(±)-13-ethyl-3-methoxygona-1,3,5(10),8-tetraen-17-one

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (bacterial reverse mutation assay / Ames test): positive in S. typhimurium TA 1537, TA 1538 and TA 98 without S9-mix [Reimann & Görke, 2000]

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

other information

Study period:

from September to October 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: comparable to guideline study with acceptable restrictions; the applied strains of bacteria may not detect certain oxidising mutagens, cross-linking agents

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

- TA 102 or E.coli WP2 strains are not included

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine gene locus

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced male Wistar rat liver S9 mix

Test concentrations with justification for top dose:

100, 250, 500, 1000, 2500, 5000 µg/plate

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

cyclophosphamide

other: anthracen-2-amine

Species / strain:

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

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

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

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

TA 1537

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: strain/cell type: TA 1537, TA 1538, TA98

Remarks:

Migrated from field 'Test system'.

None of the two tester strains (TA 1535, TA 100) which detect base-pair substitutions as genetic endpoint exhibited a mutagenic response. In contrast all of the three tester strains which detect frame-shift mutations (TA 1537, TA 1538 and TA98) showed increased reversion to prototrophy in the absence of S9 mix. However, no mutagenic response could be observed in the experiments which included rat liver S9 as an extrinsic metabolizing system. Growth inhibition of the background lawn was only observed in the experiments with TA 1537(+S9), TA1535 (-S9) and TA100 (-S9) at the highest dose tested (5 mg/plate).

There were precipitates in the agar found starting from 1.0 mg/plate in strains TA 1535, TA 100 and TA 1537 in the absence and presence of S9 mix and in the tests with TA 1538 and T A98 without 89 mix from 0.5 mg/plate and from 2.5 mg/plate with S9 mix.

Appropriate positive control chemicals induced marked increases in revertant colony numbers with all strains.

Executive summary:

The mutagenic potential of the test substance was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 1535, 1538 and TA 1537 in the presence and absence of S9 mix according to OECD TG 471. Evaluation of the data indicates that the test substance is a mutagen in the Ames Salmonella/microsome test. However, the mutagenic effect could only be observed in the experiments without S9 mix. Since the mutagenic effect was only observed in strains TA 1537, TA 1538 and TA98 the genotoxic potential of the test substance is based on the induction of frame-shift mutations.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Additional information

Additional information from genetic toxicity in vitro:

The mutagenic potential of the test substance was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 1535, 1538 and TA 1537 in the presence and absence of S9 mix according to OECD TG 471. Evaluation of the data indicates that the test substance is a mutagen in the Ames Salmonella/microsome test. However, the mutagenic effect could only be observed in the experiments without S9 mix. Since the mutagenic effect was only observed in strains TA 1537, TA 1538 and TA98 the genotoxic potential of the test substance is based on the induction of frame-shift mutations.

Justification for selection of genetic toxicity endpoint
Only one study available

Justification for classification or non-classification

Based on the available information (restricted to one in vitro study detecting gene mutations in bacteria) a classification according to Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP) is not required although the test result is positive.