Dipraseodymium tricarbonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 February 2013 - 21 February 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP 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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

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 (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Dipraseodymium tricarbonate

EC Number:

227-578-9

EC Name:

Dipraseodymium tricarbonate

Cas Number:

5895-45-4

Molecular formula:

CH2O3.2/3Pr

IUPAC Name:

dipraseodymium tricarbonate

Test material form:

other: solid (unspecified)

Details on test material:

- Storage conditions: room temperature in the dark.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Strain: Hsdlf:NZW
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.38 or 2.44 kg
- Housing: The animals were individually housed in suspended cages.
- Diet: ad libitum
- Water: Free access to mains drinking water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): At least 15 per hour.
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give twelve hours continuous light (0600 to 1800) and twelve hours darkness.

IN-LIFE DATES: From: 11 February 2013 To: 21 February 2013

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye of each animal remained untreated and was used for control purposes.

Amount / concentration applied:

A volume of 0.1 mL of the test material, which was found to weigh approximately 86 mg (as measured by gently compacting the required volume into an adapted syringe).

Duration of treatment / exposure:

The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The eye was not rinsed.

Observation period (in vivo):

The observation period was 72 hours. There was no ocular irritation in either animal at the 48 hour observation; therefore no further observation was required after the 72 hour observation.

Number of animals or in vitro replicates:

Initially, one animal was treated; after consideration of the ocular response, a second animal was treated.

Details on study design:

Immediately after administration of the test material, an assessment of the initial pain reaction was made against as 6 point scale.

SCORING SYSTEM: Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the Draize numerical evaluation.
Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period. Any clinical signs of toxicity, if present, were also recorded.

Draize Scale for Scoring Ocular Irritation

1. CONJUNCTIVAE

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

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

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

2. IRIS

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

3. CORNEA

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

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


TOOL USED TO ASSESS SCORE: Any additional ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: mean score at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: mean score at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: mean score at 24, 48 and 72 hours

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: mean score at 24, 48 and 72 hours

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

other: discharge score

Basis:

mean

Time point:

other: mean score at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

Individual scores for ocular irritation are given in Table 1.
No corneal effects were noted during the study. Iridial inflammation (Grade 1) was noted in both treated eyes one hour after treatment.
Moderate conjunctival irritation (Grade 2 redness, Grade 2 chemosis and Grade 1 discharge) was noted in both treated eyes one hour after treatment. Minimal conjunctival irritation (Grade 1 redness and Grade 1 chemosis) was noted in both treated eyes at the 24 hour observation.
Both treated eyes appeared normal at the 48 hour observation and the study was terminated after the 72 hour observation.

Other effects:

BODYWEIGHT
One animal showed expected gain in bodyweight and one animal showed no gain in bodyweight during the study.

Any other information on results incl. tables

Table 1 Individual Scores for Ocular Irritation

Rabbit Number and Sex	72957 Male				72986 Male
	IPR = 2				IPR = 2
Time After Treatment	1 hour	24 hours	48 hours	72 hours	1 hour	24 hours	48 hours	72 hours
Cornea Degree Area	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
Iris	1	0	0	0	1	0	0	0
Redness	2	1	0	0	2	1	0	0
Chemosis	2	1	0	0	2	1	0	0
Discharge	1	0	0	0	1	0	0	0

 IPR = Initial pain reaction; a score of 2 indicates slight initial pain. The rabbit blinks and tries to open the eye but reflex closes it.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test material requires no classification in accordance with EU criteria.

Executive summary:

The irritancy potential of the test material was assessed in vivo in accordance with the standardised guidelines OECD 405 and EU Method B.5.

A single application of 0.1 mL of the test material (which was found to weigh approximately 86 mg) was sequentially administered to the right eye of two New Zealand White rabbits. The treated eyes were not irrigated; the left eye remained untreated and served as the control. The animals were observed for ocular effects 1, 24, 48 and 72 hours after administration of the test material.

The individual mean scores for corneal opacity and iritis were 0.0 for both animals. The individual mean scores for conjunctival redness and chemosis were 0.3 for both animals. Both treated eyes appeared normal at the 48 hour observation and the study was terminated after the 72 hour observation.

Under the conditions of this study, the test material requires no classification in accordance with EU criteria.