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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 from peer reveiwed journals

Data source

Reference
Reference Type:
publication
Title:
An animal model assessment of common dye-induced allergic contact dermatitis
Author:
JOE DINARDO, RaleighN, C; and ZOE DIANA DRAELOS
Year:
2007
Bibliographic source:
JOURNAL OF COSMETIC SCIENCE, 58, 209-214 May/June 2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: modified Buehler and the Klecak method
Principles of method if other than guideline:
A modified Buehler and Klecak method for open epicutaneous testing[OET] was performed to assess the sensitization potential of Tartrazine
GLP compliance:
no
Type of study:
Buehler 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 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:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data available

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, open
Vehicle:
propylene glycol
Concentration / amount:
0.1 ml of test chemical
Day(s)/duration:
3 times weekly(Monday, Wednesday , Friday)
Adequacy of induction:
not specified
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, open
Vehicle:
propylene glycol
Concentration / amount:
0.1 ml of test chemical
Day(s)/duration:
24-hrs
Adequacy of challenge:
not specified
No.:
#2
Route:
epicutaneous, open
Vehicle:
propylene glycol
Concentration / amount:
1,0.5,0.25%
Adequacy of challenge:
other: rechallenge for positive reaction at 10% in challenge exposure
No. of animals per dose:
10 albino guinea pigs
Details on study design:
Details on study design
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:3 times weekly(Monday, Wednesday , Friday)
- Exposure period:3 weeks
- Test groups:Yes
- Control group:No
- Site:Left flank shaved albino guinea pigs
- Frequency of applications:3 times weekly
- Duration:3 weeks
- Concentrations:0.1 ml of tartrazine

B. CHALLENGE EXPOSURE
- No. of exposures:Once
- Day(s) of challenge:After 2 weeks of rest period from induction exposure
- Exposure period:No data available
- Test groups:Yes
- Control group:No
- Site:Right flank of shaved guinea pig
- Concentrations:10,5 and 2.5 % of the induction concentration
- Evaluation (hr after challenge):24-hrs

C: Rechallenge
- Concentrations: 0.25,0.5 and 1% of the induction concentration


OTHER: All test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale
0 = no reaction,
1 -- slight reaction,
2 = moderate reaction,
3 = severe reaction
Challenge controls:
no data available
Positive control substance(s):
yes
Remarks:
0.5% of 2,4-dinitrochlorobenzene (DNCB) in ethanol was included for both the induction and challenge phases

Results and discussion

Positive control results:
The positive control DNCB at the 0.5% induction/challenge concentration elicited positive responses in all animals tested

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
2.5% in propylene glycol
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no dermal reactions observed
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
other: challenge group
Dose level:
5% in propylene glycol
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no dermal reactions observed
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
signs of dermal sensitization were observed
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Group:
test group
Dose level:
1.0,0.5,0.25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no dermal reactions observations
Remarks on result:
other: at 1% concentration only 1 guinea pig showed some signs of dermal sensitization, but no dermal reactions were observed at 0.5,0.25%

Any other information on results incl. tables

Table 1: Allergic contact dermatitis of dyes

Name of the dye

Color Index

Chemical class

Induction concentration in propylene glycol

Challenge concentration in propylene glycol*

10%

5%

2.5%

Tartrazine

19140

Monoazo

10%

+(20%)

Negative

Negative

 

Table 2: Dose-response of dyes eliciting positive response at 10% concentration

Name of the dye

Color Index

Chemical class

Induction concentration in propylene glycol

Challenge concentration in propylene glycol*

1%

0.5%

0.25%

Tartrazine

19140

Monoazo

1%

+(10%)

Negative

Negative

*results expressed as negative or positive (+) with percent of animals in the group demonstrating an allergic reaction in parenthesis

Applicant's summary and conclusion

Interpretation of results:
other: not sensitizing
Conclusions:
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 doesnot induce any sensitization in guinea pigs when tested below 10% concentration.
Executive summary:

A modified Buehler and Klecak method for open epicutaneous testing[OET] was performed to assess the sensitization potential of Tartrazine.

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.