Dibutoxydibutylstannane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 05 August 2010 and 26 August 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

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dibutoxydibutylstannane

EC Number:

222-103-1

EC Name:

Dibutoxydibutylstannane

Cas Number:

3349-36-8

Molecular formula:

C16H36O2Sn

IUPAC Name:

dibutoxydibutylstannane

Details on test material:

Sponsor's identification: CAS No 3349-36-8
Purity: >95%
Description: yellow liquid
Batch number: 2009175996
Date received: 24 June 2010
Expiry date: 07 May 2011
Storage conditions: room temperature in the dark

The integrity of supplied data relating to the identity, purity and stability of the test material is the responsibility of the Sponsor.
A Certificate of Analysis was supplied by the Sponsor.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Oxon, UK.
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 168-188g
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing.
- Housing: The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet/water (e.g. ad libitum): With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014 Teklad Global Rodent diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

DOSAGE PREPARATION (if unusual):
For the purpose of the 2000 mg/kg dose level, the test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg dose level, the test material was freshly prepared, as required, as a solution in arachis oil BP.

The test material was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
No analysis was conducted to determine the homogeneity, concentration or stability of the test material formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Doses:

300 & 2000 mg/kg

No. of animals per sex per dose:

1 female for the 300 mg/kg dose
5 females for the 2000 mg/kg dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. If possible the signs of evident toxicity were also identified. Evident toxicity is defined as the toxic effects which are of a severity such that administration at the next highest level could result in mortality.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:

Results for 300 mg/kg dose level:

There was no mortality.

Clinical Observations: No signs of systemic toxicity were noted during the observation period.

The animal showed expected gains in bodyweight over the observation period.

No abnormalities were noted at necropsy.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal was found dead seven days after dosing.

Clinical signs:

other: Signs of systemic toxicity noted were hunched posture, diarrhoea, diuresis, pilo erection, emaciation and dehydration. Surviving animals appeared normal ten to thirteen days after dosing.

Gross pathology:

Dark liver and pale kidneys were noted at necropsy of the animal that died during the study but the stomach could not be examined as the animal was cannibalised. Pale liver was noted at necropsy of one animal that was killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

Any other information on results incl. tables

Table 4              Individual Clinical Observations and Mortality Data - 2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	0	0	H	H	0	0	0	0	0	0	0	DDu	DDu	DDu	0	0	0	0
	3-0 Female	0	0	0	0	0	0	0	0	0*	HPDDu	HPDDu	HEmD	HDh	0	0	0	0	0
	3-1 Female	0	0	0	0	0	0	0	0	0*	HPDDu	X
	3-2 Female	0	0	0	0	0	0	0	0	0*	HPDDh	HPDDh	HEmDh	HDh	H	H	0	0	0
	3-3 Female	0	0	0	0	0	0	0	0	0*	HPDDu	HPDh	HEmDh	HDh	H	H	H	0	0

0 = No signs of systemic toxicity

H = Hunched posture

D = Diarrhoea

Du = Diuresis

P = Pilo-erection

Em = Emaciation

Dh = Dehydration

X = Animal dead

* = Diarrhoea and diuresis noted (pm) after Day 5 observation performed

Table 5              Individual Bodyweights and Bodyweight Changes - 2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight (g) at Death	Bodyweight Gain (g) During Week
		0	7	14		1	2
2000	2-0 Female	188	188	194		0	6
	3-0 Female	187	145	180		-42	35
	3-1 Female	176	-	-	123	-	-
	3-2 Female	168	141	163		-27	22
	3-3 Female	184	143	163		-41	20

- = Animal dead

Table 6             Individual Necropsy Findings - 2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	2-0 Female	Killed Day 14	No abnormalities detected
	3-0 Female	Killed Day 14	No abnormalities detected
	3-1 Female	Found dead 7	Liver: dark Kidneys: pale Stomach: unable to examine, animal cannibalised
	3-2 Female	Killed Day 14	No abnormalities detected
	3-3 Female	Killed Day 14	Liver: pale

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight

Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

- OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (2001)

-  Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

One animal treated at a dose level of 2000 mg/kg was found dead seven days after dosing.

Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were hunched posture, diarrhoea, diuresis, pilo-erection, emaciation and dehydration. Surviving animals treated at a dose level of 2000 mg/kg appeared normal ten to thirteen days after dosing. There were no signs of systemic toxicity noted in the animal treated at a dose level of 300 mg/kg.

Surviving animals treated at a dose level of 2000 mg/kg showed either no gain in bodyweight or bodyweight loss during the first week but expected gains in bodyweight during the second week. The animal treated at a dose level of 300 mg/kg showed expected gains in bodyweight during the study.

Dark liver and pale kidneys were noted at necropsy of the animal treated at a dose level of 2000 mg/kg that died during the study but the stomach could not be examined as the animal was cannibalised. Pale liver was noted at necropsy of one animal treated at a dose level of 2000 mg/kg that was killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

The acute oral median lethal dose (LD₅₀) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.