Dibutoxydibutylstannane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 22 September 2010 and 29 September 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

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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
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 item is the responsibility of the Sponsor.
A Certificate of Analysis was supplied by the Sponsor.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/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: at the start of the study the animals weighed at least 200g
- Housing: The animals were individually housed in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet/water: 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 could 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): 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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: a piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after the 24-Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.77 ml/kg (2000 mg/kg)
- Concentration (if solution): used as supplied
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

1 male and 1 female

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for seven days. Individual bodyweights were recorded prior to application of the test item on Day 0 and at death (Day 7).
- Necropsy of survivors performed: yes
- Other examinations performed: 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 exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.
The results were evaluated according to EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances.

Results and discussion

Effect levels

Remarks on result:

other: Inconclusive

Mortality:

Both animals were killed for humane reasons seven days after dosing, due to the approach of the moderate severity limit set by the UK Home Office.

Clinical signs:

other: Signs of systemic toxicity noted were hunched posture, pilo-erection, lethargy, dehydration and pallor of the extremities.

Gross pathology:

Raised limiting ridge of the stomach and scattered dermal haemorrhage at the sub cutaneous site of application were noted at necropsy.

Other findings:

Very slight or well-defined erythema and hardened dark brown black coloured scab were noted at both test sites. Additional signs of dermal irritation noted at the test site of the male were hardened light brown coloured scab and scab cracking. Additional signs of dermal irritation noted in the female were haemorrhage of dermal capillaries, hardened light brown coloured scab, small areas of pale green coloured dermal necrosis scattered around the edges of the test site, blanching of the skin and hardened dark brown coloured scab, approximately 10 mm x 20 mm in size, surrounded by loss of skin elasticity and light brown discolouration of the epidermis. Adverse dermal reactions prevented accurate evaluation of erythema and oedema at both test sites six and seven days after dosing. The reactions noted in the male were considered to be indicative of dermal corrosion.

Any other information on results incl. tables

Due to severe/corrosive dermal reactions no further animals were treated with the test item.

Table 1              Individual Clinical Observations and Mortality Data

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Initiation of Exposure (Hours)				Effects Noted After Initiation of Exposure (Days)
		½	1	2	4	1	2	3	4	5	6	7
2000	1-0 Male	0	0	0	0	0	0	0	0	H	HPDh	HPDhEX*
	2-0 Female	0	0	0	0	0	0	0	0	H	HPLDh	HPLDhEX*

0 = No signs of systemic toxicity

H = Hunched posture

P = Pilo-erection

L = Lethargy

Dh = Dehydration

E = Pallor of the extremities

X* = Animal killed for humane reasons due to the approach of the moderate severity limit set by the UK Home Office

Table 2              Individual Dermal Reactions

Dose Level mg/kg		Animal Number and Sex		Observation		Effects Noted After Initiation of Exposure (Days)
			1			2		3		4		5		6		7
2000		1-0 Male		Erythema		0		1		1		1		1		?e		?e
			Oedema		0		0		0		0		0		?od		?od
			Other		0		0		0		0		0		St		SpSk
		2-0 Female		Erythema		1		1		0		0		0		?e		?e
			Oedema		0		0		0		0		0		?od		?od
			Other		0		0		0		Hd		Hd		St		NBlSt*LeBr

0 = No reactions

Hd = Haemorrhage of dermal capillaries

St = Hardened dark brown black coloured scab

Sp = Hardened light brown coloured scab

Sk = Scab cracking

N = Small areas of pale green coloured dermal necrosis scattered around the edges of the test site

Bl = Blanching of the skin

St* = Hardened dark brown coloured scab, approximately 10 mm x 20 mm in size

Le = Loss of skin elasticity

Br = Light brown discolouration of the epidermis

?e = Adverse dermal reactions prevent accurate evaluation of erythema

?od = Adverse dermal reactions prevent accurate evaluation of oedema

Table 3              Individual Bodyweights and Weekly Bodyweight Changes

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			At Death	Bodyweight Change (g) During Week
		0	7	14		1	2
2000	1-0 Male	223	-	-	166	-	-
	2-0 Female	211	-	-	160	-	-

- = Animal dead

Table 4              Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	1-0 Male	Humanely killed Day 7	Stomach: raised limiting ridge Sub-cutaneous at the site of application: scattered dermal haemorrhage
	2-0 Female	Humanely killed Day 7	Stomach: raised limiting ridge Sub-cutaneous at the site of application: scattered dermal haemorrhage

 

Applicant's summary and conclusion

Interpretation of results:

other: inconclusive

Remarks:

Criteria used for interpretation of results: not specified

Conclusions:

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat could not be determined, as due to severe/corrosive dermal reactions, the animals were killed for humane reasons at 7 days.

Executive summary:

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

 OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

 Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008

Initially, two animals (one male and one female) were given a single, 24-hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg bodyweight. Based on the results of the initial test, no further animals were treated. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Both animals were killed for humane reasons seven days after dosing, due to the approach of the moderate severity limit set by the UK Home Office.

Signs of systemic toxicity noted were hunched posture, pilo-erection, lethargy, dehydration and pallor of the extremities.

Signs of dermal irritation noted were well-defined erythema, haemorrhage of dermal capillaries, hardened light brown, dark brown or dark brown black coloured scab, scab cracking, blanching of the skin, loss of skin elasticity, light brown discolouration of the epidermis and small areas of pale green coloured dermal necrosis. The reactions noted in the male were considered to be indicative of dermal corrosion. Bodyweight loss was noted over the study period.

Raised limiting ridge of the stomach and scattered dermal haemorrhage at the sub cutaneous site of application were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat could not be determined, as due to severe/corrosive dermal reactions, the animals were killed for humane reasons at 7 days.