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EC number: 219-787-9 | CAS number: 2530-87-2
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- Ecotoxicological Summary
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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): positive with and without activation in strains TA-100 and TA-1535, and in strain TA-98 without activation (OECD Test Guideline 471 and in compliance with GLP) (Dow Corning Corporation, 1993).
Mutagenicity in mammalian cells: positive with metabolic
activation L5178Y mouse lymphoma cells (similar to OECD Test Guideline
476 and in compliance with GLP) (Dow Corning Corporation, 1995).
Link to relevant study records
- 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:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA1538, TA102
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- 0.5 ml Aroclor 1254 induced rat liver S9
- Test concentrations with justification for top dose:
- 100, 333, 1000, 3333 and 5000 µg/plate
- Vehicle / solvent:
- - Vehicle: DMSO at 50 µl
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- with activation, all strains except TA 102
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: sterigmatocystin
- Remarks:
- TA 102 with 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 and TA 1537 without activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 100 and TA 1535 without activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cumene hydroperoxide
- Remarks:
- TA 102 without activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- E coli without activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48-72 hours
- Expression time (cells in growth medium): 48-72 hours
- Fixation time (start of exposure up to fixation or harvest of cells): 48-72 hours
NUMBER OF REPLICATIONS: triplicate plates
DETERMINATION OF CYTOTOXICITY
- Method: other: condition of background lawn - Evaluation criteria:
- All cultures must demonstrate the characteristic mean number of spontaneous revertants in the vehicle control as shown below:
TA98 10 - 50
TA100 80 - 240
TA1535 5 - 45
TA1537 3 - 21
TA1538 5 - 35
TA102 200- 380
WP2uvrA 10 - 60
For the test article to be evaluated positive, it must cause a dose-related increase in the mean revertants per plate of at least one tester strain with a minimum of two increasing concentrations of test article. Data sets for strains TA1535, TA1537 and TA1538 will be judged positive if the increase in mean revertants at the peak of the dose response is equal to greater than three times the mean vehicle control value. Data sets for strains TA98, TA100, and WP2uvrA will be judged positive if the increase in mean revertants at the peak of the dose-response is equal to or greater than two times the mean vehicle control value. - Statistics:
- None
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- none
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium, other: TA100 and TA1535
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- bacteria, other: Salmonella typhimurium TA1537, TA1538, TA102; Escherichia coli/WP2uvrA
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- No precipitate or bacterial toxicity was observed in this assay.
A positive response was observed with bacterial tester strain TA-98 in the absence of metabolic activation and tester strains TA-100 and TA-1535 with and without metabolic activation. The authors concluded that under these experimental conditions, the test material caused mutagenicity in three bacterial tester strains.
Cytotoxic concentration:
* With metabolic activation: No toxicity observed at the maximum dose of 5000 ug/plate
* Without metabolic activation: No toxicity observed at the maximum dose of 5000 ug/plate
Genotoxic effects (e.g. positive, negative, unconfirmed, dose-response, equivocal):
* With metabolic activation: Positive in TA-100 and TA-1535
* Without metabolic activation: Positive in TA-98, TA-100 and TA-1535 - Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- (3-Chloropropyl)trimethoxysilane has been tested for mutagenicity in a valid gene mutation study in bacterial strains S. typhimurium TA-98,TA-100,TA-1535,TA-1537,TA-1538, TA-102 and E. coli WP2 uvr A with and without metabolic activation, conducted according to a protocol similar to OECD Test Guideline 471 and in compliance with GLP. An dose-dependent increase in the number of revertants was observed in S. typhimurium strains TA100 and TA1535 with and without metabolic activation, and in strain TA98 in the absence of metabolic activation. It is concluded that (3-chloropropyl)trimethoxysilane is positive for mutagenicity in bacteria under the conditions of this test.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- appears to be guideline but none mentioned in report
- Deviations:
- yes
- Remarks:
- positive controls used are not those recommended for the TK locus
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced Rat Liver 250 µl S9, cofactor NADP
- Test concentrations with justification for top dose:
- 25, 50, 60, 70, 80 and 90 µg/ml (however 90 µg/ml was too toxic to be evaluated for mutagenicity) in the presence of S9.
500, 1000, 1500, 2000 and 2500 µg/ml in the absence of S9
Selection of dose levels for the mutation assay was based on reduction of suspension growth relative to the solvent control. Substantial toxicity, i.e., suspension growth of less than equal to 50% of the solvent control, was observed at 5000 µg/ml without activation and greater than or equal to 50% at 50 µg/ml with S9 activation. Based on these findings, the dose chosen for the mutagenesis assay ranged from 500 to 5000 µg/ml for the non-activated cultures and 10 to 100 µg/ml for the S9 activated cultures. - Vehicle / solvent:
- Acetone was determined to be the solvent of choice based on solubility of the test article and compatibility with the target cells.
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 0.25 and 0.50 µl/ml
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- Remarks:
- with activation 0.25 and 0.50 µl/ml
- Details on test system and experimental conditions:
- The material was tested in the L5178Y/TK+/- mouse lymphoma mutagenesis assay in the absence and presence of Aroclor-induced rat liver S9. The assay was performed in two phases. The first phase, the preliminary toxicity assay was used to establish the dose range for the mutagenesis assay. The second phase, the mutagenesis assay was used to evaluate the mutagenic potential of the test article. A confirmatory assay which is required by full compliance of OECD and EPA guidelines was not performed.
Test Design: * Number of replicates: 2 - Evaluation criteria:
- In evaluation of the data, increases in the mutant frequencies which occurred only at highly toxic concentrations (i.e. less than 10% total growth) were not considered biologically relevant. All conclusions were based on sound scientific judgment; however, as a guide to interpretation of the data, the test article was considered to induce a positive response if a concentration-related increase in mutant frequency was observed and more than one dose level with 10% or greater total growth exhibited a mutant frequency two-fold greater than the solvent control. A doubling above background at one or more dose levels with 10% or greater total growth with no evidence of a dose-response was considered equivocal. Test articles not producing a doubling above background at one or more dose levels with 10% or greater total growth were concluded to be negative.
The following criteria must be met for the mutagenesis assay to be considered valid. The mutant frequency of the positive controls must be at least twice that of the appropriate solvent control cultures. The spontaneous mutant frequency of the solvent controls must be between 20 and 100 TFT-resistant mutants per 106 surviving cells. The cloning efficiency of the solvent controls must be greater than 50%. - Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- With metabolic activation: 80 and 90 µg/ml; Without metabolic activation: 2000 and 2500 µg/ml
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- In the mutagenesis assay, no non-activated test article-treated cultures and eight S9-activated test article-treated cultures exhibited mutant frequencies that were at least twice that of the solvent control. A dose-response trend was noted in the S9-activated cultures.
Toxicity in the cloned cultures, i.e., total growth of less than or equal to 50% on the solvent control, was observed at a dose of 2000 µg/ml without activation and at doses of greater than or equal to 60 µg/ml with S9 activation.
The trifluorothymidine-resistant colonies for the cloned S9-activated positive control, solvent control and test article-treated cultures were sized according to diameter over a range from 0.2 to 1.1 mm. The data on colony size distributions showed an increase in the frequency of medium to large colonies when the treated cultures were compared to the solvent control cultures.
Under the conditions of this study, the test article was considered to be negative without S9 activation and positive with S9 activation in the L5178Y/TK +/- Mouse Lymphoma Mutagenesis Assay.
Cytotoxic concentration:
* With metabolic activation: 80 and 90 µg/ml
* Without metabolic activation: 2000 and 2500 µg/ml
Genotoxic effects (e.g. positive, negative, unconfirmed, dose-response, equivocal):
* With metabolic activation: Positive
* Without metabolic activation: Negative - Conclusions:
- (3-Chloropropyl)trimethoxysilane has been tested for mutagenicity in a reliable mammalian mutagenicity study in L5178Y mouse lymphoma cells with and without metabolic activation, conducted according to a protocol similar to OECD Test Guideline 476 and in compliance with GLP. The test material was considered to be negative for mutagenicity when tested without metabolic activation and positive when tested with metabolic activation. (3-Chloropropyl)trimethoxysilane has been concluded to be positive for mutagenicity in mammalian cells under the conditions to the study.
Referenceopen allclose all
Table 1: Dose range-finding study
|
TA 100 |
E.coli WP2 uvrA |
||||
Conc. |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
0 |
122 |
129 |
no |
13 |
15 |
no |
6.7 |
140 |
163 |
no |
16 |
23 |
no |
10 |
121 |
140 |
no |
11 |
15 |
no |
33 |
142 |
129 |
no |
17 |
14 |
no |
67 |
143 |
118 |
no |
26 |
18 |
no |
100 |
144 |
119 |
no |
20 |
21 |
no |
333 |
151 |
129 |
no |
20 |
23 |
no |
667 |
148 |
158 |
no |
26 |
10 |
no |
1000 |
209 |
196 |
no |
25 |
18 |
no |
3333 |
298 |
275 |
no |
22 |
20 |
no |
5000 |
308 |
446 |
no |
23 |
27 |
no |
*solvent control with DMSO
Table 2: - Plate incorporation:Number of revertants per plate (mean of 3 plates)
|
TA 98 |
TA 100 |
TA 1535 |
||||||
Conc. |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
0* |
19 |
NT |
no |
115 |
169 |
no |
9 |
12 |
no |
100 |
12 |
NT |
no |
137 |
168 |
no |
18 |
13 |
no |
333 |
24 |
NT |
no |
148 |
166 |
no |
21 |
16 |
no |
1000 |
30 |
NT |
no |
136 |
206 |
no |
61 |
41 |
no |
3333 |
34 |
NT |
no |
232 |
271 |
no |
138 |
165 |
no |
5000 |
43 |
NT |
no |
246 |
356 |
no |
190 |
248 |
no |
Positive control |
262 |
NT |
no |
494 |
1023 |
no |
428 |
176 |
no |
*solvent control with DMSO
NT: not tested
Table 3: -Plate incorporation:Number of revertants per plate (mean of 3 plates)
TA 1537 |
TA 1538 |
TA 102 |
E.coli WP2 uvrA |
|||||||||
Conc. |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
0* |
7 |
7 |
no |
6 |
23 |
no |
263 |
359 |
no |
17 |
21 |
no |
100 |
6 |
7 |
no |
4 |
16 |
no |
30 |
348 |
no |
18 |
12 |
no |
333 |
6 |
12 |
no |
6 |
18 |
no |
309 |
358 |
no |
14 |
22 |
no |
1000 |
9 |
9 |
no |
6 |
20 |
no |
295 |
414 |
no |
20 |
22 |
no |
3333 |
6 |
9 |
no |
9 |
22 |
no |
314 |
409 |
no |
25 |
27 |
no |
5000 |
9 |
8 |
no |
11 |
18 |
no |
329 |
404 |
no |
23 |
25 |
no |
Positive control |
1052 |
129 |
no |
321 |
944 |
no |
1300 |
2312 |
no |
132 |
570 |
no |
*solvent control with DMSO
Table 1 Induced mutant frequency, without activation (average of 3 plates scored for each culture)
Concentration µg/ml |
Culture |
Mutant colonies (av) |
Viable count |
Mutant frequency |
Induced mutant frequency |
% total growth |
0* |
1 |
15 ± 3 |
171 |
18 |
- |
- |
2 |
18 ± 3 |
163 |
22 |
- |
- |
|
500 |
A |
14 ± 2 |
182 |
15 |
-5 |
104 |
B |
15 ± 4 |
193 |
16 |
-4 |
102 |
|
1000 |
A |
14 ± 5 |
168 |
17 |
-3 |
84 |
B |
24 ± 2 |
165 |
29 |
9 |
82 |
|
1500 |
A |
25 ± 5 |
174 |
29 |
9 |
71 |
B |
17 ± 2 |
169 |
20 |
0 |
56 |
|
2000 |
A |
23 ± 8 |
147 |
31 |
11 |
31 |
B |
++ |
++ |
- |
- |
- |
|
Positive control |
2.5 µg/ml |
259 ± 2 |
113 |
458 |
433 |
- |
5.0 µg/ml |
298 ± 3 |
86 |
693 |
668 |
- |
*solvent control with acetone
++ too toxic to clone
Table 2 Induced mutant frequency, with activation (average of 3 plates scored for each culture)
Concentration µg/ml |
Culture |
Mutant colonies (av) |
Viable count |
Mutant frequency |
Induced mutant frequency |
% total growth |
0* |
1 |
44 ± 5 |
145 |
61 |
- |
- |
2 |
38 ± 8 |
113 |
67 |
- |
- |
|
25 |
A |
66 ± 3 |
+ |
+ |
+ |
+ |
B |
84 ± 6 |
115 |
146 |
82 |
72 |
|
50 |
A |
90 ± 3 |
114 |
158 |
94 |
63 |
B |
83 ± 2 |
109 |
152 |
88 |
52 |
|
60 |
A |
82 ± 4 |
98 |
167 |
103 |
46 |
B |
71 ± 5 |
96 |
148 |
84 |
37 |
|
70 |
A |
69 ± 3 |
107 |
129 |
65 |
41 |
B |
60 ± 5 |
87 |
138 |
74 |
19 |
|
80 |
A |
60 ± 5 |
+ |
+ |
+ |
+ |
B |
63 ± 11 |
75 |
168 |
104 |
10 |
|
Positive control |
2.5 µg/ml |
103 ± 8 |
58 |
355 |
286 |
31 |
5.0 µg/ml |
52 ± 5 |
19 |
547 |
478 |
3 |
90 µg/ml was not evaluated for mutagenicity as too toxic to clone.
* solvent control with acetone
+ Culture lost
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Description of key information
Micronucleus assay in mouse (ip administration): Negative (similar to OECD Test Guideline 474 and in compliance with GLP) (BRRC, 1993).
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- only 1000 PCE scored for micronuclei
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- Swiss Webster
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River laboratories
- Age at study initiation: 5 weeks
- Weight at study initiation: 22-7 to 25.5 g (males); 17.9 to 21.4 g (females)
- Assigned to test groups randomly: yes, under following basis: nonstratified randomization procedure based on body weight
- Fasting period before study: no
- Housing: group housed in shoe box type plastic cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 40-70%
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 1991-07-08 To: 1991-09-03 - Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil;
- Justification for choice of solvent/vehicle: none given - standard vehicle - Details on exposure:
- (3-Chloropropyl)trimethoxysilane (CAS No. 2530-87-2) was given to both male and female Swiss-Webster mice as a single dose by intraperitoneal injection. Based upon mortality data obtained in a range-finding study, the acute intraperitoneal LD50 for the combined sexes was calculated to be 2031 mg/kg (3-Chloropropyl)trimethoxysilane (95% confidence interval, 1672 to 2456 mg/kg). The doses for the definitive micronucleus assay were selected by the study director as approximately 25%, 50%, and 90% of the LD50 or 500, 1000, and 1625 mg/kg (3-Chloropropyl)trimethoxysilane.
- Frequency of treatment:
- Single dose
- Post exposure period:
- 30, 48 and 72 hours
- Dose / conc.:
- 0 other: mg/kg
- Remarks:
- Nominal concentration. Control, corn oil
- Dose / conc.:
- 500 other: mg/kg
- Remarks:
- Nominal concentration
- Dose / conc.:
- 1 000 other: mg/kg
- Remarks:
- Nominal concentration
- Dose / conc.:
- 1 625 other: mg/kg
- Remarks:
- Nominal concentration
- No. of animals per sex per dose:
- 5 per sex per dose, except high dose where 8/sex/dose were used
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - triethylenemelamine
- dissolved in ethanol then diluted with sterile distilled water
- Justification for choice of positive control(s): none given, standard control
- Route of administration: ip
- Doses / concentrations:0.3 mg/kg - Tissues and cell types examined:
- Peripheral erythrocytes
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: based on toxicity data
DETAILS OF SLIDE PREPARATION: 1 or 2 blood smear slides prepared per animal, stained with Gurr's R-66 Giesma
METHOD OF ANALYSIS: PEC: PNEC ratio for 1000 cells per animal calculated to estimate toxicity. 100 PCE/animal scored for presence of micronuclei - Statistics:
- Mann-Whitney U test, probability value of <0.05 (1-tailed) used as critical level for significance.
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- PCE/NCE ratio decreased at 72 h, high dose
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- There were no signs of toxicity in male or female mice in the 500 mg/kg group, except that 1 female exhibited ataxia during the first hour post-treatment. All of the males and females in the 1000 mg/kg group exhibited ataxia and 2 of the males also had tremors during the first hour after treatment. In males and females treated at 1625 mg/kg chloropropyltrimethoxysilane, ataxia, tremors, and prostration were observed during the first hour after treatment. Other clinical signs in the high dose females included myoclonic jerks and vocalization. There were no significant clinical observations in male or female mice from the afternoon of Day 1 through the end of the study.
There was a significant decrease in the polychromatophilic erythrocyte (PCE) to normochromatophilic erythrocyte (NCE) ratios at the 72 hr sampling time among male mice (50.6% of control) treated with 1625 mg/kg cloropropyltrimethoxysilane. However, there was no evidence that chloropropyltrimethoxysilane was excessively toxic to the bone marrow at the concentrations chosen for the study. No significant increases in the incidences of micronucleated PCE were observed at 500, 1000, or 1625 mg/kg chloropropyltrimethoxysilane at the 30, 48 or 72 hr sampling times in mice of either sex.
RESULTS OF RANGE-FINDING STUDY
- Dose range: information not included in study report
- Rationale for exposure: based on ip LD50
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): negative
- Ratio of PCE/NCE (for Micronucleus assay): decreased
- Appropriateness of dose levels and route: yes
- Statistical evaluation: yes - Conclusions:
- (3-Chloropropyl)trimethoxysilane has been tested for clastogenicity in a valid in vivo micronucleus study, according to a protocol similar to OECD Test Guideline 474 and in compliance with GLP. (3-Chloropropyl)trimethoxysilane did not produce significant, treatment-related increases in the incidence of micronucleated polychromatophilic erythrocytes among male or female Swiss-Webster mice assessed at 30, 48 or 72 hours . It is concluded that the test substance is negative for the induction of micronuclei in peripheral erythrocytes of mice under the conditions of the test after treatment with a single dose by intraperitoneal injection. Therefore, (3-chloropropyl)trimethoxysilane was not considered to be an inducer of micronuclei in male or female Swiss-Webster mice under the conditions of the in vivo assay.
Reference
Table 2 Results of in vivo micronucleus test
Treatment
|
Solvent control |
Low dose |
Mid dose |
High dose |
Positive control |
||
Sampling time |
|
30 h |
|||||
Number of erythrocytes |
normochromatic (NCE) |
m |
NR |
NR |
NR |
NR |
NR |
|
f |
NR |
NR |
NR |
NR |
NR |
|
|
polychromatic (PCE) |
m |
5000 |
5000 |
5000 |
5000 |
5000 |
|
f |
5000 |
5000 |
5000 |
5000 |
5000 |
|
|
PCE with micronuclei (MPCE) |
m |
12 |
13 |
15 |
12 |
061 |
|
f |
9 |
5 |
4 |
11 |
67 |
|
Ratio of erythrocytes |
PCE/1000 NCE |
m |
34 |
35 |
33 |
28.4 |
24.6 |
|
f |
28.4 |
35 |
29.6 |
29.0 |
28.4 |
|
|
MPCE/NCE (%) |
m |
0.24 |
0.26 |
0.30 |
0.24 |
1.22 |
|
f |
0.18 |
0.10 |
0.08 |
.22 |
1.34 |
|
Sampling time |
|
48 h |
|||||
Number of erythrocytes |
normochromatic (NCE) |
|
NR |
NR |
NR |
NR |
NE |
|
polychromatic (PCE) |
b |
10000 |
10000 |
10000 |
10000 |
NE |
Ratio of erythrocytes |
PCE with micronuclei (MPCE) |
|
20 |
24 |
16 |
17 |
NE |
|
PCE/1000 NCE |
m |
26.8 |
24.4 |
23.4 |
19.8 |
NE |
|
f |
24.8 |
23.2 |
22.4 |
23.8 |
NE |
|
|
MPCE/NCE (%) |
|
0.2 |
0.24 |
0.16 |
0.17 |
NE |
|
72 h |
||||||
|
polychromatic (PCE) |
b |
10000 |
10000 |
10000 |
10000 |
NE |
|
PCE with micronuclei (MPCE) |
b |
16 |
15 |
16 |
16 |
NE |
|
PCE/NCE (%) |
b |
0.16 |
0.15 |
0.16 |
0.16 |
NE |
|
MPCE/NCE
|
m |
35.2 |
30.8 |
26.8 |
17.8* |
NE |
|
f |
29.2 |
33.6 |
31.4 |
20.4 |
NE |
* significantly different from control, p<0.01
b both sexes combined
NR not recorded
NE not evaluated
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Measured in vitro genotoxicity studies are available for mutagenicity in bacterial and mammalian cells. Where there was more than one result for an endpoint the most reliable study available was chosen as key study. Where there was more than one reliable study, the most recent study was selected. The results of the key in vitro studies were in agreement.
(3-Chloropropyl)trimethoxysilane has been tested for mutagenicity in a valid gene mutation study in bacterial strains S. typhimurium TA98, TA100, TA1535, TA1537, TA1538, TA102 and E. coli WP2 uvr A with and without metabolic activation, conducted according to a protocol similar to OECD Test Guideline 471 and in compliance with GLP. A dose-dependent increase in the number of revertants was observed in S. typhimurium strains TA100 and TA1535 with and without metabolic activation, and in strain TA98 in the absence of metabolic activation. It is concluded that (3-chloropropyl)trimethoxysilane is positive for mutagenicity in bacteria under the conditions of this test (Dow Corning Corporation, 1993).
(3-Chloropropyl)trimethoxysilane has been tested for mutagenicity to bacteria in a valid gene mutation study in bacterial strains Salmonella typhimurium TA-98, TA-100, TA-1535 and TA-1537 and Escherichia coli/WP2 uvrA with and without metabolic activation, conducted according to EEC Directive No. L251 and in compliance with GLP. A dose-dependent increase in the number of revertants was observed in Salmonella typhimurium strains TA-1535, TA-1537 and TA-100 with and without metabolic activation. No dose-dependent increase in the number of revertants was seen in Salmonella typhmurium TA-98 and Escherichia coli/WP2 uvrA with and without metabolic activation. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that (3-chloropropyl)trimethoxysilane is positive for mutagenicity in bacteria under the conditions of this test (Dow Corning Corporation, 1990a).
(3-Chloropropyl)trimethoxysilane has been tested for mutagenicity to bacteria in a valid gene mutation study in bacterial strains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 1538 with and without metabolic activation, conducted according to EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria) and in compliance with GLP. A dose-dependent increase in the number of revertants was observed in Salmonella typhimurium TA 1535 with and without metabolic activation. No dose-dependent increase in the number of revertants was seen in Salmonella typhmurium TA 98, TA 100, TA 1537, and TA 1538 with and without metabolic activation. It is concluded that (3-chloropropyl)trimethoxysilane is positive for mutagenicity in bacteria under the conditions of this test (Huls AG, 1993).
(3-Chloropropyl)trimethoxysilane has been tested for mutagenicity to bacteria in a valid gene mutation study in bacterial strains Salmonella typhimurium TA-98, TA-100, TA-1535 and TA-1537 and Escherichia coli/WP2 uvrA with and without metabolic activation, conducted according to OECD Test Guideline 471 and in compliance with GLP. A dose-dependent increase in the number of revertants was observed in Salmonella typhimurium strains TA-1535, TA-1537 and TA-100 both with and without activation and in TA-98 with activation. No dose-dependent increase in the number of revertants was seen in the rest of the bacterial strains with and without metabolic activation. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that (3-chloropropyl)trimethoxysilane is positive for mutagenicity in bacteria under the conditions of this test (Dow Corning Corporation, 1990b).
(3-Chloropropyl)trimethoxysilane has been tested for mutagenicity to bacteria in a valid gene mutation study in bacterial strains Salmonella typhimurium TA-98, TA-100, TA-1535 and TA-1537 and Escherichia coli/WP2 uvrA with and without metabolic activation, conducted according to a protocol similar to OECD Test Guideline 471 and in compliance with GLP. A dose-dependent increase in the number of revertants was observed in Salmonella typhimurium strains TA-1535, TA-1537 and TA-100 both with and without activation. No dose-dependent increase in the number of revertants was seen in Salmonella typhmurium TA-98 and Escherichia coli/WP2 uvrA with and without metabolic activation. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that (3-chloropropyl)trimethoxysilane is positive for mutagenicity in bacteria under the conditions of this test (Dow Corning Corporation, 1990c).
(3-Chloropropyl)trimethoxysilane has been tested for mutagenicity to bacteria in a valid gene mutation study in bacterial strains Salmonella typhimurium TA-98, TA-100, TA-1535, TA-1537 and TA-1538 with and without metabolic activation, conducted according to a protocol similar to OECD Test Guideline 471 but pre-dates GLP compliance. No dose-dependent increase in the number of revertants was seen any of the test strains with and without metabolic activation. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that (3-chloropropyl)trimethoxysilane is negative for mutagenicity in bacteria under the conditions of this test (Dow Corning Corporation, 1977).
(3-Chloropropyl)trimethoxysilane has been tested for mutagenicity in a reliable mammalian mutagenicity study in L5178Y mouse lymphoma cells with and without metabolic activation, conducted according to a protocol similar to OECD Test Guideline 476 and in compliance with GLP. The test material was considered to be negative for mutagenicity when tested without metabolic activation and positive when tested with metabolic activation. (3-Chloropropyl)trimethoxysilane has been concluded to be positive for mutagenicity in mammalian cells under the conditions of the study (Dow Corning Corporation, 1995).
(3-Chloropropyl)trimethoxysilane has been tested in a valid in vivo micronucleus study, according to a protocol similar to OECD Test Guideline 474 and in compliance with GLP. (3-Chloropropyl)trimethoxysilane did not produce significant, treatment-related increases in the incidence of micronucleated polychromatophilic erythrocytes among male or female Swiss-Webster mice assessed at 30, 48 or 72 hours. In addition to systemic toxicity, the test substance induced very clear cytotoxicity to bone marrow in males, with the PCE/NCE ratio decreased by almost 50% in high-dose males, demonstrating that the target tissue was exposed to the test substance. It is concluded that the test substance is negative for the induction of micronuclei in peripheral erythrocytes of mice under the conditions of the test after treatment with a single dose by intraperitoneal injection. Therefore, (3-chloropropyl)trimethoxysilane was not considered to be genotoxic in male or female Swiss-Webster mice under the conditions of the in vivo assay (BRRC, 1993).
(3-Chloropropyl)trimethoxysilane has been tested in a 90-day inhalation repeated dose toxicity study incorporating in vivo micronucleus assessment, conducted according to OECD Test Guideline 413 and in compliance with GLP. No biologically significant increase in the number of micronucleated PCEs was observed. The PCE/NCE ratio was not affected by exposure to the test substance, so exposure of the target tissue could not be confirmed. (Dow Corning Corporation, 1993).
The positive results in the in vitro mutagenicity assays in bacteria and in mammalian cells indicated a potential for mutagenicity. The potential for genetic toxicity observed in vitro was not confirmed when the substance was tested in an in vivo micronucleus assay. The micronucleus assay is known to detect mutagens as well as clastogens (REF).
Justification for classification or non-classification
Based on the negative result in the available in vivo micronucleus assay, known to detect mutagens, the positive results in the in vitro mutagenicity assays in bacteria and in mammalian cells were not confirmed. Therefore, it is concluded that (3-chloropropyl)trimethoxysilane does not meet the criteria for classification for mutagenicity according to Regulation (EC) No 1272/2008.
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