2-chloro-3-oxopentyl acetate

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:

25.08 - 08.09.1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The Ames test with chlorketone was performed in 1980 at Inveresk Research International (Edinburgh, Scotland), which is now part of Charles River Laboratories. The test was performed according to (at that time) state of the art practices. All steps / strains / solvents / test conditions are well described.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

no guideline available

Deviations:

not applicable

Principles of method if other than guideline:

Positive control compound: 2-aminoanthracene.
The test substance and positive control compound were dissolved
in dimethylsulphoxide ('AnalaR' grade from BDH Chemicals Limited, Poole, England).
Five strains of Salmonella typhimurium were used: TA 1535, TA 100, TA 1537, TA 1538, TA 98. The test was performed in the presence
and absence of a post-mitochondrial supernatant fraction from the livers of male rats and CO-factors required for mixed-function
oxidase activity.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-chloro-3-oxopentyl acetate

EC Number:

235-930-8

EC Name:

2-chloro-3-oxopentyl acetate

Cas Number:

13051-49-5

Molecular formula:

C7H11ClO3

IUPAC Name:

2-chloro-3-oxopentyl acetate

Method

Target gene:

All 5 strains contain the deep rough (rfa) mutation,
which deletes the polysaccharide side chain of the
lipopolysaccharide coat of the bacterial cell surface.

Species / strain

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

not applicable

Additional strain / cell type characteristics:

other: mutations in the histidine operon

Metabolic activation:

with and without

Metabolic activation system:

mixed-function oxidase system

Test concentrations with justification for top dose:

A preliminary toxicity study was performed in which strain
TA 100 was treated with the following concentrations of
chlorketone; 33.3 ug, 100.0 ug, 333.3 ug, 1.0 ug, 3.3 ug and
10.0 mg per plate. At the highest dose tested, the substance
was not toxic when S-9 mix was added to the plates, it was
therefore decided that it would be convenient to use 0.1 m1 of
undiluted chlorketone as the highest :dose in the main plate
test (0.1 ml of chlorketone weighs 132.9 mg).

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)


DURATION
- Preincubation period:
- Exposure duration: 2 days
- 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: 3


NUMBER OF CELLS EVALUATED:


DETERMINATION OF CYTOTOXICITY
- Method: relative total growth


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


OTHER:

Evaluation criteria:

see below

Statistics:

see tables

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

only for TA100 (10 mg/l)

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

not relevant

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

no remarks

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
ambiguous

Chlorketone showed a weak mutagenic effect in strain TA 100 at a concentration
of 10.0 mg/plate. Metabolic activation by the liver homogenate fraction was necessary to produce mutagenic effects.

Executive summary:

The Ames test with chlorketone was performed in 1980 at Inveresk Research International (Edinburgh, Scotland), which is now part of Charles River Laboratories. The test was performed according to (at that time) state of the art practices. The test item was weakly mutagenic in strain TA100 at a dose level of 10 mg, 13.3 mg and 20 mg/plate (different repititions of the test). At each experiment, the threshold of an increase in the number of revertants of 1.5 compared to solvent controls was only marginally reached. Samples were run in triplicates. Looking at the individual data, strong varations in revertant numbers could be noted, in controls as well as in treated samples. Thus, the biological significance of the average 1.5-fold increase in revertant numbers is doupted. Moreover, in the OECD Guideline 471 for the Bacterial Reverse Mutation Test, which is the standard of today, the maximum concentration to be tested is set to 5 mg/plate. At this concentration, Chlorketone gave a clear negative result. Thus, the result for Chlorketone in the Ames test is rather to be seen as "equivocal".

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