4-chloro-α,α,α-trifluorotoluene

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 5 to 24 June 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The test item was tested in the chromosome aberration assay using Chinese hamstar ovary cells, with and without metabolic activation. The treated cells were harvested at 14 hours and 24 hours following the initiation of chemical treatment and scored for chromosome aberration

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

4-chloro-α,α,α-trifluorotoluene

EC Number:

202-681-1

EC Name:

4-chloro-α,α,α-trifluorotoluene

Cas Number:

98-56-6

Molecular formula:

C7H4ClF3

IUPAC Name:

1-chloro-4-(trifluoromethyl)benzene

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): compound 38502
- Storage condition of test material: room temperature
- Other: received on May 26, 1983
The test article was measured and dissolved in DMSO to appropriate concentrations, immediatly before use. Approximately 10 to 20 minutes were taken between the time the test article was sulubilized and the final treatment of cells.

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

- Originally obtained from American Type Culture Collection, Rockville, Maryland
- Properly maintained: yes (cryopreserved)

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S-9 containing 2.4 mg/ml of NADP, 4.5 mg/ml of isocitric acid and 15 µl of Aroclor induced rat liver homogenate/ml.

Test concentrations with justification for top dose:

The test article was tested at six decreasing dose levels from 130.0 nl/ml to 29.99 nl/ml in the activated and non-activated systems.

Vehicle / solvent:

Solvent: DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

triethylenemelamine

cyclophosphamide

Details on test system and experimental conditions:

DURATION
Cells were treated with test substance without S9 for 12 hours, with S9 for 2 hours.

NUMBER OF CELLS EVALUATED: 100

DETERMINATION OF CYTOTOXICITY
- Method: rate of surival cells

Statistics:

Percentage of cells with aberration.

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The relative cell survival (RCS): 0% at 200 nl/ml, RCS 87% at 60 nl/ml in activated system - 0% at 200 nl/ml and 103 at 60 nl/ml in the nonactivated system.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: strain/cell type: CHO-K1

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Results of chromosome aberration assay-14 hours with activation

Test article concentration	Number of cells analyzed	Number of aberrations per cell	% of cells with aberration
130.00 nl/ml	Cells were dead	-	-
110.07 nl/ml	Cells were dead	-	-
90.25 nl/ml	100	0	0
70.40 nl/ml	100	0.02	2
49.98 nl/ml	100	0.03	2
29.98 nl/ml	100	0.04	4
Negative control	100	0.01	1
Positive control 50 µg/ml	100	1.07	59
Solvent control	100	0.01	1

Results of chromosome aberration assay-14 hours without activation

Test article concentration	Number of cells analyzed	Number of aberrations per cells	% of cells with aberration
80.00 nl/ml	Cells were dead	-	-
70.00 nl/ml	100	0.02	2
59.97 nl/ml	100	0.02	2
49.97 nl/ml	100	0.01	1
39.98 nl/ml	100	0.04	4
29.98 nl/ml	100	0.03	2
Negative control	100	0.04	3
Positive control 1.0 µg/ml	100	1.34	65
Solvent control	100	0.06	4

Results of chromosome aberration assay-24 hours with activation

Test article concentration	Number of cells analyzed	Number of aberrations per cell	% of cells with aberration
130.00 nl/ml	Cells were dead	-	-
110.07 nl/ml	Cells were dead	-	-
90.25 nl/ml	100	0.01	1
70.40 nl/ml	100	0.05	4
49.98 nl/ml	100	0.03	3
29.98 nl/ml	100	0.05	5
Negative control	100	0.04	4
Positive control 50 µg/ml	100	2.98	81
Solvent control	100	0.03	3

Results of chormosome aberration assay-24 hours without activation

Test article concentration	Number of cells analyzed	Number of aberrations per cell	% of cells with aberration
80.00 nl/ml	Cells were dead	-	-
70.00 nl/ml	100	0.02	2
59.97 nl/ml	100	0	0
49.97 nl/ml	100	0.01	1
39.98 nl/ml	100	0.01	1
29.98 nl/ml	100	0.01	1
Negative control	100	0.02	2
Positive control 1.0 µg/ml	100	1.17	47
Solvent control	100	0.03	3

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Compared to the cells with chromosome aberrations in the solvent control, none of the test doses showed a significant increase in the frequency of cells with chromosome aberrations in the activated and nonactivated system.
In this study no indication of a dose response was observed.
In this study the positive controls caused a significant increase in the number of cells with chromosome aberrations.

Executive summary:

The test item was tested in the chromosome aberration assay using Chinese hamstar ovary cells, with and without metabolic activation. The treated cells were harvested at 14 hours and 24 hours following the initiation of chemical treatment and scored for chromosome aberration. The results indicate that under the test condition, the test article did not cause a significant increase in the frequencies of chromosome abertration in the Chinese hamster ovary cells with and without rat S9 activation.