Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Principles of method if other than guideline:
The point-mutagenic effects were investigated in doses up to 12000 µg/plate on four histidine-auxotropic Salmonella typhimurium LT2 strains, for each substance, dose level and strain 4 plates were used. After an incubation period of 48 h the number of revertant colonies per plate were counted.
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
3-Aminocrotonsäuremethylester, white powder, content and identity not certified

Method

Target gene:
histidin gene locus
Species / strain
Species / strain / cell type:
other: TA 1535, TA 100, TA 1537, TA 98
Metabolic activation:
with and without
Metabolic activation system:
rat liver homogenate (S-9 mix)
Test concentrations with justification for top dose:
3-Aminocrotonsäuremethylester: 375-12000 µg/plate
Sodium azide: 10 µg/plate
Nitrofurantoin: 0.2 µg/plate
4-Nitro-o-phenylendiamin: 10 µg/plate (TA 1537) and 0.5 µg/plate (TA 98)
2-Aminoanthracene: 3 µg/plate
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
Ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Sodium azide (TA 1535, without S9-mix), Nitrofurantoin (TA 100, without S9-mix), 4-Nitro-o-phenylendiamin (TA 1537 and 98, without S9-mix), 2-Aminoanthracene (with S9-mix)

Results and discussion

Test results
Species / strain:
other: TA 1535, TA 100, TA 1537, TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at doses of 1500 µg/plate and higher bacteriotoxic effects, but these were only weak strainspecific effects, so that this range could nevertheless be used for evaluation purposes
Vehicle controls validity:
valid
Untreated negative 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

Executive summary:

Methyl 3 -aminocrotonate was tested in the Salmonella/microsome test for point-mutagenic effects in doses up to 12000 µg/plate on the four histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537 and TA 98.

Doses up to and including 750 µg/plate did not cause any bacteriotoxic effects and at higher doses the substance had only a weak strainspecific bacteriotoxic effect, so that this range could nevertheless be used for evaluation purposes.

No evidence for a mutagenic activity of methyl 3 -aminocrotonate was found.