Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the inhaled route was determined from a sub-chronic oral study in which the NOAEL was 50 mg/kg bw/day. The following correction was made to the NOAEL (oral): Correction respiratory volume rat (8 hour) 1/0.38 m³/kg bw/day, correction for respiratory volume (worker): 6.7 m³/10 m³. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 50*(1/0.38)*(6.7 m³/10 m³) = 88 mg/m³.

AF for dose response relationship:
1
Justification:
The starting point is the NOAEl which was the low dose. There was a dose response in incidence and severity of effects noted.
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral rat to inhaled human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default (workers)
AF for the quality of the whole database:
1
Justification:
Good quality guideline study
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:
0.5 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:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the dermal route was determined from a sub-chronic oral study in which the NOAEL was 50 mg/kg bw/day. No correction was applied on the dose descriptor starting point.

AF for dose response relationship:
1
Justification:
The starting point is the NOAEC which was the low dose. There was a dose response in incidence and severity of effects noted.
AF for differences in duration of exposure:
2
Justification:
Default from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral rat to dermal human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default (workers)
AF for the quality of the whole database:
1
Justification:
Good quality guideline study
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

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:
0.87 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:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the inhalation route was determined from a sub-chronic oral study in which the NOAEL was 50 mg/kg bw/day. No correction was applied on the dose descriptor starting point.

The following correction was made to the NOAEL (oral): Correction respiratory volume rat (24 hour) 1/1.15 m³/kg bw. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 50*(1/1.15)= 43.5 mg/m³.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral rat to inhalation human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (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:
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:
no hazard identified
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 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:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the oral route was determined from a sub-chronic oral study in which the NOAEL was 50 mg/kg bw/day. No correction was applied on the dose descriptor starting point.

AF for dose response relationship:
1
Justification:
The starting point is the NOAEL which was an intermediate dose. There was a dose response in incidence and severity of effects noted.
AF for differences in duration of exposure:
2
Justification:
Default from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral rat to oral human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Good quality guideline study
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