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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:
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.

Data source

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

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

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:

Administration / exposure

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.

Results and discussion

Effect levels
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.