Registration Dossier

Administrative data

Description of key information

The skin and eye irritation potential of Catalase has been tested and it was concluded that it is neither a skin nor an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 21, 2014 to October 24, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
SOURCE ANIMAL
- Source: Received from Robinson Services, Inc. Mocksville, NC, on July 23 and 30, 2014
- Sex: Female. The animals assigned to test were nulliparous and non-pregnant.
- Age at study initiation (in days): Young adult. (10-11 weeks)
- Weight at study initiation: 2524-2818 grams
- Housing: The animals were individually housed in suspended stainless steel perforated bottom caging, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals. Enrichment (e.g., toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Harlan Teklad Global High Fiber Rabbit Diet® 2031. A designated amount of the diet (approximately 150 grams/day) and a Premium Timothy CubeTM (Ontario Dehy Inc.) were available to each rabbit.
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum.
- Acclimation period: 8 or 13 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-22°C
- Humidity: 46-60%,
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From August 5, 2014 to August 10, 2014
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
Individual dose sites were scored according to the Draize scoring system immediately following patch removal (initial rabbit only) and at approximately 30-60 minutes, 24, 48, and 72 hours after patch removal.
Number of animals:
3
Details on study design:
Preparation and Selection of Animals:
Approximately 24 hours prior to application, the animals were prepared by clipping the dorsal area and the trunk. On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. Three healthy naive animals (not previously tested) without pre-existing skin irritation were selected for test. Initially, only one rabbit was placed on test. Since there was only slight dermal irritation noted at the dose site of this animal at 24 hours after patch removal, the test was completed with two additional rabbits. A systemic analgesic (Buprenorphine SR®) was administered to relieve potential discomfort associated with skin irritation which provides therapeutic relief for periods of up to 76 hours. Prior to test substance application, 0.1 mg/kg of body weight of the analgesic was administered to the animals and at appropriate intervals to maintain therapeutic blood levels.

Application of Test Substance:
Five-tenths of a milliliter of the test substance was applied to one 6-cm2 intact dose site on each animal and covered with a 1-inch x 1-inch, 4-ply gauze pad. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit and they were returned to their designated cages. No other substances were tested on these rabbits. After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleansed with a 3% soap solution followed by tap water and a clean paper towel to remove any residual test substance.
Irritation parameter:
erythema score
Basis:
animal: #1, 3
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible
Remarks:
72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within:
Remarks:
48 hours
Irritation parameter:
edema score
Basis:
animal: #2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
1
Irritant / corrosive response data:
Erythema (scores of 1 and 2) was noted for two of three treated sites and edema (score of 1) was noted at one treated site at the 30-60 minute scoring interval. Erythema and edema cleared from the dose sites by 72 hours.
Other effects:
All animals appeared active and healthy during the study. One rabbit lost body weight during the study. There were no other clinical signs observed

Table 1. INDIVIDUAL SKIN IRRITATION SCORES ( ERYTHEMA/EDEMA)

Animal No.

Sex

Time After Patch Removal

 

Immediately after patch removal 

30-60 mins 

24 hrs 

 48 hrs 

72 hrs

3501

 F 

 2/1 

 2/1 

 1/0 

 1/0 

 0/0 

3502

 F 

 N/A 

 0/0 

 0/0 

 0/0 

 0/0 

3503

 F 

 N/A 

 1/0 

 1/0 

 1/0 

 0/0 

N/A – Not Applicable

Table 2: SUMMARY OF MEAN SCORES FOR DERMAL RESPONSES

RABBIT NUMBER 

 ERYTHEMA 

 EDEMA 

3501

0,7

0

3502

0

0

3503

0,7

0

 Calculated from the 24-, 48-, and 72-hour dermal responses(EEC/GHS). 

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, Catalase should not be classified as a skin-irritant.
Executive summary:

A primary skin irritation test was conducted with rabbits to determine the potential of Catalase to produce irritation after a single topical application. This study was conducted according to the OECD Guideline 404 in compliance with the GLP.

 

The study was conducted in a stepwise manner using a single patch applied initially to one rabbit for 4 hours. Five-tenths of a milliliter of the test substance was applied to the skin of one healthy rabbit for 4 hours. The dose site was evaluated for dermal irritation immediately after patch removal and at 30-60 minutes and 24, 48, and 72 hours after patch removal. Since there was only slight dermal irritation noted at the dose site of this animal at 24 hours after patch removal, the test was completed on two additional animals, as described above, except the dose sites were not evaluated immediately after patch removal. Erythema (scores of 1 and 2) was noted for two of three treated sites and edema (score of 1) was noted at one treated site at the 30-60 minute scoring interval. Erythema and edema cleared from the dose sites by 72 hours.

Under the study conditions, Catalase should not be classified as a skin-irritant.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 21, 2014 to October 24, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2012
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Received from Robinson Services, Inc. Mocksville, NC, on July 30 and August 6, 2014.
- Sex: Female. All animals assigned to test were nulliparous and non-pregnant
- Age at study initiation: Young adult (11 weeks)
- Weight at study initiation: 2509-2644 grams
- Housing: The animals were singly housed in suspended stainless steel perforated bottom caging which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals. Enrichment (e.g., toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Harlan Teklad Global High Fiber Rabbit Diet® 2031. A designated amount of the diet (approximately 150 grams/day) and a Premium Timothy CubeTM (Ontario Dehy Inc.) were available to each rabbit.
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum.
- Acclimation period: 7 or 12 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-22ºC
- Humidity: 46-52%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From August 11, 2014 to August 16, 2014
Vehicle:
unchanged (no vehicle)
Controls:
not required
other: The other eye of each rabbit remained untreated with the test substance and served as a control.
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Eyelids were held together for about one second and then released
Observation period (in vivo):
Ocular irritation was evaluated using a white light source at 1, 24, 48, and 72 hours post-instillation.
Number of animals or in vitro replicates:
3
Details on study design:
Preparation and Selection of Animals:
Prior to instillation (within 24 hours), both eyes of a group of animals were examined using a white light source and a fluorescein dye procedure. One drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit. The eyes were rinsed with physiological saline (0.9% NaCl) after instillation of the fluorescein and then evaluated for corneal damage using an ultraviolet light source. Just prior to instillation, the eyes were re-examined with a white light source and scored for abnormalities according to the "Scale for Scoring Ocular Lesions" Draize et al. Three healthy, naive animals (not previously tested) without pre-existing ocular irritation were selected for test. Initially, only one rabbit was placed on test. In the absence of any irritation in this animal, the remaining two animals were tested to confirm the result. A systemic analgesic (Buprenorphine SR®) was administered to relieve potential discomfort associated with eye irritation which provides therapeutic relief for periods of up to 76 hours. Prior to test substance instillation, 0.1 mg/kg of body weight of the analgesic was administered to the animals and at appropriate intervals to maintain therapeutic blood levels.

Instillation:
Prior to instillation, 2-3 drops of ocular anesthetic (Tetracaine Hydrochloride Ophthalmic Solution USP, 0.5%) were placed into both the treated and control eye of each animal. One-tenth of a milliliter of the test substance was then instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The other eye of each rabbit remained untreated with the test substance and served as a control. The rabbits were then returned to their designated cages.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: #1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: #1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal: #1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
There was no ocular irritation noted in any treated eye during this study.
Other effects:
All animals appeared active and healthy and gained body weight during the study.

Table 1. INDIVIDUAL SCORES FOR OCULAR IRRITATION

   

Rabbit No.: 3401 (Female)

 

Rabbit No.: 3402 (Female)

 

Rabbit No.: 3403 (Female)

 

 

Hour

 

Hour

 

Hour

 

 

1

24

48

72

1

24

48

72

1

24

48

72

 I. Cornea 

   

   

   

   

   

   

   

   

   

   

   

   

 A. Opacity 

0

1

0

0

0

1

0

0

0

1

0

0

 B. Area 

4

4

4

4

4

4

4

4

4

4

4

4

 (AxB)x5 

0

0

0

0

0

0

0

0

0

0

0

0

 II. Iris 

   

   

   

   

   

   

   

   

   

   

   

   

 A. Values 

0

0

0

0

0

0

0

0

0

0

0

0

 Ax5 

0

0

0

0

0

0

0

0

0

0

0

0

 III. Conjunctivae 

   

   

   

   

   

   

   

   

   

   

   

   

 A. Redness 

0

0

0

0

0

0

0

0

0

0

0

0

 B. Chemosis 

0

0

0

0

0

0

0

0

0

0

0

0

 C. Discharge 

0

0

0

0

0

0

0

0

0

0

0

0

 (A+B+C)x2 

0

0

0

0

0

0

0

0

0

0

0

0

 Total 

0

0

0

0

0

0

0

0

0

0

0

0

Table 2. MEAN SCORES FOR INDIVIDUAL RABBITS

Rabbit Number 

 Corneal Opacitya 

 Iritisa 

Conjunctival Redness

 ConjunctivalChemosis 

3401

0

0

0

0

3402

0

0

0

0

3403

0

0

0

0

 Calculated from the 24-, 48-, and 72-hour scores (EEC/GHS). 

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, Catalase should not be classified as an eye-irritant.
Executive summary:

The study was conducted to assess the ocular irritation potential of Catalase according to the OECD Guideline No. 405 in compliance with GLP.

 

The study was conducted in a stepwise fashion. Initially, one-tenth of a milliliter of the test substance was instilled into the conjunctival sac of the right eye of one healthy rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The left eye remained untreated and served as a control. Since there was no irritation observed in this animal, the test was completed on two additional animals. There was no ocular irritation noted in any treated eye during this study.

 

Under the test conditions, Catalase should not be classified as an eye-irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The skin and eye irritation potential of catalase has been tested according to the OECD guidelines in compliance with GLP. In the study conducted to determine the skin irritation potential of catalase, erythema (scores of 1 and 2) was noted for two of three treated sites and edema (score of 1) was noted at one treated site at the 30-60 minute scoring interval. However, both erythema and edema cleared from the dose sites by 72 hours. No eye irritation was observed at any dose site in the eye irritation test. The conclusion was that catalase is neither a skin nor an eye irritant.

Justification for classification or non-classification

The skin and eye irritation potential of Catalase has been tested according to the OECD guidelines and in compliance with GLP. Slight erythema and edema in some treated sites was observed in the skin irritation study however it was cleared within 72 hours. No irritation was observed in the eye irritation study. The conclusion was that Catalase did not exert any skin and eye irritation and therefore Catalase should not be classified.