Androsta-3,5-dien-17-one, 3-(acetyloxy)-, cyclic 17-(2,2-dimethyl-1,3-propanediyl acetal)

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:

Oct 2002

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:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

ZK 67985

IUPAC Name:

ZK 67985

Details on test material:

- Batch No.: 51537013-021

Method

Target gene:

Histidine gene locus

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 1535, TA 100, TA 1537, TA 98, TA 102

Metabolic activation:

with and without

Metabolic activation system:

liver S9-mix from Aroclor 1254 -treated rats

Test concentrations with justification for top dose:

Dienolacetat-ketal: eight concentrations from 3 to 5000 µg/plate
Sodium azide: 10 µg/plate (TA 1535 and TA 100, without metabolic activation)
4-Nitro-o-phenyl-diamine: 10 µg/plate (TA 98, without metabolic activation) and 50 µg/plate (TA 1537, without metabolic activation)
Methyl methane sulfonate: 4 µl/plate (TA 102, without metabolic activation)
2-Aminoanthracene: 2.5 µg/plate (TA 1535, TA 1537, TA 98, TA 100, with metabolic activation) and 10 µg/plate (TA 102, with metabolic activation)

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: Sodium azide, 4-Nitro-o-phenylene-diamine, Methyl methane sulfonate, 2-Aminoanthracene

Results and discussion

Test results

Species / strain:

other: Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 98, TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative 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

The test item precipitated in the overlay agar at the following concentrations (µg/plate):

Strain	without S9 mix	with S9 mix
TA 1535	2500 -5000	-
TA 1537	5000	5000
TA 98	2500 -5000	100 -5000
TA 100	5000	5000
TA 102	2500 -5000	1000 -5000

The undissolved particles had no influence on the data recording.

Applicant's summary and conclusion

Executive summary:

Dienolacetat-ketal was tested in the Salmonella typhimurium Reverse Mutation assay for point-mutagenic effects in doses up to the highest recommended dose of 5000 µg/plate on the five histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537, TA 98 and TA 102.

Precipitates in the agar were found predominantly at 2500 and/or 5000 µg/plate in all strains tested with and without metabolic activation (except TA 1535 only without metabolic activation). The undissolved particles had no influence on the data recording.

There was no evidence for a mutagenic activity of Dienolacetat-ketal, when tested up to the highest recommended dose level in the absence and presence of S9 mix.