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Administrative data

Description of key information

Acute oral toxicity:

LD50 was considered to be > 5000 mg/kg bw when rat were treated with 2-phenylethyl 2-hydroxybenzoate orally.

Acute dermal toxicity:

LD50 was considered to be > 5000 mg/kg bw when rabbits were treated with 2-phenylethyl 2-hydroxybenzoate 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 is form peer- reviewed journal
Reference:
Composition 0
Composition 0
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Acute oral toxicity study of Phenethyl salicylate in rat
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- IUPAC name: 2-phenylethyl 2-hydroxybenzoate
- Common name: Phenethyl salicylate
- Molecular formula: C15H14O3
- Molecular weight : 242.2726 g/mol
- Smiles notation : c1ccc(cc1)CCOC(=O)c2ccccc2O
- InChl: 1S/C15H14O3/c16-14-9-5-4-8-13(14)15(17)18-11-10-12-6-2-1-3-7-12/h1-9,16H,10-11H2
- Substance type: Organic
- Physical state: Solid
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 rat
Control animals:
not specified
Details on study design:
Duration of observation period following administration: 14 days (or other?): 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No data
- Other examinations performed: Mortality and/or systemic effects were observed
Statistics:
not specified
Preliminary study:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No 50 % mortality observed
Mortality:
One death was observed in treated rats at 5000 mg/kg bw
Clinical signs:
Slight lethargy was observed during the course of the study in treated rats.
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 was considered to be > 5000 mg/kg bw when rat were treated with 2-phenylethyl 2-hydroxybenzoate orally.
Executive summary:

In a acute oral toxicity study, rat were treated with 2-phenylethyl 2-hydroxybenzoate at 5000 mg/kg bw orally and observed for 14 days. One death was observed in treated rats at 5000 mg/kg bw and Slight lethargy was observed during the course of the study in treated rats. Therefore, LD50 was considered to be > 5000 mg/kg bw when rat were treated with 2-phenylethyl 2-hydroxybenzoate orally.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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 is form peer- reviewed journal
Reference:
Composition 0
Composition 0
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Acute dermal toxicity study of 2-phenylethyl 2-hydroxybenzoate in rabbits
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- IUPAC name: 2-phenylethyl 2-hydroxybenzoate
- Common name: Phenethyl salicylate
- Molecular formula: C15H14O3
- Molecular weight : 242.2726 g/mol
- Smiles notation : c1ccc(cc1)CCOC(=O)c2ccccc2O
- InChl: 1S/C15H14O3/c16-14-9-5-4-8-13(14)15(17)18-11-10-12-6-2-1-3-7-12/h1-9,16H,10-11H2
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not specified
Type of coverage:
other: dermal
Vehicle:
not specified
Details on dermal exposure:
not specified
Duration of exposure:
not specified
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
9
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:not specified
- Necropsy of survivors performed: not specified
- Other examinations performed: Mortality and clinical signs were examined.
Statistics:
not specified
Preliminary study:
not specified
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 rabbits at 5000 mg/kg bw
Clinical signs:
No clinical sign were observed in treated rabbits at 5000 mg/kg bw
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 was considered to be > 5000 mg/kg bw when rabbits were treated with 2-phenylethyl 2-hydroxybenzoate dermally.
Executive summary:

In a acute oral toxicity study, rabbits were expose with 2-phenylethyl 2-hydroxybenzoate at 5000 mg/kg bw dermally and observed for 14 days. No mortality and clinical sign was observed in treated rabbits at 5000 mg/kg bw Therefore, LD50 was considered to be > 5000 mg/kg bw when rabbits were treated with 2-phenylethyl 2-hydroxybenzoate dermally.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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, 2-phenylethyl 2-hydroxybenzoate 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 2-phenylethyl 2-hydroxybenzoate along with the study available on structurally similar read across substance Benzyl propionate (CAS No. 122-63-4) and Methyl phenyl acetate (CAS No. 101-41-7). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a experimental study summarized by Lapczynskiet al(Food and Chemical Toxicology 45 (2007) S467–S471), rat were treated with 2-phenylethyl 2-hydroxybenzoate at 5000 mg/kg bw orally and observed for 14 days. One death was observed in treated rats at 5000 mg/kg bw and Slight lethargy was observed during the course of the study in treated rats. Therefore, LD50 was considered to be > 5000 mg/kg bw when rat were treated with 2-phenylethyl 2-hydroxybenzoate orally.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-phenylethyl 2-hydroxybenzoate. The LD50 was estimated to be 2765 mg/kg bw when Wistar male and female rats were orally exposed with 2-phenylethyl 2-hydroxybenzoate.

In another prediction done by SSS (2017) using the Danish QSAR, the acute oral toxicity was estimated for 2-phenylethyl 2-hydroxybenzoate. The LD50 was estimated to be 2500 mg/kg bw when mice were orally exposed with 2-phenylethyl 2-hydroxybenzoate.

In another experimental study conducted by Sustainability Support Services (Europe) AB (2014) on structurally similar read across substance Benzyl propionate (CAS No. - 122-63-4), The study were performed as per OECD No. 423. Six female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 3-4 hours post dosing, with food withheld but drinking water provided ad libitum. 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.Body weight gain was observed in all the animals treated with 2000 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 2000 mg/kg, animal nos. 1, 2, 3, 5 and 6 were observed normal throughout the experimental period, whereas animal no. 4 was observed normal at 30 minutes, 1, 2, 3 and 4 hours, with mild ataxia from day 1 to 4, with mild tremors on day 1, with mild chromodacryorrhea from day 2 to 6 and with moderate to mild lethargy from day 3 to 9 post dosing followed by normal observation till day 14. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. Therefore, The acute oral LD50(cut-off value) of Benzyl propionate was 5000 mg/kg body weight when female Wistar rats were treated with Benzyl propionate orally.

Further supported by experimental study summarized by McGintyet al(Food and Chemical Toxicology 50 (2012) S486–S490) on structurally similar read across substance benzyl propionate (CAS no 122-63-4), rat were treated with benzyl propionate in the concentration of 2050, 2560, 3200, 4000 or 5000 mg/kg orally. Mortality was observed as 0/10, 4/10, 5/10, 9/10 and 9/10 from low to high dose. All deaths occurred by day two. Piloerection, lethargy, tremors and chromodacryorrhea were observed at t 2560 mg/kg and above dose. Therefore, LD50 was considered to be 3300 mg/kg (330-3570) when rat were treated with benzyl propionate orally.

This is further supported by experimental study conducted by Sustainability Support Services (Europe) AB (2014) on structurally similar read across substance Methyl phenyl acetate (CAS No. -101-41-7), study was performed as per OECD No. 423. Six female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, food was withheld but drinking water providedad libitum. 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 seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. The acute oral LD50 (Cut-off value) of Methyl phenyl acetate (CAS No. – 101-41-7) were found to be 5000 mg/kg body weight.

Thus, based on the above studies and predictions on 2-phenylethyl 2-hydroxybenzoate 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, 2-phenylethyl 2-hydroxybenzoate can be classified as category V of acute oral toxicity.

Acute dermal toxicity:

In different studies, 2-phenylethyl 2-hydroxybenzoate 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 2-phenylethyl 2-hydroxybenzoate along with the study available on structurally similar read across substance 2, 2, 2-trichloro-1-phenylethyl acetate (CAS No. 90-17-5) and Benzyl propionate (CAS No. 122-63-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a experimental study summarized by Lapczynskiet al(Food and Chemical Toxicology 45 (2007) S467–S471), rabbits were expose with 2-phenylethyl 2-hydroxybenzoate at 5000 mg/kg bw dermally and observed for 14 days. No mortality and clinical sign was observed in treated rabbits at 5000 mg/kg bw Therefore, LD50 was considered to be > 5000 mg/kg bw when rabbits were treated with 2-phenylethyl 2-hydroxybenzoate dermally.

In another prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 2-phenylethyl 2-hydroxybenzoate. The LD50 was estimated to be 2765 mg/kg bw when New Zealand White male and female rabbits were dermally exposed with 2-phenylethyl 2-hydroxybenzoate.

In another experimental study conducted by Sustainability Support Services (Europe) AB (2014) on structurally similar read across substance 2, 2, 2-trichloro-1-phenylethyl acetate (CAS No. 90-17-5), Acute Dermal Toxicity Study of 2,2,2-trichloro-1-phenylethyl acetate(CAS No. – 90-17-5), This study was performed as per OECD No.402. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Twenty four 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 moistened with 0.2 ml distilled water was applied on intact skin of clipped area of rats by single dermal application the surgical gauze patch was put on to the intact skin of clipped area. This gauze patch was covered with a semi-occlusive dressing. The 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 for 14 days. No mortality and clinical signs were observed in any animal till the end of the experimental period. The male and female animals were observed with body weight gain compared to day 0 throughout the experiment. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Therefore, The acute dermal median lethal dose of 2,2,2-trichloro-1-phenylethyl acetate was found to be > 2000 mg/kg body weight.

Further supported by experimental study conducted by Sustainability Support Services (Europe) AB (2014) on structurally similar read across substance on structurally similar read across substance Benzyl propionate (CAS No. - 122-63-4), This study was performed as per OECD No.402. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Twenty four 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 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 and observed for 14 days after treatment. No mortality and clinical signs was observed in any animal till the end of the experimental period. 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. Therefore, the acute dermal median lethal dose of Benzyl propionate was found to be >2000 mg/kg body weight.

Thus, based on the above studies and predictions on 2-phenylethyl 2-hydroxybenzoate 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, 2-phenylethyl 2-hydroxybenzoate can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 2-phenylethyl 2-hydroxybenzoate 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, 2-phenylethyl 2-hydroxybenzoate can be classified as category V of acute oral and dermal toxicity.