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Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains (TA 98, 100, 102, 1535, 1537) (OECD TG 471) (LPT, 2002).

Cytogenicity in mammalian cells: read across from analogous substance dichloro(3 -chloropropyl)methylsilane (CAS 7787-93-1): negative in Chinese hamster fibroblast cells (OECD TG 473) (Hüls AG, 1997).

Mutagenicity in mammalian cells: read-across from analogous substance dichloro(3 -chloropropyl)methylsilane (CAS 7787-93-1): negative in Chinese hamster ovary cells (OECD 476) (Hüls AG, 1997).

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-03-04 to 2002-05-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
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:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
Plate incorporation test +-S9 100, 316, 1000, 3160 and 5000 µg/plate. Pre-incubation test 1, 3.16, 10, 31.6 and 100 µg/plate.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethylene glycol dimethylether

- 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:
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
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:
other: TA 98, TA 100, TA 102, TA 1535 and TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
100 µg/plate in strain TA 1535 and TA 1537
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS

COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data

Table 2: Dose range-finding study. Number of revertants per plate (2 plates)

 

TA100

 TA100  TA100

Conc.
(µg/plate)

Plate 1

Plate 2

Cytotoxic
(yes/no)

0*

142

128

No

0.316

109

112

No

1

112

114

No

3.16

106

106

No

10

123

105

No

31.6

119

106

No

100

109

112

No

316

124

123

No

1000

110

128

No

3160

151

177

No

5000

160

163

No

*solvent control with ethylene glycol dimethylether

Table 3: Experiment 1 Plate incorporation. Number of revertants per plate (mean of 3 plates)

 

 TA98

  TA98

TA98

  TA100

 TA100

TA100

  TA102

 TA102

TA102

Conc.
(
µg/plate)

— MA

+

MA

Cytotoxic
(yes/no)

MA

+

MA

Cytotoxic
(yes/no)

MA

+

MA

Cytotoxic
(yes/no)

0*

26

29.3

No

164.3

141.3

No

265

297.7

No

100

24.7

31.3

No

140.7

163

No

283.7

277.3

No

316

30

35.3

No

143.7

179.7

No

270.3

261

No

1000

25

34.3

No

175.7

177.7

No

281

278.3

No

3160

23.7

30

No

200.7

205.3

No

247

277

No

5000

21.3

29

No

207.7

248.7

No

285.7

302.7

No

Positive control

940.7

492.3

No

1283

1283

No

265

975.7

No

*solvent control with ethylene glycol dimethylether

Table 3: Experiment 1 Plate incorporation. Number of revertants per plate (mean of 3 plates)

 

 TA1535  TA1535

TA1535

 TA1537  TA1537

TA1537

Conc.
(
µg/plate)

— MA

+

 MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

22.7

23.7

No

11.7

10.3

No

100

15.3

32.7

No

7

12.3

No

316

10.3

27.3

No

7.7

10.3

No

1000

11.3

29.3

No

7.7

11.7

No

3160

14.3

32.3

No

9

11.3

No

5000

15

24.7

No

5.7

10.7

No

Positive control

955.7

813.7

No

456.7

763

No

*solvent control with ethylene glycol dimethylether

Table 4: Experiment 2 Preincubation. Number of revertants per plate (mean of 3 plates)

 

 TA98  TA98

TA98

 TA100  TA100

TA100

 TA102  TA102

TA102

Conc.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

MA

+

MA

Cytotoxic
(yes/no)

MA

+

MA

Cytotoxic
(yes/no)

0*

29.3

35

No

128.7

131.3

No

270.7

260.7

No

1

28.3

47

No

136.7

151

No

285.7

275.3

No

3.16

34

41.3

No

136

152

No

266

282.3

No

10

28.3

45

No

128

153.7

No

279

273.3

No

31.6

32.3

44

No

122.3

160.7

No

275

295

No

100

37.7

43

No

135.7

167.3

No

281

306.7

No

Positive control

330.7

334

No

1151.7

1145

No

1138.3

1053.3

No

*solvent control with ethylene glycol dimethylether

Table 4: Experiment 2 Preincubation. Number of revertants per plate (mean of 3 plates)

 

 TA1535 TA1535 

TA1535

 TA1537  TA1537

TA1537

Conc.
(
µg/plate)

— MA

+

MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

15.7

14.7

No

12

8

No

1

12.7

17.7

No

9.3

10

No

3.16

14.7

19

No

10.7

7.3

No

10

16

20.3

No

7.7

6.7

No

31.6

17.3

23.3

No

8

5.3

No

100

29.7

22

Yes

9.3

8.7

Yes

Positive control

951.7

986.3

No

836.3

829

No

*solvent control with ethylene glycol dimethylether

Conclusions:
3-chloropropyl(dimethoxy)methylsilane has been tested for mutagenicity to bacteria in compliance with OECD 471, under GLP conditions. No evidence of an increase in the number of revertants was observed in any of the Salmonella typhimurium strains tested with and without metabolic activation in either of two independent experiments, the first using the plate incorporation method and the second using the pre-incubation assay. It is concluded that the test substance is negative for mutagenicity to bacterial under the conditions of the test.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-02-10 to 1997-05-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
0.2, 12.5, 25 µg/ml -S9 mix and 50 µg/ml -S9 mix in test #2. 50, 400 and 600 µg/ml + S9 mix
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
(with activation)
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
(without activation)
Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION

- Exposure duration: 3 - 28 hours

- Expression time (cells in growth medium): 15 hours with S9 in exp 1, 18 hours without S9. 28 hours in exp 2.

- Selection time (if incubation with a selection agent): 4 and 7 days

- Fixation time (start of exposure up to fixation or harvest of cells): 18 - 28 hours

SPINDLE INHIBITOR (cytogenetic assays): Colcemid

STAIN (for cytogenetic assays): Giesma

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 200 cells per treatment group


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index
Evaluation criteria:
The test chemical is considered clastogenic if it induces chromosomal aberrations (excl. gaps) in a statistically significant manner in one or more concentrations; the induced proportion of aberrant cells exceeds the normal range of the test system (i.e. > 5%), and positive results can be verified in an independent experiment.
Statistics:
Chi-square test
Key result
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
In a reliable test conducted according to OECD 473 and under GLP, the test substance did not induce biologically significant increases in the chromosomal aberration frequency of V79 Chinese hamster cells and is therefore judged to be non clastogenic in vitro.
Endpoint:
in vitro gene mutation study in mammalian cells
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:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Version / remarks:
1984
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
mammalian cell gene mutation assay
Target gene:
HPRT locus
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
Test 1 -S9 - 120, 300, 600, 900, 1200 µg/ml +S9 - 200, 500, 1000, 1500, 2000 µg/ml Test 2 -S9 60, 120, 300, 600, 800 µg/ml, +S9 100, 200, 500, 1000, 1500 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: It is assumed by the reviewer that the choice of solvent was based on solubility properties and relative non-toxicity to CHO cells.
Untreated negative controls:
yes
Remarks:
HO medium + 1 % acetone
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-(20)-Methylcholanthrene (MCA) 10 µg/ml
Remarks:
with activation
Untreated negative controls:
yes
Remarks:
HO medium + 1 % acetone
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without activation 300 µg/ml
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 4 hours
- Expression time (cells in growth medium): 6-7 days
- Selection time (if incubation with a selection agent): 6-7 / 9 days
- Fixation time (start of exposure up to fixation or harvest of cells): 6-7 days

SELECTION AGENT (mutation assays): H10 medium

NUMBER OF REPLICATIONS: 3 for each test concentration

NUMBER OF CELLS EVALUATED: 1,000,000 cells/flask

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency; relative total growth
Evaluation criteria:
The test substance is mutagenic if it causes a statistically significant, dose related increase in mutant frequency at concentrations of the test substance resulting in greater than 20 % cell survival. The mean mutant frequency in treated cultures should reach a value above the maximum spontaneous mutant frequency.
Statistics:
Statistical significance is determined by t-test

absolute cloning efficiency (in %) = mean # of colonies per dish x 100 / number of plated cells per dish

relative cloning efficiency (in %) = absolute C.E. of treated cells x 100 / absolute C.E. of solvent control

mutation frequency = counted colonies (mean of 5 flasks) / absolute cloning efficiency (in %)
Key result
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:
valid
Positive controls validity:
valid
Additional information on results:
COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data

Table 2:Results of Mammalian Mutagenicity assay (Test 1) with CHO cells

Concentration µg/ml

Mutant* Frequency

Mutant* Frequency

% Relative cloning eff.

% Relative cloning eff.

Cytotoxicity
(yes/no)

-

— MA

+ MA

— MA

+ MA

-

0

1

3

94 / 103

98 / 107

No

0(1 % Acetone)

4

6

100

100

No

60

-

-

-

-

No

100

-

-

-

-

No

120

5

-

88 / 108

-

No

200

-

0

-

97 / 107

No

300

-

-

0

-

No

500

-

11 **

-

88 / 101

No

600

0

-

87 / 107

-

No

800

-

-

-

-

No

900

2

-

4 / 104

-

No

1000

-

7

-

73 / 101

No

1200

-

-

0

-

No

1500

-

0

-

32 / 94

No

2000

-

-

-

1

No

Positive Control

325 ###

52###

94 / 100

107 / 103

No

* x 106

** statistically significant

### highly significant, no statistics performed

Solvent control with Acetone

Table 3:Results of Mammalian Mutagenicity assay (Test 2) with CHO cells

Concentrationµg/ml

Mutant* Frequency

Mutant* Frequency

% Relative cloning eff.

% Relative cloning eff.

Cytotoxicity
(yes/no)

-

— MA

+ MA

— MA

+ MA

-

0

3

0

98 / 104

109 / 116

No

0(1 % Acetone)

3

5

100 / 100

100 / 100

No

60

4

-

102 / 106

-

No

100

-

2

-

104 / 103

No

120

6

-

94 / 99

-

No

200

-

0

-

105 / 128

No

300

-

-

0

-

No

500

-

0

-

71 / 124

No

600

3

-

98 / 103

-

No

800

3

-

93 / 102

-

No

900

-

-

-

-

No

1000

-

1

-

56 / 119

No

1200

-

-

-

-

No

1500

-

2

-

7 / 107

No

2000

-

-

-

-

No

Positive Control

306###

124###

84 / 102

110 / 95

No

* x 106

** statistically significant

### highly significant, no statistics performed

Solvent control with Acetone

Conclusions:
The substance was tested in an in vitro mutagenicity assay in CHO cells, under GLP and following OECD 476. The test substance is non-mutagenic in Chinese Hamster Ovary cells under the conditions of the test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Read-across from analogous substance 3-chloropropyl(diethoxy)methylsilane (CAS 13501-76-3): negative in mammalian micronucleus assay (intraperitoneal administration) (Hüls AG, 1996).

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-11-07 to 1995-12-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Version / remarks:
1992
Deviations:
yes
Remarks:
1600 PCE scored instead of 2000 (due to shift towards NCE)
GLP compliance:
yes (incl. certificate)
Type of assay:
micronucleus assay
Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Harlan Winklemann, Borchen, Germany

- Age at study initiation: young adult

- Weight at study initiation: 35.8 ± 7.2 grams (male) / 31.8 ± 6.4 grams (female)

- Assigned to test groups randomly: yes, under following basis: colour code applied to the back of each animal; cage cards

- Fasting period before study: 16 - 18 hours prior to dosing procedure

- Housing: conventional, 5 animals/sex/Makrolon cage type III

- Diet (e.g. ad libitum): ad libitum

- Water (e.g. ad libitum): ad libitum

- Acclimation period: ≥ 5 days

ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 ± 3 ˚c

- Humidity (%): 30 - 70 %

- Air changes (per hr): 15 changes per hour

- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light
Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
Details on exposure:
Route of exposure: intraperitoneal
Duration of treatment / exposure:
24 to 48 hours
Frequency of treatment:
Test compound and controls were administered once by intraperitoneal injection 10 ml/kg bw.
Post exposure period:
The positive control group was sacrificed 24 hours after administration of the test substance. The vehicle control and test substance groups were sacrificed 24 - 48 hours after administration of the test substance.
Dose / conc.:
1 600 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Five
Control animals:
yes, concurrent vehicle
Positive control(s):
- cyclophosphamide

- Justification for choice of positive control(s): standard guideline positive control

- Route of administration: intraperitoneal

- Doses / concentrations: 10 ml/kg bw of 0.9 % solution in physiological saline
Tissues and cell types examined:
See table 2
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: limit dose

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): no further information

DETAILS OF SLIDE PREPARATION: pure erythrocyte suspension was used to prepare flat cells on glass by means of a Shandon Cytospin 3 (2 slides per animal). Slides were air dried and stained with May-Grundwald/Giemsa

METHOD OF ANALYSIS: A MIAMED image analyser equipped with the "Micronucleus Test V 4.00" software was used for fully automated slide scoring. Where possible, a total of approximately 2000 PCE (i.e. 10,000 PCE per treatment group) were analysed for micronuclei. The corresponding NCE were also scored for micronuclei. As an indicator for chemical-induced bone marrow toxicity, for each animal the PCE/NCE ratio was determined on the basis of 2000 PCE scored.
Evaluation criteria:
A test compound is considered an inducer of micronuclei in PCE, if at least one group of mice treated with the test compound reveals a statistically and biologically relevant increase in micronucleated PCE compared with the negative control.
Statistics:
Means and standard deviations of the following parameters were calculated for each treatment group:

-the number of PCE with micronuclei

-the number of NCE with micronuclei

-the PCE/NCE ratio.

"Statgraphics" statistical software was used to analyse data. Test compound groups were compared with negative control groups of the same sampling time. Heterogeneity between animals of the same dose group was tested for by calculating the heterogeneity χ2 for the differences between the proportions of micronuclei for each animal. Pearson's contingency χ2 with one degree of freedom including a Yates correcting factor used to make comparisons in homogenous groups. In the case of inhomogeneity between groups, after transformation of the data, a one-sided two-sample t-test is performed, and can also be used to compare the micronucleus frequencies of the positive control with the negative control groups for comparison of PCE/NCE ratios.
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
PCE/NCE ratio reduced
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
See table 3

Table 3: Results of in vivo micronucleus test with Wacker BS 1701 

 

Vehicle

Control

Vehicle

Control

Positive Control

1600 mg/kg

bw

1600 mg/kg

 bw

Number of cells evaluated

2000

approx.

2000

approx.

2000

approx.

2000

approx.

2000

approx.

Sampling time (h)

24

48

24

24

48

Number of erythro-cytes

normo­chromatic

NR

NR

NR

NR

NR

poly­chromatic

2000

approx.

2000

approx.

2000

approx.

2000

approx.

2000

approx.

polychromatic with micronuclei (%)

Male

0.16 %

Female

0.13 %

Male

0.20 %

Female

0.11 %

Male

4.1 %

Female

2.2 %

Male

0.15 %

Female

0.13 %

Male

0.2 %

Female

0.18 %

Ratio of erythro­cytes

polychromatic / normochromatic

(ratio)

Male

0.7

Female

0.81

Male

0.48

Female

1.38

Male

0.57

Female

0.83

Male

0.1

Female

0.14

Male

0.07

Female

0.09

polychromatic with micro­nuclei / normochromatic

NR

NR

NR

NR

NR

 

Conclusions:
3-chloropropyl(diethoxy)methylsilane was tested in an in vivo mouse micronucleus assay to EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test) and under GLP. No evidence for test substance mediated induction of micronuclei was observed. It is noted that the PCE / NCE ratio was reduced in the test substance-treated animals indicating the test substance had reached the target tissue. It is concluded that the test substance is not genotoxic under the conditions of the test. The result is a read across from 3-chloropropyl(diethoxy)methylsilane (CAS 13501-76-3).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

The positive results observed with structural analogues were not read-across to the registered substance as there is a reliable bacterial mutagenicity study available for the registered substance, in which no evidence of mutagenicity was observed. In addition, the final conclusions from the studies on the structural analogue substances were negative, as the potential for genetic toxicity observed bacterial cells was found in only one of two in vitro mammalian mutagenicity assays, and no evidence for genetic toxicity was observed in in vivo micronucleus assays.

In a reliable bacterial mutagenicity assay, no increase in the number of revertants was observed in Salmonella typhimurium strains (TA 98, TA 100, TA 102, TA 1535 and TA 1537) tested with and without metabolic activation in either of two independent experiments, the first using the plate incorporation method and the second using the pre-incubation method. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test (LPT, 2002). The study was conducted in compliance with OECD 471 and under GLP conditions.

In a reliable in vitro cytogenicity assay in Chinese hamster fibroblasts, under GLP and following OECD 473, (3-chloropropyl)dichloromethylsilane (CAS 7787-93-1) did not induce a biologically significant increase in chromosomal aberration frequency and was found not to be clastogenic (Hüls AG, 1997).

In a reliable in vitro mutagenicity assay in Chinese hamster ovary cells, under GLP and following OECD 476, dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) showed no mutagenic potential of the test material (Hüls AG, 1997).

In a reliable in vivo mammalian micronucleus assay, no evidence of substance mediated induction of micronuclei was apparent after the administration of 1600 mg/kg bw of (3-chloropropyl)diethoxymethylsilane (CAS 13501-76-3) by intraperitoneal injection. The test was carried out in accordance with EU method B.12 under GLP (Hüls AG 1996).

For read-across justification see RAAF report in Section 13 of IUCLID.


Justification for classification or non-classification

Based on the available information on 3 -chloropropyl(dimethoxy)methylsilane (CAS 18171 -19 -2) and its structural analogues, no classification is required according to Regulation (EC) No 1272/2008.