Benzyl acetate

Repeated dose toxicity: oral

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

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study 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

Test material information

Constituent 1

Reference substance name:

Benzyl acetate

EC Number:

205-399-7

EC Name:

Benzyl acetate

Cas Number:

140-11-4

Molecular formula:

C9H10O2

IUPAC Name:

benzyl acetate

Constituent 2

Reference substance name:

alpha-acetoxytoluene; benzyl ethanoate; acetic acid, benzyl ester

IUPAC Name:

alpha-acetoxytoluene; benzyl ethanoate; acetic acid, benzyl ester

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 or test system 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 / concentrations

Doses / concentrations 1

Dose / conc.:

250 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

2 000 mg/kg bw/day (nominal)

Doses / concentrations 5

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.