Phenethyl propionate

Endpoint summary

Description of key information

Acute toxicity: oral

The acute oral median lethal dose (LD50) of phenethyl propionate in rat was observed to be 4000.0 mg/kg b.wt with 95% confidence limit of 2630 – 5370 mg/kg.

Acute toxicity: dermal

The acute dermal median lethal dose (LD50) of phenethyl propionate in rabbit was observed to be greater than 5000.0 mg/kg b.wt (>5000 mg/kg bw).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 000 mg/kg bw

Quality of whole database:

Data is Klemisch 2 and from peer-reviewed journal.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data is Klemisch 2 and from peer-reviewed journal.

Additional information

Acute toxicity: oral

In different studies, phenethyl propionate (CAS No. 122-70-3) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for phenethyl propionate along with the study available on structurally similar read across substance benzyl propionate (CAS No. - 122-63-4) and anisyl propionate (p-methoxybenzyl propionate) (CAS No. 7549-33-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data. The studies are summarized as below:

 

The acute toxicity study was published in a peer-reviewed journal (D. McGinty, D. Vitale, C.S. Letizia, A.M. Api, Fragrance material review on phenethyl propionate, Food and Chemical Toxicology 50 (2012) S430–S434 ), in which the toxic effects of administration of phenethyl propionate (CAS No. 122-70-3) in rat by the oral route was examined. The test material was administered by oral gavage to rats (10/group) at doses of 2220, 3330, 5000 or 7500 mg/kg followed by a 14 day observation period. The incidence of mortality was 0/10, 5/10, 6/10 and 10/10 from low to high dose. All deaths occurred by day two. Clinical signs of toxicity at 3330 mg/kg and above were depression, slow respiration and negative righting reflex. The acute oral median lethal dose (LD50) of phenethyl propionate in rat was observed to be 4000.0 mg/kg b.wt with 95% confidence limit of 2630 – 5370 mg/kg.

 

Also the acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017); to evaluate the toxic effects of administration of phenethyl propionate (CAS No. 122-70-3) in rat by the oral route. 50% mortality observed at 2167.99 in the treated rats. Therefore, the acute oral median lethal dose (LD50) of phenethyl propionate in rat was estimated to be 2167.99 mg/kg b.wt.

 

The above study is supported by the acute oral toxicity study of benzyl propionate (CAS No. - 122-63-4) in Rats, sponsored by Sustainability Support Services (Europe) AB (2014) was conducted at sa-FORD (Sanctuary for Research and Development), Maharashtra, India. This 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 3-4 hours post dosing, with food 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, 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.

 

From the results obtained from present investigation, it can be concluded that the test compound benzyl propionate (CAS No. - 122-63-4) is non toxic to Wistar rats at the dose level of 2000 mg/kg body weight. The acute oral LD50 of test compound benzyl propionate found to be more than 2000mg/kg b.wt. (> 2000 mg/kg b.wt.).

 

This is further supported by the experimental study published in a peer-reviewed journal (D. McGinty et al., Food and Chemical Toxicology 50 (2012) S486–S490), in which the acute toxicity study was conducted to evaluate the toxic effects of administration of Benzyl propionate (CAS No. 122-63-4) in rat by the oral route. The test material was administered by gavage to rats (10/group) at doses of 2050, 2560, 3200, 4000, or 5000 mg/kg followed by a 14 day observation period. The incidence of mortality was 0/10, 4/10, 5/10, 9/10 and 9/10 from low to high dose. All deaths occurred by day two. Clinical signs of toxicity at 2560 mg/kg and above were piloerection, lethargy, tremors and chromodacryorrhea. The acute oral median lethal dose (LD50) of benzyl propionate in rat was observed to be 3300.0 mg/kg b.wt (3030 – 3570 mg/kg).

 

Moreover in a study by D. McGinty et. al (Food and Chemical Toxicology 50 (2012) S337–S340) ,the acute oral toxicity of anisyl propionate (p-methoxybenzyl propionate) (CAS No. 7549-33-9) was determined in rats. The test material was administered by gavage to 10 rats at doses of 1600, 3300, or 5000 mg/kg followed by a 14 day observation period. Mortality was seen in 0/10 at 1600 mg/kg, 5/10 at 3300 mg/kg, and 10/10 at 5000 mg/kg within 24 h of administration. There were no clinical signs of toxicity. The acute oral median lethal dose (LD50) of anisyl propionate (p-methoxybenzyl propionate) in rat was observed to be 3330.0 mg/kg b.wt.

 

So, based on the above mentioned studies for target substance phenethyl propionate (CAS No. 122-70-3) and to its read across substance, the median lethal dose (LD50) value was found to be in the range of > 2000 mg/kg b.wt. to 4000.0 mg/kg b.wt. Thus, on the basis of these LD50 value and by comparing these studies with the criteria of CLP regulation, it infers that phenethyl propionate (CAS No. 122-70-3) does not classify as an acute oral toxicant.

 

Acute toxicity: dermal

In different studies, phenethyl propionate (CAS No. 122-70-3) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for phenethyl propionate along with the study available on structurally similar read across substance benzyl propionate (CAS No. - 122-63-4) and anisyl propionate (p-methoxybenzyl propionate) (CAS No. 7549-33-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data. The studies are summarized as below:

 

The acute toxicity study was published in a peer-reviewed journal (D. McGinty, D. Vitale, C.S. Letizia, A.M. Api, Fragrance material review on phenethyl propionate, Food and Chemical Toxicology 50 (2012) S430–S434 ), in which the toxic effects of administration of phenethyl propionate (CAS No. 122-70-3) in rabbit by the dermal route was evaluated. The test material was administered topically to 10 rabbits followed by a 14 day observation period. Mortality was observed in one animal on day four. There were no clinical signs of toxicity. The acute dermal median lethal dose (LD50) of phenethyl propionate in rabbit was observed to be greater than 5000.0 mg/kg b.wt (>5000 mg/kg bw).

 

Also the acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017); to evaluate the toxic effects of administration of phenethyl propionate (CAS No. 122-70-3) in rabbit by the dermal route. 50% mortality observed at 3829.27 mg/kg bw in the treated rabbits. Therefore, the acute oral median lethal dose (LD50) of phenethyl propionate in rabbit was estimated to be 3829.27 mg/kg b.wt.

 

The above study is supported by the acute dermal toxicity study of benzyl propionate (CAS No. - 122-63-4) in Wistar Rats, sponsored by Sustainability Support Services (Europe) AB (2014), was conducted at sa-FORD (Sanctuary for Research and Development), Maharashtra, India. 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 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.

 

Under the conditions of this; acute dermal toxicity study of Benzyl propionate (CAS No. - 122-63-4) in rats is as given below:

The acute dermal median lethal dose of Benzyl propionate was >2000 mg/kg body weight.

 

This is further supported by the experimental study published in a peer-reviewed journal (D. McGinty et al., Food and Chemical Toxicology 50 (2012) S486–S490), in which the acute toxicity study was examined to evaluate the toxic effects of administration of benzyl propionate (CAS No. 122-63-4) in rabbit by the dermal route. The test material was administered topically to 5 rabbits at a dose of 5 g/kg (5000 mg/kg) followed by a 14 day observation period. There was no mortality or clinical signs of toxicity. The acute dermal median lethal dose (LD50) of benzyl propionate in rabbit was observed to be greater than 5000.0 mg/kg bw (>5000.0 mg/kg bw).

 

Moreover in a study by D. McGintyet. al (Food and Chemical Toxicology 50 (2012) S337–S340), the acute dermal toxicity of anisyl propionate (p-methoxy benzyl propionate) (CAS No. 7549-33-9) was determined in rabbit. The test material was administered topically to 10 rabbits at a dose of 5 g/kg (5000 mg/kg) followed by a 14 day observation period. There was no mortality or clinical signs of toxicity.The acute dermal median lethal dose (LD50) of anisyl propionate (p-methoxybenzyl propionate) in rabbit was observed to be greater than 5000.0 mg/kg bw (>5000.0 mg/kg bw).

 

So, based on the above mentioned studies for target substance phenethyl propionate (CAS No. 122-70-3) and to its read across substance, the median lethal dose (LD50) value was found to be in the range of > 2000 mg/kg b.wt. to >5000 mg/kg b.wt. Thus, on the basis of these LD50 value and by comparing these studies with the criteria of CLP regulation, it infers that phenethyl propionate (CAS No. 122-70-3) does not classify as an acute dermal toxicant.

Justification for classification or non-classification

Based on the above mentioned studies for target substance phenethyl propionate (CAS No. 122-70-3) and to its read across substance, it can be found that LD50 oral and dermal value is greater than 2000 mg/kg b.wt. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the test substance phenethyl propionate (CAS No. 122-70-3) does not classify as an acute toxicant by the oral and dermal route.