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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
s9 liver microsomal fraction from rat
Test concentrations with justification for top dose:
Exp. 1 plate incorporation: 3.3 to 100 ug/plate,
Exp. 2: pre-incubation test: 6.6-333 ug/plate (TA 1535, TA1537), 1.0-100 (TA98, TA100)
Vehicle / solvent:
water
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
water
Positive controls:
yes
Remarks:
positive controls as seen below
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without S9 mix

Migrated to IUCLID6: TA 1535, TA100
Positive controls:
yes
Positive control substance:
other: 4-Nitro-o-phenylene-diamine
Remarks:
TA1537, TA98, without S9mix
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene
Remarks:
with S9 mix
Details on test system and experimental conditions:
METHOD OF APPLICATION: Experiment 1: in agar (plate incorporation); Experiment 2: preincubation


DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of revertants


Evaluation criteria:
- negative control in the laboratory historical range for each tester strain
- positive control chemicals produces responses in all tester strains within laboratory historical range
- Test substance is considered as mutagenic if:
- a dose-related and reproducible increase in the number of revertants occurs
- a substantial and reproducible increase for at least one test concentration (TA98, TA100 twofold increase, TA1535, TA1537 threefold increase compared to the corresponding solvent control)
Mean plate count should be at least three times the concurrent vehicle control group mean
- selected dose range should include a clearly toxic concentration or should exhibit limited solubility as demonstrated by the preliminary toxicity range-finding test or should extend to 5 mg/plate
Statistics:
none

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
in concentrations above 100 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
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

Under the conditions tested, the test substance did not cause gene mutations in the genome of the tester strains used.