N-(n-dodecyl)pyrrolidinone

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 26 October to 12 December 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to a method comparable with current guidelines and to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Batch No.: 20.9.88/1
Purity: Not specified

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, England
- Age at study initiation: Approximately 35 days old
- Weight at study initiation: 22 to 24 grams
- Assigned to test groups randomly: yes
- Fasting period before study:
- Housing: Each group of 2 or 5 mice was kept in a plastic disposable cage.
- Diet (e.g. ad libitum): Free access to pelleted Labsure LAD 1 rodent breeding diet.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: Approximately 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%):
- Air changes (per hr): 30 changes of air per hour.
- Photoperiod (hrs dark / hrs light): The room was illuminated by artificial light for 12 hours per day.

IN-LIFE DATES: From: 26 October 1988 To: 12 December 1988

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

Corn oil

Duration of treatment / exposure:

Immediately

Frequency of treatment:

Single dose

Post exposure period:

24, 48 or 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
5000 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

Preliminary toxicity test:
2 males and 2 females per dose for Phase I.
5 males and 5 females per dose for Phase II.

Micronucleus test:
15 males and 15 females for vehicle control.
17 males and 19 females for the test substance.
5 males and 5 females for positive control.

Control animals:

yes

Positive control(s):

Mitomycin C
- Justification for choice of positive control(s):
- Route of administration: Oral by intragastric gavage.
- Doses / concentrations: 12 mg/kg

Examinations

Details of tissue and slide preparation:

The femurs were cleared of tissue and one epiphysis removed from each bone. A direct bone marrow smear was made onto a slide containing a drop of calf serum. One smear was made from each femur. The prepared smears were fixed in methanol. The smears were air-dried and stained for 10 minutes in 10% Giemsa. Following rinsing in distilled water and differentiation in buffered distilled water, the smears were air-dried and mounted with coverslips using DPX.

Evaluation criteria:

None stated

Statistics:

For a comparison of an individual treated group with a concurrent control group, Wilcoxon's sum of ranks test is used.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Signs and mortalities:
One male and five female animals died after treatment with the test substance in the main study. On post mortem examination, none of the animals showed signs of having been mis-dosed. No clinical signs were observed in the vehicle control or positive control groups for the duration of the test.

Micronucleated polychromatic erythrocyte counts (mnp):
The test substance did not cause any statistically significant increases in the number of micronucleated polychromatic erythrocytes at any of the three kill times.
Mitomycin C caused large, highly significant increases in the frequency of micronucleated polychromatic erythrocytes.

Micronucleated normochromatic erythrocytes (mnn):
The test substance did not cause any substantial increases in the incidence of micronucleated normochromatic erythrocytes at any of the three kill times.

Ratio of polychromatic to normochromatic erythrocytes (p/n):
Statistically significant decreases in the p/n ratios were observed at the 24 hour and 72 hour sampling times, using Wilcoxon's sum of ranks test. These may be evidence of slight bone marrow cell toxicity/depression.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
From the results obtained it is concluded that the test substance shows no evidence of mutagenic potential or bone marrow cell toxicity when administered as a single oral dose in this in vivo test procedure.