Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 240-464-3 | CAS number: 16415-12-6
- 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
Gene mutation (Bacterial reverse mutation assay / Ames test, OECD TG
471):
S. typhimurium TA 1535, TA 1537, TA 98, TA 100, and TA 102: negative
with and without metabolic activation
S. typhimurium TA 1535, TA 1537, TA 98, TA 100, and E. coli WP2 uvrA:
negative with and without metabolic activation
Mammalian cytogenicity (CHO chromosome aberration assay, OECD TG
473): negative with and without metabolic activation
Mammalian Mutagenicity (Mouse Lymphoma Assay, OECD TG 476, RA from CAS
5894-60-0): negative with and without metabolic activation
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2002-04-15 to 2002-07-04
- 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
- Qualifier:
- according to guideline
- Guideline:
- other: EC 92/69/EEC L383 A: part B Determination of Toxicity-Mutagenicity
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: ICH S2A Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: ICH S2B: A Standard Battery for Genotoxicity Testing of Pharmaceuticals
- 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:
- S. typhimurium TA 102
- 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:
- Pre-test: 0.316, 1, 3.16, 10, 31.6, 100, 316, 1000, 3160, 5000 µg/plate
Main test: 100, 316, 1000, 3160, 5000 µg/plate - Vehicle / solvent:
- - Vehicle/solvent used: acetone
- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to bacteria - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- cyclophosphamide
- methylmethanesulfonate
- other: 2-anthracene amide
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 60 minutes
- Exposure duration: 48 hours
NUMBER OF REPLICATIONS: triplicates in two independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: growth of background lawn
OTHER:
Controls:
with S9: 2-anthracene amide (2-ATA - TA 1537, TA 98 and TA 102, 2 µg/plate in DMSO; cyclophosphamide (CS - TA 100 and TA1535, 1500 µg/plate in aqua ad iniectabilia)
without S9: sodium azide (NaN3 - TA 1535 and TA 100, 10 µg/plate in water); 9-aminoacridine (9-AA - TA 1537, 100 µg/plate in ethanol); 2-nitrofluorene (2-NF; TA 98, 10 µg/plate in DMSO), methyl methane sulfonate (MMS – TA 102, 1300 µg/plate in DMSO) - Evaluation criteria:
- A result is considered positive if the number of revertants is significantly increased compared to 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. In addition, a significant concentration related effect is observed in positive results, and positive results have to be reproducible and the histidine independence of revertants confirmed.
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.
- 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:
- cytotoxicity
- Remarks:
- TA 1537 (at 5000 µg/plate, +S9, only in plate incorporation test)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Non-interfering substance precipitate was noted at 5000 µg/plate in all test strains
COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data - Conclusions:
- Interpretation of results:
negative
No mutagenic effect was observed for the test substance tested up to the limit dose in any of the test strains in two independent
experiments without and with metabolic activation. - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- 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:
- (adopted 1997)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Ministerium für Arbeit, Gesundheit und Soziales des Landes Nordrhein-Westfalen, Düsseldorf, Germany
- 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:
- Experiment I+II
- 62, 185, 556, 1667, 5000 µg/plate (with and without metabolic activation)
Experiment III:
- 1000, 2000, 3000, 4000, 5000 µg/plate (with and without metabolic activation) - Vehicle / solvent:
- - Vehicle/solvent used: acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: -S9: NaN3: 2 µg/plate (TA 100, TA 1535); 9-AA: 50 µg/plate (TA 1537); 2-NF: 4 µg/plate (TA 98); 4-NQO: 1 µg/plate (E.coli WP2 uvrA); +S9: 2-AA: 7 µg/plate (TA 1535, TA 1537), 2 µg/plate (TA 100), 10 µg/plate (E.coli WP2 uvrA); BaP: 30 µg/plate (TA 98)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: triplicates in 3 independent experiments (test substance); six plates per experiment for the solvent control
DETERMINATION OF CYTOTOXICITY
- Method: growth of background lawn - Evaluation criteria:
- A test substance producing no biologically relevant positive response in any one of the bacterial strains tested is considered to be non-mutagenic in this system. A biologically relevant response is described as follows: If the number of revertants is at least twice the spontaneous reversion rate for TA 1535, TA 98, TA 100 or WP2 uvrA (or three times for TA 1537) and/or if there is a concentration related increasing number of revertants over the range tested.
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: no cytotoxicity, but tested up to limit concentration; precipitates from 1000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: no cytotoxicity, but tested up to limit concentration; precipitates from 1000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: no cytotoxicity, but tested up to limit concentration; precipitates from 1000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: no cytotoxicity, but tested up to limit concentration; precipitates from 1000 µg/plate
- 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:
- other: no cytotoxicity, but tested up to limit concentration; precipitates from 1000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: from 1000 µg/plate and higher
COMPARISON WITH HISTORICAL CONTROL DATA: Historical control data were given in the study report. The results of the solvent control cultures lied within the range of the historical control data.
OTHER:
- Revertant counts higher than 1000 were counted and calculated as 1000.
- Study plan amendment: Due to invalid positive and solvent controls for the strains Salmonella typhimurium TA 100 and Escherichia coli WP2 uvrA parts of the first experiment had to be repeated (=second experiment). - Conclusions:
- Interpretation of results:
negative
In a study according to OECD 471 and in compliance with GLP no mutagenic effect was observed for the test substance tested up to the limit concentration in any of the test strains in three independent experiments with and without metabolic activation. - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 02 Sep 2004 to 03 Dec 2004
- 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:
- (adopted 1997)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- Not applicable
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital and beta-naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- Experiment I+II:
- 10.2, 20.3, 40.6, 81.3, 163, 325, 650, 1300 µg/ml (with and without metabolic activation) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to cells - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: -S9: mitomycin: 0.3 µg/ml (3 h treatment), 0.1 µg/ml (20 h treatment); +S9: cyclophosphamide: 15 µg/ml (3 h treatment)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Preincubation period:
- Exposure duration: 3 h and 20 h
- Fixation time (start of exposure up to fixation or harvest of cells): 20 h
SPINDLE INHIBITOR (cytogenetic assays): colcemid (0.2 µg/ml; added 3 hours before harvest)
STAIN (for cytogenetic assays): Giemsa (3%)
NUMBER OF REPLICATIONS: 2 independent experiment
NUMBER OF CELLS EVALUATED: 100 cells from each culture were evaluated for chromosome abberations.
DETERMINATION OF CYTOTOXICITY
- Method: relative cell count - Evaluation criteria:
- The test item is considered to have clastogenic properties if there is a statistically significant increase in the incidence of cells bearing aberrations at any dose level over the concurrent control. The increase must exceed historical control values. The increases must be reproduced in both cultures.
- Statistics:
- Where necessary, the frequency of cells with aberrations excluding gaps, and the frequency of polyploid cells was compared with the concurrent vehicle control using Fischer's Exact test.
- Species / strain:
- Chinese hamster Ovary (CHO)
- 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:
- COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data
- Conclusions:
- Interpretation of results:
negative
The substance was tested to OECD 473 (1997) under GLP. The test material did not induce any statistically significant, dose-related increases in the frequency of cells with chromosomal aberrations either in the presence or absence of metabolic activation or after various exposure times. The test material was therefore considered to be non-clastogenic to CHO cells in vitro under the conditions of the test. - Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results:
negative with and without metabolic activation - Executive summary:
The structural analogue trichloro(hexadecyl)silane (CAS 5894-60-0) was assessed for its potential to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. It is concluded that the structural analogue is negative for mutagenicity to mammalian cells under the conditions of the test. As explained in the justification for type of information, a similar outcome is considered for the target substance as well.
Referenceopen allclose all
Table 2: Dose range-finding study number of revertants per plate (2 plates)
|
TA100 |
||
Conc. |
Plate 1 |
Plate 2 |
Cytotoxic |
0* |
114 |
137 |
No |
0.316 |
110 |
126 |
No |
1 |
123 |
134 |
No |
3.16 |
137 |
150 |
No |
10 |
129 |
159 |
No |
31.6 |
134 |
119 |
No |
100 |
133 |
137 |
No |
316 |
119 |
125 |
No |
1000 |
141 |
129 |
No |
3160 |
114 |
121 |
No |
5000 |
132 |
119 |
No |
*solvent control with acetone
Table 3: Experiment 1 (plate incorporation): number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA102 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
30.3 |
31 |
No |
128.3 |
144.3 |
No |
269 |
287.7 |
No |
100 |
38 |
27.7 |
No |
122.7 |
137.7 |
No |
265.7 |
289.3 |
No |
316 |
28 |
27.3 |
No |
122.3 |
137.3 |
No |
251.3 |
282.3 |
No |
1000 |
30.3 |
28.3 |
No |
123.3 |
119.7 |
No |
246 |
271 |
No |
3160 |
31 |
30 |
No |
127 |
136 |
No |
257.7 |
285 |
No |
5000 |
35.3 |
25.3 |
No |
119.7 |
152 |
No |
291 |
282 |
No |
Positive control |
1200.7 |
1211.3 |
No |
1226.7 |
1259.7 |
No |
1107.7 |
1277.7 |
No |
*solvent control with acetone
Table 3: Experiment 1 (plate incorporation): number of revertants per plate (mean of 3 plates)
|
TA1535 |
TA1537 |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
13.3 |
12.3 |
No |
7 |
9.7 |
No |
100 |
12.7 |
11.7 |
No |
8.7 |
8.7 |
No |
316 |
14.7 |
14.3 |
No |
9.3 |
6.3 |
No |
1000 |
12 |
12.7 |
No |
10.3 |
6.7 |
No |
3160 |
11 |
12.7 |
No |
10.7 |
6 |
No |
5000 |
12 |
14 |
No |
9.3 |
0 |
Yes |
Positive control |
364 |
350 |
No |
392.7 |
358 |
No |
*solvent control with acetone
Table 4: Experiment 2 (preincubation): number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA102 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
51 |
34.3 |
No |
127.3 |
164 |
No |
278.7 |
290.3 |
No |
100 |
51 |
37 |
No |
127 |
152.7 |
No |
167 |
278 |
No |
316 |
46.7 |
36.3 |
No |
120 |
146.7 |
No |
278.7 |
298.7 |
No |
1000 |
56.3 |
49.7 |
No |
140.7 |
153.7 |
No |
288.7 |
287 |
No |
3160 |
52 |
43.7 |
No |
132 |
158 |
No |
297.7 |
286 |
No |
5000 |
48.3 |
43 |
No |
132 |
175.7 |
No |
289.7 |
266.7 |
No |
Positive control |
910 |
906 |
No |
1179.7 |
1226.7 |
No |
1231.7 |
1220.3 |
No |
*solvent control with acetone
Table 4: Experiment 2 (preincubation): number of revertants per plate (mean of 3 plates)
|
TA1535 |
TA1537 |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
13 |
11.7 |
No |
6 |
6 |
No |
100 |
11 |
13.3 |
No |
5 |
9 |
No |
316 |
12.3 |
16.7 |
No |
4.3 |
8 |
No |
1000 |
13 |
16.3 |
No |
5.3 |
7 |
No |
3160 |
11 |
16.3 |
No |
4 |
5 |
No |
5000 |
12.3 |
14 |
No |
4 |
6 |
No |
Positive control |
524.7 |
556.3 |
No |
486.7 |
508.7 |
No |
*solvent control with acetone
Table 1: Mean values of experiment 1 and 2.
With or without S9-Mix |
Test substance concentration (µg/plate) |
Mean number of revertant colonies per plate (average of 3 plates ± Standard deviation) |
||||
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
WP2 uvrA |
||
– |
0 |
9±3 |
4±3 |
20±4 |
207±34 |
17±6 |
– |
62 |
7±3 |
3±1 |
23±6 |
202±30 |
16±3 |
– |
185 |
10±2 |
3±3 |
24±3 |
219±26 |
19±4 |
– |
556 |
6±3 |
8±3 |
20±1 |
222±39 |
15±5 |
– |
1667, P |
11±3 |
3±3 |
25±6 |
187±5 |
13±3 |
– |
5000, P |
9±5 |
5±3 |
27±3 |
200±9 |
12±2 |
Positive controls, –S9 |
Name |
NaN3 |
9-AA |
2-NF |
NaN3 |
4-NQO |
Concentrations (µg/plate) |
2 |
50 |
4 |
2 |
1 |
|
Revertants per plate |
677±107 |
328±45 |
363±64 |
1000±0 |
491±100 |
|
+ |
0 |
13±4 |
6±3 |
28±3 |
130±20 |
23±3 |
+ |
62 |
12±1 |
4±1 |
34±2 |
142±11 |
21±4 |
+ |
185 |
14±2 |
4±2 |
21±4 |
109±10 |
20±5 |
+ |
556 |
8±2 |
4±2 |
23±6 |
107±7 |
21±2 |
+ |
1667, P |
12±2 |
4±3 |
28±6 |
129±12 |
19±4 |
+ |
5000, P |
8±5 |
5±1 |
25±9 |
125±13 |
23±2 |
Positive controls, +S9 |
Name |
2-AA |
2-AA |
B[a]P |
2-AA |
2-AA |
Concentrations (µg/plate) |
7 |
7 |
30 |
2 |
10 |
|
Revertants per plate |
531±45 |
595±58 |
1000±0 |
1000±0 |
206±23 |
P: precipitation observed
Table 2: Results of experiment 3.
With or without S9-Mix |
Test substance concentration (µg/plate) |
Mean number of revertant colonies per plate (average of 3 plates ± Standard deviation) |
||||
TA 1535 |
TA 1537 |
TA 98 |
TA 100 |
WP2 uvrA |
||
– |
0 |
9±2 |
4±1 |
21±4 |
105±12 |
20±6 |
– |
1000, P |
9±3 |
4±3 |
28±4 |
140±26 |
17±6 |
– |
2000, P |
13±5 |
1±1 |
22±4 |
134±33 |
28±11 |
– |
3000, P |
10±3 |
5±2 |
23±2 |
129±5 |
22±8 |
– |
4000, P |
10±4 |
2±2 |
19±1 |
137±21 |
25±1 |
– |
5000, P |
10±2 |
3±2 |
23±4 |
117±12 |
20±7 |
Positive controls, –S9 |
Name |
NaN3 |
9-AA |
2-NF |
NaN3 |
4-NQO |
Concentrations (µg/plate) |
2 |
50 |
4 |
2 |
1 |
|
Revertants per plate |
704±73 |
147±13 |
400±71 |
1000±0 |
613±41 |
|
+ |
0 |
9±2 |
4±1 |
21±4 |
105±12 |
20±6 |
+ |
1000, P |
9±3 |
4±3 |
28±4 |
140±26 |
17±6 |
+ |
2000, P |
13±5 |
1±1 |
22±4 |
134±33 |
28±11 |
+ |
3000, P |
10±3 |
5±2 |
23±2 |
129±5 |
22±8 |
+ |
4000, P |
10±4 |
2±2 |
19±1 |
137±21 |
25±1 |
+ |
5000, P |
10±2 |
3±2 |
23±4 |
117±12 |
20±7 |
Positive controls, +S9 |
Name |
2-AA |
2-AA |
B[a]P |
2-AA |
2-AA |
Concentrations (µg/plate) |
7 |
7 |
30 |
2 |
10 |
|
Revertants per plate |
491±44 |
584±97 |
805±78 |
1000±0 |
274±103 |
P: precipitation observed
Table 2: Results of chromosome analysis Experiment 1, 3h treatment without activation (total count from 2 cultures)
|
Untreated *** |
Solvent* Control*** |
Positive Control** |
Low dose*** |
Mid dose*** |
High dose*** |
|
Cytotoxicity |
no |
no |
no |
no |
no |
no |
|
|
Mean |
||||||
Chromatid aberrations |
gaps |
0 |
0 |
3 |
0 |
0 |
1 |
deletions |
0 |
0 |
25 |
0 |
0 |
0 |
|
interchanges |
0 |
0 |
49 |
0 |
0 |
0 |
|
Chromosome aberrations |
gaps |
NR |
NR |
NR |
NR |
NR |
NR |
deletions |
0 |
0 |
3 |
0 |
0 |
0 |
|
interchanges |
0 |
0 |
0 |
0 |
0 |
0 |
|
Mitotic index |
NR |
NR |
NR |
NR |
NR |
NR |
|
Polyploidy |
0 |
0 |
0 |
0 |
0 |
0 |
|
Endo reduplication |
0 |
0 |
0 |
0 |
0 |
0 |
*Solvent control with ethanol
** Per 150 cells
*** Per 200 cells
NR not reported
Table 3: Results of chromosome analysis Experiment 1, 3h treatment with activation (total count from 2 cultures)
|
Untreated *** |
Solvent* Control*** |
Positive Control** |
Low dose*** |
Mid dose*** |
High dose*** |
|
Cytotoxicity |
no |
no |
no |
no |
no |
no |
|
|
Mean |
||||||
Chromatid aberrations |
gaps |
0 |
0 |
3 |
0 |
0 |
1 |
deletions |
0 |
0 |
25 |
1 |
0 |
22 |
|
interchanges |
0 |
0 |
49 |
0 |
0 |
40 |
|
Chromosome aberrations |
gaps |
NR |
NR |
NR |
NR |
NR |
NR |
deletions |
0 |
0 |
3 |
0 |
0 |
5 |
|
interchanges |
0 |
0 |
0 |
0 |
0 |
0 |
|
Mitotic index |
NR |
NR |
NR |
NR |
NR |
NR |
|
Polyploidy |
0 |
0 |
0 |
0 |
0 |
0 |
|
Endo reduplication |
2 |
0 |
0 |
0 |
0 |
0 |
*Solvent control with ethanol
** Per 150 cells
*** Per 200 cells
NR not reported
Table 4: Results of chromosome analysis Experiment 2, 20h treatment without activation (total count from 2 cultures)
|
Untreated *** |
Solvent* Control*** |
Positive Control** |
Low dose*** |
Mid dose*** |
High dose*** |
|
Cytotoxicity |
no |
no |
no |
no |
no |
no |
|
|
Mean |
||||||
Chromatid aberrations |
gaps |
0 |
0 |
0 |
0 |
0 |
1 |
deletions |
1 |
1 |
7 |
1 |
1 |
0 |
|
interchanges |
4 |
0 |
52 |
0 |
1 |
0 |
|
Chromosome aberrations |
gaps |
NR |
NR |
NR |
NR |
NR |
NR |
deletions |
0 |
0 |
9 |
2 |
3 |
0 |
|
interchanges |
0 |
0 |
0 |
0 |
0 |
0 |
|
Mitotic index |
NR |
NR |
NR |
NR |
NR |
NR |
|
Polyploidy |
0 |
0 |
0 |
0 |
0 |
0 |
|
Endo reduplication |
0 |
0 |
0 |
0 |
0 |
0 |
*Solvent control with ethanol
** Per 150 cells
*** Per 200 cells
NR not reported
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
In vivo testing is not required as no ambiguous or positive results for genetic toxicity were found in the in vitro studies.
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In the key Ames test according to OECD TG 471 and in compliance with GLP, Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and E. coli strain WP2 uvrA were treated with up to 5000 µg/plate hexadecyl(trimethoxy)silane in the presence and absence of a metabolic activation system in a plate incorporation assay. No increase of the number of revertants was observed in any strain and in any experiment. Precipitation was observed beginning with 1000 µg/plate and no cytotoxic effects were noted (Evonik, 2011).
In an Ames test according to OECD TG 471 and in compliance with GLP, Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and TA 102 were treated with up to 5000 µg/plate hexadecyl(trimethoxy)silane in the presence and absence of a metabolic activation system in a preincubation and a plate incorporation assay. No increase of the number of revertants was observed in any strain and in any test. Precipitation was observed at 5000 µg/plate and cytotoxic effects were observed in strain TA 1537 at 5000 µg/plate in the plate incorporation assay, only (LPT, 2002d).
The results of both studies are in agreement and give evidence that the test substance is non-mutagenic in the bacterial reverse mutation assay under the applied test conditions.
In the chromosome aberration assay, according to OECD TG 473 and in compliance with GLP, Chinese Hamster Ovary Cells were treated with up to 1300 µg/mL hexadecyl(trimethoxy)silane in the presence and absence of metabolic activation (RTC, 2005). The cells were treated for 3 h (with and without metabolic activation) and for 20 h (without metabolic activation). After 20 h the cells were fixed and stained with Giemsa after previous exposure to colcemid. The test material did not induce any statistically significant, dose-related increases in the frequency of cells with chromosomal aberrations either in the presence or absence of metabolic activation or after various exposure times. The test material was therefore considered to be non-clastogenic to CHO cells in vitro under the conditions of the test.
No data is available for in vitro mammalian mutagenicity for the registered substance. However, an OECD TG 490 study with hexadecyl(trimethoxy)silane is on-going, but the results will not be available for this current dossier update. Therefore, as an interim measure, the hazard assessment was performed based on available data from the structural analogue trichloro(hexadecyl)silane (CAS 5894-60-0). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and in accordance with the Read across assessment framework (RAAF, ECHA 2017) read across from analogue substances has been applied to support the human health hazard assessment of hexadecyl(trimethoxy)silane (CAS 16415-12-6). Further details are provided in the analogue justification attached to the respective target entry.
In the key in vitro mammalian mutagenicity study (BSL, 2012), the structural analogue substance trichloro(hexadecyl)silane (CAS 5894-60-0) was assessed for its potential to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. The study was conducted according to OECD TG 476 and in compliance with GLP. No biologically relevant increase of mutants was found after treatment with the test item (with and without metabolic activation). The Global Evaluation Factor (GEF; defined as the mean of the negative/vehicle mutant frequency plus one standard deviation; data gathered from ten laboratories) was not exceeded by the induced mutant frequency at any concentration. Concentrations with RTG values below 10% were not considered for evaluation of mutagenicity. No dose-response relationship was observed. Colony sizing showed no clastogenic effects induced by the test item under the experimental conditions (with and without metabolic activation). Appropriate solvent and positive controls were included in the test and gave the expected results. It was therefore concluded that the test substance is not mutagenic to mammalian cells under the conditions of the test.
Justification for classification or non-classification
The available data on genetic toxicity of the test substance do
not meet the criteria for classification according to Regulation (EC)
No. 1272/2008, and are therefore conclusive but not sufficient for
classification.
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.