Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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)

Justification for non-LLNA method:

not specified

Test material

Test material information

Constituent 1

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:

C16-H12-N4-O9-S2.3Na

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 sheet^a

	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 ± 0.58^a
Last evaluation	0.19 ± 0.56
Tartrazine
Baseline	b
Last evaluation	0.30 ± 0.61^n
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.