Diphenylsilanediol

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:

30-04-1994 To 14-11-1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate OECD test guideline, with acceptable restrictions. The restrictions were that the range of strains does not comply with the current guideline. Original study and read across reliability 2.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Did not include strain to detect cross-linking mutagens.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dichloro(diphenyl)silane

EC Number:

201-251-0

EC Name:

Dichloro(diphenyl)silane

Cas Number:

80-10-4

IUPAC Name:

dichloro(diphenyl)silane

Test material form:

not specified

Method

Target gene:

His operon

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

other: rfa, uvrB and pKM101 (TA98 & TA100)

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.

Test concentrations with justification for top dose:

8-5000 µg/plate - Plate incorporation method.
31.25-1200 µg/plate - Pre-incubation method.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Ethylene glycol dimethylether (EGDE, dried with a molecular sieve, 0.4 nm)

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: nitrofurantoin

Remarks:

-S9: TA 100: 0.2 µg per plate.

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

-S9: TA 1535: 10 µg per plate.

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: phenylene diamine

Remarks:

-S9: TA1537 and TA98 : 10 and 0.5 µg per plate, respectively.

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

+ S9: All strains: 3 µg per plate.

Details on test system and experimental conditions:

METHOD OF APPLICATION:in agar (plate incorporation) and preincubation;

DURATION
- Preincubation period: 30 minutes
- Exposure duration: 48 hours


NUMBER OF REPLICATIONS: 4

DETERMINATION OF CYTOTOXICITY
- Method: Gross appraisal of background growth on the plate, marked or dose-dependent reduction in the mutant count per plate and the titre was determined.


Metabolic activation system: It was made from the livers of at least six adult male Sprague-Dawley rats, of approximately 200 to 300 g in weight. For enzyme induction, the animals received a single intraperitoneal injection of Aroclor 1254, dissolved in corn oil, at a dose of 500 mg/kg bw, five days prior to sacrifice. The S9 mix also contained seventy mL of cofactor solution containing the following:

-MgCl2 x 6H2O (162.6 mg)
-KCl (246.0 mg)
-Glucose-6-phophate, disodium salt (179.1 mg)
NADP, disodium salt (315.0 mg)
-Phosphate buffer (100.0 mg)

Evaluation criteria:

A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA1535, TA 100 and TA 98 this increase should be about twice that of negative controls, whereas TA 1537, at least a threefold increase should be reached. However, these guidelines may be overruled by good scientific judgement.

Results and discussion

Test results

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:

>62.5 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY: The salmonella/ microsome plate incorporation test, employing doses of up to 5000 µg per plate, showed diphenyldichlorosilane to produce bacterial toxic effects at 40 µg per plate and above. Therefore, 5000 µg per plate could not be used for assessment. The salmonella/ microsome test, using preincubation for 30 minutes at 37 °C and employing doses of up to 1200 µg per tube, showed diphenyldichlorosilane to produce bacterial toxic effects at 100 µg per tube and above.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1. Summary of numbers of revertants per plate (mean of four plates) without metabolic activation.

Groups	Strain
	TA 1535	TA 100	TA 1537	TA 98
Plate incorporation method (µg/plate)
0	25	120	12	23
8	26	116	9	24
40	27	117	11	24
20	31	104	9	23
1000	30	105	8	29
5000	-	-	-	-
Na-azide	926
NF		378
4-NPDA			101	118
Pre-incubation method- µg/plate
0	22	143	13	31
31.25	29	146	13	31
62.5	36	157	14	31
125	30	166	15	28
250	43	134	8	27
500	38	144	6	22
1000	32	117	6	17
Na-azide	897
NF		531
4-NPDA			83	60

Table 2 Additional results for TA 1535 without metabolic activation (revertants per plate; mean of 4 plates)

Groups	Strain TA 1535
Plate incorporation method (µg/plate)
0	11	11	18
100	11	14	16
200	11	12	17
400	13	12	15
600	10	13	11
800	9	12	10
1000	10	11	9
1200	10	12	10
Na-azide	714	700	678
Pre-incubation method (µg/plate)
0	27	29	-
31.25	30	22	-
62.5	32	29	-
125	31	31	-
250	51	35	-
500	33	52	-
1000	40	55	-
Na-azide	883	848	-
Pre-incubation method (µg/plate)
0	12	15	12
100	15	19	12
200	19	18	13
400	20	15	11
600	17	17	10
800	15	8	7
1000	11	9	10
1200	8	10	7
Na-azide	855	639	648

Table 3. Summary of number of revertants per plate (mean of four plates) with metabolic activation.

Groups	Strain
	TA 1535	TA 100	TA 1537	TA 98
Plate incorporation method (µg/plate)
0	21	150	16	42
8	19	146	12	44
40	18	142	14	42
20	17	119	12	39
1000	16	119	12	34
5000	-	-	-	-
2-AA	211	1476	117	891
Pre-incubation method (µg/plate)
0	17	141	10	40
31.25	17	151	12	38
62.5	17	148	13	46
125	22	166	11	45
250	19	154	11	48
500	21	168	11	41
1000	19	119	7	36
2-AA	213	1268	126	1107

Plate incorporation method:

There was no indication of a bacterial toxic effect of diphenylchlorosilane at 8 µg per plate. The total bacterial counts consistently produced results comparable to the negative controls, or differed only insignificantly. No inhibition of growth was noted as well. None of the four strains concerned showed a dose- related and biologically relevant increase in mutant counts over those of the negative controls. This applied both to the tests with and without S9-mix.

 Pre-incubation method:

There was no indication of a bacterial toxic effect of diphenylchlorosilane at doses of up to and including 62.5 µg per tube. The total bacteria counts consistently produced results comparable to the negative controls, or differed only insignificantly. No inhibition of growth was noted as well. One of the four strains concerned revealed an increase in mutant counts to double those of negative controls. Strains TA 1535 were affected. This increase did, however, not correlate with dose and could not be confirmed (see Table 2). Therefore, it was considered to be of no relevance.

The positive controls sodium azide, nitrofurantonin, 4-nitro-1,2-phenyl diamine and 2-aminoanthracene increased mutant counts well over those of the negative controls, and thus demonstrated the system’s sensitivity and the activity of the S9 mix

Applicant's summary and conclusion

Conclusions:

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

In a bacterial mutagenicity assay according to OECD 471 and GLP, no indications of mutagenic effects of diphenyldichlorosilane was found at assessable doses of up to 1200 µg per plate in any of the Salmonella typhimurium strains used in the plate incorporation assay and in the preincubation assay.