Estra-4,9-dien-3-one, 17-hydroxy-, (17.beta.)-

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 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well reported Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

(1S,3aS,3bS,11aS)-1-hydroxy-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,10H,11H,11aH-cyclopenta[a]phenanthren-7-one

EC Number:

612-953-5

Cas Number:

6218-29-7

Molecular formula:

C18 H24 O2

IUPAC Name:

(1S,3aS,3bS,11aS)-1-hydroxy-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,10H,11H,11aH-cyclopenta[a]phenanthren-7-one

Details on test material:

- Name of test material (as cited in study report): ZK 47359
- Batch No.: 54512003
- purity: 99.916%

Method

Target gene:

Histidine (Salmonella) or Tryptophan (E. coli) gene locus

Species / strain

Species / strain / cell type:

bacteria, other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

liver S9-mix from Aroclor 1254 -treated rats

Test concentrations with justification for top dose:

Hydroxyestradienon: six concentrations from 0.1 to 5.0 mg/plate
4-Nitro-o-phenylenediamine: 10 µg/plate
2-Aminoanthracene: 2.5 and 10 µg/plate
2-Nitrofluorene: 10 µg/plate
Benzo[a]pyrene: 2.5 µg/plate
Sodium azide: 5 µg/plate
Cyclophosphamide: 400 µg/plate
N-Methyl-N-nitro-N-nitrosoguanidine: 5 µg/plate
Ethyl methanesulfonate: 5 µl/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: 4-Nitro-o-phenylenediamine, 2-Aminoanthracene, 2-Nitrofluorene, Benzo[a]pyrene, Sodium azide, Cyclophosphamide, N-Methyl-N-nitro-N-nitrosoguanidine, Ethyl methanesulfonate

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

growth inhibition was observed only in the strain TA 100 from 2.5 mg/plate onwards; precipitates in the agar were found starting at 2.5 mg/plate

Vehicle controls validity:

valid

Positive controls validity:

other: yes, but cyclophosphamide did not give a positive result with metabolic activation in strain TA1535; nevertheless, experiment was considered valid since activity of the S9 mix was demonstrated with the second positive control substance 2-Aminoanthracene

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

Hydroxyestradienon was examined for mutagenic activity up to 5000 µg/plate in the five histidine-dependent Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98 and in the tryptophan-dependent Escherichia coli strain WP2uvrA using the direct plate incorporation procedure with and without metabolic activation.

A cytotoxic effect was seen from 2.5 mg/plate onwards in the strain TA 100. Precipitates in the agar were found starting at 2.5 mg/plate.

There was no evidence for a mutagenic activity of Hydroxyestradienon, when tested up to the maximum recommended dose level of 5 mg/plate in the absence and presence of S9 mix.