Reaction mass of cerium phosphate and lanthanum phosphate and terbium phosphate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 18-JUNE-2007 to 23-NOVEMBER-2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to EU / OECD guidelines and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

cerium(3+) lanthanum(3+) terbium(3+) triphosphate

EC Number:

915-152-1

Molecular formula:

(La,Ce,Tb)PO4

IUPAC Name:

cerium(3+) lanthanum(3+) terbium(3+) triphosphate

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS:
- Source: Grimaud frères selection S.A.S., La corbière, Roussay, France
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 3.2 ± 0.1 kg
- Housing: individually in Pajon cages (50 cm x 57 cm x 75 cm)
- Food consumption: free access to 110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France)
- Water consumption: Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS :
- Temperature: 18 ± 3°C
- Humidity: 30 to 70%
- Air changes: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12 h dark/12 h light

In-life dates: From: 03-JULY-2007 To: 16-JULY-2007

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye, which remained untreated, served as control

Amount / concentration applied:

TEST MATERIAL:
- Amount applied (volume or weight with unit): 0.1 g introduced into the conjunctival sac of the left eye
- Concentration (if solution): not applicable
- pH: no applicable

VEHICLE: /

Duration of treatment / exposure:

Single conjunctival instillation

Observation period (in vivo):

1 hour, 24, 48 and 72 hours after the administration and then until reversibility of the ocular reactions (day 5)

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed

SCORING SYSTEM: according to the numerical scoring system listed in Directive 2004/73/EC

Tool used to assess score: eyes were examined under a UV lamp after instillation of 1 or 2 drops of 0.5% sodium
fluorescein solution for the evaluation of corneal opacification (presence or absence, affected area)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for corneal opacity.

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for iris lesions.

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.7 - 1.3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean scores calculated for each animal over 24, 48 and 72 hours were 1.3, 0.7 and 1.3 for redness of the conjunctiva

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.7 - 1.3

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean scores calculated for each animal over 24, 48 and 72 hours were 1.3, 0.7 and 1.0 for chemosis.

Irritant / corrosive response data:

A slight to marked chemosis (grades 1 to 3) and a slight or moderate redness of the conjunctiva (grade 1 or 2) were noted in all the animals from day 1 until day 3 (one animal) or 4 (two animals). A clear to whitish purulent discharge was observed in all the animals between day 1 and day 4.
An iritis (grade 1) was noted in 1/3 animals on day 1 only.
Mean scores calculated for each animal over 24, 48 and 72 hours were 1.3, 0.7 and 1.0 for chemosis, 1.3, 0.7 and 1.3 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity.

Other effects:

no

Any other information on results incl. tables

Report N° 33239 TAL / Eye irritation

Result Table: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	0/0/0	1/0/0	2/2/2	2/3/2
24 h	0/0/0	0/0/0	2/1/2	2/1/1
48 h	0/0/0	0/0/0	1/1/1	1/1/1
72 h	0/0/0	0/0/0	1/0/1	1/0/1
Average 24h, 48h, 72h	0	0	1.3/0.7/1.3	1.3/0.7/1.0
Area effected	0	-	-	-
Reversibility*)	-	c.	c.	c.
Average time (unit) for reversion	-	24 h	Day 5	Day 5

 

*) Reversibility: c. = completely reversible; n.c.= not completely reversible; n. = not reversible

         

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions of this study, the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was slightly irritating when administered by ocular route to rabbits. However, according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test item should not be classified as irritating to the eyes.

Executive summary:

The potential of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate to induce ocular irritation was evaluated in rabbits according to OECD No. 405 and EC B.5 guidelines and in compliance with the principles of Good Laboratory Practice Regulations.

The test item was first administered to a single male New Zealand White rabbit. Since the test item was not severely irritant on this first animal, it was then evaluated sequentially in two other animals. A single dose of 100 mg of the test item in its original form was introduced into the left conjunctival sac. The right eye was not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then until reversibility of the ocular reactions (day 5). The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

A slight to marked chemosis and a slight or moderate redness of the conjunctiva were noted in all the animals from day 1 until day 3 (one animal) or 4 (two animals). A clear to whitish purulent discharge was observed in all the animals between day 1 and day 4. An iritis was noted in 1/3 animals 1 hour after instillation only.

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.3, 0.7 and 1.0 for chemosis, 1.3, 0.7 and 1.3 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity.

Under the experimental conditions of this study, the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was slightly irritating to the eye of the rabbit but needs not to be classified according to EU criteria.

This eye irritation study is classified as acceptable. It does satisfy the guideline requirement for a skin irritation study (B.5) in the rabbit