Phenethyl valerate

Endpoint summary

Description of key information

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin sensitization potential was estimated for2-phenylethyl pentanoate. It was estimated that2-phenylethyl pentanoatewas not skin sensitizing to skin of guniea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 predicted using OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Type of study:

not specified

Justification for non-LLNA method:

Not specified

Specific details on test material used for the study:

Name of the test material: 2-phenylethyl pentanoate
- IUPAC name: 2-phenylethyl pentanoate
- Molecular formula: C13H18O2
- Molecular weight: 206.283 g/mol
- Smiles notation: O=C(OCCc1ccccc1)CCCC
- InChl: 1S/C13H18O2/c1-2-3-9-13(14)15-11-10-12-7-5-4-6-8-12/h4-8H,2-3,9-11H2,1H3
- Substance type: Organic

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

Not specified

Day(s)/duration:

Not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

Not specified

Day(s)/duration:

Not specified

Adequacy of challenge:

not specified

No. of animals per dose:

Not specified

Details on study design:

Not specified

Challenge controls:

Not specified

Positive control substance(s):

not specified

Details on study design:

Not specified

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Dose level:

Not specified

No. with + reactions:

0

Clinical observations:

No skin reaction observed

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 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 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups 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 Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters 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 OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones 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 by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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 >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 OR AN2 >> Direct carbamoylation of protein amines OR AN2 >> Direct carbamoylation of protein amines >> Isocyanates and Diisocyanates OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR Radical reactions OR Radical reactions >> ROS Generation OR Radical reactions >> ROS Generation >> Sterically Hindered Piperidine Derivatives OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes by Protein binding by OASIS v1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as High (Class III) AND Intermediate (Class II) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Similarity boundary:Target: CCCCC(=O)OCCc1ccccc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.48

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.74

Interpretation of results:

other: non skin sensitizing

Conclusions:

2-phenylethyl pentanoate was considered to be non skin sensitizing

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin sensitization potential was estimated for 2-phenylethyl pentanoate. It was estimated that 2-phenylethyl pentanoatewas not skin sensitizing to skin of guniea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

In different studies, Phenethyl valerate has been investigated for potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and human studies along with predicted data for target chemical and its structurally similar read across substances, Phenethyl butyrate (103-52-6) and Phenethyl Propionate (122-70-3).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 sensitization potential was estimated for 2-phenylethyl pentanoate. It was estimated that 2-phenylethyl pentanoate was not skin sensitizing to skin of guniea pigs.

The above predicted data was supported by experimental study conducted by Food and Chemical Toxicology, 50 (2012) S398–S401 and Food and Chemical Toxicology 50 (2012) S269–S313 for structurally similar read across substance Phenethyl butyrate (103-52-6)

A human maximization assay was conducted to evaluate the sensitization potential of phenethyl butyrate phenethyl butyrate. The assay was carried out with 8% (5520µg/cm2) phenethyl butyrate in petrolatum on 25 healthy male and female volunteers. Application was under occlusion to the same site on the forearm or back of all subjects for five alternate day 48 h periods. The patch sites were pretreated for 24 h with 2.5% or 5% aqueous sodium lauryl sulfate (SLS) under occlusion. Following a 10 day rest period, challenge patches were applied to fresh sites on the back for 48 h under occlusion. The challenge site was pretreated for 1 h with 5–10% SLS. The challenge patches were applied to fresh sites on the back for 48 h under occlusion. The challenge site was evaluated at 48 and 72 h.

No reaction was observed in any human volunteers during the assay. Therefore Phenethyl butyrate phenethyl butyrate (CAS No: 103-52-6 ) was considered to be not sensitizing to human skin.

The above result was supported by experimental study conducted by Food and Chemical Toxicology, 50 (2012) S269–S313 for structurally similar read across substance Phenethyl Propionate (122-70-3).

An Open Epicutaneous Test was carried out to estimate the sensitizing potential of Phenethyl Propionate.

6-8 guinea pigs were topically applied the test compound in100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle for 21 days for the induction exposure. It was applied 8% in vehicle for the challenge exposure. The reactions were evaluated after challenge exposure.

After induction and challenge dose no skin reaction were observed, Phenethyl propionate was considered to be non skin sensitizing to guinea pigs

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

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available (further information necessary)

Justification for classification or non-classification

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