Geranyl butyrate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Geranyl butyrate is not a gene mutant in vitro.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.4

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material: Geranyl butyrate
- Molecular formula: C14H24O2
- Molecular weight: 224.342 g/mol
- Smiles notation: C(=C\COC(CCC)=O)(\CC\C=C(\C)C)C
- Substance type: Organic

Species / strain / cell type:

S. typhimurium TA 100

Details on mammalian cell type (if applicable):

not specified

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with

Metabolic activation system:

S9 metabolic activation system

Test concentrations with justification for top dose:

not specified

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Remarks:

not specified

Details on test system and experimental conditions:

not specified

Rationale for test conditions:

not specified

Evaluation criteria:

The plates were observed for a dose dependent increase in the number of revertants.

Statistics:

not specified

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

not specified

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Terpenes by Organic Functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Carboxylic acid ester AND Overlapping groups AND Terpenes 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<] 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 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: "g"

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 >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acetates  OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides)  OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group >> N-Carbonyl heteroaryl amines OR Acylation >> Direct acylation involving a leaving group >> N-Carbonylsulfonamides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated alkyl esters  OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ester aminolysis or thiolysis >> Carbamates  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  OR Acylation >> Ring opening acylation >> beta-Lactams  OR AN2 OR AN2 >> Direct carbamoylation of protein amines OR AN2 >> Direct carbamoylation of protein amines >> Isocyanates and Diisocyanates OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives 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 activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Michael type nucleophilic addition and Schiff base formation OR AN2 >> Michael type nucleophilic addition and Schiff base formation >> Halogenated Vicinal Hydrocarbons OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines 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  >> Gallic Acid Esters OR AN2 >> Michael-type addition to quinoid structures  >> Hydroxylated Phenols OR AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines OR AN2 >> Michael-type addition to quinoid structures  >> Quinoneimine OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR AN2 >> Nucleophilic addition to alpha, beta - unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta - unsaturated carbonyl compounds >> Propargyl Alcohol derivatives OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR AN2 >> Schiff base formation with carbonyl compounds (AN2) OR AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases >> Pyrimidines and Purines OR AN2 >> Thiocarbamoylation of protein nucleophiles OR AN2 >> Thiocarbamoylation of protein nucleophiles >> Isothiocyanates OR AR OR AR >>  Radical-type addition to imino tautomer of aminoacridines OR AR >>  Radical-type addition to imino tautomer of aminoacridines >> Benzoquinoline and Аcridine derivatives OR Ionic interaction OR Ionic interaction >> Electrostatic interaction of tetraalkylamonium ion with protein carboxylates OR Ionic interaction >> Electrostatic interaction of tetraalkylamonium ion with protein carboxylates >> Tetraalkylammonium ions OR Michael addition OR Michael addition >> Michae addition on quinoide type compounds OR Michael addition >> Michae addition on quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  OR Michael addition >> Michael addition on alpha,beta-Unsaturated carbonyl compounds OR Michael addition >> Michael addition on alpha,beta-Unsaturated carbonyl compounds >> alpha,beta-Aldehydes  OR Michael addition >> Michael addition on alpha,beta-Unsaturated carbonyl compounds >> Lactones OR Michael addition >> Michael addition on azoxy compounds OR Michael addition >> Michael addition on azoxy compounds >> Azoxy compounds  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 Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Conjugated systems with electron withdrawing groups  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Nitroalkenes OR Michael addition >> Michael addition on polarised Alkenes OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkenes - sulfones  OR Michael addition >> Michael addition on polarised Alkynes OR Michael addition >> Michael addition on polarised Alkynes >> Polarised Alkynes - alkinyl pyridines, pyrazines, pyrimidines, triazines  OR Michael addition >> Michael type addition on quinone type chemicals OR Michael addition >> Michael type addition on quinone type chemicals >> Pyranones, Pyridones (and related nitrogen chemicals)  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 Radical reactions OR Radical reactions >> Free radical formation OR Radical reactions >> Free radical formation >> Hydroperoxides OR Radical reactions >> Free radical formation >> Organic peroxy compounds OR Radical reactions >> ROS Generation OR Radical reactions >> ROS Generation >> Sterically Hindered Piperidine Derivatives OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines 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 Schiff base formation >> Direct acting Schiff base formers >> Di-substituted alpha,beta-unsaturated aldehydes  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR Schiff base formation >> Schiff base formation with carbonyl compounds >> alpha-Ketoesters  OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  >> Heterocyclic Aromatic Amines OR SN1 OR SN1 >> DNA and protein alkylation via direct attack at carbonyl carbon atom and the formation of diazoalkyl cation OR SN1 >> DNA and protein alkylation via direct attack at carbonyl carbon atom and the formation of diazoalkyl cation >> N-Alkyl-N-nitrosocarbamates OR SN1 >> DNA and protein alkylation via the formation of alkyldiazonium ion OR SN1 >> DNA and protein alkylation via the formation of alkyldiazonium ion >> Alkylated nitrosoureas and nitrosoguanidines OR SN1 >> DNA and protein alkylation via the formation of alkyldiazonium ion >> N-Nitrosoamine  Derivatives OR SN2 >> DNA and protein alkylation via direct attack at carbonyl carbon atom and the formation of diazoalkyl cation OR SN2 >> DNA and protein alkylation via direct attack at carbonyl carbon atom and the formation of diazoalkyl cation >> N-Alkyl-N-nitrosocarbamates OR SN2 >> DNA and protein alkylation via the formation of alkyldiazonium ion OR SN2 >> DNA and protein alkylation via the formation of alkyldiazonium ion >> Alkylated nitrosoureas and nitrosoguanidines OR SN2 >> DNA and protein alkylation via the formation of alkyldiazonium ion >> N-Nitrosoamine  Derivatives OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at a Nitrogen atom OR SN2 >> Nucleophilic substitution at a Nitrogen atom >> N-Nitroso compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> N-Nitroso compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Phosphonates OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfonates OR SN2 >> Nucleophilic substitution at the central carbon atom of N-nitroso compounds OR SN2 >> Nucleophilic substitution at the central carbon atom of N-nitroso compounds >> N-Nitroso_compounds  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> Nucleophilic type substitution together with ring-opening of an episulfonium ion intermediate OR SN2 >> Nucleophilic type substitution together with ring-opening of an episulfonium ion intermediate >> Halogenated Vicinal Hydrocarbons OR SN2 >> Protein alkylation via direct attack at the N-alkyl group OR SN2 >> Protein alkylation via direct attack at the N-alkyl group >> Alkylated nitrosoureas and nitrosoguanidines OR SN2 >> Protein alkylation via direct attack at the N-alkyl group >> N-Alkyl-N-nitrosocarbamates OR SN2 >> Protein and/or DNA alkylation OR SN2 >> Protein and/or DNA alkylation >> Dialkyl Alkylphosphonates OR SN2 >> Protein nitrosylation via direct attack at the nitroso group OR SN2 >> Protein nitrosylation via direct attack at the nitroso group >> N-Alkyl-N-nitrosocarbamates OR SN2 >> Ring opening nucleophilic substitution involving arene oxide derivatives and proteins OR SN2 >> Ring opening nucleophilic substitution involving arene oxide derivatives and proteins >> Benzoquinoline and Аcridine derivatives OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes  OR SN2 >> Ring opening SN2 reaction >> Mustard compounds  OR SN2 >> SN2 reaction at a sulfur atom OR SN2 >> SN2 reaction at a sulfur atom >> Thiocyanates 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 OR SNAr >> Nucleophilic substitution on activated Csp2-atoms in quinolines OR SNAr >> Nucleophilic substitution on activated Csp2-atoms in quinolines >> Benzoquinoline and Аcridine derivatives OR SNVinyl OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom >> Vinyl type compounds with electron withdrawing groups  OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as Esters (Chronic toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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<] by Organic functional groups (US EPA)

Domain logical expression index: "l"

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: "m"

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: "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 Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isocyanates OR Acylation >> Isocyanates and Related Chemicals >> Isothiocyanates OR Acylation >> Isocyanates and Related Chemicals >> Thiocyanates-Acylation OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Acylation >> Ring Opening Acylation >> beta-Lactones-Acylation OR Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - aldehydes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - cyano OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - nitro OR Michael addition >> Polarised Alkynes OR Michael addition >> Polarised Alkynes >> Polarised alkyne - pyridine OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Benzoquinones OR Michael addition >> Quinones and Quinone-type Chemicals >> Pyranones (and related nitrogen chemicals) OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-diimine OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR No alert found OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-2-Dicarbonyls OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-3-Dicarbonyls OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Di-substituted alpha, beta-unsaturated aldehydes OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> 1,2-Dihaloalkane OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> Ring Opening SN2 Reaction OR SN2 >> Ring Opening SN2 Reaction >> beta-Lactones-SN2 OR SN2 >> SN2 reaction at a nitrogen atom OR SN2 >> SN2 reaction at a nitrogen atom >> N-Acetoxy-N-acetyl-phenyl OR SN2 >> SN2 reaction at a nitrogen atom >> Nitrosoureas (nitrogen) OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at a sulphur atom >> Thiocyanates-SN2 OR SN2 >> SN2 reaction at a sulphur atom >> Thiols OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halo ethers 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-Haloalkynes (and related cyano, sulfate, sulphpnate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SN2 >> SN2 reaction at sp3 carbon atom >> beta-Halo ethers OR SN2 >> SN2 reaction at sp3 carbon atom >> Nitrosoureas (carbon) OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphates OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphonates OR SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates OR SN2 >> SN2 reaction at sp3 carbon atom >> Thiophosphates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-pyridines OR SNAr >> Nucleophilic aromatic substitution >> Halo-pyrimidines OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Pyrrolizidine Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.4

Domain logical expression index: "q"

Referential boundary:The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "r"

Referential boundary:The target chemical should be classified as Allyl esters (Hepatotoxicity) Rank A OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "s"

Referential boundary:The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "t"

Referential boundary:The target chemical should be classified as Aromatic Amine Type Compounds by Oncologic Primary Classification

Domain logical expression index: "u"

Referential boundary:The target chemical should be classified as High gene expression AND High gene expression >> Activated esters by Keratinocyte gene expression

Domain logical expression index: "v"

Referential boundary:The target chemical should be classified as Not possible to classify according to these rules by Keratinocyte gene expression

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.95

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 18.1

Conclusions:

Geranyl butyrate failed to induce mutation in Salmonella typhimurium strain TA100 with S9 metabolic activation system and hence is predicted to not classify as a gene mutant in vitro.

Executive summary:

Gene mutation was predicted for Geranyl butyrate using SSS QSAR prediction database, 2016. The study assumed the use of Salmonella typhimurium strain TA100 with S9 metabolic activation system. Geranyl butyrate failed to induce mutation in Salmonella typhimurium strain TA100 in the presence of S9 metabolic activation system and hence is predicted to not classify as a gene mutant in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for geranyl nitrile. The study assumed the use of male and female mouse. Geranyl nitrile was predicted to not induce gene mutation in male and female mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4, 2017

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

Specific details on test material used for the study:

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

Species:

mouse

Strain:

not specified

Details on species / strain selection:

No data

Sex:

male/female

Vehicle:

No data

Details on exposure:

No data

Duration of treatment / exposure:

No data

Frequency of treatment:

No data

Post exposure period:

No data

Remarks:

No data

No. of animals per sex per dose:

No data

Control animals:

not specified

Positive control(s):

No data

Tissues and cell types examined:

No data

Details of tissue and slide preparation:

No data

Evaluation criteria:

Prediction was done considering chromosomal abberation in mammalian cell lne used

Statistics:

No data

Sex:

not specified

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: No mutagenic potential

Additional information on results:

No data

The prediction was based on dataset comprised from the following descriptors: "chromosome aberration"
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" )  )

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 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 Not categorized by Repeated dose (HESS)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Allyl esters (Hepatotoxicity) Rank A OR Phthalate esters (Testicular toxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "f"

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: "g"

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

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.112

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.69

Conclusions:

Geranyl butyrate was predicted to not induce gene mutation in male and female mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for geranyl butyrate. The study assumed the use of male and female mouse. Geranyl butyrate was predicted to not induce gene mutation in male and female mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Gene mutation in vitro:

Prediction model based estimation and data from read across have been summarized to determine the mutagenic nature of Geranyl butyrate:

Gene mutation was predicted for Geranyl butyrate using SSS QSAR prediction database, 2016. The study assumed the use of Salmonella typhimurium strain TA100 with S9 metabolic activation system. Geranyl butyrate failed to induce mutation in Salmonella typhimurium strain TA100 in the presence of S9 metabolic activation system and hence is predicted to not classify as a gene mutant in vitro.

Gene mutation was predicted for Geranyl butyrate using SSS QSAR prediction database, 2016. The study assumed the use of Salmonella typhimurium strain TA1535 without S9 metabolic activation system. Geranyl butyrate failed to induce mutation in Salmonella typhimurium strain TA1535 in the absence of S9 metabolic activation system and hence is predicted to not classify as a gene mutant in vitro.

Gene mutation toxicity was performed by Wild et al (1983) to determine the mutagenic nature of Allyl capronate (RA CAS no 123 -68 -2). The test was performed by plate incorporation method usingSalmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 with and without S9 metabolic activation system at 5 doses of the test substance were used upto 3600 µg/plate and the plates were incubated for 48hrs. Allyl caproate failed to induce mutation in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 in the presenceand absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

In vitro mammalian chromosome aberration test was performed by Galloway et al (1987) to evaluate the mutagenic nature of the test compound Geranyl acetate (RA CAS no 105 -87 -3). Cloned Chinese hamster ovary cells (CHO-W-B1) were cultured in Mc-Coy’s 5a medium with 10% fetal calf serum, L-glutamine, and antibiotics. Tests were carried out with and without an in vitro metabolic activation system (S9 mix). In tests without metabolic activation, the test chemical was left in culture for 19.5- 26 hrs, whereas with activation the test chemical was added along with S9 mix for only 2 hr at the beginning of the test period and the expression of the cells continued upto 19.5- 26 hrs. Concurrent solvent and positive controls were also incorporated in the study. The Dose for the study was selected on the basis ofpreliminary test of cell survival 24 hr after treatment. Doses were based on observations of cell confluence and mitotic cell availability in the SCE test. The test compound Geranyl acetate failed to induce chromosomal aberrations in Chinese hamster Ovary cells line in the presence of absence and presence of S9 metabolic activation system and hence is not mutagenic in the chromosome aberration study performed.

In another study performed by Zeiger et al (1986) for the read across chemical, Geranyl acetate (RA CAS no 105 -87 -3) was examined for its ability to cause mutagenic changes when tested in strains of the bacteria Salmonella typhimurium, specifically, TA 1535, TA 1537, TA 98 and TA 100 through the preincubation assay method. Preliminary dose range finding study was performed initially to set the doses for the main study. The test was conducted both in the presence and absence of metabolic activation using male rat and hamster liver derived S-9 mix at dose levels of 0.0, 1.0, 3.3, 10.0, 33.0, 100.0, 333.0, 1000.0, 3333.0 µg/plate. The test was repeated and atleast three plates were used at each dose level. Geranyl acetate failed to induce mutation in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 in the presence and absence of S9 metabolic activation system and hence is not mutagenic in vitro.

Based on the weight of evidence data summarized, Geranyl butyrate is not likely to classify as a gene mutant in vitro.

Gene toxicity in vivo:

Prediction model based estimation for the target chemical was used to determine the mutagenic nature of Geranyl butyrate in vivo. The study is as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for geranyl butyrate. The study assumed the use of male and female mouse. Geranyl butyrate was predicted to not induce gene mutation in male and female mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Justification for selection of genetic toxicity endpoint

Data is from prediction database

Justification for classification or non-classification

Based on the weight of evidence data summarized, Geranyl butyrate is not likely to classify as a gene mutant in vitro.