Androst-5-en-17-one, 3,15-bis(2,2-dimethyl-1-oxopropoxy)-7-hydroxy-, (3.beta.,7.beta.,15.alpha.)-

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:

other information

Study period:

Jul 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well reported GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

no bacteria strain included to detect cross-linking mutagens

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

7 beta-Hydroxy-3 beta,15 alpha-dipivaloyloxy-5-androsten-17-one

EC Number:

617-708-6

Cas Number:

85390-94-9

Molecular formula:

C29 H44 O6

IUPAC Name:

7 beta-Hydroxy-3 beta,15 alpha-dipivaloyloxy-5-androsten-17-one

Details on test material:

- Name of test material (as cited in study report): ZK 92136
- Batch No.: 21604815

Method

Target gene:

Histidine gene locus

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 1535, TA 100, TA 1537, TA 1538, TA 98

Metabolic activation:

with and without

Metabolic activation system:

liver S9-mix from Aroclor 1254 -treated rats

Test concentrations with justification for top dose:

Dipivalat: six concentrations from 0.05 to 2.5 mg/plate
Sodium azide: 5 µg/plate (TA 1535 and TA 100)
2-Nitrofluorene: 10 µg/plate (TA 1538 and TA 98)
9-Acridinamine: 100 µg/plate (TA 1537)
Benzo[a]pyrene: 2.5 µg/plate (TA 100 and TA 98)
Cyclophosphamide: 400 µg/plate (TA 1535)
2-Aminoanthracene: 2 µg/plate

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Sodium azide (TA 1535 and TA 100), 2-Nitrofluorene (TA 1538 and TA 98), 9-Acridinamine (TA 1537), Benzo[a]pyrene (TA 100 and TA 98), Cyclophosphamide (TA 1535), 2-Aminoanthracene

Results and discussion

Test results

Species / strain:

other: Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538, TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

growth inhibition was observed in all strains at 1.0 mg/plate onwards with and without S9 mix; precipitates in the agar were detectable starting at 0.5 mg/plate in all strains

Vehicle controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

Dipivalat was tested in the Salmonella/microsome test for point-mutagenic effects in doses up to 2500 µg/plate on the five histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98.

A cytotoxic effect was seen in all strains at doses of 1.0 mg/plate and above with and without metabolic activation. Precipitates in the agar were detectable starting at 0.5 mg/plate in all strains.

There was no evidence for a mutagenic activity of Dipivalat, when tested up to the cytotoxic and precipitating dose levels in the absence and presence of S9 mix.