4,5-dichloro-2-nitroaniline

Endpoint summary

Description of key information

LD50 was estimated to be 48.45mg/kg bw, when rats were exposed with 4,5-Dichloro-2-nitroaniline (6641-64-1)orally.

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 from OECD QSAR toolbox v3.3 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name ( IUPAC):4,5-Dichloro-2-nitroaniline
Molecular formula:C6H4Cl2N2O2
Molecular weight: 207.016 g/mol
Smilies:Nc1cc(Cl)c(Cl)cc1[N+]([O-])=O
Inchi:1S/C6H4Cl2N2O2/c7-3-1-5(9)6(10(11)12)2-4(3)8/h1-2H,9H2
Substance type: Organic

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

48.45 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

48.45 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" or "e" or "f" )  and "g" )  and "h" )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

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 Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR SN1 OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic nitro AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD ONLY

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"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Ac-SN2 OR Ac-SN2 >> Acylation involving an activated (glucuronidated) sufonamide group OR Ac-SN2 >> Acylation involving an activated (glucuronidated) sufonamide group >> Arenesulphonamides OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulphonamides by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.54

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.73

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

LD50 was estimated to be 48.45mg/kg bw, when rats were exposed with 4,5-Dichloro-2-nitroaniline (6641-64-1)orally.

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 4,5-Dichloro-2-nitroaniline (6641-64-1),LD50 was estimated to be 48.45mg/kg bw, when rats were exposed with 4,5-Dichloro-2-nitroaniline (6641-64-1) orally.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

48.45 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

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, 4,5-Dichloro-2-nitroaniline (6641-64-1)has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 4,5-Dichloro-2-nitroaniline (6641-64-1).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 4,5-Dichloro-2-nitroaniline (6641-64-1),LD50 was estimated to be 48.45mg/kg bw, when rats were exposed with 4,5-Dichloro-2-nitroaniline (6641-64-1) orally.

In another experimental study given by U.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017)on structurally similar read across substance 2,4-Dinitrophenol (51-28-5). Acute oral toxicity study was done in rat using 2,4-Dinitrophenol (51-28-5). 50% mortality was observed at dose 30 mg/kg bw. Hence, LD50 was considered to be 30mg/kg body weight. When rats were treated with 2,4-Dinitrophenol (51-28-5)orally.

Also it is further supported by experimental study given by U.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017)on structurally similar read across substanceParathion – methyl (298-00-0). Acute oral toxicity study was done in rat using Parathion – methyl (298-00-0). 50% mortality was observed at dose 17.8 mg/kg bw. Hence, LD50 was considered to be17.8mg/kg body weight.When rats were treated with Parathion – methyl (298-00-0) orally.

 

Thus, based on the above studies and predictions on 4,5-Dichloro-2-nitroaniline (6641-64-1) and its read across substances, it can be concluded that LD50 value is 48.45 mg/kg bw. Thus,comparing this value with the criteria of CLP 4,5-Dichloro-2-nitroaniline (6641-64-1)can be classified as “Category II”for acute oral toxicity.

 

Justification for classification or non-classification

Thus,comparing this value with the criteria of CLP 4,5-Dichloro-2-nitroaniline (6641-64-1)can be classified as “Category II”for acute oral toxicity.