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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Non GLP, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.42
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Metanilic acid wet

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: der Lippischen Versuchstierzucht, Extertal, Germany
- Weight at study initiation: average 2.1 kg
- Housing: The animals were kept in individual cages
- Diet (e.g. ad libitum): animals received "mümmel z" (SSNIF, Soest, Germany) ad libitum.
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: 7 - 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12h light- / 12h dark cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: left, untreated eye
Amount / concentration applied:
100 µL
Duration of treatment / exposure:
8 days
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
6 male animals
Details on study design:
Test Procedure
The test was carried out using 6 rabbits that had been examined before and had an average weight of 2.1 kg. Treatment consisted of a single application of a
bulk volume of 100 µL of the amorphous test substance into the conjunctival sac of the lower right eyelid. Subsequently, the Iids were gently held together for 1 sec. The eye was not rinsed after application. The secend left eye of the animals remained always untreated as a control.
The eyes were examined using an ophthalmoscope.
The finding on the cornea was verified by means of the fluorescein test (instillation of 1 drop in an ophthalmological preparation directly onto the cornea. After rinsing with physiological saline, corneal damage appears yellowish green. UV light or cobalt blue filter).

Observations were made 24, 48 and 72 h and 8 days after the start of the experiment. The observations after 8 days were not included in the evaluation of the irritation index.

SCORING:
The pathological findings on the cornea (according to the degree and area of opacity), iris and conjunctivae (according to redness, swelling and discharge) were assessed. ln detail, the assessment was carried out on the basis of the scale that was used for determining the irritation index..
Scoring system used from: The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, 1959, p .5 1

1) Cornea
(A) Opacity- degree of density (area most dense taken for reading)
- No opacity; 0
- 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

(B) Area of cornea involved
- One quarter (or less) but not zero; 1
- Greater than one quarter but less than half; 2
- Greater than half but less than three quarters; 3
- Greater than three quarters, up to whole area; 4
A x B x 5 Maximum = 80

2)Iris - iris
(A) Values
- Normal; 0
- Felds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive); 1
- No reaction to light, hemorrhage, gross destruction (any or all of these); 2
A x 5 maximum value = 10


3) Conjunctivae
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
- normal vessels; 0
- Vessels injected clearly; 1
- More diffuse, deeper crimson red, individual vessels not easily discernible; 2
- Diffuse beefy red; 3
(B) Chemosis
- No swelling; 0
- Any swelling above normal (includes nictitating membrane); 1
- Obvious swelling with partial eversion of Iids; 2
- Swelling with Iids about half closed; 3
- Swelling with Iids about half closed to completely 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 Iids and hairs just adjacent to Iids; 2
- Discharge with moistening of the Iids and hairs, and considerable area areund the eye; 3
(A + B + C) x 2 Maximum value = 20

The indices of irritation to the (1) cornea (0- 80), (2) iris (0 - 10) and (3) conjunctivae (0- 20), altogether 0 - 110, recorded after 24, 48 and 72 hours are added for all 6 animals. The total score is divided by 18 to give the primary irritation to the eye.

Classification
0-10 not irritating
11-25 slightly irritating
26-56 moderately irritating
57-110 severely irritating

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours, 8 days
Score:
0
Max. score:
80
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours, 8 days
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 hours
Score:
8
Max. score:
20
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 hours
Score:
6
Max. score:
20
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 hours
Score:
1.67
Max. score:
20
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 8 days
Score:
0
Max. score:
20
Irritation parameter:
other: primary irritation index
Basis:
mean
Time point:
other: 24-72 hours
Score:
5.2
Max. score:
110

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU