Dibutyltin dichloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 September - 7 October 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Source and composition/purity of test material not reported.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Inhalation toxicity was tested according to the method of Sachsse et al. (1973, 1976)

Deviations:

not specified

Principles of method if other than guideline:

Inhalation toxicity was tested according to the method of Sachsse et al. (1973, 1976)*.

* K. Sachsse, L. Ullmann, G. Voss and R. Hess: Measurement of inhalation toxicity of aerosols in small laboratory
animals. In: Proceedings of the Europ. Soc. for the Study of Drug Toxicity. Vol. XV, pp. 239-251, Zurich, June 1973.
K. Sachsse, L. Ullmann, K. Zbinden: Toxikologische Rundschau von Aerosolen im Tierexperiment: Aus "Chemische Rundschau" 29 (1976), Nr. 38 Seite 1-4.

GLP compliance:

no

Remarks:

Pre-dates GLP

Test type:

other: Not stated

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyltin dichloride

EC Number:

211-670-0

EC Name:

Dibutyltin dichloride

Cas Number:

683-18-1

Molecular formula:

C8H18Cl2Sn

IUPAC Name:

dibutyltin dichloride

Test animals

Species:

rat

Strain:

other: Tif:RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Internally bred
- Age at study initiation: Young adult rats
- Weight at study initiation: Males: 247-303g; Females: 207-240g
- Fasting period before study: Not specified
- Housing: The males and females were segregated and kept in Macrolon cages, type 4, (10 animals to a cage), individually marked with picric acid.
- Diet: Ad libitum (rat food, NAFAG, Gossau SG, Switzerland)
- Water: Ad libitum
- Acclimation period: Minimum of 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 10 hour light cycle day

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: 1:2.5 (v/v) Acetone:Ethanol diluted 1:1 (w/w) with distilled water

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nda
- Exposure chamber volume: nda
- Method of holding animals in test chamber:
For inhalation the rats were kept in separate PVC tubes positioned radially around the exposure chamber such that snouts and nostrils of the animals only were exposed to the aerosol.
- Source and rate of air:
The aerosol was generated by injecting the liquid test material at a rate of 0.6, 1.2, 3.0 and 6.0 ml/hr into an air stream which was discharged
into the exposure chamber through a spray nozzle under a pressure of 2 atm at a rate of 10 l/min.
- Method of conditioning air:
The concentrations was determined 5 times gravimctrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore sizeof 0.2µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 l/min.
- System of generating particulates/aerosols:
The aerosol was generated by injecting the liquid test material at a rate of 0.6, 1.2, 3.0 and 6.0 ml/hr into an air stream which was discharged
into the exposure chamber through a spray nozzle under a pressure of 2 atm. at a rate of 10 l/min.
- Method of particle size determination:
The size distribution of the particles was measured twice with a 4 stage Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 pm (Schleicher and Schuell) at an air flow rate of 17.5 l/min.
Particle size distribution analysis of the chamber airborne particles showed that 68 % were smaller than 7 µm in diameter.
- Treatment of exhaust air: nda
- Temperature, humidity, pressure in air chamber:
During the exposure period at approximately the same times as chamber concentration was measured, the following parameters were determined inside the inhalation cylinder: temperature (with a THERM 2104 contact thermometer, Ahlborn Mess- and Regeltechnik, 815 Holzkirchen, Germany), relative humidity (with a VAESALA Humidity Indicator HMI 11, Kelag AG, 8057 Zurich, Switzerland) and oxygen content (with a DRAEGER E 15 stationary control system, Draegerwerk AG, Lubeck, Germany).


TEST ATMOSPHERE
- Brief description of analytical method used:
The aerosol was generated by injecting the liquid test material at a rate of 0.6, 1.2, 3.0 and 6.0 ml/hr into an air stream which was discharged
into the exposure chamber through a spray nozzle under a pressure of 2 atm. at a rate of 10 l/min.
- Samples taken from breathing zone: nda


VEHICLE
- Composition of vehicle:
1:2.5 (v/v) Acetone:Ethanol diluted 1:1 (w/w) with distilled water
- Concentration of test material in vehicle:
The aerosol was generated by injecting the liquid test material at a rate of 0.6, 1.2, 3.0 and 6.0 ml/hr into an air stream
- Justification of choice of vehicle: nda
- Lot/batch no.: nda
- Purity: nda


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particle size distribution analysis of the chamber airborne particles showed that 68 % were smaller than 7 µm in diameter.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): nda


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: not applicable

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

The aerosol was generated by injecting the liquid test material at a rate of 0.6, 1.2, 3.0 and 6.0 ml/hr into an air stream.
Dose concentrations were 50 ± 14, 145 ± 34, 212 ± 26 and 365 ± 23 mg/m^3

No. of animals per sex per dose:

10 males and 10 females (20 per dose in total)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded prior to exposure (control weights) and at day 7 and 14
- Necropsy of survivors performed: Yes

Statistics:

LC50 including 95 % confidence limits are calculated by the logit model.

Results and discussion

Preliminary study:

n/a

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

59 mg/m³ air

Based on:

test mat.

95% CL:

36 - 81

Exp. duration:

4 h

Mortality:

No deaths occurred in the control or vehicle groups. Although no rats died during exposure to concentrations of 50 and 73 mg/mˆ3, 8 and 18 rats, respectively, died during the observation period. Exposure to 212 and 365 mg/mˆ3 resulted in the deaths of 5 and 11 rats respectively, during exposure; 19 and 20 rats, respectively, had succumbed prior to Day 4 of the observation period.

Clinical signs:

other: The surviving animals recovered within 12 to 23 days after the exposure period. Pharmacotoxic signs consisted of slight to moderate sedation, dyspnoea, ruffled fur and ventral body position which were noted at all exposure levels.

Body weight:

Because of initial body weight differences between the control, acetone-ethanol control and 50 mg/mˆ3 group (P < 0.05) meaningful comparisons of body weights at Day 7 and 14 could not be made. In addition, high mortality in the 145, 212 and 365 mg/mˆ3 exposure groups precluded such comparisons.
Exposure to acetone-ethanol vehicle resulted in a significant reduction in Day 7 and 14 body weight gains in the female as well as a difference in Day 14 body weight gains in the male. However, exposure to 50 mg/mˆ3 of the test material resulted in an additional reduction in body weight gains in both sexes at Day 7 and 14 even when compared to the acetone-ethanol control group.

Gross pathology:

No gross pathology was noted in the control or acetone-ethanol control groups at necropsy.
However, areas of discoloration of the lungs were noted in 6 males and 4 females exposed to 50 mg/mˆ3 as well as all males and females exposed to 145 mg/mˆ3, 8 males and 4 females exposed to 212 mg/mˆ3 and all males and 7 females exposed to 365 mg/mˆ3 . In addition, oedema of the lungs were noted in 1 male and 2 females exposed to 212 mg/mˆ3 and 2 females exposed to 365 mg/mˆ3. No other gross changes were noted.

Other findings:

- Organ weights: nda
- Histopathology: nda
- Potential target organs: Lungs

Applicant's summary and conclusion

Interpretation of results:

very toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LC50 of a 4 hour aerosol exposure for rats of both sexes is 59 (36-81) mg/mˆ3, when evaluated for a 14 day post-treatment observation period.

Executive summary:

In an acute aerosol inhalation toxicity study in the rat (Ciba-Geigy project number: 801469) the test material was found to have an LC50 of 59 mg/m³.

This value according to the classification of Sachsse et al. (1973, 1976) indicates the test material is highly toxic to the rat, and classification of very toxic by inhalation according to the EU scheme.

No deaths occurred in the control or vehicle groups. Although no rats died during exposure to concentrations of 50 and 73 mg/m³, 8 and 18 rats, respectively, died during te observation period. Exposure to 212 and 365 mg/m³ resulted in the deaths of 5 and 11 rats respectively, during exposure; 19 and 20 rats, respectively, had succumbed prior to Day 4 of the observation period.