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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Value:
43.75 mg/m³
Explanation for the modification of the dose descriptor starting point:

The route to route extrapolation was conducted according to Appendix R8.2 of the ECHA Guidance document "Chapter R.8: Characterisation of dose [concentration]-response for human".

The most sensitive endpoint is the oral repeated dose toxicity (NOAEL= 25 mg/kg/day). The more sensitive NOAEL for reprotoxicity is not selected due to adverse effects are specific to the developing organism.

Starting point: Derived oral NOAEL in rats: 25 mg/kg/d -> NOAEL human = 25/4 = 6.25 mg/kg/d; NOAEC worker (8 h) = NOAEL x 70/10 = 6.25 x 70/10 = 43.75 mg/m3.

The applied factors can be derived from the flow chart below. As first approach the route to route extrapolation from oral to inhalation is based on a comparable resorption for both pathways.

Explanation of factors:

4: Transfer rat->human

70: human bodyweight

10: daily respiration volume (workers per work shift) 

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Subacute->chronic, default value according to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Still applied by route to route extrapolation for deriving NOAEC by using allometric scaling
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
Default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.83 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The route to route extrapolation was conduted according to Health Risk Assessment Guidance for Metals (HERAG).

In the evaluated scenarios only dry expsosure to Tellurium dioxide dust is relevant. The Health Risk Assessment Guidance for Metals (HERAG) proposes for the dermal absorption after exposure to dust or other dry metal compounds a default value of 0.1 % (see also HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metal cations and inorganic metal substances; EBRC Consulting GmbH / Hannover /Germany; August 2007) . The starting point of the DNEL-derivation comes from an oral study on rats. As discussed in the chapter "Toxicokinetics" the bioavailability of Tellurium dioxde after oral uptake is considered to be lower than 25 %. An in vitro study stated a bioavailability in artificial gastrointestinal fluid of approx. 3 % after 24h. Typically such an in vitro study may underestimate the bioavailabilty in humans, the realistic bioavailability after oral ingestion may be between 3 % and 25 %. Based on this bandwidth the dermal bioavailability is estimated with 10 % of the oral biovailability and the extrapolated dermal NOAEL is stated with 250 mg/kg bw per day.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Subacute->chronic, default value according to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
Rat-> human; Default value according to ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
Default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The derivation of DNELs is based on available toxicological data and the toxicokinetic behaviour of tellurium compounds.

Critical parameters for DNEL derivations

NOAEL for Tellurium dioxide: 25 mg/kg bw/d

Extrapolation for time scaling subacute -> chronic: factor 6

Therefore the chronic NOAELoral after time scaling is:

25 mg/kg bw/day /6 = 4.17 mg/kgbw/day

 

The derived NOAEL for developmental toxicity was stated with 3.19 mg Tellurium dioxide/kg body weight per day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
21.88 mg/m³
Explanation for the modification of the dose descriptor starting point:

The route to route extrapolation was conducted according to Appendix R8.2 of the ECHA Guidance document "Chapter R.8: Characterisation of dose [concentration]-response for human".

Starting point: Derived oral NOAEL in rats: 25 mg/kg/d -> NOAEL human = 25/4 = 6.25mg/kg/d; NOAEC general population (24 h) = NOAEL x 70/20 = 6.25 x 70/20 = 21.88 mg/m3.

The applied factors can be derived from the flow chart below. As first approach the route to route extrapolation from oral to inhalation is based on a comparable resorption for both pathways.

Explanation of factors:

4: Transfer rat->human

70: human bodyweight

20: daily respiration volume (general population for 24 h)

 

 

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Subacute->chronic, default value according to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Still applied by route to route extrapolation for deriving NOAEC by using allometric scaling
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The route to route extrapolation was conduted according to Health Risk Assessment Guidance for Metals (HERAG).

In the evaluated scenarios only dry expsosure to Tellurium dioxide dust is relevant. The Health Risk Assessment Guidance for Metals (HERAG) proposes for the dermal absorption after exposure to dust or other dry metal compounds a default value of 0.1 % (see also HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metal cations and inorganic metal substances; EBRC Consulting GmbH / Hannover /Germany; August 2007) . The starting point of the DNEL-derivation comes from an oral study on rats. As discussed in the chapter "Toxicokinetics" the bioavailability of Tellurium dioxde after oral uptake is considered to be lower than 25 %. An in vitro study stated a bioavailability in artificial gastrointestinal fluid of approx. 3 % after 24h.  Typically such an in vitro study may underestimate the bioavailabilty in humans, the realistic bioavailability after oral ingestion may be between 3 % and 25 %.  Based on this bandwidth the dermal bioavailability is estimated with 10 % of the oral biovailability  and the extrapolated dermal NOAEL is stated with 250 mg/kg bw per day.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Subacute->chronic, default value according to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
rat-> human, default value according to ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
see chapter "toxicokinetics"
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Subacute->chronic, default value according to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
rat-> human, default value according to ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Critical parameters for DNEL derivations

NOAEL for Tellurium dioxide: 25mg/kg bw/d from an oral study with rats.

Extrapolation for time scaling subacute -> chronic: factor 6

Therefore the chronic NOAELoral after time scaling is:

25 mg/kg bw/day /6 = 4.17 mg/kg bw/day

Doses for adverse effects derived from the reproductive/developmental screening toxicity is 3.19 mg Tellurium dioxide/kg body weight per day and for this endpoint a time scaling is not required.