Praseodymium(III,IV) oxide

Endpoint summary

Description of key information

Skin Irritation

Two studies are provided. In both the key and supporting studies, no signs of dermal irritation were observed.

Eye Irritation

Two studies are provided. In both the key and supporting studies, no signs of ocular irritation were observed.

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:

26 December 1990 - 29 December 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. No irritation scores recorded for the 48 hour time point.

Qualifier:

according to guideline

Guideline:

other: FHSA 16 CFR 1500.41

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: Individually housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum; pelleted Purina Rabbit Chow
- Water (e.g. ad libitum): Tap water supplied by automatic watering system supplied ad libitum
- Acclimation period: 20 days
- Source: Davidson’s Mill Farm, S. Brunswick, New Jersey

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72 - 75 °F

IN-LIFE DATES: From: To: 26 December 1990 - 29 December 1990

Type of coverage:

occlusive

Preparation of test site:

other: shaved test sites with both intact and abraded skin

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5g undiluted

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

3 males and 3 females

Details on study design:

-The rabbits were prepared by clipping the skin free of hair over approximately 10 % of the body surface (dorsal and ventral surfaces from scapular to pelvic area). Two test application sites, each approximately 2.5 cm² were delineated. One site was left intact while the other was abraded with a needle, taking special precaution not to penetrate the stratum corneum and not to cause bleeding.
-0.5 g test material was placed on each site and was immediately covered with a 2 x 2.25 inch adhesive-backed gauze patch. The patches and entire trunk of each rabbit were then wrapped with an elastic cloth to aid in maintaining test-patch position and to minimise evaporation.
-The patches were removed after 24 hours of exposure at which time the test sites were gently wiped clean of any residual test material.

Skin sites were evaluated at approximately 24 and 72 hours after initial exposure and scored as follows:

Erythema and eschar formation:

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading 4

Oedema formation:

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24 h

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Abraded sites

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24 h

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Intact sites

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 6 animals

Time point:

72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Remarks:

Intact and Abraded sites

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Remarks:

Intact and Abraded sites

Irritant / corrosive response data:

Very slight erythema without oedema was observed at both abraded and intact sites of one rabbit only at 24 hours post-dosing. By 72 hours, no irritation was observed.

Other effects:

All animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

Table 1 Primary Dermal Irritation (PDI) Scores - Individual Results

Rabbit	24 hours		72 hours
	Abraded	Intact	Abraded	Intact
8058 8059 8060 8061 8062 8063	0/0 0/0 0/0 0/0 0/0 1/0	0/0 0/0 0/0 0/0 0/0 1/0	0/0 0/0 0/0 0/0 0/0 0/0	0/0 0/0 0/0 0/0 0/0 0/0
Total	1/0	1/0	0/0	0/0
Mean	0.17/0	0.17/0	0/0	0/0

Key: erythema and eschar / oedema

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test material is not irritating to skin and requires no classification in accordance with the EU criteria.

Executive summary:

The primary skin irritation potential of the test material was investigated in accordance with the FHSA guideline 16 CFR 1500.41.

0.5 g of the test material was applied to both an intact and abraded site on each of six New Zealand White rabbits. The sites were occluded for 24 hours. The patches were then removed and the test sites wiped to prevent further exposure. Evaluation occurred 24 and 72 hours after exposure.

With the exception of one rabbit, which exhibited very slight erythema without oedema at both the intact and abraded site at 24 hours, all sites were clear of irritation during the test period (PDII = 0.09).

Under the conditions of this study, the test material is not irritating to skin and requires no classification in accordance with the EU criteria.

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:

31 December 1990 - 3 January 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results. Irritation effects in animals only observed for 72 hours. Signs of conjunctival irriation still in evidence at 72 hour point in 2/6 rabbits, therefore observation period should have been extended.

Qualifier:

according to guideline

Guideline:

other: FHSA 16 CFR 1500.42

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: Individually housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum tap water supplied by automatic watering system
- Acclimation period: 25 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 71 - 73 °F

IN-LIFE DATES: From: To: 31 December 1990 - 3 January 1991

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye of each animal remained untreated and served as control

Amount / concentration applied:

undiluted
Amount applied: 0.1 g into the conjuctival sac of the left eye

Duration of treatment / exposure:

30 seconds for 3 of the treated eyes (washed eyes) and up to 72 hours for the 3 others (the upper and lower lids were gently held together for about 1 second to prevent loss of the test material).

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Three of the treated eyes were rinsed with 30cc of saline 30 seconds post-instillation. The remaining three eyes were not irrigated.

SCORING SYSTEM: Draize Scale for Ocular Irritation.
After instillation of the test material, ocular lesions were evaluated in accordance with Draize et al. at 24, 48 and 72 hours.
Special care was taken to look for and notate any unusual effects, such as pannus, blistering of the conjunctivae, ulceration and other indicators of corrosive action.


Draize Scale for Scoring Ocular Irritation

1. CONJUNCTIVAE

(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal............................................................................................................................................0
Vessels definitely injected above normal................................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red.........................................................................................................................................3

(B) Chemosis
No swelling..................................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids.......................................................................................2
Swelling with lids about half closed.........................................................................................................3
Swelling with lids half closed to completely closed...............................................................................4

(C) Discharge
No discharge...............................................................................................................................................0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals)......................................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids...............................................2
Discharge with moistening of the lids and hairs a considerable area around the eye...................3

THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20

2. IRIS

(D) Values
Normal.........................................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these or combination of any thereof) iris still reacting to light
(sluggish reaction is positive).................................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10

3. CORNEA

(E) Degree of Opacity (most dense area used)
No opacity...................................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible......................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity................................................................................4

(F) Area of Cornea Involved
One quarter (or less) but not zero..........................................................................................................1
Greater than one quarter but less than half...........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.......................................................................................4

THE TOTAL SCORE = (E x F) x 5 MAXIMUM TOTAL = 80

MAXIMUM TOTAL SCORE POSSIBLE = 110

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Unwashed

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: Unwashed

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

1.11

Max. score:

3

Reversibility:

other: 1 animal still exhibited a hyperaemia score of 1 after 72 hours

Remarks on result:

other: Unwashed

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Unwashed

Irritation parameter:

other: discharge

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0.11

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Unwashed

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Washed

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: Washed

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

1.11

Max. score:

3

Reversibility:

other: 1 animal still exhibited a hyperaemia score of 1 after 72 hours

Remarks on result:

other: Washed

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Washed

Irritation parameter:

other: discharge

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0.11

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Washed

Irritant / corrosive response data:

-Conjunctival irritation was observed in all treated eyes, unwashed and washed, at 24 hours post-dosing. By 72 hours, this was observed in only one washed and one unwashed treated eye.
-No corneal opacity or iritis was noted during the test period.

Other effects:

All animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

Table 1: Individual Results

Time Point (hours)	Rabbit Number	Cornea	Iris	Conjunctivae	Chemosis	Discharge
24	8087 8088 8089 8090 8091 8092	0 0 0 0 0 0	0 0 0 0 0 0	3 2 1 2 2 1	1 1 0 0 1 0	1 0 0 0 0 1
48	8087 8088 8089 8090 8091 8092	0 0 0 0 0 0	0 0 0 0 0 0	2 2 0 2 1 1	1 0 0 0 0 0	0 0 0 0 0 0
72	8087 8088 8089 8090 8091 8092	0 0 0 0 0 0	0 0 0 0 0 0	1 0 0 1 0 0	0 0 0 0 0 0	0 0 0 0 0 0

Rabbits 8090, 8091 and 8092 had the treated eye rinsed with 30 cc of saline solution 30 seconds post-installation

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The test material produced minimal irritation to both the unwashed and washed eyes; no classification is required.

Executive summary:

A primary eye irritation study was conducted in accordance with the FHSA guideline 16 CFR 1500.42.

0.1 g of the test material was instilled into the left eye of six New Zealand white rabbits, with three of the treated eyes being rinsed after 30 seconds with saline. The animals were observed for 72 hours and the eyes examined at 24, 48 and 72 hours. Irritation was scored according to the method of Draize.

 

The test material produced minimal irritation to both the unwashed and washed eyes and no classification is required under the conditions of this study in accordance with EU Criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

The key study was conducted in accordance with the standardised guideline FHSA 16 CFR 1500.41.

0.5 g of the test material was applied to both an intact and abraded site on each of six New Zealand White rabbits. The sites were occluded for 24 hours. The patches were then removed and the test sites wiped to prevent further exposure. Evaluation occurred 24 and 72 hours after exposure.

With the exception of one rabbit, which exhibited very slight erythema without oedema at both the intact and abraded site at 24 hours, all sites were clear of irritation during the test period.

Under the conditions of this study, the test material is not irritating to skin and requires no classification.

 

Supporting information is provided in the form of a second study that broadly followed the FHSA 16 CFR 1500.41 guideline. This study was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997).

Six New Zealand White rabbits were dermally exposed to 0.5 g of the test material on one intact and one abraded skin site. Test sites were covered with an occlusive dressing for 24 hours and the animals were observed for the following 72 hours. Irritation was scored by the method of Draize.

There were no signs of dermal irritation and the Primary Dermal Irritation Index = 0.0.

In this study the test material is not a dermal irritant and does not require classification.

 

Eye Irritation

The key eye irritation study was conducted in accordance with the standardised guideline FHSA 16 CFR 1500.42.

0.1 g of the test material was instilled into the left eye of six New Zealand white rabbits, with three of the treated eyes being rinsed after 30 seconds with saline. The animals were observed for 72 hours and the eyes examined at 24, 48 and 72 hours. Irritation was scored according to the method of Draize.

The test material produced minimal irritation to both the unwashed and washed eyes and no classification is required under the conditions of this study.

 

Supporting information is provided in the form of second study conducted broadly in accordance with FHSA guideline 16 CFR 1500.42. This study was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997).

0.1 g of the test material was instilled into the left eye of six New Zealand white rabbits, with three of the treated eyes being rinsed after 30 seconds with saline. The animals were observed and the eyes examined at 24, 48 and 72 hours. Irritation was scored according to the method of Draize.

The test material produced minimal irritation to both the unwashed and washed eyes and no classification is required under the conditions of this study.

Justification for selection of skin irritation / corrosion endpoint:

The key study was conducted in accordance with the standardised guideline FHSA 16 CFR 1500.41. It was well reported and adhered to sound scientific principles. It was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997).

Justification for selection of eye irritation endpoint:

The key study was conducted in accordance with the standardised guideline FHSA 16 CFR 1500.42. It was well reported and adhered to sound scientific principles. It was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997).

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the test material does not require classification for irritation or corrosion to either the skin or eye.