Silicon tetrachloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in all strains tested (similar to OECD Test Guideline 471 and in compliance with GLP) (Dow Corning Toxicology Dept., 1981).

Cytogenicity in mammalian cells: negative in L5178Y mouse lymphoma cells (similar to OECD Test Guideline 473 but not in compliance with GLP) (Litton Bionetics, 1978a).

Mutagenicity in mammalian cells: negative in L5178Y mouse lymphoma cells (similar to OECD Test Guideline 476 and pre-GLP) (Litton Bionetics, 1978b).

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:

1981-03-25 to 1981-03-28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

range of strains used, only 4 doses used which were not replicated.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium, other: TA-98, TA-100, TA-1535, TA-1537, TA-1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

0.5-500 µl/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Absolute ethanol was used for the test substance. Dimethylsulfoxide (DMSO) was used for positive control substances except sodium azide which was dissolved in water or saline.

- Justification for choice of solvent/vehicle: Previously shown to be non-mutagenic

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 100, TA 1535 (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:

2-nitrofluorene

Remarks:

TA 98, TA 1538 (without activation)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-anthramine

Remarks:

All strains (with activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation);
other: spot plate test

DURATION

- Expression time (cells in growth medium): 48 - 72 hours

NUMBER OF REPLICATIONS: 1 plate for each test concentration

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

For TA 1535, TA 1537 and TA 1538, the test substance is considered mutagenic if a positive dose response is produced over three concentrations with the lowest increase equal to twice the solvent control value.

For TA 98 and TA 100, the test substance is considered mutagenic if a positive dose response is produced over three concentrations with the highest increase equal to twice the solvent control value for TA 100, and two to three times the solvent control value for TA 98.

Species / strain:

other: Salmonella typhimurium: TA-98, TA-100, TA-1535, TA-1537, TA-1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µl/plate (TA 1535 -MA / TA 1537 +MA)

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

 

Table 2a: Experiment 1 Overlay plate test, Number of revertants per plate

Conc. (µg/plate)	TA98			TA100			TA1535
	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0	41	36	No	225	196	No	29	30	No
0.5	31	37	No	238	186	No	26	22	No
5	34	36	No	236	134	No	31	17	No
100	33	45	No	246	218	No	23	18	No
500	38	30	No	250	160	No	12	25	Yes
Positive Control	431	>10^3	No	476	>10^3	No	311	173	No

*solvent control with Ethanol

 

Table 2b: Experiment 1 Overlay plate test, Number of revertants per plate

Conc. (µg/plate)	TA1537			TA 1538
	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0	10	17	No	24	35	No
0.5	7	11	No	23	45	No
5	9	14	No	27	41	No
100	9	8	No	20	38	No
500	9	7	Yes	20	27	No
Positive Control	121	103	No	130	>10^3	No

*solvent control with Ethanol

Conclusions:

Silicon tetrachloride has been tested for mutagenicity in a reliable in vitro bacterial reverse mutation assay, conducted according to a protocol similar to OECD Test Guideline 471 and in compliance with GLP. Silicon tetrachloride did not demonstrate any genetic activity in the bacterial strains Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538, when tested in the presence and the absence of metabolic activation up to cytotoxic concentration. Appropriate solvent and positive controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity in the Salmonella typhimurium strains used under the conditions of the test .

Reference 2

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:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

no duplicates

GLP compliance:

no

Type of assay:

mammalian cell gene mutation assay

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

mouse liver S9

Test concentrations with justification for top dose:

0.04, 0.08, 0.16, 0.32 µl/ml (-S9); 0.08, 0.16, 0.32, 0.48 µl/ml (+S9)

Vehicle / solvent:

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

- Justification for choice of solvent/vehicle: none given in report

Untreated negative controls:

yes

Remarks:

media

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

(without activation)

Untreated negative controls:

yes

Remarks:

media

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-dimethylnitrosamine

Remarks:

(with activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION

- Exposure duration: 4 hours

- Expression time (cells in growth medium): 3 days

- Selection time (if incubation with a selection agent): 10 days

- Fixation time (start of exposure up to fixation or harvest of cells): 3 days

NUMBER OF REPLICATIONS: 3 plates for each test concentration

DETERMINATION OF CYTOTOXICITY

- Method: % relative growth

Evaluation criteria:

A compound is considered mutagenic if:-

a. A dose response relationship is observed over three of the four dose levels employed

b. The minimum increase at the high level of the dose response curve is at least 2.5 times greater than the solvent control value

c. The solvent control data are within the normal range of the spontaneous background for the TK locus

Statistics:

t-statistic used to evaluate statistical significance.

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: >.32 ug/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The maximum tolerated concentration was 0.32 µg/mL indicating that silicon tetrachloride has relatively high cytotoxicity activity. No genetic effects were attributable to the solvent or negative controls. EMS and DMN induced responses within the expected ranges. The following test results were noted: 

Point Mutation: The results from this assay were negative. Silicon tetrachloride was not mutagenic when evaluated over the normal concentration range. The highest concentration under activation test procedures showed an elevated mutation response but this could not be considered valid because the cell toxicity was greater than 99%.

Table 1: Results of Mammalian Mutagenicity assay with L5178Y/TK^+/- Mouse Lymphoma Cells

Concentrationµg/ml	Mutant* Frequency	Mutant* Frequency	%Relative Growth.	%Relative Growth.	Cytotoxicity (yes/no)
	— MA	+ MA	— MA	+ MA	-
Solvent Control	15	10	100	100	No
Negative Control	21.1	16.8	85.7	101.7	No
Positive Control	273.4	529.3	35	5	No
0.04	21.1	-	115.3	-	No
0.08	15.5	25	102.6	74.3	No
0.16	17.3	20.6	87.5	85.2	No
0.32	15.3	18.8	41.1	43.6	Yes
0.48	-	107.5	-	0	Yes

*Per 10⁶surviving cells

Solvent control with Ethanol

Conclusions:

Silicon tetrachloride has been tested for mutagenicity in a reliable in vitro mammalian cell gene mutation assay, conducted according to a protocol similar to OECD Test Guideline 476 and pre-GLP compliance. Silicon tetrachloride was found to be not mutagenic in mouse lymphoma L5178Y cells when tested with and without metabolic activation up to cytotoxic concentration. Appropriate solvent, negative and positive controls were included and gave the expected results. It is concluded that the test substance is not mutagenic to mammalian cells under the conditions of the test.

Reference 3

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

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 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

yes

Remarks:

only 50 cells scored - guideline requires 200. no duplicates. Number cells with 2 or more aberrations presented (rather than % with aberrations).

GLP compliance:

no

Type of assay:

in vitro mammalian chromosome aberration test

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

mouse liver S9

Test concentrations with justification for top dose:

0.02, 0.04, 0.08, 0.16 and 0.32 µl/ml

Vehicle / solvent:

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

- Justification for choice of solvent/vehicle: not specified

Untreated negative controls:

yes

Remarks:

media

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

(without activation)

Untreated negative controls:

yes

Remarks:

media

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-dimethylnitrosamine

Remarks:

(with activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION

- Expression time (cells in growth medium): 20 hours

STAIN (for cytogenetic assays): Giemsa

NUMBER OF REPLICATIONS: 1

NUMBER OF CELLS EVALUATED: 50 cells per test substance concentration

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

Evaluation criteria:

Criteria for evaluating results: Compound is considered mutagenic in the mouse lymphoma assay if: 

a. A dose response relationship is observed over three of the four dose levels employed.

b. The minimum increase at the high level of the dose response curve is at least 2.5 times greater than the solvent control value.

c. The solvent control data are within the normal range of the spontaneous  background for the TK locus.

Responses (numbers of aberrations ) to the test substance were compared  to concurrent negative and positive controls, as well as to historical data. The data was analysed by t-statistic.

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

0.16 - 0.32 μL/mL

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The maximum tolerated concentration was 0.32 µg/ml indicating that silicon tetrachloride has relatively high cytotoxicity activity.  No genetic effects were attributable to the solvent or negative controls. EMS and DMN induced responses within the expected ranges. The following test results were noted: Silicon tetrachloride exhibited positive responses in the cytogenetic analysis indicating that the material has the potential to produce chromosome alterations at concentrations approximately ½ the cytotoxic level.  These responses were accounted for by unusually low concurrent negative control values and when the test results were compared to the historical controls, the results were not significant.

Table 1: Cytogenetic analysis (without activation)

Compound and Concentration	Total No. Of Cells	Type / Frequency Aberrations per Cell (%)	No. Of Cells with 2+ Aberrations (%)	Mitotic Index (%)
Negative Control	50	0	0	3.8
Solvent Control	50	0	0	3.6
Positive Control	50	5t, 2tr, 2cr, 2tb, 2f, 4af, 1>	5	5.6
0.02	50	0	0	4.2
0.04	50	1tb	0	4.4
0.08	50	3tb	0	6.6
0.16	50	1t, 1pu+	0	2.8
0.32	TOXIC	-	-	-

 

Table 2: Cytogenetic analysis (with activation)

Compound and Concentration	Total No. Of Cells	Type / Frequency Aberrations per Cell (%)	No. Of Cells with 2+ Aberrations (%)	Mitotic Index (%)
Negative Control	50	0	0	3.2
Solvent Control	50	1f	0	3.2
Positive Control	50	1tb, 6f, 1af, 3tr, 2t, 3qr, 2cr, 2>	4	3.8
0.02	50	1f, 1t	1	3.4
0.04	50	1f	0	4.2
0.08	50	1tb	0	3.8
0.16	50	1f, 2tb	0	4.8
0.32	TOXIC	-	-	-

 Key

tb	Chromatid break
f	Fragment
qr	Quadriradial
tr	Triradial
min	Minute chromosome
af	Acentric fragment
t	Translocation
cr	Complex rearrangement
pu+	Pulverised chromosome

 

Conclusions:

Silicon tetrachloride has been tested for clastogenicity in a reliable in vitro chromosome aberration assay, conducted according to a protocol similar to OECD Test Guideline 473 but not in compliance with GLP. Silicon tetrachloride did not increase the number of chromosomal aberrations in mouse L5178Y lymphoma cells, when tested with and without metabolic activation up to cytotoxic concentration. Appropriate solvent, negative and positive controls were included and gave the expected results. It was concluded that the test substance is negative for induction of chromosome aberrations under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Silicon tetrachloride has been tested for mutagenicity in a reliable in vitro bacterial reverse mutation assay, conducted according to a protocol similar to OECD Test Guideline 471 and in compliance with GLP. Silicon tetrachloride did not demonstrate any genetic activity in the bacterial strains Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538, when tested in the presence and the absence of metabolic activation up to cytotoxic concentration. Appropriate solvent and positive controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity in the Salmonella typhimurium strains used under the conditions of the test (Dow Corning Corporation, 1981).

Silicon tetrachloride has been tested for clastogenicity in a reliable in vitro chromosome aberration assay, conducted according to a protocol similar to OECD Test Guideline 473 but not in compliance with GLP. Silicon tetrachloride did not increase the number of chromosomal aberrations in mouse L5178Y lymphoma cells, when tested with and without metabolic activation up to cytotoxic concentration. Appropriate solvent, negative and positive controls were included and gave the expected results. It was concluded that the test substance is negative for induction of chromosome aberrations under the conditions of the test (Litton Bionetics, 1978a).

Silicon tetrachloride has been tested for mutagenicity in a reliable in vitro mammalian cell gene mutation assay, conducted according to a protocol similar to OECD Test Guideline 476 and pre-GLP compliance. Silicon tetrachloride was found to be not mutagenic in mouse lymphoma L5178Y cells when tested with and without metabolic activation up to cytotoxic concentration. Appropriate solvent, negative and positive controls were included and gave the expected results. It is concluded that the test substance is not mutagenic to mammalian cells under the conditions of the test (Litton Bionetics, 1978b).

Several supporting studies were available for silicon tetrachloride which were in agreement with the key data.

Silicon tetrachloride has been tested for mutagenicity in an in vitro bacterial mutagenicity toxicity study, conducted to a protocol similar to OECD Test Guideline 471 but pre-GLP. Silicon tetrachloride did not demonstrate genetic activity in any of the tests conducted in this evaluation, both with and without metabolic activation. Appropriate solvent and positive controls were included and gave the expected results. The results indicate that the test substance was not considered mutagenic under these test conditions (Litton Bionetics, 1978g).

Silicon tetrachloride has been tested for mutagenicity in an in vitro bacterial mutagenicity, not conducted according to OECD Test Guideline but in compliance with GLP. Silicon tetrachloride did not demonstrate any genetic activity in the bacterial strains Salmonella typhimurium TA97, TA98 and TA100, when tested in the presence or absence of metabolic activation up to cytotoxic concentration. It was concluded that the test substance is not mutagenic under the conditions of the test (Microtest Research Limited, 1987).

Silicon tetrachloride has been tested in vitro for DNA damage and/or repair in a study, not conducted according to any OECD Test Guideline or GLP. Silicon tetrachloride did not cause damage to DNA in E. coli regardless of absence or presence of metabolic activation. Appropriate solvent controls were included and gave the expected results It is concluded that the test substance is not mutagenic under the conditions of the test (Litton Bionetics, 1978d).

Silicon tetrachloride has been tested in an in vitro DNA damage and/or repair study, not conducted according to OECD Test Guideline or GLP. Silicon tetrachloride did not demonstrate genetic activity in the presence or absence of metabolic activation. It was concluded that the test substance is negative under the conditions of the test (Litton Bionetics, 1978h).

Silicon tetrachloride has been tested in an in vitro DNA damage and/or repair study, conducted according to a protocol similar to OECD Test Guideline 482 but pre-GLP. Silicon tetrachloride did not demonstrate any genetic activity regardless of presence or absence of metabolic activation. Appropriate solvent and positive controls were included and gave the expected results. It was concluded that the test substance is not mutagenic under the test conditions (Litton Bionetics, 1978e).

Silicon tetrachloride has been tested in an in vitro DNA damage and/or repair study, conducted according to a protocol similar to OECD Test Guideline 471 but not in compliance with GLP. Appropriate solvent and positive controls were included and gave the expected results. Silicon tetrachloride did not cause damage to DNA in yeast (Litton Bionetics, 1978c).

Silicon tetrachloride has been tested in an in vitro sister chromatid exchange assay, not conducted according to OECD Test Guideline or GLP, silicon tetrachloride was found to be relatively cytotoxic  for L5178Y mouse lymphoma cells. However, the apparent increases in SCEs were concluded to be a result of the low concurrent controls. It was concluded that the test substance is non-clastogenic in L5178Y mouse lymphoma cells (Litton Bionetics, 1978f).

Justification for classification or non-classification

Based on the available data, silicon tetrachloride is not classified for germ cell mutagenicity according to Regulation (EC) No. 1272/2008.