Praseodymium(III,IV) oxide

Eye irritation

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: FHSA 16 CFR 1500.42

Deviations:

no

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Praseodymium(III,IV) oxide

EC Number:

234-857-9

EC Name:

Praseodymium(III,IV) oxide

Cas Number:

12037-29-5

Molecular formula:

O11Pr6

IUPAC Name:

tetrakis(λ⁴-praseodymium(4+)) dipraseodymium(3+) undecaoxidandiide

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: dark brown powder

Test animals / tissue source

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

Test system

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

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.