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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Subacute(repeated dose study)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data is from Commission of the European Communities

Data source

Reference
Reference Type:
review article or handbook
Title:
Commission of the European Communities DG XI
Author:
Prepared by-Germany
Year:
2007
Bibliographic source:
CLASSIFICATION AND LABELLING OF DANGEROUS SUBSTANCES Recommended form to be used for the proposed classification and labelling of a dangerous substance under Directive 67/548/EEC, January 2007

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD TG 407 and was performed under GLP conditions
Principles of method if other than guideline:
Repeated dose orral toxicity study of 3,7-Dimethylocta-2,6-dienenitrile in rats
GLP compliance:
not specified
Limit test:
no

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 (as cited in study report): 3,7-dimethylocta-2,6-dienenitrile
- Molecular formula (if other than submission substance): C10H15N
- Molecular weight (if other than submission substance): 149.236 g/mole
- Smiles notation (if other than submission substance): N#C\C=C(\CC\C=C(\C)C)C
- InChl (if other than submission substance): 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:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
No data

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
olive oil
Details on exposure:
No data available
Details on mating procedure:
No data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 days
Frequency of treatment:
once daily
Details on study schedule:
No data
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 150 and 450 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
Total: 60
0 mg/kg bw:10 male, 10 female
50 mg/kg bw: 5 male, 5 female
150 mg/kg bw: 5 male, 5 female
450 mg/kg bw:10 male, 10 female
Control animals:
not specified
Details on study design:
No data available
Positive control:
No data available

Examinations

Parental animals: Observations and examinations:
No data available
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
Reproductive organ weight and histopathology were examined.
Postmortem examinations (offspring):
No data available
Statistics:
No data available
Reproductive indices:
No data available
Offspring viability indices:
No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Details on results (P0)

Body weight: Decrease in body weight of 450 mg/kg bw treated male and femlae rats were observed.

Organ weights : No statistically significant differences in absolute or relative weights of testes, epididymides or ovaries were observed as compared to control, except for increased relative testes and epididymides weights in 450 mg/kg bw males. The absolute organ weights were unchanged but the body weights of 450 mg/kg bw dose group were clearly decreased thus leading to a calculated increase in the relative weights of testes and epididymides thus, the calculated organ weight differences can be regarded as to be artefacts. Repeated dose study data do thus not indicate any potential of geranylnitrile to impair fertility.

Histopathology: Histopathology did not detect any corresponding or other substance-related effects on gonads

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
450 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effect on reproductive organ weight, grosspathology and Histopathology

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Details on results (P1)

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Details on results (F1)

No data available

Effect levels (F1)

Remarks on result:
not measured/tested

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to 450 mg/kg bw when Wistar male and female rats were treated with 3,7-Dimethylocta-2,6-dienenitrile orally by gavage in olive oil for 24 days.
Executive summary:

In a repeated dose oral toxicity study, Wistar male and female rats were treated with 3,7-Dimethylocta-2,6-dienenitrile in the concentration of 0, 50, 150 and 450 mg/kg bw orally by gavage in olive oil. Decrease in body weight was observed in 450 mg/kg bw treated male rats. No statistically significant differences in absolute or relative weights of testes, epididymides or ovaries were observed as compared to control, except for increased relative testes and epididymides weights in 450 mg/kg bw males. The absolute organ weights were unchanged but the body weights of 450 mg/kg bw dose group were clearly decreased thus leading to a calculated increase in the relative weights of testes and epididymides thus, the calculated organ weight differences can be regarded as to be artefacts. Repeated dose study data do thus not indicate any potential of geranylnitrile to impair fertility. In addition, no histopathological changes were observed in reproductive organ of treated male and female rats as compared to control. Therefore, NOAEL was considered to 450 mg/kg bw when Wistar male and female rats were treated with 3,7-Dimethylocta-2,6-dienenitrile orally by gavage in olive oil for 24 days.