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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:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report date:
1975

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
The procedure used was the test for eye irritants described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO). The test was performed on 3 male and 3 female rabbits of the Russian breed weighing 1.7 to 2.1 kg. The animals were housed individually in metal cages (overall dimensions 47 x 32 x 34 cm), were kept at a constant room temperature of 18 + 1 C°, at a relative humidity of 55 + 5% and on a 14 hour light cycle day. The animals had ad libitum access to standard rabbit food - NAFAG, Gossau SG - and water. Prior to treatment they were adapted to the laboratories for a minimum of 8 days. Only rabbits with normal ophthalmic findings were used for these tests.
The test material in an amount of 0.1 mL was inserted into the conjunctival sac of the left eye of the 6 rabbits and the lids were held open for a few seconds. The right eye was not treated and served as a control. In 3 of the 6 rabbits approximately 1 minute after treatment both eyes were rinsed with physiologic saline. The reactions were appraised with a slit lamp after 1 and 6 hours; 1; 2; 3, 6 and 8 days and scored for each individual rabbit.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-(2-heptadec-8-enyl-2-imidazolin-1-yl)ethanol
EC Number:
202-414-9
EC Name:
2-(2-heptadec-8-enyl-2-imidazolin-1-yl)ethanol
Cas Number:
95-38-5
Molecular formula:
C18H34N2O - C24H46N2O
IUPAC Name:
2-(2-heptadec-8-en-1-yl-4,5-dihydro-1H-imidazol-1-yl)ethanol
Constituent 2
Chemical structure
Reference substance name:
(Z)-2-(8-heptadecenyl)-4,5-dihydro-1H-imidazole-1-ethanol
EC Number:
244-501-4
EC Name:
(Z)-2-(8-heptadecenyl)-4,5-dihydro-1H-imidazole-1-ethanol
Cas Number:
21652-27-7
Molecular formula:
C22H42N2O
IUPAC Name:
2-(2-heptadec-8-en-1-yl-4,5-dihydro-1H-imidazol-1-yl)ethanol
Specific details on test material used for the study:
- Name of test material (as cited in study report): FAT 81 004/A
- Substance type: organic
- Physical state: liquid

Test animals / tissue source

Species:
rabbit
Strain:
other: Russian breed
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.7 to 2.1 kg
- Housing: individually in metal cages (overall dimensions 47 x 32 x 34 cm)
- Diet: standard rabbit food - NAFAG, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: A minimum of 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 +/- 1 °C
- Humidity: 55 +/- 5 %
- Photoperiod: 14 hour light cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
single administration
Observation period (in vivo):
Up to 8 days
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: In 3 of the 6 rabbits approximately 1 minute after treatment both eyes were rinsed with physiologic saline.
- Time after start of exposure: 1 minute

SCORING SYSTEM: 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 Total maximum = 80

Iris
A Values Normal 0
Folds 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 Total maximum = 10

Conjunctivae
A Redness- (refers to palpebral and bulbar conjunctivae excluding cornea and iris) Vessels normal 0
Vessels definitely injected above normal 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 lids 2
Swelling with lids about half closed 3
Swelling with lids 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 lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs, and considerable area around the eye 3
(A + B + C) X 2 Total maximum = 20

Calculation of the primary eye irritation index
The mean reaction scores for cornea, iris and conjunctiva observed after 6; 24 and 72 hours were summed up and the sum divided by 3.
This procedure was carried out separately for unrinsed (A) and rinsed (B) eyes respectively.
Index
0-10 minimal
11 - 25 moderate
26 - 55 slight
56 - 84 marked
above 84 extreme

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
2.9
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
other: primary irritation index in rinsed eyes
Basis:
mean
Time point:
other: 6, 24 and 72 hours
Score:
ca. 65.7
Reversibility:
not reversible
Remarks on result:
other: Rinsing the eyes following instillation was of practically no effect.
Irritation parameter:
other: primary irritation index in unrinsed eyes
Basis:
mean
Time point:
other: 6, 24 and 72 hours
Score:
ca. 74.1
Reversibility:
not reversible
Irritant / corrosive response data:
The substance is severly irritant to eyes.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Executive summary:

In an acute eye irritation/corrosion study, single samples of 0.1 mL of the undiluted test article were instilled into one eye of each of six rabbits. In three animals, the eyes were washed out after 1 minute. The reactions were appraised with a slit lamp after 1 and 6 hours; 1; 2; 3; 6 and 8 days and scored for each individual rabbit. Under the conditions of this experiment the test preparation was found to cause marked irritation when applied to the rabbit eye mucosa. The irritation consisted of conjunctival reaction, reflex hyperemia of the iris and corneal reactions. The effects were not reversible within 8 days. Rinsing the eyes following instillation was of practically no effect.