Octahydrocyclopenta[c]pyrrole

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: other: clastogenicity and aneugenicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Octahydrocyclopenta[c]pyrrole

EC Number:

227-114-5

EC Name:

Octahydrocyclopenta[c]pyrrole

Cas Number:

5661-03-0

Molecular formula:

C7H13N

IUPAC Name:

octahydrocyclopenta[c]pyrrole

Test material form:

gas under pressure: refrigerated liquefied gas

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Details on test animals or test system and environmental conditions:

Controlled environment with 15 air changes per hour, temperature between 20.9 and 23.7°C, relative humidity of 40-70% and a cycle of 12 hours light/12 hours dark.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

physiological saline.

Duration of treatment / exposure:

Single dose.

Post exposure period:

24 and 48h.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
106
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
213
Basis:
nominal in diet

Doses / concentrations 3

Remarks:

Doses / Concentrations:
425
Basis:
nominal in diet

No. of animals per sex per dose:

5 per dose and per sampling time.

Control animals:

yes, concurrent vehicle

Positive control(s):

Substance used for positive control = cyclophosphamide at 40mg/kg bw, gavage.

Examinations

Tissues and cell types examined:

Bone marrow from femur.

Details of tissue and slide preparation:

For each animal, both femurs were removed and freed of blood and muscles. Both ends of the bone were shortened till a small opening in the marrow canal was visible. The bone was flushed with approximately 2 ml of fetal calf serum. The cell suspension was collected and centrifuged at 1000 rpm for 5 min.
The supernatant was removed, and a drop of serum was left on the pellet. The cells in the sediment were carefully mixed with the remaining serum, and a drop of the cell suspension was placed on the end of a clean slide, previously immersed in ethanol and cleaned. The preparation were air-dried, fixed for 5min in 100% methanol and air dried overnight. Two slides were prepared per animal.

Evaluation criteria:

A test substance is considered positive in the micronucleus test if :
- it induced a biologically as well as a statistically significant increase in the frequency of micronucleated polychromatic erythrocytes (at any dose or at any sampling time) and the number of micronucleated polychromatic erythrocytes are above the historical control data range.

A test substance is considered negative in the micronucleus test if :
- none of the tested concentrations or sampling times showed a statistically significant increase in the incidence of micronucleated polychromatic erythrocytes and the number of micronucleated polychromatic erythrocytes in the animals are within the historical control data range.

Statistics:

The statistically significant increase is determined following Wilcoxon Rank Sum Test, one -sided, p<0.05.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

mortality and clinical signs at 425 mg/kg

Vehicle controls validity:

valid

Positive controls validity:

valid