Phenethyl acetate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

30 October, 1996 - 22 November, 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Standard inhalation test conducted in accordance with test guideline and GLP principles.

Justification for type of information:

Based on structural, physicochemical and toxicity data, similarities between benzyl acetate is considered appropriate for use of the information by read across to phenyl ethyl acetate - see review attached in IUCLID section 13.2.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

30 October, 1996 - 22 November, 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Standard inhalation test conducted in accordance with test guideline and GLP principles.

Justification for type of information:

Based on structural, physicochemical and toxicity data, similarities between benzyl acetate is considered appropriate for use of the information by read across to phenyl ethyl acetate - see review attached in IUCLID section 13.2.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

:A single exposure level of 0.766 mg/L was used as this was the maximum attainable concentration of vapour at ambient temperature.

Principles of method if other than guideline:

The acute inhalation toxicity of benzyl acetate was assessed by exposing a group of rats, for a period of 4 hours, to the vapour of the test substance at a concentration of 0.766 mg/I of air. This was the maximum attainable concentration of vapour at ambient temperature. A further group, acting as a control, was exposed to clean air only.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Manston Road, Margate, Kent, England
- Age at study initiation: between 8 weeks and 12 weeks old
- Weight at study initiation: 198 - 273 g
- Fasting period before study: no
- Housing: The holding cages (size 35 cm x 53 cm x 25 cm height) were made of stainless steel sheet and wire mesh and were suspended on a movable rack.
- Diet (e.g. ad libitum): measured amounts
- Water (e.g. ad libitum): measured amounts
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hous light and 12 hours dark

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

ENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: whole-body exposure chambers
- Exposure chamber volume: 120 Iitres
- Method of holding animals in test chamber: The rats were held for exposure in stainless steel mesh exposure cage subdivided to provide individual compartments for the rats.
- Source and rate of air: A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 25 Iitres per minute measured at the generator outlet tube.
- Method of conditioning air: air supplied to the generator was dried, filtered and oil free.
- System of generating particulates/aerosols: The atmosphere generator, shown in Figure 1, was designed to produce and maintain an atmosphere containing vapour by evaporation of the test substance from a sintered glass disc with a countercurrent of air.
- Treatment of exhaust air: Each chamber was installed in a large fume cupboard exhausting through an absolute filter.
- Temperature, humidity, pressure in air chamber: 23°C± 5°C, 48 ± 3%

TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography: The samples from the bubblers were placed in appropriately labelled scintillation vials prior to injection onto the GC column.
Column: DB-1701fusedsilicaWCOT(J&W), 15m x 0.53mm, dF 111m. Helium carrier at 5.1mllmin. Temperature: l30°C
Detector: FlO, Range O. Temperature: 280°C.
Flow rates: hydrogen, 40 mllmin; air 400 ml/min. Retention Time Approximately 2.65 minutes Injection Volume 1 Ill. Temperature: 180°C
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable): 0.766 mg/I of air

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Five air samples were taken from the chamber during each exposure and the concentration of Benzyl acetate in the chamber air was determined by chemical analysis.

Duration of exposure:

4 h

Concentrations:

0.766 mg/I of air. This was the maximum attainable concentration of vapour at ambient temperature.

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours and then at hourly intervals during the exposure. During the observation period, the clinical signs were recorded once in the morning and then as necessary following a later check for clinical signs. All rats were weighed daily from the day of delivery to the Huntingdon Life Sciences until the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: The amount of food and water consumed by each cage of rats was measured daily from the day of arrival. The daily mean intakes of food and water for each rat were calculated from the recorded data.
All rats were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear ofsurrounding tissue and weighed in order to calculate the lung weight to bodyweight ratio.

Statistics:

Not applicable

Preliminary study:

Not relevant

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.766 mg/L air

Based on:

test mat.

Remarks:

the maximum attainable vapour concentration at ambient temperature.

Exp. duration:

4 h

Remarks on result:

other: LC50 expressed as maximum achievable benzyl acetate concentration. Phenylethyl acetate v.p. is approximately half that of benzyl acetate at 20°C and therefore the LC50 equivalent saturated vapour concentration for PEA is circa 50% less than 0.766 mg/L

Mortality:

There were no deaths following exposure to benzyl acetate.

Clinical signs:

other: All rats were normal in appearance and behaviour during exposure and during the observation period. Food and water consumption of test rats were not affected following exposure to benzyl acetate vapour.

Body weight:

Bodyweight gain for rats exposed to the vapour of benzyl acetate was similar to that of the control rats.

Gross pathology:

There were no macroscopic findings at post mortem.

Other findings:

No additional findings

The exposure concentration in this read across summary is expressed in terms of benzyl acetate which has a vapour pressure of 16 Pa at 20°C. Since the vapour pressure for phenylethyl acetate is approximately half that value at 20°C (8.5 Pa), the maximum equivalent saturated vapour concentration for phenylethyl acetate is estimated to be 0.33 mg/L and the median lethal concentration for acute inhalation exposure is expected to exceed 0.33 mg/L.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute inhalation LC50 was found to be >0.766 mg/L; the saturated vapour concentration

Executive summary:

The acute inhalation toxicity of benzyl acetate was assessed by exposing a group of rats, for a period of 4 hours, to the vapour of the test substance at a concentration of 0.766 mg/L of air. This was the maximum attainable concentration of vapour at ambient temperature. A further group, acting as a control, was exposed to clean air only. Based on the results of this study, benzyl acetate does not require classification according to Regulation EC No. 1272/2008.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

:A single exposure level of 0.766 mg/L was used as this was the maximum attainable concentration of vapour at ambient temperature.

Principles of method if other than guideline:

The acute inhalation toxicity of benzyl acetate was assessed by exposing a group of rats, for a period of 4 hours, to the vapour of the test substance at a concentration of 0.766 mg/I of air. This was the maximum attainable concentration of vapour at ambient temperature. A further group, acting as a control, was exposed to clean air only.

GLP compliance:

yes

Test type:

standard acute method

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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Manston Road, Margate, Kent, England
- Age at study initiation: between 8 weeks and 12 weeks old
- Weight at study initiation: 198 - 273 g
- Fasting period before study: no
- Housing: The holding cages (size 35 cm x 53 cm x 25 cm height) were made of stainless steel sheet and wire mesh and were suspended on a movable rack.
- Diet (e.g. ad libitum): measured amounts
- Water (e.g. ad libitum): measured amounts
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hous light and 12 hours dark

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

ENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: whole-body exposure chambers
- Exposure chamber volume: 120 Iitres
- Method of holding animals in test chamber: The rats were held for exposure in stainless steel mesh exposure cage subdivided to provide individual compartments for the rats.
- Source and rate of air: A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 25 Iitres per minute measured at the generator outlet tube.
- Method of conditioning air: air supplied to the generator was dried, filtered and oil free.
- System of generating particulates/aerosols: The atmosphere generator, shown in Figure 1, was designed to produce and maintain an atmosphere containing vapour by evaporation of the test substance from a sintered glass disc with a countercurrent of air.
- Treatment of exhaust air: Each chamber was installed in a large fume cupboard exhausting through an absolute filter.
- Temperature, humidity, pressure in air chamber: 23°C± 5°C, 48 ± 3%

TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography: The samples from the bubblers were placed in appropriately labelled scintillation vials prior to injection onto the GC column.
Column: DB-1701fusedsilicaWCOT(J&W), 15m x 0.53mm, dF 111m. Helium carrier at 5.1mllmin. Temperature: l30°C
Detector: FlO, Range O. Temperature: 280°C.
Flow rates: hydrogen, 40 mllmin; air 400 ml/min. Retention Time Approximately 2.65 minutes Injection Volume 1 Ill. Temperature: 180°C
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable): 0.766 mg/I of air

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Five air samples were taken from the chamber during each exposure and the concentration of Benzyl acetate in the chamber air was determined by chemical analysis.

Duration of exposure:

4 h

Concentrations:

0.766 mg/I of air. This was the maximum attainable concentration of vapour at ambient temperature.

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours and then at hourly intervals during the exposure. During the observation period, the clinical signs were recorded once in the morning and then as necessary following a later check for clinical signs. All rats were weighed daily from the day of delivery to the Huntingdon Life Sciences until the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: The amount of food and water consumed by each cage of rats was measured daily from the day of arrival. The daily mean intakes of food and water for each rat were calculated from the recorded data.
All rats were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear ofsurrounding tissue and weighed in order to calculate the lung weight to bodyweight ratio.

Statistics:

Not applicable

Results and discussion

Preliminary study:

Not relevant

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.766 mg/L air

Based on:

test mat.

Remarks:

the maximum attainable vapour concentration at ambient temperature.

Exp. duration:

4 h

Remarks on result:

other: LC50 expressed as maximum achievable benzyl acetate concentration. Phenylethyl acetate v.p. is approximately half that of benzyl acetate at 20°C and therefore the LC50 equivalent saturated vapour concentration for PEA is circa 50% less than 0.766 mg/L

Mortality:

There were no deaths following exposure to benzyl acetate.

Clinical signs:

other: All rats were normal in appearance and behaviour during exposure and during the observation period. Food and water consumption of test rats were not affected following exposure to benzyl acetate vapour.

Body weight:

Bodyweight gain for rats exposed to the vapour of benzyl acetate was similar to that of the control rats.

Gross pathology:

There were no macroscopic findings at post mortem.

Other findings:

No additional findings

Any other information on results incl. tables

The exposure concentration in this read across summary is expressed in terms of benzyl acetate which has a vapour pressure of 16 Pa at 20°C. Since the vapour pressure for phenylethyl acetate is approximately half that value at 20°C (8.5 Pa), the maximum equivalent saturated vapour concentration for phenylethyl acetate is estimated to be 0.33 mg/L and the median lethal concentration for acute inhalation exposure is expected to exceed 0.33 mg/L.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute inhalation LC50 was found to be >0.766 mg/L; the saturated vapour concentration

Executive summary:

The acute inhalation toxicity of benzyl acetate was assessed by exposing a group of rats, for a period of 4 hours, to the vapour of the test substance at a concentration of 0.766 mg/L of air. This was the maximum attainable concentration of vapour at ambient temperature. A further group, acting as a control, was exposed to clean air only. Based on the results of this study, benzyl acetate does not require classification according to Regulation EC No. 1272/2008.