Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11 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
DNEL value:
1 000 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
881.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
Worker Population - NOAEL of 1000 mg/kg/d/0.38 m³/kg = 2631.6 * [6.7 m³/10 m³] * [50/100] = 881.6 mg/m³ ; for derivation of the dose descriptor starting point a factor of 2 has been included for route-to-route extrapolation from oral to inhalative
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF=1.
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences
AF for intraspecies differences:
5
Justification:
For intraspecies differences the default factor is 5 for workers
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF=1. Higher factors may be applied based on scientific judgement related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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:
3.33 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
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal risk assessment is based on the oral NOAEL of 1000 mg/kg/day from a subacute toxicity test. The worst case (100% absorption) was assumed.
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF=1.
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
The allometric scaling factor for the rat
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences
AF for intraspecies differences:
5
Justification:
For intraspecies differences the default factor is 5 for workers
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF=1. Higher factors may be applied based on scientific judgement related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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:
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
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
434.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
General Population - NOAEL of 1000 mg/kg/d / 1.15 m³/kg * [50/100]= 434.8 mg/m³; for derivation of the dose descriptor starting point a factor of 2 has been included for route-to-route extrapolation from oral to inhalative
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF=1.
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences
AF for intraspecies differences:
10
Justification:
For intraspecies differences the default factor is 10 for consumers
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF=1. Higher factors may be applied based on scientific judgement related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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:
1.7 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
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal risk assessment is based on the oral NOAEL of 1000 mg/kg/day from a subacute toxicity test. The worst case (100% absorption) was assumed.
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF=1.
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
The allometic scaling factor for the rat.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences
AF for intraspecies differences:
10
Justification:
For intraspecies differences the default factor is 10 for consumers
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF=1. Higher factors may be applied based on scientific judgement related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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
DNEL value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF=1.
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
The allometic scaling factor for the rat.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences
AF for intraspecies differences:
10
Justification:
For intraspecies differences the default factor is 10 for consumers
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF=1. Higher factors may be applied based on scientific judgement related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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