Tin dioxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study in compliance with international recognized guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

1

Reference substance name:

Tin dioxide

EC Number:

242-159-0

EC Name:

Tin dioxide

Cas Number:

18282-10-5

Molecular formula:

O2Sn

IUPAC Name:

tin(4+) dioxidandiide

Test material form:

solid: nanoform

Details on test material:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material:
2012-000203
- Expiration date of the lot/batch:
07/02/2013, W0167
- Purity test date:
> 99.9%, 23/01/2011



INFORMATION ON NANOMATERIALS
- Chemical Composition:
Tin Dioxide
- Density:
6.936 g/cm³
- Particle size & distribution:
10-100 nm; 78
- Specific surface area: 7.4293 ± 0.0132 m²/g

Test animals

Species:

rat

Strain:

other: Spangue-Dawley derived, albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Number of Animals: 10
- Sex: 5 Males and 5 Females. The females assigned to test were nulliparous and non- pregnant.
- Species/Strain: Rat/Sprague-Dawley derived, albino.
- Age/Body weight: Young adult (10-11 weeks)/males 273-294 grams and females 185- 212 grams at experimental start.
- Source: Received from Harlan Laboratories, Inc. on March 14, 2012.

Enviromental conditions:
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Litter paper was placed beneath the cage and was changed at least three times per week.

- Animal Room Temperature and Relative Humidity Ranges: 20-23ºC and 46-58%, respectively.

- Animal Room Air Changes/Hour: 13. Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.

- Photoperiod: 12-hour light/dark cycle

- Acclimation Period: 14 days

- Food: Harlan Teklad Global 16% Protein Rodent Diet #2016 was supplied ad libitum, except during exposure.

- Water: Tap water was supplied ad libitum by an automatic water dispensing system except during exposure.

- Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: water

Details on inhalation exposure:

Nose-Only Exposure Chamber: A nose-only inhalation chamber with an internal volume of approximately 28 liters (Nose-Only Inhalation Chamber, ADG Developments LTD) was used for exposure. Animals were individually housed in polycarbonate holding tu exposure. The base unit terminates the chamber with a 0.5-inch diameter tube for discharged air.

Air Supply: Approximately 30.0 liters per minute (Lpm) of filtered air was supplied by an air compressor (Powerex Model: SES05) to the spray atomization nozzle. An additional 6.0 Lpm of compressed mixing air from the air compressor was introduced into the chamber to help uniformly distribute the test atmosphere by creating a vortex at the chamber inlet. Compressed airflow was measured with a Mass Flowmeter (Omega, Model #FMA-5613). Chamber airflow was monitored throughout the exposure period and recorded periodically. Mean airflow was 36.0 Lpm. Based on the volume of the inhalation chamber, this airflow provided approximately 77 air changes per hour during the study.

Ambient Conditions: The exposure tube temperature and relative humidity ranges during exposure were 20-21ºC and 16-19%, respectively. The room temperature and relative humidity ranges during exposure were 20-21ºC and 29-30%, respectively. A humidifier was used during exposure. The measurements inside the exposure tube and the room conditions were made with a Temperature-Humidity Monitor (Fisher Scientific, 11-661-18). Temperature and relative humidity values were recorded every 15 minutes for the first hour of exposure and every 15 or 30 minutes thereafter.

Atmosphere Generation: The test atmosphere was generated using a ¼ inch JCO atomizer, (Spraying Systems Co.), FC3 fluid cap (Robert Miller Associates) and 70SS air cap (Spraying Systems Co.). Compressed generator/mixing air were supplied at 30/30 psi. The test substance was metered to the atomization nozzle through size 16 Tygon tubing, using a peristaltic pump (Master Flex, Model #7520-35).

Chamber Concentration Measurements: Gravimetric samples were withdrawn at six intervals from the breathing zone of the animals. Samples were collected using 37 mm glass fiber filters (GF/B Whatman) in a filter holder attached by ¼ inch Tygon tubing to a vacuum pump (Westech). The filter was weighed before and after collection to determine the mass collected. The collections were carried out for 1 minute at airflows of 4 Lpm. Sample airflows were measured using a Mass Flowmeter (Aalborg, Model #GFC-17).

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric analysis + flowmeter analysis

Duration of exposure:

> 4 h

Remarks on duration:

the exposure period was extended of 4 min beyond 4 hours in order to reach an equilibrium in the chamber.

Concentrations:

the dry weight gravimetric and nominal chamber concentrations were 2.04 mg/L and 236.7 mg/L, respectively. 2.4 mg/L was the highest chamber concentration achieved.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Prior to initiation of the full inhalation study, pre-test trials were conducted to establish generation procedures to achieve, to the extent possible, the desired chamber concentration (2.0 mg/L) and desired particle size distribution (mass median aerodynamic diameter between 1 and 4 µm).

Prior to conducting pre-test trials, attempts were made at generating the test atmosphere as a dust. However, the test substance as a powder clogged all dust generator equipment used during preliminary testing. Therefore, the unground test substance was diluted to a 25% w/w dilution in distilled water for all trials conducted. In addition, it was decided that a dry weight gravimetric measurement procedure was to be used. The exposure procedures and atomization equipment used were based on the results of pre-test trial number 2 which provided a gravimetric concentration of 2.03 mg/L with a mass median aerodynamic diameter of 2.21 µm.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.04 other: mg/L (dry weight)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: the substance was diluted in distilled water at 25% w/w

Mortality:

All animals survived exposure to the test atmosphere.

Clinical signs:

other: Following exposure four males and all five females exhibited irregular respiration. All affected rats recovered from this symptom by Day 5, and along with the fifth male, appeared active and healthy for the remainder of the observation period.

Body weight:

Individual body weights of the animals were recorded prior to test substance exposure (initial) and again on Days 1, 3, 7 and 14 (termination).
Although all rats lost body weight by Day 1 and/or through Day 3, all animals showed a weight gain over the entire study.

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the single exposure acute inhalation LC 50 of a 25% w/w dilution of Tin dioxide in distilled water is greater than 2.04 mg/L maximum attainable (dry weight) in male and female rats.