Registration Dossier

Administrative data

Description of key information

Several acute oral studies are available both with yttrium oxide itself as well as with europium oxide itself. As all studies indicated an LD50 >2000 mg/kg no further studies were performed. No acute dermal toxicity is available as the inhalation exposure is more likely due to the small particle size of the substance. An acute inhalation toxicity study with yttrium oxide is available showing an LD50 >5.09 mg/L. These results are read-across to yttrium oxide, europium doped.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in Section 13.
Reason / purpose for cross-reference:
read-across source
Preliminary study:
3 doses (1000, 2500 and 5000 mg/kg bw) were tested. The vehicle was an aqueous dispersion of 10% arabic gum. 2 males and 2 females were used per dose. Mortality checks were performed at 1, 2, 4h, and then on days 1, 2, 4, 7 and 14.
No mortality was observed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No mortality were observed in rats dosed with 0 or 5000 mg/kg bw yttrium oxide.
Clinical signs:
No clinical signs were observed in rats dosed with 0 or 5000 mg/kg bw yttrium oxide.
Body weight:
No effect on weight gain were observed in rats dosed with 5000 mg/kg bw yttrium oxide as compared to controls.
Gross pathology:
No gross abnormalities were observed at necropsy.
Other findings:
- Organ weights: no data
- Histopathology: no data
- Potential target organs: no data
- Other observations: none
Interpretation of results:
GHS criteria not met
Conclusions:
An acute oral toxicity study was performed with yttrium oxide according to OECD guideline 401. As the LD50 in males and females (Oral LD50 Combined (males and females)) exceeded 5000 mg/kg bw,Yttrium oxide is not classified for acute oral toxicity. This result is read across to yttrium oxide, europium-doped.
Executive summary:

In an acute oral toxicity study performed according to OECD guideline 401, groups of fasted, 6-7 week old Sprague Dawley rats (5/sex) were given a single oral dose of yttrium oxide (> 99.9 % a.i.) in aqueous dispersion of 10% arabic gum at dose of 5000 mg/kg bw (limit test). The rats were observed for 14 days. No clinical signs and no mortality were observed during the study. Therefore, the oral LD50 combined (males and females) of yttrium oxide is > 5000 mg/kg bw. This result is read across to yttrium oxide, europium-doped.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
One key study is available (performed on a substance analogue) and several studies supporting the result of the selected key study.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in Section 13.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.09 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortallity observed
Clinical signs:
other: Following exposure, all animals exhibited irregular respiration. However, all animals recovered from this symptom by Day 2 and appeared active and healthy for the remainder of the 14-day observation period.
Body weight:
Although all animals lost body weight by Day 1, all animals showed a continued weight gain thereafter through Day 14.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

TABLE 1: PRE-TEST EXPOSURE TRIALS

 Trial N°  Compressed/Mixing Air Pressure (psi)    Compressed Air Volume (Lpm)  Compressed Mixing Air (Lpm) Total Air Volume (Lpm)   Dust Generator Motor Setting  Packing Pressure (lbs/in2)  Chamber Conc. (mg/L)  Particle Size Sampled
 1 30/30   30.0  6.0  36.0  15.0  2,000  11.60  No
 2  30/30  30.0  6.0  36.0  10.0  2,000  6.88  No
 3 30/30  30.0   6.0  36.0  8.0  2,000  5.13  Yes

TABLE 2: SUMMARY OF PRE-TEST EXPOSURE TRIAL

 Trial No.  Chamber Concentration (mg/L)  Mass Median Aerodynamic Diameter2 (μm)
 3  5.13  2.88

TABLE 3: GRAVIMETRIC CHAMBER CONCENTRATIONS

Sample Number Chamber Time of Sample (hour)   Mass Collected (mg) Airflow Sampled (Lpm)  Collection Time (min)   Concentration (mg/L) 
 1  0.5  20.4  4  1  5.10
 2  1  20.3  4  1  5.08
 3  2  21.2  4  1  5.30
 4  2.5  20.3  4  1  5.08
 5  3.5  19.5  4  1  4.88
 6  3.75  20.4  4  1  5.10

Average + standrad deviation: 5.09 + 0.13

Table 4: SAMMARY OF PARTICULE SIZE DISTRIBUTION:

 Sample No. Time of Sample (hours)   Collection Time (minutes) Mass Median Aerodynamic Diameter (μm)   Geometric Standard Deviation
 1  1.5  3.07  2.17
 2  3 2.86  2.14 

TABLE 5: INDIVIDUAL BODY WEIGHTS

 Animal No.  Sex  Body Weight (g)  Body Weight (g)   Body Weight (g)  Body Weight (g)   Body Weight (g) 
     Initial  Day 1 Day 3  Day 7  day 14 
 3301 309  296 304  322  340 
 3302 288  280  285  300  315 
 3303 305  294  300  318  330 
 3304 196  194  195  207  211 
3305  209  206  209  219  230 
 3306 200  194  199  209  217 
Interpretation of results:
GHS criteria not met
Conclusions:
An acute inhalation study was performed with yttrium oxide according to OECD guideline 436 and GLP principles. Under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is greater than 5.09 mg/L (limit test, OECD) in male and female rats. In accordance with the provisions of Regulation (EC) No. 1272/2008 on the Classification, Labeling, and Packaging of Substances and Mixtures, classification is not required based on the results of this study. This result is read across to yttrium oxide, europium-doped.
Executive summary:

In an acute inhalation nose only toxicity study, female and male rats were exposed to 5.13 mg/L (nominal) yttrium oxide as aerosol according to OECD test guideline 436. The gravimetric and nominal chamber concentrations were 5.09 mg/L and 9.31 mg/L, respectively. Based on graphic analysis of the particle size distribution as measured with an ACFM Andersen Ambient Particle Sizing Sampler, the mass median aerodynamic diameter was estimated to be 2.97 μm. The total amount of test substance used was 81.0 grams.

All animals survived exposure to the test atmosphere. Following exposure, all animals exhibited irregular respiration. However, all animals recovered from this symptom by Day 2 and appeared active and healthy for the remainder of the 14-day observation period. Although all animals lost body weight by Day 1, all animals showed a continued weight gain thereafter through Day 14. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period. Therefore, the LC50 was determined to be >5.09 mg/L. This result is read across to yttrium oxide, europium-doped.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 090 mg/m³
Quality of whole database:
Study on substance analogue was performed according to current OECD test guideline and GLP principles.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No study with yttrium oxide, europium doped is available. However, several studies with yttrium oxide and also with europium oxide are present. The justification for this analogue approach is described in a report (see section 13 of IUCLID).

Oral:

In an acute oral toxicity study performed according to OECD test guidelines, groups of fasted, 6-7 week old Sprague Dawley rats (5/sex) were given a single oral dose of yttrium oxide in aqueous dispersion of 10% arabic gum at dose of 5000 mg/kg bw (limit test) and observed for 14 days. No clinical signs and no mortality were observed during the study. The LD50 was determined to be >5000 mg/kg bw.

In supporting acute oral toxicity studies, groups of fasted, Sprague-Dawley rats (5/sex) were given a single oral dose of yttrium oxide or of europium oxide in distilled water at dose of 5000 mg/kg bw and observed for 14 days. The LD50 for both substances is determined to be > 5000 mg/kg bw.

Inhalation:

In an acute inhalation toxicity study performed according to OECD test guideline and GLP principles, rats were exposed to yttrium oxide aerosols at limit concentration. The gravimetric and nominal chamber concentrations were 5.09 mg/L and 9.31 mg/L, respectively. Based on graphic analysis of the particle size distribution as measured with an ACFM Andersen Ambient Particle Sizing Sampler, the mass median aerodynamic diameter was estimated to be 2.97 μm. All animals survived exposure to the test atmosphere. Following exposure, all animals exhibited irregular respiration. However, all animals recovered from this symptom by Day 2 and appeared active and healthy for the remainder of the 14-day observation period. Although all animals lost body weight by Day 1, all animals showed a continued weight gain thereafter through Day 14. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period. Therefore, the LC50 was determined to be > 5.09 mg/L.

Dermal:

No acute dermal toxicity study is available as already studies for two routes of exposure are available, and the inhalation exposure is due to its low particle size much more likely compared to the dermal exposure (low absorption potential).

Justification for classification or non-classification

Based on all the availabe data, yttrium oxide, europium doped is not classified for acute toxicity according to CLP Regulation (EC) No. 1272/2008 including its amendments.