Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl propionate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Study of artificial flavouring substances for mutagenicity in the salmonella/microsome, Basc and micronucleus tests.

Author:

Wild D, King MT, Gocke E and Eckhardt K.

Year:

1983

Bibliographic source:

Fd Chem. Toxic. Vol. 21, No. 6, pp. 707-719, 1983

Materials and methods

Test guideline

Test guideline 1

Qualifier:

no guideline followed

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

In a micronucleus test groups of male and female NMRI mice, 4 per dose (10-14 weeks old) were treated once intraperitoneally at dose levels of 841, 1893 and 2944 mg/kg in olive oil. Control animals were dosed with olive oil alone. Mice from each dose level were sacrificed at 30 hours, the bone marrow extracted and smear preparations made and stained according to the method of Schmid (1976). Polychromatic erythrocytes were then scored for the presence of micronuclei.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl propionate

EC Number:

220-410-5

EC Name:

Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl propionate

Cas Number:

2756-56-1

Molecular formula:

C13H22O2

IUPAC Name:

1,7,7-trimethylbicyclo[2.2.1]hept-2-yl propionate

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: lvanovas GmbH, Kisslegg
- Age at study initiation: 10-14 weeks
- Diet: standard chow (Altromin) ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Vehicle used: Olive oil

Duration of treatment / exposure:

Single intraperitoneal dose

Frequency of treatment:

Once

Post exposure period:

The mice were killed and bone-marrow smears were prepared 30 hr after treatment.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

841 mg/kg bw (total dose)

Doses / concentrations 2

Dose / conc.:

1 893 mg/kg bw (total dose)

Doses / concentrations 3

Dose / conc.:

2 944 mg/kg bw (total dose)

No. of animals per sex per dose:

4 animals in total per dose group, ratio of male:female not specified

Control animals:

yes, concurrent vehicle

Positive control(s):

no data

Examinations

Tissues and cell types examined:

Bone marrow was extracted and smear preparations were made and stained. Polychromatic erythrocytes were scored.

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
The smears were stained according to the method of Schmid (1976).

METHOD OF ANALYSIS:
The mean number of micronucleated polychromatic erythrocytes was expressed per 1000 cells

Evaluation criteria:

A substance is considered positive if a significant increase in the frequency of polychromatic erythrocytes from the concurrent control value is observed.

Statistics:

Statistical significance was determined according to the methods of Kastenbaum & Bowman (1970).

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

2/4 animals died in the high dose group

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Additional information on results:

- Mean number of micronucleated polychromatic erythrocytes (per 1000 cells) was 2.3, 1.0, 1.0 and 2.0 for the dose groups receiving vehicle (control), 841 mg/kg bw, 1893 mg/kg bw and 2944 mg/kg bw, respectively.
- In the high dose group 2/ 4 animals died, no mortality was observed in the other groups.

Applicant's summary and conclusion

Conclusions:

Under the conditions of the test, the substance is not clastogenic in NMRI mice in vivo.

Executive summary:

In a micronucleus test groups of male and female NMRI mice, 4 mice per dose (10-14 weeks old) were treated once intraperitoneally at dose levels of 841, 1893 and 2944 mg/kg in olive oil tested similar to OECDTG 474). Control animals were dosed with olive oil alone. Mice from each dose level were sacrificed at 30 hours, the bone marrow extracted and smear preparations made and stained. Polychromatic erythrocytes were then scored for the presence of micronuclei. In the top dose group 2/4 animals died. No significant increase in the incidence of micronucleated polychromatic erythrocytes was observed with any of the tested doses.