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Toxicological information

Genetic toxicity: in vitro

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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Mutagenesis by normal metabolites in Escherichia coli: phenylalanine mutagenesis is dependent on error-prone DNA repair
Author:
Sargentini, N. J.; Smith, K.C.
Year:
1986
Bibliographic source:
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Volume 161, Issue 2, July 1986, Pages 113-118

Materials and methods

Principles of method if other than guideline:
Scientific investigation. Principle similiar to Ames-test. In search of a model for the production of 'spontaneous' mutations induced by DNA damage produced during normal metabolism, 19 amino acids were tested for mutagenicity.
GLP compliance:
no
Remarks:
study performed prior to implementation of GLP
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
L-alanine
EC Number:
200-273-8
EC Name:
L-alanine
Cas Number:
56-41-7
Molecular formula:
C3H7NO2
IUPAC Name:
L-alanine

Method

Target gene:
uvrB, uvrB umuC
Species / strainopen allclose all
Species / strain / cell type:
E. coli, other: SR250 (uvrB5)
Details on mammalian cell type (if applicable):
derived from E coli K-12 strain, SR248 (wild-type)
Additional strain / cell type characteristics:
other: DNA repair-deficient strain
Species / strain / cell type:
E. coli, other: SR1034 ( uvrB5 umuC 122::Tn5)
Details on mammalian cell type (if applicable):
derived from E coli K-12 strain, SR248 (wild-type)
Additional strain / cell type characteristics:
other: DNA repair-deficient strain
Metabolic activation:
without
Test concentrations with justification for top dose:
2mM L-alanine
Controls
Untreated negative controls:
yes
Remarks:
(wild type of E. coli)
Negative solvent / vehicle controls:
no
True negative controls:
yes
Remarks:
(wild type of E. coli)
Positive controls:
no
Details on test system and experimental conditions:
Plate assay and tube assay
Evaluation criteria:
Median values for mutants and CFU (colony forming units) were used to determine the median mutant frequencies for each assay.
Statistics:
Significant effects on mutagenesls were defined by either of two criteria.
That is, the mean mutant frequency + 1 SD (range) for the amino-acid-supplemented plates did not overlap the range for the control plates, and the mean relative (test/control) range for the uvrB strain did not overlap the mean relative range for the uvrB umuC strain.

Results and discussion

Test results
Species / strain:
E. coli, other: Both SR250 and SR1034
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
not applicable
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

L-Alanine does not exhibit mutagenic activity under the conditions of this bacterial reverse mutation assay.