Yttrium oxide (Y2O3), europium-doped

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

Type of information:

other: other substance

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Although the publication is elaborate on the methods applied, several parameters have not been investigated. In addition, the route of exposure is not/less relevant in the use of the substance as an industrial chemical.

Data source

Reference

Reference Type:

publication

Title:

In vivo toxicity studies of europium hydroxide nanorods in mice

Author:

Patra, CR, et al.

Year:

2009

Bibliographic source:

Toxicol Appl Pharmacol 240 (1), 88-98

Materials and methods

Principles of method if other than guideline:

Mice were exposed for seven days intraperitonially, and sacrificed on day 8 or 60. Mortality, body weight, clinical signs, hemaotlogy, biochemical parameters and histological examination were observed/performed.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Europium (III) hydroxide

IUPAC Name:

Europium (III) hydroxide

Details on test material:

- Name of test material (as cited in study report): Synthesis of Eu(OH)3 nanorods was carried out in a modified domestic microwave oven prepared using an interaction in an aqueous solution of Europium(III)nitrate and aq. NH4OH using microwave irradiation. The yield of the as-prepared products was more than 95%.
- Molecular formula: Eu(OH)3
- Physical state: solid, nano (200-300 nm)
- Analytical purity: 95%

Test animals

Species:

mouse

Strain:

C57BL

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Cancer Institute, USA
- Diet: ad libitum autoclaved standard pellet food
- Water: ad libitum sterile water


ENVIRONMENTAL CONDITIONS
No information

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: TE (Tris-EDTA) buffer

Details on exposure:

A constant volume of 100 microliter was injected.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

8 or 60 days

Frequency of treatment:

Daily for seven days

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1.25, 12.5 and 125 mg/kg/day

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: based on pulbicly available data
- Rationale for selecting intraperitoneally exposure: predominantly used for its ease of administration, and a large volume can be administered

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: not known, but no clinical signs and no mortality was observed.

BODY WEIGHT: Yes
- Time schedule for examinations: not known, but no significant change in the average weight loss

FOOD CONSUMPTION: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 8 or day 60 from the date of injection
- Anaesthetic used for blood collection: Yes (ketamine-xylazine)
- Animals fasted: No data
- How many animals: 10
- Parameters examined: CBC, hematocrit, erythrocytes, MCV, RBC distribution width, leukocytes, platelet count.

CLINICAL CHEMISTRY: Yes
- see also haematology
- Parameters examined: ALP, AST, ALT, phosphorus, calcium, albumin, creatinine, glucose, total protein, total bilirubin, BUN, etc (Hanfield et al, 2006)

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: No

HISTOPATHOLOGY: Yes
Liver, kidney, spleen and lungs

Other examinations:

XRD, TEM was perfomed on the substance itself. In addition, ICP-MS was performed on the vital organs to determine bio-distribution

Statistics:

P values were calculated using the Student'Newman-Keuls Multiple Comparisons Test (ANOVA) by comparing different groups (control group vs treatment groups).

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

no mortality, no clinical signs

Mortality:

no mortality observed

Description (incidence):

no mortality, no clinical signs

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL CHEMISTRY: slight elevation of liver enzymes, especially AST, but only for the 8-day study, so the effect is reversible. In addition, no other effects were noted, e.g. bilirubin increase, therefore this effect is not considered to be adverse.

HISTOPATHOLOGY: NON-NEOPLASTIC
Lungs: Mild thickening of the alveolar membrane and localize para bronchiolar lipophagocytic changes detected at 12.5 and 125 mg/kg/day.
Liver: Mild hepatocytes cloudy swelling was observed at 12.5 mg/kg/day, at 125 mg/kg/day sinusoidal congestion and mild lobular inflammation was observed.
Kidneys: Cloudy swelling in renal cortical tubular epithelium is seen at 12.5 mg/kg/day. At 125 mg/kg/day mild glomerular mesangial cell proliferation and arteriolar congestion are detected.
Spleen: Mild follicular hypoerplasia is seen at 125 mg/kg/day.
The hisotlogic specimens showed noral histology for these organs.

Effect levels

Dose descriptor:

dose level:

Effect level:

125 mg/kg bw/day

Based on:

test mat.

Sex:

male

Basis for effect level:

other: At this highest dose tested, mild histological changes indicate mild toxicity of nanorods after intraperitoneal injection.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The combined results of XRD, TEM, TGA and DSC indicate that as-synthesised product is crystalline Eu(OH)3 nanorods.

Applicant's summary and conclusion

Conclusions:

After 7-days of intraperitoneally application of europium hydroxide nanorods, mice showed mild hisological changes at the highest dose tested, 125 mg/kg bw/d.