Dialuminium zinc tetraoxide

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): not irritating

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:

22 Jan - 01 Feb 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study (although no information on systemic effects are given in the test report, the study is considered to be reliable without restriction as the acute dermal toxicity study did not show adverse systemic effects)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

no information on systemic effects are given in the test report

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

no information on systemic effects are given in the test report

GLP compliance:

yes (incl. QA statement)

Remarks:

GROUPE INTERMINISTERIEL DES PRODUITS CHIMIQUES

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome, Quartier Labaste, Linxe, France
- Age at study initiation: 12 - 13 weeks
- Weight at study initiation: 2.48 - 2.85
- Housing: individual
- Diet: SAFE-112, ad libitum
- Water: tap-water from public distribution system
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

the test item was moistened with distilled water prior to treatment to ensure good contact with the skin

Controls:

other: not required, untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 h

Observation period:

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals:

1 female (initial test)
2 females (confirmatory test)

Details on study design:

TEST SITE
- Area of exposure: 6 cm² on the flank
- Type of wrap if used: The patch containing the test substance was secured in position with a strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was removed with distilled water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

1 h after patch removal, a very slight erythema of grade 1 was noted on the treated areas of all animals which were fully reversible after 24 h.

Other effects:

No systemic adverse effects are described in the report. Test animals gained approx. 100 g body weight during the study period of 3 days.

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

CLP: not classified

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 - Guideline study (no information on systemic effects are given in the test report, no anesthetics or analgesics were used)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24 April 2002

Deviations:

yes

Remarks:

no information on clinical signs or pain/distress are given in the test report, no anesthetics or analgesics were used

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no information on clinical signs or pain/distress are given in the test report, no anesthetics or analgesics were used

GLP compliance:

yes (incl. QA statement)

Remarks:

GROUPE INTERMINISTERIEL DES PRODUITS CHIMIQUES

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome, Quartier Labaste, Linxe, France
- Age at study initiation: 13 weeks
- Weight during study period: 2.46 - 3.00 kg
- Housing: individual
- Diet: SAFE-112, ad libitum
- Water: tap-water from public distribution system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

1 h in 2 animals; the test substance was not washed out in the 3rd animal

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

1 female (initial test)
2 females (confirmatory test)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Remaining test item was rinsed with physiological saline in 2 animals
- Time after start of exposure: 1 h

SCORING SYSTEM: similar to Draize scoring system, supplemented with scoring for discharge and extent of opacity

Discharge:
No discharge - 0
Slight discharge (normal slight secretions in the inner corner to be taken into account) -2
Discharge with moistening of the eyelids and neighbouring hairs - 2
Discharge with moistening of the eyelids and large areas around the eye -3

Cornea: Extent of opacity:
Opaque area present but covering 1/4 or less - 1
Between 1/4 or 1/2 - 2
Between 1/2 and 3/4 - 3
Between 3/4 and the entire surface - 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

The test item induced only weak reactions including redness of the conjunctivae in 2/3 animals and chemosis in 1/3 animals which were fully reversible within up to 72 or 48 h, respectively. No adverse effects on the cornea or iris were observed.

Other effects:

No information on clinical signs or pain/distress are reported.

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

In the acute dermal toxicity study, erythema were observed in all test animals on the treated skin 24 hours after substance application. Therefore, according to the data requirements given in Annex VIII of 1907/2006/EC, an in vivo dermal irritation study was conducted to evaluate the irritating properties of the test substance.

In detail, a GLP-guideline study according to OECD guideline 404 was performed (Colas, S. 2013a). 3 female New Zealand White Rabbits were exposed to 0.5 g of moistened test material for 4 hours under semi-occlusive dressings. Despite slight erythema of grade 1, which were noted on the treated areas of all animals 1 hour after patch removal, no skin reactions were determined at later time points. Body weight gain of test animals was within the expected range. Thus, the test item Zinc aluminium oxide did not show irritating properties in the conducted study. 

Eye irritation

The eye irritation potential of Zinc aluminium oxide was evaluated in a sequential testing strategy including an in vitro eye corrosion/irritation test prior to in vivo testing as outlined in the OECD test guideline 405 for eye corrosion/irritation. In detail, a Hen´s egg test-chorioallantoic membrane (HET-CAM) according to the ICCVAM recommended test method protocol was performed (Andres, 2011a). 0.3 mL of the test item were applied unchanged to the CAM´s of 6 fertilized hen´s eggs for up to 300 sec. Afterwards, the CAM was observed for the development of lysis, heamorrhage and coaggulation.0.9% NaCl, 1% SDS and 0.1 N NaOH (each dissolved in deionised water) were included as control substances. Application of the test item induced haemorrhage of the CAM observed after 61.5 s and lysis after 115.7 sec whereas no signs of coaggulation were observed corresponding to an irritation score of 8.32. In contrast, NaCl treated negative controls did not show any sign of irritation. Both positive controls substances induced severe irritation of the CAM as they induced irritation scores of 20.04 and 11.16 for 0.1 N NaOH and 1% SDS, respectively. According to the evaluation criteria, Zinc aluminium oxide was considered as moderately irritating corresponding to an irritation score within the range of 5 – 8.9. As the HET-CAM in vitro assay can only be used for classification as severe eye irritant (Serious eye damage Category 1), the result of the conducted study was considered as insufficient for classification. Thus, further evaluation of the eye irritation potency of Zinc aluminium oxide was performed in a GLP-guideline study according to OECD guideline 405. A single ocular dose of 0.1 g Zinc aluminium oxide was applied to the eye of 3 female New Zealand White Rabbits (Colas, 2013b). In 2 animals, remaining test item was rinsed with physiological saline 1 h after instillation. The test item induced only weak reactions including redness of the conjunctivae in 2/3 animals and chemosis in 1/3 animals with overall mean scores of 0.3, 0.7 and 0.3, respectively. All reactions were fully reversible within up to 72 or 48 h, respectively. No adverse effects on the cornea or iris were observed.

Based on the available data on skin and eye irritation, Zinc aluminium oxide is not considered as irritant.

Justification for classification or non-classification

Based on the available data, Zinc aluminium oxide does not meet the criteria for classification according to Regulation (EC) 1272/2008.