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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD 405 guideline study performed according to GLP regulation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris(oxiranylmethyl) benzene-1,2,4-tricarboxylate
EC Number:
230-638-7
EC Name:
Tris(oxiranylmethyl) benzene-1,2,4-tricarboxylate
Cas Number:
7237-83-4
Molecular formula:
C18H18O9
IUPAC Name:
1,2,4-tris[(oxiran-2-yl)methyl] benzene-1,2,4-tricarboxylate
Details on test material:
- Name of test material (as cited in study report): TKK 30009
- Trade name: LMB 5196
- Physical state: viscous liquid
- Analytical purity: > 75%
- Lot/batch No.: Z 2178
- Expiration date of the lot/batch: March 1995
- Storage condition of test material: room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Chemisch-pharmazeutische Fabrik D-7950 Biberach/Riss
- Weight at study initiation: 2780 to 2950 g
- Housing: individually in metal cages
-Identification: by ear tatoo
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye of each animal remained untreated and serve as control
Amount / concentration applied:
0.1 mL of the undiluted substance
Duration of treatment / exposure:
The substance was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test article.
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3 female animals
Details on study design:
SCORING SYSTEM: according to the OECD scoring system

CORNEA
Opacity: degree of density (area most dense taken for reading)

No ulceration or opacity.................................................................................................................... 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster),
details of iris clearly visible................................................................................................................1
Easily discernible translucent area, details of iris slightly obscured...........................................2
Nacreous area, no details of iris visible, size of pupil barely discernible....................................3
Opaque cornea, iris not discernible through the opacity..............................................................4


IRIS
Normal.....................................................................................................................................................0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia,
or injection, any 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

CONHJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae when compared with control eye)

Blood vessels normal..............................................................................................................................0
Some blood vessels definitely hyperemic (injected)..........................................................................1
Diffuse, crimson color, individual vessels not easily discernible....................................................2
Diffuse beefy red.....................................................................................................................................3

Chemosis: lids and/or nictitating membranes

No swelling...............................................................................................................................................0
Any swelling above normal (including nictitating membranes).......................................................1
Obvious swelling with partial eversion of lids ....................................................................................2
Swelling with lids about half-closed.....................................................................................................3
Swelling with lids more than half-closed.............................................................................................4



TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 250
Time point:
other: mean 24 - 72 hrs
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal: 330
Time point:
other: mean 24 - 72 hrs
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal: 356
Time point:
other: mean 24 - 72 hrs
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal: 250
Time point:
other: mean 24 - 72 hrs
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal: 330
Time point:
other: mean 24 - 72 hrs
Score:
0.67
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal: 356
Time point:
other: mean 24 - 72 hrs
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: 250
Time point:
other: mean 24 - 72 hrs
Score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal: 250
Time point:
other: mean 24 - 72 hrs
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: 330
Time point:
other: mean 24 - 72 hrs
Score:
2.33
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal: 330
Time point:
other: mean 24 - 72 hrs
Score:
1.67
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: 356
Time point:
other: mean 24 - 72 hrs
Score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal: 356
Time point:
other: mean 24 - 72 hrs
Score:
1.67
Reversibility:
fully reversible within: 10 days
Irritant / corrosive response data:
Scattered or diffuse corneal opacity was noted in all animals from the 1- to the 72-hour reading. Irridic effects (grade 2) was noted from the 24-hour reading to the 48-hour reading in one animal and to the 72-hour in the two remaining animals. Slight to marked reddening of the conjunctivae was observed in all animals from the 1-hour reading to the 10-day reading. Slight swelling to obvious swelling with partial eversion of the lids was also noted in all animals from the 1-hour reading to the 72-hour reading in two animals and up to the 7-day reading in one animal.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Accroding to the EEC classification the substance has to be classified as irritant to the rabbit eyes.
Executive summary:

The primary eye irritation potential was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 mL into the left eye of each of three female New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours as well as 7, 10 and 14 days after test item instillation.

 

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity were 1.00 for all three animals.

The individual mean scores for iris were 1.00, 0.67 and 1, respectively. The individual mean scores for the conjunctivae were 3.00, 2.33 and 3.00 for reddening and 2.00, 1.67 and 1.67 for chemosis, respectively.

 

The instillation of the substance into the eye resulted in early-onset and transient ocular changes, such as corneal opacity, irridic effects, reddening of the conjunctivae and chemosis. These effects were reversible and were no longer evident 14 days after treatment.

 

Based upon the referred classification criteria (Commission Directive 83/467/EEC), the substance is considered to be “irritating” to the rabbit eye.