3,7-dimethylocta-2,6-dienenitrile

Endpoint summary

Description of key information

Skin Irritation:

After 48 hours it was observed that the chemical failed to elicit any kind of skin irritation reaction. Therefore, Geranyl nitrile (CAS No: 5146 -66 -7) was considered to be not irritating in human subjects.

Eye Irritation:

The ocular irritation potential of the test chemical was estimated using OECD QSAR toolbox v3.4

Geranyl nitrile was estimated to be not irritating to rabbit eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Skin irritation study was carried out in human subjects to evaluate its irritation potential by closed patch test.

GLP compliance:

not specified

Species:

human

Strain:

other: Not applicable

Details on test animals or test system and environmental conditions:

No details available

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

other: Petrolatum

Controls:

not specified

Amount / concentration applied:

12% in petrolatum

Duration of treatment / exposure:

48-hours

Observation period:

48-hours

Number of animals:

No data

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48 hrs

Reversibility:

no data

Remarks on result:

other: Not irritating

Interpretation of results:

not irritating

Conclusions:

In skin irritation study of Geranyl nitrile ,the chemical was considered to be non-irritating when applied to human skin.

Executive summary:

Skin irritation study was performed in human subjects for test chemical Geranyl nitrile to evaluate its skin irritation potential by closed patch test.

The test chemical was applied fo 48 hours occlusion period at concentration of 12% in petrolatum and observations were made.

After 48 hours it was observed that the chemical failed to elicit any kind of skin irritation reaction. Therefore, Geranyl nitrile (CAS No: 5146 -66 -7) was considered to be not irritating in human subjects.

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:

other: data from OECD QSAR toolbox v3.4

Justification for type of information:

data from OECD QSAR toolbox v3.4

Qualifier:

according to guideline

Guideline:

other: Prediction was done using OECD QSAR toolbox v3.4

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

no

Specific details on test material used for the study:

Name of the test material: Geranyl nitrile
- Molecular formula: C10H15N1
- Molecular weight: 149.24 g/mol
- Smiles notation: C(#N)C=C(C)CCC=C(C)C
-Substance type: Organic
-Physical state: Liquid

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

no data

Observation period (in vivo):

1,24,48,72 hours afteradministration of test chemical

Duration of post- treatment incubation (in vitro):

no data

Number of animals or in vitro replicates:

3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Alkene AND Allyl AND Nitrile AND Terpenes by Organic Functional groups

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Nitrile AND Overlapping groups AND Terpenes by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Acetylenic Carbon [#C] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as AN2 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain 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) >> Single-Ring Substituted Primary Aromatic Amines 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 nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines 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 >> 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 sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates OR 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 >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters 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 nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as Alkyl carbamate and thiocarbamate OR alpha,beta-unsaturated carbonyls by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Slightly reactive (GSH) OR Slightly reactive (GSH) >> 2-Alkenyl carbonitriles (MA) by Protein binding potency

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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 SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Haloalkenes (and related cyano, sulfate and sulfonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) by Protein binding by OECD

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as Aliphatic monoalcohols OR Thiazoles and thiazolidines by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.1

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.96

Interpretation of results:

other: not irritating

Conclusions:

Geranyl nitrile was estimated to be not irritating to rabbit eyes.

Executive summary:

The ocular irritation potential of the test chemical was estimated using OECD QSAR toolbox v3.4

Geranyl nitrile was estimated to be not irritating to rabbit eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

Skin irritation studies were conducted on rabbits and humans by José L. Domingo, 1976 to evaluate the irritation potential of Geranyl nitrile.

Skin irritation study was performed in human subjects for test chemical Geranyl nitrile to evaluate its skin irritation potential by closed patch test. The test chemical was applied fo 48 hours occlusion period at concentration of 12% in petrolatum and observations were made. After 48 hours it was observed that the chemical failed to elicit any kind of skin irritation reaction. Therefore, Geranyl nitrile (CAS No: 5146 -66 -7) was considered to be not irritating in human subjects.

Another irritation test was conducted on rabbit skin to evaluate skin irritancy of chemical Geranyl nitrile. The test chemical was applied to rabbit skin for 24-hrs under occlusion at full strength.The chemical did not produce any cutaneous reaction. Hence the test chemical Geranyl nitrile can be considered as not irritating to rabbit skin.

Based on the available information for the target substance, dermal exposure to Geranyl nitrile is not likely to cause skin irritation in humans and rabbits. Hence Geranyl nitrile can be considered to be not irritating to skin.

Eye Irritation:

The ocular irritation potential of the test chemical was estimated using OECD QSAR toolbox v3.4

Geranyl nitrile was estimated to be not irritating to rabbit eyes.

An eye irritation study was performed according to OECD guideline 405 on rabbits with dose volume of 0.1 ml. The animals were observed for 72-h and mean scores were noted .Mean score was 0.0 for cornea, iris and swelling of conjunctiva at 24, 48 and 72 h. Mean score for conjunctival redness was 0.7 at 24 h. All findings were reversible after 48 h. Hence, the test chemical; 3,7-dimethylocta-2,6-dienenitrile was considered to be non-irritating to rabbit eyes.

Based on the available information for the target substance, and applying the weight of evidence approach;3,7-dimethylocta-2,6-dienenitrile can be considered to not irritating to eyes.

Justification for selection of skin irritation / corrosion endpoint:

data is from peer reviewed journals

Justification for selection of eye irritation endpoint:

data is from OECD QSAR toolbox v3.4

Justification for classification or non-classification

Available studies for Geranyl nitrile indicates that it is not likely to cause any irritation to skin and eyes.