Cyclododeca-1,5,9-triene

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference 1

Reference Type:

other: secondary source

Title:

Unnamed

Year:

1996

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

Method: see references

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

1,5,9-Cyclododecatriene

IUPAC Name:

1,5,9-Cyclododecatriene

Details on test material:

TS: 1,5,9-cyclododecatriene, purity 100%

Test animals

Species:

rat

Strain:

other: Crl:CD (SD) BR

Sex:

male

Details on test animals or test system and environmental conditions:

- Age: 51 days
- Weight at study initiation: mean 231.4 g

Administration / exposure

Route of administration:

inhalation

Vehicle:

air

Details on exposure:

ADMINISTRATION: nose-only
- vapour atmosphere generated by metering the liquid test substance into a nebulizer
Sampling times and number of samples:   
- Test atmosphere: one sample during each exposure to determine  concentration and particle size distribution; result: 3200 +/- 280 mg/m3;  mass median aerodynamic diameter 3.6 µm   

-atmospheric concentration measured by gas chromatography and gravimetric analysis

-further details: see references

Duration of treatment / exposure:

6 hours each on 2 consecutive days

Frequency of treatment:

once per day on 2 consecutive days

Doses / concentrations

Dose / conc.:

500 ppm (nominal)

Remarks:

3300 mg/m3 (aerosol/vapor); 3200 +/- 280 mg/m3 (analytical concentration)

No. of animals per sex per dose:

No. of animals per dose: 10 exposed, 5 negative control

Control animals:

yes

Positive control(s):

Control groups and treatment:
- positive: 40 mg cyclophosphamide/kg by oral intubation
-negative: concurrent houseline air   

Examinations

Tissues and cell types examined:

Bone marrow: At least 3 slides per rat (fixed, and stained with acridine orange), 2000 PCEs per rat scored for  micronuclei, 1000 erythrocytes scored for PCE/NCE ratio ; Representative slides from each rat were examined blindly.

further EXAMINATIONS: 
- Clinical observations: during exposure (including alerting stimulus)
- Organs examined at necropsy: marrow  from 1 femur
- Body weights: yes

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Remarks:

no mortalities

Additional information on results:

MORTALITY: no test substance-induced mortality

CLINICAL SIGNS:   
- During exposure: no clinical signs, response to alerting stimulus  diminished or absent   
- After exposure: lethargy and/or irregular respiration. 

BODY WEIGHT CHANGES: losses in treated and positive control rats

EFFECT ON MITOTIC INDEX OR PCE/NCE RATIO:    No statistically significant depressions in the proportion of PCEs  among 1000 erythrocytes were observed.

GENOTOXIC EFFECTS:    There were no statistically significant increases in the MNPCE  frequency in rats exposed to the test substance. A statistically  significant increase in the MNPCE frequency was found in the positive  control rats.

Applicant's summary and conclusion

Conclusions:

Under the conditions tested, the test substance did not induce chromosomal aberration in experimental animals and thus, was suggested to be non-clastogenic and non-aneugenic.