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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
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:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
traditional method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrakis(diethyldithiocarbamato-S,S')tellurium
EC Number:
244-121-9
EC Name:
Tetrakis(diethyldithiocarbamato-S,S')tellurium
Cas Number:
20941-65-5
Molecular formula:
C20H40N4S8Te
IUPAC Name:
tetrakis(diethyldithiocarbamato-S,S')tellurium
Test material form:
solid
Specific details on test material used for the study:
- Name of the test item (as cited in study report): Tellurium diethyldithiocarbamate
- Batch No.: MT-5D-494
- Appearance: Yellow, crystalline

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston Road, Margate, Kent, England, obtained on 1 November 1985
- Weight at study initiation: 133 - 190g
- Age at study initiation: 8-9 weeks
- Housing:
- polypropylene cage (size 38 x 56 cm x 18 cm height) per 10 rats (5 males and 5 females) before exposure
- Stainless steel mesh cage (30.5 x 19 x 20 cm height) per rat
- Diet: Labsure LAD 1 (ad libitum)
- Water: tap water (ad libitum)

ENVIRONMENT
- Temperature: 19.4 - 21.3 °C
- Humidity: 42%

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
> 5.5 µm
Details on inhalation exposure:
PROCEDURE
A sample of the test substance was packed into the container of the Wright dust generator using a hydraulic bench press to assist packing. Even density of the powder was achieved by packing the container in stages and applying a force of 0.4 tons weight. The packed container was weighed.
The dust generator was positioned on a stand at the side of the exposure chamber and the output connected to an inlet port in the top centre of the chamber by the aerosol neutraliser.
The gear ratio of the generator mechanism was set to give the highest possible concentration of dust.
A supply of clean, dried compressed air was connected to the dust generator and the supply pressure was adjusted to give a flow rate of 25 litres per minute measured at the generator outlet nozzle. The total chamber air supply was derived from the air flow through the dust generator.
The rats (5 males and 5 females) were placed into separate compartments of the exposure chamber.
The powder container of the Wright dust generator was advanced manually until a trace of suspended dust was in the chamber. The gearing on the generator was then engaged and the generator motor switched on to start the exposure. After a 12-minute equilibration period, the exposure was timed for 4 hours. The generator was then switched off and the chamber allowed to clear before the rats were removed for examination.
The rats were placed into individual cages and returned to the holding room for the remainder of the observation period. The rack containing the cages was placed in a ventilated cabinet drawing its air supply from the holding room.
The control group was treated similarly but received clean air only for 4 hours.

CHAMBER ATMOSPHERE ANALYSES
Eight air samples were taken from a sampling port in the chamber during exposure and weighed to determine the concentration of the test substance in the chamber air.
A further 4 samples were taken from a second sampling port in a different wall of the chamber to check the spatial distribution of the test material.
The samples were drawn through a weighed Whatman GF/A glass fibre filter, mounted in an open face filter holder, at a rate of 4 litres per minute. The volume of the air sample was measured with a wet-type gas meter.
Four further air samples were taken using an Andersen mini-sampler (Andersen 2000 Inc.) and the collected material was weighed to determine the particle size distribution of the test substance.
At a sampling rate of 1.4 litres per minute the collection characteristics of the Andersen sampler are:
Stage 1 - Particles larger than 5.5 µm aerodynamic diameter (a .d.)
Stage 2 - Particles between 3.5 µm and 5.5 µm a.d.
Stage 3 - Particles between 2.0 µm and 3.5 µm a.d.
Stage 4 - Particles between 0.3 µm and 2.0 µm a.d.
Filter - Particles smaller than 0.3 µm a.d.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Nominal: 17.7 mg/L
Analtycial: 0.51 mg/L (30% respirable)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of examination: The rats were observed continuously during exposure, hourly for 4 hours following exposure and at least twice daily throughout the observation period. All rats were weighed on Days 1 (before exposure), 2, 3, 5, 8, 11 and 15.
- Necropsy of survivors performed: Yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.51 mg/L air
Based on:
test mat.
Mortality:
There were no deaths during this study
Clinical signs:
other: During the exposure period, some animals showed partial closing of the eyes and labored breathing. This is considered a non specific effect to dust-exposure. During the observation period, some animals showed an abnormal respiratory pattern for 3 hours fo
Body weight:
Small losses of bodyweight or a reduction in the rate of weight gain on the day following exposure. Normal from Day 5.
Gross pathology:
No treatment-related abnormalities.

Any other information on results incl. tables

CHAMBER ATMOSPHERE CONDITIONS

Concentration of test substance

The mass concentrations of the test substance in the air samples taken during the exposure were:

Sample

Time taken

Concentration in air (mg/L)

2.1

0 h : 20 m

0.27

2.2

0 h : 50 m

0.45

2.3

1 h : 30 m

0.62

2.4

1 h : 50 m

0.57

2.5

2 h : 20 m

0.53

2.6

2 h : 50 m

0.52

2.7

3 h : 20 m

0.55

2.8

3 h : 50 m

0.57

Mean: 0.51

Standard deviation: 0.109

 

The results for the samples taken from a second sampling port were 0.15, 0.49, 0.58 and 0.64 mg/L for samples taken at 0 h 25 m, 1 h 35 m, 2 h 35 m and 3 h 25 m respectively. The samples were similar to those of the main series taken at approximately the same times showing that spatial distribution within the chamber was acceptable. The low values at 0 h 20 m and 0 h 25 m were due to technical difficulties with the generator.

 

Nominal concentration

The nominal concentration determined by dividing the total test substance used by the total airflow was 17.7 mg/L.

 

Particle size distribution

The analysis results for the air samples taken for the determination of particle size distribution are given in TABLE 1. The results show that, on average, 30% by weight, of the test substance in the chamber air was 5.5 µm or less in aerodynamic diameter and therefore of respirable size.

 

Sample

Time taken

Stage

Particle size (µm)

Amount in stage (mg)

% of total

% respirable

PSD 1

0 h : 55 m

1

2

3

4

Filter

> 5.5

3.5-5.5

2.0-3.5

0.3-2.0

<0.3

Total

3.99

1.18

0.42

0.20

0.01

5.80

68.8

20.3

7.2

3.4

0.2

31.2

PSD 2

1 h : 55 m

1

2

3

4

Filter

> 5.5

3.5-5.5

2.0-3.5

0.3-2.0

<0.3

Total

4.24

1.01

0.41

0.15

0.06

5.87

72.2

17.2

7.0

2.6

1.0

27.8

PSD 3

2 h : 55 m

1

2

3

4

Filter

> 5.5

3.5-5.5

2.0-3.5

0.3-2.0

<0.3

Total

3.06

0.95

0.32

0.13

0.04

4.50

68.0

21.1

7.1

2.9

0.9

32.0

PSD 4

3 h : 52 m

1

2

3

4

Filter

> 5.5

3.5-5.5

2.0-3.5

0.3-2.0

<0.3

Total

3.91

0.98

0.35

0.17

0.07

5.48

71.4

17.9

6.4

3.1

1.3

28.6

Mean respirable: 29.9%

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
The study determined a LC50 of > 0.51 mg/L, which was the highest concentration that could be generated. In order to achieve applicability of animal experiments to human exposure, the mean mass aerodynamic diameter (MMAD) should be low enough to ensure that the test substance will deposit in all regions of the rats respiratory tract of the appropriate test animal. According to OECD TG 403, the primary goal should be to achieve a MMAD of 1 - 4 µm when testing aerosols. In the study, particle size distribution analysis showed that the majority of the test substance exceeds a particle size of 5.5 µm during exposure. Because of the low efficiency of generation (measured concentration was only 2.9% of the nominal concentration) and the relative large particle size, data cannot be used for classification of acute inhalation toxicity. As sufficient data are available on the other two routes of exposure, the study is not warranted.