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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:
key study
Study period:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented, according to accepted guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
study terminated at 14 days instead of 21 with complete revisibility only seen in 3 of 6 animals
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MRD-86-962
- Physical state: liquid
- Analytical purity: 100%
- Lot/batch No.: 1
- Storage condition of test material: room temperate

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Inc. Denver, Pennsylvania
- Age at study initiation: 12 weeks
- Weight at study initiation: 2.25 to 3.06 kg
- Housing: Individual in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina certified rabbit chow ad libitum
- Water (e.g. ad libitum): Automatic watering system (Elizabethtown watering company) ad libitum
- Acclimation period: 13 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light):12/12


IN-LIFE DATES: From: June/July 1986 To: September 29-1986

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100%

Duration of treatment / exposure:
Single treatment
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3/sex/group
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): none


SCORING SYSTEM: Draize Scale

I. CONJUNCTIVAE

A. Redness (refers to palpebral and bulbar conjunctivae
excluding cornea and iris)
Vessels normal 0
Some vessels definitely injected 1
Diffuse, crimson red, individual vessels not easily discernible 2
Diffuse beefy red 3

Q. Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

C. Discharge
No discharge 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids
Discharge with moistening of the lids and hairs, and considerable area around eye 3

D. Necrosis or ulceration of palpebral and bulbar
conjunctivae or nictitating membranes

Not present 0*
Necrosis present N*
Ulceration present U*
Conjunctivae Score: (A + B + C) X 2 (maximum = 20)
* - Not included in Draize grading system

II. IRIS
A. Values
Normal 0
Markedly deepened folds, congestion, swelling, circumcorneal injection (any of these), iris still reacting to light (sluggish reaction is positive).1
No reaction to light, hemorrhage, gross destruction (any of these) 2
Iris Score: A X 5 (maximum = 10)

III. CORNEA

A. Opacity-degree of density (area most dense)
No opacity 0
Slight dulling of the normal luster +*
Scattered or diffuse areas of opacity, details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured.. 2
Nacreous areas, no details of iris visible, size of pupil barely discernible 3
Complete corneal opacity, iris not discernible 4

B. Area of cornea involved
Up to one quarter 1
Greater than one quarter, less than half 2
Greater than half, less than three quarters 3
Greater than three quarters .4

C. Stippling-area of pinpoint roughening
No stippling 0*
Up to one quarter 1*
Greater than one quarter, less than half 2*
Greater than half, less than three quarters 3*
Greater than three quarters 4*

D. Ulceration-absence of area of corneal epithelium
No ulceration P*
Up to one quarter :, 1*
Greater than one quarter, less than half 2*
Greater than half, less than three quarters 3*
Greater than three quarters 4*
Corneal Score: A X B X 5 (maximum = 80)
* - Not included in Draize grading system


TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
other: 24 hour
Score:
ca. 23
Max. score:
110
Reversibility:
not fully reversible within: 24 hours
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #2
Time point:
other: 24 hours
Score:
ca. 23
Max. score:
110
Reversibility:
not fully reversible within: 24 hours
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #3
Time point:
other: 24 hours
Score:
ca. 19
Max. score:
110
Reversibility:
not fully reversible within: 24 hours
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #4
Time point:
other: 24 hours
Score:
ca. 8
Max. score:
110
Reversibility:
not fully reversible within: 24 hours
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #5
Time point:
other: 24 hours
Score:
ca. 23
Max. score:
110
Reversibility:
not fully reversible within: 24 hours
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #6
Time point:
other: 24 hours
Score:
ca. 25
Max. score:
110
Reversibility:
not fully reversible within: 24 hours
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
other: 14 days
Score:
ca. 2
Max. score:
110
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: study terminated at 14 days, however trend of reversibility was observed
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #2
Time point:
other: 14 days
Score:
ca. 0
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #3
Time point:
other: 14 days
Score:
ca. 0
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #4
Time point:
other: 14 days
Score:
ca. 2
Max. score:
110
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: study terminated at 14 days, however trend of reversibility was observed
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #5
Time point:
other: 14 days
Score:
ca. 2
Max. score:
110
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: study terminated at 14 days, however trend of reversibility was observed
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #6
Time point:
other: 14 days
Score:
ca. 0
Max. score:
110
Reversibility:
fully reversible
Irritant / corrosive response data:
Ocular instillation of MRD-86-962 elicited conjunctival, corneal and iridial responses in all animals.
Conjunctival responses included redness, chemosis, clear/white discharge and conjunctival ulceration. Redness was noted in all animals from the 1 Hour observation through the Day 10 observation. The incidence of redness decreased after these observations and three animals were noted with redness at the Day 14 observation. Chemosis was noted in all animals from the 1 Hour observation through the 48 Hour observation. The incidence of chemosis declined after these observations and chemosis was not noted at the Day 14 observation. Clear and/or white discharge was noted in all animals at the 1 and 4 Hour observations. The incidence of discharge decreased after these observations and no discharge was noted by the Day 4 observation. Conjunctival ulceration was noted in five animals during the study.
Iridial responses were noted in all animals during the study with varying incidences at the different observation intervals. Iridial responses were not noted after the Day 7 observation.
Corneal responses included opacity, stippling and corneal ulceration. Corneal opacity was noted in five animals, stippling was noted in five animals and corneal ulceration was noted in all animals during the study. All animals were clear of corneal responses by Day 7.
Other observations noted during the study included dye retention of the nictitating membrane and conjunctiva, and conjunctival blistering.
Ocular irritation was most prominent from the 1 Hour through the Day 4 observations where the total Draize score ranged from 4 to 25.

Any other information on results incl. tables

Animal

Effect

24 hrs

48 hrs

72 hrs

24-72hr avg

4 days

7 days

10 days

14 days

1

Cornea

4

4

3

3.67

1

0

0

0

Iris

1

1

1

1.00

0

0

0

0

Redness

3

3

3

3.00

3

2

1

1

Chemosis

3

3

3

3.00

1

1

1

0

2

Cornea

4

2

0

2.00

0

0

0

0

Iris

1

1

0

0.67

0

0

0

0

Redness

3

3

3

3.00

3

1

1

0

Chemosis

3

3

2

2.67

1

1

0

0

3

Cornea

3

2

0

1.67

0

0

0

0

Iris

1

1

1

1.00

0

0

0

0

Redness

3

3

3

3.00

3

1

1

0

Chemosis

2

1

1

1.33

1

1

0

0

4

Cornea

0

0

0

0.00

0

0

0

0

Iris

1

1

0

0.67

0

0

0

0

Redness

3

3

3

3.00

3

1

1

1

Chemosis

1

1

0

0.67

1

0

0

0

5

Cornea

4

3

2

3.00

0

0

0

0

Iris

1

1

1

1.00

1

1

0

0

Redness

3

3

3

3.00

3

2

1

1

Chemosis

3

2

1

2.00

1

1

0

0

6

Cornea

2

1

0

1.00

0

0

0

0

Iris

1

0

0

0.33

0

0

0

0

Redness

3

3

2

2.67

2

2

1

0

Chemosis

4

2

1

2.33

0

0

0

0

6-animal averages:   Cornea

Iris

Redness

Chemosis

1.89

6 animals
not

fully

reversed

6 animals
not

fully

reversed

6 animals
not

fully

reversed

3 animals
not

fully

reversed

Applicant's summary and conclusion

Interpretation of results:
Category II
Remarks:
Migrated information Causes serious eye irritation Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Executive summary:

The results demonstrate a trend in reversibility; however, the study was ended at the day 14 instead of day 21 and full reversibility may have been observed at day 21.