Vinyl propionate

Genetic toxicity: in vivo

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

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

not applicable

GLP compliance:

not specified

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Vinyl acetate

EC Number:

203-545-4

EC Name:

Vinyl acetate

Cas Number:

108-05-4

Molecular formula:

C4H6O2

IUPAC Name:

vinyl acetate

additive 1

Reference substance name:

Hydroquinone

EC Number:

204-617-8

EC Name:

Hydroquinone

Cas Number:

123-31-9

Molecular formula:

C6H6O2

IUPAC Name:

hydroquinone

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 or test system 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 / concentrations

Doses / concentrations 1

Dose / conc.:

250 mg/kg bw (total dose)

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw (total dose)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw (total dose)

Doses / concentrations 4

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 validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

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.