(3-chloropropyl)dimethoxymethylsilane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a gene mutation study (Bacterial reverse mutation assay / Ames test), conducted according to OECD Test Guideline 471 and in compliance with GLP, 3-chloropropyl(dimethoxy)methylsilane (CAS 18171-19-2; EC No. 242-056-0) was negative in Salmonella typhimurium strains (TA 98, 100, 102, 1535, 1537) with and without activation (LPT, 2002, Reliability Score 1).

In a cytogenicity study in mammalian cells, conducted according to OECD Test Guideline 473 and in compliance with GLP, the analogous substance dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) was negative in Chinese hamster fibroblast cells (Hüls AG, 1997, Reliability Score 1).

In a mutagenicity in mammalian cells study, conducted according to OECD Test Guideline 476 and in compliance with GLP, the analogous substance dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) was negative in Chinese hamster ovary cells (Hüls AG, 1997, Reliability Score 1).

In vitro genetic toxicity tests conducted according to OECD Test Guideline 473 and 490 will be conducted and added to the dossier when available.

Link to relevant study records

Reference

Reference 1

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

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

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 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:

S. typhimurium TA 98

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

Key result

Species / strain:

S. typhimurium TA 100

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

Key result

Species / strain:

S. typhimurium TA 102

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

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

100 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

100 µg/plate

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:

In an in vitro gene mutation study in bacteria, conducted according to OECD 471 and in compliance with GLP, 3-chloropropyl(dimethoxy)methylsilane has been tested for mutagenicity to bacteria. 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.

Reference 2

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

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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 in vitro cytogenicity / chromosome aberration study in mammalian cells, conducted according to OECD Test Guideline 473 and in compliance with 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.

Reference 3

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

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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:

In an in vitro mutagenicity assay, conducted according to OECD Test Guideline 476 and in compliance with GLP, the test substance was 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

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. QA statement)

Type of assay:

micronucleus assay

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system 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: ad libitum

- Water: 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:

In an in vivo mammalian micronucleus study, conducted to a protocol similar to OECD Test Guideline 474 and in compliance with 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

Information is available from one reliable bacterial mutagenicity study for 3-chloropropyl(dimethoxy)methylsilane (CAS 18171-19-2; EC No. 242-056-0). No further data are available for the registered substance; however, reliable data are available for the related substances dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) and 3-chloropropyl(diethoxy)methylsilane (CAS 13501-76-3).

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, conducted according to OECD Test Guideline 471 and in compliance with GLP, 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, Reliability Score 1).

In a reliable in vitro cytogenicity assay in Chinese hamster fibroblasts, conducted according to OECD Test Guideline 473 and in compliance with GLP,

(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, Reliability Score 1).

In a reliable in vitro mutagenicity assay in Chinese hamster ovary cells, conducted according to OECD Test Guideline 476 and in compliance with GLP,

dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) showed no mutagenic potential of the test material (Hüls AG, 1997, Reliability Score 1).

In a reliable in vivo mammalian micronucleus assay, conducted according to EU method B.12 and in compliance with GLP,

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 (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.