Geranyl propionate

Endpoint summary

Description of key information

The skin sensitization potential of Geranyl Propionate was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Geranyl Propionate was predicted to be non sensitizing to the skin of male and female Hartley guinea 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 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

Type of study:

other: Estimated data

Specific details on test material used for the study:

- Name of test material : (2E)-3,7-dimethylocta-2,6-dien-1-yl propanoate
- common name : Geranyl propionate
- Molecular formula: C13H22O2
- Molecular weight: 210.3148 g/mol
- Smiles notation : CCC(=O)OC\C=C(/C)\CCC=C(C)C
- InChl : 1S/C13H22O2/c1-5-13(14)15-10-9-12(4)8-6-7-11(2)3/h7,9H,5-6,8,10H2,1-4H3/b12-9+
- Substance type: Organic
- Physical state: Liquid

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

not specified

Route:

intradermal and epicutaneous

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Concentration:

no data available

No. of animals per dose:

no data available

Details on study design:

no data available

Statistics:

no data available

Positive control results:

no data available

Other effects / acceptance of results:

no data available

Reading:

1st reading

Group:

test chemical

Dose level:

no data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no signs of sensitization observed

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

no data available

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest 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 "l" )  )

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 SN2 AND SN2 >> SN2 Reaction at a sp3 carbon atom AND SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.4

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 >> 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 AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Radical 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) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 >> Nitroarenes with Other Active Groups OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen 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, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates 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 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers 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 SN2 AND SN2 >> SN2 Reaction at a sp3 carbon atom AND SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation 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 >> 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 quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols 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 No alert found 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 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 >> alpha-Activated haloalkanes  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: "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 Group All log Kow > 9 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.67

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.72

Interpretation of results:

other: Negative

Conclusions:

Geranyl Propionate was predicted to be non sensitizing to the skin of male and female Hartley guinea pigs

Executive summary:

The skin sensitization potential of Geranyl Propionate was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Geranyl Propionate was predicted to be non sensitizing to the skin of male and female Hartley guinea pigs

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

Various studies have been investigated for assessing the dermal sensitization potential of Geranyl propionate to a greater or lesser extent. The studies are based on in vivo experiments in humans along with predicted data for target chemical and its structurally similar read across substances, Allyl butyrate[CAS: 2051-78-7],3,7-dimethylocta-2,6-dien-1-yl 2-methylpropanoate(Geranyl isobutyrate) [CAS:2345-26-8] and 3,7-dimethylocta-2,6-dien-1-yl butyrate(Geranyl butyrate)[CAS: 106-29-6]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

Skin sensitization test was conducted on 25 human volunteers(Food and Cosmetics Toxicology, Volume 12, Issues 7–8, December 1974, Page 897) to assess the dermal sensitization potential of Geranyl propionate. Geranyl propionate 4% in petrolatum was applied on the skin of 25 human volunteers and then observed for dermal reactions (duration not mentioned).

The test material failed to induce skin sensitizing effects on 25 volunteers. Hence, Geranyl propionate was considered to be not sensitizing to human skin.

The skin sensitization potential of Geranyl propionate was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Geranyl propionate was predicted to be non sensitizing to the skin of male and female Hartley guinea pigs.

Skin sensitization effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for Geranyl propionate. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, Geranyl propionate was considered to be non sensitizing.

The experimental and estimated data are in agreement with each other; substantiate the claim that Geranyl propionate is indeed not sensitizing to skin.

These results are further supported by the experimental study summarized in Food and Cosmetics Toxicology, Volume 15, Issue 6, December 1977, Pages 613-

614; for the structurally similar read across substance, Allyl butyrate[CAS: 2051-78-7].Allyl butyrate 4% in petrolatum was applied on the skin of 28 human volunteers and then observed for dermal reactions (duration not mentioned).

The test material failed to induce skin sensitizing effects on 28 volunteers. Hence, Allyl butyrate was considered to be not sensitizing to human skin.

These results are ably supported by the experimental study summarized inFood and Cosmetics Toxicology Volume 12, Issues 7–8, December 1974, Pages 889; for thestructurally similar read across substance, 3,7-dimethylocta-2,6-dien-1-yl butyrate(Geranyl butyrate)[CAS: 106-29-6]. Geranyl butyrate 4% in petrolatum was applied on the skin of 25 human volunteers and then observed for dermal reactions (duration not mentioned).

The test material failed to induce skin sensitizing effects on 25 volunteers. Hence, Geranyl butyrate (CAS No.106-29-6) was considered to be not sensitizing to human skin.

The above results are also supported by the experimental studysummarized in Fd Cosmet. Toxicol, Vol. 13, pp. 449-457, 1975; for thestructurally similar read across substance,3,7-dimethylocta-2,6-dien-1-yl 2-methylpropanoate(Geranyl isobutyrate) [CAS:2345-26-8]. 3, 7-dimethylocta-2,6-dien-1-yl 2-methylpropanoate was tested at the concentration of 10% in petrolatum in 25 human volunteers. No skin sensitizing effect was observed in any 25 human volunteers. Therefore, 3, 7-dimethylocta-2,6-dien-1-yl 2-methylpropanoate(2345-26-8)was considered to be non sensitizing in human skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,Geranyl propionate was not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data forGeranyl propionate suggests that it is not likely to cause any dermal sensitization to skin.

Geranyl propionate can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.