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EC number: 947-798-5 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From August 01, 2017 to October 30, 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- not specified
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: in vitro mammalian chromosome aberration test (migrated information)
Test material
- Reference substance name:
- Reaction mass of mono- and di- hexadecyl phosphate esters, potassium salts and phosphoric acid
- Molecular formula:
- C16H34O4P1K1 (representative: mono- C16 PSE, K+)
- IUPAC Name:
- Reaction mass of mono- and di- hexadecyl phosphate esters, potassium salts and phosphoric acid
- Test material form:
- solid: particulate/powder
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- lymphocytes:
- Details on mammalian cell type (if applicable):
- For each experiment, sufficient whole blood was drawn from the peripheral circulation of a non smoking volunteer (aged 18-35) who had been previously screened for suitability. The volunteer had not knowingly been exposed to high levels of radiation or hazardous chemicals and had not knowingly recently suffered from a viral infection. Based on over 20 years in house data for cell cycle times for lymphocytes using BrdU (bromodeoxyuridine) incorporation to assess the number of first, second and third division metaphase cells to calculate the average generation time (AGT) for human lymphocytes it is considered to be approximately 16 h. Therefore using this average the in-house exposure time for the experiments for 1.5 x AGT is 24 h.
The details of the donors used are:
Preliminary toxicity test: male, aged 28 years
Main Experiment: male, aged 26 years - Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver homogenate metabolizing system S9 fraction (20% (v/v))
- Test concentrations with justification for top dose:
- Preliminary test: 0, 3.91, 7.81, 15.63, 31.25, 62.5, 125, 250, 500 and 1000 µg/mL
Main experiment: 0, 3.91, 7.81, 15.63, 31.25, 62.5, 125 µg/mL
The test substance was insoluble in Dimethyl sulphoxide, Acetone and Tetrahydrofuran at 200, 100 and 50 mg/mL. The test substance was insoluble in Minimal Essential Medium (MEM) at 20 mg/mL but was partially soluble/ suspendable in MEM at 10 mg/mL in solubility checks performed in-house. Therefore 1000 µg/mL was considered to be the maximum achievable dose level due to formulation difficulties. The selection of the maximum dose level for the main experiment was based on the lowest precipitating dose level and was 125 µg/mL for the 4(20)-h exposure groups and for the continuous exposure group. - Vehicle / solvent:
- The test substance was insoluble in Dimethyl sulphoxide, Acetone and Tetrahydrofuran at 200, 100 and 50 mg/mL. The test substance was insoluble in Minimal Essential Medium (MEM) at 20 mg/mL but was partially soluble/ suspendable in MEM at 10 mg/mL in solubility checks performed in-house. Therefore MEM was used as vehicle.
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Identity: Minimal Essential Medium, Supplier: Sigma, Batch number: RNBF9655, Expiry Date: September 2018, Purity: Treated as 100%
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and experimental conditions:
- Cells
For each experiment, sufficient whole blood was drawn from the peripheral circulation of a non smoking volunteer (aged 18-35) who had been previously screened for suitability. The volunteer had not knowingly been exposed to high levels of radiation or hazardous chemicals and had not knowingly recently suffered from a viral infection. Based on over 20 years in house data for cell cycle times for lymphocytes using BrdU (bromodeoxyuridine) incorporation to assess the number of first, second and third division metaphase cells to calculate the average generation time (AGT) for human lymphocytes it is considered to be approximately 16 h. Therefore using this average the in-house exposure time for the experiments for 1.5 x AGT is 24 h.
The details of the donors used are:
Preliminary toxicity test: male, aged 28 years
Main experiment: male, aged 26 years
Cell Culture
Cells (whole blood cultures) were grown in Eagle's minimal essential medium with HEPES buffer (MEM), supplemented “in-house” with L-glutamine, penicillin/streptomycin, amphotericin B and 10 % foetal bovine serum (FBS), at approximately 37ºC with 5% CO2 in humidified air. The lymphocytes of fresh heparinized whole blood were stimulated to divide by the addition of phytohaemagglutinin (PHA).
Microsomal Enzyme Fraction and S9-Mix
The S9 Microsomal fractions were pre-prepared using standardized in-house procedures (outside the confines of this study). Batch Nos. PB/NF S9 30/6/17 and 20/8/17 were used in this study. Prior to use each batch of S9 is tested for its capability to activate known mutagens in the Ames test. The S9-mix was prepared prior to the dosing of the test cultures and contained the S9 fraction (20% (v/v)), MgCl2 (8mM), KCl (33mM), sodium orthophosphate buffer pH 7.4 (100mM), glucose-6-phosphate (5mM) and NADP (5mM). The final concentration of S9, when dosed at a 10% volume of S9-mix into culture media, was 2%. - Evaluation criteria:
- Data Evaluation
The following criteria were used to determine a valid assay:
1) The frequency of cells with structural chromosome aberrations (excluding gaps) in the vehicle control cultures was within the laboratory historical control data range.
2) All the positive control chemicals induced a positive response (p≤0.01) and demonstrated the validity of the experiment and the integrity of the S9-mix.
3) The study was performed using all three exposure conditions using a top concentration which meets the requirements of the current testing guideline.
4) The required number of cells and concentrations were analyzed. - Statistics:
- Statistical Analysis
The frequency of cells with aberrations excluding gaps and the frequency of polyploid cells was compared, where necessary, with the concurrent vehicle control value using Fisher's Exact test. (Richardson et al. 1989). A toxicologically significant response is recorded when the p value calculated from the statistical analysis of the frequency of cells with aberrations excluding gaps is less than 0.05 when compared to its concurrent control and there is a dose-related increase in the frequency of cells with aberrations which is reproducible. Incidences where marked statistically significant increases are observed only with gap-type aberrations will be assessed on a case by case basis.
Results and discussion
Test results
- Key result
- Species / strain:
- lymphocytes:
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Remarks:
- Tested concentrations: 0, 3.91, 7.81, 15.63, 31.25, 62.5, 125 µg/mL
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- other: no mutagenic potential
Any other information on results incl. tables
Results
Preliminary toxicity test
The dose range for the preliminary toxicity test was 3.91, 7.81, 15.63, 31.25, 62.5, 125, 250, 500 and 1000 µg/mL.The maximum dose was the maximum achievable dose level due to formulation difficulties. A precipitate of the test substance was observed in the parallel blood-free cultures at the end of the exposure, at and above 31.25 µg/mL in the 4(20)-h exposure group in the absence of S9, at and above 125 µg/mL in the presence of S9, and at and above 62.5 µg/mL in the continuous exposure group. Precipitate from the test substance was also noted on the slides at 1000 µg/mL in all three exposure groups. Microscopic assessment of the slides prepared from the exposed cultures showed that metaphase cells were present up to 1000 µg/mL in all three exposure groups. The maximum dose selected for mitotic index analysis was limited to 125 µg/mL based on the precipitate observations.The test substance induced no evidence of toxicity in any of the exposure groups. The selection of the maximum dose level for the main experiment was based on the lowest precipitating dose level and was 125 µg/mL for the 4(20)-h exposure groups and for the continuous exposure group.
Table 1: Mitotic Index - Preliminary toxicity test
Dose Level (µg/mL) |
4(20)-h Without S9 |
4(20)-h With S9 |
24-h Without S9 |
|||
Mitotic Index |
% of Control |
Mitotic Index |
% of Control |
Mitotic Index |
% of Control |
|
0 |
8.35 |
100 |
10.55 |
100 |
16.25 |
100 |
3.91 |
- |
- |
- |
- |
- |
- |
7.81 |
6.65 |
80 |
- |
- |
- |
- |
15.63 |
8.10 |
97 |
7.55 |
72 |
17.55 |
108 |
31.25 |
17.05 P |
204 |
6.95 |
66 |
14.35 |
88 |
62.5 |
- P |
- |
8.80 |
83 |
13.30 P |
82 |
125 |
8.35 P |
100 |
9.90 P |
94 |
13.95 P |
86 |
250 |
- P |
- |
- P |
- |
- P |
- |
500 |
- P |
- |
- P |
- |
- P |
- |
1000 |
- P† |
- |
- P† |
- |
- P† |
- |
- = Not assessed for mitotic index
P = Precipitate observed at end of exposure period in blood-free cultures
† = Precipitate observed on the slides
Chromosome aberration test – main experiment
The qualitative assessment of the slides determined that there was no marked toxicity as in the preliminary toxicity test and that there were metaphases suitable for scoring present up to 125 µg/mL in all three exposure groups. Precipitate observations were made at the end of exposure in blood-free cultures and precipitate was noted at and above 62.5 µg/mL in the absence of S9 and at and above 31.25 µg/mL in the presence of S9. The mitotic index data for the Main Experiment confirm the qualitative observations in that no dose-related inhibition of mitotic index was observed in any of the three exposure groups. The maximum dose level selected for metaphase analysis was the lowest precipitating dose level in each of the exposure groups and was 62.5 µg/mL in the absence of S9 and 31.25 µg/mL in the presence of S9.
Table 2: Mitotic Index – Main experiment(4(20)-h Exposure Groups)
Dose Level (mg/mL) |
4(20)-h Without S9 |
4(20)-h With S9 |
||||||
A |
B |
Mean |
% of Control |
A |
B |
Mean |
% of Control |
|
0 |
9.75 |
11.70 |
10.73 |
100 |
5.95 |
5.05 |
5.50 |
100 |
3.91 |
- |
- |
- |
- |
- |
- |
- |
- |
7.81 |
- |
- |
- |
- |
5.25 |
6.20 |
5.73 |
104 |
15.63 |
9.75 |
10.30 |
10.03 |
93 |
7.25 |
4.35 |
5.80 |
105 |
31.25 |
11.15 |
9.75 |
10.45 |
97 |
4.95 P |
5.20 P |
5.08 |
92 |
62.5 |
12.05 P |
11.05 P |
11.55 |
108 |
- P |
- P |
- |
- |
125 |
- P |
- P |
- |
- |
- P |
- P |
- |
- |
MMC 0.4 |
- P |
- P |
- |
- |
NA |
NA |
NA |
NA |
CP 2 |
NA |
NA |
NA |
NA |
4.25 |
3.35 |
3.80 |
69 |
MMC = Mitomycin C
CP = Cyclophosphamide
P = Precipitate observed at end of exposure period in blood-free cultures
NA = Not applicable
- = Not assessed for mitotic index
Table 3: Mitotic Index – Main experiment (24-h Exposure Group)
Dose Level (µg/mL) |
24-h Without S9 |
|||
A |
B |
Mean |
% of Control |
|
0 |
14.20 |
13.65 |
13.93 |
100 |
3.91 |
- |
- |
- |
- |
7.81 |
- |
- |
- |
- |
15.63 |
10.90 |
12.45 |
11.68 |
84 |
31.25 |
9.95 |
10.30 |
10.13 |
73 |
62.5 |
14.35 P |
18.10 P |
16.23 |
117 |
125 |
- P |
- P |
- |
- |
MMC 0.1 |
7.75 |
5.70 |
6.73 |
48 |
Table 4: Main experiment (4-h treatment, 24 h Harvest) without metabolic treatment
Treatment Group |
Replicate |
Mitotic Index (%) |
Number of Cells Scored |
Number of Aberrations |
Total Number of Aberrations |
Frequency of Aberrant Cells (%) |
|||||||
Gaps |
Chromatid |
Chromosome |
Others |
||||||||||
Breaks |
Exchanges |
Breaks |
Exchanges |
X |
(+ Gaps) |
(-Gaps) |
(+Gaps) |
(-Gaps) |
|||||
Vehicle Control (MEM) |
A |
9.75 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
B |
11.70 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Total |
21.45 |
300 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
(100) |
(0.0) |
(0.0) |
|||||||||||
A |
9.75 |
150 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
|
15.63 |
B |
10.30 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
µg/mL |
Total |
20.05 |
300 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
(93) |
(0.3) |
(0.0) |
|||||||||||
A |
11.15 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
31.25 |
B |
9.75 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
µg/mL |
Total |
20.90 |
300 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
(97) |
(0.0) |
(0.0) |
|||||||||||
A |
12.05 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
62.5 |
B |
11.05 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
µg/mL |
Total |
23.10 |
300 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
(108) |
(0.0) |
(0.0) |
|||||||||||
Positive Control |
A |
5.90 |
96a |
4 |
8 |
9 |
2 |
0 |
0 |
23 |
19 |
22 |
18 |
MMC 0.4 |
B |
7.60 |
46a |
0 |
10 |
11 |
1 |
0 |
0 |
22 |
22 |
15 |
15 |
µg/mL |
Total |
13.50 |
142 |
4 |
18 |
20 |
3 |
0 |
0 |
45 |
41 |
37 |
33*** |
(63) |
(26.1) |
(23.2) |
MMC - Mitomycin C
a - Slide evaluation terminated when at least 15 cells with aberrations (excluding gaps) had been observed
*** - P < 0.001
MEM - Minimal Essential Medium
Table 5: Main experiment (4-h treatment, 24 h Harvest) with metabolic treatment
Treatment Group |
Replicate |
Mitotic Index (%) |
Number of Cells Scored |
Number of Aberrations |
Total Number of Aberrations |
Frequency of Aberrant Cells (%) |
|||||||
Gaps |
Chromatid |
Chromosome |
Others |
||||||||||
Breaks |
Exchanges |
Breaks |
Exchanges |
X |
(+ Gaps) |
(-Gaps) |
(+Gaps) |
(-Gaps) |
|||||
Vehicle Control (MEM) |
A |
5.95 |
150 |
0 |
5 |
0 |
0 |
0 |
0 |
5 |
5 |
4 |
4 |
B |
5.05 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Total |
11.00 |
300 |
0 |
5 |
0 |
0 |
0 |
0 |
5 |
5 |
4 |
4 |
|
(100) |
(1.3) |
(1.3) |
|||||||||||
A |
5.25 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
7.81 |
B |
6.20 |
150 |
0 |
3 |
0 |
1 |
0 |
0 |
4 |
4 |
4 |
4 |
µg/mL |
Total |
11.45 |
300 |
0 |
3 |
0 |
1 |
0 |
0 |
4 |
4 |
4 |
4 |
(104) |
(1.3) |
(1.3) |
|||||||||||
A |
7.25 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
15.63 |
B |
4.35 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
µg/mL |
Total |
11.60 |
300 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
(105) |
(0.0) |
(0.0) |
|||||||||||
A |
4.95 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
31.25 |
B |
5.20 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
µg/mL |
Total |
10.15 |
300 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
(92) |
(0.0) |
(0.0) |
|||||||||||
Positive Control |
A |
4.25 |
104a |
0 |
17 |
2 |
0 |
0 |
0 |
19 |
19 |
15 |
15 |
CP 2 |
B |
3.35 |
109a |
1 |
11 |
5 |
1 |
0 |
0 |
18 |
17 |
16 |
15 |
µg/mL |
Total |
7.60 |
213 |
1 |
28 |
7 |
1 |
0 |
0 |
37 |
36 |
31 |
30*** |
(69) |
(14.6) |
(14.1) |
Table 6: Main experiment (24-h treatment) without metabolic treatment
Treatment Group |
Replicate |
Mitotic Index (%) |
Number of Cells Scored |
Number of Aberrations |
Total Number of Aberrations |
Frequency of Aberrant Cells (%) |
|||||||
Gaps |
Chromatid |
Chromosome |
Others |
||||||||||
Breaks |
Exchanges |
Breaks |
Exchanges |
X |
(+ Gaps) |
(-Gaps) |
(+Gaps) |
(-Gaps) |
|||||
Vehicle Control (MEM) |
A |
14.20 |
150 |
1 |
0 |
0 |
1 |
0 |
0 |
2 |
1 |
2 |
1 |
B |
13.65 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Total |
27.85 |
300 |
1 |
0 |
0 |
1 |
0 |
0 |
2 |
1 |
2 |
1 |
|
(100) |
(0.7) |
(0.3) |
|||||||||||
A |
10.90 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
15.63 |
B |
12.45 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
µg/mL |
Total |
23.35 |
300 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
(84) |
(0.0) |
(0.0) |
|||||||||||
A |
9.95 |
150 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
|
31.25 |
B |
10.30 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
µg/mL |
Total |
20.25 |
300 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
(73) |
(0.3) |
(0.3) |
|||||||||||
A |
14.35 |
150 |
0 |
0 |
0 |
2 |
0 |
0 |
2 |
2 |
2 |
2 |
|
62.5 |
B |
18.10 |
150 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
µg/mL |
Total |
32.45 |
300 |
0 |
0 |
0 |
2 |
0 |
0 |
2 |
2 |
2 |
2 |
(117) |
(0.7) |
(0.7) |
|||||||||||
Positive Control |
A |
7.75 |
45a |
4 |
24 |
1 |
3 |
0 |
0 |
32 |
28 |
19 |
18 |
MMC 0.1 |
B |
5.70 |
93a |
2 |
14 |
1 |
2 |
0 |
0 |
19 |
17 |
15 |
15 |
µg/mL |
Total |
13.45 |
138 |
6 |
38 |
2 |
5 |
0 |
0 |
51 |
45 |
34 |
33*** |
(48) |
(24.6) |
(23.9) |
Table 7: Mean Frequency of Polyploid Cells (%)
Dose Level (µg/mL) |
Exposure Group |
||
4(20)-h Without S9 |
4(20)-h With S9 |
24-h Without S9 |
|
0 |
0 |
0 |
0 |
7.81 |
- |
0 |
0 |
15.63 |
0 |
0 |
0 |
31.25 |
0 |
0 |
0 |
62.5 |
0 |
0 |
- |
MMC 0.4 |
0 |
NA |
NA |
MMC 0.1 |
NA |
NA |
0 |
CP 5 |
NA |
0 |
NA |
Validity of assay
The assay was considered valid as it met all of the following criteria:
1) The frequency of cells with chromosome aberrations (excluding gaps) in the vehicle control cultures were within the current historical control data range.
2) All the positive control chemicals induced a demonstrable positive response (p≤0.01) and confirmed the validity and sensitivity of the assay and the integrity of the S9-mix.
3) The study was performed using all three exposure conditions using a top concentration which meets the requirements of the current testing guideline.
4) The required number of cells and concentrations were analyzed.
The test substance did not induce any statistically significant increases in the frequency of cells with aberrations either in the absence or presence of metabolic activation. Thetest substancedid not induce a statistically significant increase in the numbers of polyploid cells at any dose level in any of the exposure groups.
Applicant's summary and conclusion
- Conclusions:
- Under study conditions, the test substance was considered to be non clastogenic in the chromosomal aberration assay, with and without metabolic activation.
- Executive summary:
An in vitro study was conducted to determine the clastogenicity of the test substance, 'mono- and di- C16 PSE, K+ and H3PO4' (purity: 100%) using human lymphocytes, according to the OECD Guideline 473 (Chromosome Aberration test) and Japanese Guidelines, in compliance with GLP. Duplicate cultures of human lymphocytes, treated with the test substance, were evaluated for chromosome aberrations at doses 0, 3.91, 7.81, 15.63, 31.25, 62.5 and 125 µg/mL, together with vehicle and positive controls. In this study, three exposure conditions were investigated: 4 h exposure in the presence of an induced rat liver homogenate metabolizing system (S9), at a 2% final concentration with cell harvest after a 20-h expression period, 4 h exposure in the absence of metabolic activation (S9) with a 20-h expression period and a 24-h exposure in the absence of metabolic activation. The dose levels used in the main experiment were selected using data from the preliminary toxicity test where the results indicated that the maximum concentration should be limited by precipitate. All vehicle (Minimal Essential Medium) controls had frequencies of cells with aberrations within the range expected for normal human lymphocytes. All the positive control substances (Mitomycin C and Cyclophosphamide) induced statistically significant increases in the frequency of cells with aberrations. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated. The test substance was non-toxic and did not induce any statistically significant increases in the frequency of cells with aberrations, using a dose range that included a dose level that was the lowest precipitating dose level. Under study conditions, the test substance was considered to be non-clastogenic to human lymphocytes in the chromosomal aberration assay, with and without metabolic activation (Envigo, 2017).
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