Diisooctyl 2,2'-[(dioctylstannylene)bis(thio)]diacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 April 1984 to 04 May 1984

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:

1984

Report date:

1984

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: FIFRA (Federal Insecticide, Fungicide, and Rodenticide Act): Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals

Version / remarks:

Office of Pesticide Programs, U.S. Environmental Protection Agency, Office of Pesticides and Toxic Substances, October, 1982; Section 81-1, Acute Oral Toxicity Study

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: TSCA (Toxic Substances Control Act): Health Effects Test Guidelines; Office of Toxic Substances; Office of Pesticides and Toxic Substances; United States Environmental Protection Agency

Version / remarks:

August 1982, Acute Exposure, Oral Toxicity.

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Thermolite 831 Stabilizer Octyltin Compound KARFY-511K

IUPAC Name:

Thermolite 831 Stabilizer Octyltin Compound KARFY-511K

Details on test material:

Test Material: Thermolite 831
Label Information: Thermolite 831 Stabilizer Octyltin Compound KARFY-511K
Description: Oily liquid
Date of Receipt: March 16, 1984
Received from: M&T Chemicals, Inc.
Storage: Room temperature (dark)
Density: 1.087 g/ml

Specific details on test material used for the study:

- Density: 1.087 g/mL

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CDR

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: 9 to 12 weeks
- Weight at study initiation: males: 236 to 275 g, females: 219 to 244 g
- Fasting period before study: Animals were fasted overnight (for approximately 18 hours) prior to treatment.
- Housing: Group-housed (six/cage) during equilibration. Individually housed during study, in suspended, stainless steel cages with wire mesh bottoms
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature: 67 to 76 °F
- Humidity: 30 to 70 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

600, 800, 1200, 1700 and 2500 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days
- Frequency of observations and weighing: viability checks were performed twice daily. Observations of pharmacologic and toxicological signs were performed approximately 1, 2, and 4 hours after dosing and daily thereafter for twenty-one days. Body weights were measured pre-fast and on days 7, 14 and 21.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 800 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 040 - <= 2 560

Mortality:

At 600 mg/kg 1 animal died, at 800 mg/kg 3 animals died, at 1200 mg/kg 2 animals died, at 1700 mg/kg 6 animals dies and at 2500 mg/kg 5 animals died. Table 1 shows mortalities during the study.

Clinical signs:

other: Several abnormalities were seen on the day of dosing and for several days thereafter. Signs seen in most or all groups included ataxia, hypo activity, red or clear oral, nasal or ocular discharge, wet rales, urinary and/or faecal staining, soft stool, unt

Gross pathology:

Post-mortem examinations of animals found dead revealed a variety of changes, primarily in the lungs (discolouration), adrenals (reddened), gastrointestinal tract (stomach and intestinal walls - discoloured, containing red or black fluid) and testes (found in body cavity). These changes appeared to represent post-mortem autolysis, ante mortem stress and/or an irritant or corrosive effect of the test material on the gastrointestinal mucosa. One female in the 800 mg/kg group had red fluid in the urinary bladder. Changes seen in animals killed after 21 days were generally similar to those seen in control animals killed by carbon dioxide inhalation, or were considered to represent normal physiological variation.

Any other information on results incl. tables

Table 1: Mortalities during the study

Dose level (mg/kg)	Mortality
	Male	Female	Total	Time of death
600	1/5	0/5	1/10	Day 4
800	0/5	3/5	3/10	Days 2 to 5
1200	0/5	2/5	2/10	Days 2 to 3
1700	2/5	4/5	6/10	Days 2 to 4
2500	1/5	4/5	5/10	Days 2 to 7

Applicant's summary and conclusion

Interpretation of results:

other: Acute oral (Category 4) in accordance with EU criteria

Conclusions:

Under the conditions of this study the acute oral LD50 of the test material is 1800 mg/kg with 95 % confidence interval of 1040 to 2560 mg/kg.

Executive summary:

The acute oral toxicity of the test material was investigated in accordance with FIFRA and TSCA guidelines using male and female Sprague-Dawley derived rats.

Five animals per sex were dosed at the following concentrations: 600, 800, 1200, 1700 and 2500 mg/kg and then observed for 21 days. All animals were subjected to gross post-mortem examinations when they died during the study or when the study finished.

At 600 mg/kg 1 animal died, at 800 mg/kg 3 animals died, at 1200 mg/kg 2 animals died, at 1700 mg/kg 6 animals died and at 2500 mg/kg 5 animals died.

Signs seen in most or all groups included ataxia, hypo activity, red or clear oral, nasal or ocular discharge, wet rales, urinary and/or faecal staining, soft stool, unthrifty coat, hypopnea, hypothermia, food consumption decrease, emaciation and partially closed eyes. By Day 7 the incidence of abnormalities had subsided in animals dosed at the 600, 800, 1200 and 1700 mg/kg levels, although one animal in the 800 mg/kg dose group exhibited an unthrifty coat, emaciation, hypo activity and decreased food consumption for most of the post-dose period. Some survivors at the 2500 mg/kg level exhibited unthrifty coats, alopecia, abdominal griping, emaciation, hypo activity and food consumption decrease for much of the post-dose period. Most animals were free of significant abnormalities by study termination (Day 21), however. Animals that died exhibited substantial ante mortem weight losses, and several surviving animals exhibited weight losses at Day 7. However, all survivors gained weight between Days 7 and 21.

Post-mortem examinations of animals found dead revealed a variety of changes, primarily in the lungs (discolouration), adrenals (reddened), gastrointestinal tract (stomach and intestinal walls - discoloured, containing red or black fluid) and testes (found in body cavity).

Under the conditions of this study the acute oral LD50 of the test material is 1800 mg/kg with 95 % confidence interval of 1040 to 2560 mg/kg.