Dioctyltin dilaurate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 March 2013 to 11 April 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

(On one occasion the relative humidity was recorded below the protocol range with a recording of 44 %. This study deviation neither affected the overall interpretation of study findings nor compromised the integrity of the study.)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

(On one occasion the relative humidity was recorded below the protocol range with a recording of 44 %. This study deviation neither affected the overall interpretation of study findings nor compromised the integrity of the study.)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dioctyltin dilaurate

EC Number:

222-883-3

EC Name:

Dioctyltin dilaurate

Cas Number:

3648-18-8

Molecular formula:

C40-H80-O4-Sn

IUPAC Name:

dioctyltin dilaurate

Details on test material:

- Appearance: clear yellow liquid
- Storage condition of test material: 15 - 30 °C

Test animals

Species:

rat

Strain:

other: HsdHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Limited, Bicester, UK
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 179 - 196 g
- Fasting period before study: animals were fasted from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing
- Housing: animals were housed in groups of up to five during the acclimatisation period in cages that conform to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), the rats were housed in groups of three in similar cages.
- Diet: SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham, UK, ad libitum
- Water: mains water, ad libitum
- Acclimation period: 7 - 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 45 - 65 %
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

In order to enrich both the environment and the welfare of the animals, they were provided with wooden Aspen chew blocks, nesting materials and rodent retreats. Environmental enrichment materials were removed during the period of fasting from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- Individual doses
Individual doses (mL) were calculated using the fasted body weights of the rats on the morning of dosing (Day 1) and the specific gravity for the neat material.

- Dose volume
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.
During the study, the animals were treated with a dose volume of 1.87 mL/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 animals initially then a further 3 animals once the survival of the previously treated animals was confirmed.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: All animals were examined at the beginning and end of the working day throughout the acclimatisation and study periods to ensure they were in good health. Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded immediately post dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period.
- Frequency of weighing: Individual body weights were recorded on Day 1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes. A full macroscopic necropsy was performed and all lesions were recorded. The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines. No tissue preservation or histopathological assessment of tissues was undertaken.

- Other examinations performed: yes (gene analysis)
Blood samples for gene analysis (0.5 mL nominal) were taken from all animals on Day -1 and Day 1 (24 hours after dosing).
Samples were taken from jugular vein into into trisodium citrate anticoagulant. Samples were mixed gently by hand then continuously for at least 2 minutes on automatic mixer. Once mixed the 3 samples from each group, at each timepoint, were pooled together and placed in a cooled Kryorack. The resultant plasma was separated, transferred to uniquely labelled clear polypropylene tubes and frozen immediately at <–50 °C.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study.

Clinical signs:

other: No clinical signs were seen during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Gene analysis findings were not reported.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute median dose level of the test material was found to exceed 2000 mg/kg.

Executive summary:

The acute oral toxicity of the test material was investigated in a GLP study which was conducted in accordance with the standardised guidelines OECD 423 and EU Method B.1 tris, following the Acute Toxic Class method.

During the study two groups of 3 female rats were sequentially treated with test material at dose level of 2000 mg/kg bw. The test material was administered orally, by gavage, without dilution. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no signs of toxicity. All rats achieved body weight gains during the first and second weeks of the study. No abnormalities were noted at necropsy. Therefore, under the conditions of the study, the acute median dose level of the test material was found to exceed 2000 mg/kg.