Registration Dossier

Administrative data

Description of key information

Acute dermal irritation study (in vivo) on Praseodymium oxalate: Negative
Acute dermal irritation study (in vivo) on Cerium fluoride: Negative
Acute eye irritation study (in vivo) on Praseodymium oxalate: Negative
Acute eye irritation study (in vivo) on Cerium fluoride: Negative

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1 August 1984 - 3 September 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 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.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Albino New Zealand
- Sex: males
- Age at study initiation: no data
- Weight at study initiation: 2.5 ± 0.2 kg
- Housing: individual housing, in polystyrene cages, dimensions of 540 x 360 x 315 mm, with a perforated floor
- Diet: 150 g of complete maintenance food per rabbit per day
- Water: ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 12 to 14 times per hour (pre-filtered air : 5 - 10 µ)
- Photoperiod: 12 hrs dark / 12 hrs light (0730 - 1930)

IN-LIFE DATES: From: 1 August 1984 to 4 August 1984
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Concentration: 0.5 g of the test material was applied as a paste with 0.33 mL of water
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: a surface of 6 cm ²
- % coverage: no data
- Type of wrap: semiocclusive dressing: covered with a Codex hydrophilic eight layer gauze pad 2.5 cm per side, followed by 10 cm wide adhesive perforated tape (Peloplast: M.S.R.) applied on a crimped gauze bandage (Creplux-Molinier) covering more particularly the whole clipped surface (to avoid possible orthoergic reactions) and wrapped around the animal (without blocking the respiratory and abdominal movements).


REMOVAL OF TEST SUBSTANCE
- Washing: the bandages were removed and if necessary excess test material, which had not penetrated, was wiped away with a gauze pad moistened with distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM:

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:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
No abnormalities were observed.

Table 1 Summary of Erythema Scores

Animal Number

Mean Score over 24, 48 and 72 hours

886

0

887

0

888

0

889

0

890

0

891

0

Mean

0

 

Table 2 Summary of Oedema Scores

Animal Number

Mean Score over 24, 48 and 72 hours

886

0

887

0

888

0

889

0

890

0

891

0

Mean

0

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to this study, the test material is not classified as a dermal irritant in accordance with EU criteria..
Executive summary:

A dermal irritation study was conducted in accordance with the standardised guideline OECD 404.

Six male New Zealand White rabbits were dermally exposed to 0.5 g of the test material moistened with 0.33 mL of water to form a paste. Test sites were covered with a semi-occlusive dressing for 4 hours, followed by observation of the animals for 72 hours. Irritation was evaluated based on erythema and oedema reactions observed 1, 24, 48 and 72 hours after the end of application.

No skin reactions were observed during the study. The mean score for the readings at 24, 48 and 72 hours for both erythema and oedema was equal to 0.

Under the conditions of this study, the test material is not classified in accordance with 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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
8 November 1990 - 11 November 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 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.
Qualifier:
according to
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: 5, 7 or 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23 °C

IN-LIFE DATES: From: To: 8 November 1990 - 11 November 1990
Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye of each rabbit remained untreated and served as control
Amount / concentration applied:
undiluted
Amount applied: 0.1 g
Duration of treatment / exposure:
The upper and lower lids were gently held together for 1 second post-installation to prevent loss of the test material.

Three of the treated eyes were rinsed 30 seconds post-installation.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6; 3 male, 3 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): three of the treated eyes were rinsed with saline.
- Time after start of exposure: 30 seconds post-exposure.

- Scoring system: according to the method of Draize. Ocular lesions were evaluated at 24, 48 and 72 hours post installation. Fluorescein was used at the 24 hour evaluation.

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:
other: Mean of 24, 48 and 72 hours
Score:
0.55
Max. score:
80
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.55
Max. score:
10
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1.11
Max. score:
6
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.88
Max. score:
8
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
other: discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
6
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
80
Reversibility:
other: n/a
Remarks on result:
other: Washed
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
10
Reversibility:
other: n/a
Remarks on result:
other: Washed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1.11
Max. score:
6
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Washed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.44
Max. score:
8
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Washed
Irritation parameter:
other: discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.22
Max. score:
6
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Washed
Irritant / corrosive response data:
All treated eyes exhibited conjunctival irritation 24 hours post installation. With the exception of one washed eye, this had cleared 48 hours after installation. The remaining eye was free of irritation by 72 hours.
Other effects:
All animals appeared active and healthy. No signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour were observed.

Table 1 Individual Results

Time Point (hours)

Rabbit Number

Cornea

Iris

Conjunctivae

Chemosis

Discharge

 

 

24

7758

7759

7760

7761

7762

7763

1*

0

0

0

0

0

0

0

1

0

0

0

2

1

2

2

1

1

2

1

1

1

1

0

2

1

3

1

0

0

 

 

48

7758

7759

7760

7761

7762

7763

0

0

0

0

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

 

 

72

7758

7759

7760

7761

7762

7763

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

0

0

0

0

0

Rabbits 7761, 7762 and 7763 had the treated eye rinsed with 30 cc of saline solution 30 seconds post-installation.

*The area affected by the corneal opacity was judged to be one quarter (or less) but not zero and the area of the cornea involved was therefore given a score of 1.

Interpretation of results:
not classified
Remarks:
Migrated information 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 under the conditions of this study.
Executive summary:

A primary eye irritation study was conducted in accordance with FHSA guideline16 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 three days 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 adverse effect observed (not irritating)

Additional information

A weight of evidence approach has been adopted using available data on Praseodymium oxalate and Cerium fluoride. These substances cover both the metal and salt of the substance being registered. Neither substance is classifed for irritant effects and it is considered reasonable to assume that Cerium oxalate will also not exhibit irritant properties.


Justification for selection of skin irritation / corrosion endpoint:
Data considered adequate for weight of evidence.

Justification for selection of eye irritation endpoint:
Data considered adequate for weight of evidence.

Justification for classification or non-classification

Skin

In accordance with with criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for skin irritation.

Eye

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for eye irritation.