3'H-Cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione, 1,2-dihydro-17-hydroxy-, (1.alpha.,2.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:

August to September 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

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:

1,2-Methylen-4,6-dien: six concentrations from 0.1 to 5.0 mg/plate
9-Acridinamine, hydrochloride: 100 µg/plate
2-Aminoanthracene: 2.0 µg/plate
2-Nitrofluorene: 10 µg/plate
Benzo[a]pyrene: 2.5 µg and 5.0 µg/plate
Sodium azide: 5 µg/plate
Cyclophosphamide: 400 µg/plate

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 9-Acridinamine, hydrochloride; 2-Aminoanthracene; 2-Nitrofluorene; Benzo[a]pyrene; Sodium azide; Cyclophosphamide

Key result

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

growth inhibition was observed with S9 mix from 2.5 mg/plate and without S9 mix from 1.0 mg/plate onwards

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

There were precipitates in the agar starting at 1.0 mg/plate in all tested strains in absence and presence of S9 mix.

Executive summary:

1,2 -Methylen-4,6 -dien was examined for mutagenic activity up to 5000 µg/plate in the five histidine-dependent Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98 with and without metabolic activation.

A cytotoxic effect was seen at from 2.5 mg/plate onwards with S9 mix and from 1.0 mg/plate onwards without S9 mix, adjustment of the tested concentrations to low purity of test item (> 67%) was therefore irrelevant.

There was no evidence for a mutagenic activity of 1,2 -Methylen-4,6 -dien, when tested up to the precipitating and cytotoxic dose levels and the maximum recommended dose level of 5 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

A bacterial reverse mutation assay with S. typhimurium was conducted with 1,2 -Methylen-4,6 -dien concentrations from 0.1 to 5 mg per plate using the five histidine-dependent Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98 with and without metabolic activation. A cytotoxic effect was seen at from 2.5 mg/plate onwards with S9 mix and from 1.0 mg/plate onwards without S9 mix.

There was no evidence for a mutagenic activity of 1,2 -Methylen-4,6 -dien, when tested up to the precipitating and cytotoxic dose levels and the maximum recommended dose level of 5 mg/plate in the absence and presence of S9 mix.

Short description of key information:
Gene mutation in vitro (bacterial reverse mutation assay, GLP, equivalent to OECD TG 471): negative in the Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 100 and TA 98 with and without S9 mix
[Schering AG, Report No. X180 -draft-, 1996-12-13]

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.