Benzyl butyrate

Endpoint summary

Description of key information

Acute toxicity: Oral

The reported study was designed and conducted to determine the acute oral toxicity profile of the given test chemical. Acute oral toxicity study was performed in groups of 10 young adult Osborne-Mendel rats evenly divided by sex using test chemical at dose concentration of 2330 mg/kg bw. 50% mortality was observed at dose 2330 mg/kg bw.Clinical signs like somnolence (general depressed activity), Scrawny appearance, tremors at higher doses were observed. Hence, LD50 value was considered to be 2330 mg/kg bw (1940-2800) with 95% confidence limits, when rats were treated with test chemical orally.

Acute toxicity: Inhalation

The study doesnot need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.Test chemical has very low vapour pressure (6.5061 Pa.= 0.0487997562 mmHg),So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver

Acute toxicity: Dermal

The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical. In acute dermal toxicity study, five rabbits were treated with test chemical in the concentration of 5000 mg/kg bw by dermal application followed by a 14 days observation period. No mortality was observed in treated rabbits at dose 5000 mg/kg bw. Necropsy was not conducted. Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with test chemical by dermal application. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Acute Oral toxicity test was carried out to study the effects of test chemical on rats.

GLP compliance:

not specified

Test type:

other: No data available

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young and adult rats
- Fasting period before study: 18 hours approx
- Diet (e.g. ad libitum): the food was replaced in cages as soon as animals received their respective doses.
- Water (e.g. ad libitum): ad libitum

Route of administration:

other: intubation

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material was applied undiluted

Doses:

2330 mg/kg

No. of animals per sex per dose:

10:animals
5 : males
5 : females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: No
- Other examinations performed: clinical signs, body weight, mortality

Statistics:

LD50's were computed by the method of Litchfield & Wilcoxon (1949)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 330 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 940 - <= 2 800

Remarks on result:

other: 50% mortality was observed

Mortality:

Mortality were observed in 4hrs-4 days

Clinical signs:

other: Depression, scrawny appearance, tremors with higher doses

Gross pathology:

Necropsy was not conducted

Other findings:

no data available

Acute oral toxicity of food flavourings and compounds of related structure

CAS	Species	LD50 with 95 % confidence limits (mg/kg)	Slope function with 95% confidence limits	Toxic sign and death time (D.T)
103 -37 -7	Rat	2330 (1940-2800)	1:3 (1.1- 1.6)	Depression, scrawny appearance, tremors with higher doses D.T. 4hrs-4 days

Interpretation of results:

other: not classified

Conclusions:

The lethal concentration (LD50) value for acute oral toxicity test was considered to be 2330 mg/kg bw (95% confidence limit:1940-2800),when group of 5 male and female Osborne-Mendel rats were treated with test chemical orally.

Executive summary:

Acute oral toxicity study was performed in groups of 10 young adult Osborne-Mendel rats evenly divided by sexusing test chemical at dose concentration of 2330 mg/kg bw.All doses were given by intubation. All animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal and showed weight gain. The usual observation period was 2 weeks. LD50's were computed by the method of Litchfield & Wilcoxon (1949).The substance was a liquid and it was administered undiluted.50% mortality was observed at dose 2330 mg/kg bw.Clinical signs like somnolence (general depressed activity), Scrawny appearance, tremors at higher doses were observed. Hence,LD50 value was considered to be 2330 mg/kg bw (1940-2800) with 95% confidence limits,when rats were treated withtest chemical orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 330 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from peer reviewed journal

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Clinical signs:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

waiver

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute dermal toxicity study of test chemical was performed in rabbits.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

No data available

Duration of exposure:

No data available

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 animals

Control animals:

not specified

Details on study design:

Details on study design
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs and mortality
other: No data available

Statistics:

No data available

Preliminary study:

No data available

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

No mortality was observed in rabbits dosed with 5000 mg/kg bw.

Clinical signs:

other: No clinical signs observed

Gross pathology:

No data available

Other findings:

No data available

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was considered to be >5000 mg/kg bw,when five rabbits were treated with test chemical by dermal application following 14 days of observation period.

Executive summary:

In acute dermal toxicity study, five rabbits were treated with test chemical in the concentration of 5000 mg/kg bw by dermal application followed by a 14 days observation period.No mortality was observed in treated rabbits at dose 5000 mg/kg bw. Necropsy was not conducted. Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with test chemical by dermal application. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from peer reviewed journal

Additional information

Acute toxicity: Oral

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for test chemical. The studies are summarized as below –

 

The reported study was designed and conducted to determine the acute oral toxicity profile of the given test chemical. Acute oral toxicity study was performed in groups of 10 young adult Osborne-Mendel rats evenly divided by sex using test chemical at dose concentration of 2330 mg/kg bw.All doses were given by intubation. All animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal and showed weight gain. The usual observation period was 2 weeks. LD50's were computed by the method of Litchfield & Wilcoxon (1949). The substance was a liquid and it was administered undiluted.50% mortality was observed at dose 2330 mg/kg bw.Clinical signs like somnolence (general depressed activity), Scrawny appearance, tremors at higher doses were observed. Hence, LD50 value was considered to be 2330 mg/kg bw (1940-2800) with 95% confidence limits, when rats were treated with test chemical orally.

The above study is supported with another study conducted on rats for the test chemical. Acute oral toxicity study was performed in rats using test chemical at dose concentration of 2300 mg/kg bw.50% mortality was observed at dose 2300 mg/kg bw. Hence,LD50 value was considered to be 2300 mg/kg bw,when rats were treated with test chemical orally.

 

Both the above studies were again supported by another study performed in 10 rats using test chemical at dose concentration of 1900 mg/kg bw.50% mortality was observed at dose1900 mg/kg bw. Hence, LD50 value was considered to be1900 mg/kg bw(95% confidence limits :1100 - 2600),when rats were treated with test chemical orally.

Furthermore, all the above studies were again supported performed in rats using test chemicaat dose concentration of 1850 mg/kg bw.The test chemical was administered by gavage to rats (10/group) at doses of 1480, 2220, 3330 or 5000 mg/kg bw followed by a 14 day observation period.The incidence of mortality was 0/10, 7/10, 8/10 and 9/10 from low to high dose. All deaths occurred by day 9 with most by day 2. Clinical signs of toxicity at 2220 mg/kg and above included lethargy and chromodacryorrhea. Necropsy was not conducted.Hence,LD50 value was considered to be1850 mg/kg bw(95% confidence limits :1060-2560),when rats were treated with test chemical orally via gavage.

 

Though, 1900 and 1850 mg/kg bw LD50 values for test chemical were available but most of the references suggest that the test chemical is likely to be non-toxic via oral route. Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the test chemical can be classified under “Not Classified”.

 

Acute toxicity: Inhalation

The study doesnot need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.Test chemical has very low vapour pressure (6.5061 Pa.= 0.0487997562 mmHg),So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver

Acute toxicity: Dermal

In different studies, the given test chemical has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rabbits for test chemical. The studies are summarized as below -

The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical. In acute dermal toxicity study, five rabbits were treated with test chemical in the concentration of 5000 mg/kg bw by dermal application followed by a 14 days observation period.No mortality was observed in treated rabbits at dose 5000 mg/kg bw. Necropsy was not conducted. Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with test chemical by dermal application. 

 

The above study is supported with another experimental study conducted on rats for the test chemical as per OECD No.402. 10 male and female healthy young adult Wistar rats were randomly selected and used for conducting acute dermal toxicity study at the concentration of 2000 mg/kg bw. Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item was applied by single dermal application and observed for 14 days after treatment. On test day 0, as such amount of test item, calculated based on density (1.0016) and body weight was applied directly on the intact skin of clipped area of rats; the surgical gauze patch was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating adhesive tape. The porous gauze dressing was wrapped around the abdomen and anchored with non-irritating adhesive tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. No clinical signs and any skin reaction were observed throughout the experimental period in all treated animals. The male and female animals were observed with body weight gain throughout the experiment, except on day 7 male animals were observed with decline in mean body weight gain as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Hence the LD50 was considered to be >2000 mg/kg bw,when rats were treated with test chemical by dermal application.

 

Both the above studies are further supported with a similar acute dermal toxicity study, rabbits were treated with test chemical in the concentration of 5000 mg/kg dermal application. No mortality was observed in rabbits at 5000 mg/kg. Therefore, LD50 was considered to be > 5000 mg/kg bw when rabbits were treated with test chemical by dermal application.

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the test chemical can be classified under “Not Classified”.

 

 

Justification for classification or non-classification

Based on the available results, the test chemical is likely to be non-toxic when exposed via oral, dermal or inhalation route. Hence, it can be classified under the category "Not Classified" as per CLP Regulation.