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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03-24 November 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

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
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Silicic acid (H2Si2O5), barium salt (1:1), lead-doped
EC Number:
272-271-5
EC Name:
Silicic acid (H2Si2O5), barium salt (1:1), lead-doped
Cas Number:
68784-75-8
Molecular formula:
BaSi2O5::Pb
IUPAC Name:
barium(2+) {[oxido(oxo)silyl]oxy}silanoylolate λ²-plumbane
Details on test material:
- Name of test material (as cited in study report): Silicic acid(H2Si2O5), barium salt(1:1), lead-doped
-Substance type: White powder
- Physical state: Solid
- Analytical purity: 100%
- Purity test date: 20-oct-2009
- Lot/batch No.: NP-800-11-232
- Expiration date of the lot/batch: 16 October 2010 (allocated by NOTOX, 1 year after receipt of the test substance)
- Stability under test conditions:
Stability under storage conditions Stable
Stability in vehicle 1% Aq. Carboxymethyl cellulose: Unknown

- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: approx. 12 weeks old
Animal no 7, 8 and 9 were 13 weeks old at start of treatment.
The age is only slightly higher than stated in the protocol (8-12 weeks) Based on experience this age difference is considered not to have adversely
affected the study outcome.

- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 21.5ºC
- Humidity (%): 41 - 81%)
Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 03 november 2010 To: 24 november 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% Aqueous carboxymethyl cellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml and 30 mg/ml 1% Aqueous carboxymethyl cellulose
- Amount of vehicle (if gavage): 10 mL/kg Single dosage, on Day 1
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.


Doses:
2000 mg/kg body weight
300 mg/kg body weight.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs At periodic intervals (0, 2 and 4 hours) on the day of dosing (Day 1) and once daily thereafter, until Day 15.
Body weights Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- Necropsy of survivors performed: yes
- Other examinations performed:Mortality/Viability, clinical signs, body weight,
Statistics:
None.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Three females, treated at 2000 mg/kg, were sacrificed in moribund condition on Days 1 and 2. No further mortality occurred at the dose level of 300 mg/kg.
Clinical signs:
other: Clinical signs observed during the study period were as follows: Dose level Clinical signs 2000 mg/kg Lethargy, tremor, flat and/or hunched posture, uncoordinated movements, abnormal gait, slow or quick breathing, piloerection, watery discharge from the e
Gross pathology:
In one animal treated at 2000 mg/kg many reddish foci in glandular mucosa and black-brown content of the small intestine were observed. The other animals at 2000 mg/kg showed no macroscopic abnormalities.

No abnormalities were found at macroscopic post mortem examination of the animals treated at 300 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The oral LD50 value of Silicic acid(H2Si2O5), barium salt(1:1), lead-doped in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.

Based on these results:
according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007), Silicic acid(H2Si2O5), barium salt(1:1), lead-doped should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.
according to the EC criteria for classification and labeling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), Silicic acid(H2Si2O5), barium salt(1:1), lead-doped should be labeled as: harmful if swallowed (R22).
according to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, Silicic acid(H2Si2O5), barium salt(1:1), lead-doped should be classified as Category 4 and should be labeled as H302: Harmful if swallowed.

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