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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
neither S.typh TA102 nor E. coli WP2 uvrAor E.coli WP2 uvrA (pKM101) were tested.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MRD-91-934
- Physical state: colourless liquid
- Analytical purity: considered 100%
- Lot/batch No.: 1
- Expiration date of the lot/batch: 31 May 1996
- Storage condition of test material: room temperature

Method

Species / strain
Species / strain / cell type:
other: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538
Metabolic activation:
with and without
Metabolic activation system:
S9 from Arochlor induced rat livers
Test concentrations with justification for top dose:
32, 100, 320, 1000, 3200 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controlsopen allclose all
Negative solvent / vehicle controls:
yes
Remarks:
0.1 mL/plate DMSO
Positive control substance:
other: 2-aminoanthracene (2AA) 5 µg/plate (TA98, TA100, TA1535, TA1537, TA1538 + S9); N-methyl-N-nitro-N-nitrosoguanidine (MNNG) 10 µg/plate (TA100, TA1535 -S9), 9-aminoacridine (9AA) 100 µg/plate (TA1537 -S9); 2-Nitrofluorene (2NF) 5µg/plate (TA98, TA1538 -S9).
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 2 days

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: Numbers of revertant colonies per plate counted
Evaluation criteria:
Revertant colonies counted and compared to number of revertant colonies on solvent control plates. Any value that was equal to or greater than three times the mean value of the concurrent vehicle control was considered positive.
Statistics:
Mean plate count and SD for each dose point was determined.

Results and discussion

Test results
Species / strain:
other: TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

In the initial assay neither a positive response nor a dose-related increase in revertants was observed for tester strains TA98, TA100, TA1535 and TA1538. An increase in revertant colonies which was equal to three times vehicle control was noted for TA1537 without metabolic activation at 100 µg/plate. This increase was due to the low mean value of the vehicle control. As the number of revertant colonies was identical to the non treated control this was considered not to be a positive response and was considered not to be biologically significant. Toxicity, either a reduction in the number of revertant colonies or a reduction in the background lawn, was present for all five strains.

 

In a repeat assay, increases were seen for tester strain TA1537 without metabolic activation at 320 µg/plate and with metabolic activation at 32 -1000 µg/plate. These apparent increases were due to the low mean value of the vehicle control. Since all test material dose data produced revertant colony counts that were no greater than the normal range of the vehicle control, these were considered not to be positive responses and were considered not to be of biological significance. A dose-related increase in revertant colonies was not observed for any of the tester strains. Toxicity, either a reduction in the number of revertant colonies or a reduction in the background lawn, was present for all five strains.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

MRD-91-934 was negative for genotoxicity in the microbial mutagenesis (Ames) assay. MRD-91-934 did not induce a significant increase in revertant colonies in any of the five tester strains with or without metabolic activation at doses up to and including 3200 µg/plate.
Executive summary:

MRD-91-934 was negative for genotoxicity in the microbial mutagenesis (Ames) assay. MRD-91-934 did not induce a significant increase in revertant colonies in any of the five tester strains with or without metabolic activation at doses up to and including 3200 µg/plate.