Propanoic acid, 3-chloro-, 4-chlorobutyl ester

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:

supporting study

Study period:

2000-04-17 to 2000-05-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD test under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-Chlorpropionsäure-(4'Chlorbutyl)ester (Clp-Ester)

IUPAC Name:

3-Chlorpropionsäure-(4'Chlorbutyl)ester (Clp-Ester)

Details on test material:

- Name of test material (as cited in study report): 3-Chlorpropionsäure-(4'Chlorbutyl)ester (Clp-Ester)
- Physical state: brown liquid
- Impurities (identity and concentrations): as stated in substance data
- Composition of test material, percentage of components: as stated in substance data
- Lot/batch No.: 1/99
- Expiration date of the lot/batch: 2000-07-31
- Stability under test conditions: stable
- Storage condition of test material: in original container, at room temperature, in the dark

Method

Species / strain

Species / strain 1

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S9 Mix

Test concentrations with justification for top dose:

Dose Range Finding: 3, 10, 33; 100, 333,. 1000, 3330 and 5000 µg/plate

Experiment : 100, 333,. 1000, 3330 and 5000 µg/plate (TA 1535, TA 1537, TA 98)
Experiment : 3, 10, 33; 100, 333,. 1000, 3330 and 5000 µg/plate (TA 100, WP2uvrA)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used:dimethyl sulfoxide
- Justification for choice of solvent/vehicle: the solvent was chosen becuase of its solubility properties.

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

positive control for WP2 uvr A without S9

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: methylmethanesulfonate

Remarks:

positive control for TA 100 without S9

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: daunomycine

Remarks:

positive control for TA 98 without S9

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

positive control for TA 1535 without S9

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

positive control for TA 1537 without S9

Controls 6

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-aminoanthrancene

Remarks:

positive control for all strains with S9 Mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

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

DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of revertants, bachground growth

Evaluation criteria:

in accordance with the Guideline

Results and discussion

Test results

Test results 1

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:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

only in the 3330 and 5000 µg/ml concentration without S9

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

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:

cytotoxicity

Remarks:

only in the 5000 µg/ml concentration without S9

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

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:

cytotoxicity

Remarks:

only in the 3330 and 5000 µg/ml concentration without S9

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

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:

valid

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 substance is mutagenic in the Salmonella typhimurium Reverse Mutation Assay for tester strains TA 100 and TA 1535 with and without activation. It is not mutagenic in the E.coli revese mutation assay.

Executive summary:

The Ames Test and the E.coli mutation assay according to OECD 471 did not produce any positive results with the test substance 3-Chlorpropionsäure-(4'Chlorbutyl)ester (Clp-Ester) in tester strains TA 1537, TA 98 and WP2 uvr A both with and without metabolic activation up to concentrations of 5000 µg/l. The Ames test in contrast did produce positive dose related results with and without activation in tester strains TA 1535 and TA 100. The negative, solvent and positive controls worked as expected.