Glyoxylic 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Data generated according to international accepted valid testing method.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

GLP compliance:

yes

Remarks:

Pharma Research Toxicology and Pathology, Hoechst AG, Frankfurt, Germany

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Glyoxylic acid

EC Number:

206-058-5

EC Name:

Glyoxylic acid

Cas Number:

298-12-4

Molecular formula:

C2H2O3

IUPAC Name:

2-oxoacetic acid

Details on test material:

- Name of test material: Glyoxylic acid
- Physical state: liquid
- Lot/batch No.: R 200.306
- Storage condition of test material: dark at 4 °C

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium, other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

microsomal enzyme systems (S-9 fraction) from Aroclor 1254-induced male Sprague-Dawley rat liver

Test concentrations with justification for top dose:

0, 4, 20, 100, 500, 2500, 5000 or 10000 µg/plate

Vehicle / solvent:

- Vehicle/solvent used: water bidest.

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

sterility control

Negative solvent / vehicle controls:

yes

Remarks:

solvent (background) control

True negative controls:

no

Remarks:

with and without S-9 mix , in TA 1535, TA 1537, TA 1538, TA 98 and TA 100

Controls 2

Positive control substance:

other: 2-aminoanthracene

Remarks:

with S9-mix in all strains tested

Controls 3

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

with S9-mix in all strains tested

Controls 4

Positive controls:

yes

Positive control substance:

other: N-methyl-N-nitrosoguanidine

Remarks:

without S9-mix in WP2uvrA

Controls 5

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

without S9-mix in TA 98, TA 1538

Controls 6

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without S9-mix in TA 1537

Controls 7

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

without S9-mix in TA 100, TA 1535

Details on test system and experimental conditions:

METHOD OF APPLICATION:
- in agar (plate incorporation)

DURATION
- Expression time (cells in growth medium): 48-72 hours


SELECTION AGENT :
- minimal amino acid solution 0.05 mM histidine + 0.05 mM biotin (for E.coli histidine was replaced by 0.5 mM tryptophan)

DETERMINATION OF CYTOTOXICITY
- Method: colonies (his+ revertants) were counted

Results and discussion

Test results

Test results 1

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

2500 µg/plate and higher concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

2500 µg/plate and higher concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Control plates without mutagen showed that the number of spontaneous revertant colonies was similar to that described in the literature. All the positive control compounds gave the expected increase in the number of revertant colonies.

Toxicity: The test compound proved to be toxic to most of the bacterial strains at 2500 µg/plate.
5000 µg/plate was chosen as top dose level for the mutagenicity study.

Mutagenicity: In the absence of the metabolic activation system the test compound did not show a dose dependent increase in the number of revertants in any of the bacterial strains. Also in the presence of a metabolic activation system, treatment of the cells with Glyoxylic acid did not result in relevant increases in the number of revertant colonies.

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

Executive summary:

In a reverse gene mutation assay (Müller W, 1988) in bacteria strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 of S. typhimurium and WP2 uvrA of E. Coli were exposed to Glyoxylic Acid at concentrations of 0, 4, 20, 100, 500, 2500, 5000 or 10000 µg/plate (3 plates/dose) in the presence and absence of mammalian metabolic activation applying the standard plate method. Cytotoxicity was observed at 2500 µg/plate and higher doses. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background.

This study is classified as acceptable and satisfies the requirement for test guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.