Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Endpoint summary

Description of key information

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate was estimated to be sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Weight of evidence approach based on structurally similar chemicals

Justification for type of information:

Weight of evidence approach based on structurally similar chemicals

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: Weight of evidence based on structurally similar chemicals

Principles of method if other than guideline:

The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal sensitization potential of Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

GLP compliance:

not specified

Type of study:

other: Weight of evidence based on structurally similar chemicals

Specific details on test material used for the study:

Name of the test chemical: Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonateMolecular Formula: C32H26ClN7O11S3.3Na Molecular Weight: 882.193 g/molSmiles Notation: [Na+].[Na+].[Na+].c1(c(cc(c2C(c3ccccc3C(c12)=O)=O)Nc1c(c(c(c(c1C)S(=O)(=O)[O-])C)Nc1nc(nc(n1)Cl)Nc1c(cccc1)S(=O)(=O)[O-])C)S(=O)(=O)[O-])NInChI: 1S/C32H26ClN7O11S3.3Na/c1-13-25(35-19-12-21(53(46,47)48)24(34)23-22(19)27(41)16-8-4-5-9-17(16)28(23)42)14(2)29(54(49,50)51)15(3)26(13)37-32-39-30(33)38-31(40-32)36-18-10-6-7-11-20(18)52(43,44)45;;;/h4-12,35H,34H2,1-3H3,(H,43,44,45)(H,46,47,48)(H,49,50,51)(H2,36,37,38,39,40);;;/q;3*+1/p-3Substance Type: OrganicPhysical State: Solid

Species:

other: humans and guinea pigs

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

no data available

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of induction:

not specified

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Concentration / amount:

0.1%

Day(s)/duration:

24 h

Adequacy of induction:

not specified

No.:

#1

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Concentration / amount:

0.1%

Day(s)/duration:

24 h

Adequacy of challenge:

not specified

No. of animals per dose:

1. 252. 203. 7

Details on study design:

The study is based on weight of evidence approach from the read across values

Reading:

1st reading

Group:

test chemical

Clinical observations:

dermal reactions were observed

Remarks on result:

positive indication of skin sensitisation

Interpretation of results:

other: sensitizing

Conclusions:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate was estimated to be sensitizing to skin.

Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate.

A Provocation test was conducted for the structurally similar chemical on 25 patients suffering from recurrent urticaria or angio-oedema. Provocation tests were performed when the patients had slight or no symptoms at a dose of 0.1, 1, 2, 5, and 10 mg and at increasing concentrations until a reaction was noted. 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. 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. A control group of 33 subjects did not develop urticaria.

Therefore on the basis of observed reactions, the chemical was considered as skin sensitizing.

This result is supported by the experimental study for other structurally similar read across chemical. 20 male and female Pirbright- white guinea pigs 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 was 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.1^stinduction 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 epicutaneously 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 test chemical was considered to be sensitizing to guinea pig skin.

The above results are further supported by Provocation test conducted for one more structurally similar chemical on 7 patients suffering with recurrent urticaria or angio-oedema.

 Provocation tests were performed when the patients had slight or no symptoms at 0.1, 1, and 2 mg/ dose. 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. 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 urticaria.

Therefore on the basis of observed reactions, the chemical was considered as skin sensitizing.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate was estimated to be sensitizing to skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin Sensitization

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate.

A Provocation test was conducted for the structurally similar chemical on 25 patients suffering from recurrent urticaria or angio-oedema. Provocation tests were performed when the patients had slight or no symptoms at a dose of 0.1, 1, 2, 5, and 10 mg and at increasing concentrations until a reaction was noted. 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. 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. A control group of 33 subjects did not develop urticaria.

Therefore on the basis of observed reactions, the chemical was considered as skin sensitizing.

This result is supported by the experimental study for other structurally similar read across chemical. 20 male and female Pirbright- white guinea pigs 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 was 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.1^stinduction 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 epicutaneously 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 test chemical was considered to be sensitizing to guinea pig skin.

The above results are further supported by Provocation test conducted for one more structurally similar chemical on 7 patients suffering with recurrent urticaria or angio-oedema.

 Provocation tests were performed when the patients had slight or no symptoms at 0.1, 1, and 2 mg/ dose. 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. 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 urticaria.

Therefore on the basis of observed reactions, the chemical was considered as skin sensitizing.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate was estimated to be sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate can be sensitizing to skin.Hence by applying the weight of evidence approach, Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate can be considered to be sensitizing to skin.