17H-Dicyclopropa[6,7:15,16]cyclopenta[a]phenanthren-17-one, octadecahydro-3,5-dihydroxy-10,13-dimethyl-, (3S,5R,6R,7R,8R,9S,10R,13S,14S,15S,16S)-

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:

March 1999

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:

other: S. typhimurium TA 1535, TA 100, TA 1537, TA 1538, TA 98

Metabolic activation:

with and without

Metabolic activation system:

liver S9-mix from Aroclor 1254 -treated rats

Test concentrations with justification for top dose:

Dimethylenketon: six concentrations from 0.1 to 5.0 mg/plate
Sodium azide: 5 µg/plate (TA 1535 and TA 100 without S9)
2-Nitrofluorene: 10 µg/plate (TA 1538 and TA 98 without S9)
4-Nitro-o-phenylenediamine: 10 µg/plate (TA 1537 without S9)
Benzo[a]pyrene: 2.5 µg/plate (TA 100 and TA 98 with S9)
Cyclophosphamide: 400 µg/plate (TA 1535 with S9)
2-Aminoanthracene: 5 µg/plate (with S9)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: Sodium azide (TA 1535 and TA 100, -S9), 2-Nitrofluorene (TA 1538 and TA 98, -S9), 4-Nitro-o-phenylenediamine (TA 1537, -S9), Benzo[a]pyrene (TA 100 and TA 98, +S9), Cyclophosphamide (TA 1535, +S9), 2-Aminoanthracene (+S9)

Key result

Species / strain:

other: Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538, TA 98

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

Precipitates in the agar were found at the highest dose of 5.0 mg/plate.

Conclusions:

Non-mutagenic in bacteria

Executive summary:

Dimethylenketon was tested in the Salmonella/microsome test for point-mutagenic effects in doses up to 5000 µg/plate on the five histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98.

No cytotoxic effect was seen. Precipitates in the agar were found at the highest dose of 5.0 mg/plate.

There was no evidence for a mutagenic activity of Dimethylenketon, when tested up to the highest recommended dose level of 5.0 mg/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

Dimethylenketon (ZK 34517) did not show a mutagenic potential in a bacterial reverse mutation assay (Ames test in S. typhimurium strains TA 1535, TA 100, TA 1537, TA 1538 and TA98) when tested up to the highest recommended dose level of 5.0 mg/plate in the absense or presence of extrinsic metabolic activation (liver S9 mix from Aroclor 1254 -treated rats). Growth inhibition was not observed. Precipitates in the agar were found at the highest dose of 5.0 mg/plate.

Short description of key information:
Gene mutation (bacterial reverse mutation assay / Ames test, GLP, OECD TG471): negative with and without metabolic activation
[Schering AG, Report No. X389 -draft-, 1999-10-11]

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).