3,7-dimethylocta-2,6-dienenitrile

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Data is from study report

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2006

Report date:

2006

Reference 2

Reference Type:

review article or handbook

Title:

Commission of the European Communities DG XI-DEVELOPMENTAL TOXICOLOGY

Author:

CLASSIFICATION AND LABELLING OF DANGEROUS SUBSTANCES, Germany

Year:

2007

Bibliographic source:

Commission of the European Communities DG XI, January 2007

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

Prenatal oral developmental toxicity study of 3,7-dimethylocta-2,6-dienenitrile in rats

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

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

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/mol
- Substance type: Organic
- Physical state: solid

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

Sex: Female

Administration / exposure

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

olive oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: 3,7-dimethylocta-2,6-dienenitrile was administered in olive oil.

VEHICLE
- Justification for use and choice of vehicle (if other than water): olive oil
- Concentration in vehicle:0, 25, 100, and 250 mg/kg body weight/day
- Amount of vehicle (if gavage): 5 ml/kg BW
- Lot/batch no. (if required): No data available
- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Presumed pregnant female rats were used.

Duration of treatment / exposure:

14 days

Frequency of treatment:

once daily

Duration of test:

14 days

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 25, 100, and 250 mg/kg body weight/day
Basis:

No. of animals per sex per dose:

Total: 100
0 mg/kg bw: 25 female
25 mg/kg bw: 25 female
100 mg/kg bw: 25 female
250 mg/kg bw: 25 female

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Examinations

Maternal examinations:

Body weight and food consumption clinical sign, gross pathology were observed.

Ovaries and uterine content:

corpora lutea, number and distribution of implantation sites (differentiated as resorptions, live and dead fetuses) were determined

Fetal examinations:

sexed, Fetal body weight, clinical sign,Gross pathology and histopathology were examined.

Statistics:

No data available

Indices:

No data available

Historical control data:

No data available

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Clinical signs: Clinical sign of toxicity were observed in female rats at 250 mg/kg bw

Body weight:Impaired absolute and relative body weight of treated female rats were observed as compared to control.

Food consumption: Reduced food consumption were observed in 100 and 250 mg/kg bw treated female rats as compared to control.

Reproductive performance: No effect on gestational parameters were observed in treated female rats as compared to control.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

25 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Clinical signs: Mild sign of prenatal toxicity was observed at 250 mg/kg bw .

Body weight: statistically significant decrease in fetal body weight were observed in 250 mg/kg bw

Histopathology: some skeletal variations (I.E. minor delays in fetal ossification process of skull, ertebral colum and sternebrae) were observed but, no indication od selective teratogenicity were observed upto and including 250 mg/kg bw. No substance induced sign of embryo / fetotoxicity were observed at 125 and 100 mg/kg bw.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: No effect on sexed, Fetal body weight, clinical sign,Gross pathology and histopathology

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 50 mg/kg bw for P generation and 100 mg/kg bw for F1 generation when Wistar female rats were treated with 3,7-dimethylocta-2,6-dienenitrile in olive oil orally by gavage for 14 days.

Executive summary:

In a Prenatal oral developmental toxicity study, Wistar female rats were treated with 3,7-dimethylocta-2,6-dienenitrile in the concentration of 0, 25, 100, and 250 mg/kg body weight/day in olive oil orally by gavage for 14 days .Clinical sign of toxicity were observed in female rats at 250 mg/kg bw. Impaired absolute and relative body weight and reduced food consumption was observed in 100 and 250 mg/kg bw treated female rats.No effects on gestational parameters were observed in treated female rats. Mild sign of prenatal toxicity was observed at 250 mg/kg bw. Statistically significant decrease in fetal body weight were observed in 250 mg/kg bw. In addition, some skeletal variations (I.E. minor delays in fetal ossification process of skull, ertebral colum and sternebrae) were observed but, no indication od selective teratogenicity were observed upto and including 250 mg/kg bw. No substance induced sign of embryo / fetotoxicity were observed at 125 and 100 mg/kg bw. Since, gestational parameters were observed in treated female rats. Hence, NOAEL was considered to be 50 mg/kg bw for P generation and 100 mg/kg bw for F1 generation whenWistar female rats were treated with 3,7-dimethylocta-2,6-dienenitrile in olive oil orally by gavage for 14 days.