Levoglutamide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-11-15 to 2000-12-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Original study in Japanese, only summary in English available.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Levoglutamide

EC Number:

200-292-1

EC Name:

Levoglutamide

Cas Number:

56-85-9

Molecular formula:

C5H10N2O3

IUPAC Name:

L-glutamine

Method

Target gene:

Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and Escherichia coli strain WP2uvrA

Species / strain

Species / strain 1

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not specified

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

1) Dose finding test: 1.2 µg/plate, 4.9 µg/plate, 20 µg/plate, 78 µg/plate, 313 µg/plate, 1250 µg/plate, 5000 µg/plate.
2) Main test: 313 µg/plate, 625 µg/plate, 1250 µg/plate, 2500 µg/plate, 5000 µg/plate.

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Test results 5

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Additional information on results:

In the dose-finding test and the main test, neither increase of more than two-fold in the number of revertant colonies when compared with the negative control nor dose-response relationship was observed in the plate at any dose level treated with the test article in both frameshift and base-pair substitution tester strains with or without metabolic activation.

A more than two-fold increase in the number of revertant colonies was observed in comparison with the negative control in the plate treated with the positive control article for each tester strain, thus it was determined that the study was conducted appropriately.

In conclusion, L-Glutamine was considered to be non-mutagenic under the conditions of this study.

There was neither growth inhibition nor precipitation of the test article on the plate with or without metabolic activation.

No bacterial proliferation was observed in sterility test of the test article and of the S9 mix.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

L-Glutamine did not show mutagenic acticivity in a GLP guideline study according to a Japanes test guideline. Testing was in absence and presence of the metabolic activation system S9 mix. The maximum dose was 5000 µg/plate.