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EC number: 237-415-3 | CAS number: 13776-88-0
- Life Cycle description
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- Endpoint summary
- Appearance / physical state / colour
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- Density
- Particle size distribution (Granulometry)
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- Solubility in organic solvents / fat solubility
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- Stability: thermal, sunlight, metals
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- Ecotoxicological Summary
- Aquatic toxicity
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- Short-term toxicity to fish
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- 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
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- Toxicological Summary
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Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The following studies are provided for aluminium metaphosphate:
In vitro gene mutation in bacteria: negative with and without metabolic activation (OECD 471, GLP)
In vitro gene mutation in mammalian cells: negative with and without metabolic activation (OECD 476, GLP)
In vivo micronucleus study in cultured human peripheral lymphocytes: negative with and without metabolic activation (OECD 487, GLP)
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 26/08/2014 - 04/12/2014
- 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:
- Performed in 2014. This study is now covered by the OECD 490 guideline.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)
- Version / remarks:
- Guideline was not available in 2014 when the study was performed
- GLP compliance:
- yes
- Type of assay:
- other: gene mutation in mammalian cells
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: C08567A
- Expiration date of the lot/batch: 23/01/2016
- Analytical purity: >95%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature 15-25°C
- Stability under test conditions: stable
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: sterilised via gamma irradiation
FORM AS APPLIED IN THE TEST (if different from that of starting material)
In suspension - Target gene:
- Thymidine kinase (Tk1)
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: Bayer Schering Pharma AG cell line L5178Y TK+/- 3.7.2C
- Suitability of cells: Appropriate cells used in accordance with the guideline
MEDIA USED
- Type and identity of media including CO2 concentration if applicable: Cell culture medium (RPMI 1640) containing 10% v/v horse serum. 5% CO2. - Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- 5 mg/l
1 mg/ml
0.2 mg/ml
0.04 mg/ml
0.008 mg/ml
0.0016 mg/ml
0.00032 mg/ml
Top dose is recommended by OECD GL 476. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: cell culture medium (RPMI 1640) containing 10% v/v horse serum
- Justification for choice of solvent/vehicle: medium is not suspected of chemical reaction with the test substance and is compatible with the survivial of the cells and the S9 activity. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- methylmethanesulfonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in suspension
- Cell density at seeding (if applicable): 0.5 x 1E6/ml
DURATION
- Exposure duration: 3 hours (first test) 4 hours (confirmatory test)
- Expression time (cells in growth medium): 48 hours
- Selection time (if incubation with a selection agent):11-14 days (with TFT)
NUMBER OF REPLICATIONS: 2
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: cloning efficiency
- Any supplementary information relevant to cytotoxicity: cloning for cloning effeciency was performed after the exposure time (CE1) and after the expression period (CE2).
CE1: each treated cell culture was diluted to 8 cells/ml = 1.6 cells per well with RPMI 1640 containing 20% v/v HS and cultivated in a humidified incubator with 5% CO2 in air at 37±1°C for 7 days.
CE2: An aliquot of each treated cell culture was diluted to 8 cells/ml - 1.6 cells per well with RPMI 1640 + 20% v/v HS and cultivated in a humidifier incubator with 5% CO2 in air at 37±1°C for 7 days. - Rationale for test conditions:
- Testing was performed in accordance with the guideline.
- Evaluation criteria:
- The cloning efficiency (CE) of cells and the spontaneous mutation frequency (MF) of negative controls should be within their limit valuesL CE ≥ 50%; MF (negative control) 50-300 x 10E-6.
The MF of positive controls should be increased 2x or more than the MF in corresponding negative controls in each experiment. - Statistics:
- Not specified
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- slight precipitations were seen in all test material concentrations ehich did not influence the results of the assay.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: pH did not change during the study
Mutation frequencies were determined from the number of wells without colonies, without big colonies(≥1/4 of well diameter, large and diffuse morphology), without small colonies (≤1/4 of the well diameter, compact morphology). A significant increase in mutation frequencies (2 x higher than the corresponding negative controls) was only found in positive controls.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data:
- Negative (solvent/vehicle) historical control data:
CE1:
Negative control (-S9): Min 0.88 - Max 1.25 (mean 0.84). SD: 0.15 Number of studies = 5
Negative control (+S9): Min 0.87 - Max 1.05 (mean 0.87). SD: 0.09 Number of studies = 5
Positive control (-S9): Min 0.63 - Max 1.01 (mean 1.04). SD: 0.14 Number of studies = 5
Positive control (+S9): Min 0.80 - Max 1.00 (mean 0.99). SD: 0.13 Number of studies = 5
CE2:
Negative control (-S9): Min 0.90 - Max 1.22 (mean 0.86). SD: 0.17 Number of studies = 5
Negative control (+S9): Min 0.93 - Max 1.24 (mean 0.85). SD: 0.16 Number of studies = 5
Positive control (-S9): Min 0.61 - Max 1.08 (mean 1.16). SD: 0.27 Number of studies = 5
Positive control (+S9): Min 0.73 - Max 1.12 (mean 1.06). SD: 0.11 Number of studies = 5
MF (big and small colonies):
Negative control (-S9): Min 61.13 - Max 115.14 (mean 676.57). SD: 168.46 Number of studies = 5
Negative control (+S9): Min 99.47 - Max 116.59 (mean 685.85). SD: 133.27 Number of studies = 5
Positive control (-S9): Min 496.35 - Max 900.51 (mean 94.05). SD: 19.75 Number of studies = 5
Positive control (+S9): Min 547.86 - Max 866.44 (mean 107.86). SD: 7.52 Number of studies = 5 - Conclusions:
- Aluminium metaphosphate did not cause genotoxic reactions in L5178Y mouse lymphoma cells with and without metabolic activation.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 20 Oct 2014 - 17 Feb 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254
- Test concentrations with justification for top dose:
- 313, 625, 1250, 2500 and 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: distilled water was used as solvent/vehicle, since this medium is not suspected of chemical reaction with the test substance and is compatible with the survival of the bacteria and the S9 activity. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene (10-50 µg/plate); benzo[a]pyrene (20 µg/plate)
- Remarks:
- with metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: daunomycin (6 µg/plate); sodium azide (1.5 µg/plate); ICR 191 acridine (1 µg/plate); 4-nitroquinoline-1-oxide (2 µg/plate)
- Remarks:
- without metabolic activation
- Details on test system and experimental conditions:
- INITIAL TEST
METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48-72 h
NUMBER OF REPLICATIONS: 3
CONFIRMATORY TEST
METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48-72 h
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of revertant colonies on the test plates compared to the solvent/vehicle control plates - Evaluation criteria:
- In general, a 2 or 2.5-fold increase in the number of revertant colonies per plate over the background (spontaneous revertant frequency) is used as a criterion to distinguish active mutagens from non-mutagenic materials. The presence of dose response is a further criterion for mutagenic materials.
- 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:
- valid
- Untreated negative controls validity:
- not examined
- 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:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: slight precipitation was seen at all test material concentrations, which did not influence the results of the assay
RANGE-FINDING/SCREENING STUDIES: A preliminary experiment was conducted to determine cytotoxicity and solubility of the test substance. Starting with the test material concentration of 5 mg/plate (recommended by OECD GL 471) and subsequent serial dilutions (ratio 1:2) following concentrations of test material were applied: 5, 2.5, 1.25, 0.625, 0.313 and 0.156 mg/plate on two bacteria strains (TA 98 and TA 1535) with different mutation type (frameshift and base-pair substitution) with and without metabolic activation.
The highest concentration of that solution was chosen for the main test that caused low cytotoxicity and/or where the precipitate did not interfere with the scoring according to OECD GL 471.
COMPARISON WITH HISTORICAL CONTROL DATA: The solvent and positive control values were acceptable and compatible with the historical control values. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Under the conditions of this study, the test material did not induce reverse gene mutations in Salmonella typhimurium (TA 98, TA 100, TA 1535 and TA 1537) or Escherichia coli (WP2 uvrA) tester strains. Therefore, the test material is considered to be not mutagenic in bacteria.
- Endpoint:
- in vitro cytogenicity / micronucleus study
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 09 November 2015 - 04 February 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 487 (In vitro Mammalian Cell Micronucleus Test)
- Version / remarks:
- adopted September 26, 2014
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian cell micronucleus test
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: C26967A
- Expiration date of the lot/batch: 27/06/2016
- Purity test date: 14/07/2015
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At +10°C to +25°C, in a tightly closed container and stored in a cool, dry and well-ventilated place.
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: The test item was not soluble in any of the solvents recommended: aqueous media,
dimethylsulfoxide (DMSO), ethanol, acetone or 0.05 M H2SO4 solution). However, Aluminium metaphosphate was completely soluble as 3 μg per mL 0.05 M HCl solution by employing an ultrasonic bath (45 kHz) at 37°C for 10 minutes for preparing a solution. Hence, Aluminium metaphosphate was suspended in 0.05 M HCl solution for a concentration of 10 μg per mL medium. For concentrations lower than 10.0 μg/mL medium, the test item was completely dissolved in 0.05 M HCl.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Fresh preparations of the test item were prepared on the day of the experiment and used for the treatment in all experimental parts. No correction factor was used. - Species / strain / cell type:
- lymphocytes: human peripheral lymphocytes
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: Human peripheral blood
- Suitability of cells: cells identified in OECD guideline.
- Sex, age and number of blood donors if applicable:Healthy non-smoking male of female individuals (18-35 years). No known recent exposures to genotoxic chemicals or radiation.
- Whether whole blood or separated lymphocytes were used if applicable:
Small innocula of whole blood (0.5 mL) were added to tubes containing 5 mL of Chromosome complete culture medium with Phytohemagglutinin and 1% Penicillin/Streptomycin. The tubes are sealed and incubated at 37°C, and shaken occasionally to prevent clumping. - Additional strain / cell type characteristics:
- not applicable
- Cytokinesis block (if used):
- Cytochalasin B
The concentration used for this assay was 5 μg/mL. - Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- In the preliminary experiment without and with metabolic activation concentrations of 0.01, 0.03162, 0.1, 0.3162, 1.0, 3.162 or 10.0 μg aluminium metaphosphate/mL medium were employed. Test item precipitation was noted at a concentration of 10.0 μg Aluminium metaphosphate/mL (24-hour or 4-hour exposure) in the experiment without and with metabolic activation.
Hence, the following concentrations were employed in the main study for the genotoxicity testswithout and with metabolic activation: 0.3162, 1.0, 3.162 or 10.0 μg Aluminium metaphosphate/mL medium. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: hydrochlorric acid (HCl)
- Justification for choice of solvent/vehicle: The test item was not soluble in any of the solvents recommended: aqueous media, dimethylsulfoxide (DMSO), ethanol, acetone or 0.05 M H2SO4 solution). However, Aluminium metaphosphate was completely soluble as 3 μg per mL 0.05 M HCl solution by employing an ultrasonic bath (45 kHz) at 37°C for 10 minutes for preparing a solution. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- other: Cholchicine
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
- Cell density at seeding (if applicable):
DURATION
- Preincubation period: 48 hours
- Exposure duration: 4 hours and 24 hours at +37°C
- Fixation time (start of exposure up to fixation or harvest of cells): 20 hours
STAIN (for cytogenetic assays): 10% Giemsa
NUMBER OF REPLICATIONS: 2 (main study), 1 (preliminary test)
METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: The cells were left in fixative for 30 minutes followed by centrifugation at 800 rpm. The supernatant was carefully removed and discarded, and the cell pellet was resuspended in about 0.5 mL of fresh fixative and 30% glacial acetic acid by repeated aspiration through a Pasteur pipette. Two drops of this cell suspension were dropped onto a prewarmed, pre-cleaned microscope slide and left to air-dry.
NUMBER OF CELLS EVALUATED: The micronucleus frequencies were analysed in at least 2000 binucleate cells per concentration
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth (relative increase in cell counts, RICC); cytotoxicity = 100% - RICC [%] - Evaluation criteria:
- If a test item induces a concentration-related increase or a statistical significant and reproducible increase in the number of cells containing micronuclei, it is classified as a positive result.
Consideration of whether the observed values are within or outside of the historical control range can provide guidance when evaluating the biological significance of the response. - Statistics:
- The assessment was carried out by a comparison of the samples with the positive and the vehicle control, using a chi-square test corrected for continuity according to YATES (COLQUHOUN, 1971[1]) as recommended by the UKEMS guidelines (The United Kingdom Branch of the European Environmental Mutagen Society: Report of the UKEMS subcommittee on guidelines for mutagenicity testing, part III, 1989: Statistical evaluation of mutagenicity data).
- Species / strain:
- lymphocytes: human peripheral lymphocytes
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- effects of pH / osmolality: No relevant changes in pH or osmolality of the test item formulations at
concentrations of 0.01 to 10.0 μg/mL medium were noted.
- Water solubility: substance was not soluble in water but was found to be soluble in HCl which was then used as the solvent in this test.
- Precipitation: In a preliminary study test item precipitation was noted at a concentration of 10 μg aluminium metaphosphate / ml (24 and 4 hour exposures). In the main study test item precipitation was noted in the experiments without and with metabolic activation at the top concentration of 10.0 μg test item/mL medium.
RANGE-FINDING/SCREENING STUDIES:In this preliminary experiment without and with metabolic activation concentrations of 0.01, 0.03162, 0.1, 0.3162, 1.0, 3.162 or 10.0 μg Aluminium metaphosphate/mL medium were employed. Test item precipitation was noted at a concentration of 10.0 μg Aluminium metaphosphate/mL (24-hour or 4-hour exposure) in the experiment without and with metabolic activation. Hence, 10.0 μg/mL were employed as the top concentration for the genotoxicity tests without and with metabolic activation.
CYTOKINESIS BLOCK (if used)
- Distribution of mono-, bi- and multi-nucleated cells:
NUMBER OF CELLS WITH MICRONUCLEI
- Number of cells for each treated and control culture:
- Indication whether binucleate or mononucleate where appropriate:
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data (micronucleus frequencies per 1000 cells):
Mitomycin C:
Mean: 46.9
SD: 35
range 17-137
Colchicine:
Mean: 25.9
SD: 9.5
range 15-63
cyclophosphamide:
Mean: 44.0
SD: 37.7
range 14-158
- Negative (solvent/vehicle) historical control data:
Without metabolic activation
Untreated control
mean 6.6
SD 2.9
range 2.0 - 17
95% Confidence interval 5.9 - 7.3
Vehicle control
mean 6.3
SD 3.1
range 2.0 - 18
95% Confidence interval 5.7 - 6.8
With metabolic acitvation
Untreated control
mean 6.4
SD 2.6
range 3.0 - 13
95% Confidence interval 5.7 - 7.1
Vehicle control
mean 6.1
SD 4.2
range 1-22
95% Confidence interval 5.1 - 6.7
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: CBPI or RI in the case of the cytokinesis-block method - Conclusions:
- Under the present test conditions, Aluminium metaphosphate tested up to a concentration of 10.0 μg/ml medium that led to test item precipitation in the absence
and in the presence of metabolic activation employing two exposure times (4 and 24 h, without S9) and one exposure time (4 h, with S9) revealed no indications of chromosomal damage in the in vitro micronucleus test.
Referenceopen allclose all
MF (main test):
|
MF |
|
Big colonies |
Small colonies |
|
Negative control (-S9) |
109.93 |
64.38 |
Negative control (+S9) |
124.78 |
68.03 |
Positive control (-S9) |
329.11 |
1854.44 |
Positive control (+S9) |
313.13 |
501.96 |
Concentration 1 (-S9) |
106.04 |
87.39 |
Concentration 1 (+S9) |
113.14 |
100.13 |
Concentration 2 (-S9) |
115.50 |
88.29 |
Concentration 2 (+S9) |
124.31 |
65.67 |
|
MF |
|
Big colonies |
Small colonies |
|
Negative control (-S9) |
96.68 |
51.93 |
Negative control (+S9) |
76.79 |
39.62 |
Positive control (-S9) |
358.67 |
719.25 |
Positive control (+S9) |
205.27 |
419.71 |
Concentration 3 (-S9) |
91.98 |
48.45 |
Concentration 3 (+S9) |
93.99 |
70.05 |
Concentration 4 (-S9) |
93.11 |
44.58 |
Concentration 4 (+S9) |
102.78 |
46.75 |
MF confirmatory test
|
MF |
|
Big colonies |
Small colonies |
|
Negative control (-S9) |
94.33 |
72.65 |
Negative control (+S9) |
94.09 |
81.38 |
Positive control (-S9) |
443.45 |
1571.21 |
Positive control (+S9) |
195.30 |
227.77 |
Concentration 1 (-S9) |
79.73 |
58.03 |
Concentration 1 (+S9) |
99.79 |
57.48 |
Concentration 2 (-S9) |
92.75 |
70.09 |
Concentration 2 (+S9) |
118.78 |
52.94 |
Concentration 3 (-S9) |
88.45 |
58.94 |
Concentration 3 (+S9) |
102.01 |
59.38 |
Concentration 4 (-S9) |
104.23 |
58.96 |
Concentration 4 (+S9) |
111.06 |
62.99 |
The variability of the MF of all tested concentrations are as a result of biological variance of the test system and displayed not significant increase.
The presence of S9 had no effect on the results.
The distribution of smal and big colonies showed neither chromosome nor gene mutations.
Test Material concentrations:
Concentration 1: 5 mg/plate
Concentration 2: 2.5 mg/plate
Concentration 3: 1.25 mg/plate
Concentration 4: 0.625 mg/plate
Concentration 5: 0.313 mg/plate
Table 2: Mean plate counts and standard deviations (SD); strain: TA98
Controls/ test substance conc. |
Colony count |
|||
TA98 |
||||
Main test: Preincubation method |
Confirmatory test: Plate incorporation method |
|||
Mean |
SD |
Mean |
SD |
|
NK |
18 |
3 |
11 |
4 |
NK+S9 |
22 |
4 |
18 |
3 |
PK |
308 |
38 |
761 |
87 |
PK1+S9 |
866 |
44 |
2360 |
83 |
PK2+S9 |
167 |
42 |
198 |
58 |
Conc. 1 |
19 |
6 |
11 |
4 |
Conc. 1+S9 |
22 |
2 |
15 |
3 |
Conc. 2 |
19 |
4 |
10 |
2 |
Conc. 2+S9 |
21 |
5 |
21 |
10 |
Conc. 3 |
20 |
5 |
18 |
5 |
Conc. 3+S9 |
24 |
3 |
19 |
4 |
Conc. 4 |
20 |
1 |
13 |
5 |
Conc. 4+S9 |
24 |
9 |
18 |
7 |
Conc. 5 |
16 |
5 |
14 |
2 |
Conc. 5+S9 |
22 |
3 |
16 |
3 |
Key:
SD – Standard deviation
NK - negative control
PK - positive control without S9 (daunomycin)
PK1 - positive control 1 with S9 (2-aminoanthracene)
PK2 - positive control 2 with S9 (benzo(a)pyrene)
Conc. - concentration
Table 3: Mean plate counts and standard deviations (SD); strain: TA100
Controls/ test substance conc. |
Colony count |
|||
TA100 |
||||
Main test: Preincubation method |
Confirmatory test: Plate incorporation method |
|||
Mean |
SD |
Mean |
SD |
|
NK |
60 |
n. a. |
60 |
6 |
NK+S9 |
81 |
9 |
69 |
15 |
PK |
247 |
18 |
350 |
21 |
PK1+S9 |
944 |
61 |
1910 |
68 |
PK2+S9 |
507 |
40 |
806 |
44 |
Conc. 1 |
58 |
7 |
67 |
7 |
Conc. 1+S9 |
66 |
20 |
77 |
4 |
Conc. 2 |
53 |
13 |
71 |
9 |
Conc. 2+S9 |
72 |
11 |
83 |
12 |
Conc. 3 |
64 |
11 |
65 |
10 |
Conc. 3+S9 |
61 |
16 |
70 |
8 |
Conc. 4 |
54 |
6 |
64 |
8 |
Conc. 4+S9 |
73 |
6 |
71 |
9 |
Conc. 5 |
90 |
n. a. |
73 |
1 |
Conc. 5+S9 |
91 |
13 |
69 |
8 |
Key:
SD – Standard deviation
NK - negative control
PK - positive control without S9 (sodium azide)
PK1 - positive control 1 with S9 (2-aminoanthracene)
PK2 - positive control 2 with S9 (benzo(a)pyrene)
Conc. - concentration
n. a. - not applicable due to missing value for calculation
Table 4: Mean plate counts and standard deviations (SD); strain: TA1535
Controls/ test substance conc. |
Colony count |
|||
TA1535 |
||||
Main test: Preincubation method |
Confirmatory test: Plate incorporation method |
|||
Mean |
SD |
Mean |
SD |
|
NK |
6 |
3 |
5 |
n. a. |
NK+S9 |
10 |
3 |
6 |
3 |
PK |
349 |
18 |
371 |
19 |
PK1+S9 |
127 |
8 |
65 |
12 |
Conc. 1 |
8 |
2 |
11 |
2 |
Conc. 1+S9 |
9 |
n. a. |
4 |
2 |
Conc. 2 |
5 |
2 |
6 |
4 |
Conc. 2+S9 |
10 |
n. a. |
8 |
4 |
Conc. 3 |
8 |
2 |
6 |
4 |
Conc. 3+S9 |
5 |
n. a. |
9 |
5 |
Conc. 4 |
5 |
1 |
3 |
2 |
Conc. 4+S9 |
5 |
2 |
7 |
4 |
Conc. 5 |
7 |
5 |
3 |
2 |
Conc. 5+S9 |
9 |
n. a. |
9 |
n. a. |
Key:
SD – Standard deviation
NK - negative control
PK - positive control without S9 (sodium azide)
PK1 - positive control 1 with S9 (2-aminoanthracene)
Conc. - concentration
n. a. - not applicable due to missing value for calculation
Table 5: Mean plate counts and standard deviations (SD); strain: TA1537
Controls/ test substance conc. |
Colony count |
|||
TA1537 |
||||
Main test: Preincubation method |
Confirmatory test: Plate incorporation method |
|||
Mean |
SD |
Mean |
SD |
|
NK |
4 |
1 |
3 |
1 |
NK+S9 |
6 |
1 |
3 |
3 |
PK |
283 |
10 |
126 |
9 |
PK1+S9 |
210 |
32 |
107 |
13 |
Conc. 1 |
5 |
2 |
7 |
4 |
Conc. 1+S9 |
7 |
1 |
2 |
1 |
Conc. 2 |
8 |
3 |
5 |
1 |
Conc. 2+S9 |
5 |
1 |
4 |
1 |
Conc. 3 |
8 |
2 |
6 |
3 |
Conc. 3+S9 |
7 |
3 |
3 |
2 |
Conc. 4 |
6 |
2 |
5 |
1 |
Conc. 4+S9 |
5 |
2 |
4 |
3 |
Conc. 5 |
6 |
4 |
2 |
2 |
Conc. 5+S9 |
4 |
2 |
1 |
2 |
Key:
SD – Standard deviation
NK - negative control
PK - positive control without S9 (ICR 191 acridine)
PK1 - positive control 1 with S9 (2-aminoanthracene)
Conc. - concentration
Table 6: Mean plate counts and standard deviations (SD); strain: WP2uvrA
Controls/ test substance conc. |
Colony count |
|||
WP2uvrA |
||||
Main test: Preincubation method |
Confirmatory test: Plate incorporation method |
|||
Mean |
SD |
Mean |
SD |
|
NK |
17 |
3 |
16 |
3 |
NK+S9 |
18 |
3 |
20 |
6 |
PK |
1419 |
129 |
1371 |
59 |
PK1+S9 |
309 |
26 |
407 |
55 |
Conc. 1 |
19 |
1 |
15 |
3 |
Conc. 1+S9 |
15 |
7 |
18 |
1 |
Conc. 2 |
19 |
5 |
20 |
5 |
Conc. 2+S9 |
16 |
1 |
23 |
4 |
Conc. 3 |
17 |
8 |
22 |
6 |
Conc. 3+S9 |
16 |
5 |
16 |
6 |
Conc. 4 |
18 |
4 |
17 |
5 |
Conc. 4+S9 |
10 |
2 |
16 |
4 |
Conc. 5 |
12 |
3 |
20 |
2 |
Conc. 5+S9 |
20 |
7 |
13 |
2 |
Key:
SD – Standard deviation
NK - negative control
PK - positive control without S9 (4-nitroquinoline-1-oxide)
PK1 - positive control 1 with S9 (2-aminoanthracene)
Conc. - concentration
Table 1: Experiments without metabolic activation (S9 mix)
4 hr exposure |
||||
Concentration [µg/mL medium] |
CBPI |
RI [%] |
Number of binucleate cells scored |
Number of micronucleated cells per 1000 binucleate cells |
0.05 M HCl |
||||
0 |
1.46 |
100 |
2000 |
5.0 |
Aluminium metaphosphate |
||||
0.3162 |
1.50 |
108 |
2000 |
5.0 |
1.0 |
1.50 |
108 |
2000 |
5.0 |
3.162 |
1.58 |
125 |
2000 |
8.0 |
10.0* |
1.50 |
109 |
2000 |
4.5 |
Mitomycin C |
||||
0.2 |
1.40 |
87 |
2000 |
39.0 s. |
24 hr exposure |
||||
Concentration [µg/mL medium] |
CBPI |
RI [%] |
Number of binucleate cells scored |
Number of micronucleated cells per 1000 binucleate cells |
0.05 M HCl |
||||
0 |
1.43 |
100 |
2000 |
7.5 |
Aluminium metaphosphate |
||||
0.3162 |
1.35 |
82 |
2000 |
7.0 |
1.0 |
1.42 |
98 |
2000 |
7.5 |
3.162 |
1.36 |
85 |
2000 |
4.5 |
10.0* |
1.43 |
102 |
1000 |
6.5 |
Colchicine |
||||
0.02 |
1.46 |
109 |
2000 |
28.0 s. |
CBPI = Cytokinesis block proliferation index
RI = Replicative Index
s. = significantly different from negative control (p ≤ 0.05)
* = test item precipitation
Table 2: Experiment with metabolic activation (S9 mix)
4 hr exposure |
||||
Concentration [µg/mL medium] |
CBPI |
RI [%] |
Number of binucleate cells scored |
Number of micronucleated cells per 1000 binucleate cells |
0.05 M HCl |
||||
0 |
1.47 |
100 |
2000 |
5.5 |
Aluminium metaphosphate |
||||
0.3162 |
1.49 |
106 |
2000 |
5.5 |
1.0 |
1.43 |
92 |
2000 |
4.5 |
3.162 |
1.40 |
86 |
2000 |
5.5 |
10.0* |
1.51 |
109 |
2000 |
6.5 |
Cyclophosphamide |
||||
20 |
1.40 |
86 |
2000 |
22.5 s. |
CBPI = Cytokinesis block proliferation index
RI = Replicative Index
s. = significantly different from negative control (p ≤ 0.05)
* = test item precipitation
Table 3: Experiment without metabolic activation (S9 mix) – 4 hr exposure
Culture number |
Concentration [µg/mL medium] |
Number of mononucleate cells per 500 cells scored |
Number of binucleate cells per 500 cells scored |
Number of multinucleate cells per 500 cells scored |
CBPI |
RI [%] |
Number of binucleate cells scored |
Number of micronucleated cells per 1000 binucleated cells |
Significance chi2- test |
0.05 M HCl |
|||||||||
1 |
0 |
278 |
209 |
13 |
1.47 |
100 |
1000 |
6 |
- |
11 |
0 |
290 |
196 |
14 |
1.45 |
100 |
1000 |
4 |
- |
Aluminium metaphosphate |
|||||||||
5 |
0.3162 |
282 |
199 |
19 |
1.47 |
100 |
1000 |
4 |
n.s. |
15 |
0.3162 |
258 |
226 |
16 |
1.52 |
116 |
1000 |
6 |
n.s. |
4 |
1.0 |
266 |
225 |
9 |
1.49 |
14 |
1000 |
5 |
n.s. |
14 |
1.0 |
266 |
220 |
14 |
1.50 |
111 |
1000 |
5 |
n.s. |
3 |
3.162 |
225 |
257 |
18 |
1.59 |
126 |
1000 |
7 |
n.s. |
13 |
3.162 |
239 |
243 |
18 |
1.56 |
124 |
1000 |
9 |
n.s. |
2 |
10.0* |
274 |
219 |
7 |
1.47 |
100 |
1000 |
4 |
n.s. |
12 |
10.0* |
251 |
232 |
17 |
1.53 |
118 |
1000 |
5 |
n.s. |
Mitomycin C |
|||||||||
7 |
0.2 |
302 |
191 |
7 |
1.41 |
87 |
1000 |
36 |
s. |
17 |
0.2 |
319 |
166 |
15 |
1.39 |
87 |
1000 |
42 |
s. |
n.s. = not significantly different from negative control (p ≤ 0.05)
s. = significantly different from negative control (p ≤ 0.05)
CBPI = Cytokinesis block proliferation index
RI = Replicative test
*= test item precipitation
Table 4: Experiment without metabolic activation (S9 mix) – 24 hr exposure
Culture number |
Concentration [µg/mL medium] |
Number of mononucleate cells per 500 cells scored |
Number of binucleate cells per 500 cells scored |
Number of multinucleate cells per 500 cells scored |
CBPI |
RI [%] |
Number of binucleate cells scored |
Number of micronucleated cells per 1000 binucleated cells |
Significance chi2- test |
0.05 M HCl |
|||||||||
1 |
0 |
312 |
186 |
2 |
1.38 |
100 |
1000 |
7 |
- |
11 |
0 |
271 |
222 |
7 |
1.47 |
100 |
1000 |
8 |
- |
Aluminium metaphosphate |
|||||||||
15 |
0.3162 |
329 |
165 |
6 |
1.35 |
74 |
1000 |
6 |
n.s. |
5 |
0.3162 |
335 |
160 |
5 |
1.34 |
89 |
1000 |
8 |
n.s. |
4 |
1.0 |
307 |
187 |
6 |
1.40 |
105 |
1000 |
6 |
n.s. |
14 |
1.0 |
290 |
205 |
5 |
1.43 |
91 |
1000 |
9 |
n.s. |
3 |
3.162 |
346 |
148 |
6 |
1.32 |
84 |
1000 |
4 |
n.s. |
13 |
3.162 |
306 |
189 |
5 |
1.40 |
85 |
1000 |
5 |
n.s |
2 |
10.0* |
279 |
217 |
4 |
1.45 |
118 |
1000 |
8 |
n.s. |
12 |
10.0* |
304 |
193 |
3 |
1.40 |
85 |
1000 |
5 |
n.s. |
Colchicine |
|||||||||
9 |
0.02 |
277 |
214 |
9 |
1.46 |
121 |
1000 |
26 |
s. |
19 |
0.02 |
288 |
201 |
11 |
1.45 |
96 |
1000 |
30 |
s. |
n.s = not significantly different from negative control (p ≤ 0.05)
s. = significantly different from negative control (p ≤ 0.05)
CBPI = Cytokinesis block proliferation index
RI = Replicative Index
*= test item precipitation
Table 5: Experiment with metabolic activation (S9 mix) – 4 hr exposure
Culture number |
Concentration [µg/mL medium] |
Number of mononucleate cells per 500 cells scored |
Number of binucleate cells per 500 cells scored |
Number of multinucleate cells per 500 cells scored |
CBPI |
RI [%] |
Number of binucleate cells scored |
Number of micronucleated cells per 1000 binucleated cells |
Significance chi2- test |
0.05M HCl |
|||||||||
1 |
0 |
262 |
232 |
6 |
1.49 |
100 |
1000 |
6 |
- |
9 |
0 |
286 |
209 |
5 |
1.44 |
100 |
1000 |
5 |
- |
Aluminium metaphosphate |
|||||||||
5 |
0.3162 |
259 |
228 |
13 |
1.51 |
104 |
1000 |
7 |
n.s. |
13 |
0.3162 |
275 |
213 |
12 |
1.47 |
107 |
1000 |
4 |
n.s. |
4 |
1.0 |
287 |
204 |
9 |
1.44 |
90 |
1000 |
3 |
n.s. |
12 |
1.0 |
309 |
177 |
14 |
1.41 |
93 |
1000 |
6 |
n.s. |
3 |
3.162 |
324 |
164 |
12 |
1.38 |
78 |
1000 |
4 |
n.s. |
11 |
3.162 |
299 |
196 |
5 |
1.41 |
93 |
1000 |
7 |
n.s. |
2 |
10.0* |
257 |
231 |
12 |
1.51 |
104 |
1000 |
6 |
n.s. |
10 |
1.0* |
267 |
214 |
19 |
1.50 |
114 |
1000 |
7 |
n.s. |
Cyclophosphamide |
|||||||||
7 |
20 |
333 |
160 |
7 |
1.35 |
71 |
1000 |
24 |
s. |
15 |
20 |
295 |
191 |
14 |
1.44 |
100 |
1000 |
21 |
s. |
n.s. = not significantly different from negative control (p ≤ 0.05)
s. = significantly different from negative control (p ≤ 0.05)
CBPI = Cytokinesis block proliferation index
RI replicative index
*= test item precipitation
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Mode of Action Analysis / Human Relevance Framework
Aluminium metaphosphate is not genotoxic and therefore no mode of action is identified.
Additional information
Justification for classification or non-classification
No classification for in vitro genetic toxicity is proposed for aluminium metaphosphate. The data has been generated according to the recommended guidelines and under the conditions of GLP, this data is considered to be adequate for the purposes of classification and labelling in accordance with Regulation (EC) No.1272/2008 (EU CLP) and GHS.
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