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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 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
Dose descriptor starting point:
NOAEL
Value:
50.8 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
45 mg/m³
Explanation for the modification of the dose descriptor starting point:

corrected inhalatory N(L)OAEC = oral N(L)OAEL * (1/sRVrat) * (ABSoral rat/ABSinh human) * (sRVhuman/wRV)

with:

oral N(L)OAEL = 50.8 mg/kg bw/d

sRVrat = 0.38 m3/kg bw

ABSoral-rat = 0,5       

ABSinh-human = 1       

sRVhuman = 6,7 m3/person

wRV = 10 m3/person

As recommended in the Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (version 2.1, page 19):

"It is proposed, thus, in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-to-inhalation extrapolation."

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not required
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value for worker
AF for the quality of the whole database:
1
Justification:
good reliability
AF for remaining uncertainties:
1
Justification:
not concerned
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 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
Dose descriptor starting point:
NOAEL
Value:
50.8 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As recommended in the Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (version 2.1, page 19):

"On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation."

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric value (rat)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value for worker
AF for the quality of the whole database:
1
Justification:
good reliability
AF for remaining uncertainties:
1
Justification:
not concerned
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:
0.15 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
Dose descriptor starting point:
NOAEL
Value:
50.8 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
22.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

corrected inhalatory N(L)OAEC = oral N(L)OAEL * (1/sRVrat) * (ABSoral rat/ABSinh human)

with:

oral N(L)OAEL = 50.8 mg/kg bw/d

sRVrat = 1.15 m3/kg bw/d

ABSoral-rat = 0,5       

ABSinh-human = 1       

As recommended in the Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (version 2.1, page 19):

"It is proposed, thus, in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-to-inhalation extrapolation."

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not required
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value for general population
AF for the quality of the whole database:
1
Justification:
good reliability
AF for remaining uncertainties:
1
Justification:
not concerned
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.09 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
Dose descriptor starting point:
NOAEL
Value:
50.8 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As recommended in the Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (version 2.1, page 19):

"On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation."

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric value (rat)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value for general population
AF for the quality of the whole database:
1
Justification:
good reliability
AF for remaining uncertainties:
1
Justification:
not concerned
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:
0.09 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
Dose descriptor starting point:
NOAEL
Value:
50.8 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

no modification applied

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric value (rat)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value for general population
AF for the quality of the whole database:
1
Justification:
Good reliability
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.09 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population