Registration Dossier

Administrative data

Description of key information

Skin Sensitization:

No reactions were observed in the 53 patients tested with Tartrazine Aluminium lake in a patch test performed according to  ICDRG Guidelines. Hence, Tartrazine Aluminum lake was considered to be not sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
To assess the dermal sensitization potential of Tartrazine Aluminium lake in humans
GLP compliance:
not specified
Type of study:
patch test
Specific details on test material used for the study:
- Name of test material: Aluminium, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1H-pyrazole-3-carboxylic acid complex- Common Name: Tartrazine Aluminium lake- IUPAC name: aluminum tris(4-{[3-carboxy-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazol-4-yl]diazenyl}benzenesulfonate)- Molecular formula: C48H33AlN12O27S6- Molecular weight: 1429.19 g/mole- Smiles : C1=CC(=CC=C1N=NC2C(=NN(C2=O)C3=CC=C(C=C3)S(=O)(=O)O)C(=O)O)S(=O)(=O)[O-].C1=CC(=CC=C1N=NC2C(=NN(C2=O)C3=CC=C(C=C3)S(=O)(=O)O)C(=O)O)S(=O)(=O)[O-].C1=CC(=CC=C1N=NC2C(=NN(C2=O)C3=CC=C(C=C3)S(=O)(=O)O)C(=O)O)S(=O)(=O)[O-].[Al+3]- Inchl: 1S/3C16H12N4O9S2.Al/c3*21-15-13(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;/h3*1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);/q;;;+3/p-3- Substance type: Organic- Physical state: Solid Red powder
Species:
other: humans
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Source: Patch test were performed in 53 patients with pigmented cosmetic dermatitis who had visited the authors clinic over the past 2 years
Route:
epicutaneous, occlusive
Vehicle:
other: 88 % polyethylene glycol 400 and 12 % polyethylene glycol 6000
Concentration / amount:
5 % in vehicle
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: 88 % polyethylene glycol 400 and 12 % polyethylene glycol 6000
Concentration / amount:
5% in vehicle
Day(s)/duration:
48 and 72 hours
Adequacy of challenge:
not specified
No. of animals per dose:
28 patients
Details on study design:
OTHER:Patch tests were performed according to the standardized method recommended by the ICDRGPatients had pigmented cosmetic dermatitis. The test substance was mixed at 5 % in a vehicle composed of 88 % polyethylene glycol 400 and 12 % polyethylene glycol 6000. The test were fixed with A1-test on Dermicel tape.Scoring pattern for dermal reactions:No reaction: -Slight erythema: +Erythema with slight papules: ±Erythema with edema: ++Erythema with vesicles and/or papules: +++
Challenge controls:
no data available
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
5% in vehicle
No. with + reactions:
0
Total no. in group:
53
Clinical observations:
no reactions observed
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
5% in vehicle
No. with + reactions:
0
Total no. in group:
53
Clinical observations:
no reactionns observed
Remarks on result:
no indication of skin sensitisation

Table: Results of the skin tests to representative coal tar dyes in patients with pigmented dermatitis

Name of the dye

Legal name in USE

PATCH TEST

TOTAL NUMBER OF PATIENTS

+

 

++

 

+++

 

Tartrazine aluminium lake

FDC- Y5

0

0

0

53

Interpretation of results:
other: not sensitizing
Conclusions:
Tartrazine Aluminium Lake in a patch test performed according to ICDRG Guidelines did not produce any dermal reactions in the human volunteers. Hence, Tartrazine Aluminum lake was considered to be not sensitizing to skin.
Executive summary:

Patch tests were performed to assess the dermal sensitization potential of Tartrazine Aluminium lake in humans. Patch tests were performed according to the standardized method recommended by the ICDRG. The test was performed in 53 patients with pigmented cosmetic dermatitis who had visited the author’s clinic over the past 2 years. The test substance was mixed at 5 % in a vehicle composed of 88 % polyethylene glycol 400 and 12 % polyethylene glycol 6000. The test patches were fixed with A1 -test on Dermicel tape. The skin reactions were scored at 48 and 72 hours according to the following standards:

No reaction: -; Slight erythema: +; Erythema with slight papules: ±; Erythema with edema: ++; Erythema with vesicles and/or papules: +++

Tartrazine Aluminium Lake in a patch test performed according to ICDRG Guidelines did not produce any dermal reactions in the human volunteers. Hence, Tartrazine Aluminum lake was considered to be not sensitizing to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin Sensitization:

The skin sensitization potential ofAluminium, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1H-pyrazole-3-carboxylic acid complexwas evaluated in various studies. These studies include experimental data for the target as well its parent compound Tartrazine [CAS: 1934-21-0].

Patch tests were performed (Contact Dermatitis, 3 249-256 (1977)) to assess the dermal sensitization potential of Tartrazine Aluminium lake in humans. Patch tests were performed according to the standardized method recommended by the ICDRG. The test was performed in 53 patients with pigmented cosmetic dermatitis who had visited the author’s clinic over the past 2 years. The test substance was mixed at 5 % in a vehicle composed of 88 % polyethylene glycol 400 and 12 % polyethylene glycol 6000. The test patches were fixed with A1-test on Dermicel tape. The skin reactions were scored at 48 and 72 hours according to the following standards:

No reaction: -; Slight erythema: +; Erythema with slight papules: ±; Erythema with edema: ++; Erythema with vesicles and/or papules: +++

Tartrazine Aluminium Lake in a patch test performed according to ICDRG Guidelines did not produce any dermal reactions in the human volunteers. Hence, Tartrazine Aluminum lake was considered to be not sensitizing to skin.

A modified Buehler and Klecak method for open epicutaneous testing[OET] was performed by JOE DINARDO et.al [JOURNAL OF COSMETIC SCIENCE, 58, 209-214 May/June 2007] to assess the sensitization potential of Tartrazine [CAS: 1934-21-0].

Tartrazine was tested at an induction concentration of 10% and challenge concentrations of 10.0%, 5.0%, and 2 .5%.

For the induction phase, the left flanks of ten albino guinea pigs were shaved and the dye test material applied three times weekly (Monday, Wednesday, Friday) for three consecutive weeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area. Following the induction period, the guinea pigs entered the challenge phase. The challenge phase began after a two-week rest period when the right flank of each guinea pig was shaved and exposed to three different dye test material concentrations(10.0%, 5.0%, and 2 .5%). Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions.

All test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale. A positive control of 0.5% 2,4-dinitrochlorobenzene(DNCB) in ethanol was included for both the induction and challenge phases. Since a positive response was observed in the challenge exposure at 10% challenge exposure, Tartrazine was retested using a 1% induction exposure and challenge concentrations of 1.0%, 0.5%, and 0.25%.

Tartazine produced a positive reaction at 10% challenge exposure, but in the retest no reactions were observed at 1%, 0.5 and 0.25% challenge concentrations.

Hence, it was considered that Tartrazine does not induce any sensitization in guinea pigs when tested below 10% concentration.

The above results are supported by the Double-blind, placebo-controlled food challenge (DBPCFC) performed by S. Pestana et.al [Allergol Immunopathol (Madr), 2010;38(3):142–146]to assess the sensitization potential of Tartrazine[CAS: 1934-21-0] 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.

These results are further supported by the Maximisation test conducted [Evaluation and opinion on Acid Yellow 23, SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS -SCCNFP, adopted on 23 April 2004] according to OECD guideline 406 to ascertain the dermal sensitization potential of Tartrazine[CAS: 1934-21-0]. 5 % Acid Yellow 23 solution was applied to the skin of 10 albino guinea pigs in an emulsion of Freund´s Complete Adjuvant (FCA) for the intradermal induction. 1 week later, following treatment with sodium lauryl sulfate (SLS) the epidermal induction was conducted for 48 h under occlusion with a 50 % Acid Yellow 23 solution. 2 weeks later, the animals were challenged by epidermal application of Acid Yellow 23 (25 % solution) under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 h after removal of the dressing. For challenge reading, all animals were depilated 3 h before examination to remove the discolouration.

None of the control and test animals showed skin reactions after the challenge treatment with Acid Yellow 23. The 50 % test item stained the skin orange, therefore it was not possible to determine whether erythema were present or not. However, no oedema was observed.

Based on these observations, Tartrazine was considered to be not sensitizing to skin.

In an another Human patch test performed[Contact Dermatitis, 27, 22-26, (1992)] using uniform patch tests and following procedure described in European standard series. 32 patients (20 women, 12 men) all with a positive patch test reaction p-aminoazobenzene (0.25 petrolatum%).

Eleven patients had previously also shown sensitization to para-phenylenediamine (PPD). 10 (4 women, 6 men) out of the 32 cases were negative to all the test allergens of the European standard series. 30 patients with an allergic contact dermatitis but negative to p-aminobenzene and to PPD were also tested as control group with the same patch test series.

Tartrazine did not elicit an allergic reaction in any of the test volunteers. Hence, Tartrazine can be considered to be not sensitizing to human skin.

 

Available studies for the target and parent compound [CAS:1934-21-0] indicate a very strong possibility of Tartrazine Aluminium lake being not sensitizing to skin. Hence, Tartrazine Aluminium lake can be considered to be not a skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Available data for Aluminium, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1H-pyrazole-3-carboxylic acid complex suggests that it is not likely to cause any dermal sensitization to skin.

Aluminium, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1H-pyrazole-3-carboxylic acid complex can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.