Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate

Endpoint summary

Description of key information

Acute oral toxicity:

The LD50 was estimated to be 3040 mg/kg bw, when Wistar male and female rats were orally exposed with Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5).

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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

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

GLP compliance:

not specified

Test type:

other: Estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate
- Common name: Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate
- Molecular formula: C21H21N3O2
- Molecular weight: 347.416 g/mol
- Smiles notation: N=C1C=C\C(C=C1)=C(\c1ccc(N)cc1)c1ccc(N)cc1.C(C)(=O)O
- InChl: 1S/C19H17N3.C2H4O2/c20-16-7-1-13(2-8-16)19(14-3-9-17(21)10-4-14)15-5-11-18(22)12-6-15;1-2(3)4/h1-12,20H,21-22H2;1H3,(H,3,4)
- Substance type: Organic
-Physical state: solid

Species:

rat

Strain:

Wistar

Sex:

male/female

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:

3040 mg/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

Dose descriptor:

LD50

Effect level:

3 040 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% Mortality was Observed

Mortality:

No data available

Clinical signs:

No data available

Body weight:

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" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Michael Addition AND Michael Addition >> Quinoide type compounds AND Michael Addition >> Quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  by Protein binding by OASIS v1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

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 >> Quinoneimines OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones 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 via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines 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) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 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 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 >> 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 >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers 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.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Non binder, without OH or NH2 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: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.42

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.1

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was estimated to be 3040 mg/kg bw, when Wistar male and female rats were orally exposed with Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5).

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 Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5). The LD50 was estimated to be 3040 mg/kg bw when Wistar male and female rats were orally exposed with Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 040 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

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5) 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 Wistar male and female rats for Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5).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 Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5).LD50 was estimated to be 3040 mg/kg bw when male and female Wistar rats were exposed with Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5) orally.

In another experimental study conducted by U.S. National Library of Medicine (ChemIDplus TOXNET Database, 2017) for the structurally similar read across substance C.I. Basic Red 9 (569-61-9). Acute oral toxicity study was done in mouse using test material C.I. Basic Red 9 (569-61-9). 50% Mortality was observed at dose 5000 mg/kg bw.Hence,LD50 was considered to be 5000mg/kg body weight when Mouse was treated with C.I. Basic Red 9 (569-61-9) orally.

Also these results are further supported by the experimental study conducted by U.S. National Library of Medicine (ChemIDplus TOXNET Database, 2017) for the structurally similar read across substance 4,4'-diaminostilbene-2,2'-disulphonic acid(81-11-8). Acute oral toxicity study was done in guinea pig using test material 4,4'-diaminostilbene-2,2'-disulphonic acid(81-11-8). Mortality was observed at dose 47000 mg/kg bw. Renal Function Tests Depressed. Gross pathology was performed for Kidney, Ureter, And Bladder.Liver Function Tests Impaired.Hence,LD50 value was considered to be 47000mg/kg body weight when guinea pig were treated with4,4'-diaminostilbene-2,2'-disulphonic acid (81-11-8) orally.

Thus, based on the above studies and predictions Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5) and its read across substances, it can be concluded that LD50 value was 3040 mg/kg bw. Thus, comparing this value with the criteria of CLP Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5) can be “Not classified” for Acute Oral Toxicity.

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP Bis(p-aminophenyl)-4-methylenecyclohexa-2,5-dienylideneammonium acetate (6035-94-5) can be “Not classified” for Acute Oral Toxicity.