Allyl 3-cyclohexylpropionate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

The study was performed under non-GLP conditions but in accordance with principles similar to those of OECD TG 475

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

no

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Allyl 3-cyclohexylpropionate

EC Number:

220-292-5

EC Name:

Allyl 3-cyclohexylpropionate

Cas Number:

2705-87-5

Molecular formula:

C12H20O2

IUPAC Name:

prop-2-en-1-yl 3-cyclohexylpropanoate

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ivanovas GmbH, Kisslegg
- Age at study initiation: 10 to 14 weeks
- Weight at study initiation: not reported
- Assigned to test groups randomly: not reported
- Fasting period before study: not reported
- Housing: not reported
- Diet (e.g. ad libitum): Altromin standard chow ad libitum
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

IN-LIFE DATES: not reported

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Olive oil

Details on exposure:

Test substance was mixed with olive oil and administered intraperitoneal.

Duration of treatment / exposure:

Test animals received an intraperitoneal injection of test substance at 0 and 24 hours.

Frequency of treatment:

Twice

Post exposure period:

Animals were killed 30 hours after the last dose.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

156 mg/kg bw/day (nominal)

Remarks:

in olive oil as injected

Doses / concentrations 2

Dose / conc.:

78 mg/kg bw/day (nominal)

Remarks:

in olive oil as injected

Doses / concentrations 3

Dose / conc.:

49 mg/kg bw/day (nominal)

Remarks:

in olive oil as injected

Doses / concentrations 4

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

in olive oil as injected

No. of animals per sex per dose:

4

Control animals:

yes, concurrent vehicle

Positive control(s):

No

Examinations

Tissues and cell types examined:

Bone marrow cells

Details of tissue and slide preparation:

Bone marrow smears were prepared 30 hours after the last treatment. The smears were stained with May-Grünwald and Giemsa according to the method of Schmid (1976, The micronucleus test for cytogenetic analysis. In Chemical Mutagens. Edited by A. Hollaender. Vol. 4, page 31. Plenum Press, New York).

Evaluation criteria:

Slides were scored as described by Wild and co-workers (1980, Cytogenetic effect of orthophenylenediamine in the mouse, Chinese hamster, and guinea pig and of derivatives, evaluated by micronucleus test. Archives of Toxicology 43, 249-255). 1000 polychromatic erythrocytes from each animal were analysed for micronuclei. An increased frequency of micronucleus-containing polychromatic erythrocytes indicates cytogenetic damage. The proportion of polychromatic among total (poly- and normochromatic) erythrocytes is based on the differentiation of a total number of 1000 erythrocytes.

Statistics:

Statistical significance in difference between test groups and negative controls was determined according to the methods of Kastenbaum and Bowman (Tables for determining the statistical significance of mutation frequencies, Mutation Research 9, 527-549, 1970)

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Remarks:

no signs of toxicity were reported

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): there was no induction of formation of micronuclei
- Ratio of PCE/NCE (for Micronucleus assay): not reported
- Appropriateness of dose levels and route: yes
- Statistical evaluation: not reported

Applicant's summary and conclusion

Conclusions:

The substance was considered to be not mutagenic in an in-vivo mouse bone marrow micronucleus assay.

Executive summary:

An in-vivo mouse bone marrow micronucleus assay was conducted under non-GLP conditions according to principle similar to those of OECD TG 475. Male and female NMRI mice aged 10 to 14 weeks were used in the test. The test substance allyl 3-cyclohexylproprionate was mixed with olive oil and administered to four animals per dose group twice by intraperitoneal injection at 0 and 24 hours. The substance was tested at 49, 78 and 156 mg/kg bw. A group receiving olive oil only was tested in parallel. Animals were sacrificed 30 hours after the last injection, bone marrow was isolated and smears were prepared and stained with May-Grünwald and Giemsa following the method of Schmid (1976). A total of 1000 polychromatic erythrocytes from each animal was analysed for micronuclei. Results were expressed as mean number of micronucleated polychromatic erythrocytes (MNPE) per 1000 polychromatic erythrocytes (PE) and the numbers found in the experiment were 2.2 MNPE/1000 PE in the controls, 1.8 MNPE/1000 PE in the group exposed to 49 mg/kg bw, 1.7 MNPE/1000 PE in the group exposed to 78 mg/kg bw and 4.0 MNPE/1000 PE in the group exposed to 156 mg/kg bw. The authors of the study found that the findings in the exposed animals were not statistically different from the results observed in the controls. It was concluded that the test substance allyl 3-cyclohexylproprionate was not mutagenic in the in-vivo mouse bone marrow micronucleus assay.