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
Study period:
from September to October 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restrictions; the applied strains of bacteria may not detect certain oxidising mutagens, cross-linking agents

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
- TA 102 or E.coli WP2 strains are not included
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
Histidine gene locus
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 1538 and TA 98
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced male Wistar rat liver S9 mix
Test concentrations with justification for top dose:
100, 250, 500, 1000, 2500, 5000 µg/plate








Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
benzo(a)pyrene
cyclophosphamide
other: anthracen-2-amine

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 1538 and TA 98
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 1538 and TA 98
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
TA 1537
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 1538 and TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: TA 1537, TA 1538, TA98
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

None of the two tester strains (TA 1535, TA 100) which detect base-pair substitutions as genetic endpoint exhibited a mutagenic response. In contrast all of the three tester strains which detect frame-shift mutations (TA 1537, TA 1538 and TA98) showed increased reversion to prototrophy in the absence of S9 mix. However, no mutagenic response could be observed in the experiments which included rat liver S9 as an extrinsic metabolizing system. Growth inhibition of the background lawn was only observed in the experiments with TA 1537(+S9), TA1535 (-S9) and TA100 (-S9) at the highest dose tested (5 mg/plate).

There were precipitates in the agar found starting from 1.0 mg/plate in strains TA 1535, TA 100 and TA 1537 in the absence and presence of S9 mix and in the tests with TA 1538 and T A98 without 89 mix from 0.5 mg/plate and from 2.5 mg/plate with S9 mix.

Appropriate positive control chemicals induced marked increases in revertant colony numbers with all strains.

Applicant's summary and conclusion

Executive summary:

The mutagenic potential of the test substance was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 1535, 1538 and TA 1537 in the presence and absence of S9 mix according to OECD TG 471. Evaluation of the data indicates that the test substance is a mutagen in the Ames Salmonella/microsome test. However, the mutagenic effect could only be observed in the experiments without S9 mix. Since the mutagenic effect was only observed in strains TA 1537, TA 1538 and TA98 the genotoxic potential of the test substance is based on the induction of frame-shift mutations.