Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.82 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:
other: NOAEL
DNEL value:
61.71 mg/m³
Explanation for the modification of the dose descriptor starting point:
Assuming 50% absorption for oral-rat and 100% for inhalation-human. The oral NOAEL of 70 mg/kg bw/d (dosing regime: 5 days/week) is concerted to a NOAEL by dividing by 0.38 and by multiplying by 0.67 according to ECHA Guidance.
AF for dose response relationship:
1
Justification:
corrected NOAEL of 61.71 mg/m3 is used as a starting point.
AF for differences in duration of exposure:
6
Justification:
based on an oral 28 days study (subacute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
default as 1 since no allometric scaling needed for oral to inhalation.
AF for other interspecies differences:
2.5
Justification:
no substance specific data are available.
AF for intraspecies differences:
5
Justification:
for workers the default factor of 5 is used.
AF for the quality of the whole database:
1
Justification:
available data of the substance fulfilling scientic princle is used.
AF for remaining uncertainties:
1
Justification:
no further uncertainities to be taken into account.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.82 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
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:
0.23 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
DNEL value:
70 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assuming 100% absorption for both routes (oral and dermal) in both species (rat and human).
AF for dose response relationship:
1
Justification:
NOAEL is used as a starting point
AF for differences in duration of exposure:
6
Justification:
based on an oral 28 days study (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
rat was used in the test.
AF for other interspecies differences:
2.5
Justification:
no substance specific data are avaiable.
AF for intraspecies differences:
5
Justification:
for workers the default factor of 5 is used.
AF for the quality of the whole database:
1
Justification:
available data of the substance fulfilling scientic princle is used.
AF for remaining uncertainties:
1
Justification:
no further uncertainties to be taken into account.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.23 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
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:
low 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:
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:
other: NOEAL
DNEL value:
21.93 mg/m³
Explanation for the modification of the dose descriptor starting point:
Assuming 50% absorption for oral-rat and 100% for inhalation-human. The oral NOAEL of 50 mg/kg bw/d (dosing regime: 7 days/week) is concerted to a NOAEL by dividing by 1.14 (24h) according to ECHA Guidance.
AF for dose response relationship:
1
Justification:
NOAEL is used as a starting point.
AF for differences in duration of exposure:
6
Justification:
based on an oral 28 days study (subacute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
default as 1 since no allometric scaling needed for oral to inhalation.
AF for other interspecies differences:
2.5
Justification:
no substance specific data are available.
AF for intraspecies differences:
10
Justification:
for general population the default factor of 10 is used.
AF for the quality of the whole database:
1
Justification:
available data of the substance fulfilling scientic princle is used.
AF for remaining uncertainties:
1
Justification:
no further uncertainties to be taken into account.
Acute/short 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

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:
0.08 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
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assuming 100% absorption for both route in both species, the oral NOAEL of 50 mg/kg bw/d (dosing regime: 7 days/week) is concerted to a NOAEL by dividing by 0.38 according to ECHA Guidance.
AF for dose response relationship:
1
Justification:
NOAEL is used as a starting point.
AF for differences in duration of exposure:
6
Justification:
based on an oral 28 days study (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
rat was used in the test.
AF for other interspecies differences:
2.5
Justification:
no substance specific data are available.
AF for intraspecies differences:
10
Justification:
For general population the default factor of 10 is used.
AF for the quality of the whole database:
1
Justification:
available data of the substance fulfilling scientic princle is used.
AF for remaining uncertainties:
1
Justification:
no further uncertainties to be taken into account.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
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:
0.08 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
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route-to-route extrapolation
AF for dose response relationship:
1
Justification:
NOAEL is used as a starting point.
AF for differences in duration of exposure:
6
Justification:
based on an oral 28 days study (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
rat was used in the test.
AF for other interspecies differences:
2.5
Justification:
no substance specific data are available-
AF for intraspecies differences:
10
Justification:
for general population the default factor of 5 is used.
AF for the quality of the whole database:
1
Justification:
availabe data of the substance fulfilling scientic princle is used.
AF for remaining uncertainties:
1
Justification:
no further uncertainties to be taken into account.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population