Pregna-1,4,6-triene-3,20-dione, 17-hydroxy-

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 2002 to August 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Deviations:

no

Remarks:

according to current version (2020) no bacteria strain included to detect cross-linking mutagens

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

1

Reference substance name:

17-Hydroxy-1,4,6-pregnatriene-3,20-dione

EC Number:

613-906-1

Cas Number:

66212-25-7

Molecular formula:

C21 H26 O3

IUPAC Name:

17-Hydroxy-1,4,6-pregnatriene-3,20-dione

Constituent 1

Reference substance name:

ZK 5668

IUPAC Name:

ZK 5668

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

Metabolic activation:

with and without

Metabolic activation system:

phenobarbital/beta-naphthoflavone induced liver S9-mix

Test concentrations with justification for top dose:

1,4,6-Trienol: first experiment: eight concentrations from 3 to 5000 µg/plate; second experiment 10 concentrations from 0.3 to 5000 µg/plate
Sodium azide: 10 µg/plate
4-Nitro-o-phenylenediamine: 10 µg/plate (TA 98) or 50 µg/plate (TA 1537)
Methyl methane sulfonate: 4 µl/plate
2-Aminoanthracene: 2.5 µg/plate (10 µg/plate in TA 102)

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

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

Key result

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:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Precipitation of the test item was observed without metabolic activation in strains TA 1537 and TA 102 at 5000 µg/plate in the first experiment, and from 1000 µg/plate up to 5000 µg/plate in the second experiment.

No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with ZK 5668 at any concentration level, neither in the presence nor absence of metabolic activation (S9 mix). However, in the first experiment an increase in revertant colony numbers was observed in strain TA 102 in the absence of metabolic activation, already beginning at the lowest concentration but with no dose dependent increase. The threshold of two times the number of the corresponding solvent control was reached at 100 µg/plate. In order to check this questionable effect an additional experiment was performed with an adjusted concentration range of 0.3 up to 5000 µg/plate. No increase in revertant colony numbers was observed in this additional experiment and the effects observed in the first experiment were judged to be based on biologically

irrelevant fluctuations in the number of colonies.

Applicant's summary and conclusion

Conclusions:

No increase of reverse gene mutations in bacteria induced by the test item up to maximum concentration of 5 mg/ plate.

Executive summary:

1,4,6 -Trienol (ZK 5668) was examined in two experiments for mutagenic activity up to 5000 µg/plate in the five histidine-dependent Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without metabolic activation.

No cytotoxic effects were seen up to 5000 µg/plate. Precipitation of the test item was observed without metabolic activation in strains TA 1537 and TA 102 at 5000 µg/plate in the first experiment, and from 1000 µg/plate up to 5000 µg/plate in the second experiment.

There was no evidence for a mutagenic activity of 1,4,6 -Trienol, when tested up to the maximum recommended dose level of 5000 µg/plate in the absence and presence of S9 mix.