Dichloroacetic acid

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:

1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Although some details are missing, the study is consdired to be reliable, relevant and adequate.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Sodium dichloroacetate

EC Number:

218-461-3

EC Name:

Sodium dichloroacetate

Cas Number:

2156-56-1

Molecular formula:

C2H2Cl2O2.Na

IUPAC Name:

sodium dichloroacetate

Details on test material:

- Name of test material (as cited in study report): DCA; Sodium Dichloroacetate
- Analytical purity: pharmaceutical grade
- Other:provided by Cypros Pharmaceutical Corp. (Carlsbad, CA)

Method

Target gene:

histidine

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

mutagenicity: 0, 0.333, 0.667, 1.00, 3.33, and 5.00 mg DCA/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: no data

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: , 2-aminoanthracene

Remarks:

with S9: 2.5 µg/plate

Controls 2

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

without S9: TA98 1.0 µg/plate

Controls 3

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

without S9:TA100 and TA1535 2.0 µg/plate

Controls 4

Positive controls:

yes

Positive control substance:

other: ICR-191

Remarks:

without S9: TA 1537 2.0 µg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in 2 layer plates

SELECTION AGENT (mutation assays): histidine

NUMBER OF REPLICATIONS: at least in triplicate

DETERMINATION OF CYTOTOXICITY
- Method: Background bacterial lawn was evaluated for evidence of cytotoxicity. Dose-ranging studies demonstrated no cytotoxic effects of DCA up to 5 mg per plate using Salmonella strains TA100.

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

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):
negative with and without metabolic activation

Sodium dichloroacetate tested negative for genotoxicity with and without metabolic activation under the conditions of this test.

Executive summary:

Sodium dichloroacetate (DCA) pharmaceutical grade was tested for genotoxicity in a bacterial reverse mutation assay in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 with and without metabolic activation (S9).

Dose-ranging studies demonstrated no cytotoxic effects of DCA up to 5 mg per plate using Salmonella strains TA100. The mutagenicity testing itself was done at 0, 0.333, 0.667, 1.00, 3.33, and 5.00 mg DCA or with the positive controls per plate.

In all cases, there was no evidence for a mutagenic effect of DCA. The vehicle-treated and positive control plates gave predicted results.