Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.46 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):
75
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 234.21 mg/m³
Explanation for the modification of the dose descriptor starting point:

The relevant dose descriptor selected to derive the inhalation DNEL, was the oral rat NOAEL of 1000 mg/kg bw/day derived from an OECD combined repeated dose toxicity study with the reproduction/developmental toxicity screening study. This dose descriptor which is the starting point was corrected for route-to-route extrapolation:

[i.e., NOAEL oral rat ÷ SRvrat x (SRvhuman ÷ WSRvhuman) x (ABSoral-rat/ABSinh-human) x days per week(experimental)/days per week(human population] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’) November (2012); where: NOAELoral rat = 1000 mg/kg bw/d; SRvrat = 0.38 m3/kg bw; SRvhuman = 6.7 m3; WSRvhuman = 10 m3; ABSoral-rat = 50%; ABSinh-human = 100%; days per week(experimental) = 7 days; days per week(human population) = 5 days for workers) = 1000 x 1/0.38 x 6.7/10 x 7/5 x 50/100 = 1234.21 mg/m3]

AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC
AF for other interspecies differences:
2.5
Justification:
Assessment factors for remaining non-metabolic differences
AF for intraspecies differences:
5
Justification:
Assessment factors for workers
AF for the quality of the whole database:
1
Justification:
Good quality study
AF for remaining uncertainties:
1
Justification:
No additional factors are required
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:
23.33 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
7 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The relevant dose descriptor selected to derive the dermal DNEL, was the oral rat NOAEL of 1000 mg/kg bw/day derived from an OECD combined repeated dose toxicity study with the reproduction/Developmental toxicity screening study. This dose descriptor which is the starting point was corrected for route-to-route extrapolation:

[i.e., NOAEL oral rat x (ABSoral-rat/ABSderm-human) x days per week(experimental)/days per week(human population] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’) November (2012); where: NOAELoral rat = 1000 mg/kg bw/d; ABSoral-rat = 50%; ABSderm-human = 10%; days per week(experimental) = 7 days; days per week(human population) = 5 days for workers) = 1000 x 7/5 x 50/10 = 7000 mg/kg bw/day]).

AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human))
AF for other interspecies differences:
2.5
Justification:
Assessment factor for any remaining non-metabolic differences
AF for intraspecies differences:
5
Justification:
Assessment factor for workers
AF for the quality of the whole database:
1
Justification:
Good quality study
AF for remaining uncertainties:
1
Justification:
No additional assessment factors are required
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:
2.9 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
434.78 mg/m³
Explanation for the modification of the dose descriptor starting point:

Therelevant dose descriptor selected to derive the inhalation DNEL, was the oral rat NOAEL of 1000 mg/kg bw/day derived from an OECD combined repeated dose toxicity study with the reproduction/Developmental toxicity screening study. This dose descriptor which is the starting point was corrected for route-to-route extrapolation:

[i.e., NOAEL oral rat ÷ SRvrat x (ABSoral-rat/ABSinh-human)x days per week (experimental)/days per week(human population] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’) November (2012); where: NOAELoral rat = 1000 mg/kg bw/d; SRvrat = 1.15 m3/kg bw; ABSoral-rat = 50%; ABSinh-human = 100%; days per week(experimental) = 7 days; days per week(human population) = 7 days for general population) = 1000 x 1/1.15 x 7/7 x 50/100 = 434.78 mg/m3]

AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Assessment factors for exposure duration (sub-acute to chronic study)
AF for interspecies differences (allometric scaling):
1
Justification:
No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC)
AF for other interspecies differences:
2.5
Justification:
Assessment factors for remaining non-metabolic differences
AF for intraspecies differences:
10
Justification:
Assessment factors for general population
AF for the quality of the whole database:
1
Justification:
Good quality study
AF for remaining uncertainties:
1
Justification:
No additional factors are required
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:
8.33 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The relevant dose descriptor selected to derive the dermal DNEL, was the oral rat NOAEL of 1000 mg/kg bw/day derived from an OECD combined repeated dose toxicity study with the reproduction/Developmental toxicity screening study. This dose descriptor which is the starting point was corrected for route-to-route extrapolation:

[i.e., NOAEL oral rat x (ABSoral-rat/ABSderm-human) x days per week(experimental)/days per week(human population] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’) November (2012); where: NOAELoral rat = 1000 mg/kg bw/d; ABSoral-rat = 50%; ABSderm-human = 10%; days per week(experimental) = 7 days; days per week(human population) = 7 days for general population) = 1000 x 7/5 x 50/10 = 5000 mg/kg bw/day]).

AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Assessment factors for exposure duration (sub-acute to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
AF for other interspecies differences:
2.5
Justification:
Assessment factor for any remaining non-metabolic differences
AF for intraspecies differences:
10
Justification:
Assessment factor for general population
AF for the quality of the whole database:
1
Justification:
Good quality study
AF for remaining uncertainties:
1
Justification:
No additional assessment factors are required
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:
1.67 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):
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:

Not required, as starting point is based on an oral study as well as there is no difference in experimental and the human population exposure conditions.)

AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
(Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
AF for other interspecies differences:
2.5
Justification:
(Assessment factor for any remaining non-metabolic differences
AF for intraspecies differences:
10
Justification:
Assessment factor for general population
AF for the quality of the whole database:
1
Justification:
Good quality study
AF for remaining uncertainties:
1
Justification:
No additional assessment factors are required
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