Dibutyltin maleate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 11 August 2010 and 15 September 2010.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A GLP compliant study conducted to current internationally accepted guidelines, not specific to this endpoint, but during the course of the study observations were made on (local) dermal reactions sufficient to assess the test material for skin irritation/corrosion.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyltin maleate

EC Number:

201-077-5

EC Name:

Dibutyltin maleate

Cas Number:

78-04-6

Molecular formula:

C12H20O4Sn

IUPAC Name:

dibutylstannanebis(ylium) (2Z)-but-2-enedioate

Details on test material:

Sponsor's identification : CAS No 78-04-6
Description : white powder
Batch number : 190 001 10/1
Date received : 15 April 2010
Expiry date : 08 September 2010
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.

Test animals

Species:

rat

Strain:

Wistar

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 least 200g
- Fasting period before study:
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 hour exposure period and in groups of up to four, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Free access to food (2014 Teklad Global Rodent diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout 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): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Remarks:

moistened with Arachis oil, BP

Controls:

no

Amount / concentration applied:

TEST MATERIAL
The appropriate amount of test item, moistened with arachis oil BP, was applied as evenly as possible to an area of shorn skin

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

Initially 1 animal/sex/dose was tested, a further 4 animals/sex/dose (5 animals/sex/dose in total)

Details on study design:

TEST SITE
- Area of exposure: back and flanks (clipped free of hair.)
- % 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 item.
- Time after start of exposure: 24 hours

- 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 item on Day 0 and on Days 7 and 14
- Necropsy of survivors performed: yes. 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
- Other examinations performed: Any other skin reactions, if present were also recorded.

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.

SCORING SYSTEM:
Please refer to section Any other information on materials and methods incl. tables for details of the scoring system employed during the study.

Results and discussion

In vivo

Irritant / corrosive response data:

Signs of dermal irritation noted during the study were very slight to well-defined erythema, haemorrhage of the dermal capillaries, small superficial scattered scabs, hardened light brown coloured scab, scab lifting to reveal bleeding, crust formation, glossy skin and scar tissue. The reactions noted in one female were indicative of dermal corrosion.
Treated skin sites of male animals appeared normal six to 13 days after dosing and the treated skin sites of three females appeared normal 6 or 12 days after dosing.

Other effects:

Animals showed expected gains in bodyweight over the study period, except for three males and one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. One other male showed no gain in bodyweight during the first week but expected gain in bodyweight during the second week.

Any other information on results incl. tables

Table1 Individual Dermal Reactions –Males 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 0 1 1 1 1 0 0 0 0 0 0 0 0 0 Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Other 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3-0 Male Erythema 1 1 1 1 1 1 1 1 0 0 0 0 0 0 Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Other 0 0 Hd HdCf Cf Cf 0 0 0 0 0 0 0 0 3-1 Male Erythema 1 1 1 2 1 1 1 1 1 0 0 0 0 0 Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Other 0 0 Hd HdCf HdCf Cf Cf Cf Cf Cf 0 0 0 0 3-2 Male Erythema 2 2 2 2 2 2 1 1 1 0 0 0 0 0 Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Other 0 0 Hd HdCf HdCf CfSp CfSsG CfSsG SsG SsG SsG G 0 0 3-3 Male Erythema 2 2 2 2 2 2 1 1 0 0 0 0 0 0 Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Other 0 0 Hd HdCf HdCfSs CfSs CfSs CfSs Cf Cf Cf Cf 0 0 0= No reactions Cf = Crust formation Ss = Small superficial scattered scabs Hd = Heamorrhage of the dermal capillaries G = Glossy skin Sp = Hardened light brown coloured scab   Table 2 Individual Dermal Reactions - Females 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 2-0 Female Erythema 1 2 2 2 1 1 1 1 0 0 0 0 0 0 Oedema 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Other 0 Ss Hd HdCf HdCf HdCf HdCf HdCf HdCf CfSs CfSs Ss Ss Ss 4-0 Female Erythema 1 1 1 1 1 1 1 1 0 0 0 0 0 0 Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Other 0 0 Hd HdCf CfSb CfSbSs CfSbSs CfSbSs SbSs Ss Ss 0 0 0 4-1 Female Erythema 2 2 2 1 1 1 1 1 0 0 0 0 0 0 Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Other 0 Ss SsHd HdCfSs CfSs Ss Ss Ss G SsG SsG 0 0 0 4-2 Female Erythema 1 2 1 0 0 0 0 0 0 0 0 0 0 0 Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Other 0 Ss Ss Cf Cf 0 0 0 0 0 0 0 0 0 4-3 Female Erythema 2 2 2 2 1 1 1 1 0 0 0 0 0 0 Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Other 0 0 0 HdCf CfSp CfSp CfSpSs CfSpSs SsSpG SsG SsG SsG SsSc SsSc 0= No reactions Hd = Haemorrhage of the dermal capillaries Ss = Small superficial scattered scabs Sb = Scab lifting to reveal bleeding Cf = Crust formation Sp = Hardened light brown coloured scab G = Glossy skin Sc = Scar tissue

 

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

 Signs of dermal irritation noted during the study were very slight to well-defined erythema, haemorrhage of the dermal capillaries, small superficial scattered scabs, hardened light brown coloured scab, scab lifting to reveal bleeding, crust formation, glossy skin and scar tissue. The reactions noted in one female were indicative of dermal corrosion.

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 test item to intact skin at a dose level of 2000 mg/kg bodyweight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Signs of dermal irritation noted during the study were very slight to well-defined erythema, haemorrhage of the dermal capillaries, small superficial scattered scabs, hardened light brown coloured scab, scab lifting to reveal bleeding, crust formation, glossy skin and scar tissue. The reactions noted in one female were indicative of dermal corrosion. Animals showed expected gains in bodyweight over the study period, except for three males and one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. One other male showed no gain in bodyweight during the first week but expected gain in bodyweight during the second week.