Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Draize test

Deviations:

yes

Remarks:

no details

GLP compliance:

no

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:

C16H12N4O9S2.3Na

IUPAC Name:

trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate

Test material form:

solid: particulate/powder

Details on test material:

No data

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Body weights: 3 - 3.5 kg Source: commercial supplier (Summit View Farm, Hazelton, PA, USA)Acclimation in the test area for one week prior to the start of the trial.Rabbits were individually housed in stainless steel, wire mesh-floor cages in a room with a 12-hr light/dark cycle, maintained at 16-21°C and an average relative humidity of 38%. All animals were supplied with water ad lib; feed (Certified Lab Rabbit Chow HF; Purina No. 5325) was limited to 125g/day. All animals were acclimatized for at least 2 wk prior to the start of the study at which time only healthy animals of the normal weight range found to be free from ocular irritation or damage (i.e. as determined by gross ocular examination, slit-lamp biomicroscope and indirect ophthalmoscope examination) were used for administration of test and control materials. All animals were checked for viability twice daily. Currently acceptable practices of good animal husbandry were adhered to throughout the study (NIH, 1985).

Test system

Vehicle:

other: 0.5% (w/v) hydroxypropyl methylcellulose (Methocel 90 HG, premium, 15,000 cps; Dow Chemical, Midland, MI, USA) and 0.25% (w/v) laureth°10 acetate (Solulan 98; Amerchol Corp., Edison, NJ, USA), using sterile technique and materials.

Controls:

other: the right eye serves as control

Amount / concentration applied:

10 µl of a 10% solution of the test substance (test solution: 3 %)The maximum volume capacity of the rabbit conjunctival sac is 10-30 µl (Crai et al., 1973). The maximum volume capacity of the human conjunctival sac with blinking is 10 µl (Ehlers, 1976; Wright and Meger, 1962), whereas a volume of 30µlis considered to be the maximum capacity of the human conjunctival sac in the absence of blinking (Mishima et al., 1966), and therefore represents the maximum likely accidental exposure to finished product applied to the eye area.

Duration of treatment / exposure:

1 seconds

Observation period (in vivo):

up to 21 days

Number of animals or in vitro replicates:

12 (6 males / 6 females)

Details on study design:

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. The degree of ocular staining was scored (following rinsing of residual material where necessary) and noted. 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. Both eyes of all animals were examined by slit-lamp bimicroscopy (including examinations of fluorescein stain retention to evaluate integrity of the corneal epithelium). Indirect ophthalmoscopic examinations (using 1% tropicamide as mydriatic) were performed on both eyes.SCORING SYSTEM: The ocular reactions were scored by the criteris of Consumer Product Safety Commission (1972).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

0

Reversibility:

not specified

Results 2

Irritation parameter:

conjunctivae score

Time point:

48 h

Remarks on result:

not measured/tested

Results 3

Irritation parameter:

conjunctivae score

Time point:

72 h

Remarks on result:

not measured/tested

Results 4

Irritation parameter:

cornea opacity score

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Results 5

Irritation parameter:

iris score

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Results 6

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Evaluation of eye irritation: All animals were free of significant signs of ocular irritation other than slight conjunctival redness (score of 1) or discharge (score of 1 or 2) seen sporadically in the eyes of both test and control animals throughout the study.Evaluation of eye staining and embedment: All animals were free of significant signs of eye staining and partial embedment.Ophthalmoscopic examinations. Most animals were free of ocular abnormalities in the test eye. One female rabbit in Group III (treatedwith FD & C Blue No. 1) exhibited focal injection of conjunctival blood vessels in the test eye at the end of the study. In the opinion of the study ophthalmologist, this finding did not appear to be of clinical importance.

Other effects:

Body weight: All animals survived and were free of significant clinical signs throughout the study. Most animals gained weight; single animals in both control and treated groups lost weight at one or more intervals but subsequently gained weight by the end of the study. One male rabbit in Group II (treated with FD & C Yellow No. 5) and one male rabbit in Group III (treated with FD & C Blue No.l) exhibited slight net weight losses over the 21 days of study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The tested substance needs to be considered not irritant for rabbits eyes under Regulation 1272/2008.

Executive summary:

All animals were free of significant signs of ocular irritation other than slight conjunctival redness (score of 1) or discharge (score of 1 or 2) seen sporadically in the eyes of both test and control animals throughout the study.

The tested substance is considered to be not irritant for the rabbits eyes based on the results under Regulation 1272/2008.