Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 - 23 Dec 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Groupe interministeriel des produits chimiques, France
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): lithium silicate
- Physical state: white, granular
- Analytical purity: >99%
- Lot/batch No.: 009061957
- Expiration date of the lot/batch: 28 May 2010
- Storage condition of test material: room temperature
- Other:
Molar Ratio SiO2/Li2O: 4.8 (information provided in the product information sheet for Lithium polysilicate by the data owner)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle - France)
- Age at study initiation: 8 weeks
- Weight at study initiation: 189 - 203 g
- Fasting period before study: Food was removed at D-1 and then redistributed 4 h after test item administration
- Housing: by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid; each cage contains sawdust bedding which was changed at least 2 times a week; each cage was installed in conventional air conditioned animal husbandry.
- Diet: M20-rat/mouse maintenance (made from the formulation EXTRALABO from PIETREMENT) ad libitum
- Water: ad libitum tap water from public distribution system (microbiological and chemical analyses carried out every six months by the IPL, Santé, Environnement Durables - Atlantique)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21
- Humidity (%): 28 - 68
- Air changes (per hr): approx. 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12/12 (7:00 to 19:00)/(19:00-7:00)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

DOSAGE PREPARATION (if unusual): In each step of the study, 2 g of the test item was weighed and 10 mL DMSO was added in a volumetric flask. The preparation was magnetically stirred during 24 hours to obtain a homogenous white suspension.


Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 exposed animals (3 animals in Step 1, 3 animals in Step 2), 3 control animals
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were carried out 30 min, 1 h, 3 h, 4 h post-dose and daily thereafter; body weights were determined on D0 (just before administering the test substance), D2, D7 and D14
- Necropsy of survivors performed: yes; All animals found dead during the study were immediately necropsied.
On D14, all survivors were anaesthetised with sodium pentobarbital and administration continued to fatal levels.
Necropsy examinations: oesophagus, stomach, duodenum, jejunum, ileon, caecum, colon, rectum, spleen, liver, thymus, trachea, lungs, heart, kidneys, urinary bladder, ovaries, uterus, adrenals, pancreas

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off according to OECD 423
Mortality:
2 of 6 animals were found dead during the study: one animal from step 1 died at 28 hours 55 minutes post-dose and one animal from step 2 died at 21 hours post-dose.
Clinical signs:
The mortalities were preceded by a decrease in spontaneous activity (2/2) and in body temperature (2/2), increased lachrymation (1/2), bradypnea (2/2), tremors (1/2), piloerection (1/2) and absence of righting reflex (1/2).
In the survival animals (4/6), a decrease in spontaneous activity (4/4) and in body temperature (1/4), increased lachrymation (1/4), bradypnea (2/4), piloerection (2/4) and absence of righting reflex (2/4) were observed on the first day (1 h, 3 h and 4 h post-dose). The animals recovered a normal behaviour at 24 hours post-dose.
Body weight:
The body weight evolution of the animals remained normal throughout the study. Mean body weight gain: 57.3 g ± 12.1 g
Gross pathology:
The macroscopical examination of the dead animals revealed a thinning of the corpus associated with red spots (2/2) and a thinning of the forestomach (1/2).
The macroscopical examination of the survival animals at the end of the study did not reveal treatment-related changes.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified