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Toxicological information

Genetic toxicity: in vivo

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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:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data ia from BAuA report

Data source

Reference
Reference Type:
review article or handbook
Title:
CLH REPORT FOR [3,7-DIMETHYLOCTA-2,6-DIENENITRILE]
Author:
BAuA Federal Institute for Occupational Safety and Health Federal Office for Chemicals Friedrich-Henkel-Weg 1 – 25 D-44149 Dortmund, Germany
Year:
2013
Bibliographic source:
Proposal for Harmonised Classification and Labelling Based on Regulation (EC) No 1272/2008 (CLP Regulation), Annex VI, Part 2 :Substance Name: 3,7-dimethylocta-2,6-dienenitrilen October 2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Principles of method if other than guideline:
Mammalian erthocyte micronucleus assay was performed to determine the mutagenic nature of the test compound 3,7-dimethylocta-2,6-dienenitrile in vivo.
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
3,7-dimethylocta-2,6-dienenitrile
EC Number:
225-918-0
EC Name:
3,7-dimethylocta-2,6-dienenitrile
Cas Number:
5146-66-7
Molecular formula:
C10H15N
IUPAC Name:
3,7-dimethylocta-2,6-dienenitrile
Test material form:
other: Liquid
Details on test material:
- Name of test material: 3,7-dimethylocta-2,6-dienenitrile
- Molecular formula: C10H15N
- Molecular weight: 149.236 g/mol
- Smiles notation: N#C\C=C(\CC\C=C(\C)C)C
- InChl: 1S/C10H15N/c1-9(2)5-4-6-10(3)7-8-11/h5,7H,4,6H2,1-3H3/b10-7+
- Substance type: Organic
- Physical state: Liquid

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male
Details on test animals or test system and environmental conditions:
No details available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Vehicle: olive oil
Details on exposure:
No data
Duration of treatment / exposure:
For 1st experiment:24-h and 48-h
For 2nd experiment:24-h
Frequency of treatment:
single
Post exposure period:
No data
Doses / concentrations
Remarks:
Doses / Concentrations:
312.5, 625.0, 1250.0 mg/kg bw
Basis:
no data
No. of animals per sex per dose:
5 animals per group
Control animals:
not specified
Positive control(s):
cyclophosphamide and vincrist

Examinations

Tissues and cell types examined:
No data
Details of tissue and slide preparation:
No data
Evaluation criteria:
number of polychromatic erythrocytes (PCEs) containing small micronuclei (MN).
Statistics:
No data

Results and discussion

Test results
Sex:
male
Genotoxicity:
positive
Toxicity:
yes
Vehicle controls validity:
not specified
Negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range:No data
- Solubility: No data
- Clinical signs of toxicity in test animals: squatting posture, poor general state, eyelid closure, hyperacitivity
- Evidence of cytotoxicity in tissue analyzed:
- Rationale for exposure:
- Harvest times:
- High dose with and without activation:
- Other: Both of the positive control chemicals (cyclophosphamide and vincristine),
led to the expected increase in the rate of polychromatic erythrocytes
containing small or large micronuclei.

RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels (for Cytogenetic or SCE assay):
- Induction of micronuclei (for Micronucleus assay): The administration of the test substance led to evident signs of toxicity
to a statistically significant and dose-dependent increase in the number of polychromatic erythrocytes (PCEs) containing small micronuclei (MN). The positive response was observed in two experiments carried out independently of each other.

- Ratio of PCE/NCE (for Micronucleus assay):An inhibition of erythropoiesis determined from the ratio of PCEs to normochromatic erythrocytes (NCE) was detected at 1,250 mg/kg after a sacrifice interval of 48h.
- Appropriateness of dose levels and route:
- Statistical evaluation:
For 1st experiment(24-h): probability p<0.01
For 1st experiment(48-h):Probability p<0.05
For 2nd experiment(24-h):Probability p<0.01

Any other information on results incl. tables

1stexperiment:24-h interval

Concentration(mg/kg)

Micronuclei count in 1000 PCEs

0

1.8

312.5

1.2

625

4.5

1250

6.0

1stexperiment:48-h interval

Concentration

Micronuclei count per 1000 PCEs

0 mg/kg

1.6

1250 mg/kg

6.3

2ndexperiment:24-h interval

Concentration

Micronuclei count per 1000 PCEs

0 mg/kg

1.3

1250 mg/kg

6.9

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
Mutagenic effects were known when the test substance 2,6-octadienenitrile, 3,7-dimethyl was exposed to NMRI male mouse in the in vivo micronucleus test.
Executive summary:

In vivo micronucleus test was performed to study the mutagenic effects of the test substance 2,6 -octadienenitrile, 3,7-dimethyl. The dose concentration of test chemical was 312.5, 625.0, 1250.0 mg/kg bw administered to animals by gavage route in olive oil. Two experiments were carried out, 1stat 24 and 48 h interval and 2ndexperiment at 24-h interval,The positive response was observed in two experiments carried out independently of each other.There was no increase in cells with large micronuclei. An inhibition of erythropoiesis determined from the ratio of PCEs to normochromatic erythrocytes (NCE) was detected at 1,250 mg/kg after a sacrifice interval of 48h. Both of the positive control chemicals (cyclophosphamide and vincristine), led to the expected increase in the rate of polychromatic erythrocytes containing small or large micronuclei. The test chemical causes evident signs of toxicity and statistically significant and dose-dependent increase in the number of polychromatic erythrocytes (PCEs) containing small micronuclei (MN). Hence, the chemical 2,6 -octadienenitrile, 3,7-dimethyl is mutagenic in micronucleus test when exposed to NMRI mouse.