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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD method and in accordance with GLP. Study material is well characterized.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
414-490-2
EC Name:
-
Cas Number:
154212-59-6
Molecular formula:
C11H9ClN2O5S
IUPAC Name:
4-nitrophenyl 1,3-thiazol-5-ylmethylcarbonate hydrochloride

Method

Target gene:
five histidine-requiring strains
Species / strain
Species / strain / cell type:
other: Salmonella typhimurium: TA1535, TA1537, TA98, TA100, TA102
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix(2.5%) from Aclor 1254-induced rat liver
Test concentrations with justification for top dose:
Concentration range in the main test (with metabolic activation): 1 ... 10000 µg/plate
Concentration range in the main test (without metabolic activation): 1 ... 10000 µg/plate
Vehicle / solvent:
dimethylsulfoxide
Controlsopen allclose all
Negative solvent / vehicle controls:
yes
Remarks:
vehicle controls used in parallel with the test material)
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
Migrated to IUCLID6: (mitomycin c: 0.25 ug/plate (TA102) without s-9.
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene: 1 ug/plate(TA100), 2.5 ug/plate (TA 98,TA1535&TA1537
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
Migrated to IUCLID6: 100 ug/plate (TA1537) without s-9.
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
Migrated to IUCLID6: 2.5 ug/plate (TA98) without s-9
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
Migrated to IUCLID6: 1 ug/plate (TA100,TA1535) without s-9
Details on test system and experimental conditions:
EXAMPLE--

Toxicity: precipitation was noted in the phosphate buffer from 50 ug/plate upwards, no preciptation was observed on agar plates

A toxic effect was observed:

- at XX ug /plate on TA98, TA100,TA102, and TA 1535 with and without s9 mix and on TA 1537 with S-9 mix;
- at XX ug/plate on TA100 and TA102 with and eithout S9 mix and on TA98 with S-9 mix.

No toxic effect was noted on TA 1537 without S-9 mix.
Evaluation criteria:
Evaluation criteria: test article would be considered mutagenic if:
the increase in the number of revertants is concentration-related;
at one concentration tested (at least), the number of revertant colonies is equal to or greater than twice the number of spontaneous revertants with TA 98, TA 100 and TA 102 and three times that observed with TA1535 and TA1537;
the positive responses described above were reproducible in an independent assay.
Statistics:
Mean and standard deviation of the plate counts for each treatment were determined

Results and discussion

Test results
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
500 ug upwards
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Comments: In the first assay, each strain was run under 1-10000 micrograms/plate. In the second assay, each strain was run under 10-2000 micrograms/plate.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Observations:
All positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with and without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9 mix were validated.


Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

No dose-related and reproducible increases in revertant colony frequency were observed in any tester strains at any concentration, both with and without S9. The test substance was not genotoxic in the Ames test