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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
between 11 August 2010 and 15 September 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A GLP compliant study conducted to current internationally accepted guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Limit test:
yes

Test material

Constituent 1
Chemical structure
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
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 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.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
moistened with arachis oil BP
Details on dermal exposure:
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

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 exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Initially 1 animal/sex/dose was tested, a further 4 animals/sex/dose (5 animals/sex/dose in total)
Control animals:
no
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 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.
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

Preliminary study:
No mortalities were observed in the initial two animals.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
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.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
- Other observations: 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.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
The test item does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances.
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. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths. There were no signs of systemic toxicity.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. No abnormalities were noted at necropsy. In conclusion, the acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

The test item does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances