Registration Dossier

Administrative data

Description of key information

Acute oral toxicity:

LD50 was considered to be > 5000 mg/kg bw when rat were treated with benzyl phenylacetate orally.

Acute dermal toxicity:

LD50 was considered to be > 10950 mg/kg bw when rabbits were treated with benzyl phenylacetate dermally.

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from peer- reviewed journal
Qualifier:
according to
Guideline:
other: as per mentioned below
Principles of method if other than guideline:
Acute oral toxicity study of Benzyl phenylacetate in rat
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzyl phenylacetate
- Molecular formula (if other than submission substance): C15H14O2
- Molecular weight (if other than submission substance): 226.2736 g/mole
- Substance type: Organic
- Physical state: Liquid
Purity 99%
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
No data
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
No data
Statistics:
No data
Preliminary study:
No data
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No Mortality observed
Mortality:
No Mortality was observed in treated rats at 5000 mg/kg bw
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
No data
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 was considered to be > 5000 mg/kg bw when rat were treated with benzyl phenylacetate orally.
Executive summary:

In a acute oral toxicity study, rat were treated with benzyl phenylacetate in the concentration of 5000 mg/kg bw orally. No Mortality was observed in treated rats at 5000 mg/kg bw. Therefore, LD50 was considered to be > 5000 mg/kg bw when rat were treated with benzyl phenylacetate orally.

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

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from peer- reviewed journal
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Acute dermal toxicity study of benzyl phenylacetate in rabbits
GLP compliance:
not specified
Test type:
other: No data
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzyl phenylacetate
- Molecular formula (if other than submission substance): C15H14O2
- Molecular weight (if other than submission substance): 226.2736 g/mole
- Substance type: Organic
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data available
Type of coverage:
other: Dermal
Vehicle:
not specified
Details on dermal exposure:
No data available
Duration of exposure:
No data available
Doses:
10950 mg/kg bw
No. of animals per sex per dose:
No data available
Control animals:
not specified
Details on study design:
No data available
Statistics:
No data available
Preliminary study:
No data available
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 10 950 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No Mortality observed
Mortality:
No Mortality was observed in treated rabbits at 10950 mg/kg bw
Clinical signs:
No data available
Body weight:
No data available
Gross pathology:
No data available
Other findings:
No data available
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 was considered to be > 10950 mg/kg bw when rabbits were treated with benzyl phenylacetate dermally.
Executive summary:

In a acute oral toxicity study, rabbits were treated with benzyl phenylacetate in the concentration of 10950 mg/kg bw by dermal application. No Mortality was observed in treated rabbits at 10950 mg/kg bw. Therefore, LD50 was considered to be > 10950 mg/kg bw when rabbits were treated with benzyl phenylacetate dermally.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 950 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from peer-reviewed journal

Additional information

Acute oral toxicity:

In different studies, benzyl phenylacetate 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 benzyl phenylacetate along with the study available on structurally similar read across substance Phenethyl phenyl acetate (CAS: 102-20-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies

.

In a study conducted by Owen et al (Food and Cosmetics Toxicology, pg 139, 1979), rat were treated with benzyl phenylacetate in the concentration of 5000 mg/kg bw orally. No Mortality was observed in treated rats at 5000 mg/kg bw. Therefore, LD50 was considered to be > 5000 mg/kg bw when rat were treated with benzyl phenylacetate orally.

In another prediction done by SSS (2017) using Danish QSAR, the acute oral toxicity was estimated for benzyl phenylacetate. LD50 was estimated to 2100 mg/kg bw when mice were treated benzyl phenylacetate orally.  

Also it is further supported by experimental data conducted by Sustainability Support Services (Europe) (2014) on structurally similar read across substance Phenethyl phenyl acetate (CAS: 102-20-5), Six Wistar female rats were used and studies were performed as per OECD No. 423. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, food was withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights were recorded on day 0 (prior to dosing) 7 and 14. Mean body weight of all the animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0. At 2000 mg/kg, all the animals were normal throughout the experimental period. No external and internal gross pathological changes were observed in all the six treated female rats at 2000 mg/kg body weight during terminal sacrifice. Under the conditions of this study, the acute oral LD50 (cut-off value) of “Phenethyl phenyl acetate (CAS No.102-20-5)” was determined to be 5000 mg/kg body weight indicating that the substance does not exhibit acute toxicity by oral route as per the CLP criteria.

Further it is supported by experimental data conducted by Jenner et al (Food and Cosmetics Toxicology. Vol. 2 (Year 1964), page 327-343.) and given by Lewiset al(Sax's Handbook of Dangerous Industrial Materials, 2007) on structurally similar read across substance Phenethyl phenyl acetate (CAS: 102-20-5), Osborne-Mendel male and female rats were treated with Phenethyl phenyl acetate orally by gavage. Deaths were observed at 4 to 18 hours. Depression was observed soon after treatment and scrawny appearance for several days in treated male and female rats at 15390 mg/kg bw. Therefore, LD50 was considered to be 15390 mg/kg bw (12830- 18470) when Osborne-Mendel male and female rats were treated with Phenethyl phenyl acetate orally by gavage.

Thus, based on the above studies and predictions on benzyl phenylacetate and its read across substances and by applying weight of evidance, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, benzyl phenylacetate can be “Not classified” for acute oral toxicity.

Acute dermal toxicity:

In different studies, benzyl phenylacetate 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 benzyl phenylacetate along with the study available on structurally similar read across substance Phenethyl phenyl acetate (CAS: 102-20-5).

In a study conducted by Owen et al (Food and Cosmetics Toxicology, pg 139, 1979), rabbits were treated with benzyl phenylacetate in the concentration of 10950 mg/kg bw by dermal application. No Mortality was observed in treated rabbits at 10950 mg/kg bw. Therefore, LD50 was considered to be > 10950 mg/kg bw when rabbits were treated with benzyl phenylacetate dermally.

Also it is further supported by experimental data conducted by Sustainability Support Services (Europe) (2014) on structurally similar read across substance Phenethyl phenyl acetate (CAS: 102-20-5), Five male and five female healthy young adult Wistar female rats were used and studies were performed as per OECD No 402. Rats free from injury and irritation of skin were selected for the study. Approximately, twenty four hours prior to dermal application of test item, greater than 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight based on the test item density (1.07513) and latest body weight was applied by single dermal application and observed for 14 days after treatment. On test day 0, calculated volume of test item was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating 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 and post dosing till the termination. 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. At 2000 mg/kg, all the animals were observed normal throughout the experimental period. Mean body weight was observed with gain on day 7 and 14 of male and female animals, as compared to day 0.The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Under the conditions of this study, the acute dermal median lethal dose of “Phenethyl phenyl acetate (CAS No. – 102-20-5)” was >2000 mg/kg body weight indicating that the substance does not exhibit acute toxicity by the dermal route as per the CLP criteria.

Thus, based on the above studies on benzyl phenylacetate and its read across substances and by applying weight of evidance, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, benzyl phenylacetate can be “Not classified” for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies on benzyl phenylacetate and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, benzyl phenylacetate can be “Not classified” for acute oral and dermal toxicity.