5-vinylnorborn-2-ene

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Guideline study with some deviations compared to current standards. Original study report not available.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

. Only half prescribed number of cells scored per animal for mitotic index and analysed for abberations.

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

5-vinylnorborn-2-ene

EC Number:

221-259-8

EC Name:

5-vinylnorborn-2-ene

Cas Number:

3048-64-4

Molecular formula:

C9H12

IUPAC Name:

5-ethenylbicyclo[2.2.1]hept-2-ene

Test material form:

liquid

Details on test material:

- Test substance: 5-vinyl-2-norbornene (CAS 3048-64-4)
- Purity: 98.44%
- Source: Union Carbide Corporation, South Charleston, West Virginia
- LOT 59FGC27

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: M: 219.6 - 270g, F:145.7-176.4g
- Housing: singly in stainless steel wire mesh cages.
- Diet and water: ad libitum except during exposure period
- Acclimation period: 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 66-77
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Details on exposure:

TYPE OF INHALATION EXPOSURE: whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 900l stainless steel chamber with glass window.
- Air flow rate: 200l/min
- Air change rate: 13-14/hr

TEST ATMOSPHERE
- Vapour generated by liquid metering piston pump feeding into a heated cylindrical glass column evaporator at 43-4-47.6degC.
- Brief description of analytical method used: Sampled every 30 mins, analysis by GC-FID. LOD=2ppm.
- Samples taken from breathing zone: no

Duration of treatment / exposure:

5 days

Frequency of treatment:

6hr/day

Post exposure period:

Half of exposed groups (5 males, 5 females per dose group): 24 hours.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 50, 150, 350ppm
Basis:
other: target concentration

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 48.1±1.29, 146±9.2, 336±8.5ppm
Basis:
analytical conc.

No. of animals per sex per dose:

10 (5 for positive controls)

Control animals:

yes, sham-exposed

Positive control(s):

cyclophosphamide
- Route of administration: ip
- Doses / concentrations: 30mg/kg

Examinations

Tissues and cell types examined:

Femoral bone marrow.

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION: Femoral bone marrow flushed into a centrifuge tube using 10–15 ml of freshly prepared Hank’s balanced salt solution (pH 7.0). The suspension was centrifuged and the pellet resuspended in 0.075 M KCl and incubated at 37°C for 20–30 min. Cells were centrifuged and fixed with two or three changes of 3:1 methanol–acetic acid. Fixed cells were refrigerated at 4°C for 12 h before slide preparation. Cells were then centrifuged and resuspended in fixative. The suspension was dropped onto a clean wet slide, air dried, stained with a dilute Giemsa solution, rinsed with water, air dried again and then a coverslip was applied.

Analysis of the two exposure groups was effectively at 6 and 24hrs post exposure.

METHOD OF ANALYSIS: 500 cells per animal scored to determine a mitotic index, and 50 metaphase cells per animal evaluated for frequency and type of chromosomal damage. Each cell was evaluated for chromosome number, specific chromosome or chromatid aberration or exchanges.

Statistics:

Mann–Whitney U-test to evaluate chromosome abberations

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

A statistically significant weight decrease was seen for the 6hr 50ppm males sampling group but since no effects were seen at higher concentrations the effect was deemed not biologically significant.

Applicant's summary and conclusion

Conclusions:

Negative

Executive summary:

In an in vivo chromosome abberation inhalation study using Sprague-Dawley rats, 5 -vinyl-2 -norbornene showed no evidence of clastogenic effects at any tested concentration.