Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.02 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:
228 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
201 mg/m³
Explanation for the modification of the dose descriptor starting point:

Exposure via the oral route is considered a more appropriate route of exposure than inhalation as the physical chemical properties such as physical state (liquid at room temperature and pressure) and vapour pressure indicate that exposure via inhalation is unlikely. Thus, testing via the oral route was suitable for classification and risk assessment.

AF for dose response relationship:
1
Justification:
the dose-response relationship is judged reliable
AF for differences in duration of exposure:
1
Justification:
extrapolation from a reproductive study to chronic study exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
accounts for toxicokinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
accounts for extrapolation to humans in the worker environment
AF for the quality of the whole database:
1
Justification:
use of the default assessment factor since the starting point of the DNEL calculation was the NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.08 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
228 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
201 mg/m³
Explanation for the modification of the dose descriptor starting point:

Exposure via the oral route is considered a more appropriate route of exposure than inhalation as the physical chemical properties such as physical state (liquid at room temperature and pressure) and vapour pressure indicate that exposure via inhalation is unlikely. Thus, testing via the oral route was suitable for classification and risk assessment.

AF for dose response relationship:
1
Justification:
the dose response relationship is judged reliable
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
accounts for toxicokinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
accounts for extrapolation to human in the worker environment
AF for the quality of the whole database:
1
Justification:
use of the default assessment factor since the starting point of the DNEL calculation was the NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.05 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor:
NOAEC
Value:
201 mg/m³
AF for dose response relationship:
1
Justification:
the dose response relationship is judged reliable
AF for differences in duration of exposure:
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation
AF for other interspecies differences:
1
Justification:
accounts for toxicokinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
accounts for extrapolation to human in the worker environment
AF for the quality of the whole database:
1
Justification:
use of the default assessment factor since the starting point of the DNEL calculation was the NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor starting point:
NOAEC
Value:
201 mg/m³
AF for dose response relationship:
1
Justification:
the dose response relationship is judged reliable
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation
AF for other interspecies differences:
1
Justification:
accounts for toxicokinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
accounts for extrapolation to human in the worker environment
AF for the quality of the whole database:
1
Justification:
use of the default assessment factor since the starting point of the DNEL calculation was the NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.14 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:
228 mg/kg bw/day
AF for dose response relationship:
1
Justification:
the dose response relationship is judged reliable
AF for differences in duration of exposure:
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure
AF for interspecies differences (allometric scaling):
4
Justification:
account for allometric scaling from rats
AF for other interspecies differences:
2.5
Justification:
accounts for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
accounts for extrapolation to human in the worker environment
AF for the quality of the whole database:
1
Justification:
default assessment factor applied since starting point for DNEL calculation is NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.56 mg/kg bw/day
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
228 mg/kg bw/day
AF for dose response relationship:
1
Justification:
the dose response relationship is judged reliable
AF for interspecies differences (allometric scaling):
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure
AF for other interspecies differences:
2.5
Justification:
accounts for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
accounts for extrapolation to human in the worker environment
AF for the quality of the whole database:
1
Justification:
default assessment factor applied since starting point for DNEL calculation is NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.85 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
80
AF for dose response relationship:
1
Justification:
the dose response relationship is judged reliable
AF for differences in duration of exposure:
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure
AF for interspecies differences (allometric scaling):
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure
AF for other interspecies differences:
1
Justification:
accounts for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
accounts for extrapolation to human in the worker environment
AF for the quality of the whole database:
1
Justification:
default assessment factor applied since starting point for DNEL calculation is NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.4 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
AF for dose response relationship:
1
Justification:
the dose response relationship is judged reliable
AF for interspecies differences (allometric scaling):
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure
AF for other interspecies differences:
1
Justification:
accounts for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
accounts for extrapolation to human in the worker environment
AF for the quality of the whole database:
1
Justification:
default assessment factor applied since starting point for DNEL calculation is NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

To reduce the potential for skin and/or eye irritation, workers should wear personal protective equipment (impervious gloves, eye protection for example) appropriate for the tasks they will perform.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.99 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):
100
Dose descriptor starting point:
NOAEL
Value:
228 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
99.13 mg/m³
Explanation for the modification of the dose descriptor starting point:

Exposure via the oral route is considered a more appropriate route of exposure than inhalation as the physical chemical properties such as physical state (liquid at room temperature and pressure) and vapour pressure indicate exposure via inhalation is unlikely. Therefore, testing via the oral route was suitable for classification and risk assessment.

AF for dose response relationship:
1
Justification:
dose-response relationship is judged reliable
AF for differences in duration of exposure:
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure duration
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation exposures
AF for other interspecies differences:
2.5
Justification:
toxicokinetic and toxicodynamic remaining differences
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to human general population
AF for the quality of the whole database:
1
Justification:
default assessment factor when NOAEL is used as starting point for DNEL calculation
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.97 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:
228 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
99.13 mg/m³
Explanation for the modification of the dose descriptor starting point:

Exposure via the oral route is considered a more appropriate route of exposure than inhalation as the physical chemical properties such as physical state (liquid at room temperature and pressure) and vapour pressure indicate exposure via inhalation is unlikely. Therefore, testing via the oral route was suitable for classification and risk assessment.

AF for dose response relationship:
1
Justification:
dose-response relationship is judged reliable
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation exposures
AF for other interspecies differences:
2.5
Justification:
toxicokinetic and toxicodynamic remaining differences
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to human general population
AF for the quality of the whole database:
1
Justification:
default assessment factor when NOAEL is used as starting point for DNEL calculation
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.48 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Dose descriptor:
NOAEC
Value:
99.13 mg/m³
AF for dose response relationship:
1
Justification:
dose-response relationship is judged reliable
AF for differences in duration of exposure:
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure duration
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation exposures
AF for other interspecies differences:
1
Justification:
toxicokinetic and toxicodynamic remaining differences
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to human general population
AF for the quality of the whole database:
1
Justification:
default assessment factor when NOAEL is used as starting point for DNEL calculation
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.91 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEC
Value:
99.13 mg/m³
AF for dose response relationship:
1
Justification:
dose-response relationship is judged reliable
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation exposures
AF for other interspecies differences:
1
Justification:
toxicokinetic and toxicodynamic remaining differences
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to human general population
AF for the quality of the whole database:
1
Justification:
default assessment factor when NOAEL is used as starting point for DNEL calculation
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.57 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):
400
Dose descriptor starting point:
NOAEL
Value:
228 mg/kg bw/day
AF for dose response relationship:
1
Justification:
dose response relationship is judged reliable
AF for differences in duration of exposure:
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure
AF for interspecies differences (allometric scaling):
4
Justification:
accounts for allometric scaling from rats
AF for other interspecies differences:
2.5
Justification:
toxicokinetic and toxicodynamic remaining differences
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to general human population
AF for the quality of the whole database:
1
Justification:
default assessment factor if starting point of DNEL calculation is NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Value:
2.28 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
AF for dose response relationship:
1
Justification:
dose response relationship is judged reliable
AF for interspecies differences (allometric scaling):
4
Justification:
accounts for allometric scaling from rats
AF for other interspecies differences:
2.5
Justification:
toxicokinetic and toxicodynamic remaining differences
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to general human population
AF for the quality of the whole database:
1
Justification:
default assessment factor if starting point of DNEL calculation is NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.43 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
160
AF for dose response relationship:
1
Justification:
dose response relationship is judged reliable
AF for differences in duration of exposure:
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure
AF for interspecies differences (allometric scaling):
4
Justification:
accounts for allometric scaling from rats
AF for other interspecies differences:
1
Justification:
toxicokinetic and toxicodynamic remaining differences
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to general human population
AF for the quality of the whole database:
1
Justification:
default assessment factor if starting point of DNEL calculation is NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.7 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
AF for dose response relationship:
1
Justification:
dose response relationship is judged reliable
AF for interspecies differences (allometric scaling):
4
Justification:
accounts for allometric scaling from rats
AF for other interspecies differences:
1
Justification:
toxicokinetic and toxicodynamic remaining differences
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to general human population
AF for the quality of the whole database:
1
Justification:
default assessment factor if starting point of DNEL calculation is NOAEL
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.57 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):
400
Dose descriptor starting point:
NOAEL
Value:
228 mg/kg bw/day
AF for dose response relationship:
1
Justification:
dose response relationship is judged reliable
AF for differences in duration of exposure:
4
Justification:
extrapolation from reproductive/developmental study to chronic study exposure
AF for interspecies differences (allometric scaling):
4
Justification:
accounts for allometric scaling from rat
AF for other interspecies differences:
2.5
Justification:
toxicokinetic and toxicodynamic remaining differences accounted for here
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to the human general population
AF for the quality of the whole database:
1
Justification:
default assessment factor when DNEL is calculated using NOAEL as starting point
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.28 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
100
AF for dose response relationship:
1
Justification:
dose response relationship is judged reliable
AF for interspecies differences (allometric scaling):
4
Justification:
accounts for allometric scaling from rat
AF for other interspecies differences:
2.5
Justification:
toxicokinetic and toxicodynamic remaining differences accounted for here
AF for intraspecies differences:
10
Justification:
accounts for extrapolation to the human general population
AF for the quality of the whole database:
1
Justification:
default assessment factor when DNEL is calculated using NOAEL as starting point
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties exist

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

No additional information for the general population.