(3-aminophenyl)urea

Endpoint summary

Description of key information

The skin sensitization potential of 1-(3-aminophenyl) urea (25711-72-2) 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. 1-(3-aminophenyl) urea (25711-72-2) was predicted to be sensitizing to the skin of 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 version 3.3 and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2017

GLP compliance:

not specified

Type of study:

intracutaneous test

Justification for non-LLNA method:

Not specified

Specific details on test material used for the study:

- Name of the test material: 1-(3-aminophenyl)urea
- IUPAC name:1-(3-aminophenyl)urea
- Molecular formula: C7H9N3O
- Molecular weight: 151.168 g/mol
- Substance type: Organic
- Smiles: O=C(Nc1cccc(N)c1)N

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available.

Route:

intradermal

Vehicle:

physiological saline

Route:

epicutaneous, occlusive

Vehicle:

water

Day(s)/duration:

48 hour

No. of animals per dose:

10 test animals
10 Control animals

Details on study design:

No data available.

Challenge controls:

10 Control animals

Positive control substance(s):

not specified

Statistics:

No data available.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Skin sensitization effect were observed.

Remarks on result:

positive indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "S M W N"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and "f" )  and ("g" and ( not "h") )  )  and ("i" and "j" )  )

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 Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Ketones OR Phenols OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "f"

Similarity boundary:Target: Nc1cccc(NC(N)=O)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds by Oncologic Primary Classification

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Arylazo Type Compounds OR Halogenated Aromatic Hydrocarbon Type Compounds by Oncologic Primary Classification

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.88

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.552

Interpretation of results:

other: Sensitizing .

Conclusions:

The skin sensitization potential of 1-(3-aminophenyl) urea (25711-72-2) 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. 1-(3-aminophenyl) urea (25711-72-2) was predicted to be sensitizing to the skin of guinea pig.

Executive summary:

The skin sensitization potential of 1-(3-aminophenyl) urea (25711-72-2) 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. 1-(3-aminophenyl) urea (25711-72-2) was predicted to be sensitizing to the skin of guinea pig.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitization

In different studies, 1-(3-aminophenyl) urea (25711-72-2) has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction is based on in vivo experiments in guinea pig and human for target chemical disodium 1-(3-aminophenyl) urea (25711-72-2) and its structurally similar read across substancesp-Phenylenediamine (106-50-3) and2-nitrobenzene-1,4-diamine (5307-14-2). The predicted data using the OECD QSAR toolbox and DANISH have also been compared with the experimental data of read across.

The skin sensitization potential of 1-(3-aminophenyl) urea (25711-72-2) 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. 1-(3-aminophenyl) urea (25711-72-2) was predicted to be sensitizing to the skin of guinea pig.

Another prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be positive on guinea pig and human for1-(3-aminophenyl) urea .Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for 1-(3-aminophenyl) urea (25711-72-2) estimated to be sensitizing when applied to human and guinea pig skin.

Further supported by experimental data conducted by Cosmetic Ingredient Review Expert Panel (Cosmetic Ingredient Review, 2007) on structurally similar read across substance p-Phenylenediamine (106-50-3)in guinea pigs. 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 test for p-Phenylenediamine ( 106-50-3 )was observed in Dunkin Hartley guinea pigs by Guinea pig maximisation test . A group of 20 adult Albino Dunkin-Hartley guinea pigs were observed for skin sensitization test. In induction phase, 7 successive topical applications of 10% aqueous p-Phenylenediamine were applied as 48-hour occlusive patches. After a rest period of 28 days, a 48-hour occlusive challenge patch containing 0.5% aqueous p -Phenylenediamine was applied. Eleven of the 20 guinea pigs were sensitized, and these results were confirmed at microscopic examination. Therefore p-Phenylenediamine ( 106-50-3 ) was considered to be strong sensitizer in Albino Dunkin-Hartley guinea pigs.

 

It is further supported by an experimental study conducted by COSMETIC INGREDIENT REVIEW (JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY, 1985)on structurally similar read across substance 2-nitrobenzene-1,4-diamine (5307-14-2)on guinea pigs.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. 2-nitrobenzene-1,4-diamine (5307-14-2) was assessed for its possible contact allergenic potential. 20 guinea pigs received topical applications of 3 percent test material in an aqueous solution containing 2 percent Natrosol250 HR, 2 percent Tween 80, 0.05 percent sodium sulfite, and 10 percent isopropanol, and adjusted to pH 7. The compounds were applied daily 6 days a week for 3 weeks on a 6 cm2shaved area of the flank. A 2-week rest period was followed by application of the compounds on the opposite, previously untreated flanks of the guinea pigs. Four of 20 guinea pigs were sensitized to test material; the total reaction intensity for all the animals was 4 (scores added for all animals; possible total of 60).Therefore2-nitrobenzene-1,4-diamine (5307-14-2) can be considered as weakly sensitizing to guinea pigs.

 

Thus based on the above predictions on 1-(3-aminophenyl) urea (25711-72-2) as well as its read across substances and applying weight of evidence, it can be concluded that 1-(3-aminophenyl) urea (25711-72-2) is a skin sensitizer. Thus comparing the above annotations with the criteria of CLP classification, 1-(3-aminophenyl) urea (25711-72-2) was considered to be classified for skin sensitization.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP classification, 1-(3-aminophenyl) urea (25711-72-2) was considered to be classified for skin sensitization.