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Description of key information

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:
1996-07-09 to 1996-07-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, all study parameters are well documented and based on the specific guideline.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: 5-6 weeks old upon arrival
- Weight at study initiation:
- Fasting period before study: overneight
- Housing: five animals per cage (stainless steel cages, fitted with wire screen floor and front)
- Diet (e.g. ad libitum): standard laboratory rodent diet ad libitum
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: 26 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): between 60-91 %
- Air changes (per hr): ca 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours Iight/12 hours dark cycle

Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL
MAXIMUM DOSE VOLUME APPLIED: 10 mL/ kg max. Dose volume

Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5 animals/ sex/ dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were made within 1 hour and within 4 hours after dosing, and subsequently at least once daily throughout the observation period of 14 days; body weights were recorded on day 0, 3, 7 and 14.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured during the 14-day observation period.
Clinical signs:
At 4 hours after dosing, all males showed signs of diarrhoea. No other clinical symptoms were observed.
Body weight:
Apart from a slight dip in body weight of one male on day 7, all animals gained weight during the 14-day observation period.
Gross pathology:
Examination of the animals at autopsy did not reveal any treatment-related gross alterations.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for tellurium dioxide (powder) was determined to be above 5000mg/kg bw .
Executive summary:

In an acute oral toxicity study according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method), wistar rats were given a single oral dose of tellurium dioxide (powder) in maize oil at a dose of  5000, mg/kg bw (5 animals/sex/ group) and observed for 14 days.

No mortality occurred. At 4 hours after dosing, all males showed signs of diarrhoea. No other clinical symptoms were observed.

Apart from a slight dip in body weight of one male on day 7, all animals gained weight during the 14-day observation period.

Examination of the animals at autopsy did not reveal any treatment-related gross alterations.

Since no mortality occurred during the 14-day observation period, the oral LD50of tellurium dioxide is considered to exceed 5000 mg/kg bw in both male and female rats.

 

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from a guideline study with RL1, all study parameters are well documented and based on the specific guideline.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: 5-6 weeks old upon arrival
- Weight at study initiation: mean body weight 304g males, mean females 192 g
- Fasting period before study: no data
- Housing: five animals per cage stainless steel cages fitted with wire-mesh floor and front.
- Diet (e.g. ad libitum): standard laboratory rodent diet ad libitum
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5 - 21.5 °C
- Humidity (%): between 70-85 %
- Air changes (per hr): 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours Iight/12 hours dark cycle

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: modified nose-only inhalation chamber from ADG Developments LTD.
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: plastic animal holders (Batelle).
- Source and rate of air: air from compressed air system; average flow 3.1 m³/h
- System of generating particulates/aerosols:
Due to the inhomogeneity of the particles sizes of the test material, the test material was ground during a short period of time using a grinder. In preliminary experiments it turned out that it was not possible to use any moving device for transportation of the particles to the aerosol generation device since the particles coalesced strongly during transport. Therefore, a means of transportation had to be found in which the particles did not move themselves. Hereto, a moving tray was developed with tow grooves filled with test material (effective length 58 cm). A test atmosphere was generated by moving the tray with one filled groove along the suction side of the airmover. (AIR VAC 100) which was operated with pressurized air. When reaching the end of the groove, the second groove was started. In the meantime the first groove was refilled. This procedure was repeated every 15 minutes. The generation system was placed in a hood.
The inhalation equipment was designed to expose tats to a continuous supply of fresh test atmosphere. The generated aerosol was passed to the inlet of the exposure unit. From there it was directed downward through the mixing chambers towards the animal holders. At the bottom of the unit the test atmosphere was exhausted.

- Method of particle size determination: 11 - stage cascade impactor
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: 20.3 +/- 0.1 °C; relative humidity was very low (12 +/- 1 %). Air has been used from the compressed air system has a very low relative humidity.

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetrical analysis; once each half hour by passing 10 L test atmosphere at 5 L/min through fiber glass filters.
- Samples taken from breathing zone: yes
- Particle size distribution: 72 % of the particles had an aerodynamic diameter between 1.8 and 4.2 µm.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
nominal concentration 6.7 g/m³
analytical concentration: 2.42 g/m³
No. of animals per sex per dose:
5 aminals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were visually inspected just before exposure, for reaction to treatment during the exposure, shortly after exposure, and once daily during the observation period. Body weights were recorded just prior to exposure and at days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
NA
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2 420 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: None of the rats died during or after exposure.
Mortality:
None of the rats died during or after exposure.
Clinical signs:
No abnormalities were seen during exposure except for black heads of all rats. Black heads, half closed eyes and hunched posture were observed immediately after exposure.
Grey dust was seen on the fur of all rats the first two days of the observation period. Baldness was observed on head, back and posterior of all female rats on days 7 – 14.
Body weight:
Almost all rats showed strongly decreased body weights one week after exposure compared with their pre-exposure weight; all rats had gained weight at the end of the 14-day observation period, although pre-exposure weights was just or nearly reached in female rats.
Gross pathology:
At autopsy, a garlic-like scent was smelled. Greyish, brownish spotted lungs were observed in all male rats. Female rats showed pale and/or grey-black stained lungs. In addition, a grey thymus was observed in 4 females.

The mean actual concentration and standard deviation turned out to be 2.42 (0.19) g/m³. Nominal concentration was 6.7 g/m³.

Particle size measurement showed that ca. 72 % of the particles had an aerodynamic diameter between 1.8 and 4.2 µm.

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: other: EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
The 4-hour LC50 value for tellurium was higher than 2.42 g/m³.
Executive summary:

In an acute inhalation toxicity study according to OECD guideline 403, groups of young adult wistar rats (5/sex) were exposed by inhalation route to tellurium powder (99.5 % a.i.) for 4 hours to nose only at an analytical concentration of 2.42 g/m³ corresponding to 6.7 g/m³ nominal, which was the highest attainable concentration.  Animals then were observed for 14 days.

Since none of the rats died, it was concluded that the 4-hour LC50 value was higher than 2.42 g/m³ 

No abnormalities were seen during exposure except for black heads. Black heads, half closed eyes and hunched posture were observed immediately after exposure. Grey dust on the fur was seen in all rats and baldness in female rats during the observation period.

Almost all rats showed strongly decreased body weights one week after exposure; weight gained was observed at the end of the 14-day observation period, although pre-exposure weights was just or nearly reached in female rats.

Greyish, brownish or black stained lungs were seen in all rats at autopsy. A grey thymus was observed in four out of five females.

Particle size measurement showed that ca. 72 % of the particles had an aerodynamic diameter between 1.8 and 4.2 µm.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Additional information

Acute oral toxicity:

In an acute oral toxicity study according to OECD Guideline 401 (Acute Oral Toxicity), wistar rats were given a single oral dose of tellurium dioxide (powder) in maize oil at a dose of  2000 mg/kg bw (5 animals/sex/ group) and observed for 14 days.

 

In a second acute oral toxicity study according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method), wistar rats were given a single oral dose of tellurium dioxide (powder) in maize oil at a dose of 5000 mg/kg bw (5 animals/sex/ group) and observed for 14 days.

 

In both studies no mortality occurred and examination at necropsy did not reveal any treatment-related gross alterations.

Since no mortality occurred during the 14-day observation period in both studies, the oral LD50of Tellurium dioxide is considered to exceed 5000 mg/kg bw in both male and female rats.

 

 

Acute inhalation toxicity:

Background information:

Studies with elemental Tellurium (Te) and Tellurium dioxide (TeO2) were conducted to assess their behavior in a physiological environment with regard to any toxicokinetic differences. Therefore bioavailability simulating inhalation and oral uptake was measured by their solubility in artificial alveolar fluid and in artificial saliva and gastrointestinal fluid.

The results indicate that Tellurium dioxide is of approximately three times higher solubility than Tellurium (see following table for measured solubility data):

 

 

Tellurium [mg/L]

Tellurium dioxide [mg/L]

Mean solubility in

artificial alveolar fluid after 72 hours

OECD 29 guideline study

238.4 ± 16.1

 

799.1 ± 7.3 (Te)

999.4 ± 9.1 (Tellurium dioxide)

 

 

Mean solubility in

artificial gastrointestinal fluid

OECD 29 guideline study

56.68 ± 1.46

 

156.7 ± 13.2 (Te)

196.03 ± 16.5 (Tellurium dioxide)

 

Acute inhalation toxicity data for elemental Tellurium:

For elemental Tellurium appropriate data are available for this toxicological endpoint from an OECD 403 guideline study (reliable without restrictions (RL1), TNO report V92.008, 1992, for details see robust study summary and study report):

 

Rat; 4-hour single exposure, nose only:

Ø LC0> 2.42 mg/L (analytical)

Ø LC0> 6.7 mg/L (nominal)

 

Observed effects:

None of the rats died during or after exposure.

Grey dust on the fur was seen in all rats and baldness in female rats during the observation period.

Almost all rats showed strongly decreased body weights one week after exposure; weight gained was observed at the end of the 14-day observation period, although pre-exposure weights was just or nearly reached in female rats. Greyish, brownish or black stained lungs were seen in all rats at autopsy. A grey thymus was observed in four out of five females.

 

 

Read-across rationale for Tellurium dioxide:

Elemental Tellurium is obviously reduced to Telluride [Te2-] which is further metabolized to the Mono- and dimethyl telluride (which are excreted to various degrees (also depended on route of exposure) in exhaled air, sweat, feces and urine) and also to the Trimethyl telluronium cation which is excreted in urine.

 

Since the physico-chemical behavior of elemental Tellurium and Tellurium dioxide is the same with regard to their metabolic fate (reduction to the Telluride cation) there seems to be good evidence that Tellurium from different moieties will behave very similar with regard to systemic toxicity.

 

This assumption is proven by a similar toxicological profile observed from acute oral toxicity studies in rats; for both substances the LD50value is > 5000 mg/kg body weight (for details see robust study summary and the respective study reports: for Tellurium: TNO study report no. V91.063, 1991; for Tellurium dioxide: TNO study report no. V96.514, 1996). In none of the studies an animal died.

 

Neither skin nor eye irritating properties were observed inin vitrostudies with both Tellurium and Tellurium dioxide (for details see robust study summary and the respective study reports: for Tellurium dioxide: CiToxLAB, report no. 12/088-043B, 2012 and CiToxLAB, report no. 12/088-038CS, 2012 for skin and eye irritation, respectively; for Tellurium: CiToxLAB, report no. 12/087-043B, 2012 and CiToxLAB, report no. 12/087-038CS, 2012 for skin and eye irritation, respectively).

 

The amount of dust which will reach the alveolar region of the lung depends on the granulometric characteristics of the substances to be registered, particles smaller than 100 µm are capable of entering the respiratory tract to a significant amount.

 

The following data were obtained from a granulometry study conduct within the preparation of physico-chemical data set for REACH registration of Tellurium metal and Tellurium dioxide:

 

 

Tellurium

 Siemens report no. 20110372.02

Tellurium dioxide

Siemens report no. 20110373.05

Particle size L10 µm

52.36

2.84

Particle size L50 µm

77.00

17.74

Particle size L90 µm

112.98

39.33

 

The aerodynamic diameter determined in the acute inhalation study with Tellurium, was between 1.8 and 4.2 µm for 72 % of the particles. It can be stated, that this tested range of particle size covers well the particle size distribution of both Tellurium and Tellurium dioxide, measured in the granulometry study (refer to the table above), and can be seen as a worst case assumption.

 

In conclusion it is considered justified based on a practically identical metabolic fate, a similar toxicological profile for acute endpoints and the available bioavailability data to use the acute oral inhalation data from elemental Tellurium to cover the respective endpoint for Tellurium dioxide, taking into account that measured differences in bioavailability.

 

Calculation of LC0for Tellurium dioxide by extrapolation form data for elemental Tellurium:

Considering the higher solubility of Tellurium dioxide in artificial alveolar fluid a factor of 3.35 (799.1 / 238.4, see above table for measured solubility data) is used to account for solubility differences (Te moiety); therefore

 

LC0= 2.42 / 3.35 = 0.722 mg/L (Te)

Further adaptation for molecular weight differences finally gives the calculated LC0value for Tellurium dioxide

(Factor 1.251; atomic weight for Te: 127.61 and molecular weight for TeO2: 159.61)

LC0 calculated= 0.903 mg/L (TeO2)

 

 

 


Justification for selection of acute toxicity – oral endpoint
Data from two studies in the rat conducted according to OECD guideline 401 and 423 are available.
In conclusion the LD50 was determined to be > 5000 mg/kg bw.

Justification for classification or non-classification

Acute oral toxicity:

According to the CLP Regulation (EU GHS Regulation (EC) No 1272/2008) no classification and labelling would be required for Tellurium dioxide for acute oral toxicity, based on acute oral toxicity value of LD50 > 5000 mg/kg bw.

 

Acute inhalation toxicity:

Strictly regarding the threshold values for classification according to the CLP Regulation (EU GHS Regulation (EC) No 1272/2008) Tellurium dioxide has to be classified as “Toxic if inhaled” (Cat. 3, H 331).

 

From a scientific point of view classification in category 3 is not mandatory due to the following reasons:

 

  • the calculated LC0value of 0.903 mg/L (TeO2) is near the threshold to category 4 (1.0 < ATE ≤ 5.0)
  • the obtained effect value is a clear LC0, because at the highest concentration, none of the animals died during the observation period.
  • differences in bioavailability have already been taken into consideration

Based on the above it is reasonable to classify Tellurium dioxide into Category 4 “Harmfull if inhaled” H 332, according to the CLP Regulation (EC) No 1272/2008).