Trichloro(propyl)silane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002-03-04 to 2002-09-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Trichloro(propyl)silane

EC Number:

205-489-6

EC Name:

Trichloro(propyl)silane

Cas Number:

141-57-1

Molecular formula:

C3H7Cl3Si

IUPAC Name:

trichloro(propyl)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:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

31.6-3160 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

- Justification for choice of solvent/vehicle: Solvent is not harmful to bacteria

Controls

Controls 1

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)

Controls 2

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)

Controls 3

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 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

TA 98, TA 102, TA 1537 (with activation)

Controls 5

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 6

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)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar, standard plate incorporation method, preincubation method

DURATION
- Preincubation period: 60 minutes
- Exposure duration: 48 hours

SELECTION AGENT (mutation assays): histidine deficient agar

NUMBER OF REPLICATIONS: cells were plated in triplicate; the experiment was repeated using the pre-incubation method.

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of background lawn.

ACTIVATION:
Aroclor induced rat liver S9 (protein content 32.92 mg/ml, cytochrome P-450: 0.32 nmol/mg) was added to S9 mix so that the mix contained 5% S9. glucose-6-phophate and NADP were added as co-factors. 0.5 ml S9 mix was added to 2 ml of top agar to a total volume of 2.7 ml. Final concentration S9 in agar was therefore approximately 1%.

Evaluation criteria:

The number of revertants is significantly increased compared with the solvent control to at least 2 fold of the solvent control for TA98, TA100 and TA102 and 3 fold of the solvent control for TA 1535 and TA1537 in both independent experiments. Positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking random samples on histidine free agar plates.

Statistics:

MANN and WHITNEY and Spearman's rank correlation used.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

3160 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

3160 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

See tables 2-4.

COMPARISON WITH HISTORICAL CONTROL DATA: Controls were within range of historical controls

Any other information on results incl. tables

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

	TA100
Conc. (µg/plate)	Plate 1	Plate 2	Cytotoxic (yes/no)
0*	133	142	No
0.316	122	143	No
1	141	145	No
3.16	149	136	No
10	120	129	No
31.6	105	128	No
100	108	106	No
316	103	111	No
1000	134	133	No
3160	104	112	Yes
5000	131	109	Yes

*solvent control with DMSO

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

	TA98			TA100			TA102
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	28.3	29.3	No	163	146.7	No	288	286.3	No
31.6	32	30.3	No	142.7	158.7	No	281	284.7	No
100	28.3	36.7	No	153	147.7	No	290.7	279.3	No
316	33.7	34	No	147.7	162.7	No	276.3	299.7	No
1000	34	38	No	158.3	146.3	No	297.3	292.7	No
3160	39.3	35	Yes	164	156.7	Yes	295.7	273.3	Yes
Positive control	1003	994	No	1312.3	1298.7	No	1313.7	1305	No

*solvent control with DMSO

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

	TA1535			TA1537
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	12	12.7	No	4.7	6	No
31.6	13.7	11.7	No	3	7	No
100	11.7	13	No	5.3	6.3	No
316	12.3	12	No	5	7.7	No
1000	11	12	No	7	8	No
3160	11.7	11	Yes	8.3	9	Yes
Positive control	773.3	780	No	780	783.7	No

*solvent control with DMSO

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

	TA98			TA100			TA102
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	33	41.3	No	117.7	141.7	No	274.3	298.7	No
31.6	45	43.7	No	115	138.7	No	278.3	272.7	No
100	37.7	42	No	132	138	No	274.3	279.7	No
316	36.3	38.7	No	133.7	141.7	No	298.7	265	No
1000	34	44.3	No	120.3	145	No	268.3	278	No
3160	0	0	yes	0	0	yes	0	0	yes
Positive control	1070	1059	No	1199.7	1211	No	1176.7	1214	No

*solvent control with DMSO

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

	TA1535			TA1537
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	11.7	11.3	No	3	3	No
31.6	12	10.7	No	2.3	4	No
100	11	11.3	No	3.3	3	No
316	11	12	No	3	4	No
1000	11	12	No	3	3.7	No
3160	0	0	yes	0	0	yes
Positive control	646.3	624.3	No	640.7	637.7	No

*solvent control with DMSO

Applicant's summary and conclusion

Conclusions:

Trichloro(propyl)silane has been tested for mutagenicity to bacteria according to OECD TG 471 and under GLP conditions in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537. No evidence of an increase in the number of revertants was observed for the test substance when tested up to cytotoxic concentrations with and without metabolic activation in any of the test strains in either the initial plate incorporation assay or the subsequent pre-incubation test. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of test.