Registration Dossier

Administrative data

Description of key information

Skin irritation / corrosion:
Based on the test results (in vivo study performed according to OECD guideline 404), yttrium zirconium oxide (a form of zirconium oxide stabilised with yttrium oxide) was determined not to be irritating to the skin of New Zealand White rabbit (Chemical Evaluation and Research Institute, 2000).
Eye irritation:
Based on the test results obtained with New Zealand White rabbit (in vivo study performed according to OECD guideline 405), yttrium zirconium oxide (a form of zirconium oxide stabilised with yttrium oxide) does not need to be classified as irritating to eyes (Chemical Evaluation and Research Institute, 2000).

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:
2000-02-08 to 2000-03-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented, scientifically sound study with methods similar to OECD guidline 404 with the following deviations: not GLP, no information on environmental conditions, and no mention of untreated areas used as controls.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Not GLP, no information on environmental conditions, and no mention of untreated areas used as controls.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Biotech Co., Ltd
- Age at study initiation: 3 months
- Weight at study initiation: 2.91-3.28 kg
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: From: no data To: no data
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g; moistened with distilled water for injection
- Concentration (if solution): no data

VEHICLE
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): no data
- Lot/batch no. (if required): not applicable
- Purity: not applicable
Duration of treatment / exposure:
4 hours
Observation period:
1, 24 and 48 hours after the lint removal.
Number of animals:
3 male animals
Details on study design:
TEST SITE
- Area of exposure: dorsal
- % coverage: no data
- Type of wrap if used: 0.5 g of the test agent was applied to a 2.5 cm square lint (Nankai Sangyou Inc.), and was secured with a piece of White Tape (Nichiban Co., Ltd.). Two application areas were established per animal. Each area was covered with a piece of oilpaper (Amadin Inc.), and the torso was covered by Silkytex (Alcare Co., Ltd.) to protect and secure the lint.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the area was wiped off with distilled water for injection to remove the test agent
- Time after start of exposure: 4 hours

SCORING SYSTEM: Grades were given based on the Draize scoring method. The skin irritation of the test agent was evaluated according to skin primary irritation evaluation standard of the AFNOR (1982)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
not measured/tested
Remarks:
The last observation was after 48 h, which is acceptable since no signs of irritation were observed in any of the exposed animals.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
not measured/tested
Remarks:
The last observation was after 48 h, which is acceptable since no signs of irritation were observed in any of the exposed animals.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1 hour
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
not measured/tested
Remarks:
The last observation was after 48 h, which is acceptable since no signs of irritation were observed in any of the exposed animals.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
not measured/tested
Remarks:
The last observation was after 48 h, which is acceptable since no signs of irritation were observed in any of the exposed animals.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
not measured/tested
Remarks:
The last observation was after 48 h, which is acceptable since no signs of irritation were observed in any of the exposed animals.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1 hour
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
not measured/tested
Remarks:
The last observation was after 48 h, which is acceptable since no signs of irritation were observed in any of the exposed animals.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24 and 48 hours
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No irritation was observed after 48 hours.
Other effects:
There were no abnormalities in the general condition or the weight changes to any of the 3 animals.
Interpretation of results:
GHS criteria not met
Conclusions:
No irritative reaction was observed during the observation period.
Endpoint:
skin corrosion: 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 vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000-02-08 to 2000-03-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Well documented, scientifically sound study according to a method similar to OECD guideline 405 with a few deviations. However, not GLP, no information on environmental conditions, individual eye endpoints (cornea, iris, conjunctiva) not reported in the results.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
not GLP, no information on environmental conditions, individual eye endpoints (cornea, iris, conjunctiva) were not reported in the results
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Biotech Co., Ltd
- Age at study initiation: 4 months old
- Weight at study initiation: 3.22-3.59 kg
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: no data To: no data
Vehicle:
unchanged (no vehicle)
Controls:
other: right eyes were kept as controls
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
- Concentration (if solution): not applicable

VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable
- Concentration (if solution): not applicable
- Lot/batch no. (if required): not applicable
- Purity: not applicable
Duration of treatment / exposure:
single instillation
Observation period (in vivo):
1, 24, 48, and 72 hours
Number of animals or in vitro replicates:
3 animals (administered to the left eye of each animal)
Details on study design:
SCORING SYSTEM: According to Draize's standard (1959). Cornea, iris and conjunctiva were observed, and acknowledged damages were recorded. After calculating the total scores of each observation of each animal (Individual ocular irritation index, IOI) and the average score of each observation of each group (Mean ocular irritation index, MOI), the evaluation was made according to the AFNOR (1982) evaluation criteria. The acute ocular irritation index (AOI) was defined as the maximum of the MOI.

Accident Value Test of Corneal Epithelium: After the accident value test of anterior ocular segment done 24 hours after the application, corneal epithelium were dyed with fluorescein, and the stainability was evaluated.

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
other: MOI
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 1 hour
Score:
4.7
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: MOI
Basis:
mean
Remarks:
of 3 animals
Time point:
24 h
Score:
6
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: MOI
Basis:
mean
Remarks:
of 3 animals
Time point:
48 h
Score:
2
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: MOI
Basis:
mean
Remarks:
of 3 animals
Time point:
72 h
Score:
0
Max. score:
110
Reversibility:
other: not applicable
Irritation parameter:
other: AOI
Basis:
mean
Remarks:
of 3 animals
Time point:
24 h
Score:
6
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
The AOI was determined to be 6.0 at 24 hours and the MOI after 48 hours was 2.0, therefore, this test agent was determined to be slightly irritating based on the AFNOR (1982) criteria. No irritation was observed after 72 hours.

The Accident Value Test of Corneal Epithelium 24 hours after application was zero in all three animals.
Other effects:
There were no abnormalities in the general condition or the weight changes to any of the 3 animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The test agent was determined to be slightly irritating based on the AFNOR criteria. It does however not need to be classified for eye irritation according to the CLP criteria.
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 conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation / corrosion:

One reliable studiy was identified (Klimisch 2). The study performed by Chemical Evaluation and Research Institute (2000) is a non-GLP study performed according to the OECD 404 guideline with minor deviations. Yttrium zirconium oxide (a form of zirconium oxide stabilised with yttrium oxide) was determined not to be irritating to New Zealand White rabbit skin after 4 hours of exposure.

Eye irritation:

A reliable study was performed with yttrium zirconium oxide (Chemical Evaluation and Research Institute, 2000) in New Zealand White rabbit according to OECD guideline 405 with minor deviations. The test substance was determined to be slightly irritating based on the AFNOR criteria but the observed effects were fully reversible within 72 hours. Therefore, it does not need to be classified for eye irritation according to the rules of the CLP Regulation.

Justification for classification or non-classification

Skin irritation / corrosion:

Based on to the available data and according to the criteria of the CLP Regulation, this substance should not be classified for skin corrosion / irritation or for eye irritation.