |
1.43 |
Positive control |
Monkey |
Liver |
206.49 |
26.72 |
30.32 |
9.81 |
2.82 |
Positive control |
Monkey |
Lung |
2.49 |
8.64 |
13.79 |
3.94 |
3.62 |
Positive control |
Monkey |
Testes |
2.79 |
6.91 |
8.71 |
7.10 |
3.84 |
High dose |
Monkey |
Liver |
1.60 |
15.98 |
9.51 |
5.51 |
3.06 |
Low dose |
Liver |
1.97 |
11.72 |
9.09 |
5.41 |
5.84 |
|
High dose |
Lung |
1.68 |
14.89 |
11.45 |
2.56 |
3.84 |
|
Low dose |
Lung |
2.00 |
12.41 |
8.68 |
5.75 |
2.03 |
|
High dose |
Testes |
1.22 |
8.22 |
3.26 |
2.72 |
1.09 |
|
Low dose |
Testes |
3.81 |
5.79 |
3.56 |
5.00 |
2.50 |
* Data from repeat tests
Table 1: Positive control data
Substance |
Solvent |
Dose (µg/plate) |
No. of revertants / plate (mean of 3 plates) |
|||
TA 97 |
TA 102 |
|||||
-S9 |
+S9 |
-S9 |
+S9 |
|||
9-Aminoacridine |
DMSO |
50 µg |
627 ± 2131 |
|
|
|
Mitomycin C |
DMSO |
0.5 µg |
|
|
2438 ± 236 |
|
2-Aminoanthracene |
DMSO |
5 µg |
|
2104 ± 656 |
|
1144 ± 226 |
1. mean and standard deviation (n=19)
Table 2: Results of an AMES study conducted on sodium pyrophosphate:
Substance |
Solvent |
Dose (mg/plate) |
No. of revertant / plate (mean of 3 plates) |
|||
TA 97 |
TA 102 |
|||||
-S9 |
+S9 |
-S9 |
+S9 |
|||
Sodium pyrophosphate |
DW |
10 |
122 |
187 |
334 |
328 |
5 |
125 |
195 |
348 |
333 |
||
1 |
114 |
205 |
334 |
489 |
||
0.5 |
130 |
207 |
342 |
476 |
||
0.1 |
150 |
202 |
341 |
500 |
||
0 |
151 |
184 |
340 |
496 |
Table 1: Results as presented in study:
Additive |
Max dose (mg/plate) |
Result |
Disodium dihydrogen phosphate |
10.0 |
Negative |
Table 2. Results of anstudy on MCTR-257
Test |
Dosage (μL) |
Revertants per plate |
|||||||||||
TA-1353 |
TA-1357 |
TA-1358 |
TA-98 |
TA-100 |
D4* |
||||||||
1 |
2 |
1 |
2 |
1 |
2 |
1 |
2 |
1 |
2 |
1 |
2 |
||
Non-activation |
|||||||||||||
Solvent control |
- |
11 |
|
10 |
|
11 |
|
30 |
|
154 |
|
68 |
|
Positive control |
** |
236 |
|
901 |
|
408 |
|
721 |
|
530 |
|
>1000 |
|
Test compound |
0.001 |
15 |
|
5 |
|
11 |
|
20 |
|
191 |
|
48 |
|
0.01 |
8 |
|
13 |
|
8 |
|
24 |
|
203 |
|
55 |
|
|
0.1 |
25 |
|
6 |
|
5 |
|
19 |
|
212 |
|
54 |
|
|
1.0 |
19 |
|
9 |
|
5 |
|
21 |
|
198 |
|
44 |
|
|
5.0 |
12 |
|
10 |
|
5 |
|
20 |
|
210 |
|
39 |
|
|
Activation |
|||||||||||||
Solvent control |
- |
13 |
|
16 |
|
16 |
|
43 |
|
124 |
|
35 |
|
Positive control |
*** |
242 |
|
208 |
|
428 |
|
650 |
|
>1000 |
|
82 |
|
Test compound |
0.001 |
17 |
|
23 |
|
20 |
|
45 |
|
162 |
|
50 |
|
0.01 |
19 |
|
21 |
|
22 |
|
41 |
|
170 |
|
61 |
|
|
0.1 |
16 |
|
15 |
|
23 |
|
48 |
|
170 |
|
58 |
|
|
1.0 |
14 |
|
23 |
|
18 |
|
40 |
|
154 |
|
52 |
|
|
5.0 |
16 |
|
6 |
|
21 |
|
39 |
|
179 |
|
52 |
|
* TRY+ convertants per plate.
**
TA-1535 |
MNNG |
10 μg/plate |
TA-1537 |
QM |
10 μg/plate |
TA-1538 |
NF |
100 μg/plate |
TA-98 |
NF |
100 μg/plate |
TA-100 |
MNNG |
10 μg/plate |
D4 |
MNNG |
10 μg/plate |
***
TA-1535 |
ANTH |
100 μg/plate |
TA-1537 |
AMQ |
100 μg/plate |
TA-1538 |
AAF |
100 μg/plate |
TA-98 |
AAF |
100 μg/plate |
TA-100 |
ANTH |
100 μg/plate |
D4 |
DMNA |
100 micromoles/plate |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Justification for classification or non-classification
No classification for in vitro genetic toxicity is proposed. This is based on a weight of evidence approach using all relevant data on sodium acid pyrophosphate and its analogues. No further testing is considered necessary for the following reasons:
Sodium and potassium phosphates are routinely used in the nutrient broths that support cell cultures in the laboratory and as such bacteria are constantly exposed to these inorganic phosphates. In addition, disodium dihydrogenpyrophosphate will hydrolyse to sodium orthophosphates which are also found in the metabolic activation mixture (e.g. S9-mix) which is used in a chromosomal aberration test to determine whether a test chemical can be metabolized within the body to produce a compound that may be genotoxic. The constant exposure of bacteria to these materials suggests that they pose no inherent risk of genotoxicity.
As such and in accordance with Regulation (EC) No.1272/2008 (EU CLP) no classification is proposed.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.