acrylic acid, 3-(trimethoxysilyl)propyl ester

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6th April 1994 - 9th June 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Version / remarks:

1983

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

1

Reference substance name:

-

EC Number:

419-560-6

EC Name:

-

Cas Number:

4369-14-6

Molecular formula:

C9H18O5Si

IUPAC Name:

3-(trimethoxysilyl)propyl prop-2-enoate

Method

Target gene:

histidine deficient S. typhimurium strains and tryptophan deficient E. coli strains

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Type and composition of metabolic activation system:
- Source of S9: Phenobarbital (30 mg/kg x 1, 60 mg/kg x 3) and 5,6-benzoflavon (80 mg/kg x 1) induced rat liver S9 from Sprague-Dawley rats, male, 7 weeks old prepared by Hita Research Laboratories
- Method of preparation of S9 mix: In 1 mL of S9 mix, there was 8 µmol MgCl2, 33 µmol KCl, 5 µmol glucose-6-phosphate, 4 µmol NADPH, 4 µmol NADH, 100 µmol 0.2 M sodium phosphate buffer (pH 7.4), 0.1 mL S9
- Concentration or volume of S9 mix and S9 in the final culture medium: 0.5 mL of S9 mix

Test concentrations with justification for top dose:

- Dose range-finding test: 5000, 2000, 1000, 500, 200, 100 and 50 µg/plate.
- Main test doses: The highest dose chosen for the main test 5000 µg/plate was based on the findings of the dose range-finding study and four more doses of 2500, 1250, 625 and 313 µg/plate were chosen by dilution with a geometric progression of two in two independent tests.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: No denaturation of the test solution was observed until 2 hours after preparation which demonstrated that the test substance was stable within the solvent.

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2)

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-methoxy-6-chloro-9-[3-(2-chloroethyl)-aminopropylamino]acridine (ICR-191)

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (2AA)

Details on test system and experimental conditions:

NUMBER OF REPLICATIONS:
- Number of cultures per concentration: Dose range-finding test was tested in triplicate for the negative control and in duplicate for the test and positive control groups; triplicate cultures were used for the main test.
- Number of independent experiments : 2

METHOD OF TREATMENT/ EXPOSURE:
- The tests were carried out using the preincubation method

TREATMENT AND HARVEST SCHEDULE:
- Preincubation period, if applicable: 20 minutes
- Exposure duration/duration of treatment: 48 hours
- Harvest time after the end of treatment (sampling/recovery times): After 48-hour incubation period.

FOR GENE MUTATION:
- Method used: Agar

METHODS FOR MEASUREMENT OF CYTOTOXICITY :
- Method: Background growth inhibition

Rationale for test conditions:

Based on a dose range-finding study.

Evaluation criteria:

The test substance was judged to be positive, when the number of revertant colonies is more than twice that of the negative control and a dose relationship and reproducibility are obtained.

Statistics:

Means with standard deviation, and statistical significance

Results and discussion

Test results

Test results 1

Key result

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES:
Cytotoxicity was seen at 5000 µg/plate without S9 mix; no increase in the number of revertants was seen.

STUDY RESULTS :
- Concurrent vehicle negative and positive control data : See attachment for study data tables. Positive and negative controls were within the range of the background data for the laboratory.

For all test methods and criteria for data analysis and interpretation:
- Concentration-response relationship where possible : There was no concentration driven increase in the number of revertants seen.
- Statistical analysis: Statistical analysis was performed but no statistically significant increase in the number of revertants was seen.

Ames test:
- Signs of toxicity : Yes, at 5000 µg/plate with and without S9 mix
- Individual plate counts : Yes, see attachment for study data tables
- Mean number of revertant colonies per plate and standard deviation : Yes, see attachment for study data tables

Applicant's summary and conclusion

Conclusions:

3-(Trimethoxysilyl)propyl acrylate has been tested in a bacterial reverse mutation assay, conducted according to OECD Test Guideline 471 (1983) and in compliance with GLP, using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or E. coli WP2. No increase in the number of revertants was observed in any test strain, with or without metabolic activation, when tested up to cytotoxic concentration. Appropriate positive and solvent controls were added and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.