Levoglutamide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

L-Glutamine did not exhibit genetic toxicity in two in vitro GLP guideline studies:

- In vitro bacterial reverse mutation test

- In vitro mammalian chromosome aberration test

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

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

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not specified

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.

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

L-Glutamine was tested for genetic toxicity in two in vitro GLP guideline studies, a bacterial reverse mutation test and a mammalian cell chromosome aberration test. Neither the Ames-test nor the mammalian cell chromosome aberration test (both according to Japanese Guidelines for Screening Mutagenicity Testing of Chemicals) did exhibit any genetic toxicity.

These results were foreseeable as L-glutamine is a naturally occurring amino acid. L-Glutamine is a normal constituent in living cells occurring as a free amino acid, bound to RNA and incorporated in proteins and peptides. It is ingested daily in significant amounts. Therefore human exposure through food is orders of magnitude higher than the anticipated levels of exposure from the uses covered by this dossier. L-Glutamine is present in significant amounts in human body fluids – e. g. human blood plasma (Cynober 2002) - as well as in human cells. It is a basic metabolite and building block of all living organisms and therefore a genotoxic/mutagenic potential could be excluded.

 

Cynober L (2002): Plasma Amino Acid Levels With a Note on Membrane Transport: Characteristics, Regulation, and Metabolic Significance. Nutrition 18 (9), 761-766

Justification for selection of genetic toxicity endpoint

Key study. Additional key study: 7231

Justification for classification or non-classification

L-Glutamine is negative in several in vitro mutation tests. Furthermore, as L-glutamine is a ubiquitously occurring substance in food, the environment and even in human body fluids there is no concern with respect to mutagenicity. L-Glutamine should not be classified as a mutagen.