Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2017-02-14 to 2017-05-17
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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
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

Constituent 1
Chemical structure
Reference substance name:
ytterbia stabilised yttrium disilicate
Molecular formula:
Yb2-xYxSi2O7
IUPAC Name:
ytterbia stabilised yttrium disilicate
Test material form:
solid: particulate/powder
Details on test material:
Name: ytterbium doped yttrium disilicate
Physical state: solid
Appearance: white 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 in the vehicle (1% methyl cellulose).
- No correction factor for purity of the test item was applied.

FORM AS APPLIED IN THE TEST: formulation with 1% methyl cellulose 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 dosing: young healthy adult rats, 8 weeks
- Weight at treatment: 186-200 g
- Fasting period before study: No more than 16 hours. Food but not water was withheld during an overnight period. Food was returned 3 hours after treatment.
- Housing: Standard housing conditions. Type II. polypropylene/polycarbonate cages, 3 animals/cage. Lignocel 3/4-S Hygienic Animal Bedding, and Arbocel crinklets natural, produced by J. Rettenmaier & Söhne GmbH + CO.KG (D-73494 Rosenberg, Germany) were provided.
- 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: 484 14771, expiry date: 30 June 2017)
- Water (e.g. ad libitum): ad libitum, tap water from the municipal supply
- 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: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 – 23.9 °C
- Humidity (%): 36 – 61 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE PERIOD
14 February 2017 - 28 February 2017 (females no. 6700, 6701, 6702)
15 February 2017 - 1 March 2017 (females no. 6703, 6704, 6705)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
1%
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): 2H22012N32

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): Freshly formulated on the day of administration at a concentration of 200 mg/mL in vehicle (1% methylcellulose). The formulation container was magnetic stirred continuously up to the end of the dose administration procedures. The test item formulation was used within 4 hours of preparation.

CLASS METHOD (if applicable)
- 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. Initially, three female animals were treated with the test item at a dose level of 2000 mg/kg bw. No mortality was observed, therefore a further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guidelines.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females per group, 2 groups
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 dosing and daily for 14 consecutive days thereafter.
*Individual observations were performed on the skin, fur, eyes, mucous membranes, 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), weekly thereafter (Day 7) and at necropsy (Day 14).
- Necropsy of survivors performed: Yes. The animals were sacrificed by exsanguination under pentobarbital anaesthesia. All animals were subjected to necropsy and a macroscopic examination. 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 analyses were performed.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test item did not cause mortality at a dose level of 2000 mg/kg bw
Clinical signs:
All animals were symptom-free during the observation period.
Body weight:
Body weight gains of treated animals during the study showed no indication of a test item-related effect.
Gross pathology:
There was no evidence of macroscopic changes at a dose level of 2000 mg/kg bw in any animal.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute oral LD50 value of ytterbium doped yttrium disilicate was found to be > 2000 mg/kg bw in female Crl:(WI) rats. According to these results, ytterbium doped yttrium disilicate needs not to be classified according to the CLP criteria.