Butyl benzoate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 September 2011 to 06 December 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butyl benzoate

EC Number:

205-252-7

EC Name:

Butyl benzoate

Cas Number:

136-60-7

Molecular formula:

C11H14O2

IUPAC Name:

butyl benzoate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 8684-90, Experimental

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BIOAGRl's (DF) rearing house
- Age at study initiation: 10 weeks
- Weight at study initiation: 305-347 grams
- Fasting period before study: no
- Housing: 41x34x20 cm polypropylene cages with autoclaved wood shavings and stainless steel mesh lids containing five rats of same sex per cage on the experimental phase were used
- Diet (e.g. ad libitum): Pelleted and autoclaved commercial diet for rats
- Water (e.g. ad libitum): Filtered potable water
- Acclimation period: 14 days prior to exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.2 to 21.8°C
- Humidity (%): 37.9 to 69.8%
- Air changes (per hr): 10 to 20 air changes in the room per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours light

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The chamber used was a Jaeger Inhalation Chamber, Mark II with a collision nebulizer integrated system
- Exposure chamber volume: 667 ml/min/animal
- Method of holding animals in test chamber: Rats were exposed to the aerosolized test item in plexiglass nose-only tubes applying a direct-flow exposure principle.
- Source and rate of air: The source of air used came from an air compressor
- Method of conditioning air: The compressed air was treated with a filter absolute model F - 771 K03 Trox and filter of activated carbon F - 760 Trox;
- System of generating particulates/aerosols: collision nebulizer integrated system
- Method of particle size determination: Two equally time-spaced air samples were taken from the vicinity of the breathing zone using an air sampling pump previously calibrated to a 0.500 L/min flow rate, to collect the aerosol in a Seven Stage Cascade Impactor (ln-Tox, Albuquerque, New Mexico, U.S.A.) for five minutes. Before and after sampling, the stages were weighed
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber: The study animals were maintained at a temperature from 22.3 to 23.8°C and a relative humidity from 51 to 59%. Temperature and relative humidity were recorded four times during the exposure. The equipment used to measure temperature and humidity was a digital thermo-hygrometer TFA;

TEST ATMOSPHERE
- Brief description of analytical method used: Rats were exposed to the aerosolized test item in plexiglass nose-only tubes applying a direct-flow exposure principle.
- Samples taken from breathing zone: yes/no

VEHICLE
- Composition of vehicle (if applicable):
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Duration of exposure:

4 h

No. of animals per sex per dose:

five/sex/cage

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Aerodynamic particle-size distribution: Before and after sampling, the stages were weighed
- Mortality: yes
- Necropsy of survivors performed: yes. All exposed rats were necropsied and subsequently incinerated. The presence or absence of any macroscopic finding observed on gross necropsy was recorded systematically and individually
- Clinical examinations: Following exposure, two clinical observations were made during the first 24 hours and then daily during a fourteen­ day observation period

Statistics:

Not applicable

Results and discussion

Preliminary study:

Preliminary test without animals was conducted to define the appropriate conditions to reach a test atmosphere with adequate particle-size.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

>= 15.246 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No compound-related deaths were observed during this study.

Clinical signs:

other: The compound-related clinical signs observed in this study were: piloerection, slight apathy, kyphosis, slight dyspnea, tremors, epistaxis and chromodacryorrhea. These were acute systemic signs that started on days 0 and 1 and reverted on days 1 to 3 of t

Body weight:

The mean body weight increased for both sexes in all post-exposure weighings, except in the first post-exposure weighing. All animals exceeded their initial body weight at the end of the observation period of 14 days.

Gross pathology:

No compound-related macroscopic findings were observed during this study.

Other findings:

Histopathology
It was not considered necessary due to the reversibility of the clinical signs and to the absence of compound-related macroscopic findings.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The combined (males and females) median lethal concentration in a 4-hour nose-only exposure period (4-h LC50) to the test substance aerosol inhaled by Wistar Hannover rats was greater than 15.246 mg/L.