N-(4-chlorophenyl)-3-hydroxy-4-[(2-methyl-5-nitrophenyl)azo]naphthalene-2-carboxamide

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was estimated to be 2103 mg/kg bw when Tif:MAGf male and female rats were orally exposed with N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide.

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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: estimation

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide
- Molecular formula: C24H17ClN4O4
- Molecular weight: 460.875 g/mol
- Smiles notation: c12c(c(c(C(Nc3ccc(Cl)cc3)=O)cc1cccc2)O)\N=N\c1cc(ccc1C)[N+](=O)[O-]
- InChl: 1S/C24H17ClN4O4/c1-14-6-11-18(29(32)33)13-21(14)27-28-22-19-5-3-2-4-15(19)12-20(23(22)30)24(31)26-17-9-7-16(25)8-10-17/h2-13,30H,1H3,(H,26,31)/b28-27+
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

Tif:MAGf

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

not specified

Doses:

2103 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 103 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

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" or "c" or "d" or "e" )  and "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "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 Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain by DNA binding by OASIS v.1.4

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 >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides 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  >> Carboxylic Acid Amides by Protein binding by OASIS v1.4

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 Amides AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acid anhydrides OR Aldehydes OR Aromatic amines OR Esters including acrylic and methacrylic esters OR Esters of organic sulfonic or sulfuric esters OR Inclusion rules not met OR Ketones OR Lactones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Gallates by rtER Expert System ver.1 - USEPA

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ring opening acylation at a carbonyl OR Acylation >> Ring opening acylation at a carbonyl >> Lactams OR Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Aminophenols OR Pro-Michael Addition >> Pro-quinone and related >> Hydroquinones OR Pro-Michael Addition >> Pro-quinone-methide OR Pro-Michael Addition >> Pro-quinone-methide >> 4-Hydroxymethylphenols by Respiratory sensitisation

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aromatic diazo AND H-acceptor-path3-H-acceptor AND Nitro-aromatic by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as 1,3-dialkoxy-benzene OR Alkyl carbamate and thiocarbamate OR Coumarins and Furocoumarins OR Hydrazine OR No alert found OR Oxolane OR Primary aromatic amine, hydroxyl amine and its derived esters OR S or N mustard by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "o"

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: "p"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR SN2 OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 1) ONLY

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.43

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 10

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2103 mg/kg bw when Tif:MAGf male and female rats were orally exposed with N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide.

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 N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide. The LD50 was estimated to be 2103 mg/kg bw when Tif:MAGf male and female rats were orally exposed with N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 103 mg/kg bw

Quality of whole database:

Data is klimisch 2 and from OECD QSAR toolbox

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, N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide 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 mice and rats for N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide along with the study available on structurally similar read across substance 1- (2, 4-dimethylphenylazo)-2-naphthol (CAS no 3118-97-6) and 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 N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide. The LD50 was estimated to be 2103 mg/kg bw when Tif:MAGf male and female rats were orally exposed with N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide.

In a experimental study given by COMMISSION OF THE EUROPEAN COMMUNITIES (Directorate-General Telecommunications, Information Industries and Innovation; Bâtiment Jean Monnet, LUXEMBOURG, 1988.) on structurally similar read across substance 1- (2, 4-dimethylphenylazo)-2-naphthol (CAS no 3118-97-6), mice were treated with 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol orally. 50 % Mortality was observed in treated mice at 20,000 mg/kg bw. Therefore, LD50 was considered to be 20,000 mg/kg bw. When mice were treated with 1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol orally.

In another experiment summarized by Jan Ahlerset al(OECD SIDS, 1999) on structurally similar read across substance Bariumbis [2-Chloro-5-(Hydroxy-1-Naphthyl) Azotoluene-4—Sulphonate (CAS no 5160-02-1),rats and mice were treated Bariumbis [2-Chloro-5-(Hydroxy-1-Naphthyl) Azotoluene-4--Sulphonate in the concentration of 10000 mg/kg bw orally. No 50% mortality was observed in treated mice and rats at 10000 mg/kg bw. Therefore, LD50 was considered to > 10000 mg/kg bw when mice and rats were treated with Bariumbis [2-Chloro-5-(Hydroxy-1-Naphthyl) Azotoluene-4--Sulphonate orally.  

Thus, based on the above studies and predictions on N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl) diazen-1-yl] naphthalene-2-carboxamide and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl) diazen-1-yl] naphthalene-2-carboxamide can be classified as category V of acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl) diazen-1-yl] naphthalene-2-carboxamide and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl) diazen-1-yl] naphthalene-2-carboxamide can be classified as category V of acute oral toxicity.