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Registration Dossier
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EC number: 222-222-9 | CAS number: 3390-61-2
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Bacterial reverse mutation assay: the substance 1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane was negative with and without metabolic activation in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 (LPT, 2002) (OECD TG 471).
Cytogenicity in mammalian cells: the substance
1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane was negative with and
without metabolic activation in peripheral human lymphocytes (WIL
Research, 2016) (OECD TG 473).
Mammalian mutagenicity study: the substance
1,3,5-trimethyl-1,1,3,5,5-pentaphenyltrisiloxane was negative with and
without metabolic activation in mouse lymphoma L5178Y cells (Charles
River, 2016) (OECD TG 490).
The studies were conducted according to an appropriate OECD test guideline, and in compliance with GLP.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2002-05-10 to 2002-09-02
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor induced rat liver S9
- Test concentrations with justification for top dose:
- See table 1
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solvent was chosen because of its solubility properties and its relative nontoxicity to the bacteria - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535, TA 100 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- TA 98 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA 1537 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- TA 102 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-anthracene amide
- Remarks:
- TA 98, TA 102, TA 1537 (with activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- TA 100, TA 1535 (with activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 60 minutes
- Expression time (cells in growth medium): 48 hours
NUMBER OF REPLICATIONS: 3 plates for each test concentration
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; background lawn assessment - Evaluation criteria:
- A result is positive if the number of revertants is significantly increased compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of the solvent control for TA 1535 and TA 1537 in both experiments.
Positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking on histidine-free agar plates.
Cytotoxicity is defined as a reduction in the number of colonies by >50% compared with the solvent control and/or a sparse background lawn. - Statistics:
- MANN and WHITNEY and Spearman’s rank.
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- 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 applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: precipitation noted at 3160 - 5000 μg/plate
COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data - Remarks on result:
- other: No mutagenic potential
- Conclusions:
- In a highly reliable test, conducted under OECD 471, with GLP, no mutagenic effect was observed for the test substance tested up to cytotoxic concentration in any of the test strains in two independent experiments without and with metabolic activation. The test substance is non-mutagenic in test strains used.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016-01-15 to 2016-03-08
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- 2014
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- other: Peripheral human lymphocytes
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI 1640 medium
- Properly maintained: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital (80 mg/kg body weight) and ß-naphthoflavone (100 mg/kg) induced rat liver S9
- Test concentrations with justification for top dose:
- Experiment 1: 1.7, 5.4, 17, 52, 164 µg/ml, with and without metabolic activation
Experiment 2: 5.4, 17 and 52 µg/ml, without metabolic activation - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: dimethyl sulfoxide (DMSO)
- Justification for choice of solvent/vehicle: The solvent was chosen based on the results from the solubility test. - Untreated negative controls:
- yes
- Remarks:
- DMSO
- Negative solvent / vehicle controls:
- no
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- without metabolic activation, 48 hour exposure period
- Untreated negative controls:
- yes
- Remarks:
- DMSO
- Negative solvent / vehicle controls:
- no
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation, 3 hour exposure period
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
ACTIVATION: To 0.5 ml S9-mix components 0.5 ml S9-fraction was added (50% (v/v) S9-fraction) to complete the S9-mix. The added co-factores were: 1.63 mg MgCl2.6H2O; 2.46 mg KCl; 1.7 mg glucose-6-phosphate; 3.4 mg NADP; 4 µmol HEPES.
DURATION
- Exposure duration:
Experiment 1: 3 hours, with and without metabolic activation
Experiment 2: 24 and 48 hours, without metabolic activation
- Expression time (cells in growth medium):
Experiment 1: 20-22 hours
- Fixation time (start of exposure up to fixation or harvest of cells):
Experiment 1: 24 hours
Experiment 2: The cells were fixed immediately after exposure
SPINDLE INHIBITOR (cytogenetic assays): colchicine (0.5 µg/ml medium) was added during the last 2.5 - 3 h of the culture period
STAIN (for cytogenetic assays): 5 % v/v Giemsa
NUMBER OF REPLICATIONS: duplicate cell cultures
NUMBER OF CELLS EVALUATED: 1000 cells
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index
OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes - Evaluation criteria:
- A test item is considered positive (clastogenic) in the chromosome aberration test if all of the following criteria are met:
a) at least one of the test concentrations exhibits a statistically significant (Fisher’s exact test, one-sided, p < 0.05) increase compared with the concurrent negative control.
b) The increase is dose related when evaluated with an Cochran Armitage trend test.
c) Any of the results are outside the 95% control limits of the historical control data range. - Statistics:
- Fisher’s exact test and Cochran Armitage trend test
- Key result
- Species / strain:
- other: Peripheral human lymphocytes
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation:
Experiment 1: At the 3 h exposure time a concentration of 164 µg/ml the test item precipitated in the culture medium
Experiemnt 2: ). At 24 and 48 hour exposure times a concentration of 52 µg/ml test item precipitated in the culture medium
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Polyploidy: The test item did not increase the number of polyploid cells.
- Endoreplication: The test item did not increase the number of endoreplicated chromosomes - Remarks on result:
- other: No mutagenic potential
- Conclusions:
- 1,3,5-Trimethyl-1,1,3,5,5-pentaphenyltrisiloxane has been tested in a valid study for ability to induce chromosome aberrations in Peripheral human lymphocytes according to OECD TG 473 (2014), and in compliance with GLP. No statistically significant or biologically relevant increase in the number of cells with chromosome aberrations was observed either with or without metabolic activation when tested up to precipitating concentrations. Appropriate positive and negative controls were used and gave the expected results. It is concluded that the test item is negative for the induction of chromosome aberrations under the conditions of the study.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016-06-07 to 2016-08-22
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)
- Version / remarks:
- 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: in vitro mammalian cell gene mutation assay
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 0006760363
- Expiration date of the lot/batch: 8th November 2016
- Purity test date: 8th October 2015
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: dimethyl sulfoxide
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: stable in dimethyl sulfoxide
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: no specific handling conditions required
- Preliminary purification step (if any): no correction was made for the purity/composition of the test item - Target gene:
- thymidine kinase locus
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: American Type Culture Collection, USA
- Suitability of cells: recommended test system in international guidelines
- Cell cycle length, doubling time or proliferation index: no data
- Sex, age and number of blood donors if applicable: no data
- Whether whole blood or separated lymphocytes were used if applicable: no data
- Number of passages if applicable: no data
- Methods for maintenance in cell culture if applicable: no data
- Modal number of chromosomes: no data
- Normal (negative control) cell cycle time: no data
MEDIA USED
- Type and identity of media including CO2 concentration if applicable:
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically 'cleansed' against high spontaneous background: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- of phenobarbital (80 mg/kg body weight) and ß-naphthoflavone (100 mg/kg body weight) induced rat liver S9
- Test concentrations with justification for top dose:
- Dose range finding test: 1.7, 5.4, 17, 52, 164, 512 μg/ml (with and without S9 mix)
Experiment I: 0.056, 0.18, 0.55, 1.7, 5.4, 17, 52 and 164 μg/ml (with and without S9 mix)
Experiment II: 0.018, 0.056, 0.18, 0.55, 1.7, 5.4, 17, 52 and 164 μg/ml (without S9 mix)
Doses were selected based on cytotoxicity results from dose-range finding test - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: dimethyl sulfoxide
- Justification for choice of solvent/vehicle: based on solubility in dimethyl sulfoxide observed during a solubility test. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- dimethyl sulfoxide
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- dimethyl sulfoxide
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
- Cell density at seeding: 9.6 x 10⁵ cells/ concentration
ACTIVATION: S9 mix was prepared immediately before use and kept on ice. S9-mix components contains per ml physiological saline: 1.63 mg MgCl2 H2O; 2.46 mg KCl; 1.7 mg glucose-6-phosphate; 3.4 mg NADP; 4 µmol HEPES. The final concentration of the S9-fraction in the exposure medium was 4%.
DURATION
- Exposure duration:
Dose-range finding test: 3-hour treatment with and without metabolic activation
Experiment I: 3-hour treatment, with and without metabolic activation
Experiment II: 24-hour treatment, without metabolic activation
- Expression time (cells in growth medium): the remaining cells were cultured for 2 days after the treatment period.
- Selection time (if incubation with a selection agent): 11-12 days
- Fixation time (start of exposure up to fixation or harvest of cells):
SELECTION AGENT (mutation assays): selective medium (TFT-selection agent)
NUMBER OF REPLICATIONS: duplicate plates
METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: the plates of the TFT-selection were stained for 2 hours by adding 0.5 mg/ml 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) (Sigma) to each well.
NUMBER OF CELLS EVALUATED:
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency; relative total growth
- Any supplementary information relevant to cytotoxicity: suspension growth
OTHER EXAMINATIONS:
- Determination of polyploidy: no
- Determination of endoreplication: no - Rationale for test conditions:
- The test concentrations in experiment I and II were selected based on cytotoxicity data from a dose-range finding study.
- Evaluation criteria:
- A test item is considered positive (mutagenic) in the mutation assay if it induces a mutation frequency (MF) of more than MF(controls) + 126 in a dose-dependent manner. Any observed increase should be biologically relevant and will be compared with the historical control data range.
- Statistics:
- A Cochran Armitage trend test (p < 0.05) was performed to test whether there was a significant trend in the induction of mutations.
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: the test item was insoluble in exposure medium and ethanol
- Water solubility: no data
- Precipitation: when mixing with exposure medium the test item precipitated at the concentration of 16.4 mg/ml and higher.
- Definition of acceptable cells for analysis: no data
RANGE-FINDING/SCREENING STUDIES: No toxicity in the suspension growth was observed up to and including the highest test item concentration of 512 μg/ml compared to the suspension growth of the solvent control both in the absence and presence of S9-mix. No toxicity in the relative suspension growth was observed up to the test item concentrations of 512 μg/ml compared to the solvent control.
HISTORICAL CONTROL DATA
- Positive historical control data: within the ranges of historical control data
- Negative (solvent/vehicle) historical control data: within the ranges of historical control data. One of the solvent/negative control cultures in experiment II was just above the 95% control limits of the historical control data range. The observed mutation frequency, however, was within the acceptability criteria of this assay.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: No cytotoxicity was observed in experiment I and II.
- Other observations when applicable: In experiment I the number of small and large colonies in the test item treated cultures were comparable to the number of small and large colonies of the solvent controls. In experiment II the test item precipitated in the exposure medium at concentration of 52 µg/ml after 24-hour treatment. - Remarks on result:
- other: No mutagenic potential
- Remarks:
- Experiment I and II
- Conclusions:
- 1,3,5-Trimethyl-1,1,3,5,5-pentaphenyltrisiloxane has been tested for mutagenicity in mouse lymphoma L5178Y cells, according to OECD 490 and in compliance with GLP. No test substance induced increase in the number of mutations was observed when tested up to precipitating concentration. Appropriate solvent and positive controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study.
Referenceopen allclose all
Table 2: Dose range-finding study Number of revertants per plate (2 plates - MA)
TA 100 |
|||
Concentration (μg/Plate) |
Plate 1 |
Plate 2 |
Cytotoxic (Yes/No) |
0 |
143 |
146 |
No |
0.316 |
154 |
138 |
No |
1 |
188 |
140 |
No |
3.16 |
171 |
144 |
No |
10 |
161 |
162 |
No |
31.6 |
144 |
145 |
No |
100 |
145 |
138 |
No |
316 |
115 |
130 |
No |
1000 |
156 |
135 |
No |
3160 |
195 |
154 |
No |
5000 |
171 |
146 |
No |
*solvent control with DMSO
Table 3: Experiment 1 Plate incorporation Assay Number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA102 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
32 |
36 |
No |
131 |
137.3 |
No |
298 |
279.7 |
No |
10 |
39.3 |
43 |
No |
130.7 |
133.3 |
No |
272 |
280.3 |
No |
31.6 |
38.3 |
39.3 |
No |
122 |
136.7 |
No |
258.3 |
260.7 |
No |
100 |
34.3 |
31.3 |
No |
131 |
123.7 |
No |
265.3 |
283.3 |
No |
316 |
27.7 |
36.7 |
No |
113 |
131 |
No |
276 |
284.3 |
No |
1000 |
23.3 |
24.7 |
No |
120 |
132.3 |
No |
293.7 |
285.3 |
No |
Positive control |
1255 |
1295.7 |
No |
1194 |
1169 |
No |
1130.7 |
1289 |
No |
*solvent control with DMSO
Table 3: Experiment 1 Plate incorporation Assay Number of revertants per plate (mean of 3 plates)
|
TA1535 |
TA 1537 |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
13.7 |
13.7 |
No |
5.3 |
6 |
No |
10 |
12.7 |
13.7 |
No |
4 |
5.3 |
No |
31.6 |
13 |
13 |
No |
3.7 |
7.3 |
No |
100 |
14.3 |
13.3 |
No |
3 |
7 |
No |
316 |
13 |
12 |
No |
5.3 |
6 |
No |
1000 |
12.7 |
14 |
No |
5 |
5 |
No |
Positive control |
564.3 |
563 |
No |
570.7 |
566.7 |
No |
*solvent control with DMSO
Table 4: Experiment 2 Pre incubation test Number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA102 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
31 |
34.7 |
No |
144.7 |
160.7 |
No |
286.3 |
280 |
No |
100 |
37.3 |
36.7 |
No |
128.3 |
135 |
No |
288 |
281 |
No |
316 |
35 |
33.3 |
No |
155.7 |
164.3 |
No |
257.3 |
261.7 |
No |
1000 |
31.3 |
27.3 |
No |
150.7 |
155 |
No |
271.3 |
267.7 |
No |
3160 |
30.3 |
37.3 |
No |
145.3 |
127 |
No |
270.3 |
268.7 |
No |
5000 |
30.7 |
33 |
No |
131 |
129 |
No |
282.7 |
264.3 |
No |
Positive control |
1033.7 |
1141 |
No |
1186.7 |
1139.7 |
No |
1163.3 |
1103.7 |
No |
*solvent control with DMSO
Table 3: Experiment 2 Pre incubation test Number of revertants per plate (mean of 3 plates)
|
TA1535 |
TA 1537 |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
15 |
14 |
No |
5.7 |
5.7 |
No |
100 |
13.7 |
13.7 |
No |
3.7 |
5 |
No |
316 |
13 |
13.7 |
No |
4.7 |
6 |
No |
1000 |
14.3 |
13 |
No |
5 |
5.7 |
No |
3160 |
15.7 |
12.7 |
No |
5.7 |
5.7 |
No |
5000 |
14 |
13 |
No |
4.7 |
5 |
No |
Positive control |
554.3 |
548 |
No |
553.3 |
550 |
No |
*solvent control with DMSO
Table 1: Mitotic index of human lymphocyte cultures treated with the test item in the first (experiement 1) cytogenetic assay
Test item concentration (µg/ml) |
Number of metaphases |
|
|
|
Absolute |
Number of cells scored |
Percentage of control |
3 hour exposure, 24 hour fixation time, without metabolic activation |
|||
Control (DMSO) |
96 - 110 |
1027 - 1011 |
100 |
17 |
82 - 89 |
1018 - 1010 |
83 |
52 |
86 - 95 |
1008 - 1011 |
88 |
164 |
72 - 93 |
1015 - 1002 |
80 |
MMC-C; 0.5 µg/ml |
55 - 63 |
1020 - 1011 |
57 |
MMC-C; 0.75 µg/ml |
45 - 43 |
1022 - 1007 |
43 |
3 hour exposure, 24 hour fixation time, with metabolic activation |
|||
Control |
107 – 98 |
1007 – 1014 |
100 |
17 |
99 – 85 |
1009 – 1026 |
90 |
52 |
95 – 101 |
1016 – 1008 |
96 |
164 |
94 – 82 |
1002 – 1012 |
86 |
CP; 10 µg/ml |
62 - 50 |
1014 - 1004 |
55 |
Table 2: Chromosome aberrations in human lymphocyte cultures treated with the test item in the absence of S9-mix in the first (experiment 1) cytogenetic assay (3 h exposure time, 24 h fixation time)
Concentration |
DMSO (1.0% v/v) |
17 µg/ml |
52 µg/ml |
164 µg/ml |
MMC-C 0.5µg/ml |
||||||||||
Culture |
A B A+B |
A B A+B |
A B A+B |
A B A+B |
A B A+B |
||||||||||
Mitotic Index (%) |
100 |
83 |
88 |
80 |
57 |
||||||||||
No. of Cells scored |
150 150 300 |
150 150 300 |
150 150 300 |
150 150 300 |
150 150 300 |
||||||||||
No. of Cells with aberrations (+ gaps)a) |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
40 |
48 |
***) 88
|
No. of Cells with aberrations (- gaps) |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
40 |
46 |
***) 86
|
total aberr (+ gaps) |
1 |
0 |
|
0 |
0 |
|
0 |
0 |
|
0 |
0 |
|
51 |
48 |
|
total aberr (- gaps) |
1 |
0 |
|
0 |
0 |
|
0 |
0 |
|
0 |
0 |
|
51 |
46 |
|
Table 3: Chromosome aberrations in human lymphocyte cultures treated with the test item in the presence of S9-mix in the first (experiment 1) cytogenetic assay (3 h exposure time, 24 h fixation time)
Conc |
DMSO (1.0% v/v) |
17 µg/ml |
52 µg/ml |
164 µg/ml |
CP 10µg/ml |
||||||||||
Culture |
A B A+B |
A BA+B |
A BA+B |
A BA+B |
A B A+B |
||||||||||
Mitotic Index (%) |
100 |
90 |
96 |
86 |
55 |
||||||||||
No. of Cells scored |
150 150 300 |
150 150300 |
150 150300 |
150 150300 |
150 150 300 |
||||||||||
No. of Cells with aberrations (+ gaps)a) |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
36 |
30 |
***) 66
|
No. of Cells with aberrations (- gaps) |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
36 |
30 |
***) 66
|
total aberr (+ gaps) |
0 |
1 |
|
0 |
0 |
|
0 |
0 |
|
0 |
0 |
|
42 |
37 |
|
total aberr (- gaps) |
0 |
1 |
|
0 |
0 |
|
0 |
0 |
|
0 |
0 |
|
42 |
37 |
|
|
Table 4: Mitotic index of human lymphocyte cultures treated with the test item in the second (experiement 2) cytogenetic assay
Test item concentration (µg/ml) |
Number of metaphases |
|
|
|
Absolute |
Number of cells scored |
Percentage of control |
24 hour exposure, 24 hour fixation time, without metabolic activation |
|||
Control |
69 - 78 |
1021 - 1013 |
100 |
5.4 |
68 - 69 |
1013 - 1016 |
93 |
17 |
76 - 66 |
1033 -1002 |
97 |
52 |
73 - 69 |
1030 - 1018 |
97 |
MMC-C; 0.2 µg/ml |
39 - 45 |
1029 - 1005 |
57 |
MMC-C; 0.3 µg/ml |
18 - 23 |
1017 - 1010 |
28 |
48 hour exposure, 48 hour fixation time, without metabolic activation |
|||
Control |
44 - 44 |
1014 - 1013 |
100 |
5.4 |
47 – 43 |
1013 - 1021 |
102 |
17 |
37 - 37 |
1003 - 1004 |
84 |
52 |
38 - 37 |
1013 - 1006 |
85 |
MMC-C; 0.1 µg/ml |
34 - 36 |
1020 – 1016 |
80 |
MMC-C; 0.15 µg/ml |
29 - 31 |
1003 - 1021 |
68 |
Table 5: Chromosome aberrations in human lymphocyte cultures treated with the test item in the absence of S9-mix in the second (experiment 2) cytogenetic assay (24 h exposure time, 24 h fixation time)
Conc |
DMSO (1.0% v/v) |
5.4 µg/ml |
17 µg/ml |
52 µg/ml |
MMC-C 0.2µg/ml |
||||||||||
Culture |
A B A+B |
A B A+B |
A B A+B |
A B A+B |
A B A+B |
||||||||||
Mitotic Index (%) |
100 |
93 |
97 |
97 |
57 |
||||||||||
No. of Cells scored |
150 150 300 |
150 150 300 |
150 150 300 |
150 150 300 |
150 150 300 |
||||||||||
No. of Cells with aberrations (+ gaps)a) |
0 |
1 |
1 |
1 |
1 |
2 |
2 |
0 |
2 |
1 |
0 |
1 |
53 |
43 |
***) 96
|
No. of Cells with aberrations (- gaps) |
0 |
1 |
1 |
1 |
1 |
2 |
2 |
0 |
2 |
1 |
0 |
1 |
52 |
42 |
***) 94
|
total aberr (+ gaps) |
0 |
1 |
|
1 |
1 |
|
2 |
0 |
|
1 |
0 |
|
60 |
56 |
|
total aberr (- gaps) |
0 |
1 |
|
1 |
1 |
|
2 |
0 |
|
1 |
0 |
|
59 |
53 |
|
Table 6: Chromosome aberrations in human lymphocyte cultures treated with the test item in the absence of S9-mix in the second (experiement 2) cytogenetic assay (48 h exposure time, 48 h fixation time)
Conc |
DMSO (1.0% v/v) |
5.4 µg/ml |
17 µg/ml |
52 µg/ml |
MMC-C 0.1µg/ml |
||||||||||
Culture |
A B A+B |
A B A+B |
A B A+B |
A B A+B |
A B A+B |
||||||||||
Mitotic Index (%) |
100 |
102 |
84 |
85 |
80 |
||||||||||
No. of Cells scored |
150 150 300 |
150 150 300 |
150 150 300 |
150 150 300 |
150 150 300 |
||||||||||
No. of Cells with aberrations (+ gaps)a) |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
1 |
1 |
0 |
0 |
0 |
42 |
53 |
***) 95
|
No. of Cells with aberrations (- gaps) |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
42 |
52 |
***) 94
|
total aberr (+ gaps) |
0 |
1 |
|
0 |
0 |
|
0 |
1 |
|
0 |
0 |
|
51 |
66 |
|
total aberr (- gaps) |
0 |
1 |
|
0 |
0 |
|
0 |
0 |
|
0 |
0 |
|
51 |
65 |
|
*) Significantly different from control group (Fisher’s exact test), * P < 0.05, ** P < 0.01 or *** P < 0.001
Table 1: Experiment I, 3 -hour exposure without metabolic activation
Test Group |
Concentrations µg/ml |
RCE % |
RTG % |
RSG % |
MF (mutants/106cells) |
GEF exceeded |
Statistical Significant Increase |
SC1 |
0 |
100 |
100 |
100 |
79 |
- |
- |
SC2 |
0 |
100 |
100 |
100 |
124 |
- |
- |
1 |
0.056 |
102 |
101 |
99 |
93 |
- |
- |
2 |
0.18 |
104 |
92 |
89 |
97 |
- |
- |
3 |
0.55 |
111 |
102 |
92 |
106 |
- |
- |
4 |
1.7 |
134 |
126 |
94 |
95 |
- |
- |
5 |
5.4 |
105 |
103 |
98 |
51 |
- |
- |
6 |
17 |
111 |
100 |
90 |
64 |
- |
- |
7 |
52 |
104 |
96 |
93 |
76 |
- |
- |
8 |
164* |
116 |
104 |
90 |
94 |
- |
- |
MMS |
15 |
63 |
39 |
62 |
632 |
+ |
+ |
Table 2: Experiment I, 3 -hour exposure with metabolic activation
Test Group |
Concentrations µg/ml |
RCE % |
RTG % |
RSG % |
MF (mutants/106cells) |
GEF exceeded |
Statistical Significant Increase |
SC1 |
0 |
100 |
100 |
100 |
91 |
- |
- |
SC2 |
0 |
100 |
100 |
100 |
117 |
- |
- |
1 |
0.056 |
100 |
90 |
90 |
105 |
- |
- |
2 |
0.18 |
86 |
75 |
87 |
116 |
- |
- |
3 |
0.55 |
104 |
97 |
93 |
100 |
- |
- |
4 |
1.7 |
97 |
83 |
86 |
136 |
- |
- |
5 |
5.4 |
110 |
82 |
75 |
81 |
- |
- |
6 |
17 |
110 |
96 |
87 |
85 |
- |
- |
7 |
52 |
94 |
82 |
87 |
97 |
- |
- |
8 |
164* |
118 |
103 |
87 |
92 |
- |
- |
CP |
7.5 |
25 |
7 |
27 |
1938 |
+ |
+ |
Table 3: Experiment II, 24 -hour treatment without metabolic activation
Test Group |
Concentrations µg/ml |
RCE % |
RTG % |
RSG % |
MF (mutants/106cells) |
GEF exceeded |
Statistical Significant Increase |
SC1 |
0 |
100 |
100 |
100 |
118 |
- |
- |
SC2 |
0 |
100 |
100 |
100 |
133 |
- |
- |
1 |
0.018 |
117 |
109 |
93 |
72 |
- |
- |
2 |
0.056 |
104 |
95 |
91 |
122 |
- |
- |
3 |
0.18 |
104 |
93 |
89 |
102 |
- |
- |
4 |
0.55 |
117 |
111 |
95 |
70 |
- |
- |
5 |
1.7 |
106 |
107 |
101 |
108 |
- |
- |
6 |
5.4 |
124 |
120 |
97 |
81 |
- |
- |
7 |
17 |
114 |
109 |
96 |
85 |
- |
- |
8 |
52* |
99 |
87 |
88 |
108 |
- |
- |
MMS |
15 |
88 |
65 |
74 |
583 |
+ |
+ |
* the test item precipitated in the exposure medium
RSG: Relative suspension growth
RCE: Relative cloning efficiency
RTG: Relative total growth
SC: solvent control
MMS: methylmethanesulfonate
CP: cyclophosphamine
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
1,3,5-Trimethyl-1,1,3,5,5-pentaphenyltrisiloxane has been tested in a valid bacterial reverse mutation assay, according to the OECD TG 471, and in compliance with GLP, using Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 (LPT, 2002). No increase in the number of revertants was observed in any test strain, with or without metabolic activation, up to limit concentration. Appropriate positive and solvent controls were added and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.
1,3,5-Trimethyl-1,1,3,5,5-pentaphenyltrisiloxane has been tested in a valid study for ability to induce chromosome aberrations in peripheral human lymphocytes according to OECD TG 473 (2014), and in compliance with GLP. No statistically significant or biologically relevant increase in the number of cells with chromosome aberrations was observed either with or without metabolic activation when tested up to precipitating concentrations. Appropriate positive and negative controls were used and gave the expected results. It is concluded that the test item is negative for the induction of chromosome aberrations under the conditions of the study.
1,3,5-Trimethyl-1,1,3,5,5-pentaphenyltrisiloxane has been tested for mutagenicity in Mouse lymphoma L5178Y cells, according to OECD 490 and in compliance with GLP (Charles River, 2016). No test substance induced increase in the number of mutations was observed when tested up to precipitating concentration. Appropriate solvent and positive controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study.
Justification for classification or non-classification
Based on the available data for 1,3,5 -trimethyl-1,1,3,5,5-pentaphenyltrisiloxane, no classification is required for genetic toxicity according to Regulation (EC) No 1272/2008.
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