Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

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.

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 402 (Acute Dermal Toxicity)
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: 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

Administration / exposure

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

Results and discussion

Effect levels
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.

Any other information on results incl. tables

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         

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 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.