(17α)-17-hydroxy-3-oxoandrost-4-ene-17-carbonitrile

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:

Jan to Feb 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well reported GLP study, comparable to Guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

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 (e.g. TA 102)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

17 beta-Cyano-17 alpha-hydroxy-4-androstene-3-one

IUPAC Name:

17 beta-Cyano-17 alpha-hydroxy-4-androstene-3-one

Details on test material:

- Name of test material (as cited in study report): ZK 74.804
- Batch No.: BA 76700

Method

Target gene:

Histidine gene locus

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

liver S9-mix from Aroclor 1254 -treated rats

Test concentrations with justification for top dose:

AD-Cyanhydrin: six concentrations from25 to 1000 µg/plate
9-Acridinamine: 100.0 µg/plate
2-Aminoanthracene: 2.0 µg/plate
2-Nitrofluorene: 10.0 µg/plate
Benzo[a]pyrene: 5.0 µg/plate
Sodium azide: 2.0 µg/plate
Cyclophosphamide: 400 µg/plate

Controls

Negative solvent / vehicle controls:

yes

Remarks:

DMSO or phosphate buffer pH 7.4, 0.1 mol/l

Positive controls:

yes

Positive control substance:

other: 9-Acridinamine, 2-Aminoanthracene, 2-Nitrofluorene, Benzo[a]pyrene, Sodium azide, Cyclophosphamide

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

growth inhibition were observed on TA 1535, TA 1537 and TA 1538 starting at 500 µg/plate and on TA 98 at 1000 µg/plate without S9-mix

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

Precipitates in the agar were found at least in the highest concentration.

Applicant's summary and conclusion

Executive summary:

AD-Cyanhydrin was examined for mutagenic activity up to 1000 µg/plate in the five histidine-dependent Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98 with and without metabolic activation. Growth inhibition could be observed on TA 1535, TA 1537 and TA 1538 starting at 500 µg/plate and on TA 98 at 1000 µg/plate without S9-mix. Precipitates in the agar were found at least in the highest concentration

There was no evidence for a mutagenic activity of AD-Cyanhydrin, when tested up to the dose level of 1000 µg/plate in the absence and presence of S9 mix.