Butyltris[(2-ethyl-1-oxohexyl)oxy]stannane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 July 1988 to 04 October 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butyltris[(2-ethyl-1-oxohexyl)oxy]stannane

EC Number:

245-912-1

EC Name:

Butyltris[(2-ethyl-1-oxohexyl)oxy]stannane

Cas Number:

23850-94-4

Molecular formula:

C28H54O6Sn

IUPAC Name:

butyltris[(2-ethyl-1-oxohexyl)oxy]stannane

Test material form:

liquid

Details on test material:

- Appearance: clear liquid with very slight yellow tint
- Storage: room temperature

Test animals

Species:

rat

Strain:

other: CD (Sprague-Dawley derived)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 9 - 12 weeks old
- Weight at study initiation: Males: 289 - 351 g; Females: 214 - 260 g
- Fasting period before study: Animals were fasted overnight (for approximately 18 hours) prior to dosing
- Housing: Group-housed (six/cage) during equilibration and individually housed during study in suspended, stainless steel cages with wire mesh bottoms
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 21 or 22 days

ENVIRONMENTAL CONDITIONS
- Temperature: 67 - 76°F
- Humidity: 30 - 70%
- Photoperiod: 12 hours light, 12 hours dark (controlled by an automatic timer)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4.6 mL/kg

Doses:

Range-finding study: 100, 500, 1000, 2500 and 5000 mg/kg
LD50 determination study: 2500, 3000, 3500 and 5000 mg/kg (3000 mk/kg: females only and 5000 mg/kg: males only)

No. of animals per sex per dose:

Range-finding study: 1 animal per sex per dose
LD50 determination study: 5 animals per sex per dose (3000 mk/kg: females only and 5000 mg/kg: males only)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Viability Check: twice daily
Observations of Pharmacologic and Toxicological Signs: approximately 1, 2 and 4 hours after dosing and daily thereafter for fourteen days.
Body Weights: pre-fast (weights used for calculation of doses), day 7 and 14 and terminal: any animals which did not survive for 14 days were weighed at the time of death or at the time they were found dead.
- Necropsy of survivors performed: yes, gross post-mortem examinations were performed on all animals which died or were found dead during the study. At termination of the observation period (Day 14), all surviving animals were killed by carbon dioxide inhalation and examined grossly. All abnormalities
were recorded but no tissues were saved.
- Animals used for range-finding screens were observed for viability twice daily for seven days and deaths were recorded. No post-mortem examinations were made on animals used for range-finding screens.

Results and discussion

Preliminary study:

In the range-finding study, there were no deaths at 100, 500, 1000 or 2500 mg/kg but 2/2 animals died at 5000 mg/kg.

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

3 200 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 871 - <= 3 529

Mortality:

- A sex-related difference was apparent, with females more affected than males. In males no mortality was seen at doses of up to 5000 mg/kg, while the LD50 in females was 3200 mg/kg.
- Mortality is summarised in Table 1.

Clinical signs:

other: - Signs seen on the day of dosing in most or all groups included ataxia, nasal, oral and ocular discharge, hypopnea, hypoactivity, wet rales, faecal and urinary staining, irregular breathing and prostration. - On the day after dosing, unthrifty coat, hypo

Gross pathology:

- Gross post-mortem observations were generally unremarkable.
- Post-mortem examinations of animals which were found dead revealed changes which generally appeared to represent autolytic changes or normal variability.
- Changes in animals killed after 14 days were similar to those seen in control animals in this laboratory killed by carbon dioxide inhalation or were considered to represent normal physiological variation.

Any other information on results incl. tables

Table 1: Summary of Mortality During the Study

Dose Level (mg/kg)	Mortality		Time of Death
	Male	Female
2500	0/5	1/5	Day 1
3000	-	0/5	-
3500	0/5	4/5	22 hrs - Day 2
5000	0/5	-	-

Applicant's summary and conclusion

Interpretation of results:

other: Not classified in accordance with EU Criteria

Conclusions:

Under the conditions of this study the male LD50 was greater than 5000 mg/kg and the female LD50 was 3200 mg/kg.

Executive summary:

The acute oral toxicity of the test material was investigated in a study similar to OECD 401.

During the study, male and female CD (Sprague-Dawley derived) rats were dosed with a single oral dose of the test material and observed for 14 days. The doses were chosen based on the results of a range finding study. For the definitive test males were dosed at 2500, 3500 and 5000 mg/kg and females were dosed at 2500, 3000 and 3500 mg/kg.

A sex-related difference was apparent, with females more affected than males. In males no mortality was seen at doses of up to 5000 mg/kg, while the LD50 in females was 3200 mg/kg.

Signs seen on the day of dosing in most or all groups included ataxia, nasal, oral and ocular discharge, hypopnea, hypoactivity, wet rales, faecal and urinary staining, irregular breathing and prostration. On the day after dosing, unthrifty coat, hypothermia, abdominal griping, soft stool and/or decreased food consumption were evident in some animals in all groups. Abnormalities continued in some animals for several days after dosing, but all animals were free of significant abnormalities at study termination (one male in the 5000 mg/kg group continued to exhibit an unthrifty coat).

The majority of surviving animals in the 2500 and 3000 mg/kg dose groups gained weight both 7 and 14 days after dosing. Several surviving animals in the 3500 and 5000 mg/kg dose groups exhibited weight losses at Day 7 but gained weight between Days 7 and 14. Gross post-mortem observations were generally unremarkable.

Under the conditions of this study the male LD50 was greater than 5000 mg/kg and the female LD50 was 3200 mg/kg.