Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.303 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
4.33 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
3.79 mg/m³
Explanation for the modification of the dose descriptor starting point:

In the absence of a suitable repeated dose inhalation toxicity studies, the dose descriptor starting point was derived from the most stringent NOAEL obtained in the available, fully reliable oral repeated dose toxicity studies in accordance with ECHA guidance R.8.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
A chronic NOAEL is used.
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
5
Justification:
Default value.
AF for the quality of the whole database:
1
Justification:
Data from fully reliable studies are used.
AF for remaining uncertainties:
1
Justification:
Remaining uncertainty is low.
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:
3.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A fully reliable 28-day dermal repeated dose toxicity study is available, which provided a NOAEL of 1000 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
5
Justification:
Default value.
AF for the quality of the whole database:
1
Justification:
A fully reliable study is available.
AF for remaining uncertainties:
1
Justification:
The remaining uncertainty is low.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

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:
0.075 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):
25
Dose descriptor starting point:
NOAEL
Value:
4.33 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1.88 mg/m³
Explanation for the modification of the dose descriptor starting point:

In the absence of a suitable repeated dose inhalation toxicity studies, the dose descriptor starting point was derived from the most stringent NOAEL obtained in the available, fully reliable oral repeated dose toxicity studies in accordance with ECHA guidance R.8.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
A chronic NOAEL is used.
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling of inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
10
Justification:
Default value.
AF for the quality of the whole database:
1
Justification:
Data from fully reliable studies are used.
AF for remaining uncertainties:
1
Justification:
The remaining uncertainty is low.
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:
1.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A fully reliable 28-day dermal repeated dose toxicity study is available, which provided a NOAEL of 1000 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
10
Justification:
Default value.
AF for the quality of the whole database:
1
Justification:
A fully reliable study is available.
AF for remaining uncertainties:
1
Justification:
The remaining uncertainty is low.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.043 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):
100
Dose descriptor starting point:
NOAEL
Value:
4.33 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
4.33 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The starting point is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
A chronic NOAEL is used.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
10
Justification:
Default value.
AF for the quality of the whole database:
1
Justification:
Fully reliable data on oral repeated dose toxicity are available.
AF for remaining uncertainties:
1
Justification:
The remaining uncertainty is low.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population