3,6,9,12-Tetraoxatetradeca-1,13-diene

Genetic toxicity: in vivo

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

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

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 validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

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.