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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
reproductive toxicity, other
Remarks:
chronic toxicity study
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 from peer reviewed journal

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:
Fd Cosmet. Toxicol. Vol 5, pp. 141-157. 1967

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: As mention below
Principles of method if other than guideline:
Reproductive toxicity study of 2-phenylethyl 2-phenylacetate was performed on Osborne-Mendel rats.
GLP compliance:
not specified
Limit test:
no
Justification for study design:
not specified

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
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Phenethyl phenylacetate
- IUPAC Name: 2-phenylethyl 2-phenylacetate
- Molecular formula : C16H16O2
- Molecular weight : 240.30 g/mole
- Inchi: 1S/C16H16O2/c17-16(13-15-9-5-2-6-10-15)18-12-11-14-7-3-1-4-8-14/h1-10H,11-13H2
- Smilies notation:c1(CC(OCCc2ccccc2)=O)ccccc1
- Substance type: Organic
- Physical state: Colorless Liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Phenethyl phenylacetate
- IUPAC Name: 2-phenylethyl 2-phenylacetate
- Molecular formula : C16H16O2
- Molecular weight : 240.30
- Inchi: 1S/C16H16O2/c17-16(13-15-9-5-2-6-10-15)18-12-11-14-7-3-1-4-8-14/h1-10H,11-13H2
- Smilies notation:c1(CC(OCCc2ccccc2)=O)ccccc1
- Substance type: Organic
- Physical state: Colorless Liquid

Test animals

Species:
rat
Strain:
Osborne-Mendel
Details on species / strain selection:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing:The animals were housed individually in wire cages
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
corn oil
Details on exposure:
Details on exposure
PREPARATION OF DOSING SOLUTIONS: test material soluble in corn oil.
DIET PREPARATION
- Rate of preparation of diet (frequency):Fresh diets were made and distributed weekly
- Mixing appropriate amounts with (Type of food )
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): corn oil
- Concentration in vehicle: 0,500 mg/kg bw/day
- Amount of vehicle (if gavage): 1ml of solution/kg daily

- Lot/batch no. (if required): No data available
- Purity: No data available
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
17 weeks
Frequency of treatment:
Daily
Details on study schedule:
not specified
Doses / concentrations
Dose / conc.:
500 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Total:40
0 mg/kg bw/day: 10 male and 10 female
500.00 mg/kg bw/day: 10 male and 10female
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified

Examinations

Parental animals: Observations and examinations:
Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes

DETAILED CLINICAL OBSERVATIONS: Yes

Time schedule: every week.


BODY WEIGHT: Yes
Time schedule for examinations: every week.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Food consumption was determined every week.

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: Yes / No / No data: No data available


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
Time schedule for examinations:
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
not specified
Postmortem examinations (parental animals):
SACRIFICE:At the termination of the experiments the rats were sacrificed and exsanguinated.

- Gross necropsy : yes

HISTOPATHOLOGY / ORGAN WEIGHTS: 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% buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin. 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.
Postmortem examinations (offspring):
not specified
Statistics:
not specified
Reproductive indices:
not specified
Offspring viability indices:
not specified

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
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:
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
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
effects observed, treatment-related
Description (incidence and severity):
No effects on reproductive organ weight

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: No effects on reproductive organ was noted

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: 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:
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 (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

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 (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)

Description (incidence and severity):
The animals were housed individually in wire cages

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:
No Observed Adverse Effect Level (NOAEL) for reproductive toxicity was considered to 500mg/kg/day, When male and female Osborne-Mendel rats were treated with phenethyl phenylacetate (102-20-5) orally for 17weeks.
Executive summary:

In a Reproductive /chronic toxicity study, 10 male and female Osborne-Mendel rats were treated with phenethyl phenylacetate in the concentration 0 and 500 mg/kg bw/day orally by gavage from 17 weeks. No treatment-related clinical signs and premature deaths were observed. No relevant necropsy findings were noted. No effects on reproductive organ i.e testes was noted in treated rats at 500 mg/kg bw. Hence Now Observed Adverse Effect Level (NOAEL) for reproductive toxicity was considered to 500 mg/kg/day, when male and female Osborne-Mendel rats were treated with phenethyl phenylacetate (102-20-5) orally for 17 weeks.