Reaction mass of cerium dioxide and lanthanum oxide and lanthanum fluoride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

November 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD TG 405-compliant study, using a main constituent of the reaction mass for a read-across purpose

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cerium dioxide

EC Number:

215-150-4

EC Name:

Cerium dioxide

Cas Number:

1306-38-3

Molecular formula:

CeO2

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Roucher, Couhé France - EGAV, Passais-la-Conception France - Elevage Scientifique des Dombes, Châtillon-sur-Chalaronne France - Gwen Meur, Trégonneau France
- Age at study initiation: not specified
- Weight at study initiation: 2.5 kg +/- 200 g
- Housing: individual polystyrene cages (54 x 36 x 31.5 cm)
- Diet: 150 g pelleted diet/animal/day
- Water: ad libitum
- Acclimation period: at least 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12 (7.30 am - 7.30 pm)


IN-LIFE DATES: 25 November 1982 (instillation)

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g

Duration of treatment / exposure:

Single conjunctival instillation

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- No washing


SCORING SYSTEM:

- Conjunctivae
* Chemosis: Swelling (refers to lids and/or nictating membranes)
Normal -> 0
Some swelling above normal -> 1
Obvious swelling, with partial eversion of lids -> 2
Swelling, with lids about half closed -> 3
Swelling, with lids more than half closed -> 4
(VALUE A)

* Discharge
No discharge -> 0
Slight discharge -> 1
Discharge with humidification of lids and hair around -> 2
Discharge with humidification of lids and large area around -> 3
(VALUE B)

* Redness (refers to palpebral and bulbar conjunctivae; excluding cornea and iris)
Normal -> 0
Some blood vessels hyperaemic (injected) -> 1
Diffuse, crimson colour; individual vessels not easily discernible -> 2
Diffuse beefy red -> 3
(VALUE C)

- Iris
Normal -> 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia;
or injection; iris reactive to light (a sluggish reaction is considered to be an effect -> 1
Hemorrhage, gross destruction, or no reaction to light -> 2
(VALUE D)

- Cornea
* Opacity: degree of density (readings from most dense area)
No ulceration or opacity -> 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre);
details of iris clearly visible -> 1
Easily discernible translucent area; details of iris slightly obscured -> 2
Nacrous area; no details of iris visible; size of pupil barely discernible -> 3
Opaque cornea; iris not discernible through the opacity -> 4
(VALUE E)

* Surface of opacity:
Less than 1/4 -> 1
Between 1/4 and 1/2 -> 2
Between 1/2 and 3/4 -> 3
Between 3/4 and whole surface -> 4
(VALUE F)

=> Conjunctiva score = 2 x (A + B + C)
=> Iris score = 5 x D
=> Cornea score = 5 x E x F
=> Individual total score (per time-point) = Conjunctiva + Iris + Cornea scores (maximum 110)
=> Maximum Mean Total Score (at a given time-point)


TOOLS USED TO ASSESS SCORE: Heine's ophthalmoscope +/- slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 hour

Score:

9.33

Max. score:

110

Reversibility:

fully reversible within: 3 days from instillation

Results 2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 day

Score:

1.33

Max. score:

110

Reversibility:

fully reversible within: 3 days from instillation

Results 3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 2 days

Score:

0.67

Max. score:

110

Reversibility:

fully reversible within: 3 days from instillation

Irritant / corrosive response data:

See table below for details

Any other information on results incl. tables

Summary of the observed ocular irritation scores (3 rabbits):

Time after instillation		1 hour			1 day			2 days			3 days			4 days			7 days
Rabbit No.		448	449	450	448	449	450	448	449	450	448	449	450	448	449	450	448	449	450
Conjunctiva	Chemosis	2	1	1	1	0	1	1	0	0	0	0	0	0	0	0	0	0	0
	Discharge	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Redness	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Iris		1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cornea	Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Surface	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Individual Total Score		13	11	4	2	0	2	2	0	0	0	0	0	0	0	0	0	0	0
Mean Total Score		9.33			1.33			0.67			0			0			0

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Cerium Oxide is not classified as an eye irritant.

Executive summary:

In a primary eye irritation study (Institut Français de Toxicologie report No. 302314), 0.1 g of Cerium dioxide were instilled into the conjunctival sac of the right eye of 3 male New Zealand White rabbits. Exposed eyes were not washed. Animals then were observed for 7 days. Irritation was scored 1 hours after instillation and on days 1, 2, 3, 4 and 7 by calculating ocular irritation scores, based on the grading of conjunctiva, iris and cornea scores.

 

Slight to moderate conjunctival chemosis was observed in all 3 rabbits within 48 hours after instillation, together with slight conjunctival discharge in all animals and conjunctival enanthema and iris congestion in 2 animals, at 1 hour after instillation. All the irritation signs had reversed by day 3. Mean ocular irritation scores were 9.33, 1.33 and 0.67 at 1 h after instillation and on days 1 and 2, respectively.

 

The test substance was therefore not classified as irritant to the eye, according to the criteria of Annex VI Directive 67/548/EEC.

 

This study is classified as acceptable. It satisfies the OECD 405 guideline requirements for acute eye irritation or corrosion.