3,7-dimethylocta-2,6-dienenitrile

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

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

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

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

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

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

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

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: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

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

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

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: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

not specified

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

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

No data available

Remarks on result:

not measured/tested

Reproductive effects observed:

not specified

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.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

450 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is Klimisch 2 and from Commission of European Communities

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity:

Based on the data available for target Geranyl nitrile (CAS no 5146-66-7) for reproductive toxicity are summarized below

In a study given by Commission of European Communities (2007), repeated dose oral toxicity was evaluated in Wistar male and female rats by using 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 for P generation when Wistar male and female rats were treated with 3,7-Dimethylocta-2,6-dienenitrile orally by gavage in olive oil for 24 days.

Based on the prediction done by using QSAR Toolbox 3.4 (2016), reproductive toxicity was estimated in Crj: CD (SD) male and female rats by using Geranyl nitrile orally by gavage in corn oil. No effect on reproductive toxicity was observed in treated male and female rats. Therefore, estimated NOAEL was considered to be 429 mg/kg bw when Crj: CD (SD) male and female rats were treated with Geranyl nitrile orally by gavage in corn oil.

In a study report given by Fragrance Materials Association of the United States (2006), reproductive toxicity was evaluated inWistar female rats by using 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 250 mg/kg bw for P generation whenWistar female rats were treated with 3,7-dimethylocta-2,6-dienenitrile in olive oil orally by gavage for 14 days.

Thus, based on weight of evidence for target Geranyl nitrile (CAS no 5146-66-7) is likely to be non hazardous as reproductive toxicant by oral route of exposure.

Short description of key information:

Geranyl nitrile (CAS no 5146-66-7) is likely to be non hazardous as reproductive toxicant by oral route of exposure.

Justification for selection of Effect on fertility via oral route:

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

Effects on developmental toxicity

Description of key information

Geranyl nitrile (CAS no 5146-66-7) is likely to be non hazardous as developmental toxicant by oral route of exposure.

Link to relevant study records

Reference

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

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

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

Sex: Female

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

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

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

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.

Dose descriptor:

NOAEL

Effect level:

25 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

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.

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

Abnormalities:

not specified

Developmental effects observed:

not specified

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.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is Klimisch 2 and fromby Fragrance Materials Association of the United States (2006) and Commission of the European Communities DG XI (2007)

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Developmental toxicity:

Based on the data available for target Geranyl nitrile (CAS no 5146-66-7) for reproductive toxicity are summarized below

In a study report given by Fragrance Materials Association of the United States (2006) and Commission of the European Communities DG XI (2007), Prenatal oral developmental toxicity was evaluated in Wistar female rats by using 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 when Wistar female rats were treated with 3,7-dimethylocta-2,6-dienenitrile in olive oil orally by gavage for 14 days.

Thus, based on weight of evidence for target Geranyl nitrile (CAS no 5146-66-7) is likely to be non hazardous as developmental toxicant by oral route of exposure.

Justification for selection of Effect on developmental toxicity: via oral route:

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.

Justification for classification or non-classification

Based on weight of evidence for target Geranyl nitrile (CAS no 5146-66-7) is likely to be non hazardous as reproductive and Developmental toxicity:toxicant by oral route of exposure.