Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Toxicology and carcinogenesis of benzyl acetate (CAS NO. 140-11-4) in F344/N rats and B6C3F1 mice (gavage studies)
Author:
Abdo, K. et al
Year:
1986
Bibliographic source:
National Toxicology Program, Publication No. 86-2506, USA, 1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
Male and female F344/N rats obtained from Harlan Industries and observed for 12 days. Animals were approximately 6 weeks old when placed on study. Groups of five rats of each sex were administered 0, 250, 500, 1,000, 2,000, or 4,000 mg/ kg benzyl acetate in corn oil by gavage for 14 consecutive days. Animals were housed five per cage and received water and feed ad libitum. Rats were observed daily for mortality and were weighed weekly. On day 16, surviving animals were killed and necropsies were performed on all animals.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Benzyl Acetate
- Physical state: water-white liquid with a pear-like odour
- Other:
Melting Point: -51.3°C
Boiling Point: 213°C
Vapor Pressure: 1.99 mm Hg at 60'C
Density: 1.05
Refractive Index: 1.4998
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzyl Acetate
- Physical state: water-white liquid with a pear-like odour

Melting Point: -51.3°C
Boiling Point: 213°C
Vapor Pressure: 1.99 mm Hg at 60'C
Density: 1.05
Refractive Index: 1.4998

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Harlan Industries Indianapolis. I N
- Age at study initiation: 6 weeks
- Weight at study initiation: 103.0-127.4g
- Housing: Bedding: Beta-Chips heat treated hardwood chips
Cages: Polycarbonate
Cage filters: Spun-bonded polyester filters
- Diet (e.g. ad libitum): Wayne Lab-Blox Allied Mills. ad libitum
- Water (e.g. ad libitum): Tap water supplied through automatic watering system. ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 40-60
- Air changes (per hr): 15

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: Doses were prepared on a weight-to-volume basis by pipetting the appropriate amount of benzyl acetate into a vessel and adding enough corn oil to give the desired concentration. Solutions were mixed until they were visually homogeneous. Rats received 5 ml/kg. Benzyl acetate/corn oil mixtures were analyzed at Midwest Research Institute and found to be stable at room temperature for at least 7 days. Once prepared, benzyl acetate/corn oil mixtures were stored at 5O°C for no longer than 11 days.


VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Concentration in vehicle: Male and female rats: 0, 250, 500, 1,000, 2,000 or 4,000 mg/kg body weight in corn oil
- Amount of vehicle (if gavage): 5 ml/kg for rat
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Samples of benzyl acetate in corn oil were selected at random and analyzed periodically at Southern Research Institute. Results of these analyses and of referee analyses at Midwest Research Institute indicated that benzyl acetate/ corn oil mixtures were properly formulated.
Duration of treatment / exposure:
14 consecutive days
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Dose / conc.:
2 000 mg/kg bw/day (nominal)
Dose / conc.:
4 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5 animals
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: based on an acute study
Positive control:
No

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Obserted daily for mortality and clinical signs.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Observed daily for mortality and clinical signs.

BODY WEIGHT: Yes
- Time schedule for examinations: at the start and end of dosing

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: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: Necropsies performed on all animals
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: No
Other examinations:
No further data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY All rats that received 4,000 mg/kg body weight were dead by the afternoon of day 2, and all rats that received 2,000 mg/ kg were dead by the afternoon of day 5. No other rats died.

BODY WEIGHT AND WEIGHT GAIN Final mean body weights of both sexes of dosed rats were comparable to control animals

GROSS PATHOLOGY The cecum was redder than normal in 3/5 males and 3/ 5 females that received 4,000 mg/ kg.

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects clinical signs; mortality; body weight

Target system / organ toxicity

Critical effects observed:
no

Any other information on results incl. tables

Male/Female

Dose

Survival

Final weight relative to control %

Male

0

5/5

-

250

5/5

99.2

500

5/5

96.1

1000

5/5

95.4

2000

0/5

-

4000

0/5

-

Female

0

5/5

-

250

5/5

97.8

500

5/5

99.5

1000

5/5

97.7

2000

0/5

-

4000

0/5

-

Applicant's summary and conclusion

Conclusions:
The NOAEL was found to be 500 mg/kg body weight after dosing rats with benzyl acetate in corn oil for 14 days.
Executive summary:

Male and female F344/N rats were obtained from Harlan Industries and observed for 12 days. Animals were approximately 6 weeks old when placed on study. Groups of five rats of each sex were administered 0, 250, 500, 1,000, 2,000, or 4,000 mg/ kg

benzyl acetate in corn oil by gavage for 14 consecutive days. Animals were housed five per cage and received water and feed ad libitum. Rats were observed daily for mortality and were weighed weekly. On day 16, surviving animals were killed and necropsies were performed on all animals. The NOAEL was found to be 500 mg/kg body weight after dosing rats with benzyl acetate in corn oil for 14 days.