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

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Urticaria induced by preservative and drugs

Author:

GERD MICHAELSSON et.al

Year:

1973

Bibliographic source:

British Journal of Dermatology, 1973

Reference 2

Reference Type:

secondary source

Title:

Mono Azo Dyes and Pigments - Toxicological Profiles

Author:

NTIS report

Year:

1981

Bibliographic source:

PB83168757, 1981

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

A Provocation test was conducted for chemical on 25 patients suffering with recurrent urticaria or angio-oedema.

GLP compliance:

not specified

Type of study:

other: Provocation test

Justification for non-LLNA method:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium 1-(1-naphthylazo)-2-hydroxynaphthalene-4',6,8-trisulphonate

EC Number:

220-036-2

EC Name:

Trisodium 1-(1-naphthylazo)-2-hydroxynaphthalene-4',6,8-trisulphonate

Cas Number:

2611-82-7

Molecular formula:

C20H14N2O10S3.3Na

IUPAC Name:

Trisodium 1-(1-naphthylazo)-2-hydroxynaphthalene-4',6,8-trisulphonate

Test material form:

solid

Details on test material:

1,3-Naphthalenedisulfonic acid, 7-hydroxy-8-((4-sulfo-1-naphthalenyl)azo)-, trisodium salt /Acid Red 18/ 2611-82-7/ 220-036-2- Name of test material (as cited in study report): Acid red 18/ New coccine- Molecular formula: C20H11N2Na3O10S3- Molecular weight: 604.5 g/mol- Substance type: Organic- Physical state: Solid- Smiles:c12c(cc(S(=O)(=O)[O-])cc2S(=O)(=O)[O-])ccc(c1\N=N\c1c2c(c(S(=O)(=O)[O-])cc1)cccc2)O.[Na+].[Na+].[Na+]- InChI: 1S/C20H14N2O10S3.3Na/c23-16-7-5-11-9-12(33(24,25)26)10-18(35(30,31)32)19(11)20(16)22-21-15-6-8-17(34(27,28)29)14-4-2-1-3-13(14)15;;;/h1-10,23H,(H,24,25,26)(H,27,28,29)(H,30,31,32);;;/q;3*+1/p-3/b22-21+;;;

In vivo test system

Test animals

Species:

other: Human (patients )

Strain:

other: Not applicable

Sex:

male/female

Details on test animals and environmental conditions:

-Patients :Patients with symptoms of recurrent urticaria and angio-oedema were tested. No patients with urticaria factitia, cold or heat urticaria were included in the group.- Diet and drugs during the testing period:For 3 days before admission to hospital, the patients were requested not to use antihistamines or any other drugs, if possible. The patients with frequent recurrences of urticaria had been on a diet free from dyes and preservatives before being admitted.

Study design: in vivo (non-LLNA)

Induction

Route:

other: epicutaneous

Vehicle:

not specified

Concentration / amount:

0.1, 1, 2, 5, and 10 mg in the provocation- test, at increasing concentrations until a reaction was noted.

Day(s)/duration:

14 hours

Adequacy of induction:

not specified

Challenge

No.:

#1

Route:

other: epicutaneous

Vehicle:

not specified

Concentration / amount:

0.1, 1, 2, 5, and 10 mg in the provocation- test, at increasing concentrations until a reaction was noted.

Day(s)/duration:

14 hours

Adequacy of challenge:

not specified

No. of animals per dose:

25 (patients)

Details on study design:

Provocation tests were performed when the patients had slight or no symptoms. After a light breakfast, the substance to be tested was given in the lowest dose at 8 a.m. If no objective reaction could be noted, additional and increased doses were given at 1h intervals. When a positive reaction occurred, the provocation was stopped and no further doses were given. Only one substance was given per day. 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.

Challenge controls:

Thirty-three healthy persons served as controls. Two of them have a moderate allergic rhinitis and one sometimes has an itching of unknown cause.

Results and discussion

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

14

Group:

test chemical

Dose level:

0.1, 1, 2, 5, and 10 mg

No. with + reactions:

9

Total no. in group:

27

Clinical observations:

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.

Remarks on result:

positive indication of skin sensitisation

In vivo (LLNA)

Cellular proliferation data / Observations:

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. Other objective symptoms which often appear during the first hours, but which can easily be overlooked, include erythema of the neck and face, nasal congestion, sneezing, hoarseness, and wheezing. Subjective symptoms which have been difficult to verify are, for example, itching and a sensation of being swollen or warm (Table 1). Most patients who developed urticaria also mentioned these symptoms.

Any other information on results incl. tables

TABLE 2. RESULTS OF PROVOCATION TESTS
Substance	Urticaria	Other objective signs	Only subjective symptoms	No reaction	Total no. tested
New Coccine	9	1	6	9	25

Applicant's summary and conclusion

Interpretation of results:

other: sensitizing

Conclusions:

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.

Executive summary:

A Provocation test was conducted for 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.