Vinyl acetate

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo

Remarks:

Type of genotoxicity: other: genotoxicity in germ cells of male mice

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP, non-guideline study, published in peer reviewed literature, adequate for assessment

Data source

Reference

Reference Type:

publication

Title:

Effects of vinyl acetate and acetaldehyde on sperm morphology and meiotic micronuclei in mice

Author:

Lahdetie J

Year:

1988

Bibliographic source:

Mutation Research 202, 171-178

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The testicular genotoxic effects of vinylacetate and its hydrolysis product, acetaldehyde, were studied in mice by analyzing the induction of meiotic micronuclei.

GLP compliance:

not specified

Type of assay:

other: genotoxicity in germ cells of male mice

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:

ethenyl acetate

Details on test material:

- Name of test material (as cited in study report): Vinylacetate
- Supplied by: Fluka AG, Buchs, Switzerland

Test animals

Species:

mouse

Strain:

other: (C57B1/6J x C3H/He)F1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: University of Helsinki, Finland (parents from Zentralinstitut fur Versuchstierzucht GmbH, Hannover, FRG) or Zentralinstitut fur Versuchstierzucht GmbH, Hannover, FRG directly.

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: olive oil for vinylacetate; (cold physiological saline for acetaldehyde)

Duration of treatment / exposure:

Single ip dose

Frequency of treatment:

Single ip dose

Post exposure period:

13 days

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1000, 750, 500, 250 mg/kg bw
Basis:
other: nominal in olive oil - vinylacetate

Doses / concentrations 2

Remarks:

Doses / Concentrations:
500, 375, 250, 125 mg/kg bw
Basis:
other: nominal in cold physiological saline - acetaldehyde

No. of animals per sex per dose:

1, 3, 4, 4, 4 for 1000, 750, 500, 250 and 0 (olive oil) mg/kg vinyl acetate. 4, 4, 4, 7 for 375, 250, 125 and 0 (saline) mg/kg acetaldehyde. 4 for each of the positive control groups.

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide 75 mg/kg or adriamycin 6 mg/kg

Examinations

Tissues and cell types examined:

Preparations of 1 mm segments of seminiferous tubules, representing seminiferous epithelial stages XII-I, were made from newly divided round spermatids at stage 1 of mouse spermatogenesis.

Details of tissue and slide preparation:

The mice were killed 13 days after ip injection (the time interval allowed for analysis of cells exposed at the preleptotene stage of meiosis). Newly divided round spermatids at stage 1 of mouse spermatogenesis were collected using a micro-dissection technique. Preparations of 1 mm segments of seminiferous tubules were made and stained with Hoechst 33258; these represented seminiferous epithelial stages XII-I.

Evaluation criteria:

1000 early spermatids per mouse were scored for the number of micronuclei.

Statistics:

The statistical evaluation of meiotic micronuclei was based on Poisson distribution.

Results and discussion

Test results

Test results 1

Sex:

male

Genotoxicity:

negative

Remarks:

vinylacetate

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Sex:

male

Genotoxicity:

negative

Remarks:

acetaldehyde

Vehicle controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Table 1: Meiotic micronucleus frequencies in early spermatids of mice 13 days after a single injection of vinylacetate or acetaldehyde (frequency in 1000 early spermatids)

 

treatment	vinylacetate				oli	acetaldehyde			sal	cp	adm
dose level (mg/kg)	1000	750	500	250	0	375	250	125	0	75	6
number of mice	1	3	4	4	4	4	4	4	7	4	4
frequency (mean± SE)	0	0.33 ± 0.33	2.25 ± 0.85	2.00 ± 1.08	2.00 ± 0.71	1.00 ± 0.71	1.25 ± 0.48	1.5 ± 0.50	1.57 ± 0.61	4.75** ± 0.75	4.75** ± 3.77
(range)		0-1	0-4	0-5	0-3	0-3	0-2	0-2	0-4	2-9	0-16
** p<0.01 compared to saline controls oli = olive oil, cp =cyclophosphamide, sal = saline, adm = adriamycin

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Neither vinylacetate nor acetaldehyde (its hydrolysis product) induced micronuclei in meiotic cells.

Executive summary:

Neither vinylacetate nor acetaldehyde (its metabolite) induced micronuclei in meiotic cells.