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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
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:
Safety Evaluation of Certain Food Additives and Contaminants
Author:
Joint FAO/WHO Expert Committee on Food Additives (JECFA) World Health Organization
Year:
2002
Bibliographic source:
WHO Food Additive Series: 48, 2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Repeated dose oral toxicity test was performed on male and female rats to determine the oral toxic nature of Citral diethylacetal
GLP compliance:
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: Citral diethylacetal
- IUPAC name: 1,1-diethoxy-3,7-dimethylocta-2,6-diene
- Molecular formula: C14H26O2
- Molecular weight: 226.357 g/mol
- Substance type: Organic
- Physical state: Solid
- Purity: No data
- Impurities (identity and concentrations): No data

Test animals

Species:
rat
Strain:
not specified
Details on species / strain selection:
No data
Sex:
male/female
Details on test animals and environmental conditions:
No data available

Administration / exposure

Route of administration:
oral: unspecified
Details on route of administration:
No data
Vehicle:
not specified
Details on oral exposure:
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:
84 days (12 weeks)
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
0 or 56 mg/Kg bw
No. of animals per sex per dose:
Total: 42
0 mg/Kg bw: 21 rats
56 mg/Kg bw: 21 rats
Control animals:
yes, concurrent vehicle
Details on study design:
No data available
Positive control:
No data available

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: During the study
- Cage side observations checked in table [No.?] were included. The animals were observed for behaviour, appearance and growth

DETAILED CLINICAL OBSERVATIONS: Not specified
- Time schedule: Not specified

BODY WEIGHT: Not specified
- Time schedule for examinations: Not specified

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

FOOD EFFICIENCY: Yes
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations: Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Not specified
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters checked in table [No.?] were examined. Haemoglobin concentration was determined

CLINICAL CHEMISTRY: Not specified
- Time schedule for collection of blood: Not specified
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters checked in table [No.?] were examined. Not specified

URINALYSIS: Not specified
- Time schedule for collection of urine: Not specified
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified
- Parameters checked in table [No.?] were examined. Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not specified

IMMUNOLOGY: Not specified
- Time schedule for examinations: Not specified
- How many animals: Not specified
- Dose groups that were examined: Not specified
- Parameters checked in table [No.?] were examined. Not specified

OTHER: Not specified
Sacrifice and pathology:
No dataGROSS PATHOLOGY: Yes, gross examination was performed to determine the organ weight

HISTOPATHOLOGY: Not specified
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
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:
no effects observed
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Clinical signs and mortality:
Clinical signs: The treated animals had normal behaviour and appearance during the study
Mortality: No data

Body weight and weight gain: No data

Food consumption and compound intake: The animals were note affected for food consumption

Food efficiency : The animals were note affected for food efficiency

Water consumption and compound intake: No data

Opthalmoscopic examination: No data

Haematology: No changes in haemoglobin concentration were observed

Clinical chemistry: No data

Urinanalysis: No data

Neurobehaviour: No data

Organ weights: Gross examination revealed no changes in organ weights

Gross pathology: No data

Histopathology: No data

Effect levels

Dose descriptor:
NOAEL
Effect level:
56 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant changes were observed

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No Observed Adverse Effect Level (NOAEL) for Citral diethylacetal is 56 mg/kg in male and female rats.
Executive summary:

Repeated dose oral toxicity test was performed on male and female rats to determine the oral toxic nature of Citral diethyacetal. The animals were treated with the test chemical Citral diethylacetal at a dose level of 0 or 56 mg/Kg bw for 12 weeks (84 days). The animals were observed for Daily food consumption, growth rate, food intake and efficiency, gross pathology including organ weight and haemoglobin concentration. The treated animals had normal behaviour and appearance during the study. Growth, food intake, and efficiency of food use were reported not to be affected, and gross examination revealed no changes in organ weights or haemoglobin concentration. Hence, the No Observed Adverse Effect Level (NOAEL) for Citral diethylacetal is 56 mg/kg in male and female rats.