4-aminonaphthalene-1,8-dicarboximide

Endpoint summary

Description of key information

1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino- was non toxic by oral and dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Data is from database

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Acute oral toxicity of 1-HBenz( de)isoquinoline-1,3( 2H)-dione,6-amino- in rats

GLP compliance:

not specified

Test type:

other: No data

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

10000 mg/kg/day

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality observed

Mortality:

No mortality observed in treated rats.

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 was considered to be > 10000 mg/kg/day when rats were treated with 1-HBenz( de)isoquinoline-1,3( 2H)-dione,6-amino- orally.

Executive summary:

In acute toxicity study rats were treated with 1-HBenz ( de)isoquinoline-1,3( 2H)-dione,6-amino-  in the concentration of 10000 mg/kg/day. No effect on survival of treated rats were observed at 10000 mg/kg bw. Therefore,LD50 was considered to be> 10000 mg/kg/day when rats were treated with 1-HBenz( de)isoquinoline-1,3( 2H)-dione,6-amino- orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

Data is from RTECS database

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

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:

other: Data is from QSAR Toolbox 3.4.0.17 (2016

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: No data

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

No data available

No. of animals per sex per dose:

5 male, 5 female

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 938 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

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" or "f" )  and "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and ("r" and "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) OR 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 >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain AND Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines AND Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines 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 SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines 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 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "f"

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: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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: "k"

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

Domain logical expression index: "l"

Similarity boundary:Target: Nc1ccc2c3c1cccc3C(=O)NC2=O
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Enol form OR Keto form (5-membered heteroarenes) - 1,3-H shift by Tautomers unstable

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Methyldopa (Hepatotoxicity) Alert OR Nitrobenzenes (Hemolytic anemia with methemoglobinemia) Rank A OR Nitrobenzenes (Hepatotoxicity) Rank C OR Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B OR o-/ p-Aminophenols (Hemolytic anemia with methemoglobinemia) Rank B OR Oxyphenistain (Hepatotoxicity) Alert OR p-Aminophenols (Renal toxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.274

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.27

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Estimated LD50 was considered to be 4938 mg/kg bw when New Zealand White male and female rabbits by using 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino- - closely applied on the skin for 24 hours.

Executive summary:

Acute dermal toxicity was estimated using QSAR Toolbox 3.4.0.17(2016) in New Zealand White male and female rabbits by using 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino- closely applied on the skin for 24 hours. 50 % mortality were observed in treated rats at 4938 mg/kg bw. Therefore, estimated LD50 was considered to be 4938 mg/kg bw when New Zealand White male and female rabbits by using 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino- - closely applied on the skin for 24 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 938 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR Toolbox 3.4.(2016)

Additional information

Acute oral toxicity:

Based on the data available for target 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino-(CAS no 1742-95-6) and its read across Phthalimide (CAS no 85-41-6) are summarized below

In a RTECS database (2015), acute oral toxicity was given for rats by using 1-HBenz ( de)isoquinoline-1,3( 2H)-dione,6-amino-  in the concentration of 10000 mg/kg/day. No effect on survival of treated rats were observed at 10000 mg/kg bw. Therefore, LD50 was considered to be > 10000 mg/kg/day when rats were treated with 1-HBenz( de)isoquinoline-1,3( 2H)-dione,6-amino- orally.

Based on the prediction done by usingQSAR Toolbox 3.4.0.17(2016), acute oral toxicity was estimated in Wistar male and female rats by using 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino- orally by gavage. 50 % mortality were observed in treated rats at 2164.7 mg/kg bw. Therefore, estimated LD50 was considered to be 2164.7 mg/kg bw when Wistar male and female rats by using 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino- orally by gavage for 24 hours.

In a study given by OECD HPV SIDS (2005) for read across, acute oral toxicity was evaluated in Crj: CD(SD) male and female rats by using Phthalimide in the concentration of 0 and 2000 mg/kg/day in 1% (w/v) Carboxymethylcellulose orally by gavage and observed for 14 days. No effect on survival, general appearance, body weights, gross pathology and histopathology of treated male and female rats were observed at 2000 mg/kg bw as compared to control. Therefore, LD50 was considered to be > 2000 mg/kg/day when Crj: CD (SD) male and female rats were treated with Phthalimide orally by gavage.

In a above similar source for read across, acute oral toxicity was evaluated in Wistar male rats by using Phthalimide in the concentration of 5000 mg/kg/day in lutrol orally by gavage and observed for 14 days. No effect on survival and general appearance of treated male rats were observed at 5000 mg/kg bw. Therefore, LD50 was considered to be > 5000 mg/kg/day when Wistar male and female rats were treated with Phthalimide orally by gavage.

Thus, Based on weight of evidence for target 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino-(CAS no 1742-95-6) and its read across Phthalimide (CAS no 85-41-6) is likely to be non hazardous by oral route as per CLP criteria of classification.

Acute dermal toxicity:

Based on the data available for target 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino-(CAS no 1742-95-6) and its read across (CAS no ) and (CAS no) are summarized below

Based on the prediction done by usingQSAR Toolbox 3.4.(2016), acute dermal toxicity was estimated in New Zealand White male and female rabbits by using 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino- closely applied on the skin for 24 hours. 50 % mortality were observed in treated rats at 4938 mg/kg bw. Therefore, estimated LD50 was considered to be 4938 mg/kg bw when New Zealand White male and female rabbits by using 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino- - closely applied on the skin for 24 hours.

In a study given by OECD HPV SIDS (2005) for read across, acute dermal toxicity was evaluated in New Zealand white 2 male and 1 female rabbits by using Phthalimide in the concentration of 5010 and 7940 mg/kg bw 40% solution-suspension in corn oil by dermal application and observed for 14 days. No effect on survival of treated male and female rabbits were observed at 5010 and 7940 mg/kg bw. Reduced appetite and activity for one to two days were observed in treated rabbits. The viscera appeared normal at end of 14 day. Therefore, LD50 was considered to be > 7940 mg/kg/day when New Zealand white male and female rabbits were treated with Phthalimide by dermal application. 

In a above similar source for read across, acute dermal toxicity was evaluated in 2 male and 2 female rabbits by using Phthalimide in the concentration of 3160, 5000 and 7940 mg/kg bw 25 % solution-suspension in corn oil to clipped, intact skin by dermal application and observed for 14 days. No effect on survival of treated male and female rabbits were observed at 3160, 5000 and 7940 mg/kg bw . Reduced appetite and activity were observed in treated rabbits. The viscera appeared normal at end of 14 day. Therefore, LD50 was considered to be > 7940 mg/kg/day when male and female rabbits were treated with Phthalimide by dermal application.  

Thus, Based on weight of evidence for target 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino-(CAS no 1742-95-6) and its read across Phthalimide (CAS no 85-41-6) is likely to be non hazardous by dermal route as per CLP criteria of classification.

Justification for selection of acute toxicity – oral endpoint

LD50 was considered to be > 10000 mg/kg/day when rats were treated with 1-HBenz( de)isoquinoline-1,3( 2H)-dione,6-amino- orally.

Justification for selection of acute toxicity – dermal endpoint

estimated LD50 was considered to be 4938 mg/kg bw when New Zealand White male and female rabbits by using 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino- -  closely applied on the skin for 24 hours.

Justification for classification or non-classification

Based on weight of evidence for target 1h-benz[de]isoquinoline-1,3(2h)-dione, 6-amino-(CAS no 1742-95-6) and its read across Phthalimide (CAS no 85-41-6) is likely to be non hazardous by oral and dermal route as per CLP criteria of classification.