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

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (bacterial reverse mutation assay / Ames test, GLP, OECD TG 471): negative with and without metabolic activation

 

Link to relevant study records

Reference

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

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

Target gene:

Histidine gene locus

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)

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

1,4,6 -Trienol (ZK 5668) did not show a mutagenic potential in two experiments of a bacterial reverse mutation assay (S. typhimurim strains TA 1535, TA 1537, TA 98, TA 100 and TA 102) when tested up to the maximum recommended dose level of 5000 µg/plate in the absence and presence of extrinsic metabolic activation (liver S9 mix from phenobarbital/beta-naphthoflavone-treated rats). 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.

Short description of key information:
Gene mutation (Ames-Test, OECD TG471): negative with and without metabolic activation
[Schering AG, Report No. X512 -draft-, 2001-01-30]

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results there is no classification required according to Directive 67/548/EEC and Regulation (EC) 1272/2008 (CLP).