Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5th January to 2nd February 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Sachsse et al
Deviations:
not specified
Principles of method if other than guideline:
Acute inhalation toxicity study:
K. Sachsse, L. Ullmann, G. Voss and R. Hess, Proceedings of the Europ. Soc. for the Study of Drug Toxicity, XV, 239-251, Zuerich, June 1973
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Dibutyltin maleate
EC Number:
201-077-5
EC Name:
Dibutyltin maleate
Cas Number:
78-04-6
Molecular formula:
C12H20O4Sn
IUPAC Name:
dibutylstannanebis(ylium) (2Z)-but-2-enedioate

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: Bred and raised on the premises.
- Age at study initiation: Young adult rats.
- Weight at study initiation: 217 ± 12 g (males) and 204 ± 15 g (females)
- Housing: The rats, segregated by sex, were group-housed (10 animals per cage) in Macrolon cages, type 4 (Ehret, 783 Emmendingen/Germany).
- Diet: Rat chow (NAFAG, Gossau/SG, Switzerland) was provided ad libitum.
- Water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %
- Photoperiod (hrs dark / hrs light): 12 hour/day light cycle.


Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: ethanol
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: All exposures were conducted in a nose-only exposure system with a plexiglass exposure chamber holding approximately 100 litres
- Exposure chamber volume: 100 litres
- Method of holding animals in test chamber: For the inhalation period, the rats were placed in individual PVC-tubes positioned radially around the exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol
- Source and rate of air: The air flow rate for the sample collection was 10 1/min.The air flow through the chamber was measured with a Brooks Sho-Rate flow meter (A. Bohny, 4056 Basel/Switzerland). Adjustments to maintain a flow of 10 l/min (0.6 m3/h) could be made with a needle valve. However, in all 4 exposures, no deviations were observed, once the equilibrium was reached (within the first 10 minutes).
- Method of conditioning air: After sampling, an equal amount of clean air was aspirated through the filter to remove most of the solvent.
- System of generating particulates/aerosols:
The aerosol was generated by injecting a 30 % (w/w) solution of TK-10422 in ethanol with a Perfusor IV Syringe System (Bender and Hobein, 8051 Zuerich, Switzerland) at a rate of 0.949, 3, 6.01, and 12 ml/h into a spray nozzle (JATO, Luzern, Switzerland) through which compressed filtered air (2 atmospheres) was discharged into the inhalation chamber. The control animals were exposed to the pure solvent under the same conditions as described above. The ethanol concentration was equal to the highest nominal solvent concentration used in the test material exposure.
- Method of particle size determination:
Particle size analysis was conducted twice during each exposure, using a 4 stage Cascade Impactor (C.F. Casella and Co., Ltd., Regent House, Britannia Walk, London) with Selectron filters (Schleicher u. Schuell AG, Feldbach, Switzerland) of 25 mm diameter and a pore size of 0.2 µm. The air flow rate for the measurements was adjusted to 17.5 l/min. The amount of particles in the four size classes was determined gravimetrically, and the particle size distribution was calculated and plotted with a desk top computer.
- Treatment of exhaust air: The exhaust air was decontaminated by subsequent passage through two gas washing bottles containing 5 % NaOH.
- Temperature, humidity, pressure in air chamber:
- Temperature was measured with a Therm 2104 Contact Thermometer (Ahlborn Mess- and Regeltechnik, Holzkirchen/Germany.),
- Relative humidity was measured with a Vaisala Humidity Indicator HMI 11 (Kelag AG, 8051 Zuerich/Switzerland).
- Oxygen content was measured with a Draeger E 15 Stationary Control System (Draegerwerk AG, Luebeck/Germany).
- The chamber was maintained at a slightly negative pressure to prevent leakage of the aerosol from the system.
- Samples taken from breathing zone: Yes, the aerosol concentration in the chamber was determined 5 times (after 30 minutes, 1, 2, 3, and 4 hours of exposure) by gravimetric sampling of the test atmosphere through a Selectron Filter of 50mm diameter and a pore size of 0.2 µm.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The aerosol concentration in the chamber was determined 5 times (after 30 minutes, 1, 2, 3, and 4 hours of exposure) by gravimetric sampling of the test atmosphere through a Selectron Filter of 50mm diameter and a pore size of 0.2 µm.
Duration of exposure:
4 h
Concentrations:
Nominal concentrations used:
104, 212, 478 and 1004 mg/mˆ3.
No. of animals per sex per dose:
Each of the 4 dosage groups consisted of 20 rats (10 males and 10 females), which were approximately matched in weight.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: Animals were examined for clinical symptoms and mortalities during the exposure at 1, 2, and 4 hours, as well as 2 hours after the exposure and daily thereafter for 14 days.
- Frequency of observations and weighing: Animals were examined for clinical symptoms and mortalities during the exposure at 1, 2, and 4 hours, as well as 2 hours after the exposure and daily thereafter for 14 days. Body weights were recorded immediately prior to exposure and on day 7 and 14 of the observation period.
- Necropsy of survivors performed: Yes, gross pathological examinations were performed on all animals dying within the 14 day observation period as well as the survivors which were killed after 14 days by asphyxiation with COˇ2. Particular attention was given to the respiratory tract.
Statistics:
The inhalation LC50 values including their 95% confidence limits during the 4-hour treatment and the 14 days post-exposure period were calculated using the probit method.
The body weights of the treated animals and the controls were compared by analysis of variance.

Results and discussion

Preliminary study:
n/a
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
313 mg/m³ air (nominal)
Based on:
test mat.
95% CL:
214 - 459
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
319 mg/m³ air (nominal)
Based on:
test mat.
95% CL:
198 - 504
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
317 mg/m³ air (nominal)
Based on:
test mat.
95% CL:
240 - 416
Exp. duration:
4 h
Mortality:
Mortalities were seen in concentrations of 212, 478 and 1004 mg/mˆ3 in both sexes.
Clinical signs:
other: Slight exophthalmus and ruffled fur was seen in the control animals. Slight dyspnoea, exophthalmus, ruffled fur and curved body position was seen in animal exposed at 104 mg/mˆ3. Slight sedation and ventral body position and moderate dyspnoea, exophthalmu
Body weight:
A significant decrease in bodyweight was noted at exposure concentrations of 478 and 1004 mg/mˆ3 when compared with the control animals.
Gross pathology:
Mottled effects in the lungs were noted in some animals at all exposure concentrations. Odema of the lungs can be seen in some animals at exposure concentrations of 207 mg/mˆ3 and above.
Other effects such such as mottled liver, stomach expansion and small/large intestine expansion were seen in some animals at exposure concentrations of 474 mg/mˆ3 and above.
At an exposure concentration of 1004 mg/mˆ3 effects on the contents fluid in the thoracic cavity were seen as well as nose secretion in some animals. Also cannabalism was seen in one animal.

Any other information on results incl. tables

Upon a 4 hour aerosol exposure and a 14 day post-treatment observation period, the following lethal concentration values (with 95% confidence limits) were determined for dibutyltin maleate:

LC50 to male rats = 313 (214-459) mg/m3 air

LC50 to female rats = 319 (198-504) mg/m3 air

LC50 to both sexes = 317 (240-416) mg/m3 air

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category II
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS (CLP), Regulation (EC) No. 1272/2008
Conclusions:
In an acute aerosol inhalation toxicity study in the rat, the test material was found to have an LD50 of 317 mg/m3 with confidence limits of 240 - 416 mg/m3 in males/female. The LD50 for males is 313 mg/m3 and for females 319 mg/m3.
Executive summary:

In an acute aerosol inhalation toxicity study in the rat, the test material was found to have an LD50 of 317 mg/kg with confidence limits of 240 - 416 mg/m3 in males/female. The LD50 for males is 313 mg/m3 and for females 319 mg/m3.