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Toxicological information

Skin sensitisation

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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 journals

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Urticaria induced by preservatives and dye additives in food and drugs
Author:
GERD MICHAELSSON AND LENNART JUHLIN
Year:
1973
Bibliographic source:
British Journal of Dermatology (1973) 88, 525
Reference Type:
secondary source
Title:
Mono Azo Dye and Pigment Toxicological Profiles
Author:
Susan Feinman
Year:
1981
Bibliographic source:
NTIS report PB83168757, August 1981

Materials and methods

Test guideline
Qualifier:
according to
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Name of the test chemical : 1,3-Naphthalenedisulfonic acid, 7-hydroxy-8-((4-sulfo-1-naphthalenyl)azo)-, trisodium saltCommon Name: Acid Red 18Molecular Formula: C20H11N2Na3O10S3Molecular Weight: 604.5 g/molSubstance Type: OrganicPhysical State: Solid

In vivo test system

Test animals

Species:
other: Human (patients )
Strain:
other: Not applicable
Sex:
male/female
Details on test animals and environmental conditions:
Source:Department of Dermatology, tJppsala University Hospital, Uppsala, Sweden
-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 group
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. RESULTS OF PROVOCATION TESTS

Urticaria

Other

objective

signs

Only

subjective

symptoms

No

reaction

Total

no.

tested

9

1

6

9

25

Applicant's summary and conclusion

Interpretation of results:
other: sensitizing
Conclusions:
The chemical was considered as sensitizing to the skin in a provocation test conducted on 25 patients suffering from recurrent urticaria or angio-oedema.
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.