Pentyl phenylacetate

Endpoint summary

Description of key information

Skin Irritation:

The dermal irritation potential of pentyl 2-phenylacetate was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

Pentyl 2-phenylacetate was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, pentyl 2-phenylacetate can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation: 

The ocular irritation potential of pentyl 2-phenylacetate was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

Pentyl 2-phenylacetate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, pentyl 2-phenylacetate can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

Data is from modelling databases

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

To estimate the skin irritation potential of pentyl phenylacetate in rabbits

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of the test material: pentyl 2-phenylacetate
- IUPAC name: pentyl 2-phenylacetate
- Molecular formula: C13H18O2
- Molecular weight: 206.283 g/mol
- Substance type: Organic
- Smiles: C(=O)(Cc1ccccc1)OCCCCC
- Physical State: Liquid

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data

Duration of treatment / exposure:

No data

Observation period:

No data

Number of animals:

No data

Details on study design:

No data

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: no data available

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation was observed.

Table showing skin irritation estimation by three different models i.e, Leadscope, battery and SciQSAR &CASE Ultra,the average skin irritation results was given by the fourth model i.e, Battery model.

	Exp	Battery	CASE Ultra	Leadscope	SciQSAR
Severe Skin Irritation in Rabbit	NA	NEG_IN	NEG_IN	NEG_IN	NEG_IN

NEG: negative

IN: inside applicability domain

Interpretation of results:

other: not irritating

Conclusions:

No Severe skin irritation effects of Pentyl Phenylacetate were estimated in rabbit skin by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database.

Executive summary:

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for Pentyl phenylacetate. Based on estimation, no severe skin irritation effects were known when Pentyl phenylacetate was exposed to rabbit skin.

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:

data is from OECD QSAR toolbox v3.4 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of the test material: pentyl 2-phenylacetate
- IUPAC name: pentyl 2-phenylacetate
- Molecular formula: C13H18O2
- Molecular weight: 206.283 g/mol
- Substance type: Organic
- Smiles: C(=O)(Cc1ccccc1)OCCCCC
- Physical State: Liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

1, 24, 48, and 72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

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

Domain logical expression index: "a"

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: "b"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Organic Azides OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Organic Azides OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after nitrene formation OR SN1 >> Nucleophilic attack after nitrene formation >> Organic Azides OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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 Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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 Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isocyanates OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group C Surface Tension > 62 mN/m by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CHal Melting Point > 65 C OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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: "m"

Referential boundary: The target chemical should be classified as Alkylarylether OR Ether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "n"

Similarity boundary:Target: CCCCCOC(=O)Cc1ccccc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: CCCCCOC(=O)Cc1ccccc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.84

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.61

Interpretation of results:

other: not irritating

Conclusions:

Pentyl 2-phenylacetate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of pentyl 2-phenylacetate was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

Pentyl 2-phenylacetate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, pentyl 2-phenylacetate can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

In different studies, pentyl phenylacetate has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical and its structurally and functionally similar read across substances, Benzyl propionate [CAS: 122-63-4], Phenethyl butyrate [CAS: 103-52-6]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated forpentyl phenylacetate. Pentyl phenylacetate was not irritating to New Zealand White rabbit skin.

 

Skin irritation effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for pentyl phenylacetate. Based on estimation, No severe skin irritation effects were known when pentyl phenylacetate was exposed to rabbit skin.

Both the estimated results are in agreement with each other, indicating the possibility of pentyl phenylacetate being not irritating to skin.

Also these results are further supported by the experimental study conductedin an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) for the structurally andfunctionally similar read across substance,Benzyl propionate [CAS: 122-63-4]. This study was performed as per OECD guideline No. 404. Three healthy young adult female rabbits were used for conducting acute dermal irritation 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 and Classified as “Category- Not Classified” as per CLP Regulation.

Various studies were conducted on human volunteers and rabbits by D. McGinty et. al, 2012 to assess the irritation potential of the structurally andfunctionally similar read across substance, Phenethyl butyrate[CAS: 103-52-6] on skin.

A maximization test was conducted on25 healthy patients (male and female) for test chemical phenethyl butyrate (CAS No: 103-52-6) to assess its irritation potential. During the test, 8% concentration of phenethyl butyrate in petrolatum was applied under occlusion for 48 h to the forearm or back of 25 healthy patients and then observations were made. There was no irritation seen in any of the 25 patients. Hence the test chemical, Phenethyl butyrate (CAS No: 103-52-6) was considered to be not irritating on skin of 25 healthy patients.

In another skin irritation study, undiluted phenethyl butyrate was administered topically to four rabbits at a dose of 5 ml/kg (4.97 g/kg) and observed after 24 hours. Mild erythema was observed that resolved after 24 hours. Hence the test substance, Phenethyl butyrate (103-52-6) was considered to be not irritating on skin of rabbits.

Based on the available data for the target and read across substances and applying the weight of evidence approach, pentyl phenylacetate can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye Irritation:

In different studies,pentyl phenylacetate  has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its structurally and functionally similar read across substances,Benzyl propionate [CAS: 122-63-4], Methyl phenylacetate [CAS: 101-41-7] and Benzyl acetate [CAS: 140-11-4].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated forpentyl phenylacetate. Pentyl phenylacetate was estimated to be not irritating to eyes of New Zealand White rabbits.

This result is supported by the experimental study conductedin an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) for the structurally and functionally similar read across substance,Benzyl propionate [CAS: 122-63-4]. The study was performed according to OECD 405 Guidelines.

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: 122-63-4) is “Non Irritant” to New Zealand White Male rabbit eyes and is being classified as “Not Classified” as per the CLP regulation.

These results are also supported by the experimental studyconductedin an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) for the structurally and functionally similar read across substance,Methyl phenylacetate [CAS: 101-41-7].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 as such test item was instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48 and 72 hour after test item instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test, 0.1 ml of as such test item was instilled into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions hence a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3);0.1 ml of as such test item was instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control. Untreated eye of all the three 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 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 all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals. 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 all the animals; Chemosis: No swelling (normal) 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 all the animals. 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 - Blood vessels normal in all the animals; Chemosis: No swelling (normal) was observed in all the animals. The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours (at treated site)for corneal opacity, iris, conjunctiva and chemosis were determined to be 0.00, 0.00, 0.33, 0.00; 0.00, 0.00, 0.33, 0.00 and 0.00, 0.00, 0.33, 0.00 respectively.

Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of rabbits was observed within 72 hours.  Hence, it was concluded that Methyl phenyl acetate (CAS: 101-41-7) was Non-Irritating to the eyes of Male New Zealand White rabbits under the experimental conditions tested and is Classified as “Category- Not Classified" as per CLP criteria for Classification.

These results are further supported by the experimental study summarized in Food and Chemical Toxicology 50 (2012) S363–S384; for thestructurally andfunctionally similar read across substance, Benzyl acetate [CAS: 140-11-4]. A 0.1 mL aliquot of 3%, 7.5% or 18.7% benzyl acetate petrolatum was instilled into the right eye of three albino rabbits. The left eye of the rabbits served as the control. The observation period was once every 24 h for the first 4 days and at day 7. The eyes were scored according to the Draize scale. There were no effects in any rabbits when petrolatum was used as the vehicle.

No irritating effects were reported in eye irritation study of chemical benzyl acetate (in petrolatum) when exposed to albino rabbits.

Based on the available data for the target and read across substances and applying the weight of evidence approach, pentyl phenylacetate can be considered to be not irritating to skin. 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

Based on the available information, pentyl 2-phenylacetateis not likely to cause any irritation to eyes and skin. Hence,pentyl 2-phenylacetate can be classified under the category “Not Classified” as per CLP regulation.