3'H-Cycloprop[15,16]androst-15-en-17-one, 3-(2,2-dimethyl-1-oxopropoxy)-5,6-epoxy-15,16-dihydro-7-hydroxy-, (3.beta.,5.beta.,6.beta.,7.beta.,15.alpha.,16.alpha.)-

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 TG471): 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:

June - August 1997

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:

Methylenepoxidpivalat: six concentrations from 0.1 to 5 mg/plate
Sodium azide: 5 µg/plate (TA 1535 and TA 100)
2-Nitrofluorene: 10 µg/plate (TA 1538 and TA 98)
9-Acridinamine: 100 µg/plate (TA 1537)
Benzo[a]pyrene: 2.5 µg/plate (TA 100 and TA 98)
Cyclophosphamide: 400 µg/plate (TA 1535)
2-Aminoanthracene: 2 µg/plate

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Sodium azide (TA 1535 and TA 100), 2-Nitrofluorene (TA 1538 and TA 98), 9-Acridinamine (TA 1537), Benzo[a]pyrene (TA 100 and TA 98), Cyclophosphamide (TA 1535), 2-Aminoanthracene

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:

cytotoxicity

Remarks:

growth inhibition and precipitates in the agar were observed in all strains starting at 2.5 mg/plate with and without S9 mix

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Executive summary:

Methylenepoxidpivalat 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.

A cytotoxic effect was seen in all strains at doses of 2.5 mg/plate and above with and without metabolic activation. Precipitates in the agar were also detectable starting at 2.5 mg/plate in all strains.

There was no evidence for a mutagenic activity of Methylenepoxidpivalat, 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

Methylenepoxidpivalat (ZK 90346) did not show a mutagenic potential in a bacterial reverse mutation assay (Ames test in S. typhimurim strains TA 1535, TA 100, TA 1537, TA 1538 and TA98) when tested up to the highest recommended dose level of 5 mg/plate in the absense or presence of extrinsic metabolic activation (liver S9 mix from Aroclor 1254 -treated rats). Growth inhibition and precipitates in the agar could be observed starting at 2.5 mg/plate in all strains both with and without S9 mix.

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. X248 -draft-, 1997-09-26]

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).