Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.882 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:
12.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
22.04 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation as the oral route is the only one available: oral NOAEL rat males (90 days) = 12.5 mg/kg/day. Then extrapolated NOEC by inhalation is calculated assuming that inhalation absorption is 100% and oral absorption is 100% : NOAEC = (12.5/0.38) *(6.7/10) = 22.04 mg/m3.

AF for dose response relationship:
1
Justification:
Default value REACH guidance
AF for differences in duration of exposure:
2
Justification:
Default value REACH guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not used for inhalation route (REACH guidance)
AF for other interspecies differences:
2.5
Justification:
Default value REACH guidance
AF for intraspecies differences:
5
Justification:
Default value REACH guidance
AF for the quality of the whole database:
1
Justification:
The overall database is of a moderate quality, however, the selection of a NOAEL of 12.5 mg/kg bw from a 90 days toxicity study is considered to be a worst case scenario, taking into account this uncertainties.
AF for remaining uncertainties:
1
Justification:
Default value REACh guidance
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 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
Dose descriptor starting point:
NOAEL
Value:
12.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation needed as the oral route is the only one available: oral NOAEL rat (90 days) = 12.5 mg/kg/day.

The starting point is modified assuming a dermal absorption of 50% and an oral absorption of 100%: 12.5*(100%/50%) = 25 mg/kg/day.

AF for dose response relationship:
1
Justification:
Default value REACH guidance
AF for differences in duration of exposure:
2
Justification:
Default value REACH guidance
AF for interspecies differences (allometric scaling):
4
Justification:
Default value REACH guidance
AF for other interspecies differences:
2.5
Justification:
Default value REACH guidance
AF for intraspecies differences:
5
Justification:
Default value REACH guidance
AF for the quality of the whole database:
1
Justification:
The overall database is of a moderate quality, however, the selection of a NOAEL of 12.5 mg/kg bw from a 90 days toxicity study is considered to be a worst case scenario, taking into account this uncertainty.
AF for remaining uncertainties:
1
Justification:
Default value REACH guidance
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 is classified acute toxicity dermal cat. 4. The danger is considered as a low hazard, therefore, only a qualitative assessment is necessary.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

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:
0.22 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:
12.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
10.87 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation as the oral route is the only one available: oral NOAEL rat males (90 days) = 12.5 mg/kg/day. Then extrapolated NOEC by inhalation is calculated assuming that inhalation absorption is 100% and oral absorption is 100% : NOAEC = (12.5/1.15) *(100%/100%) = 22.04 mg/m3.

AF for dose response relationship:
1
Justification:
Default value REACH guidance
AF for differences in duration of exposure:
2
Justification:
Default value REACH guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Default value REACH guidance
AF for other interspecies differences:
2.5
Justification:
Default value REACH guidance
AF for intraspecies differences:
10
Justification:
Default value REACH guidance
AF for the quality of the whole database:
1
Justification:
The overall database is of a moderate quality, however, the selection of a NOAEL of 12.5 mg/kg bw from a 90 days toxicity study is considered to be a worst case scenario, taking into account this uncertainty.
AF for remaining uncertainties:
1
Justification:
REACH guidance
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:
0.125 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:
12.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation as the oral route is the only one available: oral NOAEL rat males (90 days) = 12.5 mg/kg/day.

Then extrapolated NOEL by dermal route is calculated assuming a dermal absorption of 50% and an oral absorption of 100%: NOAEL = 12.5*(100%/50%) = 25 mg/kg/day

AF for dose response relationship:
1
Justification:
Default value REACH guidance
AF for differences in duration of exposure:
2
Justification:
Default value REACH guidance
AF for interspecies differences (allometric scaling):
4
Justification:
Default value REACH guidance
AF for other interspecies differences:
2.5
Justification:
Default value REACH guidance
AF for intraspecies differences:
10
Justification:
Default value REACH guidance
AF for the quality of the whole database:
1
Justification:
The overall database is of a moderate quality, however, the selection of a NOAEL of 12.5 mg/kg bw from a 90 days toxicity study is considered to be a worst case scenario, taking into account this uncertainty.
AF for remaining uncertainties:
1
Justification:
Reach guidance
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:

Category 4

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.062 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):
40
Dose descriptor starting point:
NOAEL
Value:
12.5 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is NOAEL (ECETOC TRA 110)
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic (ECETOC TRA 110)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factors when the species is rats (ECETOC TRA 110)
AF for other interspecies differences:
2.5
Justification:
ECETOC report 110
AF for intraspecies differences:
10
Justification:
Default factor of 5 for general public (ECETOC report 110)
AF for the quality of the whole database:
1
Justification:
Reach guidance
AF for remaining uncertainties:
1
Justification:
Reach guidance
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population