Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04.03.2002 - 04.09.2002
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 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

Target gene:
Histidine
Species / strain
Species / strain / cell type:
other: TA 1537, TA 102, TA 98, TA 1535, TA 100
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
Experiment 1: 10 - 1000 µg/plate; Experiment 2: 1 - 100 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Abs. ethylene glycol dimethylether
- Justification for choice of solvent/vehicle: Solvent was chosen because of its solubility properties and its relative non-toxicity to the bacteria.
Controlsopen allclose all
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 metabolic activation conc 10 µg/plate
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 metabolic activation conc 10 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
TA 102 without metabolic activation conc 1300 µg/plate
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 metabolic activation conc 100 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Anthracene amide 2 µg/plate
Remarks:
TA 98, TA 102, TA 1537 with metabolic activation
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 metabolic activation 1500 µg/plate
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation); preincubation

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

SELECTION AGENT (mutation assays): Histidine deficient agar

NUMBER OF REPLICATIONS: Triplicate plates: independent repeat experiment


DETERMINATION OF CYTOTOXICITY
- Method: other: Inhibition of background lawn and greater than 50% reduction in the number of revertants

Evaluation criteria:
A chemical is considered positive if it shows a statistically significant dose dependent and reproducible increase in the number of revertants relative to the solvent control.
Statistics:
Mann and Whitney U-test and Spearman's rank correlation coefficient

Results and discussion

Test results
Key result
Species / strain:
other: TA98, TA100, TA102, TA1536, TA1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH:
- Effects of osmolality:
- Evaporation from medium:
- Water solubility:
- Precipitation: None
- Other confounding effects:



COMPARISON WITH HISTORICAL CONTROL DATA: The results for solvent and positive controls fall within the range of the historical controls

Any other information on results incl. tables

Plate incorporation test

Treatment µg/plate

       TA 98

 

TA 100

TA 102

TA 1535

TA 1537

- S9

+ S9

- S9

+ S9

- S9

+ S9

- S9

+ S9

- S9

+ S9

0

34.0

44.3

142.0

160.3

262.0

279.3

13.7

13.3

4.3

4.0

10

37.7

44.0

145.3

137.3

262.0

276.3

12.0

12.7

3.0

3.7

31.6

34.7

44.3

130.0

131.3

264.0

282.3

13.7

12.3

3.3

2.7

100

42.7

40.3

133.0

137.3

273.0

289.3

11.7

12.0

3.0

4.3

316

41.7

36.3

136.3

126.0

258.0

280.3

13.0

12.7

3.0

3.0

1000

39.7

47.7

151.0#

155.3

294.3

289.7

13.0

12.7

3.3

3.3

Pos con

1031.0

1032.7

1359.3

1345.7

1364.3

1363.3

620.3

995.7

1072.3

1072

 

 

 

 

Pre-incubation test

Treatment µg/plate

       TA 98

 

TA 100

TA 102

TA 1535

TA 1537

- S9

+ S9

- S9

+ S9

- S9

+ S9

- S9

+ S9

- S9

+ S9

0

42.7

53.3

160.7

172.0

275.7

299.3

13.3

15.0

6.0

6.3

1

34.3

41.3

174.7

157.7

261.0

281.0

14.3

13.0

7.0

7.7

3.16

54.7

39.3

168.7

168.3

284.7

271.7

14.0

14.3

6.3

6.7

10

30.3

42.3

169.7

146.7

267.7

256.0

12.0

16.3

6.3

7.3

31.6

36.3

50.3

181.7

155.0

278.0

272.7

13.7

12.7

7.0

6.3

100

26.0#

0.0#

153.3#

177.7#

269.0#

298.0

14.7#

13.7#

5.0#

8.0#

Pos con

758.7

969.7

1284.3

1324.0

1267.0

1236.3

327.3

347.7

353.3

350.7

 

# = scarce background lawn

Applicant's summary and conclusion

Conclusions:
Dichloro(methyl)(phenyl)silane has been tested in a reliable bacterial mutagenicity assay according to OECD TG 471 and under GLP. The test substance did not induce an increase in the number of revertants in either the initial plate incorporation assay or the repeat pre-incubation assay. Solvent and positive controls gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.