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Toxicological information

Eye irritation

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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 from peer reviewed journals

Data source

Reference
Reference Type:
publication
Title:
EVALUATION OF THE CUMULATIVE (REPEATED APPLICATION) EYE IRRITATION AND CORNEAL STAINING POTENTIAL OF THE TEST CHEMICALS
Author:
S.D Gettings et.al
Year:
1992
Bibliographic source:
Food and Chemical Toxicology, 1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: Modification of Draize method
Principles of method if other than guideline:
Ocular irritation was determined according to a modification of the Draize test (Draize, 1959). Test material (3%,wt./vol. 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.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report):FD&C Blue 1- IUPAC Name: Dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)]amino]-2'-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt- Molecular formula:C37H36N2O9S3.2Na- Molecular weight :792.86 g/mol- Substance type:Organic- Physical state:Solid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Sex: male and femaleTEST ANIMALS Source: Summit View Farm, Hazelton, PA, USA- Weight at study initiation: 3.0-3.5 kg- Housing: individually housed in stainless steel, wire mesh-floor cages.- Diet (e.g. ad libitum): Certified Lab Rabbit Chow HF; Purina No. 5325 ;ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: 2 weeksENVIRONMENTAL CONDITIONS- Temperature (°C): 16-21°C- Humidity (%): 38%- 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:
other: Vehicle control also untreated eye acted as control
Amount / concentration applied:
Test and vehicle control materials (30µl) were administered to the right eye of New Zealand White rabbits
Duration of treatment / exposure:
1 application/day
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
6 of each sex per group (Total 12)
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): no data- Ophthalmic observations: 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: 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 SafetyCommission (1972). All eyes were scored for ocularirritation pretest (8 days, 24 hr and immediately priorto the initial dose) and approximately 24 hr after eachtreatment, 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.TOOL USED TO ASSESS SCORE: slit-lamp bimicroscopy (including examinations of fluorescein stain retention to evaluate integrity of the corneal epithelium)

Results and discussion

In vivo

Results
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
21 d
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
All animals were free of significant signs of ocular irritation, staining and particle embedment.
Other effects:
All animals survived and were free of significant clinical signs of toxicity throughout the study. Ophthalmoscopic examinations revealed that all animals were free of abnormalities considered to be of clinical importance.

Any other information on results incl. tables

Table 3: Summary of ocular effects in evaluation of the (repeated application) eye irritation potential of the test chemical

 

Group

Eye

Observation

 

 

Test day

1

7

14

21

I - Control

Test eye

Conjunctivae

 

 

 

 

Redness --score of 1

-

-

-

-

Discharge--score of 1

1

-

1

-

I - Control

Control eye

Conjunctivae

 

 

 

 

Discharge – score of 1

1

-

1

-

Apparent hemorrhage

-

-

-

1

III- test chemical

Test eye

Conjunctivae

 

 

 

 

Redness --score of 1

-

-

2

1

Discharge--score of 1

5

2

1

-

III- test chemical

Control eye

Conjunctivae

 

 

 

 

Redness --score of 1

-

-

1

-

Chemosis--score of 1

-

-

1

-

 

 

 

 

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
Conclusions:
The test substance when administered once daily, for 21 days, to the conjunctival sac of the right eye of New Zealand White Rabbits at a dose volume of 30 µl showed no significant signs of ocular irritation, staining and particle embedment. All animals survived and were free of significant clinical signs of toxicity throughout the study. Thus it was considered that the test substance was not irritating to eyes.
Executive summary:

Ocular irritation potential of the test chemical was determined according to a modification of the Draize test (Draize, 1959).The test chemical 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.

It (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 ocularirritation pretest (8 days, 24 hr and immediately priorto 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.

All animals survived and were free of significant clinical signs of toxicity throughout the study.

Ophthalmoscopic examinations revealed that all animals were free of abnormalities, all animals were free of significant signs of ocular irritation, staining and particle embedment.Thus it was concluded that the test substance was not irritating to eyes.