Registration Dossier

Administrative data

Description of key information

Calcium peroxide was found to be not irritating to the skin, but severely irritating to unwashed eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP study.
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Version / remarks:
1984
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
GLP compliance:
yes
Remarks:
EPA Good Laboratory Practice Standards
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Animals, Inc., Denver, Pennsylvania
- Received: 1988-12-16
- Age at study initiation: young
- Weight at study initiation: 2.74 ± 0.128 kg (ranging from 2.64 kg to 2.97 kg)
- Housing: individually in stainless stail cages
- Diet: ad libitum (Purina High Fiber Rabbit Chow 5326)
- Water: ad libitum (fresh tap water)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 34-47
- Photoperiod (hrs dark / hrs light): 12/12:
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
physiological saline
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g
Duration of treatment / exposure:
approximately 4 h
Observation period:
72 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: one test site was located on each side of the spinal column
- Type of wrap if used: semi-occlusive cheesecloth bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test sites were wiped with clean gauze moistened with methanol, then rinsed with tap water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize (1944)
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal: all animals
Time point:
other: 4.5, 24, 48 and 72 hours
Score:
0
Max. score:
8
Reversibility:
other: not applicable, no irritation observed
Irritant / corrosive response data:
No irritation was noted on any of the test sites during any of the scoring intervals.
Other effects:
All animals remained healthy throughout the study.

Scoring interval (h)

Overall score

Edema

Erythema

4.5

0

0

0

24

0

0

0

48

0

0

0

72

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study no irritation was observed in any of the animals, on any of the test sites during any of the scoring intervals. As a consequence, the test material is judged to be non-irritating to intact skin when applied topically to New Zealand White rabbits.
Executive summary:

Three male and three female New Zealand White rabbits were treated topically on each of 2 test sites which were previously clipped free of hair. One-half gram of Calcium peroxide (high purity > 75% assay) was placed in contact with each test site. The test sites were covered with gauze patches and the trunk of each animal was wrapped with a sheet of cheesecloth. The test material was in contact with the skin for 4 h, after which the animals were unwrapped and the test material removed. Approximately 30 min after the end of the exposure period, the test sites were scored for irritation using the method of Draize. The test sites were scored daily thereafter for three days.

No irritation (edema nor erythema) was noted on any of the test sites during any of the scoring intervals.

Under the conditions of this study, the test material is judged to be non-irritating to intact skin when applied topically to New Zealand White rabbits.

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:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to internationally accepted protocol. No deviations.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
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: Hazleton Research Animals, Inc., Denver, Pennsylvania
- Age at study initiation: young adult
- Weight at study initiation: 2.48 - 3.82 kg
- Housing: individually, in stainless steel rabbit cages
- Diet (e.g. ad libitum): Furina High Fiber Rabbit Chow 5326, ad libitum
- Water (e.g. ad libitum): tab water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65 - 74 °F
- Humidity (%): 32 - 56 %
- Photoperiod (hrs dark / hrs light): 12h fluorescent light, / 12h dark
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.10 g
Duration of treatment / exposure:
The eyes of six of he rabbits remained unwashed.
The eyes of 3 of the rabbits were gently washed with 100 mL of tap water approximately 20-30 seconds after treatment.
Observation period (in vivo):
22 days
Number of animals or in vitro replicates:
9
Details on study design:
REMOVAL OF TEST SUBSTANCE
The eyes of six of he rabbits remained unwashed. The eyes of 3 of the rabbits were gently washed with 100 mL of tap water approximately 20-30 seconds after treatment.

SCORING SYSTEM: Method of Draize

TOOL USED TO ASSESS SCORE: penlight type light, 2% sodium fluorescein
Irritation parameter:
overall irritation score
Remarks:
Primary Eye Irritation Index
Basis:
mean
Time point:
other: 1 h
Score:
10 - 23.7
Max. score:
110
Remarks on result:
other: score: washed / unwashed
Irritation parameter:
overall irritation score
Remarks:
Primary Eye Irritation Index
Basis:
mean
Time point:
other: 24 h
Score:
14 - 33.2
Max. score:
110
Remarks on result:
other: score: washed / unwashed
Irritation parameter:
overall irritation score
Remarks:
Primary Eye Irritation Index
Basis:
mean
Time point:
other: 48 h
Score:
1.3 - 28.7
Max. score:
110
Remarks on result:
other: score: washed / unwashed
Irritation parameter:
overall irritation score
Remarks:
Primary Eye Irritation Index
Basis:
mean
Time point:
other: 72 h
Score:
0 - 28.3
Max. score:
110
Remarks on result:
other: score: washed / unwashed
Irritation parameter:
overall irritation score
Remarks:
Primary Eye Irritation Index
Basis:
mean
Time point:
other: 7 d
Score:
0 - 22.8
Max. score:
110
Remarks on result:
other: score: washed / unwashed
Irritation parameter:
overall irritation score
Remarks:
Primary Eye Irritation Index
Basis:
mean
Time point:
other: 22 d
Score:
0 - 8.3
Max. score:
110
Remarks on result:
other: score: washed / unwashed
Irritant / corrosive response data:
One hour post-dosing slight corneal opacities, iritis and moderate to severe conjunctivitis was noted in unwashed eyes. Washed eyes had mild conjunctivitis. Irritation worsened after the 1-hour scoring and unwashed eyes developed pannus, hemorrhagic conjuctivae, vascularization, blanched areas on the cornea and bulging of the cornea.

Washed eyes recovered within 72 hours. However, severe irritation persisted in 2 of the unwashed eyes througout study day 22.

Cornea effects (opacity and area):

#

Wash

24h

48h

72h

mean

 

 

Opac.

Area

Opac.

Area

Opac.

Area

Opac.

Area

1

No

1

3

1

4

1

3

1

3.3

2

No

1

2

1

2

1

2

1

2

3

No

2

4

2

2

1

4

1.6

3.3

4

No

1

2

1

2

1

2

1

2

5

No

1

1

1

3

1

2

1

2

6

No

1

3

1

3

1

3

1

3

7

Yes

1

1

0

0

0

0

0.3

0.3

8

Yes

0

0

0

0

0

0

0

0

9

Yes

1

1

0

0

0

0

0.3

0.3

Iritis:

#

Wash

24h

48h

72h

Mean

1

No

0

0

1

0.3

2

No

1

0

0

0.3

3

No

0

0

0

0

4

No

0

0

0

0

5

No

0

0

0

0

6

No

1

0

1

0.6

7

Yes

0

0

0

0

8

Yes

0

0

0

0

9

Yes

0

0

0

0

Effects on the conjuncitvae (redness, chemosis and discharge):

#

Wash

24h

48h

72h

Mean

 

 

R

C

D

R

C

D

R

C

D

R

C

D

1

No

2

3

3

2

1

3

2

1

3

2

1.6

3

2

No

2

2

3

2

1

3

2

0

2

2

1

2.6

3

No

2

3

3

3

3

3

3

2

3

2.6

2.6

3

4

No

2

3

3

2

2

3

2

2

3

2

2.3

3

5

No

2

3

3

2

2

3

3

2

3

2.3

2.3

3

6

No

3

2

3

3

1

2

3

1

3

3

1.3

3

7

Yes

3

2

3

1

0

0

0

0

0

1

0.6

1

8

Yes

1

0

0

0

0

0

0

0

0

0.3

0

0

9

Yes

3

1

3

1

0

0

0

0

0

1.3

0.3

1

Reversibility of effects: all parameters on day 22:

#

Wash

Cornea

Iris

Conjunctivae

 

 

Opac.

Area

 

R

C

D

1

No

2

2

0

0

0

0

2

No

0

0

0

0

0

0

3

No

3

2

0

0

0

0

4

No

0

0

0

0

0

0

5

No

0

0

0

0

0

0

6

No

0

0

0

0

0

0

7

Yes

0

0

0

0

0

0

8

Yes

0

0

0

0

0

0

9

Yes

0

0

0

0

0

0

Conclusions:
Under the conditions of this study , the test material is judged to be severely irritating to unwashed eyes.
Executive summary:

Calcium peroxide was instilled into the eyes of 9 New Zealand White rabbits at a dose of 0.10 g. The eyes of 6 rabbits remained unwashed while the eyes of 3 rabbits were gently washed with 100 mL of tap water approx. 20 -30 secondes after treatment. The eyes were assessed using the method of Draize and Primary Eye Irritation Indexes were calculated.

Under the conditions of this study, the test material is judged to be severely irritating to unwashed eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

A reliable and well-documented in vivo skin irritation study is available that assessed the skin irritation effects upon exposure of calcium peroxide on clipped rabbit skin. The study was performed according to GLP and internationally accepted protocols. No effects of irritation were observed on any of the test sites at any of the scoring intervals. As a consequence it was concluded that the test substance is not irritating to the skin.

Eye irritation

A reliable and well-documented in vivo eye irritation study is available that assessed the eye irritation effects upon instillation of calcium peroxide into the eyes of 9 New Zealand White rabbits. The eyes of 3 animals were washed with water approximately 20-30 seconds after treatment, whereas the eyes of the remaining 6 animals remained unwashed. The study was performed according to GLP and internationally accepted protocols. Severe effects of eye irritation were observed in the unwashed eyes, and irritation persisted beyond the 21 day observation period in two of the animals. The eyes that were washed shortly after exposure showed less severe effects, and the eye irritation subsided within 72 hours.

Respiratory irritation

No studies are available that addresses the effects of respiratory irritation following inhalation exposure to the reaction mass of calcium carbonate and calcium dihydroxide and calcium peroxide. Nevertheless, relevant information can be extracted from the studies available for read-across substances hydrogen peroxide and calcium oxide in the sections on acute inhalation toxicity and the studies with human volunteers.

A reliable acute inhalation toxicity (Hoffman, 1990) study is available for hydrogen peroxide in which male and female Sprague-Dawley rats received a single 4 -hour whole-body exposure to a 50% aqueous solution of hydrogen peroxide at the maximum attainable aerosol concentration of 170 mg/m3. All tested animals survived the exposure and subsequent 14 -day post-exposure observation period. Signs of treatment were minimal during the exposure but a few responses such as nasal discharge were noted during the whole 14 -day observation period.

Two reliable studies are available addressing respiratory irritation in human volunteers (Cain, 2004 and Cain, 2008). In the first study, 12 male healthy volunteers age 18-35 exercised against a light load for 20 minutes while they breathed air in a dome fed with controlled dust levels of 1, 2 or 5 mg calcium oxide / m3. In the second study, 6 male and 6 female volunteers were exposed to 2.5 mg calcium oxide / m3 for 45 minutes. In both experiments, test subjects reported sensory irritation, mainly in the nose, at the highest doses (2.5 and 5 mg/m3). Effects were less pronounced at lower doses.


Justification for selection of skin irritation / corrosion endpoint:
Reliable and well documented study according to internationally accepted guideline.

Effects on eye irritation: highly irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

In accordance to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for skin irritation based on the available test data for calcium peroxide in which no skin irritation effects are observed.

As some of the effects of irritation observed in the in vivo eye irritation study were not reversible within the 21 day observation period, classification of the reaction mass of calcium carbonate and calcium dihydroxide and calcium peroxide with an ‘Irreversible effects on the eye, Category 1’ classification is warranted.

The effects of respiratory irritation observed upon exposure to both hydrogen peroxide as well as calcium dihydroxide lead to a STOT-SE Cat. 3 classification for both substances. Therefore, a STOT-SE Cat. 3 with the respiratory tract as affected organ is also adopted for the reaction mass of calcium carbonate and calcium dihydroxide and calcium peroxide.