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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: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: WTP-101
Deviations:
yes
Remarks:
Please see details below.
Principles of method if other than guideline:
Species: New Zealand White rabbit
Exposure: A single one tenth gram of actual undiluted material was placed in the right eye of nine rabbits (6 male and 3 female).
Examinations: Irritation potential.


1. Because it took about 60 seconds to instill the total volume of test substance, washing occurred at 60 seconds instead of 30 seconds after
instillation began.
2. Due to a mix up, animal 1101-04 had his eye washed about 8 minutes after instillation, rather than 30 seconds.
3. Animals were received on 10 March instead of 24 March (date assigned by protocol) so that pretreatment adaptation period would be increased.

These deviations did not materially affect the outoome of the study or its validity.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Camm Research Institute, Inc.
- Age at study initiation: No data
- Weight at study initiation: 2.6 to 3.2 kg.
- Housing: Individual hanging-type stainless steel cage.
- Diet: ad libitum, Purina Lab Rabbit Chow 5321
- Water: ad libitum, Tap water, Edstrom automatic watering system
- Acclimation period: 27-days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.8° - 21.2°C (setpoint 20° + 1.2°C) except for 2 days when the recorder shifted to read 17.6°C before it was corrected.
- Humidity (%): The humidity remained within the acoeptable 40-70% range except once when it rose to 74% for 1/4 hour and another day when it fluctuated between 30 and 40% for several hours.
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye was not treated and served as a comparative control.
Amount / concentration applied:
TEST MATERIAL
Approximately one-tenth gram of the test material was instilled into the right eye of each rabbit. Because one-tenth gram of this material was so large in
volume, some difficulty was encountered in getting the entire amount into the eye. In most cases, small amounts were lost but the amounts were not
considered significant when compared to the total volume (estimated loss of 1-3 mg/100 mg).
Duration of treatment / exposure:
Approximately one-tenth gram of the test material was instilled into the right eye of each rabbit. The eye was held closed for a few seconds to allow for dispersion of the material over the surface of the globe.

Three males whose eyes were designated to be washed had their eye was flushed with approximately 300 ml of tap water (at room temperature)
approximately 60 seconds after instillation of the test material.

The remaining animals eyes were left unwashed.

Observation period (in vivo):
Observations were made at 1, 24, 48, and 72 hours, and at 7 and 14 days after treatment.
Number of animals or in vitro replicates:
9 animals (6 males, 3 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
Three males whose eyes were designated to be washed had their eye was flushed with approximately 300 ml of tap water (at room temperature)
approximately 60 seconds after instillation of the test material.

The remaining animals eyes were left unwashed.

SCORING SYSTEM: At each observation interval, the cornea, iris, and conjunctiva were scored for irritation according to the criteria of Draize:

Cornea
Opacity (A) - degree of density (area which is most dense is read). Grade

Scattered or diffuse area, details of iris clearly visible. 1
Easily discernible translucent areas, details of iris slightly obscured. 2
Opalescent areas, no details of iris visible, size of pupil barely discernible. 3
Opaque, iris invisible. 4

Area of Cornea Involved (B)
One quarter (or less) but not zero. 1
Greater than one-quarter but less than one-half. 2
Greater than one-half but less than three-quarters. 3
Greater than three-quarters, up to whole area. 4

Score equals A x B x 5 Maximum = 80

Iris
Values
Folds above normal, congestion, swelling, circumcorneal 1
injection (any or all of these or a combination of any
thereof), iris still reacting to light (sluggish reaction
is positive).
No reaction to light, hemorrhage, gross destruction (any or all of these). 2

Score equals Value x 5 Maximum = 10

Conjunctiva
Redness (C)
Redness - refers to palpebral conjunctiva only. 1
Vessels definitely injected above normal.
More diffuse, deeper crimson red, individual vessels not 2
easily discernible.
Diffuse, beefy red. 3

Chemosis (D)
Any swelling above normal (includes nictitating membrane). 1
Obvious swelling with partial eversion of the lids. 2
Swelling with lids about half-closed. 3
Swelling with lids about half-closed to completely closed. 4

Discharge (E)
Any amount different from normal (does not include small 1
amount observed in inner canthus of normal animals).
Discharge with moistening of the lids and hairs just adjacent to the lids. 2
Discharge with moistening of the lids and hairs and considerable area 3
around eye.

Score equals (C + D + E) x 2 Maximum = 20

Note: A reading of "normal" in any of the above categories (cornea, iris, conjunctiva) is given a grade of 0.

Total Score equals Cornea score + Iris soore + Conjunctiva score.
Total Maximum score = 110.

TOOL USED TO ASSESS SCORE: 1% ophthalmic fluoroscein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(Opacity)
Basis:
other: range between 3 animals (males 101-02, 101-08 & 101-10)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0.33 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 7 days (101-02), 48 hours (101-08 & 101-10)
Remarks on result:
other: Scores, 1, 0.33 & 0.33 respectively.
Irritation parameter:
cornea opacity score
Remarks:
(Opacity)
Basis:
other: range between 3 animals (females 101-01, 101-07 & 101-11)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 14 days (101-11), 7 days (101-01) and no effects noted (101-07)
Remarks on result:
other: Scores, 1, 0 & 1 respectively.
Irritation parameter:
iris score
Basis:
other: range between 3 animals (male 101-02, 101-08 & 101-01)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0 - <= 1
Max. score:
2
Reversibility:
fully reversible within: 7 days (101-02), no effects noted in remaining animals.
Remarks on result:
other: Scores, 1, 0 & 0 respectively.
Irritation parameter:
iris score
Basis:
other: range between 3 animals (females 101-01, 101-07 & 101-11)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0 - <= 1
Max. score:
2
Reversibility:
fully reversible within: 7 days (101-11), 48 hours (101-01), no effects noted in remaining animal.
Remarks on result:
other: Scores, 0.33, 0 & 1 respectively.
Irritation parameter:
conjunctivae score
Remarks:
(Redness)
Basis:
other: range between 3 animals (male 101-02, 101-08 & 101-01)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0.66 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 14 days (101-02 & 101-10) & 48 hours (101-08)
Remarks on result:
other: Scores, 2, 0.66 & 1 respectively.
Irritation parameter:
conjunctivae score
Remarks:
(Redness)
Basis:
other: range between 3 animals (females 101-01, 101-07 & 101-11)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 1.66 - 2
Max. score:
3
Reversibility:
fully reversible within: 14 days (101-11) & 7 days (remaining animals).
Remarks on result:
other: Scores, 2, 1.66 & 2 respectively.
Irritation parameter:
chemosis score
Basis:
other: range between 3 animals (male 101-02, 101-08 & 101-01)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0.33 - <= 1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days (101-02), 72 hours (101-10) & 48 hours (101-08).
Remarks on result:
other: Scores, 1.33, 0.33 & 0.66 respectively.
Irritation parameter:
chemosis score
Basis:
other: range between 3 animals (females 101-01, 101-07 & 101-11)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0.66 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 14 days (101-11) & 7 days remaining animals.
Remarks on result:
other: Scores 2, 0.66 & 1.66 respectively.
Irritation parameter:
cornea opacity score
Remarks:
(Opacity)
Basis:
other: range between 3 animals (males 101-04, 101-06 and 101-12)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0 - <= 0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours (101-04), no effects noted in remaining animals.
Remarks on result:
other: Scores, 0.33, 0 & 0 respectively. Eye flushed with tap water 30 seconds after exposure.
Irritation parameter:
iris score
Basis:
other: range between 3 animals (males 101-04, 101-06 and 101-12)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0 - <= 0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours (101-04), no effects noted in remaining animals.
Remarks on result:
other: Scores, 0.33, 0 & 0 respectively. Eye flushed with tap water 30 seconds after exposure.
Irritation parameter:
conjunctivae score
Remarks:
(Redness)
Basis:
other: range between 3 animals (males 101-04, 101-06 and 101-12)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0.33 - <= 1
Max. score:
3
Reversibility:
fully reversible within: 7 days (101-04) & 48 hours (101-06 & 101-12). Redness noted at 14 days (101-12).
Remarks on result:
other: Scores, 1, 0.33 & 0.33 respectively. Eye flushed with tap water 30 seconds after exposure.
Irritation parameter:
chemosis score
Basis:
other: range between 3 animals (males 101-04, 101-06 and 101-12)
Time point:
other: mean of 24, 48 and 72 hours
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 72 hours (101-04), 48 hours (101-06), no effects noted in remaining animal.
Remarks on result:
other: Scores, 1, 0.33 & 0 respectively. Eye flushed with tap water 30 seconds after exposure.
Irritant / corrosive response data:
Based on the scoring methods and classifications, a maximum mean total irritation score of 18.8 out of a possible maximum of 110.0 was observed for non washed eyes at 24 hours following treatment. A maximum mean irritation score of 10.0 was seen for washed eyes 24 hours after treatment, washing the eyes with water therefore provided slight protection against irritation. According to the eye irritation classification system, Crude Catalyst 32899 is categorized as "moderately irritating" to the rabbit eye.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the Draize method a maximum mean total irritation score of 18.8 out of a possible maximum of 110.0 was observed for nonwashed eyes at 24 hours
following treatment.
A maximum mean irritation score of 10.0 was seen for washed eyes 24 hours after treatment, washing the eyes with water therefore provided slight protection against irritation.

Based on this the eye irritation of Crude Catalyst 32899 can be categorized as "moderately irritating" to the rabbit eye using Draize scoring.

The test material, Crude Catalyst 32899, was found to be non-irritant to rabbit eyes.
Executive summary:

The objective of the study was to evaluate the eye irritation potential of Crude Catalyst 32899 in nine New zealand white rabbits. One tenth gram of actual undiluted material was placed into the right eye of 3 male and 3 female rabbits. The eyes of an additional group of 3 male rabbits were flushed with tap water 30 seconds after exposure. The eyes were examined and scored for irritation one hour and 1, 2, 3, 7, and 14 days after treatment. Crude Catalyst 32899 was found to be "moderately irritating" to the nonwashed rabbit eye with a maximum mean irritation score of 18.8 (maximum of 110) seen 24 hours after exposure. The maximum mean irritation score for washed eyes was 10.0 seen 24 hours after exposure, washing the eyes with water therefore provided slight protection against irritation.