alpha-[butyl(dimethylsilyl)]-omega-[3-(2-{[2- (methacryloyloxy)ethyl]carbamoyloxy}ethoxy) propyl]poly[oxy(dimethyl)silylene]

Genetic toxicity: in vitro

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:

13 Aug to 12 Sept 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in 2005 according to OECD Method 471 and EU Annex V test B14 and in accordance with GLP. Study material is well characterized

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Test material form:

liquid

Method

Target gene:

four histidine-requiring strains and one tryptophan-requiring strain

Species / strain

Species / strain / cell type:

other: bacteria, other: Salmonella typhimurium: TA1535, TA1537, TA98, TA100 Escherichia coli: WP2uvrA

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbitone/B-napthoflavone rat liver homogenate

Test concentrations with justification for top dose:

Preliminary toxicity (Range finding) experiment carried out at concentrations of 0., 0.15. 0.5, 1.5, 5, 15 ,50, 150, 500, 1500 and 5000 ug/plate . For experiment 1 concentrations (with & without metabolic activation) used: 50, 150, 500, 1500 and 5000 µg/plate . For experiment 2 the same doses were used as for test 1.

Vehicle / solvent:

acetone

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Remarks:

(vehicle controls used in parallel with the test material

Positive controls:

yes

Remarks:

other: 2-Aminoanthracene at 1 ug/plate for TA100, 2 ug/plate for TA1535 &TA1537 and 10 ug/plate for WP2uvrA with metabolic activation.

Controls 2

Positive controls:

yes

Remarks:

benzo(a)pyrene (5 ug/plate for TA98 with metabolic acti

Controls 3

Positive controls:

yes

Remarks:

N-ethyl-N-nitro-N-nitrosoguanidine (3 ug/plate for TA 100, 5 ug/plate for TA1535 and 2 ug/plate for WP2uvrA)

Controls 4

Positive controls:

yes

Remarks:

9-aminoacridine (80 ug/plate for TA1537)

Controls 5

Positive controls:

yes

Remarks:

4-nitroquinoline-N-oxide (0.2 ug/plate for TA98)

Details on test system and experimental conditions:

A toxicity range finding experiment was conducted with strain TA100 and WP2uvrA at ten concentrations plus negative (vehicle) controls in absence and in the presence of metabolic activation S-9. No evidence of toxicity was observed following this treatment and formulation and S9 mix were shown to be sterile. This test was acceptable and no evidence of toxicity was observed following this treatment. For experiment 1 five concentrations were assayed in triplicate against each tester strain with and without metabolic activation. Experiment 2 was performed using the same methodology. No evidence of toxicity was observed following this treatment. Negative and positive control treatments were included for all strains in both experiments. The mean numbers of revertant colonies on negative control plates were all acceptable.

Evaluation criteria:

Evaluation criteria: Acceptance criteria for validity of assay : the mean negative control counts fell within normal ranges, the positive control chemical induced clear increases in revertant numbers confirming discrimination between different strains and an active S-9 preparation, and no more than 5 % of the plates were lost through contamination or some other unforeseen event. Evaluation criteria: test article would be considered mutagenic if: the assay was valid, Dunnett's test gave significant response and the data set(s) showed a significant dose correlation and the positive responses described above were reproducible in atleast one strain of bacteria.

Statistics:

Mean and standard deviation of the plate counts for each treatment were determined

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 100

Metabolic activation:

not specified

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(> 5000 µg/plate

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

not specified

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(> 5000 µg/plate

Test results 3

Species / strain:

other: Salmonella typhimurium: TA1535, TA1537, TA98, TA100 Escherichia coli: WP2uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

main test- experiment 1&2

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(> 5000 µg/plate)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Observations: All positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with and without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9 mix were validated. The test substance caused no visible reduction in the growth of the bacterial lawn at any dose level. The test substance was, therefore, tested up to the maximum recommended dose of 5000 ug/plate. Precipitate (oily) was observed on the plates at equal to and greater than 1500 ug/plate.

Remarks on result:

other: other: preliminary test

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

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

No statistically significant increases in revertant colony frequency were observed in any of the bacterial strains at all dose levels with and without S9.