Registration Dossier

Acute toxicity: oral
The acute oral LD50 value of the test substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione to rat is estimated to be 6658.47 mg/kg bw by OECD QSAR toolbox.

Acute toxicity: inhalation
The study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Acute toxicity: dermal
The acute dermal LD50 value of the test substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione to rat is estimated to be 8157.12 mg/kg bw by OECD QSAR toolbox.

Reference

Endpoint:

acute toxicity: oral

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 predicted by OECD QSAR Toolbox version 3.4. The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Data is predicted by OECD QSAR Toolbox version 3.4

GLP compliance:

not specified

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: gavage

Vehicle:

not specified

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

6 658.475 mg/kg bw

Based on:

test mat.

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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" and ( not "i") ) ) and ("j" and ( not "k") ) ) and ("l" and "m" ) )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN1 AND SN1 >> Alkylation after metabolically formed carbenium ion species AND SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN2 AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Imides by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN1 AND SN1 >> Alkylation after metabolically formed carbenium ion species AND SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN2 AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition, quinoid structures OR AN2 >> Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Carbamoylation after isocyanate formation 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 >> Schiff base formation OR AN2 >> Schiff base formation >> Dicarbonyl compounds 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 >> 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 AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR No alert found OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine 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 >> N-Hydroxyethyl Lactams OR Non-covalent interaction >> DNA intercalation >> Organic Azides OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes 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 ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Organic Azides 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) >> Coumarins 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) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes 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-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes 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 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrene formation OR SN1 >> Nucleophilic attack after nitrene formation >> Organic Azides OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> 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 >> Nitroarenes with Other Active Groups 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 >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction 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 P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom 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 >> DNA alkylation 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 at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives 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 by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4.18

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.11

Interpretation of results:

other: Not classified

Conclusions:

The acute oral LD50 value of the test substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione to rat is estimated to be 6658.47 mg/kg bw by OECD QSAR toolbox.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated

for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione. The acute oral LD50 value of the test substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione to rat is estimated to be 6658.47 mg/kg bw. This value indicates that the substance is not toxic via oral rout and hence considered as Not Classified as per classification criteria of CLP regulation.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 658.47 mg/kg bw

Quality of whole database:

Data is of k2 reliability and predicted fromQSAR toolbox.

Reference

Endpoint:: acute toxicity: inhalation
Data waiving:: other justification
Justification for data waiving:: the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion:

no study available

Reference

Endpoint:

acute toxicity: dermal

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 predicted by OECD QSAR Toolbox version 3.4. The supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: as mentioned below

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

8 157.12 mg/kg bw

Based on:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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" and ( not "i") ) ) and ("j" and ( not "k") ) ) and ("l" and ( not "m") ) ) and "n" ) and "o" ) and ("p" and ( not "q") ) ) and ("r" and "s" ) )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN1 AND SN1 >> Alkylation after metabolically formed carbenium ion species AND SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN2 AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Imides by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) 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 >> 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 >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group >> N-Haloacylamides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents OR AN2 OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael type 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 quinoid structures OR AN2 >> Michael-type addition to quinoid structures >> Carboxylic Acid Amides 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 Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls OR SN2 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 sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes 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 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters 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 v1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkali Earth OR Transition Metals by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "n"

Similarity boundary:Target: CCCCNc1ccc2c3c1cccc3C(=O)N(CCCC)C2=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: CCCCNc1ccc2c3c1cccc3C(=O)N(CCCC)C2=O
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Imide AND Naphtalene AND Quinolone/ Quinolinedione/ Isoquinolinedione by Organic Functional groups

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.85

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.16

Interpretation of results:

other: Not classified

Conclusions:

The acute dermal LD50 value of the test substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione to rat is estimated to be 8157.12 mg/kg bw by OECD QSAR toolbox.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated

for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione. The acute dermal LD50 value of the test substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione to rat is estimated to be 8157.12 mg/kg bw. This value indicates that the substance is not toxic via dermal route and hence considerd as Not Classified as per classification criteria of CLP regulation.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 157.12 mg/kg bw

Quality of whole database:

Data is of k2 reliability and predicted fromQSAR toolbox.

Acute toxicity: oral
Predicted data for the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione and its read across substance were reviewed for acute oral toxicity endpoint and are represented here as weight of evidence approach:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione. The acute oral LD50 value of the test substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione to rat is estimated to be 6658.47 mg/kg bw.

Acute oral toxicity was determined for the read across substance 2-(cyclohexylsulfanyl)-1H-isoindole-1,3(2H)-dione (CAS No. 17796-82-6) in Sprague-Dawley albino rat (HSDB database, 2017). The acute oral toxicity value of the substance is determined to be 2600 mg/kg bw/day.

Acute oral toxicity study was conducted on rats to determine the oral toxic nature of the structurally related substance 4-Amino-1, 8-naphthalimide (CAS 1742-95-6) as cited in RTECS database. 50% mortality was not observed at the doses studied and the acute oral lethal dose (LD50) for the test compound4-Amino-1, 8-naphthalimide is found to be >10000 mg/kg.

Considering above data and by applying weight of evidence approach it can be concluded that the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is not toxic via oral route and is considered to not classified as per CLP regulation.

Acute toxicity: inhalation
The study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Acute toxicity: dermal
Predicted data for the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione and its read across substance were reviewed for acute dermal toxicity endpoint and are represented here as weight of evidence approach:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione. The acute dermal LD50 value of the test substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione to rat is estimated to be 8157.12 mg/kg bw.

Acute dermal toxicity test was performed (HPVIS database, 2017) for the read across chemical 2-methyl-1H-isoindole-1,3(2H)-dione (CAS No. 550-77-4). Doses of 200 mg/kg and 2000 mg/kg were used. Two New Zealand White rabbits (one male and one female) were used at each of two dosage levels. The rabbits weighed from 2760 to 2952 grams at the start of the study period. Food and water were available ad libitum. Body weights were measured initially and at 14 days after compound application. The hair was removed from the back of each rabbit with an electric clipper. The test substance was applied once only to the back of each rabbit. Two rabbits received 200 mg/kg and two rabbits received 2000 mg/kg of the test substance. The area of application was then wrapped with a gauze bandage and occluded with Saran Wrap. After a 24-hour exposure period, the bandages were removed and the backs were washed with tepid tap water. The rabbits were observed for mortality for a period of 14 days. Neither of the rabbits at either dose level died during the 14-day post-exposure observation period. All four of the rabbits exhibited body weight gains during this time period. Based upon the results obtained, the test substance is considered a non toxic material by the dermal route of administration.

Acute dermal toxicity was determined for the other read across substance 2-(cyclohexylsulfanyl)-1H-isoindole-1,3(2H)-dione (CAS No. 17796-82-6) in New Zealand white rabbits. The acute dermal toxicity value of the substance is determined to be >5010 mg/kg bw/day as cited in HSDB database.

Considering above data and by applying weight of evidence approach it can be concluded that the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is not toxic via dermal route and is considered to not classified as per CLP regulation.

Considering above data and by applying weight of evidence approach it can be concluded that the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is not toxic via oral and dermal and is considered to not classified as per CLP regulation.