Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from collection of data.

Data source

Reference
Reference Type:
secondary source
Title:
Comparison of estimated daily intakes of flavouring substances with no-observed-effect levels
Author:
I.C. Munro, B. Danielewska-Nikiel
Year:
2006
Bibliographic source:
Food and Chemical Toxicology 44 (2006) 758–809

Materials and methods

Principles of method if other than guideline:
Benzyl alcohol is the parent compound and p-anisyl acetate is its alkoxy derivate and a metabolite. Based on this correlation, benzyl alcohol has been used as a read across.
Two years toxicity study was conducted to evaluate the chronic toxic nature of the test compound Benzyl alcohol.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): Benzyl alcohol
- Molecular formula (if other than submission substance): C7-H8-O
- Molecular weight (if other than submission substance): 108.139 g/mol
- Substance type: Organic
- Physical state: No data available
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzyl alcohol
- Molecular formula (if other than submission substance): C7-H8-O
- Molecular weight (if other than submission substance): 108.139 g/mol
- Substance type: Organic

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
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:
2 years
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
0, 200 or 400 mg/Kg bw/day


No. of animals per sex per dose:
No data available
Control animals:
yes, concurrent vehicle
Details on study design:
No data available

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
- Cage side observations checked in table [No.?] were included. Mortality was noted

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule:

BODY WEIGHT: No data
- Time schedule for examinations:

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

FOOD EFFICIENCY: No data
- 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: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data - Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data
Sacrifice and pathology:
No data available
Other examinations:
No data available
Statistics:
No data available

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
mortality observed, non-treatment-related
Description (incidence):
Mortality: In comparison to controls, a 50% reduction was observed in the survival of female rats at both dose levels; deaths were attributed to gavage error rather than to compound- related toxicity.
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
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified

Effect levels

Dose descriptor:
NOEL
Effect level:
400 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects noted
Remarks on result:
other: No toxic effect observed.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No Observed Effect Level (NOEL) for the test compound Benzyl alcohol (100-51-6)is considered to be 400 mg/Kg bw/day in rats by oral gavage.
Executive summary:

Two years chronic toxicity study was conducted on rats to evaluate the toxic nature of the test compound Benzyl alcohol. The test substance was exposed to male and female rats at the concentration of 0, 200 or 400 mg/Kg bw/day by oral gavage. The animals were observed for mortality and clinical signs. No significant mortality or clinical sign observed. The No Observed Effect Level (NOEL) for the test compound Benzyl alcohol is considered to be 400 mg/Kg bw/day. Based on the results of the rat study a NOEL of 400 mg/kg body weight/day was selected for the calculation of the margin of safety of Benzyl alcohol