Phenethyl propionate

Endpoint summary

Description of key information

Skin irritation:

The test material 2-phenylethyl propanoate (CAS No: 122-70-3) wasevaluated for primary skin irritation insix New Zealand albinorabbits. It was observed to have a Mean Primary Irritation Score of 1.2. Thusaccording to FIFRA categories for skin irritation,2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not irritating on skin of New Zealand albinorabbits(Primary Irritation Score <5).

Eye irritation:

An ocular irritation study was conducted for 2-phenylethyl propanoate (CAS No: 122-70-3) on six New Zealand albino rabbits to assess its adverse effects on eye.The 0.1ml dose of 70%2-phenylethyl propanoatewas installed into the conjunctival sac of the right eye of each of six rabbit. Grading for eye injury was made at 1 , 24, 48 and 72 hr and at 7 days after treatment according to the grading and scoring system of Draize et al.The mean irritation scorewas observed to be 0.0 after 72 hours. Therefore chemical 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not irritating to the eyes of six New Zealand albino rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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:

The primary skin irritation test for 2-phenylethyl propanoate (CAS No: 122-70-3) was conducted on six New Zealand albino rabbits to assess its adverse effects on skin.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 2-phenylethyl propanoate
- Common name: Phenethyl propionate (PEP)
- Molecular formula: C11H14O2
- Molecular weight: 178.2296 g/mol
- Smiles notation: c1(CCOC(=O)CC)ccccc1
- InChl: 1S/C11H14O2/c1-2-11(12)13-9-8-10-6-4-3-5-7-10/h3-7H,2,8-9H2,1H3
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

other: New Zealand albino

Details on test animals or test system and environmental conditions:

Weight at study initiation: 1.9-3.1 kg

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

intact and abraded

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

concentration applied :70%
Amount :0.5 ml per dose

Duration of treatment / exposure:

24 hours

Observation period:

24/72 hours

Number of animals:

6 rabbits (Male and Female)

Details on study design:

TEST SITE
Area of exposure: back and flanks
% coverage: Not reported
Type of wrap if used: 2-in.-square gauze patches that were secured with masking tape, and the trunk of each animal was wrapped with plastic sheeting to maintain the patches in position
REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 and 72 hours

SCORING SYSTEM: Draize scoring system; maximum score is 8.0

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24and 72 hours

Score:

1.2

Max. score:

8

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was observed in treated animals.

Interpretation of results:

other: Not irritating

Conclusions:

The test material 2-phenylethyl propanoate (CAS No: 122-70-3) was evaluated for primary skin irritation in six New Zealand albino rabbits. It was observed to have a Mean Primary Irritation Score of 1.2. Thus according to FIFRA categories for skin irritation, 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not irritating (Primary Irritation Score <5).

Executive summary:

The primary skin irritation test for chemical 2-phenylethyl propanoate (CAS No: 122-70-3) was conducted on six New Zealand albino rabbits to assess its adverse effects on skin.

 

 During the test,the hairs were clipped from the back and flanks of rabbits, and two sites located lateral to the midline of the back and approximately 10 cm apart were selected for the test; one site was abraded by making four epidermal incisions, two perpendicular to the other were selected for the test; one site was abraded by making four epidermal incisions, were selected for the test; one site was abraded by making four epidermal incisions, two perpendicular to the other two.

 

A 0.5-ml dose of 70%2-phenylethyl propanoatewas applied to each site. The sites were immediately covered with 2-in.-square gauze patches that were secured with masking tape, and the trunk of each animal was wrapped with plastic sheeting to maintain the patches in position and retard evaporation of the test material.

 

 After 24 hr the plastic wrappings and gauze patches were removed, and the intact and abraded skin sites were scored separately for erythema and edema on a graded scale of 0 to 4 according to Draize scoring system after 72 hr, the sites were scored again. The mean primary irritation score (maximum = 8) represents an average of the 24- and 72-hr ratings of the intact and abraded sites.

 

For skin irritation, the category for to be not an irritant was, if no irritation was observed or the primary irritation score was <5according to FIFRA.

 

The 2-phenylethyl propanoatewas observed to have a Mean Primary Irritation Score of 1.2. Thusaccording to FIFRA categories for skin irritation,2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not irritating (Primary Irritation Score <5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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:

An ocular irritation study was conducted for 2-phenylethyl propanoate (CAS No: 122-70-3) on six New Zealand albino rabbits to assess its adverse effects on eye.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 2-phenylethyl propanoate
- Common name: Phenethyl propionate (PEP)
- Molecular formula: C11H14O2
- Molecular weight: 178.2296 g/mol
- Smiles notation: c1(CCOC(=O)CC)ccccc1
- InChl: 1S/C11H14O2/c1-2-11(12)13-9-8-10-6-4-3-5-7-10/h3-7H,2,8-9H2,1H3
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

other: New Zealand albino

Details on test animals or tissues and environmental conditions:

Weight at study initiation: 1.9-3.1 kg

Vehicle:

not specified

Controls:

yes

Amount / concentration applied:

concentration applied :70%
Amount : 0.1 ml per dose

Duration of treatment / exposure:

7 days

Observation period (in vivo):

1,24,48, 72 hours and 7 days

Number of animals or in vitro replicates:

6 rabbits

Details on study design:

TEST SITE
- Area of exposure: conjunctival sac of right eye of each animal.

SCORING SYSTEM: According to the grading and scoring system of Draize et al. (1944) in which a zero score indicates no irritation and the maximum score at any one scoring period is 110 (maximum irritation and damage to the cornea, iris, and conjunctiva).

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

110

Reversibility:

fully reversible within: 3 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Slight ocular lesions were observed but all the effects were reversible within 3 days.

Table 1: Primary Irritation score in rabbits

Time Point	Primary Irritation Score
1 hour	12
24 hour	7.5
48 hours	4.6
72 hours	0
7 days	0

Interpretation of results:

other: Not irritating

Conclusions:

The mean irritation score of chemical 2-phenylethyl propanoate (CAS No: 122-70-3) was observed to be 0.0 after 72 hours. Therefore chemical 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not irritating to the eyes of six New Zealand albino rabbits.

Executive summary:

An ocular irritation study was conducted for 2-phenylethyl propanoate (CAS No: 122-70-3) on six New Zealand albino rabbits to assess its adverse effects on eye.

 

The 0.1ml dose of 70% 2-phenylethyl propanoatewas installed into the conjunctival sac of the right eye of each of six rabbit while the left eye of each animal served as the control.

 

Grading for eye injury was made at 1 , 24, 48 and 72 hr and at 7 days after treatment according to the grading and scoring system of Draize et al. (1944) in which a zero score indicates no irritation and the maximum score at any one scoring period is 110 (maximum irritation and damage to the cornea, iris, and conjunctiva).

 

Slight ocular lesions were observed but all the effects were cleared within 3 days. Hence the chemical 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not irritating to the eyes of six New Zealand albino rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

Various studieshas been investigated for the test chemical2-phenylethyl propanoate (CAS No: 122-70-3)  to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits, guinea pigs and humans for target chemical2-phenylethyl propanoate (CAS No: 122-70-3) and its structurally similar read across substancesBenzyl propionate (CAS No. -122-63-4) andBenzylformate(CAS No: 104-57-4).The predicted data usingDanish QSAR databasethe has also been compared with the experimental data and summarized as below;

 

 

MORTON BEROZA, M. N. INSCOE, P. H. SCHWARTZ, JR., M. L. KEPLINGER, AND C. W. MASTRI in 1975 conductedprimary skin irritation test for chemical 2-phenylethyl propanoate (CAS No: 122-70-3) on six New Zealand albino rabbits to assess its adverse effects on skin. During the test,the hairs were clipped from the back and flanks of rabbits, and two sites located lateral to the midline of the back and approximately 10 cm apart were selected for the test; one site was abraded by making four epidermal incisions, two perpendicular to the other were selected for the test; one site was abraded by making four epidermal incisions, were selected for the test; one site was abraded by making four epidermal incisions, two perpendicular to the other two.A 0.5-ml dose of 70%2-phenylethyl propanoatewas applied to each site. The sites were immediately covered with 2-in.-square gauze patches that were secured with masking tape, and the trunk of each animal was wrapped with plastic sheeting to maintain the patches in position and retard evaporation of the test material. After 24 hr the plastic wrappings and gauze patches were removed, and the intact and abraded skin sites were scored separately for erythema and edema on a graded scale of 0 to 4 according to Draize scoring system after 72 hr, the sites were scored again. The mean primary irritation score (maximum = 8) represents an average of the 24- and 72-hr ratings of the intact and abraded sites.For skin irritation, the category to be not an irritant was, if no irritation was observed or the primary irritation score was <5according to FIFRA.The 2-phenylethyl propanoatewas observed to have a Mean Primary Irritation Score of 1.2. Thusaccording to FIFRA categories for skin irritation,2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not irritating (Primary Irritation Score <5).

 

 

Another skin irritation studies of 2-phenylethyl propanoate (CAS No: 122-70-3) were reported by D. L. J. Opdyke (1979) andBelsito, D. Bickers, M. Bruze, P. Calow, M.L. Dagli, A.D. Fryer,H. Greim, Y. Miyachi, J.H. Saurat, I.G. Sipes (2012)in ten rabbits and 5 male subjects as follows;

In the rabbit skin irritation test, each rabbit received undiluted 2-phenylethyl propanoate dermally on intact or abraded skin for 24 hours and later observed for skin reactions. No known signs of skin irritation were observed.

 

In next study, a closed patch test of 2-phenylethyl propanoate (CAS No: 122-70-3) was performed in 5 male subjects as a part ofHuman Maximization (Pre- test). 2-phenylethyl propanoate was applied at concentration of 8% in petrolatum on skin of each subject under occlusive condition for 48 hours. None of the subjects showed any cutaneous reaction within the 48 hour.

 

In both the studies, the chemical did not produce any skin irritating reaction. Therefore, 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not irritating to the skin of rabbits and human subjects.

 

 

According Danish QSAR database, the Skin irritation effects of for 2-phenylethyl propanoate (CAS No: 122-70-3) were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra. Based on estimation, no severe skin irritation effects were known when 2-phenylethyl propanoate (CAS No: 122-70-3) was exposed to rabbit skin.

 

 

Also the above results were supported by the experimental study conducted in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) for the structurally similar read across substanceBenzyl propionate (CAS No.-122-63-4)as per OECD guideline No. 404 in three healthy young adult female rabbits.In this study, body weights were re­corded on day 0 (prior to application) and at termination. Rabbits with good intact skin were selected for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment. A dose of0.5 ml of test item (as such) was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits. The other untreated side was kept as control area and 0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water without altering the integrity of the epidermis.  Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. After 4 hours of exposure in Animal No. 1, there was no erythema and oedema observed at 1, 24, 48 and 72 hours observation. Hence the confirmatory test was conducted on additional two rabbits (No. 2 and 3)to confirm the non irritant nature of the test item. In Animals No. 2 and 3 after post patch removal, revealed no erythema and oedema at 1, 24, 48 and 72 hours observation. The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per Draize method. The individual mean score at 24, 48 and 72 hours for Animal Nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively.   Hence, it was concluded that “Benzyl propionate (CAS No. - 122-63-4)” was Non-Irritating to the skin of Female New Zealand White rabbits under the experimental conditions tested.

 

 

The above results were further supported by thePreliminary irritation testcarried out by D.W. Sharp (1978) inHartley albino guinea pigs of same sexforstructurally similar read across substance Benzylformate (CAS No: 104-57-4)to determine the concentration suitable for the sensitization study[injection challenge concentration (ICC) and application challenge concentration(ACC)].In the preliminary test, the guinea pigs were treated intradermally and dermally. 4 guinea pigs were injected intradermally in the clipped and shaved flanks with 0.1ml aliquots of a range of concentration of test substance in a suitable solvent. 24 hours later, the skin was examined for erythema and edema. The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC). Aliquots of 0.1ml using a range of concentration of the test substance in a suitable solventwere applied in small circular areas to the shaved flanks of 4 previously untreated guinea pigs.24 hours later, the skin was examined for erythema and the highest concentration which caused no irritation was selected as the application challenge concentration (ACC). As a result of preliminary studies, the concentrations of Benzyl formate at which no irritation was observed were 0.25% for the ICC and 20% for ACC. Since the test chemical did not induce any cutaneous effects at these concentrations (0.25% for the ICC and 20% for ACC), the chemical Benzyl formate (CAS No: 104-57-4) was considered to be not irritating to the skin of guinea pigs.

 

 

Thus on the basis of theavailable data for thetarget chemical2-phenylethyl propanoate (CAS No: 122-70-3) and its structurally similar read across substancesBenzyl propionate (CAS No. -122-63-4) andBenzylformate (CAS No: 104-57-4),it can be concluded thatchemical 2-phenylethyl propanoate (CAS No: 122-70-3) is unable to cause skin irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation:

In different studies,the test chemical2-phenylethyl propanoate (CAS No: 122-70-3) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical-phenylethyl propanoate (CAS No: 122-70-3) and its structurally similar read across substancesBenzyl propionate (CAS No. -122-63-4) andBenzylformate (CAS No: 104-57-4) which are summarized as below;

 

 

MORTON BEROZA, M. N. INSCOE, P. H. SCHWARTZ, JR., M. L. KEPLINGER, AND C. W. MASTRI in 1975 andD. Belsito, D. Bickers, M. Bruze, P. Calow, M.L. Dagli, A.D. Fryer,H. Greim, Y. Miyachi, J.H. Saurat, I.G. Sipes (2012) conductedan ocular irritation studytest for chemical 2-phenylethyl propanoate (CAS No: 122-70-3) on six New Zealand albino rabbits to assess its adverse effects on eye.About 0.1ml dose of 70%2-phenylethyl propanoatewas installed into the conjunctival sac of the right eye of each of six rabbit while the left eye of each animal served as the control.Grading for eye injury was made at 1 , 24, 48 and 72 hr and at 7 days after treatment according to the grading and scoring system of Draize et al. (1944) in which a zero score indicates no irritation and the maximum score at any one scoring period is 110 (maximum irritation and damage to the cornea, iris, and conjunctiva).Slight ocular lesions were observed but all the effects were cleared within 3 days. Hence the chemical 2-phenylethyl propanoate (CAS No: 122-70-3) was considered to be not irritating to the eyes of six New Zealand albino rabbits.

 

 

Also the above result was supported by the experimental study conducted in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) for the structurally similar read across substanceBenzyl propionate (CAS No.-122-63-4)as per OECD guideline No. 405 in three healthy young adult rabbits. Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas;0.1 ml of test item (as such)was instilled in the other (treated) eye of rabbits. The eye was observed at 1, 24, 48, 72 hours after test item instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test,0.1 ml of test item was applied into the conjunctival sac of the right eye of Animal No.1. The left eye of the rabbit served as the control. Animal No. 1 presented ocular lesions at 1 hour observation period. Hence the confirmatory test was conducted on additional two rabbits (Animal No. 2 and 3);0.1 ml of test item was instilled into the conjunctival sac of right eye and left eye served as the control. Ocular lesions were observed at 1, 24 and 48 hour in Animal Number 2 whereas in Animal Number 3 ocular lesions presented only at 1 hour observation period. Untreated eye of the treated rabbits was normal throughout the experimental period of 72 hours. The following grading scores were observed in treated eye of tested rabbits. Observation at 1 hour after instillation of test item revealed: Cornea-No ulceration or opacity in all 3 animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) in all the animals; Chemosis: Some swelling above normal (includes nictating membranes) were observed in animal number 1 and 3 whereas animal number 2 was normal. Observation at 24 hours after instillation of test item revealed: Cornea-No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observed in animal no. 2. Animal no. 1 and 3 recovered to normal; Chemosis: No swelling was observed in all the Animals. At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0 % damage in Animal Nos 1, 2 and 3, respectively. Observation at 48 and 72 hours after instillation of test item revealed: Cornea-No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observed in animal no. 3 at 48 hours which was recovered to normal at 72 hours observation whereas blood vessels were normal in Animal Numbers 1 and 3 at 48 and 72 hours observation; Chemosis: No swelling was observed in all the animals. The individual mean score for Animal Nos. 1, 2 and 3at 24, 48, 72 hours for Corneal opacity, iris, conjunctiva, chemosis were found 0.00, 0.00, 0.00, 0.00 ; 0.00, 0.00, 0.67, 0.00 and 0.00, 0.00, 0.00, 0.00, respectively. Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of rabbits was observed at 72 hours. Hence under the experimental test conditions, Benzyl propionate (CAS No. - 122-63-4) was considered to be “Non Irritant” to New Zealand White Male rabbit eyes.

 

 

 

The above results were further supported by An eye irritation test carried out by D. McGinty, C.S. Letizia, A.M. Api (2012) in four female SPF alibino rabbits forstructurally similar read across substance Benzylformate (CAS No: 104-57-4). About 0.1ml of undiluted Benzyl formate was installed into the one of each animal while the other untreated eye served as control. The observations were made at 1, 48, 72 h and 7 days after treatment. At 24 h after dosing, corneal opacity was scattered or diffuse on more than one quarter but less than one half of the cornea. Application of fluorescein confirmed this finding. The conjunctiva were still diffuse, crimson red with individual vessels not easily discernible, swelling was still noted as well as an abnormal discharge. At 48 h after dosing, the scattered or diffuse area of opacity was still noted on one quarter or less of the cornea, even after instillation of fluorescein. The conjunctiva was still diffusely red; the individual vessels were not easily discernible and abnormal swelling still present. At 72 h after dosing, the conjunctival vessels were still injected and following the instillation of fluorescein a scattered or diffuse area of opacity on one quarter or less of the cornea was noted. By 7 days after dosing the animals were free of any signs of eye irritation. Since all the observed effects were cleared within 7 days, the chemical yl formate (CAS No 104-57-4) was considered to be non-irritant to the eyes of SPF alibino rabbits.

 

 

Thus on the basis of theavailable data for thetarget chemical2-phenylethyl propanoate (CAS No: 122-70-3) and its structurally similar read across substancesBenzyl propionate (CAS No. -122-63-4) andBenzylformate (CAS No: 104-57-4),it can be concluded thatchemical 2-phenylethyl propanoate (CAS No: 122-70-3) is unable to cause ocular irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical2-phenylethyl propanoate (CAS No: 122-70-3) and its structurally similar read across substancesBenzyl propionate (CAS No. -122-63-4) andBenzylformate (CAS No: 104-57-4)were observed in various studies. The results obtained from these studies indicate that the chemical2-phenylethyl propanoateis unlikely to cause skin and eye irritation. Hence2-phenylethyl propanoate (CAS No: 122-70-3)can be classified under the category “Not Classified” for skin and eye as per CLP.