Registration Dossier

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:
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
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
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. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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 eyes, pale appearance and/or ptosis were noted up to the day of death.
300 mg/kg Hunched posture and/or piloerection between Days 1 and 3.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
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.