Registration Dossier

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

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
olive oil
Duration of treatment / exposure:
The animais of the vehicle control and the dose groups were treated twice at a 24-hour interval and samples of bone marrow were taken 24 hours after the last treatment. Animals of the positive control groups were treated only once and samples of bone marrow were taken after 24 hours.
Frequency of treatment:
two intraperitoneal administrations
Doses / concentrations
Remarks:
Doses / Concentrations:
250, 500, 1000 ml/kg
Basis:

No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide, vincristine sulphate

Results and discussion

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

Any other information on results incl. tables

As a negative control, olive oil (the selected vehicle) was administered to male mice by the same route, and gave frequencies of micronucleated polychromatic erythrocytes within the historical control range.

Both of the positive control chemicals, i.e. cyclophosphamide for clastogenic effects and vincristine for induction of spindle poison effects, led to the expected increase in the rate of polychromatic erythrocytes containing small or large micronuclei.

Animals which were administered the vehicle or the positive control substances, cyclophosphamide or vincristine, did not show any clinical signs of toxicity.

The administration of the test substance Triethylenglykoldivinylether led to evident signs of toxicity. The intraperitoneal administration of Triethylenglykoldivinylether did not lead to any increase in the number of polychromatic erythrocytes containing either small or large micronuclei. The rate of micronuclei was always in the same range as that of the negative control in all dose groups and at all sacrifice intervals. A slight inhibition of erythropoiesis, determined from the ratio of polychromatic to normochromatic erythrocytes, was detected at the highest dose of 1,000 mg/kg body weight.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Under the experimental conditions of the study, the test substance does not have any chromosome-damaging (clastogenic) effect and there were no indications of any impairment of chromosome distribution in the course of mitosis.
Executive summary:

The substance Triethylenglykoldivinylether was tested for clastogenicity and for the ability to induce spindle poison effects in NMRI mice using the micronucleus test method. For this purpose, the test substance, dissolved in olive oil was administered twice intraperitoneally to male animals at dose levels of 250 mg/kg, 500 mg/kg and 1,000 mg/kg body weight in a volume of 10 ml/kg body weight in each case. As a negative control, olive oil (the selected vehicle) was administered to male mice by the same route, and gave frequencies of micronucleated polychromatic erythrocytes within the historical control range. Both of the positive control chemicals, i.e. cyclophosphamide for clastogenic effects and vincristine for induction of spindle poison effects, led to the expected increase in the rate of polychromatic erythrocytes containing small or large micronuclei. Animals which were administered the vehicle or the positive control substances, cyclophosphamide or vincristine, did not show any clinical signs of toxicity. The administration of the test substance Triethylenglykoldivinylether led to evident signs of toxicity. The intraperitoneal administration of Triethylenglykoldivinylether did not lead to any increase in the number of polychromatic erythrocytes containing either small or large micronuclei. The rate of micronuclei was always in the same range as that of the negative control in all dose groups and at all sacrifice intervals. Thus, the test substance Triethylenglykoldivinylether does not have any chromosome-damaging (clastogenic) effect, and there were no indications of any impairment of chromosome distribution in the course of mitosis.