Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
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:
other: OECD 422
Principles of method if other than guideline:
Developmental toxicity 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:
1,1-diethoxy-3,7-dimethylocta-2,6-diene
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 test animals and environmental conditions:
Sex Female

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
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
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
Duration of treatment / exposure:
approx 46 days.
Frequency of treatment:
Daily
Duration of test:
7 days prior to cohabitation and through cohabitation, gestation, delivery and day 4 of lactation
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

Examinations

Maternal examinations:
Clinical signs, body weight, food consumption and gross lesions examined.
Ovaries and uterine content:
No data available
Fetal examinations:
Body weights and body weight gains were observed.
Statistics:
No data available
Indices:
No data available
Historical control data:
No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
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
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Effects on pregnancy duration:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Other effects:
not specified
Details on maternal toxic effects:
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 (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
125 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
clinical signs
body weight and weight gain
other: No effect
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: reproductive toxicity

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Reduction in number of live offspring:
not specified
Changes in sex ratio:
not specified
Fetal/pup body weight changes:
effects observed, treatment-related
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
not specified
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
Body weight: Lower body weight compared to controls was observed only at 500 mg/kg-day.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes
other: No effect observed

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified
Relation to maternal toxicity:
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. But, developmental toxicity was observed as decrease in pups body weight 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.