Registration Dossier

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Administrative data

Description of key information

Skin irritation / corrosion: Three reliable studies are available for cerium trinitrate and they are used in a weigh-of-evidence approach: one K1 study (Krivograd (2012) and two in vivo K2 studies, (Shapiro (1990) published later by Lambert et al. (1993)) and Gonnet & Guillot (1980)). The first in vivo study was performed according to the Federal Guideline 16 CFR 1500.41 and the second one performed by Gonnet & Guillot (1980) accroding to Draize method. After appraisal of the evidence it is concluded that the substance is not irritant/corrosive to the skin.
Eye irritation: Two K2 studies are available and are used in a weight-of-evidence approach: Shapiro (1990) (published later by Lambert et al. (1993)) and Gonnet & Guillot (1980). As the eye irritation effects in these studies are irreversible, cerium trinitrate is classified for serious eye damage category 1.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From October 29 to November 1 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Well documented study according to Guideline FHSA, 16 CFR 1500.4. The study can be considered similar to OECD Guideline 404 but represents a worst-case approach as the animals were exposed for 24 hours (instead of 4 hours) using an occlusive dressing (instead of semi-occlusive), and next to intact skin also abraded skin was exposed.
Qualifier:
according to guideline
Guideline:
other: FHSA, 16 CFR 1500.41
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
- no scoring at 1 and 48 hours; 24 hours of exposure instead of 4 hours; occlusive wrap instead of semi-occlusive; also abraded skin exposed; no 14d observation period
GLP compliance:
not specified
Specific details on test material used for the study:
- Other: The test material was used as received, undiluted
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farm, S. Brunswick, NJ
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: Individually in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): Pelleted Purina Rabbit Chow ad-libitum
- Water (e.g. ad libitum): Tap water supplied by automatic water system
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 - 22.2 °C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Type of coverage:
occlusive
Preparation of test site:
other: shaved intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/test site
Duration of treatment / exposure:
24 hours of exposure
Observation period:
Skin sites were evaluated at approximately 24 and 72 hours after initial exposure and scored according to 16 CFR 1500.41.
Number of animals:
6 animals in total (3 males and 3 females)
Details on study design:
TEST SITE
- Area of exposure: two application sites (dorsal and ventral surfaces from scapular to pelvic area) of 2.5 cm2 were delineated
- % coverage: 10% of body surface
- Type of wrap if used: 2 x 2-1/4 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 minimize evaporation. Neck collars were placed on each rabbit and the rabbits were returned to their individual cages.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The neck collars and patches were removed after 24 hours of exposure at which time the test sites were gently wiped clean of any residual test material.

SCORING SYSTEM: Skin sites were evaluated at approximately 24 and 72 hours after initial exposure and scored according to 16 CFR 1500.41.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
2
Max. score:
8
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24 and 72 hours
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Scores taken from intact skin only
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24 and 72 hours
Score:
0.67
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Scores taken from intact skin only
Irritant / corrosive response data:
At 24 hours post dose, slight erythema and edema was noted at most sites. By 72 hours, irritation had cleared from both the abraded and intact sites of two rabbits and had decreased in severity at most other test sites.

Other effects:
From days 1-3, one animal had soft feces, ano-genital staining and appeared thin and pale in color. Another animal had ano-genital staining on day 1 only. All other animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologica effects or abnormal behaviour.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the scoring system used, cerium trinitrate is classified as a mild primary skin irritant when applied as received undiluted. Based on the criteria of the CLP Regulation, cerium trinitrate should not be classified as skin irritant. Although the animals were not observed for 14 days, a decrease in irritant response was observed from 24h to 72h. It can be reasonably assumed that after 14 days, the irritant scores would be zero.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study is sufficiently documented and the test conditions are similar to current test guidelines (the deviations are not judged to affect the validity of the study). The study was conducted before GLP implementation. No certificate of analysis is available.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: Draize method
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Weight at study initiation: 2.5 - 3.5 kg
- Source, Age at study initiation, Housing, Diet, Water, Acclimation period: data not available

ENVIRONMENTAL CONDITIONS:
- Temperature, Humidity, Air changes, Photoperiod: data not available

IN-LIFE DATES: data not available
Type of coverage:
occlusive
Preparation of test site:
other: shaved, intact or abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Test material: Amount applied: 0.5 mL undiluted
pH: data not available
Duration of treatment / exposure:
24 hour(s)
Observation period:
3 days. Observations were done 25 h (1 hour after patch removal) and 72 h after topical application for both test sites (intact and scarified).
Number of animals:
4
Details on study design:
TEST SITE:
- Area of exposure: disk of ca. 3 cm of diameter
- % coverage: data not available
- Type of wrap if used: gauze covered with an aluminium disk

REMOVAL OF TEST SUBSTANCE: no

SCORING SYSTEM: according to Draize
- Erythema and Eschar Formation:
No erythema -> 0
Very slight erythema (barely perceptible) ->1
Well defined erythema -> 2
Moderate to severe erythema -> 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema -> 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 (raised approximately 1 mm) -> 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure) -> 4

- Primary Dermal Irritation Index = (Sum of individual Erythema scores + Sum of individual Edema scores) / 12
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 25, 72 hours
Score:
0.75
Max. score:
4
Reversibility:
not fully reversible within: 3 days
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 25, 72 hours
Score:
0.25
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 25, 72 hours
Score:
1.25
Max. score:
8
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: scarified and intact skin
Irritant / corrosive response data:
SEE INDIVIDUAL SCORES IN TABLE 1 BELOW
Other effects:
the test item coloured the skin in yellow

Table 1: 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

normal

scarified

normal

scarified

25 h

0 / 1 / 2 / 1

1 / 1 / 2 / 1

0 / 1 / 1 / 0

0 / 1 / 1 / 1

72 h

0 / 1 / 1 / 0

1 / 1 / 1 / 1

0 / 0 / 0 / 0

0 / 0 / 0 / 0

Average 24h, 72h

 0 / 1 / 1.5 / 0.5

1 / 1 / 1.5 / 1

0 / 0.5 / 0.5 / 0

0 / 0.5 / 0.5 / 0.5

Reversibility*)

n.c.

n.c.

c. 

c.

Average time (unit) for reversion

 -

-

 72 h

72 h

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is considered not to be classified as irritating.
Executive summary:

In a primary dermal irritation study (Gonnet JF & Guillot JP, 1980), New Zealand white rabbits (4 animals) were dermally exposed to 0.5 mL of undiluted cerium nitrate 98% (Ce(NO3)3, 6 H2O) solution. Intact and abraded test sites were covered with an occlusive dressing for 24 hours. Skin sites were then scored for erythema and oedema 25 and 72 h after the beginning of the study. Irritation was scored by the method of Draize. In this study, cerium nitrate 98% was found slightly irritating to the skin and then warranting no classification according to the EU criteria.

Endpoint:
skin corrosion: in vitro / ex vivo
Remarks:
other: Determination of pH-value
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
31-05-2012 - 14-06-2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
Well reported determination of pH value and acid reserve according to accepted scientific methods.
Principles of method if other than guideline:
Electrochemic determination of pH: The determination of the pH-value was in compliance with TIAG standard operating procedures AANC Determination of the pH value (2012).
GLP compliance:
no
Remarks:
The study is well reported according to accepted scientific methods.
Details on study design:
Preparation of test item:
At first, a 10% solution of the test item was prepared by stirring 10 g sample material with 90g H2O dem. (Milli-Q water - Type 1 water grade) for 30 minutes and then adjusting it to a temperature of 20°C.

Calibration of the pH-meter:
Prior to the measurement the pH meter was checked and calibrated with a buffer solution in the expected measurement range. The pH meter was calibrated via a 3-point calibration. The slope of the electrode and the result of the control buffer were either listed in the "Prüfmittelkontrollblatt" or "calibration report". The electrode was rinsed with H2O dem., wiped dry and immersed for measurement into the solution;

Determination of the pH-value of the test item
The pH is determined 3 times from a 10% solution of the test item under continuous stirring. The measured pH was protocolled.

Apparatus and auxiliary material:
- Analytical scales with an accuracy of 0.01g
- pH-meter with pH electrode or 809 Titrando v. Metrohm
- Buffer solutions 1.09, 4.01, 6.00
- Magnetic stirrer with magnetic stir bar
- Beakers
- Flask
- Water bath
- Pipettes
- Milli-Q water
Irritation / corrosion parameter:
other: corrosivity
Remarks on result:
other: the substance is considered not corrosive

Since the determined pH-value was 4.58, a determination of the acid reserve was not applicable.

Interpretation of results:
GHS criteria not met
Conclusions:
The pH value was determined to be 4.58. Because of this pH value a determination of the acid reserve was not applicable. Based on the results of this test the test item was considered not corrosive.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1990 (no other information available)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
The test is presented in a short summary. However, the information necessary for the assessment are given, and the test conditions are in accordance with US guideline.
Qualifier:
equivalent or similar to guideline
Guideline:
other: similar to EPA OPPTS 870.2400 (Acute eye irritation)
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Source, Age at study initiation, Weight at study initiation, Housing, Diet, Water, Acclimation period: data not available

ENVIRONMENTAL CONDITIONS:
- Temperature, Humidity, Air changes, Photoperiod: data not available

IN-LIFE DATES: data not available
Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye of each rabbit was untreated
Amount / concentration applied:
undiluted
Amount applied: 0.1 g
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6
Details on study design:
- Removal of test system: 3 of the treated eyes were rinsed with saline 30 seconds post-instillation
- Scoring system: according to the method of Draize
- Tool used to assess score: data not available
Irritation parameter:
other: draize scores
Basis:
mean
Time point:
other: 24-48-72 hours
Score:
41 - 42.3
Max. score:
110
Reversibility:
not specified
Remarks on result:
other: Unwashed eyes (3 rabbit mean): 41.0 (24h), 42.3 (48h), 42.3 (72h)
Irritation parameter:
other: draize scores
Basis:
mean
Time point:
other: 24-48-72 hours
Score:
18 - 23
Max. score:
110
Reversibility:
not specified
Remarks on result:
other: Washed eyes (3 rabbit mean): 23.0 (24h), 21.3 (48h), 18.0 (72h)
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Classification: risk of serious damage to eyes;
In this study, cerium nitrate was found to be severely and moderately irritating to unwashed and washed eyes respectively.
Executive summary:

In a primary eye irritation study (Lambert CE, 1993), 0.1 g of cerium nitrate (purity unknown) was instilled into the left eye of New Zealand Albino rabbits (6 animals). 3 treated eyes were rinsed after 30 seconds. Animals then were observed for 3 days. Irritation was scored by the method of Draize. In this study, cerium nitrate was found severely irritating to the eye of rabbit.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From October 31 to November 3, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Well documented study performed according to Federal Hazardous Substance Control Act, 16 CFR 1500.42 and similar to OECD Guideline 405. No 21-day observation period was used, so reversibility of eye effects could not be proved.
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substance Control Act, 16 CFR 1500.42
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
observation period limited to 72 hours instead of 21 days; no observation at 1 hour after instillation of the substance; in half of the rabbits the eyes were washed already after 30 sec.
GLP compliance:
not specified
Specific details on test material used for the study:
- Other: The sample was instilled as received, undiluted
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farm, S. Brunswick, NJ.
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: Individually in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): Pelleted Purina Rabbis Chow ad-libitum
- Water (e.g. ad libitum): Tap water supplied by automatic water system.
- Acclimation period: 5 or 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 °C - 23.9°C
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eyes served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g/treated eye
Duration of treatment / exposure:
The substance was placed in the conjunctival sac of the right or left eye of each rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about 1 second to prevent loss of the test material before releasing. The other eye of each rabbit remained untreated and served as a control.
Observation period (in vivo):
Ocular lesions were evaluated in accordance with Draize et al. at 24, 48 end 72 hours.
Number of animals or in vitro replicates:
6 animals in total (4 males and 2 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Three of the treated eyes were rinsed with saline 30 seconds post-instillation. The remaining three eyes were not irrigated. The rabbits were restrained with neck collars and were returned to their respective cages for 24 hours.
- Time after start of exposure:

SCORING SYSTEM: After instillation of the test material, ocular lesions were evaluated in accordance with Draize et al. at 24, 48 and 72 hours. The eye scores were further classified by the system of Kay and Calandra, modified. 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.

MMTS: 0.0-0.5: Non-irritating
MMTS: 0.6 - 2.5: Practically non-irritating
MMTS: 2.6-15.0: Minimally irritating
MMTS: 15.1-25.0: Mildly irritating
MMTS: 25.1-50.0: Moderately irritating
MMTS: 50.1-80.0: Severely irritating
MMTS: 80.1-100.0: Extremely irritating
MMTS: 100.1-110.0: Maximally irritating
Maximum mean total score - Kay and Calandra, J. Soc. Cos. Chem. 13: 281 -289 1962. If more than 40% of the rabbits tested have scores > 10 or if an individual rabbits score is > 30, the preliminary classification is raised to the next highest level.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of unwashed eyes
Time point:
other: 24 hours
Score:
41
Max. score:
110
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of washed eyes
Time point:
other: 24 hours
Score:
23
Max. score:
110
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24, 48, 72h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Unwashed eyes only
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24, 48, 72h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Unwashed eyes only
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24, 48, 72h
Score:
2.56
Max. score:
3
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Unwashed eyes only
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24, 48, 72h
Score:
2.89
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Unwashed eyes only
Irritant / corrosive response data:
All unwashed treated eyes had corneal opacity, iritis and conjunctival irritation throughout the 72 hour observation period. One washed eye had corneal opacity throughout the test period. Iritis was observed in all treated washed eyes 24 hours post-instillation and in 2 eyes at 48 and 72 hours. All washed eyes had conjunctival irritation at each scoring interval.
Other effects:
All animals appeared active and healthy. Apart from the eye irritation noted, there were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The 24 hour Maximum Mean Total Score (MMTS) was 41.0 and 23.0 for the unwashed and washed eyes, respectively. Based on the scoring system used, cerium nitrate, is considered to be severely and moderately irritating to the unwashed and washed eyes respectively, when instilled as received, undiluted. However, according to the criteria in CLP, the substance would be at least classified as eye irritant category 2 when using the readings of the three unwashed eyes. As the eye irritation effects were irreversible within the observation period, the substance is classified as category 1 eye irritant substance.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study is sufficiently documented and the test conditions are similar to current test guidelines (the deviations are not judged to affect the validity of the study). The study was conducted before GLP implementation. No certificate of analysis is available.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
other: Draize method
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Weight at study initiation: 2 - 3 kg
- Source, Age at study initiation, Housing, Diet, Water, Acclimation period: data not available

ENVIRONMENTAL CONDITIONS:
- Temperature, Humidity, Air changes, Photoperiod: data not available

IN-LIFE DATES: data not available
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
8 (4 unrinsed and 4 rinsed)
Details on study design:
- Removal of test system: yes (The eye of 4 rabbits were rinsed 30 s after instillation. The eye of the other 4 rabbits were not rinsed)
- Scoring system: according to Kay and Calandra scale ("Interpretation of eye-irritation tests" : J. Soc.Cosmet. Chem., 13, 281, 1962)
- Tool used to assess score: data not available
- Evaluation of the eyes were made 1 hour and 1, 2, 3 , 4 and 7 days after ocular application of test substance.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24,48 and 72 hours
Score:
3.6
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: not rinsed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: not rinsed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2.7
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: not rinsed
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: not rinsed
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2.6
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: rinsed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: rinsed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2.1
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: rinsed
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: rinsed
Irritant / corrosive response data:
Scores were not always readable due to the intense effect observed.
Other effects:
Permanent myosis, circumcorneal injections, congestion of iris, blackish colouration of the internal face of the eyelid, desquamative membrane on the corneal surface, whitish humour (all these signs were observed all along the study in one or more animals). Rabbit N° 146 (group of non-rinced eye) and rabbit N° 424 (group of rinced eye) were found dead on Day 3 (cause unknown) and Day 2 (broken spine), respectively. They were replaced by animals which received same treatment.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

(product  instilled as such, no rinse)

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

3/4/4/4

 1/1/1/1

1/1/1/1 

4/4/4/4 

24 h

4/4/4/4 

 1/1/2/1

?/2/?/? 

4/4/4/4

48 h

2/2/4/4 

 1/1/2/1

 2/2/?/2

 4/4/4/4

72 h

 4/4/4/4

 1/1/2/1

 3/3/3/3

 4/4/4/4

Average 24h, 48h, 72h

3.6 

1.2

2.7

 4.0

Area effected

 2.5

- 

 -

- 

Reversibility*)

 n.

n. 

n.

 n.

Average time (unit) for reversion

 -

- 

 -

 -

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible; ? = unreadable

Table 2: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

(product  instilled as such, with rinsing 30 s after  instillation)

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

3/3/2/2

1/1/1/1

1/1/1/1

3/3/3/4

24 h

4/3/2/2

1/1/1/1

?/2/2/?

4/4/4/4

48 h

2/3/2/2

1/1/1/1

?/2/2/?

4/4/4/4

72 h

?/4/3/2

?/1/1/1

?/3/2/2

4/4/4/4

Average 24h, 48h, 72h

2.6

1

2.1

4.0

Area effected

 2.0

- 

 -

- 

Reversibility*)

 n.

n. 

n.

 n.

Average time (unit) for reversion

 -

- 

 -

 -

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

? = impossible reading or unreadable

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Classification:
CLP: Eye damage category 1, H318; causes serious eye damage

Executive summary:

In a primary eye irritation study (Gonnet JF & Guillot JP, 1980), 0.1 mL of cerium trinitrate hexahydrate 98% (purity unspecified) was instilled into the conjunctival sac of one eye of New Zealand White rabbits (8 animals). 4 eyes were rinsed 30 seconds after instillation. Animals were then observed for 7 days. Irritation was scored by the method of Draize.

In this study, cerium nitrate at 98% in aqueous solution was found severely irritating to the eye based on the EU criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

One K1 study (Krivograd (2012) and two K2 in vivo studies are available: Shapiro (1990), later published by Lambert et al. (1993), and Gonnet & Guillot (1980)). These studies are used in a weight of evidence.

The pH-value was determined electrochemically with a calibrated pH-meter at 20 ± 1°C (Krivograd, 2012) in order to evaluate the irritant or corrosive potential of cerium trinitrate. The obtained pH-value was the basis for deciding if it was necessary to determine the acid reserve. A 10% solution of the test item was prepared by stirring 10 g sample material with 90 g H2O dem. (Milli-Q water - Type 1 water grade) for 30 minutes and then adjusting it to a temperature of 20°C. Prior to the measurement the pH meter was calibrated via a 3 -point calibration with a buffer solution in the expected measurement range. The pH was measured 3 times from a 10% solution of the test item under continuous stirring. The measured pH was protocolled. As the pH value was determined to be 4.58, a determination of the acid reserve was not applicable.

In an in vivo study by Shapiro (1990) (published later by Lambert et al. (1993))

New Zealand White rabbits (6) were exposed for 24 hours to 0.5 g (solid) cerium nitrate under occlusive dressing (shaved intact and abraded skin sites). At 24 hours post dose, slight erythema and edema was noted at most sites. By 72 hours, irritation had cleared from both the abraded and intact sites of two rabbits and had decreased in severity at most other sites. From days 1 -3, one animal had soft feces, ano-genital staining and appeared thin and pale in color. Another animal had ano-genital staining on day 1 only. All other animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacological effects or abnormal behaviour.

In an in vivo study by Gonnet JF & Guillot JP (1980) observations of the skin of 4 New Zealand White rabbits were done 25 h (1 hour after patch removal) and 72 h after topical application of 0.5 mL (liquid) cerium trinitrate at two test sites (intact and scarified). Skin sites were then scored for erythema and oedema 25 and 72 h after the beginning of the study. Irritation was scored by the method of Draize. In this study, cerium nitrate 98% was found slightly irritating to the skin and then warranting no classification according to the EU criteria.

Based on the results of these three studies it can be concluded that cerium trinitrate does not show skin irritation potential.

Eye irritation:

2 weight of evidence K2 studies were available (Shapiro (1990)/Lambert et al (1993) and Gonnet & Guillot (1980)).

In the study of Shapiro R (1990), published by Lambert et al. (1993), 6 rabbits were instilled 0.1 g of test substance in one eye, while the other eye served as control. The eyes were examined at 24, 48 and 72 hours after treatment. All unwashed treated eyes had corneal opacity, iritis and conjunctival irritation throughout the 72 hour observation period. One washed eye had corneal opacity throughout the test period. Iritis was observed in all treated washed eyes 24 hours post-instillation and in 2 eyes at 48 and 72 hours. All washed eyes had conjunctival irritation at each scoring interval. All animals appeared active and healthy. Apart from the severe eye irritation noted, there were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

In a primary eye irritation study (Gonnet & Guillot, 1980), 0.1 mL of cerium trinitrate hexahydrate 98% (purity unspecified) was instilled into the conjunctival sac of one eye of New Zealand White rabbits (8 animals). 4 eyes were rinsed 30 seconds after instillation. Animals were then observed for 7 days. Irritation was scored by the method of Draize. In this study, cerium nitrate at 98% in aqueous solution was found severely irritating to the eye based on the EU criteria.

Based on the above-mentioned studies, cerium trinitrate was found severely irritating to the eye.


Justification for classification or non-classification

Based on the results of one K1 study and two K2 studies (weight-of-evidence) and the criteria of the CLP Regulation, cerium trinitrate should not be classified as irritating to the skin.

According to the results of the eye irritation studies and the fact that the eye irritation effects were irreversible, cerium trinitrate would be classified as serious eye damage Cat. 1 (H318).