Registration Dossier

Administrative data

Description of key information

The skin sensitization potential ofGeranyl phenylacetate (102-22-7)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substancesGeranyl phenylacetate (102-22-7)was predicted to be not sensitizing to the skin of female albino guinea pig.

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 from OECD QSAR toolbox v3.4 and the QMRF report has been attached.
Reference:
Composition 1
Qualifier:
equivalent or similar to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.4, 2017
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
No data available
Test material information:
Composition 1
Specific details on test material used for the study:
Name of the test chemical: (2E)-3,7-dimethylocta-2,6-dien-1-yl 2-phenylacetate
Common Name: Geranyl phenylacetate
Molecular formula: C18H24O2
Molecular weight: 272.3856 g/mol
Smiles Notation: c1(CC(OC\C=C(\CC\C=C(\C)C)C)=O)ccccc1
InChI: 1S/C18H24O2/c1-15(2)8-7-9-16(3)12-13-20-18(19)14-17-10-5-4-6-11-17/h4-6,8,10-12H,7,9,13-14H2,1-3H3/b16-12+
Substance Type: Organic
Physical State: Liquid (colorless)
Species:
guinea pig
Strain:
other: albino
Sex:
female
Details on test animals and environmental conditions:
No data available
No. of animals per dose:
No data available
Details on study design:
No data available
Challenge controls:
No data available
Positive control substance(s):
not specified
Statistics:
No data available
Positive control results:
No data available
Reading:
1st reading
Group:
test group
No. with + reactions:
0
Clinical observations:
No skin sensitization reaction was 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 mode value from the 5 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 ( not "l") )  )  and "m" )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Chronic 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 SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Esters AND Vinyl/Allyl 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, 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 Radical OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds 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) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups 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) >> Haloalcohols 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 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 >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups 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 by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols 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: "g"

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: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Esters including acrylic and methacrylic esters OR Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.39

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.39

Interpretation of results:
other: not sensitising
Conclusions:
The skin sensitization potential of Geranyl phenylacetate (102-22-7) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances Geranyl phenylacetate (102-22-7) was predicted to be not sensitizing to the skin of female albino guinea pig.
Executive summary:

The skin sensitization potential of Geranyl phenylacetate (102-22-7)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substancesGeranyl phenylacetate (102-22-7)was predicted to be not sensitizing to the skin of female albino guinea pig.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitization 

In different studies, Geranyl phenylacetate (102-22-7) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig and human for target chemical Geranyl phenylacetate (102-22-7) and its structurally similar read across substancesGeranyl butyrate (CAS No.106-29-6)andBenzyl phenylacetate (102-16-9) the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of Geranyl phenylacetate (102-22-7) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substancesGeranyl phenylacetate (102-22-7) was predicted to be not sensitizing to the skin of female albino guinea pig.

Prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be negative on guinea pig and human for estimated Geranyl phenylacetate (102-22-7). Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for Geranyl phenylacetate (102-22-7) estimated to be not sensitizing when applied to human and guinea pig skin.

 

The experimental study conducted by D.L.J. Opdyke(Food and Cosmetics Toxicology Volume 12, Issues 7–8, December 1974, Page 895) to evaluate the skin sensitizing potential of Geranyl phenylacetate(102-22-7) in human. In skin sensitization study, 25 volunteers were tested by maximization test at a concentration of 4% in petrolatum. No reaction was observed therefore, the Geranyl phenylacetate(102-22-7)was considered to be not sensitizing to humans.

Supported by experimental study conducted by D.L.J. Opdyke(Food and Cosmetics Toxicology Volume 12, Issues 7–8, December 1974, Pages 889) to evaluate the skin sensitizing potential of read across substance Geranyl butyrate (CAS No.106-29-6) in human. Skin sensitization test was conducted on 25 volunteers for test chemical Geranyl butyrate (CAS No.106-29-6) via human maximization test. In this test, the material was tested at a concentration of 4% in petrolatum on 25 volunteers and then skin reactions were observed. The test material failed to induce skin sensitizing effects on 25 volunteers. Hence the test chemical Geranyl butyrate (CAS No.106-29-6) was considered to be not sensitizing on skin of humans.

Also it is further Supported by experimental study conducted by D.L.J. Opdyke(Food and Cosmetics Toxicology, pg 139, 1979)to evaluate the skin sensitizing potential of read across substance Benzyl phenylacetate (102-16-9) in human. A maximization test was carried out for benzyl phenylacetate (102-16-9) on 25 human volunteers. Benzyl phenylacetate was tested at a 2 % concentration in petrolatum. The test material does not produce any sensitization reaction in any 25 human. Therefore Benzyl phenylacetate (102-16-9) was considered to be not sensitizing in human.

Thus based on the above predictions on Geranyl phenylacetate (102-22-7) as well as its read across and applying weight of evidence, it can be concluded that Geranyl phenylacetate (102-22-7) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, Geranyl phenylacetate (102-22-7) can be considered as not classified for skin sensitization.

 

 

 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, Geranyl phenylacetate (102-22-7) can be considered as not classified for skin sensitization.