1,4-diamino-2,3-dichloroanthraquinone

Endpoint summary

Description of key information

Acute oral toxicity

LD50 was estimated to be 875.122 mg/kg bw, when male Sprague-Dawley rats were exposed with 1,4-diamino-2,3-dichloroanthraquinone (81-42-5) orally.

Acute dermal toxicity

LD50 was estimated to be 9260.18mg/kg bw. When male and female New Zealand White rabbits were exposed with 1,4-diamino-2,3-dichloroanthraquinone (81-42-5) by dermal application.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

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 from OECD QSAR toolbox v3.3 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name of the test chemical: 1,4-diamino-2,3-dichloroanthraquinone
Molecular formula: C14H8Cl2N2O2
Molecular weight: 307.135 g/mol
Smiles Notation: c1cc2c(cc1)C(=O)c1c(c(c(c(c1N)Cl)Cl)N)C2=O
InChI: 1S/C14H8Cl2N2O2/c15-9-10(16)12(18)8-7(11(9)17)13(19)5-3-1-2-4-6(5)14(8)20/h1-4H,17-18H2
Substance Type: Organic
Physical State: Solid crystal powder (purple-black)

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

875.122mg/kg bw

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:

male

Dose descriptor:

LD50

Effect level:

875.122 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aminoaniline, para OR Anthracenone/ Antracendione OR Aryl halide OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR Aryl chloride OR Aryl halide OR Carbonyl compound OR Halogen derivative OR Ketone OR Primary amine OR Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as 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 >> Arenes 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 ketones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes by DNA binding by OECD

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides 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 >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Michael Addition >> Quinoide type compounds OR Michael Addition >> Quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  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 Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes 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 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: "g"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg AND Group All Melting Point > 200 C AND Group CNHal Aqueous Solubility < 0.004 g/L AND Group CNHal Aqueous Solubility < 0.1 g/L AND Group CNHal log Kow > 3.8 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow > 9 OR Group All Molecular Weight > 650 g/mol OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Molecular Weight > 290 g/mol OR Group CNHal Molecular Weight > 370 g/mol OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Chlorphentermine (Hepatotoxicity) Alert OR Halobenzenes (Hepatotoxicity) Rank A OR Halobenzenes (Renal toxicity) Rank A OR Halogenated aliphatic compounds (Hepatotoxicity) Rank A OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Phenones (Branched) by rtER Expert System ver.1 - USEPA

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.84

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.89

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 was estimated to be 875.122 mg/kg bw, when male Sprague-Dawley rats were exposed with 1,4-diamino-2,3-dichloroanthraquinone (81-42-5) orally.

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 1,4-diamino-2,3-dichloroanthraquinone(81-42-5) ,LD50 was estimated to be 875.122 mg/kg bw, when male Sprague-Dawley ratswereexposed with 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)orally.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

875.122 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

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:

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: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name of the test chemical: 1,4-diamino-2,3-dichloroanthraquinone
Molecular formula: C14H8Cl2N2O2
Molecular weight: 307.135 g/mol
Smiles Notation: c1cc2c(cc1)C(=O)c1c(c(c(c(c1N)Cl)Cl)N)C2=O
InChI: 1S/C14H8Cl2N2O2/c15-9-10(16)12(18)8-7(11(9)17)13(19)5-3-1-2-4-6(5)14(8)20/h1-4H,17-18H2
Substance Type: Organic
Physical State: Solid crystal powder (purple-black)

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:

No data available

Doses:

9260.18mg/kg bw

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:

male/female

Dose descriptor:

LD50

Effect level:

9 260.18 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

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 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aminoaniline, para OR Anthracenone/ Antracendione OR Aryl halide OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR Aryl chloride OR Aryl halide OR Carbonyl compound OR Halogen derivative OR Ketone OR Primary amine OR Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Vinyl pyridines OR Low reactive OR Low reactive >> Alicyclic ketones OR Low reactive >> alpha-alkyl cinnamaldehyde derivatives OR Moderate reactive OR Moderate reactive >> Activated 1,3,5-triazine derivatives OR Moderate reactive >> Glycidyl ether epoxides OR Moderate reactive >> Phenyl substituted cinnamaldehydes by DPRA Cysteine peptide depletion

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-methides OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-3-Dicarbonyls 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 Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Metalloids 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 AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Amineptine (Hepatotoxicity) Alert OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Chlorphentermine (Hepatotoxicity) Alert OR Halobenzenes (Hepatotoxicity) Rank A OR Halobenzenes (Renal toxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "n"

Similarity boundary:Target: Nc1c(Cl)c(Cl)c(N)c2c1C(=O)c1ccccc1C2=O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as C9 Aromatics hydrocarbon solvents OR Xylenes by OECD HPV Chemical Categories

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.03

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.9

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 9260.18mg/kg bw. When male and female New Zealand White rabbits were exposed with 1,4-diamino-2,3-dichloroanthraquinone (81-42-5) by dermal application.

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 1,4-diamino-2,3-dichloroanthraquinone(81-42-5),LD50 was estimated to be 9260.18mg/kg bw. When male and female NewZealand Whiterabbits wereexposed with 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)by dermal application.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

9 260.18 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Additional information

Acute oral toxicity

In different studies, 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 1,4-diamino-2,3-dichloroanthraquinone(81-42-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

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 1,4-diamino-2,3-dichloroanthraquinone(81-42-5) ,LD50 was estimated to be 875.122 mg/kg bw, when male Sprague-Dawley ratswereexposed with 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)orally.

 In experimental study given by U.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017) on structurally similar read across substance 4-Amino-4-chloroanthraquinone (2872-47-1). In acute oral toxicity study, mice were treated with4-Amino-4-chloroanthraquinoneorally. 50% mortality was observed in treated mouse at 1320 mg/kg bw. Therefore, LD50 was considered to be 1320 mg/kg bw When mouse were treated with 4-Amino-4-chloroanthraquinone (2872-47-1) orally. 

   

Also it is further supported by experimental study given by U.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017) on structurally similar read across substance 1,4-Diamino-2-methoxyanthraquinone(2872-48-2) .In

In acute oral toxicity study, rats were treated with1,4-Diamino-2-methoxyanthraquinone orally. 50% mortality was observed in treated rats at 891 mg/kg bw. Clinical signs like Behavioural changes as somnolence (general depressed activity) and gastrointestinal changes on kidney, ureter, and bladder were observed .Also changes in urine composition were noted in treated rats. Therefore, LD50 was considered to be 891mg/kg bw. When rats were treated1,4-Diamino-2-methoxyanthraquinone(2872-48-2) orally.  

Thus, based on the above studies and predictions on 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)and its read across substances, it can be concluded that LD50 value is less than875.122 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)can be classified as“Category IV”for acute oral toxicity.

Acute dermal toxicity

In different studies,1,4-diamino-2,3-dichloroanthraquinone(81-42-5)has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for1,4-diamino-2,3-dichloroanthraquinone(81-42-5),The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

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 1,4-diamino-2,3-dichloroanthraquinone(81-42-5),LD50 was estimated to be 9260.18mg/kg bw. When male and female New Zealand White rabbits were exposed with 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)by dermal application.

 Also it is further supported by experimental study given by U.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017) on structurally similar read across substance1,3-Diisopropenylbenzene (3748-13-8).Acute dermal toxicity study was done in rabbits using test material1,3-Diisopropenylbenzene.No mortality was observed at dose 2000mg/kg bw. HenceLD50 was considered to be >2000mg/kg body weight. When rabbits were treated with 1,3-Diisopropenylbenzene (3748-13-8) by dermal application.

Also it is further supported by experimental study given by U.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017) on structurally similar read across substance1,4-Diamino-2-methoxyanthraquinone(2872-48-2).In acute dermal toxicity study, rabbits were treated with1,4-Diamino-2-methoxyanthraquinoneby dermal application . No mortality was observed in treated rabbits at 2000 mg/kg bw. Clinical signs like the skin after systemic exposure causes dermatitis and other changes in skin and appendages were observed. Also effect on kidney, ureter, and bladder and changes in urine composition were noted .Therefore, LD50 was considered to be>2000mg/kg bw. When rabbits were treated1,4-Diamino-2-methoxyanthraquinone(2872-48-2) by dermal application.

 Thus, based on the above studies and predictions on1,4-diamino-2,3-dichloroanthraquinone(81-42-5)and its read across substances, it can be concluded that LD50 value is 9260.18mg/kg bw. Thus, comparing this value with the criteria of CLP1,4-diamino-2,3-dichloroanthraquinone(81-42-5)can be “Not classified” for acute dermal toxicity.

 

 

 

 

 

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP1,4-diamino-2,3-dichloroanthraquinone(81-42-5)can be

classified as“Category IV”for acute oral toxicity and “Not classified” for acute dermal toxicity.