Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 September 2009 to 14 October 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
Standard method - a group of five male and five female rats were exposed topically for 24 hours to a dose of 2000 mg/kg bw applied under a semi-occlusive dressing to intact dorsal skin. Clinical signs and bodyweight progression were monitored over the following two weeks and a full macroscopic examination completed at termination
GLP compliance:
yes (incl. certificate)
Test type:
standard acute 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): tin metal powder (2-11 µm )
- Substance type: metal powder ground to ensure particle size was within the range of 2-11 µm
- Physical state: grey metallic powder
- Lot/batch No.: 090418
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK BIcester, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: at least 200 g (males - 225 to 247 g; females - 202 to 227 g on day 0)
- Fasting period before study: not applicable
- Housing: suspended polypropylene caging. Individually housed during treatment and group housed up to 5 rats per sex after dressing removal
- Diet: Available ad libitum. 2014 Teklan Global Rodent diet supplied by Harlan Teklad, Blackthorn Bicester, Oxon, UK.
- Water: Available ad libitum. Mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 % RH
- Air changes: 15 per hr
- Photoperiod: 12/12 (hrs dark / hrs light)

IN-LIFE DATES: From: 30 September 2009 To: 14 October 2009

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- Area of exposure: 8 x 10 cm area on the dorsum
- % coverage: 10 %
- Type of wrap if used: surgical gauze and adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton wool moistened with arachis oil
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw adjusted for individual rat bodyweight on Day 0
- Concentration (if solution): not applicable
- Constant volume or concentration used: no
- For solids, paste formed: yes - powder moistened with arachis oil BP

VEHICLE
- Amount(s) applied (volume or weight with unit): Sufficient to moisten individual doses
- Concentration (if solution): not applicable
- Lot/batch no. (if required): not specified
- Purity: not specified (arachis oil BP)
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing, and subsequently once daily for fourteen days.
- Frequency of observations and weighing:daily observations. Bodyweights recorded at day 0, 7 and 14. After the removal of the dressings and subsequently once daily the test sites were examined for evidence of primary irritation.
- Necropsy of survivors performed: At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominaal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Data evaluations included the relationship, if any, between the exposure of the animal to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test amterial was made.

Results and discussion

Effect levels
Key result
Sex:
male/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:
There were no deaths.
Clinical signs:
No clinical signs indicative of reaction to treatment or of systemic toxicity were observed
Body weight:
No treatment related effects on bodyweight or weight gain were observed. All rats gained weight as expected over the observation period.
Gross pathology:
No macroscopic abnormalities were evident during necropsy.
Other findings:
There were no dermal reactions at the treated sites.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
The acute median lethal dermal dose to Wistar rats was greater than 2000 mg/kg bw.
Executive summary:

A group of five male and five female Wistar rats was topically treated with 2000 mg/kg bw of tin metal powder (prepared to provide a particle size in the range 2 -11 µm) in a GLP compliant study conducted to current internationally accepted guidelines (OECD 402 and EU Method B.3). No evidence was found for dermal toxicity at the limit dose level.