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Toxicological information

Genetic toxicity: in vitro

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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
Controlsopen allclose all
Untreated negative controls:
yes
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
without metabolic activation
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 resultsopen allclose all
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with
Genotoxicity:
positive
Remarks:
(Weakly positive)
Cytotoxicity / choice of top concentrations:
cytotoxicity
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.