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Diss Factsheets

Administrative data

Description of key information

The skin sensitization potential of 4,5-Dichloro-2-nitroaniline (6641-64-1) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances of 4,5-Dichloro-2-nitroaniline (6641-64-1)was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
in vivo
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:
according 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
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
No data available
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:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
No data available
No. of animals per dose:
Total :30
test group:20
negative control:10
Details on study design:
No data available
Challenge controls:
No data available
Positive control substance(s):
not specified
Statistics:
No data available
Positive control results:
No data available
Reading:
1st reading
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No skin sensitization reaction was observed
Remarks on result:
no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

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 Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 16 - Sulfur S OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg AND Group CNHal Aqueous Solubility < 0.1 g/L by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group CN Melting Point > 180 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.1

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.23

Interpretation of results:
other: not sensitizing
Conclusions:
The skin sensitization potential of 4,5-Dichloro-2-nitroaniline (6641-64-1) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances of 4,5-Dichloro-2-nitroaniline (6641-64-1)was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pig.
Executive summary:

The skin sensitization potential of4,5-Dichloro-2-nitroaniline (6641-64-1)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances of 4,5-Dichloro-2-nitroaniline (6641-64-1)was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pig.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitization

In different studies, 4,5-Dichloro-2-nitroaniline (6641-64-1)has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig for target chemical, 4,5-Dichloro-2-nitroaniline (6641-64-1)and its structurally similar read across substances 2-nitroaniline(88-74-4),2-Chloro-4-nitroaniline(121-87-9) and 2-Chloroaniline (95-51-2), the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 4,5-Dichloro-2-nitroaniline (6641-64-1)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances of 4,5-Dichloro-2-nitroaniline (6641-64-1)was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pig.

The experimental study conducted byInstitute for Arbeitsschutz der Deutschen Gesetzlichen Unfallversicherung (IFA) GESTIS-database on hazardous substance(IFA GESTIS, 2017)to evaluate the skin sensitizing potential of read across substance2-nitroaniline(88-74-4).The skin sensitization study of 2-nitroaniline (88-74-4) was

performed by guinea pig maximization method using OECD guideline 406 on guinea pig. The 30 animals were classified into two groups, test group 20 were as in control group 10 animals. In induction phase, first induction given by intracutaneous route in concentration 5 % while in 2nd Induction 50 % active substance as occlusive epicutaneous applied .Challenge given using 50% concentration of active substance by epicutaneous route as occlusive patch. No skin sensitization was observed after the challenge application Hence2-nitroaniline(88-74-4) was considered as not skin sensitizing in guinea pig.

The experimental study conducted byInstitute for Arbeitsschutz der Deutschen Gesetzlichen Unfallversicherung (IFA) GESTIS-database on hazardous substance(IFA GESTIS, 2017)to evaluate the skin sensitizing potential of read across substance 2-Chloro-4-nitroaniline(121-87-9) .The skin sensitization study of 2-Chloro-4-nitroaniline(121-87-9) was performed by Buehler test using OECD guideline 406 on guinea pig. No skin sensitization was observed after the challenge application Hence2-Chloro-4-nitroaniline (121-87-9) was considered as not skin sensitizing in guinea pig.

The experimental study conducted byInstitute for Arbeitsschutz der Deutschen Gesetzlichen Unfallversicherung (IFA) GESTIS-database on hazardous substance(IFA GESTIS, 2017)to evaluate the skin sensitizing potential of read across substance 2-Chloroaniline (95-51-2).The skin sensitization study of 2-Chloroaniline (95-51-2) was performed by Guinea pig maximisation test on guinea pig. No skin sensitization was observed after the

challenge application Hence 2-Chloroaniline (95-51-2) was considered as not skin sensitizing in guinea pig.

Thus based on the above predictions on4,5-Dichloro-2-nitroaniline (6641-64-1) as well as its read across and applying weight of evidence, it can be concluded that 4,5-Dichloro-2-nitroaniline (6641-64-1)is not a skin sensitizer. Thus comparing the above studies with the criteria of CLP regulation, 4,5-Dichloro-2-nitroaniline

(6641-64-1)can be considered as not classified for skin sensitization.

 

 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, 4,5-Dichloro-2-nitroaniline (6641-64-1)can be considered as not classified for skin sensitization.