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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:
1989-03-21 - 1989-05-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Slight modifications from the guideline (e.g. precise description and scoring of corneal defects, additional examination of aqueous humour) do not affect the validity of the outcome of this study.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Test compound: Triisopropylbenzoldiisocyanat
Chemical name: 2,4-Diisocyanato-1,3,5-tris-(1-methylethyl)-benzene
Colour: yellowish
Physical state: liquid
Analytical purity: 98.6 %
Solubility: not soluble in water
Identity/Stability: guaranteed for the study period
Storage: room temperature, in dark

Test animals / tissue source

Species:
rabbit
Strain:
other: HC:NZW
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- healthy adult albino rabbits, females were nulliparous and not pregnant.
- Source: breeder Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation: adult
- Weight at study initiation: 3.0 - 4.0 kg (weighed directly before application of the test compound)
- Housing: under standardised conventional conditions in individual stainless steel cages. Excrement trays beneath the cages contained low-dust wood shavings (type S 8/15, Ssniff Spezialdiäten GmbH, Soest). Shavings were regularly spot-checked for contaminants at the instance of the Department of Laboratory Animal Services.
All the animals in this study were kept in one room. For capacity reasons, rabbits treated with other test compounds were also housed in the same room. Adequate separation, clear cage and individual marks, and appropriate organisation of working procedures ensured that the test animals were not mixed up.
- Cleaning, disinfection; pest control: room surfaces are cleaned at least once per month, and the room floor once per week, and disinfected with Zephirol®-10% (1% in water). In so doing contamination of the diet and contact with the animals is excluded. No pest control was performed in the animal rooms. The drinking apparatus were cleaned once a week.
- Diet (e.g. ad libitum): standard diet "Ssniff K 4" (Ssniff Spezialdiäten GmbH, Soest), approx. 100 - 120 g per animal and day; feeding once per day in the morning.
- Water (e.g. ad libitum): tap water was available ad libitum (between 7 and 19 hrs. by automatic watering apparatus)
- Acclimation period: at least 14 days in the quarantine station of the Department of Laboratory Animal Services before treatment and monitored for diseases (clinical). shortly after arrival collective faeces specimens were examined for Coccidia oocysts.

Vaccination or treatment with antibiotics was performed neither prior to receipt of the animals nor during the acclimatization or study period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): approx. 50 %
- Air changes (per hr): approx. 10 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours, artificial illumination from 6 to 18 hrs CET
- Intensity of illumination: approx. 27 Watt/m2 floor area

RANDOMIZATION
The individual rabbits were randomly assigned to the respective treatment groups. Randomisation was performed by means of a random number generator with varying starting conditions, using an Apple 2e.

For reasons of animal welfare, rabbits from former studies that tolerated treatment without signs are also used. In these animals the opposite skin area/eye which served as control in the preceding study is treated in the following study to prevent interactions of different test compounds.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as the control
Amount / concentration applied:
100 µl
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours (If irritation was observed, animals were monitored for not more than 21 days after application)
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with physiological NaCl solution
- Time after start of exposure: 24 hours

SCORING SYSTEM: cornea, fluorescein staining (epithelial defects), iris, aqueous flare, conjunctivae and discharge

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
opacity and area
Basis:
animal: H7, H25 and H26
Time point:
other: 1h, 24h and 7d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
other: fluorescein (intensity and area)
Basis:
animal: H7, H25 and H26
Time point:
other: 24h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal: H7, H25 and H26
Time point:
other: 1h, 24h and 7d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: H7, H25 and H26
Time point:
other: 1h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: H7, H25 and H26
Time point:
other: 24h and 7d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
swelling
Basis:
animal: H7, H25 and H26
Time point:
other: 1h, 24h and 7d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
other: discharge
Basis:
animal: H7, H25 and H26
Time point:
other: 1h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
other: discharge
Basis:
animal: H7 and H25
Time point:
other: 24h and 7d
Score:
0
Max. score:
1
Reversibility:
other: not applicable
Irritation parameter:
other: discharge
Basis:
animal: H26
Time point:
other: 24h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
other: discharge
Basis:
animal: H26
Time point:
other: 7d
Score:
0
Max. score:
1
Reversibility:
other: not applicable
Irritant / corrosive response data:
No irritation of the eye was noted after the end of the observation period.
Other effects:
No other findings stated

Any other information on results incl. tables

Table 1: Test for irritant effect on the eye (expos . 24 hrs)

 Animal no. (body weight)  tissue     signs  DRAIZE grades  Irritation index
 1 h  24 h  48 h  72 h  7 d  14 d  21 d
H7(3.4 kg)  cornea  o  0  0  0  0  0  -  - 0.0
 a  0  0  0  0  0  -  -  
 fluorescein  i  -  0  -  -  -  -  -  
 a  -  0  -  -  -  -  -  
 iris / conjuncitvae / conjunctivae    0  0  0  0  0  -  - 0.0
 r  1  0  0  0  0  -  - 0.0
 s  0  0  0  0  0  -  - 0.0
 aqueous humour discharge       0  0  0  0  0  -  -  
   1  0  0  0  0  -  -  
 H25 (3.1 kg)  cornea     o  0  0  0  0  0  -  - 0.0
 a  0  0  0  0  0  -  -  
 fluorescein     i  -  0  -  -  -  -  -  
 a  -  0  -  -  -  -  -  
 iris / conjunctivae / conjunctivae    0  0  0  0  -  - 0.0 
 r  1  0  0  0  0  -  - 0.0
 s  0  0  0  0  0  -  - 0.0
 aqueous humour discharge       0  0  0  0  0  -  -  
   1  0  0  0  -  -  
 H26 (3.2 kg)  cornea     o  0  0  0  0  -  -  0.0
 a  0  0  0  0  0  -  -  
 fluorescein     i  -  0  -  -  -  -  -  
 a  -  0  -  -  -  -  -  
 iris / conjunctivae / conjunctivae    0  0  0  0  0  -  -  0.0
 r  1  0  0  0  0  -  -  0.0
 s  0  0  0  0  0  -  -  0.0
 aqueous humour discharge       0  0  0  0  0  -  -  
   1  1  1  1  0  -  -  

o = opacity

a = area

i = intensity

r = redness

s = swelling

- = not examined

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The study was performed according to the OECD TG405 with only minor deviations and according to the good laboratory practice principles, it is considered to be of the highest quality (reliability Klimisch 1). The criteria of validity of the test system are fulfilled. The test material did not induce any irritation or corrosion on rabbit eyes. The test material was considered to be not irritating under the conditions of the test (exposure duration 24 hours).
Executive summary:

Triisopropylbenzoldiisocyanat was investigated for its potential to cause irritation in the rabbit eye according to OECD TG405 (Märtins, 1989). 100 µL of pure substance were instilled into the conjunctival sac, the untreated eye served as control. Interpretation of results was based on the nature, intensity, and reversibility of the responses observed. Under the conditions of this experiment the test compound was found to cause no irritation when applied to the rabbit eye mucosa. No corrosion effect was observed at each of the measuring intervals.