Santicizer 2148

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-11-14 to 1990-01-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

not specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Phenol

EC Number:

203-632-7

EC Name:

Phenol

Cas Number:

108-95-2

Molecular formula:

C6H6O

IUPAC Name:

phenol

Constituent 2

Reference substance name:

1-chlorododecane

Molecular formula:

C12H25Cl

IUPAC Name:

1-chlorododecane

Constituent 3

Reference substance name:

1-Dodecanol

Cas Number:

112-53-8

Molecular formula:

C12H26O

IUPAC Name:

1-Dodecanol

Constituent 4

Reference substance name:

1-Tetradecanol

Cas Number:

112-72-1

Molecular formula:

C14H30O

IUPAC Name:

1-Tetradecanol

Constituent 5

Reference substance name:

triphenyl phosphate

Cas Number:

115-86-6

Molecular formula:

C18H15O4P

IUPAC Name:

triphenyl phosphate

Constituent 6

Reference substance name:

-

EC Number:

431-760-5

EC Name:

-

Cas Number:

27460-02-2

Molecular formula:

C24H35O4P

IUPAC Name:

dodecyl diphenyl phosphate

Constituent 7

Reference substance name:

diphenyl tetradecyl phosphate

Cas Number:

142474-86-0

Molecular formula:

C26H39O4P

IUPAC Name:

diphenyl tetradecyl phosphate

Constituent 8

Reference substance name:

Didodecyl phenyl phosphate

Cas Number:

56827-93-1

Molecular formula:

C30H55O4P

IUPAC Name:

Didodecyl phenyl phosphate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
Source: Monsanto Company
Lot/batch no: 4321285
Purity: Not stated/determined

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

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, Hazleton, Pennsylvania
- Age at study initiation: Young Adults
- Housing: Individually housed in suspended stainless steel cages with wire mesh bottom
- Diet (e.g. ad libitum): Lab rabbit chow HF ad libitum
- Water (e.g. ad libitum): Automatic watering system ad libitum
- Acclimation period: 62 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-21°C (given as 60-70°F)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IN-LIFE DATES: From: 14/11/89 To: 18/01/90

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

0.1 ml was introduced into the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for 1 second prior to releasing to prevent loss of material. No wash was performed after application, however, ~24 hours after application the treated eye was rinsed to remove any residual test material

Observation period (in vivo):

All animals were checked for viability twice daily.
Ocular irritation was evaluated at 1, 24, 48, and 72 hours after treatment.

Number of animals or in vitro replicates:

6 (4 males, 2 females)

Details on study design:

On the day before dosing, both eyes of each animal were examined using fluorescein dye to check for presence of corneal ulceration. Just prior to test material application, the eyes were examined again without fluorescein. Animals showing pre-existing corneal or conjunctival injury or irritation were not placed on study.

A single dose of 1 ml was administered to the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for 1 second prior to releasing to prevent loss of material. The left eye served as the control. The treated eyes were washed 24 hours after application to remove residual test material.

Scores were given for treated eyes according to EPA testing guidelines, included in appendix A of the report. "Eye irritation" is the production of reversible changes in the eye following application of test material to the anterior surface of the eye. "Eye corrosio" is the production of irreversible tissue damage in the eye following application of test material to the anterior surface of the eye. Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no stain retention for 2 observations.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #1

Remarks:

No. 8655

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #2

Remarks:

8659

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #3

Remarks:

8658

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #4

Remarks:

8659

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #5

Remarks:

8660

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #6

Remarks:

8661

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 7

Irritation parameter:

iris score

Basis:

mean

Remarks:

Animals 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

Animals 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

Animals 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Conjunctival irritation (redness, chemosis, discharge) in all animals at 1 hour, redness present in 1 male at 24 and 48 hours. 2 males exhibited slight dulling of cornea at 1 hour but recovered by 24 hours. No significant corneal or iridial changes were seen. All 6 animals were free of ocular irritation 24-72 hours after instillation of test material.

Any other information on results incl. tables

Scores are given for treated eyes. Unless otherwise noted, control (untreated) eyes had negative scores for all parameters. Scored according to scale presented in the scoring system presented in the section 'Any other information on materials and methods incl. tables'.

 

Table 1. Eye Irritation study in rabbits- individual ocular scores

	Time after Administration (Hours)
	1	24	48	72	Positive scores
Animal No. 8655 M
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.
A.	0	0	0	0	No
B.	0	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8657 M
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	1	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.
A.	+	0	0	0	No
B.	4	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8658 F
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.
A.	0	0	0	0	No
B.	0	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8659 M
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.
A.	0	0	0	0	No
B.	0	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8660 F
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3. Cornea
A.	0	0	0	0	No
B.	0	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8661 M
1.
A.	2	1	1	0	Yes
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.	Cornea
A.	+	0	0	0	No
B.	4	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No

f - Observation confirmed with fluorescein

M - Male

F - Female

 

Table 2. Summary of responses

	Positive (+) or Negative (-) Scores*
	Cornea		Iris	Conjunctivae
	Opacity	Ulceration		Redness	Chemosis	Necrosis or Ulceration
8655 M	-	-	-	-	-	-
8657 M	-	-	-	-	-	-
8658 F	-	-	-	-	-	-
8659 M	-	-	-	-	-	-
8660 F	-	-	-	-	-	-
8661 M	-	-	-	+	-	-

* = Reference for positive and negative scores: See scoring system presented in the section 'Any other information on materials and methods incl. tables'.

M - Male

F - Female

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

XP-2563 produced mild, transient ocular irritation.

Executive summary:

A key EPA OPPTS Guideline 81-4 study was conducted to evaluate the ocular irritation potential of the test material (XP-2563) in rabbits (Bio/dynamics Inc., 1990c). 0.1 mL of the test material was introduced into the lower conjunctival sac of the right eye of six New Zealand White albino rabbits (3/sex). The upper and lower eye lids were gently held together for one second prior to releasing to prevent loss of the test material. The contralateral eye served as the control.

No wash was performed subsequent to application but 24 hours post exposure, the treated eyes were rinsed to remove any residual test material. Eyes were evaluated and scored for ocular reactions at approximately 1, 24, 48, and 72 hours after treatment. Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24-hour observation and at each subsequent observation until there was no stain retention for two observations.

Irritation observed consisted primarily of conjunctival irritation (redness, chemosis, discharge) with most effects occurring at 1 hour. Two animals exhibited a slight dulling of the corneal surface but no significant corneal or iridial changes were observed. All six animals were free of ocular irritation within 24 to 72 hours post instillation of the test material.

It was concluded that the test material (XP-2563) produced mild, transient ocular irritation.