Registration Dossier

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary literature

Data source

Reference
Reference Type:
secondary source
Title:
SCREENING-LEVEL HAZARD CHARACTERIZATION Terpenoid Primary Alcohols and Related Esters Category
Author:
U.S. Environmental Protection Agency
Year:
2009
Bibliographic source:
U.S. Environmental Protection Agency September, 2009 Hazard Characterization Document.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
Reprotoxicity test was performed on rats by using citral diethylacetal .
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: 1,1-diethoxy-3,7-dimethylocta-2,6-diene
- Molecular formula: C14H26O2
- Molecular weight: 226.35 g/mole
- Smiles notation: O(C(OCC)C=C(CCC=C(C)C)C)CC
- Substance type: Liquid
- Physical state: Organic
- Impurities (identity and concentrations): No data
Specific details on test material used for the study:
- Name of test material: 1,1-diethoxy-3,7-dimethylocta-2,6-diene
- Molecular formula: C14H26O2
- Molecular weight: 226.35 g/mole
- Smiles notation: O(C(OCC)C=C(CCC=C(C)C)C)CC
- Substance type: Liquid
- Physical state: Organic

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on species / strain selection:
No data available
Sex:
female
Details on test animals and environmental conditions:
No data available

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: Corn oil or methylcellulose
Details on exposure:
No data available
Details on mating procedure:
- M/F ratio per cage: No data available
- Length of cohabitation: Mention but duration was not given specific
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy No data available
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)] No data available
- After successful mating each pregnant female was caged (how): No data available
- Any other deviations from standard protocol: No data available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data available
Duration of treatment / exposure:
approx 46 days
Frequency of treatment:
Daily
Details on study schedule:
No data available
Doses / concentrations
Remarks:
0, 125, 250 and 500 mg/kg-day

No. of animals per sex per dose:
No data available
Control animals:
not specified
Details on study design:
No data available
Positive control:
No data available

Examinations

Parental animals: Observations and examinations:
Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data
Oestrous cyclicity (parental animals):
No data
Sperm parameters (parental animals):
No data
Litter observations:
Mortality and body weight were examined.
Postmortem examinations (parental animals):
Postmortem examinations (Parent Animal)
SACRIFICE
- Male animals: No data available
- Maternal animals: Yes
GROSS NECROPSY
- Yes
HISTOPATHOLOGY / ORGAN WEIGHTS
- Yes
Postmortem examinations (offspring):
Postmortem examinations (offspring)
SACRIFICE
- Yes
GROSS NECROPSY
- Gross necropsy : Yes

HISTOPATHOLOGY / ORGAN WEIGTHS
-Yes
Statistics:
No data available
Reproductive indices:
No data available
Offspring viability indices:
yes, viability on day 4 were observed

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Dams showed clinical signs
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
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
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Details on results (P0)

Clinical signs: Clinical signs were observed in treated female rats at 500 mg/kg bw/ day as compared to control.

Body weight: lower body weights and body weight gains were observed at 250 and 500 mg/kg-day as controls.

Reproductive performance: No reproductive toxicity was observed in treated female rats at 125, 250 and 500 mg/kg-day as compared to control.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
body weight and weight gain
Remarks on result:
other: No effect observed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

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

Effect levels (P1)

Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Target system / organ toxicity (P1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
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:
effects observed, treatment-related
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)

Body weight:
Decrease in pups body weight were observed at 500 mg/kg-day

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
other: No effect

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F2 generation

General toxicity (F2)

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 (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Dose descriptor:
other: not specified
Generation:
other: not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Target system / organ toxicity (F2)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 500 mg/kg-day for p genearrtion and 250 mg/kg-day for F1 generation when Sprague-Dawley female rat were treated with 1,1-diethoxy-3,7-dimethylocta-2,6-diene orally by gavage for approx 46 days.
Executive summary:

In Combined reproductive/developmental toxicity screening test, Sprague-Dawley female rat were treated with 1,1-diethoxy-3,7-dimethylocta-2,6-diene in the concentration of 0, 125, 250 and 500 mg/kg-day orally by gavage in Corn oil or methylcellulose. Clinical signs and lower body weights and body weight gains were observed at 250 and 500 mg/kg-day as controls. In addition, no reproductive toxicity was observed in treated female rats at 125, 250 and 500 mg/kg-day. Decrease in pups body weight were observed at 500 mg/kg-day. Therefore, NOAEL was considered to be 500 mg/kg-day for p genearrtion and 250 mg/kg-day for F1 generation when Sprague-Dawley female rat were treated with 1,1-diethoxy-3,7-dimethylocta-2,6-diene orally by gavage for approx 46 days.