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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral, other
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 handbook or collection of data

Data source

Reference
Reference Type:
publication
Title:
Food Flavourings and Compounds of Related Structure. II. Subacute and Chronic Toxicity
Author:
E. C. Hagan, W. H. Hansen, O. G. Fitzhugh, P. M. Jenner, W. I. Jones, Jean M. Taylor, Eleanor L. Long, A. A. Nelson And J. B. Brouwer
Year:
1967
Bibliographic source:
Food & Cosmetic Toxicology; Vol 5, p. 141-157, 1967

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: As mention below
Principles of method if other than guideline:
To evaluate the toxic potential of test substance in male and female rats by oral feed for 17 weeks.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Phenethyl phenylacetate
EC Number:
203-013-1
EC Name:
Phenethyl phenylacetate
Cas Number:
102-20-5
Molecular formula:
C16H16O2
IUPAC Name:
2-phenylethyl phenylacetate
Details on test material:
- Name of test material (as cited in study report): phenethyl phenylacetate
- Substance type: organic
- Physical state: Liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Phenethyl phenyl acetate
- Molecular formula : C16H16O2
- Molecular weight : 240.30 g/mole
- Substance type:Organic
- Physical state: Colorless Liquid

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals or test system and environmental conditions:
T and had access to food and water at all times.TEST ANIMALS

TEST ANIMALS
- Housing: he animals were housed individually in wire cages
- Diet (e.g. ad libitum): Rodent diet ad libitum
- Water (e.g. ad libitum): water ad libitum

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: Rodent diet
Details on oral exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency):The compound was fed in the diet and fresh diets were made and distributed weekly.


Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Not specified.
Duration of treatment / exposure:
17 weeks
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
1000, 2500 and 10000 ppm, corresponding to an average daily intake of 0, 50, 250 or 500 mg/kg bw
Basis:
no data
No. of animals per sex per dose:
Total number of animals 80
0 mg/kg/day-10 male and 10 female
50 mg/kg/day-10 male and 10 female
250 mg/kg/day-10 male and 10 female
500 mg/kg/day-10 male and 10 female
Control animals:
yes, plain diet
Details on study design:
Groups of 10 male and 10 female Osborne-Mendel rats were given diets containing phenethyl phenylacetate at a concentration of 0, 1000, 2500 or 10000 ppm, corresponding to an average daily intake of 0, 50, 250 or 500 mg/kg bw, for 17 weeks. The compound was fed in the diet and fresh diets were made and distributed weekly. The rat's weight, food intake and general condition were recorded every week.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

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

FOOD EFFICIENCY:
- 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:

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

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Haematological examinations were made at termination of the subacute studies
- Parameters checked in table [No.?] were examined. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits

CLINICAL CHEMISTRY: Not specified

URINALYSIS: Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified

IMMUNOLOGY: Not specified


OTHER: The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes , At the termination of the experiments the rats were sacrificed and exsanguinated.

HISTOPATHOLOGY: Yes , The tissues of all the rats were examined macroscopically at the time of sacrifice. These organs, the remaining abdominal and
thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 % buffered formalin-saline solution for histopathological
examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin.
Other examinations:
Tissues from rats dying during the experiment were examined for gross changes and were preserved if autolysis was not advanced. Organs were not weighed but abnormalities and the suspected reason for death were noted
Statistics:
Not specified

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.
Mortality:
no mortality observed
Description (incidence):
No mortality were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Weekly measurement of body weight showed no significant difference between test and control animals.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Weekly measurement of food intake showed no significant difference between test and control animals.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
At termination, haematological examination revealed no effects due to treatment. No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.
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
Description (incidence and severity):
At necropsy, no difference between test and control animals in the weights of major organs was reported.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Gross examination of tissues from all animals revealed no remarkable changes, and histological examination of three to four animals of each sex at the high dose and from the control group revealed no treatment-related lesions.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

Dose descriptor:
NOEL
Effect level:
500 other: mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect were observed at this dose.
Remarks on result:
other: No toxic effect were obnserved at this dose.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The toxicity of test substance was tested in rats by oral exposure for 17 weeks at the dose concentration of 0, 50, 250 or 500 mg/kg bw. No adverse effects were observed at these dose levels.
Executive summary:

Repeated dose oral study for Phenethyl phenylacetate was assessed for its possible toxic potential. For this purpose Subchronic study for 17 weeks was conducted on Osborne-Mendel male and female rats. The test material was exposed at the concentration of 0, 50, 250 and 500 mg/kg bw (1000.2500 and 10000ppm)by oral feed. The animal’s weight, food intake and general condition were recorded every week. Haematological examinations were made at termination of the subacute studies. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits. At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 ~o buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin. No mortality observed. No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control in clinical sign, Body weight, Food intake , Haematology, organ weight ,gross and histopathology . Hence the NOAEL was considered to be 500 mg/kg bw for Phenethyl phenylacetate in male and female rats by oral feed for 17 weeks study.

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