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

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1981
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
; if relevant deviations exist they are described under materials and methods or as appropriate entries in this endpoint study record
Principles of method if other than guideline:
The original test report was submitted to the sponsor with cover letter  dated 02 April 1981. Thus it cannot have been performed according to the  adapted OECD Test Guideline. Probably a late / final draft was used.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Isophorone diisocyanate, no data on purity

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: 
- Strain: New Zealand white
- Sex: male - Source: Lippische Versuchstierzucht, Extertal (Germany)
- Weight at study initiation: 2.3 kg (average)
- Controls: no housing conditions: room temperature: 16-18°C; humidity: 40%; light: 12h/d; acclimatization period before start of experiment: 7-14d; diet: "muemmelZ" (Ssniff, Soest); water: ad libitum

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
Duration of treatment / exposure:
Rinsing: right eye after 30 s for 3 min with physiol. sodium chloride  solution
Observation period (in vivo):
Postexposure period: 8 days
Number of animals or in vitro replicates:
6
Details on study design:
ADMINISTRATION/EXPOSURE 
- Administration of test substance: both eyes; eyes closed for 1 s after  administration
- Amount of substance instilled: 0.1 ml into each eye - Rinsing: right eye after 30 s for 3 min with physiol. sodium chloride  solution
- Postexposure period: 8 days
EXAMINATIONS
- Ophtalmoscopic examination: 1; 24; 48; 72 hours; 8 days
- Scoring system: maximum 110 scores (Draize)
- Observation period: 8 days
- Tool used to assess score: ophthalmoscope; fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Remarks:
according to Draize
Basis:
mean
Time point:
other: 24h; 48h; 72h
Score:
26.4
Max. score:
110
Reversibility:
not fully reversible within: 8d
Remarks on result:
other: rinsed (right) eye
Irritation parameter:
overall irritation score
Remarks:
according to Draize
Basis:
mean
Time point:
other: 24h; 48h; 72h
Score:
36.4
Max. score:
110
Reversibility:
not reversible
Remarks on result:
other: not rinsed (left) eye
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24h; 48h; 72h
Score:
0.9
Max. score:
4
Reversibility:
not fully reversible within: 8d
Remarks on result:
other: opacity; rinsed (right)eye
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24h; 48h; 72h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: opacity; not rinsed (left) eye
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24h,; 48h; 72h
Score:
0.1
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: rinsed (right) eye
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24h; 48h; 72h
Score:
0.67
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: not rinsed (left) eye
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24h; 48h; 72h
Score:
2.7
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: rinsed (right) eye
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24h; 48h; 72h
Score:
2.8
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: not rinsed (left) eye
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24h; 48h; 72h
Score:
3.9
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: rinsed (right) eye
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24h; 48h; 72h
Score:
3.9
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: not rinsed (left) eye
Irritant / corrosive response data:
AVERAGE SCORE (not rinsed / rinsed)
- Cornea (opacity): 1.0 / 0.9 (max. 4)
- Cornea (area): 2.9 / 1.6 (max. 4)
- Iris: 0.67 / 0.1 (max. 2)
- Conjunctivae (Redness): 2.8 / 2.7 (max. 3)
- Conjunctivae (Chemosis): 3.9 / 3.9 (max. 4)
- Conjunctivae (Exsudation): 2.8 / 2.3 (max. 3)
- Overall irritation score: 36.4 / 26.4 (max. 110)
Other effects:
OTHER EFFECTS:  Severe irritation of the conjunctiva: high degree of chemosis with  unchanged condition after 8 d both on rinsed and non-rinsed 
eye; slight  cornea damage, to a lesser degree on the rinsed eye, with significant  retrogression within 8 d

Any other information on results incl. tables

no further remarks

Applicant's summary and conclusion

Conclusions:
Under conditions of the study Isophorone Diisocyanate showed highly irritating effects in eyes of rabbits, which are not reversible.
Executive summary:

A study was performed to examine eye irritating effects of Isophorone Diisocyanate according to OECD TG 405 in rabbits.

In this study where both eyes were treated (0.1 ml undiluted per eye) and only one eye was rinsed, severe irritation of the conjunctiva was observed. There was a constantly high degree of chemosis throughout the 8 days observation period both on rinsed and non-rinsed eyes, and slight cornea damage, to a lesser degree on the rinsed eye, with significant retrogression within 8 days. The irritation score was 36.4/110 (not rinsed) or 26.4/110 (rinsed eye). Under conditions of the study Isophorone Diisocyanate showed highly irritating effects in eyes of rabbits, which are not reversible.