Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.035 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:
NOAEC
DNEL value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
2.64 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point: NOAEL oral 28 day = 3 mg/kg bw/daCorrected inhalatory NOAEC = NOAEL * 1/0.38 m3/kg bw d * ABSoral rat/ABSinh human * 6.7 m3/ 10 m3 = 5.28 mg/m3 * ABSoral rat / ABSinh human "Assumed absorption via inhalation is twice absorption via oral" = 2.64 mg / m3.

AF for dose response relationship:
1
Justification:
default factor for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Taken into account in the route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
remaining interspecies differences
AF for intraspecies differences:
5
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
default factor for good quality of the database, taking into account completeness, consistency and the standard information requirements
AF for remaining uncertainties:
1
Justification:
No indication for remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEC
DNEL value:
600 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
600 mg/m³
AF for dose response relationship:
1
Justification:
NOAEC
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling rat
AF for other interspecies differences:
2.5
Justification:
remaining interspecies differences
AF for intraspecies differences:
5
Justification:
workers population
AF for the quality of the whole database:
1
Justification:
default factor for good quality of the database, taking into account completeness, consistency and the standard information requirements
AF for remaining uncertainties:
2
Justification:
Limited number of endpoints have been examined in the acute toxicity study: only mortality

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 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:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Oral route to dermal route extrapolation was performed.
AF for dose response relationship:
1
Justification:
default factor for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
remaining interspecies differences
AF for intraspecies differences:
5
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
default factor for good quality of the database, taking into account completeness, consistency and the standard information requirements
AF for remaining uncertainties:
1
Justification:
no indication for remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.11 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
LOAEL
DNEL value:
316 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The LD50 in that study was determined at 756 mg/kg bw, the LOAEL 316 mg/kg bw. The LOAEL was selected as startpoint.

AF for dose response relationship:
3
Justification:
LOEAL used as dose descriptor
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
remaining interspecies differences
AF for intraspecies differences:
5
Justification:
default AF for workers
AF for the quality of the whole database:
1
Justification:
default factor for good quality of the database, taking into account completeness, consistency and the standard information requirements
AF for remaining uncertainties:
1
Justification:
No indication for remaining uncertainties

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.009 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:
NOAEC
DNEL value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
1.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
Dose descriptor starting point: NOAEL oral 28 day = 3 mg/kg bw/day. Corrected inhalatory NOAEC = NOAEL * 1/1.15 m3/kg bw d * ABSoral rat/ABSinh human = 2.61 mg/m3 * ABSoral rat / ABSinh human "Assumed absorption via inhalation is twice absorption via oral" = 1.30 mg / m3
AF for dose response relationship:
1
Justification:
default factor for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Taken into account in the route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
default factor for the general population
AF for the quality of the whole database:
1
Justification:
default factor for good quality of the database, taking into account completeness, consistency and the standard information requirements
AF for remaining uncertainties:
1
Justification:
no indication for remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Modified dose descriptor starting point:
NOAEC
DNEL value:
600 mg/m³
AF for dose response relationship:
1
Justification:
NOAEC
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
default AF for the general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
Justification:
Limited number of endpoints have been examined in the acute toxicity study: only mortality

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.005 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:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Oral route to dermal route extrapolation
AF for dose response relationship:
1
Justification:
default factor for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
default factor for the general population
AF for the quality of the whole database:
1
Justification:
default factor for good quality of the database, taking into account completeness, consistency and the standard information requirements
AF for remaining uncertainties:
1
Justification:
no indication for remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.05 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
LOAEL
DNEL value:
316 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The LD50 in that study was determined at 756 mg/kg bw, the LOAEL 316 mg/kg bw. The LOAEL was selected as startpoint.

AF for dose response relationship:
3
Justification:
LOAEL was used as dose descriptor
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
remaining interspecies differences
AF for intraspecies differences:
10
Justification:
default AF for general population
AF for the quality of the whole database:
1
Justification:
default factor for good quality of the database, taking into account completeness, consistency and the standard information requirements
AF for remaining uncertainties:
1

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
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:
0.005 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:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation
AF for dose response relationship:
1
Justification:
default AF for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
remaining interspecies differences
AF for intraspecies differences:
10
Justification:
default AF for general population
AF for the quality of the whole database:
1
Justification:
default AF for good quality of the database, taking into account completeness, consistency and the standard information requirements
AF for remaining uncertainties:
1
Justification:
no indication for remaining differences
Acute/short 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL (from repeated dose study, consequently conservative value)
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
default AF for general population
AF for the quality of the whole database:
1
Justification:
default AF for good quality of the database, taking into account completeness, consistency and the standard information requirements. 2 acute and 3 repeated dose toxicity tests were evaluated
AF for remaining uncertainties:
1
Justification:
Sublethal endpoints were taken into consideration

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population