Gona-1,3,5(10)-trien-17-ol, 13-ethyl-3-methoxy-, (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:

Januar to February 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

- Justification why the confirmation of the negative result is not considered necessary is not provided.

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-Methoxy-18-methyl-1,3,5(10)-estratrien-17 beta-ol

EC Number:

609-222-8

Cas Number:

3625-82-9

Molecular formula:

C20 H28 O2

IUPAC Name:

3-Methoxy-18-methyl-1,3,5(10)-estratrien-17 beta-ol

Method

Target gene:

Histidine gene locus

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced male rat liver S9 mix

Test concentrations with justification for top dose:

3, 10, 33, 100, 333, 1000, 2500, 5000 µg/plate

Vehicle / solvent:

DMF

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: without metabolic activation: Sodium azide, 4-Nitro-o-phenylenediamine, Methyl methane sulfonate; with metabolic activation: 2-Aminoanthracene

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

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

Precipitation of the test item was observed at the following concentrations (µg/plate):

Strain	Without S9 mix	with S9 mix
TA 1535	2500, 5000	2500, 5000
TA 1537	3 -5000	2500, 5000
TA 98	2500, 5000	5000
TA 100	5000	5000
TA 102	1000 - 5000	5000

Toxic effects were observed at the following concentrations (µg/plate):

Strain	Without S9 mix	with S9 mix
TA 1535	5000	-
TA 1537	2500, 5000	5000
TA 98	5000	-
TA 100	-	-
TA 102	2500, 5000	5000

The background growth was normal in all strains up to the highest concentrations with and without metabolic activation.

 

No substantial increases in revertant colony numbers of any of the five tester strains were observed following treatment with the test substance at any concentration level, either in the presence or absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

 

Appropriate control mutagens were used as positive controls and showed a distinct increase of induced revertant colonies.

Applicant's summary and conclusion

Executive summary:

The mutagenic potential of the test substance was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 in the presence and absence of S9 mix according to OECD TG 471. Evidence of mutagenic activity was not seen up to the maximum recommended dose level of 5000 µg/plate. No substantial increases in revertant colony numbers of any of the five tester strains were observed at any dose level in the presence and absence of metabolic activation. There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance. Appropriate control mutagens were used as positive controls and showed a distinct increase of induced revertant colonies.

Therefore, the test substance was considered to be non-mutagenic in the Salmonella typhimurium reverse mutation assay.