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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-05-06 to 2002-08-08
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Species / strain
Species / strain:
other: TA 98, TA 100, TA 102, TA 1535, TA1537
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
100-5000 µg/plate
Vehicle:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: none given in report
Controlsopen allclose all
Negative controls:
no
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
TA 1535, TA 100 without metabolic activation
Negative controls:
no
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
TA 98 without metabolic activation
Negative controls:
no
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA 1537 without metabolic activation
Negative controls:
no
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
TA 102 without metabolic activation
Negative controls:
no
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-anthracene amide
Remarks:
TA 98, TA102, TA 1537 with metabolic activation
Negative controls:
no
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
TA 100, TA 1535 with metabolic activation
Details on test system and conditions:
ACTIVATION: Aroclor induced rat liver S9; NADP and glucose-6-phosphate as cofactors; S9 mix contained 5% S9; 0.5 ml S9 mix added to 2.2 ml agar/cell suspension/test material

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

SELECTION AGENT (mutation assays): minimal agar

NUMBER OF REPLICATIONS: 3 plates per concentration; 2 independent experiments, the first plate incorporation, the second pre-incubation

NUMBER OF CELLS EVALUATED: 10 E07 to 10 E08 cells

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of bacterial lawn
Evaluation criteria:
A chemical is considered positive if there is a reproducible dose-related statistically significant increase in the number of revertants compared with solvent control to at least 2 fold (strains TA 98, TA100 and TA 102) or 3-fold (strains TA 1535 and TA 1537). In addition, the histidine independence of teh revertants has to be confirmed.
Statistics:
Statistically significant: p

Results and discussion

Test results
Species / strain:
other: TA 98, TA 100, TA 102, TA 1535, TA1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Remarks:
3160 µg/plate (TA 98, preincubation)
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

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

Concentration µg/plate

TA 98

TA 100

TA 102

TA 1535

TA 1537

-MA

+MA

-MA

+MA

-MA

+MA

-MA

+MA

-MA

+MA

5000

35.7

41.0

132.3

128.3

269.3

310.3

11.7

12.0

8.0

7.0

3160

31.3

38.0

128.7

136.7

259.3

302.7

12.3

11.3

6.3

7.3

1000

34.7

36.0

117.0

125.0

258.7

300.0

11.7

11.0

5.7

7.7

316

31.7

37.3

116.7

126.0

310.7

307.3

11.0

11.7

5.3

6.3

100

25.0

39.7

134.3

144.0

276.7

280.7

11.3

12.7

4.0

5.0

0**

36.0

42.0

127.0

122.7

265.0

298.3

12.3

11.3

5.7

6.3

Positive control

986.3

990.3

1206.3

1196.7

1005.0

1135.0

213.3

207.0

207.7

208.7

** Solvent control with DMSO

Table 2 Experiment 2 Pre-incubation: Number of revertants per plate (mean of 3 plates)

Concentration µg/plate

TA 98

TA 100

TA 102

TA 1535

TA 1537

-MA

+MA

-MA

+MA

-MA

+MA

-MA

+MA

-MA

+MA

5000

33.7*

0.0*

122.3*

118.0*

261.0*

281.3*

12.3*

15.0*

3.3*

0.0*

3160

38.3*

27.7*

143.3

122.0

274.7

278.7

11.7

14.7

3.0

4.0

1000

39.7

36.3

148.0

151.7

250.3

265.0

10.7

15.3

2.7

2.7

316

50.7

30.0

141.0

154.3

282.0

287.3

12.0

13.3

3.0

3.3

100

38.0

31.0

145.7

159.0

284.7

285.3

13.0

16.7

3.3

3.0

0**

29.0

40.0

121.7

137.7

290.0

287.0

13.3

15.7

3.0

3.7

Positive control

1164.0

1139.3

1181.3

1189.0

1179.7

1188.0

674.0

671.7

696.0

700.3

* Scarce background lawn

** Solvent control with DMSO

Applicant's summary and conclusion

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

Tetramethylsilane was tested in valid study according to OECD 471 and under GLP. No increase in the number of revertants was observed in the plate incorporation assay with and without metabolic activation. The results was confirmed in the repeat pre-incubation experiment, also with and without metabolic activation. Vehicle and positive controls gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.