Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.6 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:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
441 mg/m³
Explanation for the modification of the dose descriptor starting point:

As a worst case the DNEL for systemic effects via the inhalation route is determined on the basis of route-to-route extrapolation from the oral NOAEL of 250 mg/kg bw/day. The following correction was made to the NOAEL(oral) to derive the NOAEC(inhalation): Correction for respiratory rate and volume (rat to human worker): (6.7 m³/d/10 m³/d)*(1/0.38 m³/kg) (default). Therefore, the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: [250 mg/kg/day*(6.7 m³/d /10 m³/d)*(1/0.38 m³/kg)] = 441 mg/m³.

AF for dose response relationship:
1
Justification:
A clear NOAEL has been determined.
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Default for inhalation route
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
The available studies were conducted according to relevant OECD test guidelines and in compliance with GLP.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
2.5 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):
100
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No correction to the NOAEL is required.

AF for dose response relationship:
1
Justification:
A clear NOAEL has been determined.
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for oral rat to dermal human extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
The available studies were conducted according to relevant OECD test guidelines and in compliance with GLP
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

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:
4.3 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):
50
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
217.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEL(oral) to derive the NOAEC(inhalation): Correction for respiratory rate and volume (rat to human consumer): (1/1.15) (default) Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: [250 mg/kg/day*(1/1.15 m³/kg)] = 217.4 mg/m³.

AF for dose response relationship:
1
Justification:
A clear NOAEL was established.
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Default for inhalation route
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
The available studies were conducted in accordance with appropriate OECD test guidelines and in compliance with GLP.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
1.25 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):
200
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No correction to the NOAEL is required.

AF for dose response relationship:
1
Justification:
A clear NOAEL was established.
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default for oral rat to dermal human extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
The available studies were conducted in accordance with appropriate OECD test guidelines and in compliance with GLP.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
1.25 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):
200
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No correction to the NOAEL is required.

AF for dose response relationship:
1
Justification:
A clear NOAEL was established.
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default for rat oral to human oral route of exposure
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
The available studies were conducted according to appropriate OECD test guidelines and in compliance with GLP.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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