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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The purpose of this study was to evaluate whether washing with distilled water or 0.85% saline would diminish or enhance the eye irritation caused by the test material in the rabbit. One-tenth milliliter of undiluted test material was applied to the cornea of the left eye of male New Zealand White rabbits (2 rabbits per group). The treated eyes of one group of rabbits received no further treatment after dosing. The treated eyes of the remaining four groups of rabbits were irrigated with either distilled water or 0.85% saline beginning either 4 or 30 seconds after dosing. The degree of eye irritation for each animal was scored according to Draize's procedure at 24, 48, and 74 hr and at 7, 14, and 21 days.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Animals, Denver, pennsylvania, USA
- Age at study initiation: not reported
- Weight at study initiation: not reported
- Housing: 1/cage in stainless steel cages
- Diet (e.g. ad libitum): ad libitum; Purina laboratory rabbit chow high fiber
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 13 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3 degrees C
- Humidity (%): not reported, but was monitored continuously
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark


IN-LIFE DATES: From: March 19, 1986 To: May 6, 1986

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Only one eye of each animal was treated; the other eye served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): none


VEHICLE not applicable, no vehicle
Duration of treatment / exposure:
Group 6 remained unwashed; groups 7 to 10: 4 or 30 seconds
Observation period (in vivo):
24, 48 and 72 hours and at 7, 14 and 21 days post exposure
Number of animals or in vitro replicates:
10
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye of group 6 was unwashed. The treated eyes of groups 7 and 8 were irrigated with distilled water for 60 seconds beginning 4 or 30 seconds after dosing. The treated eyes of groups 9 and 10 were irrigated with 0.85% saline for approximately 60 seconds beginning 4 or 30 seconds after dosing.
- Time after start of exposure: 4 or 30 seconds after dosing in groups 7 to 10


SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein- 2% sodium fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 h
Score:
37
Max. score:
80
Remarks on result:
other: unwashed eyes
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
4.2
Max. score:
10
Remarks on result:
other: unwashed eyes
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
19
Max. score:
20
Remarks on result:
other: unwashed eyes
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 h
Score:
19.2
Max. score:
80
Remarks on result:
other: washed for 30 sec with distilled water
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
4.2
Max. score:
10
Remarks on result:
other: Washed for 30 sec with distilled water
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
18.3
Max. score:
20
Remarks on result:
other: washed for 30 sec with distilled water
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 h
Score:
33.3
Max. score:
80
Remarks on result:
other: washed for 30 sec with 0.85% saline
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
4.2
Max. score:
10
Remarks on result:
other: washed for 30 sec with 0.85% saline
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
17
Max. score:
20
Remarks on result:
other: washed for 30 sec with 0.85% saline
Irritant / corrosive response data:
In rabbits dosed with the test material and receiving no further treatment (i.e., unwashed eyes), both rabbits exhibited corneal, iridal, and conjunctival effects at 24 hr. Conjunctival and iridal effects were no longer present at Day 14. Corneal effects were still present by Day 21. In addition, blood vessels extending onto the cornea, blanched nictitating membrane, eschar on eyelids, bulging of the cornea, and hair loss around the treated eye were observed during the 21-day observation period. In groups receiving a distilled water or saline wash 4 seconds after treatment with the test material, both animals in each group exhibited corneal, iridal, and conjunctival effects at 24 hr. Iridal and conjunctival effects in animals washed with distilled water 4 seconds after dosing were recovered by Day 7 and 14, respectively. Iridal and conjunctival effects in animals washed with saline 4 seconds after dosing were recovered by 72 hr and Day 14, respectively. Corneal effects were present at 21 days in both groups. In addition, blood vessels extending onto the cornea, blanched nictitating membrane, hair loss around the treated eye and eyelids pinched together at corners were observed during the 21-day observation period. In groups receiving a distilled water or saline was 30 seconds after treatment with the test material, both animals in each group exhibited corneal, iridal, and conjunctival effects at 24 hr. Iridal and conjunctival effects in animals washed with distilled water 30 seconds after dosing were recovered by Day 7 and 14, respectively. Iridal and conjunctival effects in animals washed with saline 30 seconds after dosing were recovered by Day 7 and Day 21, respectively. Corneal effects were present at 21 days in both groups. In addition, circumcorneal blood vessels, blanched nictitating membrane, hair loss around eye, eschar on eyelids, bulging of the cornea, and eyelids pinched together at corners were observed during the 21-day observation period
Other effects:
In rabbits dosed with the test material and receiving no further treatment (i.e., unwashed eyes), blood vessels extending onto the cornea, blanched nictitating membrane, eschar on eyelids, bulging of the cornea, and hair loss around the treated eye were observed during the 21-day observation period. In groups receiving a distilled water or saline wash 4 seconds after treatment with the test material, blood vessels extending onto the cornea, blanched nictitating membrane, hair loss around the treated eye and eyelids pinched together at corners were observed during the 21-day observation period. In groups receiving a distilled water or saline was 30 seconds after treatment with the test material, circumcorneal blood vessels, blanched nictitating membrane, hair loss around eye, eschar on eyelids, bulging of the cornea, and eyelids pinched together at corners were observed during the 21-day observation period

Any other information on results incl. tables

  Group  10  10 
Time  Structure  Unwashed  Unwashed  4 seconds distilled water  4 seconds distilled water  30 seconds distilled water  30 seconds distilled water  4 seconds 0.85% saline  4 seconds 0.85% saline  30 seconds 0.85% saline  30 seconds 0.85% saline 
24 hours  Cornea  20  40  20  20  20  20  20  20  20  20 
24 hours  Iris 
24 hours  Conjunctivae  20 a  20 a  20 a  20 a  20 a  16 a  14 a  20 a  18 a  18 a 
48 hours  Cornea  40  40  20  20  20  20  10  20  40  40 
48 hours  Iris  2.5  2.5  2.5  2.5 
48 hours  Conjunctivae  20 a  20 a  18 a  20 a  20 a  18 a  12  16  14 a  20 a 
72 hours  Cornea  40  40  20  20  20   15  10  20  40  40 
72 hours  Iris  2.5  2.5  2.5 
72 hours  Conjunctivae  18 a  18 a  18 a  18  18 a  18  16  14 a  20 a 
7 day  Cornea  40 b  40 b  40 b  20 b  40 b  0 bf  0 k  10  15 bce  60 j 
7 day  Iris  2.5 
7 day  Conjunctivae  8.0 cd  8 cd  8 e  4 cd  12 acd  4 cd  10  16 acde 
14 day  Cornea  30 bh  15 b  10 b  10 b  10 bh  0 bi  0 m  0 kb  0 bm  60 j 
14 day  Iris 
14 day  Conjunctivae  0 c  0 c  0 c  0 c  0 c  0 c  0 d  0 c  6 c 
21 day  Cornea  20 bh  0 f  0 f  10  10 b  0 i  0 m  0 m  0 bm  40 l 
21 day  Iris 
21 day  Conjunctivae  0 c  0 c  0 c  0 c 

a a) Nictating membrane blanched b) Blood vessels approximately 1 -3 mm in length extended onto the cornea c) Hair loss around the treated eye d) Eschar on eyelids e) Eyelids pinched together at corners f) After application of 2.0% sodium fluorescein the entire cornea appeared hazy. This finding was judged to be treatment related. h) Cornea appears to bulge above the surface approximately 3 mm. i) After application of 2.0% sodium fluorescein, a 2 x 3 mm area appeared hazy in the center of the cornea. This finding was judged to be treatment related. j) Circumcorneal blood vessels approx. 1 -3 mm in length on cornea. k) After application of 2.0% sodium fluorescein a slight haze appeared on the cornea. This finding was judged to be treatment related. l) Circumcorneal blood vessels approx. 4 -6 mm in length on cornea. m) After application of 2.0% sodium fluorescein, 50% of the cornea appeared hazy. This finding was judged to be treatment related.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
The test material produced severe eye irritation. When compared to unwashed treated eyes, washing with either water or saline 4 or 30 seconds after treatment resulted in no significant increases or decreases in the corneal, iridal, or conjunctival effects.
Executive summary:

The purpose of this study was to evaluate whether washing with distiled water or 0.85% saline would diminish or enhance the eye irritation caused by the test material in the rabbit. One-tenth milliliter of undiluted test material was applied tot he cornea of the left eye of male New Zealand White rabbits (2 rabbits per group). The treated eyes of one group of rabbits received no further treatment after dosing. The treated eyes of one group of rabbits received no further treatment after dosing. The treated eyes of the remaining four groups of rabbits were irrigated with either distilled water or 0.85% saline beginning either 4 or 30 seconds after dosing. The degree of eye irritation for each animal was scored according to Draize procedure at 24, 48 and 72 hr and 7, 14 and 21 days after dosing.

The test material produced severe eye irritation. When compared to unwashed treated eyes, washing with either water or saline 4 or 30 seconds after treatment resulted in no significant increase or decrease in the corneal, iridal or conjunctival effects.