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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 December 2008 to 13 January 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Elemental tin powder (2-11 µm)
- Substance type: metallic tin powder
- Physical state: powder
- Analytical purity: 99.97 %
- Lot/batch No.: 070402
- Expiration date of the lot/batch: 5 March 2009
- Stability under test conditions: stable at room temperature
- Storage condition of test material: room temperature 15-25 °C

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD (SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd, Margate
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: 180-225 g
- Fasting period before study: yes overnight
- Housing:The animals were housed in groups of up to five during the acclimatisation period. From the day prior to dosing (Day-1), the rats were housed in groups of three in similar cages. The animals were provided on a weekly basis clean Aspen wood chips (Datesand Ltd, Manchester UK) as bedding. The bedding had been analysed for specific contaminants and the results retained on file at Covance.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham UK was available ad libitum except for a period of fasting from the evening of the day prior to dosing. Each batch of diet had been analysed for specific constituents and contaminants by the manufacturer.
- Water (e.g. ad libitum): Mains water in cage mounted water bottles, available ad libitum. The water had been periodically analysed for specific contaminatns.
- Acclimation period: 7-14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 40-70 % RH
- Air changes: 15 air changes per hour
- Photoperiod: The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

IN-LIFE DATES: From: 22 December 2008 To: 13 January 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: 1 % aqueous carboxymethylcellulose (sodium salt) was found to be an appropriate suspending agent giving a homogeneous stable formulation

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Information from acute toxicity investigations suggested tin was not toxic at the regulatory limit dose
Doses:
Two groups of three females dosed at 2000 mg/kg bw
No. of animals per sex per dose:
Three females
Control animals:
no
Details on study design:
- Duration of observation period following administration: Animals were sacrificed on day 15.
- Frequency of observations and weighing: Treated rats were observed for clinical sign of reaction to treatment. Clinical signs were recorded immediately post-dose at approximately 15 and 30 minutes post-dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3, and 4 and once daily from the fifth to last day of the observation period. The second observation was not conducted on day 4 for the first group of animals. Rats were weighed on Day-1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: Yes. Rats were killed on Day 15. Each animal was given an intraperitoneal injection of sodium pentobarbitone. Once a suitably deep plane of anaesthesia had been established, the animal was exsanguinated by the severing of major blood vessels. After exsanguination a full macroscopic necrospy was performed and all lesions were recorded.
The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines. No tissue preservation or histopathological assessment of tissues was undertaken.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortalities
Clinical signs:
No clinical signs of reaction to treatment observed
Body weight:
All rats gained weight over weeks 1 and 2 following dosing.
Gross pathology:
No macroscopic abnormalities were observed
Other findings:
No indications of systemic toxicity following oral administration of the limit dose, 2000 mg/kg bw, of metallic tin powder rendered highly absorbale by grinding to produce a standardised powder with granules in the range of 2-11 µm.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
The acute median lethal oral dose level of the test article, Elemental Tin Powder (2 – 11 µm), was found to exceed 2000 mg/kg.
Executive summary:

Oral administration of a suspension of Tin powder (2 -11 µm) in aqueous CMC was administered to two groups of three female rats at the limit dose level according to the Acute Toxic Class guideline, OECD 423 (performed in compliance with GLP). The treated rats were observed for mortality and clinical signs over a 14 day observation period. Bodyweights were recorded prior to, and on, the day of dosing and on days 4, 8 and 15. Necropsy was completed on day 15.

There were no mortalities, no signs of reaction to treatment, no effects on bodyweight and no abnormalities observed during necropsy.

The acute median lethal oral dose level of the test article, Elemental Tin Powder (2 – 11 µm), was found to exceed 2000 mg/kg.