Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance has a low vapour pressure and during use no exposure to aerosols with droplets in the inhalable or respirable range is expected.

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.167 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:
LOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A safety factor of 3 has been used to convert the LOAEL from the oral study to a NOAEL

Route to route extrapolation taking into account that dermal absorption is set at 10%, while oral absorption is set at 50% (in view of the systemic effects on liver and kidney seen in the repeated dose study) leads to the NOAEL of 50 mg/kg bw that is taken as starting point for the calculation of the DNEL.

AF for dose response relationship:
1
Justification:
the safety factor for extrapolation from LOAEL to NOAEL has already been included in the starting NOAEL
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
species tested is the rat
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
worker exposure
AF for the quality of the whole database:
1
Justification:
based on guideline study under GLP
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
65.6 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
90
Dose descriptor:
other: EC3 --> LOAEL
AF for dose response relationship:
3
Justification:
EC3 is considered to be a LOAEL, default factor to extrapolate LOAEL to NOAEL
AF for differences in duration of exposure:
1
Justification:
not applicable
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable
AF for other interspecies differences:
10
Justification:
default
AF for intraspecies differences:
1
Justification:
default
AF for the quality of the whole database:
1
AF for remaining uncertainties:
3
Justification:
effects of the matrix
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

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:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.083 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:
LOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A safety factor of 3 has been used to convert the LOAEL from the oral study to a NOAEL

Route to route extrapolation taking into account that dermal absorption is set at 10%, while oral absorption is set at 50% (in view of the systemic effects on liver and kidney seen in the repeated dose study) leads to the NOAEL of 50 mg/kg bw that is taken as starting point for the calculation of the DNEL.

AF for dose response relationship:
1
Justification:
the safety factor for extrapolation from LOAEL to NOAEL has already been included in the starting NOAEL
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
The species tested is the rat
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
consumer exposure
AF for the quality of the whole database:
1
Justification:
Based on guidelines study under GLP
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
65.6 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
90
Dose descriptor:
other: EC3 --> LOAEL
AF for dose response relationship:
3
Justification:
LOAEL to NOAEL default value
AF for differences in duration of exposure:
1
Justification:
not applicable
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable
AF for other interspecies differences:
10
Justification:
default
AF for intraspecies differences:
1
AF for the quality of the whole database:
1
AF for remaining uncertainties:
3
Justification:
matrix effects
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
other: LD50/NOAEL
Value:
2 000 mg/kg bw/day
AF for interspecies differences (allometric scaling):
4
Justification:
study in rat
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
consumer exposure

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population