1-ethylpyrrolidin-2-one

Genetic toxicity: in vivo

Administrative data

Endpoint:

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

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

1-ethylpyrrolidin-2-one

EC Number:

220-250-6

EC Name:

1-ethylpyrrolidin-2-one

Cas Number:

2687-91-4

Molecular formula:

C6H11NO

IUPAC Name:

1-ethylpyrrolidin-2-one

Details on test material:

purity: 99.8%

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Details on test animals or test system and environmental conditions:

The investigations were carried out in healthy male CIr:NMRI mice. Animals with a mean weight of about 30 g (with an age range of about 5 - 8 weeks according to the information of the breeder) were used for the study. For the duration of at least 5 days the animals were housed in Makrolon cages. During this time the animals were accommodated in fully air-conditioned rooms in which central air conditioning guaranteed a range of 20 - 24°C for temperature and a range of 30 - 70% for relative humidity . Before the start of the treatment the animals were transferred to Makrolon cages, type MI , and housed individually under the same conditions until the end of the test. The day/night rhythm was 12 hours (12 hours light from 6 .00 - 18.00 hours and 12 hours darkness from 18.00 - 6.00 hours). Standardized pelleted feed and drinking water from bottles were available ad libitum. Due to individual housing in appropriately labeled cages using cage cards, there was no identification of the animals.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

The animals were sacrificed and the bone marrow of the two femora was prepared 24 and 48 hours after administration in the highest dose group of 2000 mg/kg body weight and in the vehicle controls. In the test groups of 1000 mg/kg and 500 mg/kg body weight and in the positive control group, the 24-hour sacrifice interval was investigated only. About 2 - 3 hours before the animals were sacrificed, they were intraperitoneally injected with 3.3 mg Colcemid/kg body weight in order to arrest mitosis at the stage of metaphase. After preparation of the bone marrow and staining of the preparations with Giemsa, 100 metaphases were analyzed per animal.

Duration of treatment / exposure:

single oral administration

Frequency of treatment:

The animals were treated once and samples of bone marrow were taken 24 hours and 48 hours after the treatment.

Doses / concentrations

Remarks:

Doses / Concentrations:
500, 1000, 2000 mg/kg bw
Basis:

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

As a positive control chemical, cyclophosphamide for clastogenicity was administered to male animals once orally in a volume of 10 ml/kg body weight.

Examinations

Evaluation criteria:

The test is considered valid if the following criteria art met:
- The quality of slides allowed the identification and evaluation of a sufficient number of analyzable cells.
- The proportion of chromosomally damaged cells in negative control animals was within the expected range (<= 2 % incl. gaps).

The test chemical is consideres positive in the assay if the following criteria are met:
- A dose-related and significant increase in the number of metaphases containing chromosomal aberrations at any of the intervals.
- The proportion of aberrant metaphases must significantly exeed the value of the concurrent negative control range.

A test substance is generally considered negative in this test system if:
- There was no significant increase in the number of chromosomally damaged cells at any dose above concurrent control frequencies an at any time.
- The frequencies of cells containing structurally damaged chromosomes were within th negative control range.
- The positive control article induced a significant increase in the number of aberrant metaphases.

Statistics:

The asymptotic U test according to MANN-WHITNEY (modified rank test according to WILCOXON) was carried out to clarify the question whether there were significant differences between the control group and dose groups with regard to aberrant metaphases. The relative frequencies of aberrant metaphases of each animal was used as a criterion for the rank determination for the U test.

Results and discussion

Test results

Sex:

male

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative