Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
141 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
3 526 mg/m³
Explanation for the modification of the dose descriptor starting point:
see Discussion
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not required
AF for other interspecies differences:
2.5
Justification:
default value for systemic effects
AF for intraspecies differences:
5
Justification:
default value for workers
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
See Discussion
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric value (rat)
AF for other interspecies differences:
2.5
Justification:
default value for systemic effects
AF for intraspecies differences:
5
Justification:
default value for workers
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

The starting point for the derivation of the DNELs is the NOAEL obtained in rat in an oral 13-week repeated toxicity study: NOAEL = 2000 mg/kg bw/d.

When calculating DNELs according to Chapter R.8 of Guidance on Information Requirements and Chemical Safety Assessment (2008) the overall AFs for oral and dermal repeated dose toxicity are 200 (for general population) and 100 (for workers). This is established by taking into account an interspecies factor of 10 (4 for metabolic rate differences × 2.5 for remaining differences), an intraspecies factor of 10 (for general population) and 5 (for workers), and a further factor of 2 to allow for subchronic to chronic extrapolation. The overall AFs for inhalation repeated dose toxicity which should be applied to the corrected NOAECs (2,000 mg/kg bw/day/0.38 m3/kg/day × 6.7 m3/10 m3 for worker and 2,000 mg/kg bw/day/1.15 m3/kg/day for general population) are 25 (for workers) and 50 (for general population) respectively. This is established by taking into account an interspecies factor of 2.5 (for remaining differences), an intraspecies factor of 5 (for workers) and 10 (for general population), and a further factor of 2 to allow for subchronic to chronic extrapolation.

As no hazard was identified for acute toxicity and local effects, no DNELs were calculated.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
34 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 739 mg/m³
Explanation for the modification of the dose descriptor starting point:
See Discussion
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not required
AF for other interspecies differences:
2.5
Justification:
default value for systemic effects
AF for intraspecies differences:
10
Justification:
default value for general population
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
See Discussion
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric value (rat)
AF for other interspecies differences:
2.5
Justification:
default value for systemic effects
AF for intraspecies differences:
10
Justification:
default value for general population
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:
10 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric value (rat)
AF for other interspecies differences:
2.5
Justification:
default value for systemic effects
AF for intraspecies differences:
10
Justification:
default value for general population
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

The starting point for the derivation of the DNELs is the NOAEL obtained in rat in an oral 13-week repeated toxicity study: NOAEL = 2000 mg/kg bw/d.

When calculating DNELs according to Chapter R.8 of Guidance on Information Requirements and Chemical Safety Assessment (2008) the overall AFs for oral and dermal repeated dose toxicity are 200 (for general population) and 100 (for workers). This is established by taking into account an interspecies factor of 10 (4 for metabolic rate differences × 2.5 for remaining differences), an intraspecies factor of 10 (for general population) and 5 (for workers), and a further factor of 2 to allow for subchronic to chronic extrapolation. The overall AFs for inhalation repeated dose toxicity which should be applied to the corrected NOAECs (2,000 mg/kg bw/day/0.38 m3/kg/day × 6.7 m3/10 m3 for worker and 2,000 mg/kg bw/day/1.15 m3/kg/day for general population) are 25 (for workers) and 50 (for general population) respectively. This is established by taking into account an interspecies factor of 2.5 (for remaining differences), an intraspecies factor of 5 (for workers) and 10 (for general population), and a further factor of 2 to allow for subchronic to chronic extrapolation.

As no hazard was identified for acute toxicity and local effects, no DNELs were calculated.