5-nitrovanillin

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

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]: 47,3 mg/kg bw/day (nominal); Estimation for NOAEL 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: OECD Guideline 415 (One-Generation Reproduction Toxicity Study);OECD Guideline 452 (Chronic Toxicity Studies);OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test);OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

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:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Duration of treatment / exposure:

Subchronic

Control animals:

not specified

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

23.3 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects were observed

Remarks on result:

other: not specified

Target system / organ toxicity (P0)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Results: F2 generation

Effect levels (F2)

Remarks on result:

not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

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,"NOAEL reproductive toxicity","NOAEL (single application)",NOAEL
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 ("g" and "h" )  )

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 Very fast by Bioaccumulation - metabolism half-lives

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.927

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.14

Applicant's summary and conclusion

Conclusions:

The NOAEL value of 5-Nitrovanillin on rat was found to be 23.3 mg/kg bw/day (nominal) for Subchronic duration.

Executive summary:

WoE Summary for Cas:6635-20-7

 

The NOAEL value of 5-Nitrovanillin is estimated to be 47.3 mg/kg bw/day (nominal) for sub acute duration on rat (23.3mg/kg bw/day (nominal) 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	1671-49-4	NOAEL	15 mg/kg bw/day (nominal)	Rat	0 (control), 2, 15, 100 mg/kg/day	10 weeks	no effects were observed
2	119313-12-1	NOAEL reproductive toxicity	79.6mg/kg bw/day (nominal))	Dog	0.57, 3.9, 35 mg/kg bw/d	chronic	No effects on body weight; food consumption and compound intake organ weights; histopathology

 

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 in the range of 15 – 79.6 mg/kg bw/day(nominal) the no effects observed on the above doses are listed as follows.

 

·        body weight; food consumption and compound intake organ weights; histopathology

Thus based on above discussion it can be concluded that estimated value 47.3 mg/kg/day(actual dose recived) (23.3mg/kg bw/day (nominal) for 90 days)) for the substance (CAS: 6635-20-7) and it is close to the 15 mg/kg bw/day (nominal).

 

CAS no	End point	Value	Species	Duaration
1671-49-4	NOAEL	7.5 mg/kg bw/day (nominal)	Rat	90 days
25321-14-6	NOAEl	55.7mg/kg bw/day (nominal)	Rat	90 days

 

 

 

 

 

Thus the calculated NOAEL of analogues for 90 days for the species rat is within the range of 7.5 – 55.6 mg/kg bw /day(nominal). Thus the predicted NOAEL value is (calculated to be) 31.6 mg/kg/day(nominal) 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 NOAEL 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.