4-(phenylazo)benzene-1,3-diamine acetate

Endpoint summary

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity ,LD50 value was predicted based on OECD QSAR toolbox for target substance 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) was estimated to be 694.42 mg/kg bw,and for different studies available on the structurally similar read across substance 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) was considered to be 1000 mg/kg bw and for 2,6-DIAMINO-3-(PHENYLAZO)PYRIDINE (94-78-0) was considered to be 403 mg/kg bw. All these studies concluded that the LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) can be classified as “Category IV” for acute oral toxicity.

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 v3.3,2018

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: 4-(phenylazo)benzene-1,3-diamine acetate
- IUPAC name: 4-(phenylazo)benzene-1,3-diamine acetate
- Molecular formula: C14H16N4O2
- Molecular weight: 272.306 g/mole
- Smiles : c1(ccc(c(N)c1)\N=N\c1ccccc1)N.C(C)(=O)O
- Inchl: 1S/C12H12N4.C2H4O2/c13-9-6-7-12(11(14)8-9)16-15-10-4-2-1-3-5-10;1-2(3)4/h1-8H,13-14H2;1H3,(H,3,4)/b16-15+;
- 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:

694.42 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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

694.42 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" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and ("m" and ( not "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 Anilines (Acute toxicity) AND Not categorized 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 >> Aromatic azo 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 Anilines (amino-meta) AND Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Very strong binder, OH group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.3

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 Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aliphatic acids and (Met)acrylic acids AND Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Inclusion rules not met OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "o"

Similarity boundary:Target: CC(O)=O_Nc1ccc(N=Nc2ccccc2)c(N)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic Amine, secondary OR Alkoxy by Organic Functional groups

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0777

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.42

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 value was estimated to be 694.42 mg/kg bw,when male and female wistar rats were orally exposed with 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) via gavage.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6).The LD50 was estimated to be 694.42 mg/kg bw,when male and female wistar rats were orally exposed with 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) via gavage.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

694.42 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

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, 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) along with the study available on the structurally similar read across substance 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) and 2,6-DIAMINO-3-(PHENYLAZO)PYRIDINE (94-78-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6).The LD50 was estimated to be 694.42 mg/kg bw,when male and female wistar rats were orally exposed with 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) via gavage.

The above study was further supported by Sustainability Support Services (Europe) AB (study number: 19138, 2017-07-18) for the structurally similar read across substance 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5). The study was designed and conducted to determine the acute oral toxicity profile of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) in Sprague Dawley ratsaccording to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).Polyethylene Glycol – 400 was used as vehicle.Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg resulted in reduced locomotor activity and ataxic gait with onset at 4 hours after the dosing and no mortality at 24 hours after the dosing. As no mortality was observed at  24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg resulted in reduced locomotor activity and ataxic gait with onset at 4 hours after the dosing and no mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in polyurea, diarrhoea, reduced locomotor activity and ataxic gait with onset at 30 minutes to day 1 after the dosing. Two animals died on day 1 after the dosing. All animals from 300 mg/kg dose group survived and exhibited normal body weight gain through the study period of 14 days.Gross pathological examination did not reveal any abnormalities in animals sacrificed terminally from 300 mg/kg and 2000 mg/kg dose groups.Gross pathological examination revealed distended stomach with test item coloured ingesta and small and large intestine with liquid test item coloured ingesta in found dead animals from 2000 mg/kg dose group. The acute oral LD50 (Cut-off value) of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) was 1000 mg/kg body weight,when female Sprague Dawley rats were treated with4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5)orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

This is further supported by Maryadele J. O'Neil (The Merck Index. 14th ed.,2006,pg.1245) and U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank); US national Library of Medicine,2017) for the structurally similar read across substance 2,6-DIAMINO-3-(PHENYLAZO)PYRIDINE (94-78-0). Acute oral toxicity study was performed in rats using test material 2,6-DIAMINO-3-(PHENYLAZO)PYRIDINE(94-78-0).50% mortality was observed at dose 403 mg/kg bw. Hence,LD50 value was considered to be 403 mg/kg bw,when rats were treated with 2,6-DIAMINO-3-(PHENYLAZO)PYRIDINE (94-78-0) orally.

Thus, based on the above studies on 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) and it’s structurally similar read across substances 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) and 2,6-DIAMINO-3-(PHENYLAZO)PYRIDINE (94-78-0), it can be concluded that LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) can be classified as “Category IV” for acute oral toxicity.

Justification for classification or non-classification

Based on the above experimental studies and prediction on 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) and it’s structurally similar read across substances 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) and 2,6-DIAMINO-3-(PHENYLAZO)PYRIDINE (94-78-0), it can be concluded that LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-(phenylazo)benzene-1,3-diamine acetate(79234-33-6) can be classified as “Category IV” for acute oral toxicity.