Disilane, chloro Me derivs.

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2002-0806 to 2003-02-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. It is considered that read-across to the registered substance is scientifically justified.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

1992

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: ICH Guideline S2A: Genotoxicity (CPMP/ICH/141/95)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: ICH Guideline S2B: Genotoxicity (CPMP/ICH/174/95).

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Chlorodimethylsilane

EC Number:

213-912-0

EC Name:

Chlorodimethylsilane

Cas Number:

1066-35-9

IUPAC Name:

chloro(dimethyl)silane

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

Arolor induced rat liver S9

Test concentrations with justification for top dose:

93.6 to 4680 µg/plate for the plate incorporation test and 39 to 1950 µg/plate for the preincubation test

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethylene glycol dimethyl ether
- Justification for choice of solvent/vehicle: solubilty properties and relative nontoxicity to bacteria

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

ethylene glycol dimethyl ether

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535, TA 100 without activation

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 98 without activation

Controls 3

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

Controls 4

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

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-antracene amide

Remarks:

TA 98, TA 102, TA 1537 with activation

Controls 6

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
- Exposure duration: 48 hours
- Expression time (cells in growth medium): 48 hours
- Fixation time (start of exposure up to fixation or harvest of cells): 48 hours

NUMBER OF REPLICATIONS: triplicate

DETERMINATION OF CYTOTOXICITY
- Method: other: reduction in number of colonies by more than 50% and/or a scarce background lawn

Evaluation criteria:

A reproducible and statistically significant increase in the number of revertants by at least two-fold (three-fold for TA 1535 and 1537), and a statistically significant log concentration-dose effect.

Statistics:

Mann and Whitney's U-test and Spearman's rank correlation coefficient.

Results and discussion

Test results

Species / strain:

S. typhimurium, 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:

1950 µg/plate with and without activation

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

PRECIPITATION: no precipitation occurred,

RANGE-FINDING/SCREENING STUDIES: Scarce background lawn was observed at the top concentration in the preliminary cytotoxicity test.

COMPARISON WITH HISTORICAL CONTROL DATA: Not presented in report.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: Salmonella typhimurium TA 98, TA 100, TA 102, TA 1535 and TA 1537

Any other information on results incl. tables

Table 1: Dose range-finding study Number of revertants per plate

	TA100
Conc. (µg/plate)	- MA plate 1	- MA plate 2	Cytotoxic (yes/no)
4680	117	155	yes
2340	127	123	no
936	139	134	no
468	125	124	no
93.6	118	129	no
46.8	133	130	no
9.36	133	111	no
4.68	141	125	no
0.936	112	122	no
0.468	128	141	no
0*	134	144	no

*solvent control with ethylene glycol dimethyl ether

 

Table 2: Experiment 1: Plate incorporation.Number of revertants per plate (mean of 3 plates)

	TA 98			TA 100			TA 102
Conc. (µg/plate)	- MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)
4680	29.7	33.7	yes	167.0	156.0	yes	271.7	273.3	yes
2340	30.0	36.7	no	158.3	161.0	no	252.7	265.7	no
936	31.3	40.0	no	169.7	153.0	no	309.0	271.0	no
468	32.3	45.0	no	165.0	139.0	no	283.3	274.0	no
93.6	30.3	39.0	no	165.0	154.3	no	270.0	273.0	no
0*	35.7	45.3	-	164.3	151.3	-	289.3	281.7	-
Positive control	774.3	773.0	-	809.0	813.0	-	1233	1221	-

*solvent control with ethylene glycol dimethyl ether

 

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

	TA 1535			TA 1527
Conc. (µg/plate)	- MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)
4680	14.3	12.7	yes	4.0	5.0	yes
2340	17.3	16.7	no	7.3	5.0	no
936	17.0	15.3	no	4.3	7.0	no
468	17.3	17.0	no	4.7	5.7	no
93.6	18.0	13.7	no	4.0	5.0	no
0*	16.0	16.0	-	6.0	6.3	-
Positive control	429.0	1500	-	345.7	344.0	-

*solvent control with ethylene glycol dimethyl ether

 

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

	[Strain a]			[Strain b]			[Strain c]
Conc. (µg/plate)	- MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)
1950	0	0	yes	0	0	yes	0	0	yes
975	29.7	30.3	yes	100.0	137.7	yes	260.7	256.7	yes
390	39.0	40.0	no	137.0	138.3	no	256.3	270.7	no
195	46.0	48.3	no	140.3	134.7	no	253.7	269.7	no
39	37.0	39.7	no	156.0	144.7	no	259.0	265.7	no
0*	40.0	40.0	-	120.3	176.0	-	270.0	252.3	-
Positive control	759.3	759.7	-	1154.3	1132	-	1131.0	1223	-

*solvent control with ethylene glycol dimethyl ether

 

Table 5: Experiment 2: Preincubation.Number of revertants per plate (mean of 3 plates)

	[Strain a]			[Strain b]
Conc. (µg/plate)	- MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)
1950	0	0	yes	0	0	yes
975	14.0	13.0	yes	4.0	4.0	yes
390	14.0	14.3	no	5.0	5.0	no
195	14.3	14.7	no	3.3	6.0	no
39	13.3	14.3	no	4.0	3.7	no
0*	15.3	15.3	-	6.3	6.0	-
Positive control	336.7	336.0	-	351.0	352.0	-

*solvent control with ethylene glycol dimethyl ether

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

Chlorodimethylsilane, CAS No. 1066-35-9 when tested in OECD 471 under GLP up to 4860 µg/plate caused no mutagenic effect in the Salmonella strains tested in the presence and the absence of metabolic activation either in the plate incorporation or in the preincubation test. It is concluded that the substance is negative for mutagenicity to bacteria under the conditions of the test.