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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:
22nd July 1991 to 19th August 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Propargite
EC Number:
219-006-1
EC Name:
Propargite
Cas Number:
2312-35-8
Molecular formula:
C19H26O4S
IUPAC Name:
propargite
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Omite® Technical
- Stability under test conditions: at least one year at room temperature
- Storage condition of test material: sealed container at room temperature

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, USA
- Age at study initiation: young adult
- Weight at study initiation: 3072-3324 g
- Housing: individually suspended mesh-bottom cages
- Diet: Purina® Certified Rabbit Chow® #5322 ad libitum
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 66-76 ºF
- Humidity: 50-88 %
- Photoperiod: 12 hours light/12 hours dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Eyelid closed for approximately one second
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
1 male, 5 females
Details on study design:
OCULAR OBSERVATIONS
Both eyes of all rabbits were examined for ocular abnormalities prior to the study initiation. The pre-initiation examination included the use of sodium fluorescein and ultraviolet light.
Both eyes of all rabbits were examined macroscopically for ocular irritation using a hand-held penlight in accordance with the method of Draize at approximately 1, 24, 48 and 72 hours after dosing and at 4, 7, 10, 14, 17 and 21 days if irritation persisted. In addition, both eyes of all rabbits were further examined at 72 hours and 7, 10, 14, 17 and 21 days with sodium fluorescein and ultraviolet light.

SCORING SYSTEM:
(1) Cornea
(A) Opacity-degree of density
No ulceration or opacity 0
Dulling of normal luster,details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Nacerous areas, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through opacity 4

(B) Area of cornea involved
No ulceration or opacity 0
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

(2) Iris
(A) Values
Normal 0
Markedly deepened rugae, congestion, swelling, circumcorneal injection (any or all of these of combination of any thereof) 1
No reaction to light, haemorrhage, gross destruction (any or all) 2

(3) Conjunctivae
(A) redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Blood vessels normal 0
Some blood vessels definitely hyperemic (injected above) normal 1
Diffuse, deeper crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3

(B) Chemosis: kids and /or nicitating membranes
No swelling 0
Any swelling above normal 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 1
Discharge with moistening of the lids and hairs just adjacent to the lids 2
Discharge with moistening of the lids and hair and considerable area around the eye 3

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
1.9
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.39
Max. score:
2
Reversibility:
not fully reversible within: 10 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
2.94
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
Positive conjunctival reactions were observed in the treated eyes of all animals. Corneal and iridial reactions were observed in the right eye of three and four rabbits, respectively. Corneal and iridial irritation subsided by day 10 or earlier. Conjunctival irritation was seen in all six rabbits and subsided by day 21 or earlier. Conjunctival irritation only persisted to day 21 in three animals and this was considered to be minor and reversible (see Table 1). Mean scores of 2.9, 1.9, 0.39 and 0.22 can be calculated for conjunctival chemosis, conjunctival redness, iridial lesion and corneal opacity, respectively, for the six animals, based on individual irritancy scores at 24, 48 and 72 hours.
Other effects:
There were no mortalities or significant body weight changes.

Any other information on results incl. tables

Table 1: Individual ocular irritancy scores

 Animal (sex)  Tissue  1 h  24 h  48 h  72 h  4 d  7 d  10 d  14 d  17 d  21 d
 12701 (M)  Cornea (O-A)  0 0  0 0  0 0  0 0  0 0  1 1  0 0  0 0  0 0  0 0
   Iris  0  0  0  0  0  0  0  0  0  0
   Conjunctivae (R-C-D)  1 1 0  2 2 1  2 2 1  2 3 2  2 4 2  2 4 1  1 4 0  1 2 0  1 2 0  0 1 0
 12702 (F)  Cornea (O-A)  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0
   Iris  0  0  0  1  0  0  0  0  0  0
   Conjunctivae (R-C-D)  1 1 1  2 3 1  2 3 1  1 3 1  1 3 1  1 4 1  1 4 1  1 2 0  1 2 0  0 0 0
 12705 (F)  Cornea (O-A)  0 0  0 0  1 2  1 2  1 2  1 2  0 0  0 0  0 0 0 0
   Iris  0  1  1  1  1  1  0  0  0  0
   Conjunctivae (R-C-D)  1 1 1  2 2 2  2 4 2  2 4 1  2 4 1  1 4 1  1 4 1  1 2 0  1 2 0  1 1 0
 12716 (F)  Cornea (O-A)  0 0  0 0  0 0  0 0  0 0  0 0  NA  0 0  0 0 0 0
   Iris  0  0  0  0  0  0  NA  0  0  0
   Conjunctivae (R-C-D)  2 2 0  2 3 1  2 3 1  2 3 2  2 4 2  1 4 1  NA  1 2 0  0 1 0  0 0 0
 12722 (F)  Cornea (O-A)  0 0  0 0  1 1  1 2  1 2  1 2  0 0  0 0  0 0  0 0
   Iris  0  1  1  1  1  1  0  0  0  0
   Conjunctivae (R-C-D)  1 0 2  1 2 1  2 3 2  2 3 2  1 4 2  1 4 1  1 4 0  1 2 0  0 2 0  0 1 0
 12723 (F)  Cornea (O-A)  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0  0 0
   Iris  0  0  0  0  0  1  0  0  0  0
   Conjunctivae (R-C-D)  1 1 0  2 3 1  2 3 1  2 4 2  2 4 1  1 4 1  1 4 0  1 2 0  1 1 0  0 0 0

Applicant's summary and conclusion

Interpretation of results:
other: Category 1 in accordance with EU criteria
Conclusions:
Under the conditions of the test, mean scores of 2.9, 1.9, 0.39 and 0.22 can be calculated for conjunctival chemosis, conjunctival redness, iridial lesion and corneal opacity, respectively, for the six animals, based on individual irritancy scores at 24, 48 and 72 hours.
Executive summary:

0.1 mL of test material was instilled into the lower conjunctival sac of the right eyes of six albino rabbits. The eyelids were held closed for approximately 1 second and released. Left eyes served as contralateral controls.

The eyes were examined for ocular reactions in accordance with the method of Draize at approximately 1, 24, 48 and 72 hours after dosing and at 4, 7, 10, 14, 17 and 21 days if irritation persisted. Sodium fluorescein was used to aid in revealing possible corneal damage at 72 hours, 7, 10, 14, 17 and 21 days.

Positive conjunctival reactions were noted in the treated eye of all animals. Corneal and iridal reactions were observed in the right eye of three and four rabbits, respectively. Corneal and iridal irritation subsided by day 10 or earlier. Positive conjunctival irritation subsided by 21 or earlier. Minor conjunctival irritation not considered a positive score persisted through day 21 for three animals.

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