Reaction mass of cerium phosphate and lanthanum phosphate and terbium phosphate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 18-JUNE-2007 to 21-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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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: 3.0 ± 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: 26-JUNE-2007 To: 01-JULY-2007

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated skin served as control

Amount / concentration applied:

- TEST MATERIAL:
Amount applied (volume or weight with unit): 0.5 g of the test item in its original form were placed on a gauze pad moistened with purified water
Concentration (if solution): undiluted
pH: no applicable

- VEHICLE:
none

Duration of treatment / exposure:

3 min, 1 hour and 4 hours in one animal, 4 hours in 2 animals

Observation period:

1, 24, 48 and 72 hours after removal of the dressing. The study was ended on day 4 in the absence of persistent irritation reactions.

Number of animals:

3 males

Details on study design:

TEST SITE:
- Area of exposure: 6 cm2 of the anterior left flank (application for 3 minutes), the anterior right flank (application for 1 hour) or the
posterior right flank (application for 4 hours) of the animals.
- % coverage: no data
- Type of wrap if used: The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE:
- Washing (if done): After removal of the dressing, any residual test item was wiped off by means of a dry cotton pad.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema and eschar formation and edema formation were scored according to the numerical scoring system listed in the Commission Directive 2004/73/EC (scale 0 to 4).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.3 - 0.7

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean scores over 24, 48 and 72 hours for each animal were 0.7, 0.3 and 0.0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

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

Irritant / corrosive response data:

After a 3-minute or 1-hour exposure (one animal) : no cutaneous reactions were observed.
After a 4-hour exposure (three animals): A very slight erythema (grade 1) was noted in all the animals on day 1; it persisted on day 2 in one of them and until day 3 in the third animal. Mean scores over 24, 48 and 72 hours for each animal were 0.7, 0.3 and 0.0 for erythema and 0.0, 0.0 and 0.0 for edema.

Other effects:

no

Any other information on results incl. tables

Report N° 33238 TAL / Skin 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	Erythema	Edema
	Max. score: 4	Max. score: 4
60 min	1/1/1	0/0/0
24 h	1/1/0	0/0/0
48 h	1/0/0	0/0/0
72 h	0/0/0	0/0/0
Average 24h, 48h, 72h	0.7/0.3/0.0	0/0/0
Reversibility*)	c.	-
Average time (unit) for reversion	72 h.	-

*) 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 was slightly irritating when applied topically to rabbits. However, according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate should not be classified as irritating to the skin.

Executive summary:

The potential of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate to induce skin irritation was evaluated in rabbits according to OECD No. 404 and EC B.4 guidelines and in compliance with the principles of Good Laboratory Practice Regulations.

The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test item was neither severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals.

A single dose of 500 mg of the test item in its original form was applied to the closely-clipped skin of one flank. The test item was held in contact with the skin by means of a semi-occlusive dressing.

Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. The mean values of the scores for erythema and edema were calculated for each animal.

After a 3-minute or 1-hour exposure (one animal), no cutaneous reactions were observed.

After a 4-hour exposure (three animals), a very slight erythema was noted in all the animals on day 1; it persisted on day2 inone of them and until day3 inthe third animal.

Mean scores over 24, 48 and 72 hours for each animal were 0.7, 0.3 and 0.0 for erythema and 0.0, 0.0 and 0.0 for edema.

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 applied topically to rabbits. However, according to EU classification criteria, the test item should not be classified as irritating to the skin.

This skin irritation study is classified as acceptable. It does satisfy the guideline requirement for a skin irritation study (B.4) in the rabbit