5-nitrovanillin

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

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:

16.03.2014 10:56 [R]: 257 mg/kg/day; Estimation for LOEL, NOEL for CAS 6635-20-7

Author:

SSS

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

Administration / exposure

Route of administration:

oral: unspecified

Duration of treatment / exposure:

Subchronic

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

85 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Remarks on result:

other: not specified

Maternal abnormalities

Abnormalities:

not specified

Localisation:

not specified

Description (incidence and severity):

not specified

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Fetal abnormalities

Abnormalities:

not specified

Localisation:

other: not specified

Description (incidence and severity):

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Treatment related:

not specified

Relation to maternal toxicity:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: NOEL,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 "i" )  and ("j" and "k" )  )

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 Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers 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 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> Thiophosphates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Similarity boundary:Target: c1(OC)c(O)c(N(=O)=O)cc(C=O)c1
Threshold=40%,
Dice(Atom centered fragments)

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.55

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.64

Applicant's summary and conclusion

Conclusions:

The NOEL no observed effect level of 5-Nitrovanilin on rat was predicted to be 85 mg/kg bw/day for 90 days

Executive summary:

WoE Summary for Cas: 6635-20-7

 

The NOEL value of 5,nitrovanillain isestimated to be 255 mg/kg bw/day for sub-acute duration (85 mg/kg bw/day for 90 days) of rat using the toolbox version 3.2.

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	6358-09-4	NOEL	350 mg/kg bw/day	Rat	6,87.5,175,350 mg/kg/day	15 days	-no effects
2	5307-14-2	NOEL	160 mg/kg/day	Mouse	17,64,32,128,160 mg/kg/day	14 days	no adverse effects

The above table consist of various developmental toxicity studies available for the read across substances for CAS: 6635-20-7.Based on the above results it can be observed that NOEL values are in the range of 160 – 350 mg/kg bw./day for rat . The no effects observed on the above doses .

Thus based on above discussion it can be concluded that toxicity of the target chemical 255 mg/kg bw/day (85 mg/kg bw/day for 90 days) is predicted from category members using read-across based on above values and it is close to ( 350 mg/kg/day) for sub-acute duration of rat from nearest neighbors compared by prediction descriptors.

 

Sr no.	CAS no	End point	Value	Species	Duration	Remarks
1	6358-09-4	NOEL	116 mg/kg bw/day	Rat	90 days
2	5307-14-2	NOEL	93.27 mg/kg/day	Rat	90 days

 

Thus the calculated NOEL of analogues for 90 days for the species rat is within the range of 93 .27 – 116 mg/kg bw /day. Thus the predicted NOEL value is (calculated to be)104 .6mg/kg bw/dwith 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.