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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
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

Reference
Reference Type:
publication
Title:
Safety of ingestion of yellow tartrazine by double-blind placebo controlled challenge in 26 atopic adults
Author:
S. Pestana, M. Moreira, B. Oleja
Year:
2010
Bibliographic source:
Allergol Immunopathol (Madr). 2010;38(3):142–146

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: as method below
Principles of method if other than guideline:
Double-blind, placebo-controlled food challenge (DBPCFC) was performed to assess the sensitization potential of Tartrazine in humans
GLP compliance:
not specified
Type of study:
other: Double-blind, placebo-controlled food challenge (DBPCFC)

Test material

Constituent 1
Chemical structure
Reference substance name:
Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate
EC Number:
217-699-5
EC Name:
Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate
Cas Number:
1934-21-0
Molecular formula:
C16H12N4O9S2.3Na
IUPAC Name:
Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate
Test material form:
solid
Details on test material:
- Name of test material (IUPAC name): trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate
- Common name: Acid Yellow 23,Tartrazine
- Molecular formula: C16H9N4Na3O9S2
- Molecular weight:534.3681 g/mol
- Smiles notation: n1(c2ccc(cc2)S(=O)(=O)[O-])c(c(c(n1)C(=O)[O-])/N=N/c1ccc(cc1)S(=O)(=O)[O-])O.[Na+].[Na+].[Na+]
-InChl:1S/C16H12N4O9S2.3Na/c21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29;;;/h1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);;;/q;3*+1/p-3/b18-17+;;;
- Substance type: Organic
- Physical state:Soild
Specific details on test material used for the study:
- Name of test material (IUPAC name): trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate
- Common name: Acid Yellow 23,Tartrazine
- Molecular formula: C16H9N4Na3O9S2
- Molecular weight:534.3681 g/mol
- Smiles notation: n1(c2ccc(cc2)S(=O)(=O)[O-])c(c(c(n1)C(=O)[O-])/N=N/c1ccc(cc1)S(=O)(=O)[O-])O.[Na+].[Na+].[Na+]
-InChl:1S/C16H12N4O9S2.3Na/c21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29;;;/h1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);;;/q;3*+1/p-3/b18-17+;;;
- Substance type: Organic
- Physical state:Soild

In vivo test system

Test animals

Species:
other: humans
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Antonio Pedro University Hospital
- Age at study initiation: 18–65 years old
- Weight at study initiation: No data available
- Housing: No data available
- Diet (e.g. ad libitum): Dye–free, nutritionally balanced meal
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Study design: in vivo (non-LLNA)

Induction
Route:
other: oral
Vehicle:
unchanged (no vehicle)
Concentration / amount:
5, 10, 20 and 35 mg
Adequacy of induction:
not specified
Challenge
No.:
#1
Route:
other: oral
Vehicle:
unchanged (no vehicle)
Concentration / amount:
5, 10, 20 and 35 mg
Adequacy of challenge:
not specified
No. of animals per dose:
26
Details on study design:
RANGE FINDING TESTS: No data available

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: No data available
- Exposure period: No data available
- Test groups: No data available
- Control group: No data available
- Site: No data available
- Frequency of applications: No data available
- Duration: No data available
- Concentrations: No data available

B. CHALLENGE EXPOSURE
- No. of exposures: 3
- Day(s) of challenge: 1 week
- Exposure period: 60 min
- Test groups: 1
- Control group: No data available
- Site: No data available
- Concentrations: 5, 10, 20 and 35 mg
- Evaluation (hr after challenge): Erythematous rash, Pruritus, Urticaria/angioedema was examined.

OTHER: Double-blind placebo controlled cross-over challenge (DBPCC) was used, gold standard method in the diagnosis of allergic reactions to food and drugs. Capsules were manufactured by an external pharmacist who maintained the code until all the challenges were completed. Briefly, each volunteer was challenged either with tartrazine (Yellow dye no. 5, FD & C) in one visit, or placebo (talc) on another visit, one week apart. In the first visit, patients were randomised to receive three identical opaque capsules containing tartrazine or placebo (talc) in three steps. The administered dose of tartrazine was progressively increased from 5mg in the first administration to 10mg in the second one and to 20 mg in the last one.

Results and discussion

In vivo (non-LLNA)

Results
Reading:
1st reading
Hours after challenge:
2
Group:
test chemical
Dose level:
35 mg
No. with + reactions:
0
Total no. in group:
26
Clinical observations:
No Erythematous rash, Pruritus, Urticaria/angioedema observed
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Symptoms score sheeta

 

0

(absent)

1 (mild)

2 (moderate)

3 (severe)

Skin

 

 

 

 

Erythematous rash

 

Few areas of faint

Erythema

Areas of erythema,

macular and raised rash

Generalised marked erythema (450%); extensive raised lesion

(25%); vesiculation

and/or piloerection

Pruritus

 

Occasional scratching

Scratching continuously

for 42 min at a time

Hard continuous scratching,

excoriations

Urticaria/angioedema

 

< 3 hives

< 10 hives to > 3

Generalised Involvement

Double-blind placebo controlled challenge with yellow tartrazine in atopic adults

 

Bock’s score

 

Cutaneous

Placebo

 

Baseline

0.11 ± 0.58a

Last evaluation

0.19 ± 0.56

Tartrazine

 

Baseline

b

Last evaluation

0.30 ± 0.61n

Placebo vs. tartrazine

0.15

aMean7SD.

bScore zero.

np < 0.05 vs. baseline.

Applicant's summary and conclusion

Interpretation of results:
other: not sensitizing
Conclusions:
No Erythematous rash, Pruritus, Urticaria/angioedema observed in any of the 26 human volunteers.Tartrazine was considered to be not sensitizing when atopic adults were tested by using Double-blind placebo controlled challenge.
Executive summary:

Double-blind, placebo-controlled food challenge (DBPCFC)  was performed to assess the sensitization potential of Tartrazine in humans

Double-blind placebo controlled cross-over challenge (DBPCC) was used, gold standard method in the diagnosis of allergic reactions to food and drugs. Capsules were manufactured by an external pharmacist who maintained the code until all the challenges were completed. Briefly, each volunteer was challenged either with tartrazine (Yellow dye no. 5, FD & C) in one visit, or placebo (talc) on another visit, one week apart. In the first visit, patients were randomised to receive three identical opaque capsules containing tartrazine or placebo (talc) in three steps. The administered dose of tartrazine was progressively increased from 5mg in the first administration to 10mg in the second one and to 20 mg in the last one.

Patients were examined for Erythematous rash, Pruritus and Urticaria/angioedema fifty minutes after the ingestion of each capsule, and 2 h after the last one. All patients stayed under observation for three hours after taking the last dose. All the subjects answered a questionnaire about symptoms after this period and were interviewed by phone the next day.

No Erythematous rash, Pruritus, Urticaria/angioedema  observed in any of the 26 human volunteers. Tartrazine was considered to be not sensitizing when atopic adults were tested by using Double-blind placebo controlled challenge.