Registration Dossier

Skin Irritation:

A skin irritation study was performed as a part of Acute dermal toxicity study to evaluate the irritation potential of 2-nonanone.

5.0g/kg of undiluted 2-nonanone was applied under occlusion patch test to rabbits for 24 hours. Irritation effects and scaly skin was observed at necropsy in the test animals.

Based on the observations, 2-nonanone can be considered as a skin irritant.

Eye Irritation:

The ocular irritation potential of 2-nonanone was predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the seven closest read across substances.

2-nonanone was estimated to be moderately irritating to the eyes of New Zealand White rabbits.

On the basis of the estimated result,2-nonanonecan be considered to be moderately irritating to skin and can be classified under the category "Eye 2" as per CLP regulation.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Skin irritation test was performed for Methyl heptyl ketone in rabbit over a period of 24 hour by patch test method.

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-nonanone
- Molecular formula: C9H18O
- Molecular weight: 142.24g/mol
- Smiles notation: C(CCCCC)CC(C)=O
- InChI: 1S/C9H18O/c13456789(2)10/h38H2,12H3
- Substance type: Organic
- Physical state: colorless to pale yellow clear oily liquid

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

other: Undiluted material was applied on the skin.

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

>5000 mg/kg

Duration of treatment / exposure:

24 hour

Observation period:

24 hour

Number of animals:

no data available

Details on study design:

No data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

Irritation effects and scaly skin was observed at necropsy in the test animals.
Based on the observations, 2-nonanone can be considered as a skin irritant.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Irritation effects and scaly skin was observed at necropsy in rabbits.
Based on the observations, 2-nonanone can be considered as a skin irritant.

Executive summary:

A skin irritation study was performed as a part of Acute dermal toxicity study in rabbits to evaluate the irritation potential of 2-nonanone.

5.0g/kg of undiluted 2-nonanone was applied under occlusion patch test to rabbits for 24 hours. Irritation effects and scaly skin was observed at necropsy in rabbits.

Based on the observations, 2-nonanone can be considered as a skin irritant.

Endpoint conclusion:

adverse effect observed (irritating)

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:

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 v3.3 and the QMRF report has been attached

Qualifier:

equivalent or similar to guideline

Guideline:

other: predicted data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-nonanone
- Molecular formula: C9H18O
- Molecular weight: 142.24g/mol
- Smiles notation: C(CCCCC)CC(C)=O
- InChI: 1S/C9H18O/c13456789(2)10/h38H2,12H3
- Substance type: Organic
- Physical state: colorless to pale yellow clear oily liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.1 ml, undiluted

Duration of treatment / exposure:

single ocular instillation of the test material.

Observation period (in vivo):

Ocular reactions were assessed at 1, 24, 48 and 72 hours after treatment and on days 8, 15 and 22.

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

Moderate irritation was observed

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" or "i" or "j" or "k" or "l" ) and ("m" and ( not "n") ) ) and (("o" or "p" or "q" or "r" or "s" ) and ("t" and ( not "u") ) ) and (("v" or "w" or "x" or "y" or "z" ) and ("aa" and ( not "ab") ) ) and (("ac" or "ad" or "ae" or "af" or "ag" ) and ("ah" and ( not "ai") ) ) ) and "aj" ) and ("ak" and ( not "al") ) ) and ("am" and ( not "an") ) ) and "ao" ) and "ap" ) and "aq" ) and ("ar" and ( not "as") ) ) and ("at" and "au" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Ketone by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Ketone 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 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 Carbonyl compound AND Ketone 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 >> Flavonoids OR AN2 >> Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Michael-type addition, quinoid structures >> Quinones OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> Hydroxamic Acids OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Nucleophilic addition to metabolically formed thioketenes OR AN2 >> Nucleophilic addition to metabolically formed thioketenes >> Haloalkene Cysteine S-Conjugates OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR AN2 >> Schiff base formation >> Halofuranones OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives 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 >> Schiff base formation by aldehyde formed after metabolic activation >> N-methylol 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 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 AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Aminoacridine DNA Intercalators OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with nucleoside bases OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with nucleoside bases >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical attack after one-electron reduction of diazonium cation OR Radical >> Radical attack after one-electron reduction of diazonium cation >> Arenediazonium Salts OR Radical >> Radical mechanism by ROS formation 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 by ROS formation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Anthrones OR Radical >> Radical mechanism via ROS formation (indirect) >> C-Nitroso Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Flavonoids OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Haloalcohols OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline 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) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> DNA bases alkylation by carbenium ion formed OR SN1 >> DNA bases alkylation by carbenium ion formed >> Diazoalkanes OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Acyclic Triazenes OR SN1 >> Nucleophilic attack after carbenium ion formation >> N-Nitroso Compounds 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 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 >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation >> C-Nitroso Compounds OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN1 >> SN1 reaction at nitrogen-atom bound to a good leaving group or on nitrenium ion OR SN1 >> SN1 reaction at nitrogen-atom bound to a good leaving group or on nitrenium ion >> N-Acyloxy(Alkoxy) Arenamides OR SN1 >> SN1 reaction at nitrogen-atom bound to a good leaving group or on nitrenium ion >> N-Aryl-N-Acetoxy(Benzoyloxy) Acetamides OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Hydroxamic Acids 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 by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards 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 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives 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 >> Monohaloalkanes 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 >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Arenediazonium Salts OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution after carbenium ion formation OR SN2 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Halofuranones 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 Nitrogen Atom OR SN2 >> SN2 at Nitrogen Atom >> N-acetoxyamines OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 at sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides 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 OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group >> N-Acetoxyamines OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium ion OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium ion >> N-Acyloxy(Alkoxy) Arenamides OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium ion >> N-Aryl-N-Acetoxy(Benzoyloxy) Acetamides by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Ketone by Organic Functional groups

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Ketone 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 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 Carbonyl compound AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isothiocyanates OR Acylation >> P450 Mediated Activation to Acyl Halides OR Acylation >> P450 Mediated Activation to Acyl Halides >> 1,1-Dihaloalkanes OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Sulfonylureas OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Thiazolidinediones OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Thioureas OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans 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 >> 5-alkoxyindoles 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 >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated aldehydes OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imines OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal >> Ethylenediamines (including piperazine) 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 >> Chemicals Activated by P450 to Mono-aldehydes >> N-methylol derivates OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Thiazoles OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Aliphatic N-Nitro OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Carbenium Ion Formation >> Alpha halo ethers (including alpha halo thioethers) OR SN1 >> Carbenium Ion Formation >> Diazoalkanes OR SN1 >> Carbenium Ion Formation >> Hydrazine OR SN1 >> Carbenium Ion Formation >> N-Nitroso (alkylation) OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Carbenium Ion Formation >> Pyrrolizidine alkaloids 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 ester hydroxylamine OR SN1 >> Nitrenium Ion formation >> Aromatic N-hydroxylamines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic nitroso OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic ester hydroxylamine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic nitro OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic nitroso OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic phenylureas OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Aziridines OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> Direct Acting Epoxides and related >> Sulfuranes OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> 1,2-Dihaloalkanes OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Phenoxy polarised alkenes OR SN2 >> Nitrosation-SN2 OR SN2 >> Nitrosation-SN2 >> Nitroso-SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> P450 Mediated Sulfoxidation OR SN2 >> P450 Mediated Sulfoxidation >> Thioureas-SN2 OR SN2 >> Ring opening SN2 Reaction OR SN2 >> Ring opening SN2 Reaction >> Lactones OR SN2 >> SN2 at a Nitrogen atom OR SN2 >> SN2 at a Nitrogen atom >> N-acyloxy-N-alkoxyamides OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Alkyl carbamates OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphates OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphonic esters OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Ketone by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Ketone by Organic Functional groups (nested)

Domain logical expression index: "r"

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 Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Carbonyl compound AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR 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, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Ketone by Organic Functional groups

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Ketone by Organic Functional groups (nested)

Domain logical expression index: "y"

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 Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Carbonyl compound AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acyl transfer via nucleophilic addition reaction OR Acylation >> Acyl transfer via nucleophilic addition reaction >> Isocyanates, Isothiocyanates 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 >> Diacyl peroxides, anhydrides (sulphur analogues of diacyl peroxides) OR Acylation >> Direct acylation involving a leaving group >> N-Acylated heteroaromatic amines OR Acylation >> Direct acylation involving a leaving group >> N-Acylsulfonamides OR Acylation >> Direct acylation involving a leaving group >> Sulphonyl halides or cyanides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Acylation >> Ester aminolysis >> Dithioesters 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 >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents OR Acylation >> Ring opening acylation >> beta-Lactams 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 Ionic interaction >> Substituted guanidines OR Ionic interaction >> Substituted guanidines >> Guanidines OR Michael Addition OR Michael Addition >> alpha,beta-Unsaturated carbonyl compounds OR Michael Addition >> alpha,beta-Unsaturated carbonyl compounds >> alpha,beta-Aldehydes OR Michael Addition >> alpha,beta-Unsaturated carbonyl compounds >> Lactones OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Activated electrophilic ethenylarenes 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 >> alpha,beta-Carbonyl compounds with polarized triple bond 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 conjugated systems with electron withdrawing group >> N-Sulfonylazomethynes OR Michael Addition >> Michael type addition on azoxy compounds OR Michael Addition >> Michael type addition on azoxy compounds >> Azoxy compounds OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> alpha,beta-Unsaturated oximes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines OR Michael Addition >> Polarised Alkenes >> Polarised Alkenes - sulfinyl OR Michael Addition >> Polarised Alkenes >> Polarised Alkenes - sulfones OR Michael Addition >> Quinoide type compounds OR Michael Addition >> Quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines OR Michael Addition >> Quinone type chemicals OR Michael Addition >> Quinone type chemicals >> Pyranones, Pyridones (and related nitrogen chemicals) OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Azomethyme type compounds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Nucleophilic addition >> Nucleophilic addition reaction at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition reaction at polarized N-functional double bond >> C-Nitroso compounds 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 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 >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones 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 SN1 OR SN1 >> Carbenium ion formation (enzymatic) OR SN1 >> Carbenium ion formation (enzymatic) >> Carbenium ion OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations >> Mercury compounds OR SN2 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 a Nitrogen atom >> N-Oxicarbonyl amides, N-Acyloxy-N-alkoxyamides 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 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters OR SN2 >> SN2 Reaction at a sp3 carbon atom >> alpha- or beta-Halo ether OR SN2 >> SN2 reaction at a sulfur atom OR SN2 >> SN2 reaction at a sulfur atom >> Thiocyanates OR SN2 Ionic OR SN2 Ionic >> Nucleophilic substitution at protein disulfide bonds involving O-nucleophiles OR SN2 Ionic >> Nucleophilic substitution at protein disulfide bonds involving O-nucleophiles >> Arenesulfinic acids OR SN2 Ionic >> Nucleophilic substitution at protein disulfide bonds involving S-nucleophiles OR SN2 Ionic >> Nucleophilic substitution at protein disulfide bonds involving S-nucleophiles >> Thiourea compounds 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 aromatic substitution on activated halogen, cyano, isocyano, sulfo, sulfonyl groups, etc. OR SNAr >> Nucleophilic aromatic substitution on activated halogen, cyano, isocyano, sulfo, sulfonyl groups, etc. >> Halogenated five membered aromatic compounds 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 by Protein binding by OASIS v1.3

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Ketone by Organic Functional groups

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Ketone by Organic Functional groups (nested)

Domain logical expression index: "af"

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 Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Carbonyl compound AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "ah"

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

Domain logical expression index: "ai"

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 >> Direct Acylation Involving a Leaving group >> Sulphonyl halides 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 Alkenes >> Polarised alkene - pyridines OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyrimidines OR Michael addition >> Polarised Alkynes OR Michael addition >> Polarised Alkynes >> Polarised alkyne - ketones 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 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 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 >> Epoxides and Related Chemicals >> Sulfuranes OR SN2 >> Ring Opening SN2 Reaction OR SN2 >> Ring Opening SN2 Reaction >> beta-Lactones-SN2 OR SN2 >> SN2 reaction at a halo atom OR SN2 >> SN2 reaction at a halo atom >> N-haloimides 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 >> N-Acyloxy-N-alkoxyamides OR SN2 >> SN2 reaction at a nitrogen atom >> Nitrosoureas (nitrogen) OR SN2 >> SN2 reaction at a sp2 carbon atom OR SN2 >> SN2 reaction at a sp2 carbon atom >> Polarised alkenes with a halogen leaving group OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Aromatic sulphonic acids OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at a sulphur atom >> Sulfoxides of 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 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 >> Allyl acetates and related chemicals 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: "aj"

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

Domain logical expression index: "ak"

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: "al"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 11 - Trans.Metals Cu,Ag,Au OR Group 12 - Trans.Metals Zn,Cd,Hg OR Group 13 - Metals Al,Ga,In,Tl OR Group 14 - Metalloids Si,Ge OR Group 14 - Metals Sn,Pb OR Group 15 - Nitrogen N OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At OR Group 2 - Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra OR Group 4 - Trans.Metals Ti,Zr,Hf OR Group 6 - Trans.Metals Cr,Mo,W OR Group 9 - Trans.Metals Co,Rh,Ir by Chemical elements

Domain logical expression index: "am"

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

Domain logical expression index: "an"

Referential boundary: The target chemical should be classified as Carboxylic acids (Hepatotoxicity) No rank OR Ethionine (Hepatotoxicity) Alert OR Perhexiline (Hepatotoxicity) Alert OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "ao"

Similarity boundary:Target: CCCCCCCC(C)=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "ap"

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

Domain logical expression index: "aq"

Similarity boundary:Target: CCCCCCCC(C)=O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "ar"

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: "as"

Referential boundary: The target chemical should be classified as Group C Melting Point > 55 C OR Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "at"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.55

Domain logical expression index: "au"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.83

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

2-nonanone was estimated to be moderately irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 2-nonanone was predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the seven closest read across substances.

2-nonanone was estimated to be moderately irritating to the eyes of New Zealand White rabbits.

On the basis of the estimated result,2-nonanonecan be considered to be moderately irritating to skin and can be classified under the category "Eye 2" as per CLP regulation

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

Skin Irritation:

In different studies, nonan-2-one has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical nonan-2-one and its functionally similar read across substances tridecanol(CAS: 112-70-9) and Heptan-2-one (CAS:110-43-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

Various studies for nonan-2-one were summarized in Food and Cosmetics Toxicology, Volume 26, Issue 4, 1988, Pages 393 to assess the irritation in humans and rabbits.

As part of an acute dermal LD50 study, undiluted nonan-2-one produced irritant effects and scaly skin at necropsy in rabbits patch-tested for 24 hr under occlusion at 5.0 g/kg. A 48-hr closed-patch test at a concentration of 5% in petrolatum on the backs of 35 volunteers produced no irritation.

Even though nonan-2-one is irritating to rabbit skin but human data concludes that it is not irritating to human skin. Hence, nonan-2-one was considered to be irritating to skin.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for Nonan-2-one.2-nonanone was estimated to be moderately irritating to the skin of New Zealand White rabbits.On the basis of the estimated result,2-nonanonecan be considered to be moderately irritating to skin and can be classified under the category "Skin 2" as per CLP regulation.

Also these results are further supported by the experimental study conducted by N. Kanikkannan et.al (International Journal of Pharmaceutics 248 (2002) 219-228) -.In an in-vivo skin irritation study, tridecanol was applied on CD® (SD) hrBi hairless rat skin by using Hill top chamber®. The skin irritation (erythema) was evaluated by visual scoring using a modified method of Draize. The scores were given from 0 to 4 depending on the degree of erythema as follows: no erythema*/0, slight erythema (barely perceptible- light pink)*/1, moderate erythema (dark pink)*/2, moderate to severe erythema (light red)*/3, severe erythema (extreme redness)*/4. The skin irritation was evaluated by visual scoring method and bioengineering methods such as measurement of transepidermal water loss (TEWL) and skin blood flow. Results shows lower permeation enhancement effect but caused greater skin irritation after 72 and 96 hours at a score of 1.0.

Therefore, Tridecanol was considered to be skin irritant to CD® (SD) hrBi hair less rat.

The above results are further supported by the experimental data conducted by Henry F. Smyth Jr et.al (American Industrial Hygiene Association Journal, 1962, 23:2, 95-107) for the functionally similar substanceHeptan-2-one (CAS:110-43-0).Primary skin irritation on rabbits was recorded in a 10-grade ordinal series and is based upon the severest reaction that develops on the clipped abdominal skin of each of five albino rabbits within 24 hours of the uncovered application of 0.01 ml of undiluted sample or of solutions in water, propylene glycol, or acetone. Grade 1 indicates no irritation and Grade 2 the least visible capillary injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted and Grade 10 indicates necrosis from a 0.01% solution

Primary Irritation score after 24 hours exposure to 2-heptanone was Grade 4.

Based on the grades, 2-heptanone can be considered to be moderately irritating to rabbit skin.

On the basis of the available data for the target as well as it read across substances;and applying the weight of evidence approach, it can be concluded thatnonan-2-one can be considered irritating to skin.Comparing the above annotations with the criteria of CLP regulation,nonan-2-one can be classified under the category “Category 2”.

Eye Irritation:

In different studies, nonan-2-one has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical nonan-2-one and its functionally similar read across substances tridecanol(CAS: 112-70-9) and octan-2-one (CAS:111-13-7). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for Nonan-2-one.2 -nonanone was estimated to be moderately irritating to the skin of New Zealand White rabbits.On the basis of the estimated result,2-nonanonecan be considered to be moderately irritating to skin and can be classified under the category "Skin 2" as per CLP regulation.

This result was further supported by the experimental study summarized inHSDB (Hazardous Substances Data Bank, last updated 2006 for the functionally similar read across substance octan-2-one (CAS:111-13-7). Rats were exposed to calculated vapor concentrations of the similar substance 111-13-7 (2 octanone), 8.9 mg/L (1673 ppm) for 6 hr exhibited signs of mild eye irritation.Hence, 2- octanone was mildly irritating to rat eyes

The above results were further supported by the experimental study summarized in HSDB (Hazardous Substances Data Bank, last updated 2006 for the functionally similar read across substance octan-2-one (CAS: 111-13-7). Undiluted 2- octanone was slightly irritating to rabbit eyes.

Also these results are further supported by the experimental study conducted by R. A. SCALA et.al (American Industrial Hygiene Association Journal, (1973), 34:11, 493-499) for the functionally similar substance tridecanol(CAS: 112-70-9). A single application of 0.1 ml of undiluted tridecyl alcohol was made into the conjunctival sac of the left eye of each of six rabbits. The untreated eye served as the control. The treated eye was closed for 30 seconds and eyes were not washed. Observations for irritancy and possible systemic toxicity were made at 1, 4, and 24 hours and at 2, 3, 4, and 7 days. Where positive effects persisted, observations were continued initially and at termination the eyes were examined following instillation of 2 % sodium fluorescein solution to detect any corneal lesions if not otherwise visible. Grading scale is slight-moderate-marked and severe. Signs of irritation exposure were graded and scored according to the method of Draize. Tridecyl alcohol caused little irritation in most of the animals, but persistent corneal opacity in one caused the classification as moderate.

On the basis of the available data for the target as well as it read across substances;and applying the weight of evidence approach, it can be concluded thatnonan-2-one can be considered irritating to eyes.Comparing the above annotations with the criteria of CLP regulation,nonan-2-one can be classified under the category “Category 2”.

Available studies for Nonan-2-one indicate that it is likely to cause mild to moderate irritation to eyes and skin.

Hence, Nonan-2-one can be evaluated as “Irritant” to eyes and skin and it can be classified under the category “Skin 2 and Eye 2” as per CLP regulation.