2-chloro-1,1-dimethoxyethane

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to OECD Guideline Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Ethane, 2-Chloro-1,1-Dimethoxy-

IUPAC Name:

Ethane, 2-Chloro-1,1-Dimethoxy-

Constituent 2

Reference substance name:

97-97-02

IUPAC Name:

97-97-02

Constituent 3

Reference substance name:

2-chloro-1,1-dimethoxyethane

EC Number:

202-624-0

EC Name:

2-chloro-1,1-dimethoxyethane

Cas Number:

97-97-2

Molecular formula:

C4H9ClO2

IUPAC Name:

2-chloro-1,1-dimethoxyethane

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Chloroacetaldehyde dimethylacetal
- Physical state: colourless liquid
- Analytical purity: 98%
- Purity test date: 1991-10-08
- Lot/batch No.: 007004
- Storage condition of test material: room temperature
- Containers: brown glass bottle

Method

Target gene:

Escherichia coli WP2uvrA-

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S9

Vehicle / solvent:

yes: sterile destilled water

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

WP2uvrA-, TA100; TA 1535 without S9

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA1537 without S9

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

TA 98 without S9

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

TA100, TA 1537 and TA 98 with S9

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

no

Positive control substance:

other: 2-aminoanthracene

Remarks:

TA 1537 and WP2uvrA- with S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk

DURATION
- Preincubation period: 48h
- Exposure duration: 48h
- Expression time (cells in growth medium):
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells):

SELECTION AGENT (mutation assays):
SPINDLE INHIBITOR (cytogenetic assays):
STAIN (for cytogenetic assays):

NUMBER OF REPLICATIONS:

NUMBER OF CELLS EVALUATED:

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:

OTHER EXAMINATIONS:
- Determination of polyploidy:
- Determination of endoreplication:

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

The test material , Chloroacetaldehyde dimethylacetal, was found to be mutagenic under the conditions of this test.

Executive summary:

 Salmonella typhimurium strains TA1535, TA 1537, TA68, TA100 and Escherichia coli strain WP2uvrA- were treated with Chloroacetaldehyde dimethylacetal by the Ames plate incorporation method at 5 dose levels, in triplicate both with and without the addition of a rat liver homogenate metabolizing system at 10% in standard co-factors (The study is comparable to OECD Guideline Study 472). This method conforms to the guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities including MITI, MHW, MOL, MAFF. It also meets the require ments of the OECD, EEC and USA, EPA (TSCA) guidelines. The dose range was determined in a preliminary toxicity assay and was 8 to 5000 µg/plate in the first experiment. The experiment was repeated on a separate day using different cultures of the bacterial strains and fresh chemical solutions. In this case the dose range of Chloroacetaldehyde dimethylacetal was 312,5 to 5000 µg/plate. The solvent (sterile destilled water) control plates gave counts of revertant colonies within the normal range.   All positive control chemicals gave increases in revertants, both with and without the metabolizing system, within expected ranges.   Chloroacetaldehyde dimethylacetal caused no reduction in the growth of the bacterial lawn at any dose level either with or without metabolic activation. Chloroacetaldehyde dimethylacetal was therefore tested up to the maximum recommended dose level of 5000 µg/plate.   A significant reproductible, dose-related increase in the numbers of revertant colonies was recorded for bacterial strain TA100 with doses of Chloroacetaldehyde dimethylacetal beginning at 200 µg/plate, both with and without metabolic activation. A slight increase in the numbers of revertant colonies was also observed with Salmonella strain TA1535. Chloroacetaldehyde dimethylacetal was found to be mutagenic under the conditions of this test.