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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to standard methods and GLP and is consdered adequate, reliable and relevant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
EC 440/2008, B2 (2008)
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
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
other: CRL:(WI) Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services (Germany GmbH, Sanhofer Weg 7, D-97633 Sulzfeld)
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 214 to 371 g (♂: 350-371g; ♀: 214-259 g)
- Fasting period before study: Not provided
- Housing: in groups of 5 (or 2 in the case of the sighting exposure), by sex, in solid-floor cages (Type III) with stainless steel mesh lids and softwood flake bedding
- Diet (e.g. ad libitum): ssniff SM R/M-Z+H “Autoclavable Complete Feed for Rats and Mice – Breeding and Maintenance” (ssniff Spezialdiäten GmbH, D-59494 Soest Germany, , ad libitum
- Water (e.g. ad libitum): tap water for fit for human consumption, ad libitum
- Acclimation period: 24 and 29 days for the sighting and the main study respectively

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2012-02-09 to 23 (Sighting Exposure) and 2012-02-14 to 28 (Main study)


Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: compressed air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprised of 2 concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers.
- Exposure chamber volume: Following an equilibration period of at least the theoretical chamber equilibration time (T99) (Silver, 1946), a group of 10 rats was exposed to a target atmosphere concentration of 5 mg/L for a period of 4 hours.
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber. Only the nose of each animal was exposed to the test atmosphere.
- Source and rate of air: The flow of air through each port (breathing zone) was at least 0.7 L/min. This flow rate was considered adequate to minimize re-breathing of the test atmosphere as it is about twice the respiratory minute volume of a rat.
- Method of conditioning air: The compressed air was passed through a respiratory quality filter train and condensate separator prior to use.
- System of generating particulates/aerosols: The test item formulation was aerosolized using a rotating brush powder dispenser (Palas GmbH, Karlsruhe, Germany) located at the top of the exposure chamber and compressed air.The dust aerosol produced was ducted to the exposure system using suitable tubing
- Method of particle size determination: The particle size of the test atmosphere was determined 3 times during the exposure period using a 7-stage impactor of Mercer style (TSE Systems GmbH, Bad Homburg, Germany). Such devices employ an inertial separation technique to isolate particles in the discrete aerodynamic size ranges. Samples were taken from an unoccupied exposure port (representing the animal’s breathing zone). The collection substrates and the backup filter were weighed before and after sampling and the weight of test item, collected at each stage, calculated by this difference. The total amount collected for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of dust aerosol less than 0.55, 0.96, 1.55, 2.11, 3.56, 6.66 and 10.55 µm was calculated. From these data, using software supplied with the impactor (TSE Systems GmbH, Bad Homburg, Germany), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard deviation were calculated. In addition, the proportion (%) of dust aerosol less than 4 µm (considered to be inhalable portion) was determined.
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: dust aerosol concentrations were measured gravimetrically. The test atmosphere concentration was sampled at regular intervals during each exposure period. Samples were taken from an unoccupied exposure port (representing the animal’s breathing zone) by pulling a suitable, known volume of test atmosphere through weighed GF10 glass fibre filters (Whatman GmbH, Hahnestrasse 3, D-37589 Dassel, Germany). The difference in the pre- and post-sampling weights, divided by the volume of atmosphere sampled, was equal to the actual achieved test atmosphere concentration. The nominal concentration was calculated by dividing the mass of test material disseminated into the chamber by the total volume of air that went through the chamber during the same period.
- Samples taken from breathing zone: yes

VEHICLE: not applicable

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see Table 1 below
- MMAD (Mass median aerodynamic diameter) : 3.62 µm (sighting study) & 3.91 µm (main study)
GSD (Geometric st. dev.): see Table 1 below: 2.12 µm (sighting study) & 2.13 µm (main study)

Analytical verification of test atmosphere concentrations:
yes
Remarks:
A known volume of test atmosphere was pulled through weighed GF10 glass fibre filters (Whatman). The difference in the pre- and post-sampling weights, divided by the volume of atmosphere sampled = actual achieved test concentrations.
Duration of exposure:
4 h
Concentrations:
Sighting study: mean achieved atmosphere of 5.06 mg/L (nominal: 8.18 mg/L)
Main study: mean achieved atmosphere of 5.02 mg/L (nominal: 8.23 mg/mL)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs hourly during exposure , 1 hour after exposure and once daily subsequently for 14 days; body weight day 0, 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.02 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality was observed in the study.
Clinical signs:
Wet fur and fur staining were commonly recorded on the day of exposure and several days after exposure in both groups. These observations were considered to be related to the restraint and exposure procedures and, in isolation, were considered not to be of toxicological relevance.
Sighting Exposure: The following significant clinical signs were recorded on the day of exposure: labored respiration and respiratory rate increase. In addition, weak condition and respiratory rate increases were recorded in animals on Day 1 and/or 2. All significant clinical signs ceased from Day 3 of the observation period.
Main Study: Significant clinical signs that were recorded on the day of exposure included labored respiration and respiratory rate increased. All animals recovered by Day 2.
Body weight:
Normal bodyweight gain were recorded in the sighting exposure and the main study, with the exception of one female in the main study where a slight bodyweight loss was recorded during the first three days of the observation period.
Gross pathology:
A single 4 hours nose-only exposure of Tin disulfide to CRL:(WI) Wistar rats at dose levels of 5.06 and 5.02 mg/L during Sighting exposure or Main study phase followed by a 14-day observation period, was not associated with any gross lesions.

Any other information on results incl. tables

Table 1. Test Atmosphere Particle Size Distribution Data (Main Study)

Size Range (µm)

Total Mass/stage (mg)

Cumulative Mass (%)

<0.55

0.18

1.27

0.55-0.96

0.18

2.54

0.96-1.55

0.54

6.36

1.55-2.11

1.22

14.98

2.11-3.56

4.44

46.36

3.56-6.66

4.83

80.49

6.66-10.55

1.57

91.59

>10.55

1.19

100.00

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
CLP: not classified
Conclusions:
Under the experimental conditions of this study, no deaths occurred in a group of 10 rats exposed to a mean achieved atmosphere of 5.02 mg/L for 4 hours. The acute inhalation median lethal concentration of Tin disulfide, in CRL: (WI) Wistar strain rats is therefore considered to be greater than 5.02 mg/L.
Executive summary:

In the sighting study, the mean achieved atmosphere concentration was 5.06 mg/L, MMAD was 3.62 µm ± 2.12 GSD. Wet fur and fur staining were commonly recorded on the day of exposure and several days after exposure in both groups. These observations were considered to be related to the restraint and exposure procedures and, in isolation, were considered not to be of toxicological relevance. The following significant clinical signs were recorded on the day of exposure: laboured respiration and respiratory rate increase. In addition, weak condition and respiratory rate increased were recorded in animals on Day 1 or/and 2. All significant clinical signs ceased from Day 3 of the observation period. Normal body weight gain was recorded during whole observation period. No gross macroscopic observations were apparent at necropsy.

In the main study,the mean achieved atmosphere concentration was 5.02 mg/L. The MMAD (Mean Mass Aerodynamic Diameter) was 3.91 µm ± 2.13 (GSD). Significant clinical signs were recorded on the day of exposure including laboured respiration and respiratory rate increase. All animals recovered by Day 2. Normal bodyweight gain was recorded, with the exception of one female where a slight body weight loss was recorded during the first three days of the observation period. No gross macroscopic observations were apparent at necropsy.