Retinyl palmitate

Genetic toxicity: in vitro

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:

July 28, 1982 - August 23, 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: QA checked; GLP compliance statement; Adequate and reliable

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Salmonella typhimurium strain TA 1538 additionally used

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Retinyl palmitate

EC Number:

201-228-5

EC Name:

Retinyl palmitate

Cas Number:

79-81-2

Molecular formula:

C36H60O2

IUPAC Name:

(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-yl hexadecanoate

Details on test material:

- Lot/batch No.: confidential

Method

Target gene:

His gene: Amino acid histidine - GC base pairs

Species / strain

Species / strain 1

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 2

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:

3.3, 10, 33, 40, 100, 330, 400 and 3300 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:

not specified

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
660 mg/ml: maximal solubility
82.5 mg/ml: maximal solubility 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 results

Test results 1

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

Test results 2

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 additional 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 palmitate 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 3.3, 10, 33, 40, 100, 330, 400 and 3300 µg/plate.

Executive summary:

Vitamine A palmitate was tested for mutagenic activity in the standard Salmonella/mammalian microsome plate incorporation assay (Ames test). No mutagenic effect of Vitamin A palmitate could be detected at concentrations of 3300, 400, 330, 100, 40, 33, 10 and 3.3 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 Vitamin A palmitate per se, nor one of its metabolites being formed under the described in vitro conditions are mutagenic.