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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:
September 1, 1982 - September 13, 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP Compliance statement; Adequate and reliable
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Salmonella typhimurium strain TA 1538 additionally used
Principles of method if other than guideline:
Not relevant
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
His gene: Amino acid histidine - GC base pairs
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix: phenobarbital-induced rat liver homogenate fraction
Test concentrations with justification for top dose:
750, 500, 250, 125, 41.67, 12.5 and 4.167 µg/plate.
Upper concentration defined taking into account test item precipitation information.
Vehicle / solvent:
Solvent used: acetone
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
acetone
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
Migrated to IUCLID6: 200 µg/plate with strain TA 1535; solvent H2O
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Selection time (if incubation with a selection agent): 2 days

SELECTION AGENT (mutation assays): overlay agar containing Histidine

NUMBER OF REPLICATIONS: 4 replicate plates at each dose level

DETERMINATION OF CYTOTOXICITY
No data

OTHER: Solubility
Solvent: acetone
500 mg/ml: maximal solubility
1.25 mg/ml: maximal solubilty without subsequent precipitation on the plates
Evaluation criteria:
Increase/absence in the number of his+ revertant colonies
Statistics:
Mean values and standard deviation (SD)

Results and discussion

Test resultsopen allclose all
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:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
No addtional information
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 with metabolic activation
negative without metabolic activation

It is concluded that neither Vitamine A acetate per se nor one of its metabolites formed under the described experimental conditions induced genetic damage in Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 at concentrations of 750, 500, 250, 125, 41.67, 12.5 and 4.167 µg/plate.
Executive summary:

Vitamine A acetate was tested for mutagenic activity in the standard Salmonella/mammalian microsome plate incorporation assay (Ames test). No mutagenic effect of Vitamine A acetate could be detected at concentrations of 750, 500, 250, 125, 41.67, 12.5 and 4.167 µg/plate, neither in presence nor in absence of a phenobarbital-induced rat liver homogenate fraction (S-9 mix).

Positive controls with cyclophophamide show the validity of the test procedure and the activity of the S-9 mix.

The results obtained in the Ames test show that neither Vitamine A acetate per se, nor one of its metabolites being formed under the described in vitro conditions are mutagenic.