4-nitro-o-toluidine

Endpoint summary

Description of key information

LD50 was estimated to be 270 mg/kg bw for mice treated with 2-methyl-4-nitroaniline.

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 3.3 and the supporting QMRF report has been attached

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material: p-Nitro-o-toludine
- IUPAC name: 2-methyl-4-nitroaniline
- Molecular formula: C7H8N2O2
- Molecular weight: 152.152 g/mol
- Substance type: Organic
- Purity: No data available
- Impurities (identity and concentrations): No data available

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

other: Traganth

Details on oral exposure:

not specified

Doses:

270 mg/kg bw

No. of animals per sex per dose:

2 to 5

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

270 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 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 Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aniline AND Aryl AND Nitrobenzene by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aniline AND Nitrobenzene AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitro, aromatic attach [-NO2] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Nitro compound AND Primary amine AND Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Lysine peptide depletion

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> N-substituted aromatic amides by DPRA Lysine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "i"

Similarity boundary:Target: Cc1cc(N(=O)=O)ccc1N
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.72

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.37

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

LD50 was estimated to be 270 mg/kg bw for mice treated with 2-methyl-4-nitroaniline.

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 2-methyl-4-nitroaniline. LD50 was estimated to be 270 mg/kg bw for mice treated with 2-methyl-4-nitroaniline.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

270 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, 2-methyl-4-nitroaniline has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in mice and dog for 2-methyl-4-nitroaniline along with the study available on structurally similar read across substance1-methyl-3-nitrobenzene (CAS no 99-08-1) and 1-methyl-3-nitrobenzene (CAS no 99-08-1). 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 2-methyl-4-nitroaniline.

LD50 was estimated to be 270 mg/kg bw for mice treated with 2-methyl-4-nitroaniline.

In another experimental study given by U.S. National Library of Medicine (ChemIDplus A TOXNET Database, 2017) on structurally similar read across substance 2-methyl-4-[(2-methylphenyl)diazenyl]aniline (CAS no 97-56-3). Dogs were treated with 2-methyl-4-[(2-methylphenyl)diazenyl]aniline in the concentration of 300 mg/kg bw. 50 % mortality was observed at 300 mg/kg bw in treated dog. Therefore, LD50 was considered to be 300 mg/kg bw when dog were treated with 2-methyl-4-[(2-methylphenyl)diazenyl]aniline orally.

Also it is further supported by experimental study given by U.S. National Library of Medicine (ChemIDplus A TOXNET Database, 2017) on structurally similar read across substance 1-methyl-3-nitrobenzene (CAS no 99-08-1), mice were treated with 1-methyl-3-nitrobenzene in the concentration of 330 mg/kg bw. 50 % mortality was observed at 330 mg/kg bw in treated mice. Therefore, LD50 was considered to be 330 mg/kg bw when mice were treated 1-methyl-3-nitrobenzene orally.

Thus, based on the above studies and predictions on 2-methyl-4-[(2-methylphenyl)diazenyl]aniline and its read across substances, it can be concluded that LD50 value is less than 300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-methyl-4-[(2-methylphenyl)diazenyl]aniline can be classified as Category III of acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 2-methyl-4-[(2-methylphenyl)diazenyl]aniline and its read across substances, it can be concluded that LD50 value is less than 300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-methyl-4-[(2-methylphenyl)diazenyl]aniline can be classified as Category III of acute oral toxicity.