Geranyl isobutyrate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

(Q)SAR

Adequacy of study:

key study

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 version 3.3 and the supporting QMRF report has been attached.

Data source

Reference

Reference Type:

other: Predicted data .

Title:

[R]: not sensitising; Estimation for Skin Sensitisation for CAS 2345-26-8

Author:

Sustainability Support Services (Europe) AB

Year:

2017

Bibliographic source:

OECD QSAR toolbox version 3.3.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

As mention below

Principles of method if other than guideline:

Prediction is from OECD QSAR toolbox version 3.3, 2017

GLP compliance:

not specified

Type of study:

Buehler test

Justification for non-LLNA method:

Not specified.

Test material

Test material information

Constituent 1

Reference substance name:

Geranyl isobutyrate

EC Number:

219-062-7

EC Name:

Geranyl isobutyrate

Cas Number:

2345-26-8

Molecular formula:

C14H24O2

IUPAC Name:

geranyl isobutyrate

Details on test material:

SMILES:CC(C)C(=O)OCC=C(C)CCC=C(C)C

Specific details on test material used for the study:

- Name of the test material: Geranyl isobutyrate
- IUPAC name: 3,7-dimethylocta-2,6-dien-1-yl 2-methylpropanoate
- Molecular formula: C14H24O2
- Molecular weight: 224.342 g/mol
- Substance type: Organic
- Smiles: C(OC\C=C(\CC\C=C(/C)C)C)(C(C)C)=O

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adult
- Weight at study initiation: 401 ± 29 g
- Housing: conventional, 5 animals per cage in Makrolon Type IV
- Diet: Ssniff G 4
- Complete feed for guinea pigs (Ssniff, Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70 - Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Challenge

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

No. of animals per dose:

20 animals

Details on study design:

RANGE FINDING TESTS: A preliminary test was conducted in order to establish a non-irritant test substance concentration which could be used in the main test. Amounts of 0.4 mL of test substance preparations (25, 50 and 75% (w/w) in corn oil) and the undiluted test substance were applied to the skin of 4 animals under occlusive conditions. Exposure duration was 6 h, after which the patches were removed and the areas of application were wiped off with corn oil and a cellulose swab. Dermal reactions were assessed directly after patch removal and 24 and 48 h post-application according to the Draize scoring system for erythema and edema.The mean erythema and edema scores out of all 4 animals over 6, 24 and 48 h post-application were both 0.0. Thus, no primary dermal irritation was observed on the skin of the treated animals up to a test substance concentration of 100% at any reading time point. Therefore, the main study was performed using the undiluted test substance.

MAIN STUDYA.
INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance
- Control group: corn oil
- Site: left flank
- Frequency of applications: every 7 days
- Duration: Days 0-14- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28- Exposure period: 6 h
- Test groups: test substance
- Control group: test substance
- Site: right flank
- Concentrations: 100%
- Evaluation (hr after challenge): 6, 24, 48 and 72 h after application of the test substance.

Challenge controls:

No data available.

Positive control substance(s):

not specified

Study design: in vivo (LLNA)

Statistics:

No data available.

Results and discussion

In vivo (non-LLNA)

Results

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization reaction was observed.

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 7 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 ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

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 Alkene AND Allyl AND Carboxylic acid ester AND Isopropyl by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Allyl AND Carboxylic acid ester AND Isopropyl AND Overlapping groups 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 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<] AND Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as 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 No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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 AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols 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) >> 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) >> 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 metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic 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 SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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, 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 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates 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.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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 OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers 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 >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "k"

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, without OH or NH2 group OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

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 Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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: "r"

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: "s"

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

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Formic acid and formates OR Monoethylene glycol ethers by OECD HPV Chemical Categories

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.73

Applicant's summary and conclusion

Interpretation of results:

other: not sensitising

Conclusions:

The skin sensitization potential of 3, 7-dimethylocta-2,6-dien-1-yl 2-methylpropanoate(2345-26-8) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3, 7-dimethylocta-2,6-dien-1-yl 2-methylpropanoate(2345-26-8)was predicted to be non sensitizing to the skin of female Dunkin-Hartley guinea pig.

Executive summary:

The skin sensitization potential of 3, 7-dimethylocta-2,6-dien-1-yl 2-methylpropanoate(2345-26-8) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3, 7-dimethylocta-2,6-dien-1-yl 2-methylpropanoate(2345-26-8)was predicted to be non sensitizing to the skin of female Dunkin-Hartley guinea pig.