Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.01 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):
75
Dose descriptor starting point:
NOAEL
DNEL value:
298 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
525.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Using bioavailability of 100% for the oral and 100% for the inhalation route and assuming that rat oral and inhalation absorptions are equal to human oral and inhalation absorption, a NOAEC corr of 298 mg/kg/day / 0.38 m³/kg * 6.7/10 * 100/100 = 525.4 mg/m³ is used.

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL/NOAEC
AF for differences in duration of exposure:
6
Justification:
due to subacute study data used
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
for worker, a default AF of 5 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.9 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
DNEL value:
298 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 980 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Using bioavailability of 100% for the oral and 10% for the dermal route and assuming that rat oral and dermal absorptions are equal to human oral and dermal absorption, thus the corrected dermal NOAEL is 298 * 100/10 = 2980 mg/kg/day based on the oral NOAEL of 298 mg/kg bw/d derived from a subacute study.

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
due to subacute study data used
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
for worker, a default AF of 5 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.73 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
DNEL value:
298 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
259.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

Using bioavailability of 100% for the oral and 100% for the inhalation route and assuming that rat oral and inhalation absorptions are equal to human oral and inhalation absorption, a NOAEC corr of 298 mg/kg/day / 1.15 m³/kg * 100/100 = 259.1 mg/m³ is used.

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL/NOAEC
AF for differences in duration of exposure:
6
Justification:
due to subacute study data used
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
for consumer, a default AF of 10 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.97 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
DNEL value:
298 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 980 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Using bioavailability of 100% for the oral and 10% for the dermal route and assuming that rat oral and dermal absorptions are equal to human oral and dermal absorption, thus the corrected dermal NOAEL is 298 * 100/10 = 2980 mg/kg/day based on the oral NOAEL of 298 mg/kg bw/d derived from a subacute study.

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
due to subacute study data used
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
for consumer, a default AF of 10 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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
DNEL value:
298 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
298 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is required.

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
due to subacute study data used
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
for consumer, a default AF of 10 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population