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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.05 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:
3.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
The hazard profile shows that the gastrointestinal lymphatic system is the most sensitive target and that other systemic effects (spleen, liver) follow at higher dosages. There is no risk for underestimation of the inhalation toxicity from route-to-route extrapolation.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
Justification:
Included in the route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
None specific known, covered in the factor for remaining differences
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.07 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
As discussed in the toxicokinetics section, criteria for assuming 10% reduction of absorption compared to the oral route are fulfilled. For the oral route, the gastrointestinal immune system is the target organ indicating efficient uptake.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 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:
1.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
The most sensitive organ was the point of entry (mesenteric lymph nodes). So no underestimation of hazard is expected by assuming equal uptake for inhalation and ingestion.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
Justification:
Included in route-to-route extrapolation
AF for other interspecies differences:
1
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
33 µg/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:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
10% absorption (Faktor 0.1) introduced based on physico-chemical properties (ECHA guidance 2004) and on available dermal toxicity data.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
3 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not needed
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

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