7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other: Predicted data

Title:

[R]: not sensitising; Estimation for Skin Sensitisation for CAS 94158-80-2

Author:

Sustainability Support Services (Europe) AB

Year:

2016

Bibliographic source:

SSS QSAR Prediction Team

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt

EC Number:

303-153-4

EC Name:

7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt

Cas Number:

94158-80-2

Molecular formula:

C28H22ClN9O12S4.xNa

IUPAC Name:

trisodium;7-[[2-(carbamoylamino)-4-[[4-chloro-6-(4-ethenylsulfonylanilino)-1,3,5-triazin-2-yl]amino]phenyl]diazenyl]naphthalene-1,3,6-trisulfonate

Constituent 2

Reference substance name:

1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4-((4-chloro-6-((4-(ethenylsulfonyl)phenyl)amino)-1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt

IUPAC Name:

1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4-((4-chloro-6-((4-(ethenylsulfonyl)phenyl)amino)-1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report):1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4-((4-chloro-6-((4-(ethenylsulfonyl)phenyl)amino)-1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt
- Molecular formula : C28H22ClN9O12S4xNa
- Molecular weight : 906.1961 gm /mol
-SMILES:C=CS(=O)(=O)c1ccc(Nc2nc(Nc3ccc(N=Nc4cc5c(cc4S(O)(=O)=O)cc(S(O)(=O)=O)cc5S(O)(=O)=O)c(NC(N)=O)c3)nc(Cl)n2)cc1

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Source: Kleintierfarm Madoerin AG, CH 4414, Fuellinsdorf, Switzerland
- Age at study initiation: 8-9 weeks
- Weight at study initiation: Males: 375-473g, Females: 376-495g
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet (e.g. ad libitum): Pelleted standard 342 Kliba, Batch 33/86 and 34/87 guinea pig breeding/ maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen ad libitum
- Acclimation period: One week under test conditions after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Induction 2

Concentration / amount:

Intradermal injections (0.1 mL/site) at concentrations of 0.1, 0.3, 0.5, 1, 3 and 5 % of the test article.
- Epidermal applications: 3, 5, 10 and 25 % of the test article.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Challenge 2

Concentration / amount:

Intradermal injections (0.1 mL/site) at concentrations of 0.1, 0.3, 0.5, 1, 3 and 5 % of the test article.
- Epidermal applications: 3, 5, 10 and 25 % of the test article.

No. of animals per dose:

10

Results and discussion

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

not sensitising

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: not sensitising.

Any other information on results incl. tables

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" or "f" or "g" )  and ("h" and ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives AND Not possible to classify according to these rules by DPRA Cysteine peptide depletion

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 phenylureas by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as High reactive AND High reactive >> Activated 1,3,5-triazine derivatives by DPRA Lysine peptide depletion

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Michael addition on polarised Alkenes AND Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkenes - sulfones  AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Polarised Alkenes AND Michael addition >> Polarised Alkenes >> Polarised alkene - sulfinyl AND Michael addition >> Polarised Alkenes >> Polarised alkene - sulfone AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) AND Highly reactive (GSH) >> Phenyl vinyl sulfone (MA) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN2 OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.4

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 No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) sufonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sufonamide group >> Arenesulphonamides OR AN2 OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulphonamides by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.481

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.771

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Conclusions:

The test substance 1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4-((4-chloro-6-((4-(ethenylsulfonyl)phenyl)amino)-1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt is estimated to be not sensitizing to the guinea pig skin.

Executive summary:

The skin sensitization potential for 1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)- 4-((4-chloro-6-( (4-(ethenylsulfonyl) phenyl) amino)-1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt is estimated using OECD QSAR toolbox version 3.3. The test substance 1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4- ((4-chloro-6-((4-(ethenylsulfonyl)phenyl)amino)- 1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt is estimated to be not sensitizing to the guinea pig skin.