Vinyl neononanoate

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: The study was conducted according to an O.E.C.D. Testing Guideline with GLP compliance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Details on test material:

As per IUCLID5 Sections 1.1 -1.4.

Test animals

Species:

mouse

Strain:

Swiss Webster

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Swiss-Webster mice weighing approximately 20 to 30 grams were obtained from Charles River Laboratories. The animals were housed in filter-top cages in a ventilated cage rack with 5 male or female mice in each cage. Food (Purina Rodent Laboratory Chow No. 5001C) and water were provided ad libitum, and the mice were acclimated for up to seven days before initial dosing.

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

The test substance was delivered neat.

Details on exposure:

The test substance and controls were administered i.p. to male and female mice at each dose level on each of three consecutive days. Doses administered were: 0.01, 0.02, 0.03, and 0.04 ml per mouse (0.3, 0.6, 0.9, and 1.3 mi/kg for male mice and 0.3, 0.6, 0.9, and 1.2 mi/kg for female mice).

Duration of treatment / exposure:

3 days

Frequency of treatment:

1/day

Post exposure period:

24 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
0.3, 0.6 0.9, 1.3 ml/kg
Basis:
nominal conc.

No. of animals per sex per dose:

5

Control animals:

yes

Positive control(s):

0.4 mg/kg triethylenemelamine

Examinations

Tissues and cell types examined:

erythrocytes

Details of tissue and slide preparation:

Slides of peripheral blood smears were made for all surviving animals approximately 24 hours after the last dosing by the following procedure. Approximately 2-3 il of serum was placed on a slide pre-cleaned with 95% ethanol. Each mouse was sacrificed by cervical dislocation, and approximately 2-3 .tl of blood per slide was obtained from the mid- ventral tail vein of a mouse and placed on top of the serum. The blood was mixed with the serum and spread on the slide to produce a thin, even film, then the slide was allowed to air-dry on a flat surface. After the slide was dry, the erythrocytes were fixed by placing the slide in absolute methanol for approximately five minutes, then, allowed to air-dry vertically. Three slides were prepared per mouse. The slides were stained for 20 minutes in 5% Giemsa stain in phosphate buffer containing 3% methanol and 3% 0.1M citric acid, rinsed by dipping them in deionized water until clear, and allowed to air dry vertically. Coverslips were attached with Permount before the erythrocytes are analyzed.

Evaluation criteria:

• Positive. A test material is considered to have elicited a positive response in the mouse erythrocyte micronucleus test if there is a significant dose-related increase in micronuclei and if one or more of the doses induces a statistically significant (p <0.05) increase in micronuclei induction.

• Negative. A test material is considered to have elicited a negative response if the criteria for a positive response are not met.

Statistics:

Binomial comparison of Kastenbaum and Bowman (1970), and the Cochran-Armitage trend test (Armitage, 1955; Cochran, 1984) as described in Margolin and Risko (1986).

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

PCE ratios were reduced 50-60% relative to untreated controls.

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

The %o micronuclei per PCEs or per NCEs were not significantly elevated for any dosage group of male or female mice. Thus, it is concluded that vinyl neononanoate was not clastogenic in this assay.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Vinyl neononanoate did not induce chromosome damage in vivo in mice at dose levels that were cytotoxic to the bone marrow cells.

Executive summary:

Vinyl neononanoate was assessed for its ability to induce chromosome damage in vivo in mice by an O.E.C.D. 474 Testing Guideline study conducted with GLP compliance. Following i.p.administration for three consecutive days vinyl neononanoate did not induce chromosome damage in vivo in mice at dose levels that were cytotoxic to the bone marrow cells. Therefore, vinyl neononanoate is not genotoxic in this in vivo assay.