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Description of key information

The skin sensitization potential of 2-methyl-4-nitroaniline (99-52-5) 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 2-methyl-4-nitroaniline (99-52-5) was predicted to be not sensitizing to the skin of Pirbright-White 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:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Type of study:
Buehler test
Justification for non-LLNA method:
No data avaliable
Specific details on test material used for the study:
Name of test material (as cited in study report): 2-methyl-4-nitroaniline
- Molecular formula: C7 H8 N2 O2
- Molecular weight: 152.152 g/mol
- Smiles notation: c1(cc(c(N)cc1)C)[N+](=O)[O-]
- InChI: 1S/C7H8N2O2/c1-5-4-6(9(10)11)2-3-7(5)8/h2-4H,8H2,1H3
- Substance type: Organic
- Physical state: Solid
Species:
guinea pig
Strain:
other: Pirbright-White guinea pig
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, breeding colony
- Weight at study initiation: 275 - 357 g
- Housing: in fully air·conditioned rooms in Makrolon cages on soft wood granulate, in groups of 5 animals
- Diet (e.g. ad libitum): Standard feed for guinea pigs and rabbits (Altromin 3112), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +-3
- Humidity (%): 50 +-20
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
other: deionisied water
Concentration / amount:
0.5 g substance moistened with 0.35 mL deionised water
Day(s)/duration:
6hr
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Deionised water
Concentration / amount:
0.5 g substance moistened with 0.35 mL deionised water
Day(s)/duration:
6hr
No. of animals per dose:
Total :30
Test group :20
Control group:10
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 6hr
- Test groups: 20
- Control group: 10
- Site: the front part of the left flank
- Frequency of applications: once a week in 15 days
- Duration: 15days
- Concentrations: 0.5 g of test substance moistened with 0.35 mL deionised water

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on 29 day
- Exposure period: 6hr
- Test groups: 20
- Control group: 10
- Site: the hind part of the right flank ( 2 x 2 cm cellulose patch, which was fixed to the front part of the left flank of the 20 animals of the treatment group and then covered with an occlusive polyethylene film and a bandage. )
- Concentrations: 0.5 g of test substance moistened with 0.35 mL deionised water
- Evaluation (hr after challenge): 24hr,48hr
.
OTHER:After removal of the occlusive bandage, any remnants of the substance were carefully washed off with warm water in induction and challenge phase .
on day 31, Macroscopic examination of the skin. Terminal body weight determination.
Challenge controls:
yes
Positive control substance(s):
no
Statistics:
No data avaliable
Reading:
other: Challlenge
Hours after challenge:
48
Group:
test group
Dose level:
0.5 g of test substance moistened with 0.35 mL deionised water
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 mode 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 ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and "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 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 Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

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, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Anilines (Hemolytic anemia with methemoglobinemia) Rank A AND Anilines (Hepatotoxicity) Rank C AND Nitrobenzenes (Hemolytic anemia with methemoglobinemia) Rank A AND Nitrobenzenes (Hepatotoxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Chlorphentermine (Hepatotoxicity) Alert OR Not categorized by Repeated dose (HESS)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.08

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.17

Interpretation of results:
other: Not sensitizing
Conclusions:
The skin sensitization potential of 2-methyl-4-nitroaniline (99-52-5) 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 2-methyl-4-nitroaniline (99-52-5) was predicted to be not sensitizing to the skin of Pirbright-White guinea pig.
Executive summary:

The skin sensitization potential of 2-methyl-4-nitroaniline (99-52-5) 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 2-methyl-4-nitroaniline (99-52-5) was predicted to be not sensitizing to the skin of Pirbright-White guinea pig.

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

Skin sensitization

In different study,2-methyl-4-nitroaniline (99-52-5)has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction is based on in vivo experiments in guinea for target chemical2-methyl-4-nitroaniline (99-52-5)and its structurally similar read across substances 2-Methoxy-4-nitroaniline(99-52-9). The predicted data using the OECD QSAR toolbox have also been compared with the experimental data of read across.

The skin sensitization potential of 2-methyl-4-nitroaniline (99-52-5) 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 2-methyl-4-nitroaniline (99-52-5) was predicted to be not sensitizing to the skin of Pirbright-White guinea pig.

Supported by experimental data conducted by U.S. (NTP) (Prepared for NCI to support chemical nomination by Technical Resources International, 2006) on structurally similar read across substance2-Methoxy-4-nitroaniline (99-52-9)in Guinea pig. The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance.The skin sensitization study of 2-Methoxy-4-nitroaniline (99-52-9) was performed in Dunkin Hartley guinea pig by Guinea pig maximization test .In induction phase, for intradermal injection7.5 percent (w/w) solution inAlembicol D, a coconut oil triglyceride and for dermal application 75% in Water concentration were used.In challenge phase 75% and 40% solution in distilled water was used .No evidence of sensitivity was noted. Hence it is considered that 2-Methoxy-4-nitroaniline (99-52-9) was not skin sensitizing in guinea pig.

 Thus based on the above predictions on2-methyl-4-nitroaniline (99-52-5) aswell as its read across substances and applying weight of evidence, it can be concluded that2-methyl-4-nitroaniline (99-52-5) isnot a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation,2-methyl-4-nitroaniline (99-52-5)) can be considered as ‘not classified’ for skin sensitization effects.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation,2-methyl-4-nitroaniline (99-52-5)) can be considered as ‘not classified’ for skin sensitization effects.