Dilutetium oxide silicate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 October 2016 - 20 January 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dilutetium oxide silicate

EC Number:

235-337-4

EC Name:

Dilutetium oxide silicate

Cas Number:

12168-86-4

Molecular formula:

Lu2O5Si

IUPAC Name:

Dilutetium oxide silicate

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in report): dilutetium oxide silicate, lutetium oxide silicate
- Physical state: solid
- Appearance: light grey to grey powder
- Further information on test material confidential.

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: On the day of administration, the test item was freshly formulated at a concentration of 200 mg/mL (anhydrous form) with the vehicle.
- A correction factor of 1.05 was applied when preparing the dose formulations (to correct for the water content of the test item).

FORM AS APPLIED IN THE TEST (if different from that of starting material): formulation with 1% methylcellullose at a concentration of 200 mg/mL

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:(WI)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: young healthy adult rats, 10 weeks old
- Weight at study initiation: 210 - 256 g. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: The night before treatment the animals were fasted for a maximum of 16 hours. Food, but not water, was withheld overnight. Food was replaced 3 hours after treatment.
- Housing: Group caging (3 animals/cage) in type II. polypropylene/polycarbonate cages. “Lignocel 3/4-S Hygienic Animal Bedding” and “Arbocel crinklets natural” nest building material produced by J. Rettenmaier & Söhne GmbH & Co.KG (D-73494 Rosenberg, Germany) were available to animals during the study.
- Diet (e.g. ad libitum): ad libitum; ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by Ssniff Spezialdiäten GmbH, D-59494 Soest Germany (batch number: 141 8884, expiry date: January 2017 and batch number: 278 5652, expiry date: November 2016)
- Water (e.g. ad libitum): ad libitum; tap water from the municipal supply, as for human consumption from a 500-mL bottle
- The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Water quality control analysis was performed once every three months and microbiological assessment was performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A. u. 36., Hungary).
- Acclimation period: 26-27 days before start of treatment under laboratory conditions. Health inspection was performed at arrival of the animals. Only healthy animals were used for the test. The health status was certified by the veterinarian.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3ºC
- Humidity (%): 30-70%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light, lighting period from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES:
- From: 2016-10-25 To: 2016-11-08 (females no. 2954, 2955, 2956)
- From: 2016-10-26 To: 2016-11-09 (females no. 2957, 2958, 2959)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

aqueous solution of methylcellulose at 1%

Details on oral exposure:

VEHICLE (1% methylcellulose)
- Concentration in vehicle: 200 mg/L
- Justification for choice of vehicle: The selection of the vehicle was based on trial formulations with the test item. In order of preference, the recommended vehicles were the following: distilled water, 0.5 or 1% methylcellulose or carboxymethylcellulose, PEG 400, corn oil, sunflower oil or DMSO. 1% methylcellulose appeared to be most suitable.
- Lot/batch no. (if required): S11122

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): Test item was freshly formulated on the day of administration. To limit the impact, the formulations were used within 4 hours after adding the vehicle to the test item and the test item preparation was performed with approved procedures and documented in detail. The formulation was homogenised to visually acceptable levels and was stirred up to finishing the treatment to ensure sufficient homogeneity.

- Rationale for the selection of the starting dose: The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose. The limit dose (= starting dose level) for this study was 2000 mg/kg bw.

Doses:

2000 mg/kg

No. of animals per sex per dose:

2 groups; 3 females/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
*Clinical signs: Animals were observed individually after dosing at 30 minutes, then 1, 2, 3, 4 and 6 hours after the treatment and once each day in the morning for 14 consecutive days thereafter.
*Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
*Body weight: The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: Yes, all animals were subjected to a necropsy and a macroscopic examination. The animals were exsanguinated after verification of narcosis following an injection of pentobarbital sodium (Euthanimal 40%; Lot No.: 1409236-06, Expiry Date: September 2017, Produced by: AlfasanNederland BV, Woerden, The Netherlands). After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross macroscopic changes were recorded for each animal.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks:

anhydrous lutetium oxide silicate

Mortality:

None

Clinical signs:

other: None

Gross pathology:

There was no evidence of macroscopic observations at a dose level of 2000 mg/kg bw.

Other findings:

No data

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the acute oral LD50 value of lutetium oxide silicate was found to be above 2000 mg/kg bw in female Crl:(WI) rats. According to these results, lutetium oxide silicate needs not to be classified according to CLP criteria.