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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
Study period:
June to July 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restrictions: E.coli WP2 strain or S. typhimurium TA 102 were not tested

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
no plate incorporation procedure performed
Principles of method if other than guideline:
Preincubation modification was performed
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diflucortolone-21-valerate (ZK 22612)
- Lot/batch No.: 41054493

Method

Target gene:
Histidine gene locus
Species / strainopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced male rat liver S9 mix
Species / strain:
S. typhimurium TA 1538
Additional strain characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced male rat liver S9 mix
Test concentrations with justification for top dose:
All strains: 0.05, 0.1, 0.25, 0.5, 1.0, 2.0 mg/plate
Vehicle:
DMSO
Controls
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: without metabolic activation: 9-AA, 2-NF, NaN3; with metabolic activation: 2-AA, BP, CP, DMNA.

Results and discussion

Test results
Key result
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes

Any other information on results incl. tables

None of the five tester strains showed increased reversion to prototrophy with diflucortolone-21-valerate at the concentrations tested, either in the absence or presence of S9 mix.

Precipitates in the agar were found starting at 0.25 or 0.50 mg diflucortolone-21-valerate/plate without S9 mix and 2 mg diflucortolone-21-valerate /plate with S9 mix.

Growth inhibition of the background lawn was not observed.

Negative controls and positive controls with known mutagens (9-acridinamine, hydrochloride; anthracen-2-amine; benzo[a]pyrene; cyclophosphamide; 2-nitro-9H-fluorene; sodium azide; N-nitrosodimethylamine) produced the expected numbers of revertant colonies.

Applicant's summary and conclusion

Conclusions:
negative

Executive summary:

The purpose of the Ames test was to investigate whether diflucortolone-21-valerate can induce point mutations using the preincubation modification. The five histidine-dependent strains of S. typhimurium TA1535, TA100, TA1537, TA1538 and TA98 were tested. The study was performed with and without metabolic activation, employed a range of diflucortolone-21-valerate concentrations from 0.05 to 2.0 mg per plate. No increased reversion to prototrophy were seen neither without nor with metabolic activation. Precipitates in the agar were found starting at 0.25 or 0.50 mg diflucortolone-21-valerate/plate without S9 mix and 2 mg diflucortolone-21-valerate /plate with S9 mix. Growth inhibition of the background lawn was not observed.