TCA

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Method similar to OECD guideline 476 and no data on GLP.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Trichloroacetic acid

EC Number:

200-927-2

EC Name:

Trichloroacetic acid

Cas Number:

76-03-9

IUPAC Name:

trichloroacetic acid

Details on test material:

- Name of test material (as cited in study report): trichloroacetic acid (TCA)

Method

Target gene:

TK+/- -3.7.2c heterozygote of the L5178Y mouse lymphoma cell line

Species / strain

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

TK +/- -3.7.2.C cells

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

750 - 2150 µg/mL

Controls

Controls 1

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

without metabolic activation

Controls 2

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

with metabolic activation

Details on test system and experimental conditions:

DURATION
- Exposure duration: 4 h
- Expression time (cells in growth medium): 2 days

NUMBER OF REPLICATIONS: two independent experiments

EVALUATION: Colonies were counted and the colony-size distribution determined using Artek model 880 automatic colony counter modified with a 10-turn potentiometer.

DETERMINATION OF CYTOTOXICITY
- Method: relative survival values were calculated according to the method described by Clive and Spector (1975) and include both the measure of the growth in the suspension and cloning phases of the assay.

Results and discussion

Test results

Test results 1

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

(Weakly positive)

Cytotoxicity / choice of top concentrations:

cytotoxicity

Test results 2

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

without

Genotoxicity:

ambiguous

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

When trichloroacetic acid was tested without activation, some concentrations caused a doubling of the background mutant frequency, while in other cultures at similar or higher concentrations, it induced mutant frequencies that were less than twice the background. Thus,

without activation, trichloroacetic acid was equivocal. The addition of S9 induced a slight increase in the mutant frequency at concentrations yielding greater than 10% survival. Both small and large colony mutants were induced. This was repeated in a separate

experiment, which confirmed the very weak positive response.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
other: very weak positive response

When trichloroacetic acid was tested without activation, some concentrations caused a doubling of the background mutant frequency, while in other cultures at similar or higher concentrations, it induced mutant frequencies that were less than twice the background. Thus, without activation, trichloroacetic acid was equivocal. The addition of S9 induced a slight increase in the mutant frequency at concentrations yielding greater than 10% survival. Both small and large colony mutants were induced. This was repeated in a separate experiment, which confirmed the very weak positive response.

Executive summary:

The mutagenic activity of trichloroacetic acid has been studied in L5178Y/TK^+/-- 3.7.2.C mouse lymphoma cells at the tk focus. It was tested over a range of 750 - 2150 µg/mL. When trichloroacetic acid was tested without activation, some concentrations caused a doubling of the background mutant frequency, while in other cultures at similar or higher concentrations, it induced mutant frequencies that were less than twice the background. Thus, without activation, trichloroacetic acid was equivocal. The addition of S9 induced a slight increase in the mutant frequency at concentrations yielding greater than 10% survival. Both small and large colony mutants were induced. This was repeated in a separate experiment, which confirmed the very weak positive response.