Cerium terbium magnesium undecaaluminum nonadecaoxide (hexagonal) ((Ce, Tb)MgAl11O19) and aluminium oxide (Al2O3) from calcination of Al2O3, CeO2, MgO and Tb4O7

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 17, 2010 - January 19, 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Although since 1 June 2008 it has been mandatory to first consider and use whenever possible in vitro testing when generating new data for the eye irritation endpoint, an in vitro test was not performed before generating in vivo data because the registrant was incorrectly informed by the testing facility that "No validated in vitro method is available for assessing acute eye irritation/corrosion". As reported in their study report on page 14 as justification for the selection of the test method.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(2002)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

(1998)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Cerium terbium magnesium undecaaluminum nonadecaoxide

Molecular formula:

Ce0.5Tb0.5MgAl11O19 -Ce0.7Tb0.3MgAl11O19

IUPAC Name:

Cerium terbium magnesium undecaaluminum nonadecaoxide

Constituent 2

Reference substance name:

Aluminium oxide

EC Number:

215-691-6

EC Name:

Aluminium oxide

Cas Number:

1344-28-1

Molecular formula:

Al2O3

IUPAC Name:

aluminium trioxide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): CAT
- Physical state: colourless solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 23 weeks old
- Weight at study initiation: >2 kg
- Housing: individually housed in ABS - plastic rabbit cages, floor 4200 cm^2
- Diet: autoclaved hay and Altromin 2123 maintenance diet (lot no. 0955), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: November 28, 2010 To: December 20, 2010

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g

Duration of treatment / exposure:

Not applicable (the treated eyes were not rinsed)

Observation period (in vivo):

The animals were observed for 72 hours after dosing. To determine the reversibility of the observed effects in animal no. 1, the observation period was extended to the maximum of 21 days after dosing.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE: Not applicable
SCORING SYSTEM: in accordance with OECD 405
TOOL USED TO ASSESS SCORE: fluorescein (only 72 hours after installation)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

- In animal #1, effects on the cornea (score: 1) were observed starting from 24 hours after installation up to the end of the observation period (21 days)
- In none of the animals, any effects on the iris were observed
- In animal #1, conjunctival redness (score: 1) was observed starting from 1 hour after installation up to day 6. In the other 2 animals, conjunctival redness (score: 1) was observed starting from 1 hour after installation up to 48 hours after installation.
- In animal #1, chemosis (score: 1) was observed starting from 1 hour after installation up to 72 hours after installation. In the other 2 animals, chemosis (score: 2) was observed 1 hour after installation and chemosis (score: 1) was observed at 24 and 48 hours after installation.

Other effects:

- All 3 animals had a slight discharge after 1 hour

Any other information on results incl. tables

- No mortalities nor significant clinical signs of toxicity were observed

Applicant's summary and conclusion

Interpretation of results:

other: Category 1 (irreversible effects on the eye) based on GHS and CLP criteria

Conclusions:

In an acute eye irritation study in 3 rabbits, conducted in accordance with OECD 405 (2002), EU Method B.5 (2008), EPA OPPTS 870.2400 (1998) and according to GLP principles, irritant effects were observed which were not all fully reversible. Based on the results of this study, the substance needs to be classified as causing irreversible effects on the eye (Category 1).

Executive summary:

An acute eye irritation study was conducted in 3 rabbits in accordance with OECD 405 (2002), EU Method B.5 (2008), EPA OPPTS 870.2400 (1998) and according to GLP principles. In none of the animals, any effects on the iris were observed. In one animal, effects on the cornea (score: 1) were observed starting from 24 hours after installation up to the end of the observation period (21 days). In the same animal also conjunctival redness (score: 1) was observed starting from 1 hour after installation up to day 6 and chemosis (score: 1) starting from 1 hour after installation up to 72 hours after installation. In the other 2 animals, conjunctival redness (score: 1) was observed starting from 1 hour after installation up to 48 hours after installation and chemosis (score: 2) was observed 1 hour after installation and chemosis (score: 1) was observed at 24 and 48 hours after installation. Based on the results of this study, the substance needs to be classified as causing irreversible effects on the eye (Category 1).