Trisodium 2-[[4,5-dihydro-3-methyl-5-oxo-1-[4-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]-1H-pyrazol-4-yl]azo]naphthalene-1,5-disulphonate

Eye irritation

Administrative data

Endpoint:

eye irritation: 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:

Evaluation of the cumulative (repeated application) eye irritation and corneal staining potential of FD&C yellow no. 5, FD&C blue no. 1 and FD&C blue no. 1 aluminium lake.

Author:

S D Gettings, D L Blaszcak, M T Roddy, A S Curry, G N McEwen.

Year:

1992

Bibliographic source:

Food & Chemical Toxicology, Vol. 30, No. 12, pp. 1051-1055, 1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Draize test

Principles of method if other than guideline:

To determine the ocular irritation potential of Tartrazine (FD & C Yellow No. 5) produced by repeated topical application to rabbit eyes

GLP compliance:

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

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:Summit View Farm, Hazelton, PA, USA
- Age at study initiation:N/A
- Weight at study initiation:3.0-3.5 kg
- Housing:Rabbits were individually housed in stainless steel, wire mesh-floor cages in a room.
- Diet (e.g. ad libitum):Feed (Certified Lab Rabbit Chow HF; Purina No. 5325) was limited to 125g/day.
- Water (e.g. ad libitum):ad libitum
- Acclimation period:All animals were acclimatized for at least 2 wk prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):16-21°C
- Humidity (%):38%
- Air changes (per hr):N/A
- Photoperiod (hrs dark / hrs light):12-hr light/dark cycle

Test system

Vehicle:

other: aqueous vehicle containing 0.5% (w/v) hydroxypropyl methylcellulose and 0.25% (w/v) laureth-10 acetate

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution):30 μl of test solution

VEHICLE
- Amount(s) applied (volume or weight with unit):3%
- Concentration (if solution):3 % (w/v) Acid Yellow 23 in aqueous solution with 0.5 % (w/v) hydroxypropyl methylcellulose and 0.25 % (w/v) laureth-10 acetate
- Lot/batch no. (if required):N/A
- Purity:N/A

Duration of treatment / exposure:

21 days

Observation period (in vivo):

All eyes were scored for ocular irritation pretest (8 days, 24 hr and immediately prior to the initial dose) and approximately 24 hr after each treatment, prior to the next instillation of test material; on days 1, 3, 7, 14 and 21, the eyes were also evaluated for irritation 1 hr after treatment

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

6 of each sex per group

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure:Ophthalmic observations were performed 7 days and 24 hr prior to the initial dose,on days 3, 7 and 14 (prior to daily dosing), and at the end of the study.

SCORING SYSTEM:Draize test
All eyes were scored for ocular irritation pretest (8 days, 24 hr and immediately prior to the initial dose) and approximately 24 hr after each treatment, prior to the next instillation of test material; on days 1, 3, 7, 14 and 21, the eyes were also evaluated for irritation 1 hr after treatment

TOOL USED TO ASSESS SCORE: Determined by gross ocular examination,slit-lamp biomicroscope (including examinations of fluorescein stain retention to evaluate integrity of the corneal epithelium) and indirect ophthalmoscope examination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 7 out of 12

Time point:

other: 3,4,7 and 8 days after 1 hr and 24 hr treatmennt

Score:

4

Max. score:

7

Reversibility:

not specified

Remarks on result:

other: Slight conjunctival redness seen in the eyes of both test and control animals throughout the study.

Results 2

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal: 6 out of 12

Time point:

other: 1,3 and 4 days after 1 hr and 24 hr treatment

Score:

1

Max. score:

6

Reversibility:

not specified

Remarks on result:

other: Slight conjunctival discharge seen in the eyes of both test and control animals throughout the study.

Results 3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 3, 7, 14, and 21 days

Score:

0

Max. score:

12

Reversibility:

not specified

Remarks on result:

other: All animals were free of significant signs of ocular irritation.All animals were free of significant signs of eye staining and partial embedment.

Irritant / corrosive response data:

No lethality or significant clinical signs, and no substance-related weight change were observed. Except slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed.

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Conclusions:

No lethality or significant clinical signs, and no substance-related weight change were observed. Except slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed.
Hence, FD&C Yellow No.5 (tartrazine) was not expected to cause any irritant effects following repeated exposure to rabbit eyes.

Executive summary:

A study was performed to evaluate the staining, embedment and ocular irritation potential of Tartrazine (FD & C Yellow No. 5) in rabbits. The study was performed according to a modification of the Draize test (Draize, 1959).

Tartrazine (FD & C Yellow No. 5) was prepared daily as a 3% (w/v) suspension in aqueous vehicle containing 0.5% (w/v) hydroxypropyl methylcellulose and 0.25% (w/v) laureth -10 acetate.Tartrazine (FD & C Yellow No. 5) 3% w/v in aqueous vehicle was administered once daily, for a total of 21 days, to the conjunctival sac of the right eye of New Zealand White Rabbits (6 of each sex/ group) at a dose volume of 30µl. Control animals (6 of each sex) received 30/µl of the vehicle daily. Ocular irritation was determined according to a modification of the Draize test (Draize, 1959). Interpretation of observations and assignment of scores were consistent with those described by the Consumer Product Safety Commission (1972).All eyes were scored for ocular irritation pretest (8 days, 24 hr and immediately prior to the initial dose) and approximately 24 hr after each treatment, prior to the next instillation of test material; on days 1, 3, 7, 14 and 21, the eyes were also evaluated for irritation 1 hr after treatment. In addition, all readily observable ocular structures were evaluated for eye stain and particle embedment 24 hr after each treatment.

No lethality or significant clinical signs, and no substance-related weight change were observed. Except slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed.

Hence, FD&C Yellow  No.5 (tartrazine) was not expected to cause any irritant effects following repeated exposure to rabbit eyes.