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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 April 1998 and 03 June 1998.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Conducted to a recognised guideline and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

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:

- Name of test material (as cited in study report): NEOSTANN U-220
- Physical state: yellow liquid
- Lot/batch No.: TO-141
- Storage condition of test material: room temperature in the dark
- Other: Data relating to the identity, purity and stability of the test material are the responsibility of the Sponsor.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: eight to twelve weeks old.
- Weight at study initiation: males weighed 205 to 215g, and the females 200 to 226g
- Fasting period before study: overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: The animals were housed in groups of up to five by sex in solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): free access to food (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Water (e.g. ad libitum): free access to mains drinking water was allowed throughout the study.
- Acclimation period: After a minimum acclimatisation period of five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 48 to 61 %.
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light):lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

For the purpose of the study 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.
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

Doses:

1000, 1414 and 2000 mg/kg

No. of animals per sex per dose:

5 females per dose and 5 males tested only at 2000 mg/kg

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
At the end of the study the surviving animals were killed by cervical dislocation. All animals including those that died during the study, but excluding one that died during the study and was cannibalised, were subjected to gross pathological examination. This consisted of an external examination and examination of the major organs of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

The acute oral median lethal dose (LD50) and 95% confidence limits of the test material, NEOSTANN U-220, in the Sprague-Dawley CD strain rat were calculated by a probit method of Finney D J.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

1 864 mg/kg bw

Based on:

test mat.

95% CL:

1 039 - 3 344

Mortality:

The mortality data are given in Table 2.
Deaths were noted one to eight days after dosing.

Clinical signs:

other: Common signs of systemic toxicity noted in all dose groups were ataxia, hunched posture and lethargy. Clinical observations noted in animals treated with 1414 or 2000 mg/kg were ptosis, decreased respiratory rate, laboured respiration and splayed or tipto

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver or patchy pallor of the liver, pale spleen, dark kidneys, haemorrhagic gastric mucosa, sloughing of the non-glandular epithelium of the stomach and haemorrhage of the small and large intestines. One female animal treated with 1000 mg/kg that died during the study was found cannibalised. A necropsy was therefore not performed. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) and 95% confidence limits of the test material, NEOSTANN U-220, in the Sprague-Dawley CD strain rat were calculated by a probit method of Finney D J to be:
Females only = 1864 (1039 - 3344) mg/kg bodyweight

Male animals were not considered to be markedly more sensitive to the test substance than female animals.

Executive summary:

In an acute oral toxicity to rats study (SPL project number: 1194/001) the test material was found to have an acute oral median lethal dose (LD50) and 95% confidence limits of 1864 (1039 - 3344) mg/kg bodyweight (Females only).

The test material was classified as HARMFUL and the symbol "Xn" and risk phrase R 22 "HARMFUL IF SWALLOWED" are therefore required according to EU labelling regulations.

Male animals were considered not to be markedly more sensitive to the test material than female animals.