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Toxicological information

Genetic toxicity: in vivo

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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993
Reference Type:
publication
Title:
Long-term Inhalation Toxicity of N-Vinylpyrrolidone-2 Vapours. Studies in Rats
Author:
Klimisch, et. al.
Year:
1997
Bibliographic source:
Food and Chemical Toxicology, Volume 35, Issues 10-11, October-November 1997, Pages 1041-1060

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes (incl. certificate)
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): N-Vinylpyrrolidone-2 (NVP)
- Physical state: liquid, colorless to yellowish
- Analytical purity: 99.8%
- Storage condition of test material: room temperature (protected from light)

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River GmbH, Sulzfeld
- Weight at study initiation: mean weight of about 28 g
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: for the duration of about one week the animals were housed in groups of 5 separately according to sex; before the start or the treatment the animals were transferred and housed individually under the same conditions until the end of the test
- Diet: standardized pelleted feed (Kliba diet, Klingentalmühle AG, Switzerland) ; assayed for chemical and microbiological contaminants
- Water: ad libitum; assayed for chemical contaminants
- Acclimation period: about one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
- Vehicle(s)/solvent(s) used: distilled water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: all test substance formulations were prepared immediately before administration


Duration of treatment / exposure:
24 hrs (additionally: 16 and 48 hrs in the 600 mg/kg bw N-Vinylpyrrolidone-2 treatment)
Frequency of treatment:
single administration (10 ml/kg bw)
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
150, 300, 600 mg/kg bw (15, 30, 60 mg/ml)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
16.1, 33.2, 57.7 mg/ml
Basis:
analytical conc.
No. of animals per sex per dose:
5 (negative control, N-Vinylpyrrolidone-2)
positive controls: cyclophosphamide (2 male, 3 female), vincristine (3 male, 2 female)
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide, vincristine
- Justification for choice of positive control(s): cyclophosphamide: positive control for clastogenicity; vincristine positive control for spindle poison effects
- Route of administration: cyclophosphamide: orally; vincristine: intraperitoneal
- Doses / concentrations: cyclophosphamide: 20 mg/kg bw, vincristine: 0.15 mg/kg bw

Examinations

Tissues and cell types examined:
1000 polychromatic erythrocytes were evaluated per animal and investigated for micronuclei. The normocytes with and without micronuclei occuring per 1000 polychromatic erythrocytes were also registered.
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
In a pretest for the determination of the acute oral toxicity one death each was still observed down to doses of 681 mg/kg bw and 562 mg/kg body weight; therefore a dose of 600 mg/kg bw was selected as the highest dose in the present cytogenetic study; 300 and 150 mg/kg bw were administered as further doses.


Statistics:
a statistical evaluation was not necessary to perform

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Clinical examinations:

The administration of the vehicle was tolerated by all animals without any signs or symptoms.

The administration of N-vinylpyrrolidone-2 led to the following clinical signs:

600 mg/kg bw group: irregular respiration, piloerection and squatting posture were found about 15 minutes after treatment. Some of these signs were still observed two days after treatment and the general state of the animals was poor.

300/150 mg/kg bw group: irregular respiration and piloerection were found about 15 minutes after treatment; squatting posture was additionally observed after one hour. Some of these signs were still observed the day after treatment.

Both positive controls did not cause any evident signs of toxicity.

 

Substance

Dose (mg/kg)

Sex

post exposure period (h)

PCE with micronuclei

NCE with micronuclei

Ratio PCE/NCE

vehicle

solvent

male

24

2.80

0.6

4.67

female

24

1.60

1.0

1.60

test substance

150

male

24

2.60

1.0

2.60

female

24

0.80

1.0

0.80

test substance

300

male

24

1.60

0.6

2.67

female

24

1.40

0.6

2.33

test substance

600

male

16

1.00

1.0

1.00

female

16

2.80

1.2

2.33

test substance

600

male

24

3.20

0.8

4.00

female

24

1.80

1.2

1.50

test substance

600

male

48

1.60

0.0

female

48

1.80

0.6

3.00

positive ctrl

20

male

24

14.50

0.5

29.00

female

24

11.77

0.7

17.57

positive ctrl

0,15

male

24

129.67

2.0

64.84

female

24

112.50

2.0

56.25

PCE = polychromatic erythrocytes (1000 were scored for micronuclei)

NCE = normochromatic erythrocytes

The PCE/NCE ratio is based on the scoring of 1000 erythrocytes

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative