Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study 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
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
2,3,5-trimethylhydroquinone
EC Number:
211-838-3
EC Name:
2,3,5-trimethylhydroquinone
Cas Number:
700-13-0
IUPAC Name:
2,3,5-trimethylbenzene-1,4-diol
Details on test material:
- Name of test material (as cited in study report): 2,3,6-trimethylhydroquinone
- Batch: Feb. 20, 1990

Test animals / tissue source

Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: GAUKLER; D-6050 OFFENBACH/MAIN, Germany
- 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; FIRMA KLINGENTALMUEHLE AG, CH-4303 KAISERAUGST, SWITZERLAND (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


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated other eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (ca. 12 mg)
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
21 d
Number of animals or in vitro replicates:
3
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:
other: 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Remarks on result:
other: Study discontinued after 8 days for 2/3 animals
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: Study discontinued after 8 days for 2/3 animals
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
2.6
Max. score:
3
Reversibility:
not fully reversible within: 21 d
Remarks on result:
other: Study discontinued after 8 days for 2/3 animals
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
3.2
Max. score:
4
Reversibility:
fully reversible within: 15 d
Remarks on result:
other: Study discontinued after 8 days for 2/3 animals

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 Symptons
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:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU