Registration Dossier

Administrative data

Description of key information

Acute toxicity of Tin disulfide powder was tested in key studies according to standard methods for 
oral, inhalation and dermal toxicity in rats. Resulting LD50 values were > 2000 mg/kg bw for oral
and dermal application and > 5 mg/L for inhalation (nose only) administration. Laboured respiration
and respiratory rate increase were recorded in the inhalation study. Supporting studies based on
read-across with Tin sulfide were available for oral, dermal and inhalation application, showing
similar results.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
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 for classification.
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
other: Wistar- HsdCpd: WU
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: In-house random bred ( Toxicology, Department of Safety Assessment, Advinus Therapeutics Limited, Bangalore, India)
- Age at study initiation: 8-12 weeks
- Weight at study initiation: At the selection of animals for each treatment step, the weight variation of animals will be minimal and will not exceed ± 20% of the mean body weight of any previously dosed animals.
- Fasting period before study: 16-18 hours before administration ( access to water will not be interrupted)
- Housing: individually in standard polysulfone cages (Size: approximately L 425 x B 266 x H 175 mm), with stainless steel top grill having facilities for pelletted food and drinking water
- Diet (e.g. ad libitum): Teklad Certified (2014C) Global 14% Protein Rodent Maintenance Diet-Pellet (Certified) manufactured by Harlan Laboratories B.V. Maasheseweg 87c PO Box 553, 5800, AN Venray, The Netherlands, ad libitum
- Water (e.g. ad libitum): deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd., Mumbai 400 001, India in polycarbonate bottles with stainless steel sipper tubes
- Acclimation period: cannot be fixed since the procedure is a step by step method, at least 5 days.

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

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
other: Milli-Q water
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: stable suspension up to 24 hour

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
The main test consists of a single ordered dose progression in which animals are dosed, one at a time, at a minimum of 48-hour intervals. The first animal received a limit dose of 2000 mg/kg body weight, the animal survived, the dosing was continued with additional four animals sequentially with the same dose each animal was observed carefully for up to 48 hours before making a decision on whether and how much to dose the next animal. This decision is based on the 48 hour survival pattern of all the animals up to the time. A combination of stopping criteria is used to keep the number of animals low while adjusting the dosing pattern to reduce the effect of a poor starting value or a low slope. Dosing is stopped when one of these criterions is satisfied, at which time an estimate of the LD50 and the confidence intervals are calculated for the test based on the status of all the animals at termination.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: The animals were observed five times on test day 1 (day of administration) i.e., at 30 minutes, 1, 2, 3 and 4 hours after dose administration and once daily during days 2 – 15. Individual body weights of animals were recorded on test day 1 (Pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
The AOT425 Stat Programme was downloaded from Web Site http://www.epa.gov/oppfead1/international/harmonization.html and implemented in the test facility’s system for LD50 calculation.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
As there were no clinical signs of toxicity and no mortality in all five rats tested, the test was terminated.
Clinical signs:
There were no clinical signs of toxicity in any of the animals.
Body weight:
All rats gained body weight throughout the observation period.
Gross pathology:
There were no abnormalities detected at necropsy.

Table 1. Body weight, Body weight change and Pre-terminal deaths

Step and

Dose

(mg/kg

Body weight)

Rat

No.

Sex

Body weight (g)

Initial

(Day 1)

 

Day 8

Weight change

(Day 8 – Initial)

Day 15

Weight change

(Day 15 – Initial)

Step 1

(2000)

Rm751

F

194.8

204.6

9.8

210.9

16.1

Step 2

(2000)

Rm752

F

192.6

212.5

19.9

215.6

23

Step 3

(2000)

Rm753

F

194.8

214.1

19.3

223.6

28.8

Step 4

(2000)

Rm754

F

193.5

206.6

13.1

214.7

21.2

Step 5

(2000)

Rm755

F

201.6

217.3

15.7

225.1

23.5

 

 Table 2. Short-Term And Long-Term Results

Step

No.

Dose

(mg/kg body weight)

Rat

No.

Short-term

Result #

Long-term

Result @

1

 

2000 

Rm751

Survived

Survived

2

 

2000 

Rm752

Survived

Survived

3

 

2000 

Rm753

Survived

Survived

4

 

2000 

Rm754

Survived

Survived

5

 

2000 

Rm755

Survived

Survived

#: The survival pattern used to determine whether and how to dose next animal is a short term outcome. 

@: The status of the animals at termination is the long term outcome.

 

Table 3. Individual Clinical Signs and Necropsy Findings

Step

Dose (mg/kg body weight)

Rat

No.

S

e

x

Observations

Necropsy

Findings

Day 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

30 min.

1 hour

2 hours

3 hours

4 hours

1

 

2000

Rm751

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

2

 

2000

Rm752

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

3

2000

Rm753

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

4

2000

Rm754

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

5

2000

Rm755

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

F: Female;         min: minutes;             N: Normal;         NAD: No Abnormality Detected

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
CLP: not classified
Conclusions:
Based on the present study results, the estimated acute oral LD50 of Tin Disulfide (CAS 1315-01-1) is greater than 2000 mg/kg body weight in female rats.
Executive summary:

An acute oral toxicity test (Up-and-Down Procedure) was conducted with female Wistar rats to determine the potential of Tin disulfide (CAS 1315-01-1). The test item was diluted in Milli-Q water and administered as a single oral dose at 2000 mg/kg, first in one female rat, followed by four additional animals at the same dose. Those four animals survived, and the test was concluded. All animals were active and gained body weight during 14 days observation period. All animals were subjected to necropsy at sacrifice and there were no abnormalities observed in any of the rats. Based on the present study results, the estimated acute oral LD50 of Tin disulfide is greater than 2000 mg/kg body weight in female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
High (Klimisch 1)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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.
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
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)


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
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
5.02 mg/m³
Quality of whole database:
High (Klimisch 1)

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar– HsdCpb: WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxicology, Department of Safety Assessment, Advinus Therapeutics Limited, Bangalore 560 058, INDIA
- Age at study initiation: 11 to 12 weeks
- Weight at study initiation: Males: 259.2 - 295.7 g ; Females : 209.4 - 221.9 g
- Housing: Individually in standard polysulfone cages (Size: approximately L425 x B 266 x H 175 mm), with stainless steel top grill having facilities for pelletted food and drinking water. Steam sterilized clean corn was used as bedding and changed along with the cage at least twice a week.
- Diet (e.g. ad libitum): Teklad Certified (2014C) Global 14% Protein Rodent Maintenance Diet - Pellet (Certified) manufactured by Harlan Laboratories B.V. Maasheseweg 87c PO Box 553, 5800, AN Venray, The Netherlands was provided ad libitum to animals.
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd., Mumbai - 400 001, India, was provided to animals in polycarbonate bottles with stainless steel sipper tubes. The water bottles were replenished once daily and the water bottles were changed once a week.
- Acclimation period: females 5 days, males 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): 54-66%
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 2012-02-22 TO 2012-03-09
Type of coverage:
semiocclusive
Vehicle:
other: Milli-Q water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsolateral thoracic surface of the skin
- % coverage: about 10% of body surface of the animal (9x6 cm in males; 8x5 cm in females)
- Type of wrap if used: cotton gaze and adhesive type

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the applied area was washed initially with water and with Johnson’s Baby Soap (Johnson & Johnson U.S.A.© J&J*TM) and again with water. Washed animals were wiped dry with a cotton hand towel.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg bw
- Concentration (if solution):
- Constant volume used: no
- For solids, paste formed: yes

VEHICLE: milli-Q water

Duration of exposure:
24 h
Doses:
2000mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Observations included clinical signs of toxicity and mortality four times on test day 1 (at hourly intervals after application) and once daily during days 2 - 15. Individual body weights of animals were recorded on test days 1 (Pre-application), 8 (7 days post application), and 15 (14 days post application). The site of application was observed for skin reactions once daily during the 15-day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality observed during the study.
Clinical signs:
There were no clinical signs of toxicity, nor local skin reaction observed during the study.
Body weight:
All rats gained body weight throughout the observation period.
Gross pathology:
There was no abnormality detected at necropsy.

Table 1. Body Weight, Body Weight Changes and Pre-Terminal Deaths

Group and

Dose

(mg/kg

body weight)

Rat

No.

S

e

x

Body weight (g)

No.dead /

No.tested

Pre- terminal deaths (%)

Initial

8th day

Weight change

(day 8 – Initial)

15thday

Weight change

(day 15 – Initial)

G1

2000

 

Rm741

F

215.6

218.6

3.0

225.9

10.3

0/10

0

Rm742

F

209.4

210.7

1.3

219.6

10.2

Rm743

F

213.6

219.3

5.7

228.3

14.7

Rm744

F

209.4

210.1

0.7

219.3

9.9

Rm745

F

221.9

224.8

2.9

231.6

9.7

Rm746

M

280.9

301.6

20.7

316.5

35.6

Rm747

M

259.2

276.1

16.9

286.5

27.3

Rm748

M

270.3

280.4

10.1

298.5

28.2

Rm749

M

281.5

309.8

28.3

320.5

39.0

Rm750

M

295.7

311.5

15.8

323.9

28.2

F: Female;       M: Male         

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
CLP: not classified
Conclusions:
Based on the present study results, the acute dermal LD50 of Tin disulfide (CAS 1315-01-1) is greater than 2000 mg/kg body weight in male and female Wistar rats.
Executive summary:

An acute dermal toxicity test was conducted with Wistar rats (male and female) to determine the potential for Tin disulfide (CAS 1315-01-1) to produce toxicity from a short term exposure via the dermal route. The test item at the dose of 2000 mg/kg body weight was made into a paste by adding sufficient volume of Milli-Q water, transferred on to the cotton gauze (size: Males: 9 x 6 cm; Females: 8 x 5 cm of 6 ply) and applied on to the clipped dorsolateral thoracic surface of the skin of the rats to cover about 10% of body surface of the animal under adhesive tape wound around torso. The test item contact period with the skin was for 24 hours. After the 24 hour contact period, the dressing was removed and the applied area was washed and dried with a cotton hand towel. There were no clinical signs of toxicity, local skin reaction or mortality. At the end of observation period, all surviving animals were euthanized and subjected to necropsy. There were no abnormalities detected at the necropsy. Based on the present study results, the acute dermal LD50 of Tin disulfide > 2000 mg/kg body weight in male and female Wistar rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
High (Klimisch 1)

Additional information

A key acute oral toxicity test (Up-and-Down Procedure) was conducted with 5 female Wistar rats at 2000 mg/kg bw (Mohan Kumar, 2012a). All animals survived, were active and gained body weight during 14 days observation period. All animals were subjected to necropsy at sacrifice and there were no abnormalities observed in any of the rats. Based on the present study results, the estimated acute oral LD50 of Tin disulfide is > 2000 mg/kg body weight in female rats. A supporting oral acute toxicity study (Acute Toxic Class method) with read-across substance Tin sulfide also showed an LD50 >2000 mg/kg bw, without any clinical signs or adverse effects on body weights and necropsy findings (Yasso, 2010). Tin disulfide and Tin sulfide showed a comparable toxicological profile for this endpoint.

 

A key inhalation toxicity study was performed in Wistar rats (sighting exposure using 2 males and 2 females, followed by main study 5 males and 5 females) at target dust aerosol concentration of 5 mg/L Tin disulfide (Nagy, 2012). The animals were exposed for 4 hours using a nose-only exposure system, followed by a 14 day observation period. In the main study, the mean achieved atmosphere concentration was 5.02 mg/L. The MMAD 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 body weight 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. LC50 > 5 mg/L. Tin disulfide and Tin sulfide showed a comparable toxicological profile for this endpoint.

 

A key acute dermal toxicity test was conducted in male and female Wistar rats with Tin disulfide at 2000 mg/kg bw into a paste by adding sufficient volume of Milli-Q water (Mohan Kumar, 2012b). The test item contact period to 10% of body surface was 24 hours, after which the dressing was removed and the applied area was washed and dried. There were no clinical signs of toxicity, local skin reaction or mortality. At the end of observation period, all surviving animals were euthanized and subjected to necropsy. There were no abnormalities detected at the necropsy. Based on the present study results, the acute dermal LD50 of Tin disulfide > 2000 mg/kg body weight in male and female Wistar rats. A supporting dermal acute toxicity study was also available for Tin sulfide at 2000 mg/kg bw (DiDonato, 2010). Test article staining was noted on all dose sites at all observation periods, however there were no abnormal physical and clinical signs noted during the observation period, nor any adverse findings for body weight or necropsy. Tin disulfide and Tin sulfide showed a comparable toxicological profile for this endpoint.

Justification for selection of acute toxicity – oral endpoint Key study with reference substance 
Justification for selection of acute toxicity – inhalation endpoint Key study with reference substance 
Justification for selection of acute toxicity – dermal endpoint Key study with reference substance

Justification for classification or non-classification

No classification and labelling is needed for acute toxicity (oral, inhalation, dermal) of Tin disulfide according to EU labelling regulations Commission Directive 93/21/EEC and CLP regulation (No. 1272/2008 of 16 December 2008).