Dibutylbis(pentane-2,4-dionato-O,O')tin

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 16 June 2010 and 30 June 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:

Dibutylbis(pentane-2,4-dionato-O,O')tin

EC Number:

245-152-0

EC Name:

Dibutylbis(pentane-2,4-dionato-O,O')tin

Cas Number:

22673-19-4

Molecular formula:

C18H32O4Sn

IUPAC Name:

Tin, dibutylbis(2,4-pentanedionato-kO2,kO4)-,

Details on test material:

Sponsor's identification: CAS No 22673-19-4
Description: amber coloured liquid
Lot number: TIB KAT 226 VP10-055
Date received: 01 March 2010
Expiry date: 01 March 2011
Storage conditions: room temperature in the dark over silica gel

The integrity of supplied data relating to the identity, purity and stability of the test material is the responsibility of 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: animals weighed at least 200g
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually throughout the test period.
- Diet/water (e.g. ad libitum): 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 test. 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: acclimatisation period of 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: The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe.
- 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): 1.66 ml/kg

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

1

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 for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: At the end of the study 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 exposure of the animal 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.
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:

After consideration of the skin reactions produced in the first two animals, no additional animals were treated.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths. See Table 1.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy. See Table 4.

Other findings:

Dermal Reactions
Individual dermal reactions are given in Table 2.
Signs of dermal irritation noted were well-defined erythema, very slight oedema, loss of skin elasticity, small superficial scattered scabs, hardened dark brown/black coloured scab, scab cracking, scab lifting at edges to reveal dried blood, scab lifting to reveal glossy skin or further deep scabbing, scab undulating, dried blood, thickening of the skin and scar tissue. Adverse dermal reactions prevented accurate evaluation of erythema and oedema at both test sites during the test. The reactions were considered to be indicative of dermal corrosion.
The dermal reactions noted at both test sites were indicative of dermal corrosion.

Any other information on results incl. tables

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	8	9	10	11	12	13	14
2000	1-0 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = No signs of systemic toxicity

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

8

9

10

11

12

13

14

2000

1-0 Male

Erythema

2

2

2

2

2

?e

?e

?e

?e

?e

?e

?e

?e

?e

Oedema

1

1

1

1

1

?od

?od

?od

?od

?od

?od

?od

?od

?od

Other

0

0

0

Ss

SsLe

SbStSw

StSwSkBd

StSwSkBd

SkBdSgSw

StSwSkSgBd

StSwSgSk

StSwSgSk

StSgSk

StSgSdThSc

2-0 Female

Erythema

2

2

2

2

?e

?e

?e

?e

?e

?e

?e

?e

?e

?e

Oedema

1

1

1

1

?od

?od

?od

?od

?od

?od

?od

?od

?od

?od

Other

0

Le

Le

LeSs

StSk

StSkSg

StSkSg

SsSkSg

SsSkSg

StSgSs

StSgSs

StSgSs

StSgSs

SsSgSbThSc

0 = No reactions

Le = Loss of skin elasticity

Ss = Small superficial scattered scabs

St = Hardened dark brown/black coloured scab

Sk = Scab cracking

Sb = Scab lifting at edges to reveal dried blood

Sd = Scab lifting to reveal further deep scabbing

Sg = Scab lifting to reveal glossy skin

Sw = Scab undulating

Bd = Dried blood

Th = Thickening of the skin

Sc = Scar tissue

?e = Adverse reactions prevent accurate evaluation of erythema

?od = Adverse 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			Bodyweight Change (g) During Week
		0	7	14	1	2
2000	1-0 Male	313	293	312	-20	19
	2-0 Female	201	198	211	-3	13

Table 4              Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	1-0 Male	Killed Day 14	No abnormalities detected
	2-0 Female	Killed Day 14	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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

Executive summary:

The study was performed to assess the acute dermal toxicity of the test material 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 Method.

Two animals (one male and one female) were given a single, 24 Hour, semi occluded dermal application of the undiluted test material to intact skin 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. There were no deaths and no signs of systemic toxicity.

Signs of dermal irritation noted were well-defined erythema, very slight oedema, loss of skin elasticity, hardened dark brown/black coloured scab, small superficial scattered scabs, scab cracking, scab lifting at edges to reveal dried blood, further deep scabbing or glossy skin, scab undulating, dried blood, thickening of the skin and scar tissue. Adverse skin reactions prevented accurate evaluation of erythema and oedema at both test sites during the study. The reactions were considered to be indicative of dermal corrosion.

Both animals showed bodyweight loss during the first week but expected gain in bodyweight during the second week.

No abnormalities were noted at necropsy.

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