1,1,3-trichloroacetone

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987 to 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: comparable to OECD Guideline study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

1,1,3-trichloroacetone

EC Number:

213-063-6

EC Name:

1,1,3-trichloroacetone

Cas Number:

921-03-9

Molecular formula:

C3H3Cl3O

IUPAC Name:

1,1,3-trichloropropan-2-one

Details on test material:

as purchased by Aldrich Chemical Company, Milwaukee, WI, USA

Method

Target gene:

not applicable

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

- Type and identity of media: McCoy's 5a medium supplemented with 15% fetal bovine serum, 2mM L-glutamine and 1% penicillin-steptomycin
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination:no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

0.8; 1.5, and 3.0 µg/ml (without metabolic activation)
7.5; 15.1, and 30.2 µg/ml (with metabolic activation)

Vehicle / solvent:

0.04%(v/v) Emulphor El-620

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

none

Migrated to IUCLID6: without metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

none

Migrated to IUCLID6: with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 6-8 h without, 2 h with metabolic activation
- Expression time (cells in growth medium): 8-10 h
- Fixation time (start of exposure up to fixation or harvest of cells): 8-10 h


STAIN (for cytogenetic assays): Giemsa


NUMBER OF REPLICATIONS:2 per concentration


NUMBER OF CELLS EVALUATED: at least 2000 for mitotic index, 100 for aberration assay


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

Evaluation criteria:

number of cells with structural chromosomal abberations

Statistics:

The numbers of cells with structural chromosomal abberations were analyzed using chi-square, with differences considered significant at p< 0.05.

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

Test 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

Substance induced structural chomosomal aberrations (chromatid deletions and exchanges)

Executive summary:

1,1,3 -Trichloroacetone was assessed in a chromosomal aberration assay in Chinese Hamster Ovary cells (CHO cells) with and without metabolic activation (S9 -mix) in vitro. The substance induced significant increases in structural chromosomal abberationsin CHO cells in the presence and in the absence of S9 rat metabolic activation. The clastogenic activities was reduced in the assay conducted with metabolic activation which might be the result of the shorter exposure time of cells with metabolic activation (2 hours) compared to that without metabolic activation (6 -8 hours). 1,1,3 -Trichloroacetone showed a stron cytotoxic reaction against the cells and induced structural chomosomal aberrations (chromatid deletions and exchanges).