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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:
guideline study with acceptable restrictions
Remarks:
e.g. non-GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1981)
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-methylenedicyclohexyl diisocyanate
EC Number:
225-863-2
EC Name:
4,4'-methylenedicyclohexyl diisocyanate
Cas Number:
5124-30-1
Molecular formula:
C15H22N2O2
IUPAC Name:
1,1'-methylenebis(4-isocyanatocyclohexane)
Details on test material:
- Purity: > 99.3 %

Test animals / tissue source

Species:
rabbit
Strain:
other: Small white Russians, Chbb-SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:  
- Strain: Small white Russians, Chbb-SPF
- Sex: male and female
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Age at study initiation: no data
- Weight at study initiation: 1.9 - 2.4 kg
- Housing: singly in stainless steel cages
- Diet and water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye that remains untreated served as control
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
The test substance was applied into the conjunctival sac of the right eye, except for one animal where the left eye was treated; no rinsing of the eyes was done after exposure.
Observation period (in vivo):
Eye irritation was scored 1, 24, 48, and 72 hours and 6, 8, 10, and 14 days after start of exposure.
Number of animals or in vitro replicates:
3 males / 3 females
Details on study design:
0.1 mL unchanged test substance was instillated in the lower lid of one eye of each animal. No rinsing of the eyes was done after exposure. The eyes were assessed 1, 24, 48, and 72 hours and 6, 8, 10, and 14 days post-treatment.

TOOL USED TO ASSESS SCORE: sodium fluorescein / ophthalmic lamp /  visual inspections

SCORING SYSTEM: Draize (Appraisals of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, Austin 1, Texas, 1959, page 51)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #4
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: mean score: 1.3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
>= 0 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: mean score: 1
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: mean score: 1.7
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
>= 1 - <= 3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: mean score: 1.7
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: mean score: 0.7
Irritation parameter:
chemosis score
Basis:
animal: #1, #5
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: mean score: 0.7
Irritation parameter:
chemosis score
Basis:
animal: #2, #4
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score: 0.3
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
other: Irritation index
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
other: 1, 24, 48 and 72 hours
Score:
5.67
Max. score:
110
Irritant / corrosive response data:
Mean Scores (24, 48, and 72 hours): Cornea: 0; Iris: 0, Conjunctivae (Redness): 1.28, Conjunctivae (Chemosis): 0.50

Scheme used for assessment (Irritation index, corresponding to classification as): not irritant 0-10, slightly irritant11-25, moderately irritant 26-56, severly irritant 57-110
Other effects:
On Day 6 inelastic eyelids were noted and on Day 10 hair loss around the eye.

Applicant's summary and conclusion

Executive summary:

The eye irritation properties of 4,4'-methylenedicyclohexyl diisocyanate was investigated in a study according to OECD TG 405. In this study 0.1 mL of the undiluted test substance was instilled into the lower lid of each one eye of 3 female and 3 male rabbits; the untreated contralateral eye served as control. The eyes remained unrinsed and there was no removal of test substance. The animals were observed for a period of 2 weeks post application. Eye irritation was scored using the Draize scale.

The average scores at 24, 48 and 72 hours after treatment were 0 for cornea and iris, 1.28 for conjunctiva (redness), and 0.5 for chemosis. An irritation index (time points 1, 24, 48 and 72 hours) was calculated 5.67 of 110. This leads to the conclusion "not irritant" (0 -10 = not irritant) according to the scheme applied by the author. On Day 6 inelastic eyelids were noted and on Day 10 hair loss around the eye.