Registration Dossier

Administrative data

Description of key information

Both hydroquinone and trimethylhydroquinone are classifed for being highly irritating to eyes. Hydroquinone is not classified for skin irritation. The findings in the OECD 404 study with trimethylhydroquinone are mild and do not warrant classification as a skin irritant. Therefore, 2-methylhydroquinone is considered to be severely irritating to eyes and only mildly irritating to skin (UN GHS Cat 3).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin 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. Observation period only 7 days.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: GAUKLER; D-6050 OFFENBACH/MAIN, Germany
- Weight at study initiation: mean 2.55 kg (male), 2.85 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
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped at least 15 h before beginning of study
Vehicle:
other: the test material was moistened with water for better application
Controls:
other: untreated skin of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 100%
Duration of treatment / exposure:
4 h
Observation period:
8 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: area of 2.5x2.5 cm; upper third of the back or flanks
- Type of wrap if used: TEST PATCHES WERE SECURED IN POSITION WITH A POROUS DRESSING (FOUR LAYERS OF ABSORBENT GAUZE + POROUS BANDAGE) .


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Lutrol and Lutrol:water (1:1)
- Time after start of exposure: 4 h


SCORING SYSTEM:

Erythema:
0 = No erythema
1 = Very slight erythema (barely perceptible)
2 = Well defined erythema
3 = Moderate to severe erythema
4 = Severe erythema (beet-redness) to slight, eschar formation (injuries in depth)

Edema:
0 = No edema
1 = Very slight edema (barely perceptible)
2 = Slight edema (edges of area well defined by definite raising)
3 = Moderate edema (raised approx. 1 mm)
4 = Severe edema (raised more than 1 mm and extending beyond the area of exposure)

Mean irritation score was calculated according to 83/467/EEC criteria (1983), using the readings of 24, 48, and 72 hours.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 7 d

Animal1: male, 2.61 kg

Animal 2: male, 2.49 kg

Animal 3: female, 2.82 kg

Results:

Readings Animal Erythema Edema Additional findings
4 h 1 1 0  
2 1 0  
3 1 0  
24 h 1 1 0  
2 2 0  
3 3 1  
48 h 1 0 0  
2 2 0  
3 3 0  
72 h 1 0 0  
2 2 0  
3 2 0  
7 d 1     d
2 0 0 s
3 0 0 s
mean 24 - 72 h 1 0.3 0.0  
2 2.0 0.0  
3 2.7 0.3  
mean 24 - 72 h   1.7 0.1  

d: discontinued due to absence of irritation

s: scaling

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
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
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
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

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

 

 

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The experimental data for hydroquinone is not provided. It is referred to the legal classification of hydroquinone in the EU (Annex I index no. 604 -005 -00 -4).


Effects on eye irritation: highly irritating

Justification for classification or non-classification