3-phenylpropyl acetate

Endpoint summary

Description of key information

Skin Irritation:

3-Phenylpropyl acetate (CAS No: 122-72-5) was considered as non-irritating to the skin of humans.

Eye Irritation:

The ocular irritation of 3-phenylpropyl acetate was estimated using OECD QSAR toolbox v3.4.

3-phenylpropyl acetate was estimated to be not irritating to New Zealand White rabbit eyes.

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:

other: Data is from publication

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Skin irritation study was conducted on the human subjects to evaluate the irritating potential of 3- Phenylpropyl acetate

GLP compliance:

not specified

Species:

human

Strain:

other: not applicable

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: Petrolatum

Controls:

not specified

Amount / concentration applied:

8%

Duration of treatment / exposure:

48 hours

Observation period:

48 hours after application

Number of animals:

5 adult patients

Details on study design:

In preliminary study to a maximization test, an 8% concentration of 3-phenylpropyl acetate was applied under occlusion for48 h to five adult patients.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48 hours

Reversibility:

no data

Remarks on result:

other: Non-irritating

Irritant / corrosive response data:

none of the adult patient showed skin irritation effects.

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The test chemical 3- Phenylpropyl acetate (CAS No: 122-72-5) was considered to be non-irritating to the skin of 5 adult human patients.

Executive summary:

Skin irritation study was conducted on 5 adult human patients to evaluate the irritating potential of the 3- Phenylpropyl acetate (CAS No: 122-72-5)as a preliminary study to a maximization test,.

 

The test material was tested at 8% in petrolatum for 48 hours as a closed patch and observations were made.

 

On the basis of observations made, 3-Phenylpropyl acetate (CAS No: 122-72-5) was considered as non-irritating to the skin of humans.

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:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction was done using OECD QSAR toolbox v 3.4

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v 3.4

GLP compliance:

no

Specific details on test material used for the study:

Name of test material (as cited in study report): 3-phenylpropyl acetate- Molecular formula : C11H14O2- Molecular weight : 178.23 g/mol- Substance type: Organic- Physical state: LiquidSMILES: O=C(OCCCc(cccc1)c1)C

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

single instillation into rabbit eyes

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

2

Details on study design:

not specified

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation observed

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "d" or "e") and("f" and(not "g")) ) and("h" and(not "i")) ) and("j" and(not "k")) ) and "l") and "m") and("n" and(not "o")) ) and("p" and(not "q")) ) and "r") and("s" and "t") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Acetoxy AND Aryl AND Carboxylic acid ester by Organic Functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aryl AND Carboxylic acid ester by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Ester, aliphatic attach [-C(=O)O] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid ester by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> (Tio)carbamoylation of protein nucleophiles OR Acylation >> (Tio)carbamoylation of protein nucleophiles >> Isothiocyanates, Isocyanates OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ester aminolysis or thiolysis >> Carbamates  OR AN2 OR AN2 >> Direct carbamoylation of protein amines OR AN2 >> Direct carbamoylation of protein amines >> Isocyanates and Diisocyanates OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Schiff base formation with carbonyl compounds (AN2) OR AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases >> Pyrimidines and Purines OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Conjugated systems with electron withdrawing groups  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones OR SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfonates OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as Alkali Earth OR Halogens by Groups of elements

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "q"

Referential boundary:The target chemical should be classified as Group 15 - Nitrogen N OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "r"

Similarity boundary:Target: CC(=O)OCCCc1ccccc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.56

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.44

Interpretation of results:

other: not irritating

Conclusions:

3-phenylpropyl acetate was estimated to be not irritating to New Zealand White rabbit eyes.

Executive summary:

The ocular irritation of 3-phenylpropyl acetate was estimated using OECD QSAR toolbox v3.4.

3-phenylpropyl acetate was estimated to be not irritating to New Zealand White rabbit eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

Various studies were summarized in Food and Chemical Toxicology 50 (2012) S457–S461 to evaluate the dermal irritation potential of 3-Phenylpropylacetate in rabbits and humans.

Skin irritation study was conducted on 5 adult human patients to evaluate the irritating potential of the 3- Phenylpropyl acetate (CAS No: 122-72-5) as a preliminary study to a maximization test. The test material was tested at 8% in petrolatum for 48 hours as a closed patch and observations were made.

On the basis of observations made, 3-Phenylpropyl acetate (CAS No: 122-72-5) was considered as non-irritating to the skin of humans.

Skin irritation study was conducted on the rabbits to evaluate the irritating potential of the 3- Phenylpropyl acetate. The test material was applied full strength to the intact/abraded skin of rabbits for 24 hours under occlusion and observations were made.

On the basis of observations made, 3-Phenylpropyl acetate (CAS No: 122-72-5) is non-irritating to the intact/abraded skin of rabbits.

Based on the QSAR prediction done using the Danish (Q)SAR Database, the skin irritation was estimated to be non-irritant on rabbits for 3- Phenylpropyl acetate (CAS No: 122-72-5) Thus it can be concluded that the substance 3- Phenylpropyl acetate (CAS No: 122-72-5) has negative skin irritation effects.

The dermal irritation potential of test article was determined according to the OECD 439 In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method”. The MatTek EpiDerm™ model was used to assess the potential dermal irritation of the test article by determining the viability of the tissues following exposure to the test article via MTT. The objective of this study was to assess the dermal irritation potential of test article Tissues were exposed to test article and controls for ~one hour, followed by a 42 hour post-exposure recovery period. The viability of each tissue was determined by MTT assay. 

The MTT data shows that the assay quality controls were met. The mean tissue viabilities for the Positive control, Methyl acetate were 6.5%, 10.7% respectively in the first and second run, whereas the tissue viabilities of the negative control, Tissue culture water remained at 100% in the both the runs.

 

The Mean % tissue viability compared to negative control (n=3) of 3-phenylpropyl acetate[CAS: 122-72-5] was determined to be 83.6%.

Hence, under the experimental test conditions it was concluded that 3-phenylpropyl acetate[CAS: 122-72-5] was considered to be not irritating to the human skin and being classified as “Not Classified'' as per CLP Regulation.

Based on the available studies, 3-Phenylpropylacetate can be considered as not irritating to skin.

 

Eye Irritation:

Various studies for the target and its read across substances have been summarized as follows:

The ocular irritation of 3-phenylpropyl acetate was estimated using OECD QSAR toolbox v3.4.

3-phenylpropyl acetate was estimated to be not irritating to New Zealand White rabbit eyes.

 

Acute Eye Irritation/Corrosion Study of the similar substance 122-63-4 in Rabbits, sponsored by Sustainability Support Services (Europe) AB was conducted at SA-FORD (Sanctuary for Research and Development), Maharashtra, India. This study was performed as per OECD guideline No. 405.

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 itemwas 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) is “Non Irritant” to New Zealand White Male rabbit eyes and is being classified as “Unclassified” as per the CLP regulation.

Various studies summarized by D. McGinty et.al, 2012 indicate that the similar substance 140-11-4 (benzyl acetate) does not cause any irritation in rabbit eyes.

An eye irritation test was conducted to evaluate the irritation potential of benzyl acetate. The test was performed in accordance with the Draize test procedure. Six albino rabbits received a 0.1-mL aliquot of benzyl acetate in the right eye. The left eye served as the control. The eyes were examined at 24, 48 and 72 h; then again on days 4 and 7.After 7 days of observation, no irritation was observed.

Hence benzyl acetate was considered to be not irritating to the eyes of albino rabbits.

Another Eye irritation study was conducted on rabbits for the chemical benzyl acetate. Three rabbits received a 0.1 mL aliquot of neat benzyl acetate in one eye and were observed for seven days. Well-defined conjunctival irritation was reported. The irritation cleared 2 days after instillation. Hence it was considered that Benzyl acetate was not irritating to rabbit eyes.

The similar substance 10402-25-2 was evaluated for eye irritation (Food and Chemical Toxicology; 50 (2012); S507–S511) in healthy albino rabbits. Doses of 0.1 ml at 2.5% in alcohol SPA 39c were instilled into one eye of 3 healthy albino rabbits. The untreated eye served as control. Observations were made every 24 h for 4 days and then again on day 7. Mild conjunctival irritation was observed in all rabbits which got cleared by day 4.

Hence 2-phenylpropyl acetate (CAS: 10402-25-2) was considered to be not irritating to rabbit eyes.

Based on the available information for the target as well its various read across substances, and applying the weight of evidence approach, 3-Phenylpropyl acetate can be considered as not irritating to eyes.

Justification for selection of skin irritation / corrosion endpoint:

data is from peer reviewed article having Klimisch rating 2

Justification for selection of eye irritation endpoint:

data is from OECD QSAR toolbox v 3.4

Justification for classification or non-classification

Available studies for 3-Phenylpropyl acetate indicate that it is not likely to cause any irritation to eyes and skin.

Hence 3-Phenylpropylacetate can be evaluated as "Non-irritant" to eyes and skin