azido(trioctyl)stannane

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 Aug. 2003 - 10 Feb. 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Specific details on test material used for the study:

Sample of TOTA (solution), batch No. 03/03-4. The sample was stored at room temperature and protected from light in accordance with the Sponsor's instructions.
Appearance: Slight yellow liquid. The test material is a mixture of Stannane, azidotrioctyl- and toluene (in 40- 60 % toluene solution).

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CHS (Controlled Health Status) Sprague-Dawley.

Sex:

female

Details on test animals or test system and environmental conditions:

Sex: Female. Females were nulliparous and non-gravid.

Origin: Dépré breeding centre, Z.I de Malitorne, 3 rue Joliot Curie, BP 70, 18230 Saint Doulchard, France.

Identification: Animals were identified individually by marking the tail with a felt tip marker.

Age: 8-12 weeks at the time of administration.

Number: 3 animals per step.

Weight: within ± 20% of the mean weight of any previously dosed animals.

Acclimatization: Seven to ten days before treatment in the laboratory animal house where the experiment took piace.

Housing: Daily observations were performed at the time of delivery of the animals and during the period of acclimatization. Animals were housed in cages of standard dimensions with sawdust bedding (or equivalent). Cages were cleaned at least once per week. The animals were placed in an air-conditioned (19-23 °C) animal house kept at relative humidity between 45% and 65% in which non-recycled filtered air was changed approximately 10 times per hour. The artificial day/night cycle involved 12 hours light and 12 hours darkness with light on at 7.30 a.m.

Feeding: RM1 (E)-SQC SDS/DIETEX (quality controlled/radiation sterilised) was available ad libitum except during the fasting experimental period. The criteria for acceptable levels of contaminants in the feed supply were within the limits of the analytical specifications established by the diet manufacturer.

Drinking water: Potable water was available ad libitum in polycarbonate feeder bottles with a stainless steel nipple. A specimen of water is obtained every 6 months and sent to the Laboratoire Départemental d'Analyse du Cher- 216, Rue Louis Mallet- 18014 Bourges Cedex, France, for analysis.
The criteria for acceptable levels of contaminants in the water supply were within the limits of the analytical specifications.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test substance was administered diluted as a homogeneous suspension in corn oil.

Timing, frequency and duration of administration
TOTA (solution) was administered to animals deprived of food since the previous day. It was administered to the animals as a single dose, by gavage, using a cannula of appropriate size.

Volume administered
The dose volume was 2.03 mL/kg. The dose volume was calculated on the basis of the density of TOTA (solution), which was 0.984 as supplied by the Sponsor.

Doses:

Choice of doses
The dose level used as the starting dose was selected from one of four fixed levels, 5, 50, 300 and 2000 mg/kg body weight. The starting dose level was that which was most likely to produce mortality in some of the dosed animals.
At the Sponsor' s request, a limit test at one dose level of 2000 mg/kg body weight was carried out with six anirnals (three animals per step). As test substance-related mortality was produced, further testing at the next lower levels were carried out with three other animals each.
The flow chart of Annex 2d of OECD No. 423, describes the procedure that has been followed for the starting dose.
The time interval between treatment groups was determined by the onset, duration, and severity of toxic signs. Treatment of animals at the next dose was delayed until one was confident of survival of the previously dosed animals.

Dose adjustment
Each dose was expressed in mg/kg of TOTA (solution) and adjusted to individuai body weight as determined immediately before administration.

No. of animals per sex per dose:

3 animals per step.

Control animals:

no

Details on study design:

It is the principle of the test that, based on a stepwise procedure with the use of a minimum number of animals per step, sufficient information is obtained on the acute toxicity of the test substance to enable its classification. The substance is administered orally to a group of experimental animals at one of the defined doses. The substance is tested using a stepwise procedure, each step using three animals of a single sex. Absence or presence of test substance-related mortality of the animals dosed at one step was determined the next step, i. e.;
• no further testing is needed
• dosing of three additional animals, with the same dose
• dosing of three additional animals at the next higher or the next lower dose level.
Details of the test procedure are described in Annex 2d of OECD No. 423.
The method enabled a judgement with respect to classifying the test substance to one of a series of toxicity classes defined by fixed LD50 cut-off values.

Statistics:

Analysis of resnlts
All data were recorded as and when obtained using forms identified by the study number. Data were presented tabulated by dose level and time, nature, severity and duration of effects. Results of the body weight were given as means ± SEM (Standard Error of the Mean). When the number of animals is not sufficient ( < 3), the SEM is not calculated.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 - < 50 mg/kg bw

Based on:

test mat.

Mortality:

Three mortalities were recorded on D1 at the dose level of 2000 mg/kg (Step 1).
No mortality occurred during the step 2 at the dose level of 300 mg/kg.
Two mortalities (2/6) occurred on D2 of the step 3 at the dose level of 300 mg/kg.
Three mortalities were recorded on D1 at the dose level of 50 mg/kg (Step 4).
No mortality occurred during each step at the dose level of 5 mg/kg (Steps 5 and 6).

Clinical signs:

Step 1: On D1 before death, no locomotor activity, ventral decubitus, polypnoea were mainly observed in all animals.
Steps 2 and 3: On D1, slight decrease of locomotor activity, bent back, piloerection, polypnoea and hyperreactivity to pinching of tail were noted in all animals treated at 300 mg/kg during the second step of the study.
On D1, slight to very strong decrease of locomotor activity piloerection or bent back were recorded in all animals treated at 300 mg/kg during the third step of the study. From D2 to D5, these signs persisted in the surviving animals.
Step 4: On D1, about 3 hours post-dose, slight decrease of locomotor activity and piloerection were seen in all animals treated at 50 mg/kg.
Steps 5 and 6: No clinical signs were observed during the course of each step.

Body weight:

Mean weight gains in surviving animals treated at 300 mg/kg and 5 mg/kg body weight were normal when compared with strain data.

Gross pathology:

Step 1: No organ or tissue gross findings were seen at necropsy of all animals dosed at 2000 mg/kg body weight.
Steps 2 and 3: A presence of black to white spots on the glandular zone of the stomach in two anirnals, and a clear mass on lungs in one of these animals were seen at necropsy of animals treated at 300 mg/kg (Step 3). The glandular zone of the stomach of the two found dead animals appeared fine and presented slight ulcers.
Steps 4, 5 and 6: No organ or tissue gross findings were seen at necropsy of all animals dosed at 50 mg/kg or 5 mg/kg body weight.

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Under the experimental conditions adopted, oral administration of the test substance TOTA (solution) (batch 03/03-4) caused three mortalities (3/3) at the dose of 2000 mg/kg, two mortalities (2/6) at the dose of 300 mg/kg, three mortalities (3/3) at the dose of 50 mg/kg, and no mortality (0/6) at the dose of 5 mg/kg in the female Sprague-Dawley Rat.
According to the Globally Harmonised Classification System (GHS), TOTA (solution) is in category 2. Under the experimental conditions adopted, the LD50 is comprised between 5 mg/kg and 50 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

50 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Oral administration of the test substance TOTA (solution) (batch 03/03-4) caused three mortalities (3/3) at the dose of 2000 mg/kg, two mortalities (2/6) at the dose of 300 mg/kg, three mortalities (3/3) at the dose of 50 mg/kg, and no mortality (0/6) at the dose of 5 mg/kg in the female Sprague-Dawley Rat.

According to the Globally Harmonised Classification System (GHS), TOTA (solution) is in category 2. Under the experimental conditions adopted, the LD50 is comprised between 5 mg/kg and 50 mg/kg body weight.