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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:
comparable to guideline study with acceptable restrictions
Remarks:
study according to guideline without GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Adopted May 12th, 1981
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Trimethylhydroquinone
- Physical state: yellow powder
- Analytical purity: 99 .8%
- Purity test date: Nov 09, 1994
- Lot/batch No.: 4361662
- Stability under test conditions:
purity and chemical identification of the test material was determined prior to the start of the study and at the end of the study.
- Storage condition of test material:
room temperature (19/08/93 to 14/09/93)
afterwards: room temperature in the dark, over
silica gel, under nitrogen gas

Test animals / tissue source

Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: GAUKLER
- Weight at study initiation: mean 2.86 kg (male), 2.61 kg (female)
- Housing: stainless stell cages with wire mesh floor (area 40 cm x 51 cm)
- Diet (e.g. ad libitum): 4 MM; about 130 g per animal per day
- Water (e.g. ad libitum): About 250 ml tap water per animal per day
- Acclimation period: at least 8 days

The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteeed a range of 20 - 24°C for temperature and of 30 - 70% for relative humidity. There were no deviations from these ranges which influenced the results of this study.
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml bulk volume (about 12 mg of the comminuted test substance)
Duration of treatment / exposure:
single application
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
1 male, 2 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
Cornea Opacity-degree of density (area most dense taken for reading)
0 = No opacity
1 = Scattered or diffuse area, details of iris clearly visible
2 = Easily discernible translucent areas, details of iris slightly obscured
3 = Opalescent areas, no details of iris visible, size of pupil barely discernible
4 = Opaque, iris invisible

Area of cornea involved
1 = One quarter (or less) but not zero
2 = Greater than one quarter, but less than half
3 = Greater than half, but less than three quarters
4 = Greater than three quarters, up to whole area

Iris
0 = Normal
1 = Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination af any thereof) iris still reacting to light (sluggish reactions is positive)
2 = No reaction to light, hemorrhage, gross destruction (any or all of these)

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
0 = Vessels normal
1 = Vessels definitely injected above normal
2 = More diffuse, deeper crimson red, individual vessels not easily discernible
3 = Diffuse beefy red

Chemosis
0 = No swelling
1 = Any swelling above normal (includes nictitatinq membrane)
2 = Obvious swelling with partial eversion of lids
3 = Swelling with lids about half closed
4 = Swelling with lids about half closed to completely closed

Discharge
0 = No discharge
1 = Any amount different from normal (does not include small amounts observed in inner canthus of normal animals
2 = Discharge with moistening of the lids and hairs just adjacent to lids
3 = Discharge with moistening of the lids and hairs, and considerable area around the eye

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21d
Remarks:
pupil contacted, loss of corneal tissue, marginal vascularization of the cornea,
Remarks on result:
probability of severe irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks:
pupils contracted
Remarks on result:
probability of severe irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.2
Max. score:
4
Reversibility:
fully reversible within: 15 d

Any other information on results incl. tables

Animal 1: male, 2.94 kg

Animal 2: female, 2.61 kg

Animal 3: male, 2.77 kg

Table: Individual irritation findings (Draize scores) at the different reading times

Readings Animal cornea Iris conjunctiva Symptoms
opacity area redness swelling discharge
1 h 1 0* 0* 0* 2* 4 2  
2 0 0 0 2 3 2  
3 0* 0* 0 2 4 3  
24 h 1 1 4 0 3 3 2 pc,c
2 1* 4* 0* 2 3 2 db,s
3 1* 4* 0* 2 4 2 db,s
48 h 1 1 4 0 3 3 1 pc,s,re
2 1* 4* 0* 2 3 3 db,s
3 1* 4* 0* 2 4 3 db,s
72 h 1 1 4 0 3 2 1 pc,s,re
2 1* 4* 0* 3 3 3 s
3 1* 4* 0* 3 4 3 db,s
8 d 1 2 2 0 2 1 1 pc,s,re,mv,lh,lc
2 2* 2* 0* 2 2 3 s,re,st
3 2* 2* 0* 2 3 2 s,re.lh
15 d 1 1 1 0 2 0 0 pc,re,mv,lh,lc
2           study discontinued
3             study discontinued
21 d 1 1 1 0 1 0 0 pc,re,mv,lh,lc
2            
3              
mean 24 - 72 h 1 1.0   0.0 3.0 2.7    
2 1.0   0.0 2.3 3.0    
3 1.0   0.0 2.3 4.0    
mean   1.0   0.0 2.6 3.2    

*: score could not be read due to severe edema or suppuration
The study was discontinued for animals no 2 and 3 by study day 8 due to severe irritation.

Abbreviations:
db = discharge of blood
lh = loss of hair at the margins of the eyelids
lc = loss of corneal tissue
mv = marginal vascularization of the cornea
pc = pupil contracted
re = small retractions in the eyelids
s = suppuration
st = staphyloma

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test substance trimethylhydroquinone produced in three animals effects on the cornea and conjunctiva that have not fully reversed within an observation period of 21 days and therefore has to be classified as "serious eye damage, category 1".
Executive summary:

A Draize test according OECD Guideline 405 method was performed to assess the potential eye irritation/corrosion property of trimethylhydroquinone.

Under experimental conditions of this study, the test item trimethylhydroquinone induced severe damages to the eyes of Vienna Whites rabbits.