Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.63 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:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
197.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Oral rat systemic NOAEL of 160 mg/kg bw (Schladt, 2012) served as the starting point for the DNEL derivation. NOAEL was converted into inhalatory NOAEC by using the default respiratory volume for rats (8 h), assuming 50% absorption by oral route and 100% absorption by inhalation route (default procedure in case of oral-to-inhalation extrapolation). The NOAEC is additionally corrected by a factor of 1.4 to account for differences in exposure conditions (5 days/week for workers and 7 days for week for animals in the test).

corrected NOAEC = 160 mg/kg bw/d / 0.38 m3/kg bw * (6.7 m3/d / 10 m3/d) * 1.4 / 2 = 197.5 mg/m3

AF for dose response relationship:
1
Justification:
default, NOAEL is used as starting point
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
already regarded by deriving a corrected NOAEC
AF for other interspecies differences:
2.5
Justification:
default for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
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:
0.747 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:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
224 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed, that the dermal absorption will not be higher than the oral absorption (ECHA's Guidance R.8, v2.1, Nov 2012). Therefore, the NOAEL obtained via the oral route is regarded as a worst-case staring point to determine the dermal DNEL. This NOAEL is corrected by a factor of 1.4 to account for differences in exposure conditions (5 days/week for workers and 7 days for week for animals in the test).

160 mg/kg bw/day * 1.4 = 224 mg/kg bw/day

AF for dose response relationship:
1
Justification:
default, starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

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:
0.464 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:
NOAEC
DNEL value:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
69.57 mg/m³
Explanation for the modification of the dose descriptor starting point:

Oral rat systemic NOAEL of 160 mg/kg bw (Schladt, 2012) served as the starting point for the DNEL derivation. NOAEL was converted into inhalatory NOAEC by using the default respiratory volume for rats (24 h), assuming 50% absorption by oral route and 100% absorption by inhalation route (default procedure in case of oral-to-inhalation extrapolation).

corrected NOAEC = 160 mg/kg bw/d / 1.15 m3/kg bw / 2 = 69.57 mg/m3

AF for dose response relationship:
1
Justification:
default, NOAEL is used as starting point
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
already regarded by deriving a corrected NOAEC
AF for other interspecies differences:
2.5
Justification:
default for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.267 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:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
160 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed, that the dermal absorption will not be higher than the oral absorption (ECHA's Guidance R.8, v2.1, Nov 2012). Therefore, the NOAEL obtained via the oral route is regarded as a worst-case starting point to determine the dermal DNEL.

AF for dose response relationship:
1
Justification:
default, starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.267 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:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
160 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of the starting point required.

AF for dose response relationship:
1
Justification:
default, starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population