Methoxycarbonyloxycyclooct-4-ene

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 1, 1985 - October 21, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Methoxycarbonyloxycyclooct-4-ene

EC Number:

401-620-8

EC Name:

Methoxycarbonyloxycyclooct-4-ene

Cas Number:

87731-18-8

Molecular formula:

C10H16O3

IUPAC Name:

(1R,3aS,6aS)-octahydropentalen-1-yl methyl carbonate; (1S,3aS,6aS)-octahydropentalen-1-yl methyl carbonate; (3Z)-cyclooct-3-en-1-yl methyl carbonate; (4Z)-cyclooct-4-en-1-yl methyl carbonate; bicyclo[3.2.1]octan-8-yl methyl carbonate

Test material form:

liquid

Method

Target gene:

- S. typhimurium: Histidine gene
- E. coli: Tryptophan gene

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium, other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and only in the dose range finding test: TA 1538

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9-mix induced by Aroclor 1254

Test concentrations with justification for top dose:

Dose range finding test: 5, 50, 500 and 5000 µg/plate
Experiment 1 and 2: 15, 50, 150, 500 and 1500 µg/plate
Experiment 3 (without and with S9), TA1537: 15, 50, 150, 500 and 1500 µg/plate

Vehicle / solvent:

- Solvent used: DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: see section "Any other information on materials and methods incl. tables"

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 72 hours

NUMBER OF REPLICATIONS:
- Doses of the test substance were tested in triplicate in each strain. Two independent experiments were conducted and an additional experiment with TA1537 only.

DETERMINATION OF CYTOTOXICITY
- Method (dose range finding test): The reduction of the bacterial background lawn
- Method (main study): The reduction of the revertant colonies.

Evaluation criteria:

A compound is deemed to provide evidence of mutagenic potential if
(1) a statistically significant dose-related increase in the number of revertant colonies is obtained in two separate experiments and
(2) the increase in the number of revertant colonies is at least twice the concurrent solvent control value

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

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

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

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

Test results 3

Key result

Species / strain:

S. typhimurium 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

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

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

Test results 5

Key result

Species / strain:

E. coli WP2 uvr A

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

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: no data

RANGE-FINDING/SCREENING STUDIES:
- In all strains, toxicity was observed at 5000 μg/plate.

COMPARISON WITH HISTORICAL CONTROL DATA:
- The positive control substances produced the expected mutagenic results.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
No cytotoxicity was observed in the 3 tests for strain TA98, TA1535 and TA1537 (+/- S9), therefore, higher concentrations could have been tested.

Applicant's summary and conclusion

Conclusions:

Under the test conditions, the test substance is not considered mutagenic in the Salmonella typhimurium and Escherichia coli reverse mutation assay (OECD TG 471).

Executive summary:

The substance is tested in the Ames test (OECD TG 471), using Salmonella typhimurium strains TA100, TA1535, TA98 and TA1537 and E. coli strain WP2uvrA. The test was performed in a direct plate assay up to 1500 µg/plate due to cytotoxicity in the preliminary test, both in the absence and presence of S9-mix. Adequate negative and positive controls were included. The substance did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the four S. typhimurium tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in tester strain WP2uvrA, both in the absence and presence of S9-metabolic activation. These results were confirmed in two independently repeated experiments for TA1537 and in one repeated experiment for all other strains. Based on these results, the substance is not mutagenic in the Ames test.