Reaction mass of cerium phosphate and lanthanum phosphate and terbium phosphate

Endpoint summary

Description of key information

- Skin irritation: really slightly irritating but not classified
- Eye irritation: slightly irritating but not classified

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:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

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

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).

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

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

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

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

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

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

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

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)

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.

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.

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

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

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

         

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate was tested in one dermal irritation study and one eye irritation study, both performed according to internationally recognized guidelines and GLP, scored as validity 1 according to Klimisch criteria, and considered as key studies acceptable for the assessment.

Skin Irritation

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 (CIT, 2007).

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 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.

Under the experimental conditions of this study, the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was slightly irritant when applied topically to rabbits. However, according to EU classification criteria, the test item should not be classified as irritating to the skin.

Eye Irritation

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 (CIT, 2007).

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 irritant to the eye of the rabbit but doesn't need to be classified as an eye irritant according to EU criteria.

Justification for selection of skin irritation / corrosion endpoint:
Only one study is available.
Key study quoted as reliability 1 according to Klimisch criteria (performed according to OECD guidelines and in accordance with GLP)

Justification for selection of eye irritation endpoint:
Only one study is available.
Key study quoted as reliability 1 according to Klimisch criteria (performed according to OECD guidelines and in accordance with GLP)

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Based on the results of these studies, Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate was considered as very slighty irritant to the skin and to the eye.

Based on the low level of dermal and eye irritation observed in rabbits, no classification for skin and eye irritation is warranted, according to the criteria of Annex VI Directive 67/548/EEC or UN/EU GHS.