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

Endpoint summary

Description of key information

The skin sensitization potential of target chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   was assessedin various experimental studies which were conducted on guinea pigs and humans for target chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   and its structurally similar read across substance Reactive Orange 12 (CAS No.-70161-14-7) andfunctionally similar read across substancesNew coccine (CAS No:2611-82-7) and Amaranth Dye (CAS No: 915-67-3).. The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   is able to cause skin sensitization and thus can be considered as sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Skin Sensitizer”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (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

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Specific details on test material used for the study:

Name of the test chemical: 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid
Molecular formula: C20H16ClN9O10S3
Molecular weight: 674.0504 g/mol
Smiles Notation: S(=O)(=O)(c1c(/N=N/c2c(NC(=O)N)cc(Nc3nc(nc(n3)Cl)N)cc2)cc2c(S(=O)(=O)O)cc(S(=O)(=O)O)cc2c1)O
InChI: 1S/C20H16ClN9O10S3/c21-17-26-18(22)28-20(27-17)24-9-1-2-12(13(5-9)25-19(23)31)29-30-14-7-11-8(4-16(14)43(38,39)40) 3-10(41(32,33)34)6-15(11)42(35,36)37/h1-7H,(H3,23,25,31)(H,32,33,34)(H,35,36,37)(H,38,39,40)(H3,22,24,26,27,28)/b30-29+
Substance Type: Organic
Physical State: solid

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

No data available

Vehicle:

propylene glycol

Concentration:

No data available

No. of animals per dose:

No data available

Details on study design:

No data available

Statistics:

No data available

Positive control results:

No data available

Parameter:

SI

Value:

0.79

Remarks on result:

other: Positive indication of skin sensitization

Cellular proliferation data / Observations:

No data available

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" or "d" or "e" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and "j" )  and ("k" and "l" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Substituted Triazines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "c"

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: "d"

Referential boundary: The target chemical should be classified as 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 v1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid moiety OR Anilines (Unhindered) OR Substituted Ureas OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Sulfonic acid AND Triazine AND Urea derivatives by Organic Functional groups ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Sulfonic acid AND Triazine AND Urea derivatives by Organic Functional groups ONLY

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.08

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.83

Interpretation of results:

other: sensitizing

Conclusions:

The skin sensitization potential of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (35642-64-9) 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 of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (35642-64-9)was predicted to be sensitizing to the skin of female CBA mouse .

Executive summary:

The skin sensitization potential of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (35642-64-9)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 of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (35642-64-9) was predicted to be sensitizing to the skin of female CBA mouse .

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitization:

Various studieshas been investigated for the test chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    and its structurally similar read across substance Reactive Orange 12 (CAS No.-70161-14-7) andfunctionally similar read across substancesNew coccine (CAS No:2611-82-7) and Amaranth Dye (CAS No: 915-67-3). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    was estimated to be sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    can be considered to be sensitizing to Dunkin-Hartley guinea pigs.

 

 

The Provocation tests were conducted byGerd Michaelsson and Lennart Juhlin (British Journal of Dermatology (1973) 88, 525)for read across chemicals New coccine (CAS No:2611-82-7) and Amaranth Dye (CAS No: 915-67-3) on patients suffering from recurrent urticaria or angio-oedema that supported the above mentioned estimated result.Theseprovocation tests were performed when the patients had slight or no symptoms.Thirty-three healthy persons served as controls. Two of them have a moderate allergic rhinitis and one sometimes has an itching of unknown cause. Both objective and subjective symptoms were carefully noted after each test.The provocation results were judged as positive when the patient developed an unquestionable urticaria or angio-oedema after having had an inactive period before provocation. The reaction, especially angio-oedema, sometimes occurred within the first few hours after provocation, whereas the urticaria often did not develop until 6-14 h afterwards.

 

In case of chemicalNew coccine (CAS No:2611-82-7)the 25 patients were treated ata dose of 0.1, 1, 2, 5, and 10 mg and at increasing concentrations until a reaction was noted.Of the 25 patients studied, 9 evidenced urticaria and 1 showed other objective signs; 6 patients’ evidenced only subjective symptoms and 9 had no reaction.

While the chemical Amaranth Dye (CAS No: 915-67-3) was tested at 0.1, 1, and 2 mg/ dose on 7 patients.Of the 7 patients studied,two had no reactions, three had only subjective symptoms, one had urticaria, and one had other objective signs of a "take.

 A control group of 33 subjects did not develop urticarial in each test.Therefore on the basis of observed reactions, the chemicalsNew coccine (CAS No:2611-82-7) and Amaranth Dye (CAS No: 915-67-3) was considered as skin sensitizing.

 

Also these results were further supported by the experimental study conducted by NTRL (NTRL report, OTS0571820, 1992) for the structurally similar read across substance, Reactive Orange 12 (CAS No.-70161-14-7) in guinea pig.The skin sensitization study of Reactive Orange 12 (CAS No.-70161-14-7) was performed on male and female Pirbright white guinea pig. 20 animals in treated group while control group contains 20 animals 10/sex. All the animals provided with Standard guinea pigs pallets NAPAG No.830, Gossus BG and fresh carrots ad libitum.The test material dissolved in Physiological saline and used in dose concentration 0.1%. In induction phase, the animals received one injection every second days (except weekend) to a total of 10 intradermal injection of a fresh prepared 0.1% solution of test material in physiological saline.1st induction injection on right flank and back while other induction injection given on only back. All the animals were observed 24hr after each induction injection for any skin reaction.14 days after last induction injection, Challenge injection given using freshly prepared 0.1% test material in same vehicle on left flank and reactions were observed after 24hr While 10 days after the intradermal challenges injection, subirritant doses of the test compound were applied epiecutaneously under occlusive dressing which was left in place for 24hr.Before examination, the reaction sites were depilated chemically. The two largest perpendicular diameter (in mm) were measured and by multiplication of these values a reaction volume was obtained (in µl) for each reading from each animals. The mean volume plus one standard deviation of the induction reaction observed in the individual animals in the first week was taken as representing the skin irritation threshold for each animal. Any challenge reaction greater than this threshold value in the induction period was graded as an allergic reaction and animals termed as positive. The number of positive animals in test group was compared with number of animals in the control group. Following the intra dermal challenge injection 20/20 treated animals showed positive response (compared with 0/19 control).Epicutaneous challenge result in 11/20 positive reaction to the test material (1/19 control positives).Hence the Reactive Orange 12(CAS No:70161-14-7) was considered to be sensitizing in guinea pig.

 

Thus on the basis of available data for thetarget chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    and its structurally similar read across substance Reactive Orange 12 (CAS No.-70161-14-7) andfunctionally similar read across substancesNew coccine (CAS No:2611-82-7) and Amaranth Dye (CAS No: 915-67-3),it can be concluded thatchemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    is able to cause skin sensitization and considered as skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Skin Sensitizer”.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)     and its structurally similar read across substance Reactive Orange 12 (CAS No.-70161-14-7) andfunctionally similar read across substancesNew coccine (CAS No:2611-82-7) and Amaranth Dye (CAS No: 915-67-3)were observed in various studies. From the results obtained from these studies it is concluded that the chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    is likely to cause skin sensitization and hence can be classified as skin sensitizer.