Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

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

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1000, 750, 500, 250 mg/kg bw
Basis:
other: nominal in olive oil - vinylacetate
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 resultsopen allclose all
Sex:
male
Genotoxicity:
negative
Remarks:
vinylacetate
Vehicle controls validity:
valid
Positive controls validity:
valid
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.