Hydrogen [4-[4-(diethylamino)-5'-hydroxy-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, monosodium salt

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 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

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

Test material information

Constituent 1

Reference substance name:

Dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)]amino]-2'-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt

EC Number:

223-339-8

EC Name:

Dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)]amino]-2'-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt

Cas Number:

3844-45-9

Molecular formula:

C37H34N2Na2O9S3

IUPAC Name:

disodium 2-({4-[ethyl(3-sulfonatobenzyl)amino]phenyl}{4-[ethyl(3-sulfonatobenzyl)iminio]cyclohexa-2,5-dien-1-ylidene}methyl)benzenesulfonate

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.