Registration Dossier

Administrative data

Description of key information

Skin irritation / corrosion

Based on the results of the in vivo skin irritation study in rabbits performed by Shapiro (1991b; Klimisch 2) and the criteria of the CLP Regulation, yttrium trinitrate should not be classified as irritating/corrosive to skin. This conclusion is in line with the outcome of a pH/acid reserve determination (see IUCLID Section 4.20).


Eye irritation / corrosion

Shapiro (1991c; Klimisch 2) also performed an in vivo eye irritation study in rabbits. As no observation period of 21 days was taken into account, no definite conclusion on classification can be drawn. However, as the eye irritation effects were not reversible within the observation period in this test and as the pH of the substance is 1.81 (Rhodia, 2012 - see IUCLID Section 4.20), the substance is classified for serious eye damage (irreversible effects on the eye Cat. 1) and needs a H318 hazard classification according to the CLP Regulation as a worst case approach.

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:
key study
Study period:
From 1991-02-19 to 1991-03-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The study contains some relevant methodological deficiencies. When comparing the method used with the OECD 404 test guideline, the size of the exposed area was too small (2.5 cm2 instead of 6 cm2), and no scoring was done at 48 hours after patch removal. It should be noted that the study 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). Additionally, next to intact skin, also abraded skin was exposed.
Qualifier:
according to
Guideline:
other: 16 CFR 1500.41
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
no scoring at 48 h after patch removal; 24 h of exposure instead of 4 h; occlusive wrap instead of semi-occlusive; also abraded skin exposed; no 14-d observation period; exposed skin site is small (2.5 cm2 instead of ca. 6 cm2)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farm, S. Brunswick, NJ, USA
- 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): ad libitum
- Acclimation period: 5 days of rest period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9-23.9°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: one intact and one abraded site
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/site
Duration of treatment / exposure:
24 hours
Observation period:
The test sites were evaluated 24 and 72 hours after initial exposure.
Number of animals:
6 (4 males, 2 females)
Details on study design:
TEST SITE
- Area of exposure: Two test application sites, each approximately 2.5 cm².
- % coverage: 10% of the body surface (dorsal and ventral surfaces from scapular to pelvic area).
- Type of wrap if used: Adhesive-backed gauze patches and the entire trunk of each rabbit were then wrapped with an elastic cloth to aid in maintaining test-patch position and to minimise evaporation. Neck collars were placed on each rabbit and the rabbits were returned to their individual cages.

REMOVAL OF TEST SUBSTANCE
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. Skin sites were evaluated at approximately 24 and 72 hours after initial exposure.

SCORING SYSTEM: Scoring system of 16 CFR 1500.41 (Erythema and eschar formation, edema formation); Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 h and 72 h
Score:
3.6
Max. score:
8
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: both intact and abraded skin taken into account
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.25
Max. score:
4
Reversibility:
not fully reversible within:
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 3 (abraded), 3 (intact) / 72h: 2 (abraded), 1 (intact)
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.25
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 3 (abraded), 3 (intact) / 72h: 2 (abraded), 1 (intact)
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.75
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks:
fully reversible within 72 h in intact skin
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 3 (abraded), 2 (intact) / 72h: 2 (abraded), 0 (intact)
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 3 (abraded), 2 (intact) / 72h: 2 (abraded), 1 (intact)
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 3 (abraded), 3 (intact) / 72h: 1 (abraded), 1 (intact)
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 3 (abraded), 3 (intact) / 72h: 2 (abraded), 2 (intact)
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 2 (abraded), 2 (intact) / 72h: 1 (abraded), 1 (intact)
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 3 (abraded), 3 (intact) / 72h: 1 (abraded), 1 (intact)
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks:
fully reversible within 72 in intact skin
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 2 (abraded), 1 (intact) / 72h: 1 (abraded), 0 (intact)
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks:
fully reversible within 72 h in intact skin
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 3 (abraded), 2 (intact) / 72h: 1 (abraded), 0 (intact)
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.25
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 2 (abraded), 3 (intact) / 72h: 0 (abraded), 0 (intact)
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: mean for intact and abraded skin
Remarks:
24h: 2 (abraded), 2 (intact) / 72h: 1 (abraded), 1 (intact)
Irritant / corrosive response data:
At 24 hours post-dosing, the intact and abraded sites of all rabbits had well-defined to severe erythema, and very slight to moderate edema. A small area of blanching at the dose site was observed in 2 animals (1 abraded, 1 intact skin).
By 72 hours, most abraded sites had well-defined erythema and very slight edema. Most intact sites had decreased to very slight erythema, while edema remained in only three rabbits. A small area of blanching at the dose site was observed in 1 animal (intact skin).
Other effects:
In two animals a small area of blanching at dose site is observed.
All animals were active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour. At 24 hours post-dose most treated sites had moderate erythema and edema. By 72 hours the incidence and severity of irritation had decreased. Erythema at most abraded sites was well defined; at most intact sites it was considered barely perceptible.
Interpretation of results:
not classified
Conclusions:
Based on the scoring system used, yttrium trinitrate is classified as moderately irritating when applied as a powder. Based on the criteria of the CLP Regulation, the substance should not be classified as irritating to the skin, assuming that the readings at 24 h after patch removal would be equal or less severe than the readings immediately after patch removal, and assuming that the readings at 72 h after patch removal would be equally or less severe than the readings at 48 h after patch removal. Furthermore it can be reasonably assumed that the skin effects would be reversible within 14 days.
Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1990-10-31 to 1991-01-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: 16 CFR 1500.42
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
observation period limited to 72 h instead of 21 days; no observation at 1 h after instillation of the substance; in half of the rabbits the eyes were washed already after 30 seconds
GLP compliance:
not specified
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, USA
- 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): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6-22.8°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 per treated eye
Duration of treatment / exposure:
The substance was placed in the conjunctival sac of the 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 and 72 hours.
Number of animals or in vitro replicates:
6 (3 males, 3 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.

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: Severly 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:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 2/2/2
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 1/1/1
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable, no corneal opacity observed at any time point
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 0/0/0
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable, no corneal opacity observed at any time point
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 0/0/0
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 1/1/2
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable, no corneal opacity observed at any time point
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 0/0/0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 1/1/1
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 1/1/1
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 1/1/1
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 1/1/1
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 1/1/1
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 1/1/1
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 2/2/2
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 2/2/2
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 2/3/2
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 2/2/2
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 2/3/3
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 2/3/2
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 4/4/4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 4/4/3
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes, mean value
Remarks:
24/48/72h: 3/3/1
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 3/3/3
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 3/4/3
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes, mean value
Remarks:
24/48/72h: 3/3/1
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
24 h
Score:
34
Max. score:
110
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: unwashed eyes
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
24 h
Score:
27.7
Max. score:
110
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: washed eyes
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
48 h
Score:
37.7
Max. score:
110
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
48 h
Score:
29
Max. score:
110
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
72 h
Score:
30.7
Max. score:
110
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: unwashed eyes
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
72 h
Score:
29
Max. score:
110
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: washed eyes
Irritant / corrosive response data:
Corneal opacity was observed in 2 unwashed eyes and 1 washed eye at each scoring interval. Iritis and conjunctival irritation was observed in all treated eyes (unwashed and washed) at all scoring intervals. Based on the scoring system used, yttrium trinitrate is considered to be severely irritating to the unwashed and washed eyes when instilled as received, undiluted.
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:
Based on the scoring system used, yttrium trinitrate was observed to be severely irritating to the unwashed and washed eyes when instilled as received, undiluted. As no observation period of 21 days was taken into account, no definite conclusion on classification can be drawn. However, as the eye irritation effects were not reversible within the observation period in this test, the substance is classified for serious eye damage (eye damage category 1, H318) as worst case approach.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

A pH/acid reserve study (Rhodia, 2012 - see IUCLID Section 4.20) indicated that the test substance should not be considered as corrosive (pH value of 1.81, acid reserve value of 0.448, corrosivity value of 1.773 (higher than -0.5)). This is confirmed by the in vivo skin irritation study in New Zealand White Rabbits performed by (Shapiro, 1991b; Klimisch 2). This non-GLP study was performed according to the Federal Guideline 16 CFR 1500.41. It should be noted that the study contains some relevant methodological deficiencies. When comparing the method with that described in OECD guideline 404, the size of the exposed area was too small (2.5 cm² instead of 6 cm²). The study 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.

Following mean scores were noted for the intact sites of the 6 rabbits at 24 and 72 hours after exposure: 1.83 (erythema) and 1.33 (edema). At 24 hours post-dosing, the intact and abraded sites of all rabbits had well-defined to severe erythema, and very slight to moderate edema. A small area of blanching at the dose site was observed in 2 animals (1 abraded, 1 intact skin).

By 72 hours, most abraded sites had well-defined erythema and very slight edema. Most intact sites had decreased to very slight erythema, while edema remained in only three rabbits. A small area of blanching at the dose site was observed in 1 animal (intact skin).

Based on the scoring system used in the study, yttrium trinitrate was classified as moderately irritating when applied as a powder. However, based on the criteria of the CLP Regulation, the substance should not be classified as irritating to skin, assuming that the readings at 24 hours after patch removal would be equal or less severe than the readings immediately after patch removal, and assuming that the readings at 72 hours after patch removal would be equally or less severe than the readings at 48 hours after patch removal. Furthermore it can be reasonably assumed that the skin effects would be reversible within 14 days.

The study of Shapiro (1991b) is considered to be the key study for endpoint coverage.

Eye irritation

A well-documented in vivo eye irritation study was performed in New Zealand White rabbits according to Federal Hazardous Substance Control Act, 16 CFR 1500.42 and similar to OECD Guideline 405 (Shapiro, 1991c; Klimisch 2). In this study, 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. Corneal opacity was observed in 2 unwashed eyes and 1 washed eye at each scoring interval. Iritis and conjunctival irritation was observed in all treated eyes (unwashed and washed) at all scoring intervals. Based on the scoring system used, yttrium trinitrate was considered to be severely irritating to the unwashed and washed eyes when instilled as received, undiluted. This study was considered to be reliable with restrictions since no observation period of 21 days was taken into account. However, as the eye irritation effects were not reversible within the observation period in the test, and as the pH of the substance is 1.81 (Rhodia, 2012 - see IUCLID Section 4.20) the substance is classified for serious eye damage (Eye damage Category 1) as a worst case approach.

The study of Shapiro (1991c) is considered to be the key study for endpoint coverage.

Justification for classification or non-classification

Based on the results of the available in vivo skin irritation study and according to the criteria of the CLP Regulation, yttrium trinitrate should not be classified as irritating to skin.

Since the eye irritation effects observed in the in vivo eye irritation study were not reversible within the short observation period in the test, and taking into account its pH of 1.81, yttrium trinitrate is concluded to be classified as Eye damage Category 1 as a worst case approach, and needs a H318 hazard statement, according to the CLP Regulation.