Benzyl isobutyrate

Endpoint summary

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats and mouse for the test chemical. The LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

 

Acute Inhalation Toxicity:

Test chemical has very low vapour pressure (0.0428 mm Hg = 5.7 Pa),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 Dermal toxicity:

The acute dermal toxicity dose (LD50) was considered based on different studies conducted on rats for the test chemical. The studies concluded that LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

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:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Acute oral toxicity of test chemical was determined in rats.

GLP compliance:

not specified

Test type:

other: No data

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

2510, 3160, 3980 and 5000 mg/kg

No. of animals per sex per dose:

Total:40
2510 mg/kg bw: 5 male, 5 female
3160 mg/kg bw: 5 male, 5 female
3980 mg/kg bw: 5 male, 5 female
5000 mg/kg bw: 5 male, 5 female

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:No data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and gross pathology were observed.

Statistics:

No data available

Preliminary study:

In preliminary studies, dose levels of 316, 1260 and 5000 mg/kg resulted in mortality in 0/2, 0/2 and 2/2 rats from low to high dose.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 850 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 252 - <= 3 608

Remarks on result:

other: No effect on survival, clinical sign and gross pathology

Mortality:

When treated with 5000 mg/kg bw, all animals were died, at 3980 mg/kg bw, 9 animals were died, at 3160 mg/kg bw, 6 animals were died and at 2510 mg/kg 4 animals were died.

Clinical signs:

other: sedation and tremors were observed in treated rats.

Gross pathology:

No gross pathological alterations were observed in treated male and female rats at necropsy.

Other findings:

No data available

Dose (mg/kg)	Mortality / number of animals treated
2510	4/10
3160	6/10
3980	9/10
5000	10/10

Summary of acute toxicity studies

Route	Species	NO. animals/dose group	LD50 (g/kg)
Oral	Rat	10	2.85

Interpretation of results:

other: not classified

Conclusions:

Therefore, LD50 was considered to be 2850 mg/kg bw (2252-3608 mg/kg) when male and female rats were treated with test chemical orally by gavage.

Executive summary:

Ina acute oral toxicity study, male and female rats were treated with test chemical in the concentration of 2510, 3160, 3980 or 5000 mg/kg orally by gavage and observed for 14 days. In preliminary studies, dose levels of 316, 1260 and 5000 mg/kg resulted in mortality in 0/2, 0/2 and 2/2 rats from low to high dose. In main study, all animals were died at 5000 mg/kg bw, 9 animals died at 3980 mg/kg bw, 6 animals died at 3160 mg/kg bw and 4 animals died at 2510 mg/kg. Sedation and tremors were observed in treated rats. No gross pathological alterations were observed in treated male and female rats at necropsy. Therefore, LD50 was considered to be 2850 mg/kg bw (2252-3608 mg/kg) when male and female rats were treated with test chemical orally by gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 850 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:

other justification

Justification for data waiving:

other:

Endpoint conclusion

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:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Acute dermal toxicity of test chemical was determined in rabbits.

GLP compliance:

not specified

Test type:

other: No data

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

male/female

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:

TEST SITE
- Area of exposure: intact and abraded sites

Duration of exposure:

No data available

Doses:

5000 mg/kg

No. of animals per sex per dose:

2 male ,2 female

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:No
- Necropsy of survivors performed:Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Gross pathology were examined.

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No effect on gross pathology and gross pathology

Mortality:

No effect on survival of treated rabbits were observed at 5000 mg/kg bw.

Clinical signs:

other: Slight to moderate erythema that resolved by day eight was seen at intact and abraded sites of all animals. Edema was not observed.

Gross pathology:

No gross pathological changes were observed in treated male and female rabbits.

Other findings:

No data available

Summary of acute toxicity studies

Route	Species	NO. animals/dose group	LD50 (g/kg)
Dermal	Rabbit	4	>5.0

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was considered to be >5000 mg/kg bw,when 2 male and female rabbits were treated with test chemical by dermal application following 14 days of observation period.

Executive summary:

In acute dermal toxicity study, 2 male and female rabbits were treated withtest chemicalin the concentration of 5000 mg/kg bw which was applied on intact and abraded sites of skin.No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Slight to moderate erythema that resolved by day eight was seen at intact and abraded sites of all animals. Edema was not observed.No effect on survival of treated rabbits were observed at 5000 mg/kg bw and No gross pathological changes were observed in treated male and female rabbits.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 oral toxicity:

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 and mice for test chemical. The studies are summarized as below –

The reported study was mentioned in authoritative database ,handbook,review article,peer reviewed journal,and secondary report to designed and conducted to determine the acute oral toxicity profile of the given test chemical.In a acute oral toxicity study, male and female rats were treated with test chemical in the concentration of 2510, 3160, 3980 or 5000 mg/kg orally by gavage and observed for 14 days. In preliminary studies, dose levels of 316, 1260 and 5000 mg/kg resulted in mortality in 0/2, 0/2 and 2/2 rats from low to high dose. In main study, all animals were died at 5000 mg/kg bw, 9 animals died at 3980 mg/kg bw, 6 animals died at 3160 mg/kg bw and 4 animals died at 2510 mg/kg. Sedation and tremors were observed in treated rats. No gross pathological alterations were observed in treated male and female rats at necropsy. Therefore, LD50 was considered to be 2850 mg/kg bw (2252-3608 mg/kg) when male and female rats were treated with test chemical orally by gavage.

The above study is supported with another study mentioned in publication,authoritative databse and handbook and conducted on rats for the test chemical. Acute oral toxicity study was performed in male and female rats using test chemical.50% mortality was observed at dose 2850 mg/kg bw. Hence,LD50 value was considered to be 2850 mg/kg bw (95% confidence limit:2111-3847),when rats were treated with test chemical orally.

Both the above studies are further supported with predicted data by Danish QSAR. Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 4400 mg/kg bw on rat for test chemical having Reliability Index: 0.91 (high prediction quality.) and the LD50 was estimated to be 2900 mg/kg bw on mouse for test chemical having Reliability Index: 0.57 ( moderate prediction quality).

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 given test chemical cannot be classified for acute oral toxicity.

 

Acute Inhalation Toxicity:

Test chemical has very low vapour pressure (0.0428 mm Hg = 5.7 Pa),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 Dermal toxicity:

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 rats for test chemical. The studies are summarized as below -

The reported study was mentioned in peer reviewed journal and to designed and conducted to determine the acute dermal toxicity profile of the given test chemical.In acute dermal toxicity study, 2 male and female rabbits were treated with test chemical in the concentration of 5000 mg/kg bw which was applied on intact and abraded sites of skin.No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Slight to moderate erythema that resolved by day eight was seen at intact and abraded sites of all animals. Edema was not observed.No effect on survival of treated rabbits were observed at 5000 mg/kg bw and No gross pathological changes were observed in treated male and female rabbits.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. Acute Dermal Toxicity Study was conducted using test chemical as per OECD No.402 in 10 male and female healthy young adult Wistar rats which 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 the study mentioned in peer reviewed journal. In a acute dermal toxicity study, rabbits were treated wtih 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 given test chemical cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral and acute dermal toxicity. For acute inhalation toxicity wavier was added so, not possible to classify.