Dibutylbis(dodecylthio)stannane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

In life dates: 9th September to 15th October 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study conducted to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dibutylbis(dodecylthio)stannane

EC Number:

214-688-7

EC Name:

Dibutylbis(dodecylthio)stannane

Cas Number:

1185-81-5

Molecular formula:

C32H68S2Sn

IUPAC Name:

dibutylbis(dodecylsulfanyl)stannane

Details on test material:

Identity: Dabco T120 Catalyst
Batch No.: 817231
Date Received: 08/13/10
Storage: Room temperature and humidity
Description: Clear liquid
Specific Gravity: 1.00
Sample Preparation: The test article was used as received.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animals were received from Myrtle's Rabbitry Incorporated, Thompsons Station, TN on 08/26/10 & 09/23/10.
- Age at study initiation: The animals were born on 05/13/10 & 05/30/10 and so were approximately 15-17 weeks old.
- Weight at study initiation: The pretest body weight range was 2.6 - 3.4 kg. The weight variation of the animals used did not exceed + 20% of the mean weight.
- Housing: The animals were identified by cage notation and a uniquely numbered metal eartag and housed 1/cage in suspended wire cages. Paper bedding was placed beneath the cages and changed at least three times/week.
- Diet: Fresh PMI Rabbit Chow (Diet #5321) was provided daily.
- Water: Water was available ad libitum
- Acclimation period: Following an acclimation period of at least one week, six healthy, non-pregnant and nulliparous female New Zealand White rabbits were randomly assigned to the treatment group using standard methods of randomization.

ENVIRONMENTAL CONDITIONS
The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12-hour light/dark cycle, and was kept clean and vermin free.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ~10 x 15 cm
- % coverage: The prepared site was approximately 10% of the body surface and remained intact.
- Type of wrap if used: The torso was wrapped with plastic that was secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test article was removed by gently washing with water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The doses were based on the sample weight as calculated from the specific gravity.

Duration of exposure:

24 hours

Doses:

1000 & 2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for 14 days for mortality.
Body weights were recorded pretest, weekly and at death, or termination in the survivors.
- Necropsy of survivors performed: yes
- Other examinations performed: All animals were examined for gross pathology. Abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination.

Statistics:

An estimate of the LD50 was made based on the survival during the study.

Results and discussion

Preliminary study:

n/a

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

1000 mg/kg: Two out of three survived.

2000 mg/kg: One out of three female animals survived.

Clinical signs:

other: 1000 mg/kg: All animals were normal through Day 2. On Days 3 - 5, two out of three animals were observed with few feces, one was normal. On Day 6, one animal was found dead. Out of the remaining two animals, one remained normal through the end of the stud

Gross pathology:

1000 mg/kg: A moderately pale liver and markedly pale stomach filled with brown liquid and white mucous were noted for animal H3667 female, that was found dead on Day 6. One of the remaining two animals had fluid in the peritoneal cavity and scattered red areas on the walls of the cavity. Both animals had treated skin abnormalities and localized areas of alopecia with thickened crusty skin around the muzzle similar to what was observed on the treated dorsal site.

2000 mg/kg: Moderately pale livers and markedly pale stomachs were noted for all animals. Two were noted with brown fluid and white mucous in the stomach and one had markedly red areas on the intestines. The two animals that were found dead had soiled anogenital areas. The animal that was found dead on Day 5 had an area of the stomach that appeared to be ulcerated, a small opening in the wall and excessive amounts of fluid in the peritoneal cavity. The spleen appeared smaller than normal and pale. A blood clot approximately 2.5 cm was located beneath the stomach. The animal that survived to Day 14 had an enlarged gallbladder that was distended with brown fluid. This animal also exhibited localized areas of alopecia with thickened crusty skin around the muzzle similar to what was observed on the treated dorsal site. Reddened and pale areas and sloughing skin was also observed on the ears of the surviving animal, most likely due to the contact with the treated dorsal site.

Other findings:

- Other observations: Dermal observations at 24 hours were absent to very slight (erythema and edema). On Day 7, erythema remained absent to very slight while edema was moderate. By Day 14, the remaining animals had severe erythema with moderate eschar and necrosis, one was noted with cracking and peeling skin. Edema was slight.

Any other information on results incl. tables

Table 1. Body weights, Dose volumes and Dermal observations.

Animal number	Sex	Dose Volume (mL)	Bodyweight (kg)			24 hours		Day 7		Day 14
			Day 0	Day 7	Day 14	Erythema	Edema	Erythema	Edema	Erythema	Edema
Dose: 1000mg/kg
H3666	F	3.4	3.4	2.6	3.1	1	1	0	3	>4m	2
H3667	F	3.3	3.3			1	1	Dead Day 6
H3668	F	3.3	3.3	3.2	3.3	1	0	1	3	>4n,c,pe	2
Mean			3	2.9	3.2
S.D.			0.1	0.4	0.1
#			3	2	2
Dose: 2000 mg/kg
H3734	F	5.2	2.6	2		3	1	3,p	3	Dead Day 8
H3735	F	5.4	2.7	2.2	1.8	2	0	2,c,e	3	1,c,e	2
H3736	F	5.4	2.7			1	1	Dead Day 5
Mean			2.7	2.1
S.D.			0.1	0.1
#			3	2

S.D. = standard deviation

# = number of surviving animals

c = cracking skin

e = eschar formation

p = pale areas

Table 2. Systemic observations.

	Dose levels
	1000 mg/kg			2000 mg/kg
Animal number	H3666	H3367	H3668	H3734	H3735	H3736
Time periods
Hour 1
Hour 2
Hour 4
Day 1
Day 2
Day 3	X	X		X	X	X
Day 4	X	X		X	X	X
Day 5	X	X		X	X, D	Z (2.4kg)
Day 6	X, W	Z (2.8 kg)		X	X	-
Day 7	W, X	-		X, W	X, W	-
Day 8	X, W	-		Z	X, W	-
Day 9	X, W	-		-	X, W	-
Day 10	X, W	-		-	X, W	-
Day 11	X, W	-		-	X, W	-
Day 12	W	-		-	X, W	-
Day 13		-		-	X, W	-
Day 14		-		-	X, W	-

No entry indicates the animal appeared normal at that observation period.

D = diarrhea

X = few feces

W = emaciated

Z = dead

Table 3. Necropsy observations.

	Dose levels	1000 mg/kg			2000 mg/kg
	Animal number	H3666	H3367	H3668	H3734	H3735	H3736
	Sex	F	F	F	F	F	F
	Death (D) / Sacrifice (S)	S	D	S	D	S	D
Observations
Emaciated						X
Treated skin abnormalities		X		X	X	X	X
Anogenital area: soiled					X		X
Gall bladder: enlarged and distended with brown fluid						X
Liver: pale areas			2		2	2	2
Stomach: pale			3
Stomach: filled with dark brown liquid and white mucous			X		X	X
Intestines: red areas					3
Ears: areas of erythema and paleness with the outermost layers of skin sloughing off, the skin was very soft and mucous-like.						X
Peritoneal cavity: excess fluid				X
Cavity walls: red areas				1
Alopecia: localised alopecia on muzzle with thickened crusty skin appearing similar to the dorsal dose site		X		X		X
Stomach: area appeared to be ulcerated (small opening on the stomach wall)							X
Stomach contents: white mucous and dark brown/red substance							X
Peritoneal cavity: excessive amounts of red fluid							X
Spleen: appeared smaller than normal and pale							X
Kidney sized blood clot located beneath the stomach							X

X = observed

1 = slight or scattered

2 = moderate or few

3 = pronounced or many

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 of the test material is greater than 1000 mg/kg but less than 2000 mg/kg of body weight.

Executive summary:

The study was conducted to determine the potential for toxicity of the test article when applied dermally and was designed to comply with the standards set forth in OECD Guidelines for Testing Chemicals, Number 402, adopted February 24, 1987.

Three healthy female New Zealand White rabbits were dosed dermally with the test material at 1000 mg/kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded at 24 hours postdose and on days 7 and 14. Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 hours postdose and once daily for 14 days. Based on the data from the 1000 mg/kg level and at the request of the Sponsor, an additional three female rabbits were dosed and observed at 2000 mg/kg in the same manner as the 1000 mg/kg level. All animals were observed twice a day for mortality. Body weights were recorded pretest, weekly and at death or termination in the survivors. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination.

In the 1000 mg/kg dose, two out of three survived. All animals were normal through Day 2. On Days 3 - 5, two out of three animals were observed with few feces, one was normal. On Day 6, one animal was found dead. Out of the remaining two animals, one remained normal through the end of the study and the other (H3666) was emaciated with few feces until Day 13 and 14 when it was observed as normal. All animals lost weight, the animal that had remained normal weighed the same as pretest on Day 14.

Dermal observations at 24 hours were absent to very slight (erythema and edema). On Day 7, erythema remained absent to very slight while edema was moderate. By Day 14, the remaining animals had severe erythema with moderate eschar and necrosis, one was noted with cracking and peeling skin. Edema was slight.

A moderately pale liver and markedly pale stomach filled with brown liquid and white mucous were noted for animal H3667 female, that was found dead on Day 6. One of the remaining two animals had fluid in the peritoneal cavity and scattered red areas on the walls of the cavity, Both animals had treated skin abnormalities and localized areas of alopecia with thickened crusty skin around the muzzle similar to what was observed on the treated dorsal site.

In the 2000 mgkg dose, one out of three female animals survived. All animals were normal through Day 2. On Days 3 and 4, all animals were observed with few feces. On Day 5, one animal was found dead. Out of the remaining two animals both had few feces and one had diarrhea. On Day 6, both had few feces and by Day 7 were also emaciated. On Day 8, another animal was found dead. The remaining animal had few feces and was emaciated until the end of the study. Due to the condition of the animals the cervical collar was removed from the surviving animal on Day 5, this did not have an affect on the animal's condition. All animals lost weight.

Moderately pale livers and markedly pale stomachs were noted for all animals. Two were noted with brown fluid and white mucous in the stomach and one had markedly red areas on the intestines. The two animals that were found dead had soiled anogenital areas. The animal that was found dead on Day 5 had an area of the stomach that appeared to be ulcerated, a small opening in the wall and excessive amounts of fluid in the peritoneal cavity. The spleen appeared smaller than normal and pale. A blood clot approximately

2.5 cm was located beneath the stomach. The animal that survived to Day 14 had an enlarged gallbladder that was distended with brown fluid. This animal also exhibited localized areas of alopecia with thickened crusty skin around the muzzle similar to what was observed on the treated dorsal site. Reddened and pale areas and sloughing skin was also observed on the ears of the surviving animal, most likely due to the contact with the treated dorsal site.

The dermal LD50 of the test material is greater than 1000 mg/kg but less than 2000 mg/kg of body weight.