5-nitrovanillin

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: Studty report

Title:

[R]: 1,42E3 mg/kg/day; Estimation for effect LOEL, NOEL calculated, study LOEL, study NOEL for CAS 6635-20-7

Author:

SSS QSAR Prediction Team

Year:

2014

Bibliographic source:

SSS QSAR Prediction Team

Materials and methods

Test guideline

Guideline:

other: Prediction using category approach; QSAR Toolbox 3.1; Read Across; 5 nearest analogues; Log Kow as descriptor

Principles of method if other than guideline:

Prediction using category approach; QSAR Toolbox 3.1; Read Across; 5 nearest analogues; Log Kow as descriptor

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-nitrovanillin

EC Number:

229-633-2

EC Name:

5-nitrovanillin

Cas Number:

6635-20-7

Molecular formula:

C8H7NO5

IUPAC Name:

4-hydroxy-3-methoxy-5-nitrobenzaldehyde

Details on test material:

SMILES:c1(OC)c(O)c(N(=O)=O)cc(C=O)c1

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

chronic

No. of animals per sex per dose:

no data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Effect levels

Dose descriptor:

NOEL

Effect level:

2 840 other: mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects were observed

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 calculated","study NOEL","study LOEL","effect LOEL"
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 "k" )  and ("l" and "m" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aldehydes (Mono) AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism by ROS formation AND Radical >> Radical mechanism by ROS formation >> Nitro Compounds AND SN1 AND SN1 >> Nitrenium ion formation AND SN1 >> Nitrenium ion formation >> Nitro Compounds by DNA binding by OASIS v.1.1

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Schiff base formation AND Schiff base formation >> Schiff base formation with carbonyl compounds AND Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes by Protein binding by OASIS v1.1

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B by Repeated dose (HESS)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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 >> Anhydrides OR Acylation >> Direct Acylation Involving a Leaving group >> Sulphonyl halides OR Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isocyanates 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 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 - oximes OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyrimidines OR Michael addition >> Polarised Alkenes >> Polarised alkene - sulfinyl OR Michael addition >> Polarised Alkenes >> Polarised alkene - sulfonate OR Michael addition >> Polarised Alkenes >> Polarised alkene - sulfone OR Michael addition >> Polarised Alkynes OR Michael addition >> Polarised Alkynes >> Polarised alkyne - aldehyde OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Benzoquinones 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 Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-2-Dicarbonyls OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-3-Dicarbonyls OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Di-substituted alpha, beta-unsaturated aldehydes OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls OR SN2 OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> 1,2-Dihaloalkane OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> SN2 reaction at a nitrogen atom OR SN2 >> SN2 reaction at a nitrogen atom >> N-Acetoxy-N-acetyl-phenyl OR SN2 >> SN2 reaction at a nitrogen atom >> N-Acyloxy-N-alkoxyamides OR SN2 >> SN2 reaction at a nitrogen atom >> Nitrosoguanidine (nitrogen) OR SN2 >> SN2 reaction at a nitrogen atom >> Nitrosoureas (nitrogen) 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 >> Aromatic sulphonic acids OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at a sulphur atom >> Sulfenyl halides 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 >> Nitrosoureas (carbon) OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphates OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphonates OR SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates OR SN2 >> SN2 reaction at sp3 carbon atom >> Thiophosphates 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 by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Schiff base formation AND Schiff base formation >> Schiff base formation with carbonyl compounds AND Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes by Protein binding by OASIS v1.1

Domain logical expression index: "i"

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 >> Carbamates OR Acylation >> Direct acylation involving a leaving group >> N-acylamides OR Acylation >> Direct acylation involving a leaving group >> N-acylsulphonamides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated alkyl or aryl esters OR Michael addition 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 >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Nitroalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Nitrosoalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Vinyl sulfonyl compounds OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes >> Activated electrophilic ethenylarenes OR Michael addition >> Michael-type addition on azoxy compounds OR Michael addition >> Michael-type addition on azoxy compounds >> Azoxy compounds OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Naphtoquinone and naphtoquinone imines OR No alert found OR Nucleophilic addition OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Ketones OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond >> C-Nitroso compounds OR Schiff base formation >> Nucleophilic cycloaddition to diketones OR Schiff base formation >> Nucleophilic cycloaddition to diketones >> Diketones OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Azoxy compounds-forming carbenium ion OR SN2 OR SN2 >> Nucleophilic substitution at Nitrogen atom OR SN2 >> Nucleophilic substitution at Nitrogen atom >> N-nitroso compounds OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-activated haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> N-nitroso compounds OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Phosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Thiophosphates OR SN2 >> Nucleophilic substitution on benzylic carbon atom OR SN2 >> Nucleophilic substitution on benzylic carbon atom >> alpha-activated benzyls OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides >> Heterocyclic sulfenamides OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes OR SN2 >> Ring opening SN2 reaction >> Isothiazolones derivatives OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated halogens OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Activated haloarenes OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Halogenated five membered heteroaromatic compounds by Protein binding by OASIS v1.1

Domain logical expression index: "j"

Similarity boundary:Target: c1(OC)c(O)c(N(=O)=O)cc(C=O)c1
Threshold=30%,
Dice(Atom centered fragments)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.05

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.55

Applicant's summary and conclusion

Conclusions:

The NOEL(no observed effect level ) value of Vanillian on rat was found to be 2840 mg/kg bw/day for subchronic duaration.

Executive summary:

WoE Summary for Cas:6635-20-7

 

The NOEL value of 5-nitrovanillin isestimated to be 1420 mg/kg bw/day for chronic duration on rat (2840 mg/kg bw/day ) for 90 days) using the toolbox .

The data is estimated to be based on the data summarized below

Sr no.	CAS no	End point	Value	Species	Doses	Duration	Effects	Remarks
1	121-32-4	NOEL	1440 mg/kg/day	Rat	1000,5000 10000 mg/kg/day	chronic	no effects were observed
2	121-33-5	NOEL	1440 mg/kg/day	Dog	1000,5000 10000 mg/kg/day	chronic	no effects were observed

 

The above table consist of various reproductive toxicity studies available for the read across substances for CAS: 6635-20-7.Based on the above results it can be observed that NOAEL values are close to 1440 mg/kg bw/day the no effects were observed on the above doses follows.

 

Thus based on above discussion it can be concluded that estimated value 1420 mg/kg/day(actual dose recived) (2840 mg/kg bw/day for 90 days)) for the substance (CAS: 6635-20-7) and it is close to the 1440 mg/kg bw/day (nominal).

 

CAS no	End point	Value	Species	Duaration
121-32-4	NOEL	2840mg/kg bw/day	Rat	90 days
121-33-5	NOEl	2840 mg/kg bw/day	Rat	90 days

 

 

 

 

 

the predicted NOAEL value is (calculated to be) 2840 mg/kg/day with 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.