2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile was predicted to be not sensitizing to the skin of female guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 v3.4 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 v3.4

GLP compliance:

not specified

Type of study:

other: Estimated data

Specific details on test material used for the study:

- Name of test material: 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile
- IUPAC name: 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile
- Molecular formula: C18H19N5O4
- Molecular weight: 369.38 g/mole
- Smiles Notation: Cc1cc(N(CCO)CCO)ccc1N=Nc1ccc(N(=O)=O)cc1C#N
- Substance type: Organic
- Physical state: Solid powder (violet)

Species:

guinea pig

Strain:

not specified

Sex:

female

Details on test animals and environmental conditions:

no data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, semiocclusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

no data available

Reading:

1st reading

Group:

test chemical

Clinical observations:

no signs of sensitization 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" )  and ("c" and ( not "d") )  )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and "j" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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) >> Nitro Azoarenes OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes by DNA binding by OASIS v.1.4 ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 11 - Trans.Metals Cu,Ag,Au OR Group 15 - Phosphorus P OR Group 16 - Sulfur S OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At OR Group 6 - Trans.Metals Cr,Mo,W by Chemical elements

Domain logical expression index: "e"

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 AND Group All Melting Point > 200 C AND Group CN Aqueous Solubility < 0.1 g/L AND Group CN Melting Point > 180 C AND Group CN Molecular Weight > 290 g/mol AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Group CN Aqueous Solubility < 0.0001 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Molecular Weight > 540 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B by Repeated dose (HESS)

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.19

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.69

Interpretation of results:

other: Negative

Conclusions:

2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile was predicted to be not sensitizing to the skin of female guinea pigs.

Executive summary:

The skin sensitization potential of 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile was predicted to be not sensitizing to the skin of female guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

Several studies were performed to ascertain the extent of dermal sensitization caused by 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrilein living organisms. These studies include in vivo studies in guinea pigs as well as predicted data for the target chemical as well its structurally similar read across substances,2,2'-[[4-[(4-aminophenyl)azo]phenyl]imino]bisethanol (Disperse Black 9)[CAS: 20721-50-0] and 1-(4-Methyl-2-nitrophenylazo)-2-naphthol(C.I. Pigment Red 3, Toluidine Red)[CAS: 2425-85-6].The experimental results are also supported by theresults obtained from OECD QSAR toolbox.

The skin sensitization potential of 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile was predicted to be not sensitizing to the skin of female guinea pigs.

This is supported by the experimental study summarized in JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY, Volume 5, Number 3, 1986; for thestructurally similar read across substance, 2,2'-[[4-[(4-aminophenyl)azo]phenyl]imino]bisethanol (Disperse Black 9)[CAS: 20721-50-0]. The study was performed according to the Kligman – Magnusson procedure.10 female Hartley guinea pigs were used for the study.

Three pairs of injections (0.05 ml each) were administered intradermally into the shaved interscapular area of each guinea pig: Freund’s complete adjuvant (in equal parts water), 0.1% Disperse Black 9, and a mixture of equal parts of the adjuvant and dye. One week later, the sites were shaved again, and a 48-h occlusive patch containing 25% Disperse Black 9 in petrolatum was applied. Two weeks later, an occlusive challenge patch containing 25% Disperse Black 9 in propylene glycol was applied to the shaved flank of each guinea pig. Sites were evaluated 24, 48, and 72 hours after patch removal.

No signs of dermal sensitization were observed on female guinea pig skin at any time point after challenge exposure.

Hence, Disperse Black 9 was considered to be not sensitizing to guinea pig skin.

The above results are further supported by the experimental study conducted by TAKEHITO KGZUKA et.al (Contact Dermatitis; Volume 6; Pg. no. 330-336; 1980) in human patients suffering from pigmented contact dermatitis caused by the commercial Brilliant Lake Red R for structurally similar read across substance, 1-(4-Methyl-2-nitrophenylazo)-2-naphthol(C.I. Pigment Red 3, Toluidine Red)[CAS: 2425-85-6] to detect its contact sensitivity.The patch of Toluidine Red was applied onto the back of 8 healthy patients for 24 hours by using Finn Chambers® on Scanpor® (Epitest, Ltd. Oy) at a dose of 1% in petrolatum. After removal of patch, skin reactions were assessed according to the ICDRG classification for 2 days. Twenty-eight healthy female volunteers, aged 20 and 21, were also tested with the sample as controls. None gave a positive reaction.

The negative skin sensitizing effects were observed in all treated patients. Thus the test chemical, Toluidine Red(CAS No: 2425-85-6)was considered to be not sensitizing in human patients suffering from pigmented contact dermatitis caused by the commercial Brilliant Lake Red R.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for 2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile indicates that it is not likely to cause dermal sensitization to skin.

2-[[4-[bis(2-hydroxyethyl)amino]-o-tolyl]azo]-5-nitrobenzonitrile can be considered to be not sensitizer to skin.