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Description of key information

The LD50 value for acute oral toxicity was >5000 mg/kg bodyweight in rats.

The LC50 value for acute inhalation toxicity was >0.51 mg/L air in rats.

The LD50 value for acute dermal toxicity was >2000 mg/kg bodyweight in rats.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
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, powder
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
- Weight at study initiationt: 282-300g for males and 237-250 for females
- Age at study initiation: 4-6 weeks
- Housing: Rats were housed individually in metal cages with wire mesh floors
- Diet: Labsure LAD 1 (ad libitum)
- Water: tap water (ad libitum)
- Acclimation period: 7 days

ENVIRONMENT
- Temperature: 20-22 °C
- Humidity: 63%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
A group of ten rats (five males and five females) was treated with a single dose of 5 g/kg bw. The test substance was prepared at 50% w/v in distilled water and administered at a volume of 10.0 ml/kg
Doses:
5 g/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of examination: Twice daily for clinical signs. On Days 1, 2, 3, 5, 8, 11 and 15, body weight was measured
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities following a single oral dose of test substance at 5.0 g/kg bodyweight.
Clinical signs:
Pilo-erection was seen in all rats shortly after dosing. On Day 2 soft faeces were observed for all animals. No other signs of reaction to treatment were observed. Recovery was judged by external appearance and behaviour was apparently complete by Day 3.
Body weight:
Bodyweight losses were recorded for two male and four female rats on Day 3, one female rat on Day 5 and one female rat on Day 15. An unchanged bodyweight was recorded for one female rat on Day 15. Bodyweight gains were recorded on all other occasions.
Gross pathology:
Terminal autopsy findings were normal.

TABLE 1 Individual bodyweights (g) of rats dosed orally with tellurium diethyldithiocarbamate

 

Sex

Bodyweight (g) at Day

1

2

3

5

8

11

15

m

282 286 296 300 299

315 304 318 320 319

309 295 326 340 329

328 320 346 355 354

339 336 366 377 378

353

354

398

390

402

366 370 424 409 430

f

242 244 240 237 250

264 259 252 250 263

256 253 251 243 275

270 260 250 250 277

273 265 263 252 285

276

274

264

268

293

280 277 264 267 305

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
traditional method
Limit test:
no
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
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%
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
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.

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%

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
510 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity 

In a pre-GLP acute toxicity study similar to OECD 401, 5 rats per sex were orally exposed to 5000 mg/kg bw test substance. The test substance was prepared at 50% (w/v) in distilled water and administered at a volume of 10.0 ml/kg bodyweight. Animals were observed for 14 days and clinical signs and bodyweight were reported. After 14-days, all animals were necropsied and abnormal macroscopic appearance of organs was recorded. No mortality was observed. Pilo-erection was observed shortly after dosing in all rats. On Day 2, soft faeces was observed for all animals. Bodyweight losses were recorded for two male and four female rats on Day 3, one female rat on Day 5 and one female rat on Day 15. An unchanged bodyweight was recorded for one female rat on Day 15. Bodyweight gains were recorded on all other occasions. Terminal autopsy findings were normal. The LD50 was determined to be greater than 5.0 g/kg bodyweight.

 

In a pre-GLP acute toxicity study similar to OECD 401, 5 rats per sex/dose were orally exposed to 3000, 3600, 4320, 5190 and 6210 mg/kg bw test substance. The test substance was prepared at 30% (w/v) in DMSO and administered at a volume of 10.0, 12.0, 14.4, 17.3, 20.7 ml/kg bodyweight. Animals were observed for 14 days and clinical signs were reported. After 14-days, all surviving animals were necropsied and abnormal macroscopic appearance of organs was recorded. Two animals died in the 4320 mg/kg bodyweight group, three animals died in the 5190 mg/kg bodyweight group and nine animals died in the 6210 mg/kg bodyweight group during observation period. Most deaths occurred between 4 hours and 3 days after dosing. Two animals exposed to the highest dose died on the 10th post-treatment day. Macroscopic examination revealed pale discolouration of liver and kidneys of rats exposed to 4320 and 5190 mg/kg bodyweight. The LD50 was calculated to be 5310 mg/kg bodyweight (95% CL; 4800 - 5850 mg/kg bodyweight).

 

Acute inhalation toxicity

In a GLP acute toxicity study similar to OECD 403, 5 rats per sex were continuously exposed (whole body) for 4 hours to the highest possible generated concentration of an aerosol of the test substance (0.51 mg/l; 30% respirable) using a Wright dust generator. A control group received clean air only for 4 hours. Animals were observed for 14 days and clinical signs and bodyweight were reported. No mortality was observed. Small losses of bodyweight or a reduction in the rate of weight gain were observed in the exposed rats on the day following exposure. Terminal autopsy findings were normal. The LC50 was determined to be greater than 0.51 mg/l.

 

Acute dermal toxicity

In a pre-GLP acute toxicity study similar to OECD 402, 5 rabbits per sex were dermally exposed for 24 hours to 2000 mg/kg bw test substance (occlusive). Animals were observed for 14 days and clinical signs, dermal irritation and body weight were reported. After 14-days, all animals were necropsied and abnormal macroscopic appearance of organs was recorded. One female rabbit was found dead on Day 12. Body weight loss was observed prior to death in this animal.

Autopsy of the dead female rabbit revealed gaseous filled stomach and autopsy of the dead female rabbit revealed gaseous filled stomach and intestines. Clinical signs observed in the surviving animals include abnormal gait, pilo-erection, poor food consumption and mucoid discharge from the anus. Bodyweight loss and poor weight gain were recorded in several animals throughout the observation period. Terminal autopsy revealed a diffuse minimal congestion in the lungs of one male rabbit. The LD50 was determined to be greater than 2.0 g/kg bodyweight.


Justification for classification or non-classification

The available data for acute oral and dermal toxicity are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral and dermal toxicity according to Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008.

Inhalation toxicity

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.