4-(phenylazo)benzene-1,3-diamine acetate

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 4-(phenylazo)benzene-1,3-diamine acetate was predicted to be sensitizing to the skin of male Hartley guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

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: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Type of study:

other: Estimated data

Specific details on test material used for the study:

- Name of test material: 4-(phenylazo)benzene-1,3-diamine acetate
- IUPAC name: 4-(phenylazo)benzene-1,3-diamine acetate
- Molecular formula: C14H16N4O2
- Molecular weight: 272.306 g/mole
- Smiles Notation: c1(ccc(c(N)c1)\N=N\c1ccccc1)N.C(C)(=O)O
- InChl: 1S/C12H12N4.C2H4O2/c13-9-6-7-12(11(14)8-9)16-15-10-4-2-1-3-5-10;1-2(3)4/h1-8H,13-14H2;1H3,(H,3,4)/b16-15+;
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

no data available

Route:

epicutaneous, open

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

intradermal

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Positive control results:

no data available

Other effects / acceptance of results:

no data available

Reading:

1st reading

Group:

test chemical

Clinical observations:

signs of dermal sensitization observed

Remarks on result:

positive 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 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and "ab" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Anilines (amino-meta) AND Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aliphatic acids and (Met)acrylic acids AND Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aliphatic acids and (Met)acrylic acids AND Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens by Groups of elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aliphatic Amine, secondary OR Alkene by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Benzamide by Organic Functional groups

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Sulfone by Organic Functional groups

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Sulfonamide by Organic Functional groups

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Pyridine by Organic Functional groups

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Carboxylic acid ester by Organic Functional groups

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.513

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.22

Interpretation of results:

other: Positive

Conclusions:

4-(phenylazo)benzene-1,3-diamine acetate was predicted to be sensitizing to the skin of male Hartley guinea pigs

Executive summary:

The skin sensitization potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 4-(phenylazo)benzene-1,3-diamine acetate was predicted to be sensitizing to the skin of male Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin Sensitization:

Various studies have been investigated for assessing the dermal sensitization potential of 4-(phenylazo)benzene-1,3-diamine to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs as well predicted data for target chemical and its structurally similar read across chemicals, 4-nitrobenzene-1,3-diamine[CAS: 5131-58-8] and 4-Methoxybenzylamine[CAS: 2393-23-9]. The predicted data has also been compared with the experimental data.

The skin sensitization potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 4-(phenylazo)benzene-1,3-diamine acetate was predicted to be sensitizing to the skin of male Hartley guinea pigs.

This is supported by an experimental study summarized in GESTIS - Substance Database (Information system on hazardous substances of the Berufsgenossenschaften), 2011 for the structurally similar read across chemical, 4-nitrobenzene-1,3-diamine[CAS: 5131-58-8].

A test on the skin-sensitizing effects of the substance on guinea pigs yielded positive results and confirmed a moderate allergic potential. Therefore 4-nitrobenzene-1,3-diamine( 5131-58-8) was considered to be sensitizing in Guinea pig.

Guinea pig Maximization assay was performed (OTS0546455, NTRL report, 1992) to determine the degree of dermal sensitization caused by the structurally similar read across chemical, 4-Methoxybenzylamine[CAS: 2393-23-9]. 10 female Hartley guinea pigs were used for the study.

During the induction phase, the test chemical in Freund's Adjuvant was injected into the skin of guinea pigs, then 1% of the test material was applied onto the skin. Negative control was also used (name not specified). After few days, the induced guinea pigs were challenged with 1% test chemical and observed for signs of erythema.

5 animals showed slightly greater degree of erythema than control animals. Five of ten animals induced with the test material in Freund's Adjuvant responded to challenge with a slightly greater degree of erythema than seen in animals previously injected with Freund's Adjuvant only.

Based on these observations, 4-Methoxybenzylamine was considered to be sensitizing to guinea pig skin.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach,4-(phenylazo)benzene-1,3-diamine was considered to sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for 4-(phenylazo)benzene-1,3-diamine acetate indicates that it is likely to cause dermal sensitization to skin.

4-(phenylazo)benzene-1,3-diamine acetate can be considered to be sensitizer to skin.