Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.2 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:
36 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
635 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalative study available, according to Guidance on information requirements and chemical safety assessment Chapter R.8 route-to-route extrapolation is possible.
AF for dose response relationship:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for differences in duration of exposure:
3
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6, an initial AF of 6 is chosen based on the study used for deriving the starting point.
As a chronic study is available as well, indicating no increased severity, the AF is lowered to 3.
AF for interspecies differences (allometric scaling):
4
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-3
AF for other interspecies differences:
2.5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for intraspecies differences:
5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for the quality of the whole database:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for remaining uncertainties:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.24 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):
150
Dose descriptor starting point:
NOAEL
Value:
36 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
36 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No long-term dermal exposure study available, according to Guidance on information requirements and chemical safety assessment Chapter R.8 route-to-route extrapolation is possible. The dermal absorption is not expected to be higher than oral absorption, therefore no AF for route-to-route Extrapolation is needed.
AF for dose response relationship:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for differences in duration of exposure:
3
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6, an initial AF of 6 is chosen based on the study used for deriving the starting point.
As a chronic study is available as well, indicating no increased severity, the AF is lowered to 3.
AF for interspecies differences (allometric scaling):
4
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-3
AF for other interspecies differences:
2.5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for intraspecies differences:
5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for the quality of the whole database:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for remaining uncertainties:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

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:
2.1 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):
300
Dose descriptor starting point:
NOAEL
Value:
36 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
635 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalative study available, according to Guidance on information requirements and chemical safety assessment Chapter R.8 route-to-route extrapolation is possible.
AF for dose response relationship:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for differences in duration of exposure:
3
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6, an initial AF of 6 is chosen based on the study used for deriving the starting point.
As a chronic study is available as well, indicating no increased severity, the AF is lowered to 3.
AF for interspecies differences (allometric scaling):
4
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-3
AF for other interspecies differences:
2.5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for intraspecies differences:
10
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for the quality of the whole database:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for remaining uncertainties:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 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:
36 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
36 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No long-term dermal exposure study available, according to Guidance on information requirements and chemical safety assessment Chapter R.8 route-to-route extrapolation is possible. The dermal absorption is not expected to be higher than oral absorption, therefore no AF for route-to-route Extrapolation is needed.
AF for dose response relationship:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for differences in duration of exposure:
3
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6, an initial AF of 6 is chosen based on the study used for deriving the starting point.
As a chronic study is available as well, indicating no increased severity, the AF is lowered to 3.
AF for interspecies differences (allometric scaling):
4
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-3
AF for other interspecies differences:
2.5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for intraspecies differences:
10
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for the quality of the whole database:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for remaining uncertainties:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 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):
30
Dose descriptor starting point:
NOAEL
Value:
36 mg/kg bw/day
AF for dose response relationship:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for differences in duration of exposure:
3
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6, an initial AF of 6 is chosen based on the study used for deriving the starting point.
As a chronic study is available as well, indicating no increased severity, the AF is lowered to 3.
AF for interspecies differences (allometric scaling):
4
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-3
AF for other interspecies differences:
2.5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for intraspecies differences:
10
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for the quality of the whole database:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
AF for remaining uncertainties:
1
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8: Table R.8-6
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population