2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

other: predicted data

Title:

[R]: 360 mg/kg/day; Estimation for NOEL for CAS 70879-65-1

Author:

Sustainability Support Services (Europe) AB

Year:

2014

Bibliographic source:

QSAR toolbox Version 3.1

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Prediction report OECD QSAR Toolbox 3.2 Prediction

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.

EC Number:

274-972-1

EC Name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.

Cas Number:

70879-65-1

Molecular formula:

C23H17N4O

IUPAC Name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs

Details on test material:

SMILES:c1(O)c(N=Nc2c(C)cc(N=Nc3c(C)cccc3)cc2)c2c(cccc2)cc1

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Duration of treatment / exposure:

90 days

Doses / concentrations

Remarks:

Doses / Concentrations:
60,150 and 250 mg/kg/day
Basis:
no data

Control animals:

not specified

Examinations

Observations and examinations performed and frequency:

General signs

Sacrifice and pathology:

Histopathology

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

No effects observed in any of the examined parameters

Effect levels

Dose descriptor:

NOEL

Effect level:

120.165 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Organ weight,body weight,General signs,haematological and histopathological findings

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: NOEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: Out of Domain

(((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and (("h" or "i" or "j" or "k" or "l" )  and ("m" and ( not "n") )  )  and (("o" or "p" or "q" or "r" or "s" )  and ("t" and ( not "u") )  )  )  and "v" )  and "w" )  and ("x" and "y" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Precursors quinoid compounds by Organic functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Azo AND Fused carbocyclic aromatic AND Naphtalene AND Overlapping groups AND Precursors quinoid compounds by Organic functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound AND Azo compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup 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 Strong binder, NH2 group OR Weak binder, NH2 group OR Weak binder, OH group OR Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Precursors quinoid compounds by Organic functional groups

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Azo AND Fused carbocyclic aromatic AND Naphtalene AND Overlapping groups AND Precursors quinoid compounds by Organic functional groups (nested)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aromatic compound AND Azo compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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 Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving group >> Sulphonyl halides OR Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isothiocyanates OR Acylation >> Isocyanates and Related Chemicals >> Thiocyanates-Acylation OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Acylation >> Ring Opening Acylation >> beta-Lactones-Acylation OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - aldehydes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - cyano OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - nitro OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines OR Michael addition >> Polarised Alkenes >> Polarised alkene - sulfonate OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Pyranones (and related nitrogen chemicals) OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-diimine OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine 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 >> Mono-carbonyls OR SN2 OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> Ring Opening SN2 Reaction OR SN2 >> Ring Opening SN2 Reaction >> beta-Lactones-SN2 OR SN2 >> SN2 reaction at a sp2 carbon atom OR SN2 >> SN2 reaction at a sp2 carbon atom >> Polarised alkenes with a halogen leaving group OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at a sulphur atom >> Thiocyanates-SN2 OR SN2 >> SN2 reaction at a sulphur atom >> Thiols OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SN2 >> SN2 reaction at sp3 carbon atom >> beta-Halo ethers OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphonates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-pyridines OR SNAr >> Nucleophilic aromatic substitution >> Halo-pyrimidines OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Precursors quinoid compounds by Organic functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Azo AND Fused carbocyclic aromatic AND Naphtalene AND Overlapping groups AND Precursors quinoid compounds by Organic functional groups (nested)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aromatic compound AND Azo compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.1

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acyation involving a leaving group OR Acylation >> Direct acyation involving a leaving group >> Geminal Polyhaloalkanes OR Elimination (E2) OR Elimination (E2) >> E2 elimination reaction with epoxide formation OR Elimination (E2) >> E2 elimination reaction with epoxide formation >> Haloalcohols OR Michael addition OR Michael addition >> alpha, beta-unsaturated carabonyl compounds OR Michael addition >> alpha, beta-unsaturated carabonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR Michael addition >> alpha, beta-unsaturated carabonyl compounds >> Four- and Five-Membered Lactones OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinoneimine Derivatives OR Michael addition >> Quinone type compounds >> Quinones OR Nucleophilic addition OR Nucleophilic addition >> Nucleophilic addition reaction with cycloisomerization OR Nucleophilic addition >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Coumarins OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Diazenes OR Radical >> Radical mechanism by ROS formation >> Geminal Polyhaloalkanes OR Radical >> Radical mechanism by ROS formation >> Hydrazine Derivatives OR Radical >> Radical mechanism by ROS formation >> Nitro Compounds OR Radical >> Radical mechanism by ROS formation >> Nitroso compounds OR Radical >> Radical mechanism by ROS formation >> Organic Peroxy Compounds OR Radical >> Radical mechanism by ROS formation >> Quinones OR Radical >> Radical mechanism by ROS formation >> Specific Imine and Thione Derivatives OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Aromatic and Heterocyclic Primary Amines OR Radical >> ROS formation after GSH depletion >> Haloalcohols OR Radical >> ROS formation after GSH depletion >> Quinoneimine Derivatives OR Schiff base fomers OR Schiff base fomers >> Direct acting Schiff base formers OR Schiff base fomers >> Direct acting Schiff base formers >> Alpha, Beta-Unsaturated Aldehydes OR Schiff base fomers >> Direct acting Schiff base formers >> Geminal Polyhaloalkanes OR Schiff base fomers >> Direct acting Schiff base formers >> Specific Acetate Esters OR Schiff base fomers >> Multi-step Shiff base formation OR Schiff base fomers >> Multi-step Shiff base formation >> Haloalkanes Containing Electron-Withdrawing Groups OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Nitroso compounds OR SN1 >> Carbenium ion formation >> Polycyclic Aromatic Hydrocarbons OR SN1 >> Carbenium ion formation >> Specific Acetate Esters OR SN1 >> Glutathione-induced nitrenium ion formation OR SN1 >> Glutathione-induced nitrenium ion formation >> Nitroso compounds OR SN1 >> Nitrenium and/or Carbenium ion formation OR SN1 >> Nitrenium and/or Carbenium ion formation >> Urea Derivatives OR SN1 >> Nitrenium ion formation OR SN1 >> Nitrenium ion formation >> Aromatic and Heterocyclic Primary Amines OR SN1 >> Nitrenium ion formation >> N-hydroxylamines OR SN1 >> Nitrenium ion formation >> Nitro Compounds OR SN1 >> Nitrenium ion formation >> Sulfonyl Azides OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation >> Nitroso compounds OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation >> Urea Derivatives OR SN2 OR SN2 >> Acylating agents OR SN2 >> Acylating agents >> Specific Acetate Esters OR SN2 >> Carbenium Ion Formation OR SN2 >> Carbenium Ion Formation >> Diazoalkanes OR SN2 >> Diazonium ion formation OR SN2 >> Diazonium ion formation >> Specific Imine and Thione Derivatives OR SN2 >> Direct Acting Epoxides and Related OR SN2 >> Direct Acting Epoxides and Related >> Epoxides, Aziridines OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Polarized Haloalkene Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Geminal Polyhaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Electron-Withdrawing Groups OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> P450-mediated epoxidation OR SN2 >> P450-mediated epoxidation >> Coumarins OR SN2 >> P450-mediated epoxidation >> Polarized Haloalkene Derivatives OR SN2 >> P450-mediated epoxidation >> Polycyclic Aromatic Hydrocarbons OR SN2 >> P450-mediated epoxidation >> Quinoline Derivatives OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> SN2 at an activated sp2 (aromatic) carbon atom OR SN2 >> SN2 at an activated sp2 (aromatic) carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> SN2 at sp3-carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides by DNA binding by OASIS v.1.1

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Similarity boundary:Target: c1(O)c(N=Nc2c(C)cc(N=Nc3c(C)cccc3)cc2)c2c(cccc2)cc1
Threshold=20%,
Dice(Atom centered fragments)

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.91

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.96

Applicant's summary and conclusion

Conclusions:

The NOEL for 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs. is estimated to be 360.496307373 mg/kg bw/day for rat for duration 28 days this subacute value when converted to subchronic value is equivalent to 120.1654 mg/kg bw/day for 90days duration using the toolbox version 3.1.

Executive summary:

The NOEL for 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs. is estimated to be 360.496307373 mg/kg bw/dayfor rat for duration 28 days this subacute value when converted to subchronic value is equivalent to 120.1654 mg/kg bw/dayfor90days durationusing the toolbox version 3.1. The data is estimated to be based on the data summarized below

CAS no.	End point	Value	Species	Doses	Duration	Effects	Remarks
1843-05-6	NOEL	1000 mg/kg/day	Rat	Minimum dose-20 mg/kg/day Maximum dose-1000 mg/kg/day	28 days	General signs,body weight,mortality	-
104-40-5	NOEL	72 mg/kg/day	Rat	10 to 100 mg/kg/day	28 days	No effects on growth,hormones and morphology	-
25154-52-3	NOEL	224 mg/kg/day 172 mg/kg/day	Rat	60,150 and 250 mg/kg/day	28 days	Organ weight,body weight	-
84852-15-3	NOEL	211 mg/kg/day	Rat	10 ,50 and 250 mg/kg/day	28 days	General signs,haematological and histopathological findings	-
96-76-4	NOEL	273 mg/kg/day	Rat	5 to 300 mg/kg/day	28 days	General signs, histopathological findings,urinalysis,organ weight,food consumption	-
140-66-9	NOEL	263 mg/kg/day	Rat	15 to 300 mg/kg/day	28 days	General signs	-

 

All the valueswhen equalized to 90 days duration by using conversion factor of 3, the values are summarized as follows

Conversion-

CAS no.	End point	Value	Species	Duration
1843-05-6	NOEL	333.333mg/kg/day	Rat	90 days
104-40-5	NOEL	36mg/kg/day	Rat	90 days
25154-52-3	NOEL	74.66666mg/kg/day 57.3333 mg/kg/day	Rat	90 days
84852-15-3	NOEL	70.3333mg/kg/day	Rat	90 days
96-76-4	NOEL	91mg/kg/day	Rat	90 days
140-66-9	NOEL	87.666mg/kg/day	Rat	90 days

 

Thus the calculated NOEL of analogues for 90 days for the species rat is within the range of36 – 333.333mg/kg/day. Thus the predicted NOEL value is (calculated to be)120.1654 mg/kg bw/daywith 90 days for rat (harmonized using assessment factors) falls within the domain using Log Kow as the descriptor and justified to be used as NOEL for further DNEL calculation for the purpose of risk assessment. Also it does not impact the classification of the substance thus the predicted value considered to be acceptable.

 

Justified to be used as NOEL for the purpose of weight of evidence