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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
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
not applicable
GLP compliance:
not specified
Type of assay:
mammalian erythrocyte micronucleus test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
additive
Specific details on test material used for the study:
purchased from Fluka A.G., Buchs, Switzerland

Test animals

Species:
mouse
Strain:
other: C57Bl/6
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Department of Pathology, University of Helsinki.
- Age at study initiation: 12-17 week
- Assigned to test groups randomly: not specified
- Fasting period before study: not specified
- Housing: standard animal housing of the Institute of Occupational Health
- Diet: commercial feed (Tamro, Helsinki), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 2 weeks

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
none- Vehicle(s)/solvent(s) used: olive oil
- Justification for choice of solvent/vehicle: not specified
- Concentration of test material in vehicle: 25 to 200 mg/ml.
- Dose volume: 0.01ml/g bw

Details on exposure:
Intraperitoneal inyection of 0.01 ml/g of:
250, 500, 1000 or 2000 mg/kg b.wt. of vinyl acetate in olive oil
olive oil (control animals)
20 mg/kg b.wt. of cyclophosphamide (positive controls).
Duration of treatment / exposure:
30 hours
Frequency of treatment:
single exposure
Post exposure period:
none
Doses / concentrationsopen allclose all
Dose / conc.:
250 mg/kg bw (total dose)
Dose / conc.:
500 mg/kg bw (total dose)
Dose / conc.:
1 000 mg/kg bw (total dose)
Dose / conc.:
2 000 mg/kg bw (total dose)
No. of animals per sex per dose:
Control: 9
Positive control: 10
250 and 500 mg/kg bw: 10
1000 and 200 mg/kg bw: 14
Control animals:
yes, concurrent vehicle
Positive control(s):
9-14 animals cyclophosphamide
- Route of administration: intraperitoneal
- Doses / concentrations: 20 mg/kg b.wt.

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
Slides for each animal fixed and stained with May-Griinwald and Giemsa solutions
Samples were analyzed by one microscopist from coded slides.
Polychromatic and normochromatic cells were simultaneously recorded until the score for one cell type reached 1000.
Statistics:
The micronucleus data were tested statistically by a Chi square test
Ratios of polychromatic to normochromatic erythrocytes were statistically tested according to a 1-tailed t-test.

Results and discussion

Test results
Key result
Sex:
male
Genotoxicity:
ambiguous
Remarks:
seen at toxic doses only
Toxicity:
yes
Remarks:
1000 and 2000 mg/kg bw
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Additional information on results:
Mortality: 6 animals died on the 1000 mg/kg bw dose group and 8 animals died on the 2000 mg/kg bw
A dose-dependent increase in micronucleated polychromatic erythrocytes was observed in the bone marrow and was statistically significant at 1000 and 2000 mg/kg.
There was no effect on the number of micronuclei in normochromatic erythrocytes.
The ratio of polychromatic to normochromatic cells decreased as a function of vinyl acetate dose, confirming citotoxicity

Any other information on results incl. tables

 Treatment  Nr. of Animals

Polychromatic cells with

micronuclei (%) + SD

Normochromatic cells with

micronuclei  (%) + SD

 

Ratio of polychromatic

to normochromatic cells + SD

 
 Control, Olive oil  9  0.60 ± 0.10  0.31 ± 0.05  1.32 ± 0.12

Positive control,

cyclophosphamide 20

 10

2.07 a ± 0.20 

 0.29 ± 0.06

 1.11 + 0.15

Vinyl acetate

250 mg/kg wb

 10

 0.55 + 0.08

 0.25 ± 0.04

 1.22 + 0.13

Vinyl acetate

500 mg/kg wb

 10

 0.72 ± 0.10

 0.23 + 0.04

 0.94 b + 0.12

Vinyl acetate

1000 mg/kg wb

 8 (6 died)

 1.33 a ± 0.29

0.20 ± 0.04

 0.67 c ± 0.11

Vinyl acetate

2000 mg/kg wb

 6 (8 died)

 1.57 a ± 0.19

 0.18 ± 0.05

0.53 d ± 0.08

a P < 0.001, compared with the frequency in control animals, X z test.

b P < 0.05, c P < 0.01, and d P< 0.001, compared with the ratio in control animals, t-test (one-tailed).

Applicant's summary and conclusion

Conclusions:
Vinyl acetate induced a dose-dependant increase in polychromatic erythrocytes in the bone marrow of male mice after 30 h of intraperitoneal injection, but only at toxic doses.
Executive summary:

A dose-dependent increase in micronucleated polychromatic erythrocytes was observed in the bone marrow of male C57B1/6 mice 30 h after a single intraperitoneal injection of vinyl acetate (250, 500, 1000 or 2000 mg/kg b.wt.; (9-14 animals per group). The effect was statistically significant at 1000 mg/kg and at 2000 mg/kg of vinyl acetate. These doses were fatal to 6 and 8 out of 14 animals of the 1000 and 200 mg/kg vinyl acetate groups respectively.

The ratio of polychromatic to normochromatic cells decreased as a function of vinyl acetate dose. Cyclophosphamide (20 mg/kg), used as a positive control chemical, induced a clear increase in micronucleated polychromatic erythrocytes. None of the treatments affected the number of micronuclei in normochromatic erythrocytes.