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Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-09-24 to 2012-12-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Objective of study:
bioaccessibility
Qualifier:
according to
Guideline:
OECD Series on Testing and Assessment No. 29 (23-Jul-2001): Guidance document on transformation/dissolution of metals and metal compounds in aqueous media
GLP compliance:
yes (incl. certificate)
Radiolabelling:
no
Details on study design:
The objective of this study is to assess the dissolution of chemical compounds in artificial alveolar fluid.
The test media is selected to simulate relevant human-chemical interactions (as far as practical), i.e. entering the human body by inhalation. The amount dissolved of the test item is specified by the mass concentration of the substance in the test media under the applied test conditions. The total amount dissolved will be determined by measuring the total concentrations of dissolved tellurium.
Bioaccessibility testing results:
Dissolved mean tellurium concentrations in alveolar fluid at a loading of 20 mg/L were measured to be:
172.8 ± 2.8 mg/L after 2 hours
209.6 ± 6 mg/L after 5 hours
197.2 ± 4.3 mg/L after 24 hours
238.4 ± 16.1 mg/L after 72 hours

Dissolved Te concentrations in test vessels and method blanks

sample

total Te
conc.
[mg/L]

mean Te
conc.
per vessel
± range
[mg/L]

mean Te
conc.
all vessels
± SD
[mg/L]

LOD
[mg/L]

LOQ
[mg/L]

2h 1a

170.8

172.8 ± 2.8

177.2 ± 5.4

0.11

0.38

2h 1b

174.7

2h 2a

180.4

181.6 ± 1.6

2h 2b

182.7

 

 

 

 

 

 

5h 1a

202.7

204.6 ± 2.7

209.6 ± 6.0

0.11

0.38

5h 1b

206.5

5h 2a

213.3

214.6 ± 1.8

5h 2b

215.8

 

 

 

 

 

 

24h 1a

192.7

193.5 ± 1.1

197.2 ± 4.3

0.65

2.16

24h 1b

194.2

24h 2a

200.7

200.9 ± 0.2

24h 2b

201.0

 

 

 

 

 

 

72h 1a

226.8

225.3 ± 2.1

238.4 ± 16.1

0.65

2.16

72h 1b

223.8

72h 2a

245.0

251.5 ± 9.2

72h 2b

258.0

 

 

 

 

 

 

2h BW 1a

< LOD

 

 

0.11

0.38

2h BW 1b

< LOD

2h BW 2a

< LOD

 

2h BW 2b

< LOD

 

 

 

 

 

 

5h BW 1a

< LOD

 

 

0.11

0.38

5h BW 1b

< LOD

5h BW 2a

< LOD

 

5h BW 2b

< LOD

 

 

 

 

 

 

24h BW 1a

< LOD

 

 

0.65

2.16

24h BW 1b

< LOD

24h BW 2a

< LOD

 

24h BW 2b

< LOD

 

 

 

 

 

 

72h BW 1a

< LOD

 

 

0.65

2.16

72h BW 1b

< LOD

72h BW 2a

< LOD

 

72h BW 2b

< LODlimit of detection

LODs (limit of detection) and LOQs (limit of quantification) depend on calibration range.A calibration with an optimal concentration range for samples was performed before each measurement series. Therefore theses limits vary. Three measurement series were performed to quantify Te concentrations.

In the vessels the pHs were not stable over the course of the test. At the start of the study a pH of 8.5 and 8.6 were measured in the two test vessles. After 72 hours the pH value was approx. 9.3.

Conclusions:
Interpretation of results (migrated information): other: mean dissolved tellurium concentration in atrificial alveolar fluid
The following dissolved mean tellurium concentrations were measured in artificial alveolar fluid at a loading of 20 g/L:
2 hours          172.8 ± 2.8 mg/L
5 hours          209.6 ± 6 mg/L
24 hours        197.2 ± 4.3 mg/L
72 hours        238.4 ± 16.1 mg/L
Executive summary:

A study was performed to assess the dissolution of tellurium powder in artificial alveolar fluid. The test media is selected to simulate relevant human-chemical interactions (as far as practical), i.e. entering the human body by inhalation.

The Test was performed on the basis of the guidance for OECD-Series on testing and assessment Number 29 and on Stopford et al., 2004.

Test conditions: Artificial alveolar fluid,one single loading of the test substance,measurements of dissolved tellurium after 2, 5, 24 and 72 hours of agitation at 37°C.

The test was performed in duplicate vessels with one single loading of the test substance, i.e. 20 g/L (10.00 g / 500 mL in vessel 1 and 2, respectively). The vessels were agitated in an incubation cabinet at 100 rpm at 37 ± 2 °C. During the test an increase of pH was observed, values were in a range between 8.5 and 9.3. 

Solved tellurium was quantified by ICP-OES.

The following dissolved mean tellurium concentrations were measured in artificial alveolar fluid:

2 hours          172.8 ± 2.8 mg/L

5 hours          209.6 ± 6 mg/L

24 hours        197.2 ± 4.3 mg/L

72 hours        238.4 ± 16.1 mg/L

 

The maximum percentage after 72 hours is calculated to be 1.2 % dissolved tellurium in relation to loading.

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-10-25 to 2012-12-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Objective of study:
bioaccessibility
Qualifier:
according to
Guideline:
OECD Series on Testing and Assessment No. 29 (23-Jul-2001): Guidance document on transformation/dissolution of metals and metal compounds in aqueous media
GLP compliance:
yes (incl. certificate)
Radiolabelling:
no
Details on study design:
The objective of this study is to assess the dissolution of chemical compounds in artificial gastrointestinal fluids.
The test media were selected to simulate relevant human-chemical interactions (as far as practical), i.e. entering the human body by ingestion. The amount dissolved of the test item is specified by mass concentration of the substance in the test media under the applied test conditions. The total amount dissolved will be determined by measuring the total concentrations of dissolved tellurium.

Dissolved Te concentrations in test vessels and method blanks at test end

sample

dilution
factor

total Te
conc.
[mg/L]

mean Te
conc.
per vessel
± range
[mg/L]

mean Te
conc.
all vessels
± SD
[mg/L]

LOD
[mg/L]

LOQ
[mg/L]

1a

100

55.40

56.48 ± 1.52

56.68 ± 1.46

0.007

0.021

1b

100

57.55

2a

100

58.28

56.89 ± 1.97

2b

100

55.50

 

 

 

 

 

 

 

BW 1a

1

0.027

0.027

0.074 ± 0.042

0.019

0.057

BW 1b

1

 < LOQ(0.016)

BW 2a

1

0.108

0.098 ± 0.013

BW 2b

1

0.089

Calculation of the mobilized amount and the resorption availability (bioaccessibility) following DIN 19738:

The mobilized amount of a compound is calculated by

Wi,mob= ρi*V/mE

Wi,mob:          mobilized amount of compound i [mg/g]

ρi                    measured conc. of compound i [mg/L]

V                    total volume [L]

mE                 inweight of sample [g]

Wi,mob= 56.68 ± 1.46 mg Te /L * 0.23 L / 2 g Te = 6.518 ± 0.168 mg/g

The resorption availability (bioaccessibility) is calculated by:

Ri,=Wi,mob100 % /Wi,fest

Ri                     resorption availability of compound i [%]

Wi,mob             as described above

mE                   inweight of sample [g]

Wi,fest              total amount of the solid sample [mg/g]

                       => 1000 mg pure tellurium

Ri= 6.518 ± 0.168 mg/g *100 % / 1000 mg/g = 0.65 ± 0.02 %

This value equals the percentage of dissolved tellurium.


 


Conclusions:
Interpretation of results (migrated information): other: mean dissolved tellurium concentration in atrificial gastrointestinal fluids
The dissolved mean tellurium concentration of 56.68 ± 1.46 mg Te/L was measured in gastrointestinal fluids at a loading rate of 2 g/L.
The bioaccessibility in gastrointestinal fluids is calculated to be 0.65 ± 0.02 %, as percentage dissolved tellurium in relation to loading.
 
Executive summary:

A study was performed to assess the dissolution of Tellurium in artificial gastrointestinal fluids. The test media is selected to simulate relevant human-chemical interactions (as far as practical), i.e. entering the human body by ingestion.

The test was on the basis of DIN 19738 and OECD Series No. 29.

2 g of the test substance were weighted in a vessel and 30 mL of artificial salvia was added. After 0.5 hours stirring, 70 mL artificial gastric juice and 10 g whole milk powder was added. The pH was corrected to pH 2.0 with HCL. After another 2 hours stirring at pH 2.0, 100 mL of artificial intestinal fluid was added. The pH was corrected to pH 7.5 with NaHCO3.

After further 6.0 hours stirring at pH 7.5 the mixture was sampled, centrifuged and filtered. Dissolved tellurium was quantified by ICP-OES.

The test was performed in duplicate vessels with one single loading of the test substance, i.e. 2 g/L (2001 mg and 2000 mg in vessel A and B, respectively). The vessels were agitated in an incubation cabinet at 200 rpm at 37 ± 2 °C. During the test pH values were monitored and adjusted if needed according to DIN 19738.

The dissolved mean tellurium concentration of 56.68 ± 1.46 mg Te/L was measured in gastrointestinal fluids at a loading rate of 2 g/L.

 

The bioaccessibility in gastrointestinal fluids is calculated to be 0.65 ± 0.02 %, as percentage dissolved tellurium in relation to loading.

 

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: supporting information; not a relevant standard method
Executive summary:

The following information was considered relevant and is cited from the publication:

Toxicokinetics:

 

Absorption

"The mean (± SD) gastrointestinal absorption in healthy volunteers ingesting between 15 and 57 µg has been estimated as ten per cent (± 4 per cent) for elemental tellurium, 23 per cent (± 9 per cent) for tellurate and 21.5 per cent (no SD given) for tellurite (Kron et al, 1991).

Ingestion of 0.5 µg tellurium oxide produced a garlic breath odour within 75 minutes which lasted for 30 hours (Reisert, 1884).

Tellurium dusts and fumes can be absorbed via the lung. Workers exposed to tellurium concentrations up to 0.1 mg/m3 had urine tellurium concentrations of up to 0.06 mg/L (Steinberg et al, 1942).

Organometallic complexes of tellurium and soluble tellurium salts can be absorbed through the skin (Blackadder and Manderson, 1975)."

 

Distribution

"Tellurium is distributed widely with high concentrations particularly in kidneys, liver, bone, brain and testes (Meditext, 1997)."

 

Excretion

"Excretion is mainly renal although small amounts of tellurium are exhaled as dimethyl telluride which has a distinctive garlic odour which may persist for many days; Reisert (1884) reported garlic breath odour for 237 days following ingestion of 15 mg tellurium oxide.

The susceptibility to this effect varies considerably between individuals and is exacerbated by alcohol consumption (Cerwenka and Cooper, 1961).

The whole body retention time of tetravalent tellurium has been estimated as more than two months (Kron et al, 1991)."

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: supporting information; not a relevant standard method
Radiolabelling:
yes
Remarks:
Tellurous acid labelled with 127 mTe
Executive summary:

The following information was considered relevant and is cited from the publication:

"Hydrocephalus has been produced in approx. 50 % of offspring of rats fed 3,300 ppm of metallic Tellurium in their diets during pregnancy. The distribution of Tellurous acid labelled with 127 mTe was studied in maternal and fetal tissues after its intravenous injection in pregnant rats fed control and metallic Tellurium diets. The labelled Tellurium freely permeated the placental barrier as well as maternal and fetal blood-brain barriers, giving the following relative distributions 4 hours after intravenous administration: Maternal tissues: kidney > liver > blood > muscle > CNS tissues > CSF; fetal tissues: blood > livery > kidney > whole brain. In addition to the induction of hydrocephalus in the fetus, the feeding of metallic Tellurium resulted in The following information was considered relevant and is cited from the publication:a significant increase in the uptake of radiotellurium by maternal brain but not by non-nervous tissues. Appreciable binding of the labelled Tellurium to plasma proteins was observed. The persistency of radioactivity in fetal and maternal tissues for 1 week after injection indicated that prolonged binding of the isotope must also occur in tissues. The possibility of a direct teratogenic action of Tellurium on the fetus was considered."

Endpoint:
basic toxicokinetics
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: supporting information; not a relevant standard method
Justification for type of information:
see section 13.1 for read-across justification
Reason / purpose:
read-across source
Radiolabelling:
yes
Remarks:
Tellurous acid labelled with 127 mTe
Executive summary:

The following information was considered relevant and is cited from the publication:

"Hydrocephalus has been produced in approx. 50 % of offspring of rats fed 3,300 ppm of metallic Tellurium in their diets during pregnancy. The distribution of Tellurous acid labelled with 127 mTe was studied in maternal and fetal tissues after its intravenous injection in pregnant rats fed control and metallic Tellurium diets. The labelled Tellurium freely permeated the placental barrier as well as maternal and fetal blood-brain barriers, giving the following relative distributions 4 hours after intravenous administration: Maternal tissues: kidney > liver > blood > muscle > CNS tissues > CSF; fetal tissues: blood > livery > kidney > whole brain. In addition to the induction of hydrocephalus in the fetus, the feeding of metallic Tellurium resulted in The following information was considered relevant and is cited from the publication:a significant increase in the uptake of radiotellurium by maternal brain but not by non-nervous tissues. Appreciable binding of the labelled Tellurium to plasma proteins was observed. The persistency of radioactivity in fetal and maternal tissues for 1 week after injection indicated that prolonged binding of the isotope must also occur in tissues. The possibility of a direct teratogenic action of Tellurium on the fetus was considered."

Description of key information

State of the art toxicokinetic studies are not available. 

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Toxicokinetic profile of elemental Tellurium

Although daily uptake of Tellurium can be estimated with approximately 100 µg per person [1], its physiological role, if any, cannot be conclusively explained at the time being.

It needs to be acknowledged that essentiality may have a specific influence on toxicokinetic behavior because it is known that for essential elements specialized systems (like transport proteins) exist to allow for stable homeostatic conditions.

 

Absorption and bioavailability

All available data hint for a rather poor absorption of elemental Tellurium after oral uptake, i.e. systemic absorption was measured in human studies with elemental Tellurium, but also with tetra- or hexavalent Tellurium salts and is stated with 10 to 25 % of the applied dose [3].

In rats and rabbits absorption after oral exposure was determined with 10 to 40 % of applied dose.

 

The dermal absorption after application onto the skin is unknown [1] as is the case for human respiratory absorption [4].

 

For the determination of equitoxic potency of various Tellurium moieties (in this case elemental Tellurium and Tellurium dioxide) and hence definition of the NOAEL and furtheron derivation of DNELs the relative bioavailability is the most important figure.

 

For this purposein vitro studies with elemental Tellurium (Te) and Tellurium dioxide (TeO2) were conducted [5,6,7,8] to assess their behavior in a physiological environment with regard to any toxicokinetic differences.

Therefore bioavailability simulating inhalation and oral uptake was measured by the substance`s solubility in artificial alveolar fluid and in artificial saliva and gastrointestinal fluid respectively.

 

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

 

Tellurium [mg/L]

Tellurium dioxide [mg/L]

Mean solubility in

artificial alveolar fluid after 72 hours

238.4 ± 16.1

 799.1 ± 7.3 (Te)

999.4 ± 9.1 (Tellurium dioxide)

 

Factor

 

3.35 (based on Te)

Mean solubility in

artificial gastrointestinal fluid

56.68 ± 1.46

 156.7 ± 13.2 (Te)

196.03 ± 16.5 (Tellurium dioxide)

 

Factor

 

2.76 (based on Te)

  

Due to the unavoidable inaccuracies of these types of studies the obtained figures should be rounded for their practical use, i.e. the bioavailability for Tellurium dioxide can be estimated to be threefold higher compared with elemental Tellurium in different body fluids.

 

It is a well accepted fact, that suchin vitrostudies with inorganic substances may underestimate thein vivobioavailability, because living cells do possess active transport systems to control for homeostatic reasons the uptake of for example essential elements. Nevertheless thein vitrodata does clearly allow for a comparative insight into the bioavailability of different redox-species of an element and are therefore suitable for comparing study results with different Tellurium compounds in particular since the element Tellurium is not thought to be essential.

Despite total lack of information, the relative absorption after dermal exposure compared with oral exposure may be estimated by using data from other metals:

The Health Risk Assessment Guidance for Metals (HERAG) proposes for dermal absorption after exposure to dust or other dry metal compounds a default value of 0.1 % [9].

From this it follows that the dermal systemic bioavailability of elemental Tellurium may be estimated to be 10 % of the oral bioavailability (based on 10 % oral uptake) which results in a systemic bioavailability of 1 % of the external dermal dose. This figure clearly exceeds the above mentioned 0.1 % as typical for other metals and can therefore be considered a very conservative approach.

 

The figure of 1 % of dermal uptake of elemental Tellurium will be used further in the exposure considerations.

 

Distribution

The majority (90 %) of Tellurium in the blood stream enters erythrocytes; the remainder is bound to plasma proteins [4]. Tellurium may therefore accumulate in red blood cells in the form of dimethylated Tellurium.

 

Tellurium can cross the placenta and blood-brain barrier as well as the fetal blood-brain barrier. [6,13].

 

Concentrations of Tellurium were < 5 µg/L in blood, < 1 µg/L in saliva and < 0.5 µg/L in urine; the body “load” for an adult person is 600 mg Tellurium.

Highest tissue concentrations have been found in the kidneys [4], but also in liver, bone, brain and testes [10].

 

The half-life time of Tellurium in humans is estimated to be 3 weeks [3].

 

 

Metabolism

Ingested Tellurium is transformed, methylated and then effluxed into the blood stream where accumulation into red blood cells as dimethylated Tellurium takes place [11].

Trimethylated Tellurium was detected in blood serum and in urine as a main metabolite, but not in red blood cells.

Based on speciation studies it was found that all inorganic Tellurium is first reduced to Telluride (Te2-) and thereafter methylated [10,11].

Since concentrations of “free” Tellurium seem to be extremely low in various media it is obvious that absorbed Tellurium is taken up and converted to the Telluride moiety in cells from which it is released into the blood stream as dimethylated Tellurium for further distribution and predominantly renal excretion.

 

Excretion

Loss of systemically available Tellurium for humans is approximately 80 % in urine, approximately 16 % in feces and approximately 2 % in exhaled air [3] as dimethylated Tellurium resulting in a typical garlic odour [10].

Excretion in urine seems to take place via Trimethyltelluronium [12].

 

But the excretion pattern seems also to depend on the chemical form and mode of administration because in rats the main route of excretion is via feces (60 to 80 %) [4].

In conclusion above short description of the toxicokinetic behavior allows for the following:

  • Determination of relative bioavailabilities (threefold higher for Tellerium dioxide than elemental Tellurium) allows for definition of equitoxic potencies of elemental Tellurium versus Tellurium dioxide.
  • Because of utmost practical importance the dermal absorption of elemental Tellurium can be fixed due to a relatively robust estimation, i.e. 1 % of dermally applied dose.
  • Once absorbed all inorganic Tellurium seems to be converted to dimethylated (and also trimethylated) Telluride/Telluronium because concentrations of “free” Tellurium are extremely low and also only the di- and trimethylated Tellurium moieties have been detected.
  • Due to this unique metabolic behavior elemental Tellurium and Tellurium dioxide seem to belong into the same class of toxicants with regard to adverse effects which do not differ by mode of action but only by their potency due to differences in bioavailability (for comparison see also reference [2]).
  • Tellurium crosses the placenta barrier and fetuses may be therefore exposed to it.

Particles size an relevance of inhalation pathway

 

Tellurium is a solid substance, i.e. the inhalation characteristics are depending on the particle sizes.

 

The particle size distribution was determinedby light scattering, which allows a measurement of the volume based diameter (seeSiemens test report 20110372.02 (03/2012)).

 

Since inhalation of particles depends on the physical size and on the density, the aerodynamic diameter has to be defined. This parameter allows for a prediction of the likelihood of a particle to be respired and deposited in the human lung.

 

The physical particle diameter can be converted to the aerodynamic diameter in a first approach by the equation:

 

 DA≈ D√r/r0          (1)

(see: Attwood, David and Florence, Alexander: FASTtrack: Physical Pharmacy,   Pharmaceutical Press, 2nd ed. 2012)

(for spherical particle > 1µm)

 

with:

D:Particle diameter:

DA:Aerodynamic diameter:

r:Density of the disperse phase

r0:Unit density = 1 kg/dm3

 

For elemental Tellurium the statistical distribution of thephysical particlediameter D was stated with:

 

Particle diameter L10: 52.36 µm

(= 10 % < 52.36 µm; 90 % > 52.36 µm)

Particle diameter L50: 77.00 µm

Particle diameter L90: 112.98 µm

 

Converting D to DAfor elemental Tellurium with a relative density of 6.2 by use of equation (1) leads to:

 

DA≈ D x 2.5

Aerodynamic diameter LA10: 130.4 µm

(= 10 % < 130.4 µm; 90 % > 130.4 µm)

Aerodynamic diameterLA50: 192.50 µm

Aerodynamic diameterLA90: 282.45 µm

 

Since the test item consists of spherical dark-grey particles with a physical particle size clearly above 10 µm (see Graph x) the conversion should be considered as very precise.

 

The calculation shows, that the distribution as of Graph X is shifted to the right hand side and no measured particles are of an aerodynamic diameter below 10 µm.

 

But also a numerical solution by using the definition of “respirable fraction” according toEN 481 (1993) can be applied:

The value, where 50 % of particles in the air with an aerodynamic diameter DAare below 4 µm is defined as “respirable fraction”.

 

From this, that the measured particles are devoid of a relevant respirable fraction.

 

Both algorithms are demonstrating, that the measured particles of elemental Tellurium are classified as “not respirable”, because practically absence of particles with an aerodynamic diameter below 10 µm can be shown,

Based on this assessment the inhalation route is consideredno relevant application pathway for this substance and animal studies by inhalation are not required.

Dermal Absorption

In the evaluated scenarios only dry exposure to Tellurium dioxide dust is relevant.In the absence of measured data on percutaneous/dermal absorption, current guidance and practice in general suggests by default the assignment of either 10% or 100% dermal absorption rates:

- 10 % dermal absorption is used for molecular weights > 500 Da and log Pow < -1 or > 4,

otherwise:

 - 100 % dermal absorption is used.

For metals and their inorganic compounds, these considerations cannot be applied: The typical model for metals requires a metal compound to dissolve prior to its penetration of the skin by diffusive mechanisms the fact of which requires formation to the metal cation, for which in turn partition coefficients from n-octanol/water are irrelevant.

Just by default for metals only a figure of 100 % dermal absorption can be used in case of lack of any specific data.

In contrast, the currently available scientific evidence on the extent of dermal absorption of metals yields substantially lower figures than 100 %, as documented for example in a guidance document from US-EPA:

US-EPA estimated the dermal absorption of metals in its Guidance Document “Assessing Dermal Exposure from Soil” by (citation from: http://www.epa.gov/risk/assessing-dermal-exposure-soil):

“Suggested ABS factors based on the pharmacokinetic properties of chemicals appeared in Ryan et al, 1987. The proposed range for dermal absorption of inorganics from soil was 0.1% to 1%. This was also consistent with a review of the studies for cadmium, an inorganic, as assessed in EPA, 1992. Region 3 recommends accepting the 1% value as a conservative assumption of ABS for inorganics, in keeping with RAGS.”

ABS = Absorption factor (unitless)

RAGS = Risk Assessment Guidance for Superfunds

This is in line with the methodology proposed in the HERAG guidance for metals (HERAG fact sheet; 2007), where the following default dermal absorption factors for metal cations have therefore been proposed (epresentative for a full-shift exposure, i. e. 8 hours):

From exposure to liquid/wet media:                  1.0 %

From dry (dust) exposure:                                  0.1 %

Due to the fact, that it is unclear how similar tellurium is to those metals, which were used for the derivation of above figures, a dermal absorption for tellurium of 10 % is proposed. This leads to an additional Margin of Safety of 100 for the relevant exposure scenario to dry tellurium dust and is in line with good industrial practice.

Also recent publications for the assessment of elemental impurities in medicinal products do support this approach (see Teasdale A., Ulman K., Domoradzki J., Walsh P; 2015): “Conclusion: Although fragmentary in nature, existing data do nevertheless show that dermal exposure to metals is limited, often well below 10% of that observed when the same materials are administered orally.”