Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.1 mg/m³
Most sensitive endpoint:
effect on fertility
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Systemic long-term DNEL for dermal contact:

Starting point: NOAEL from reprotox study with 90d exposure duration: NOAEL = 30 mg/kg bw/d.

Correcting of the starting point: correct for difference in absorption between dermal and oral route and for difference between absorption through rat or human skin: corrected NOAEL = oral rat NOAEL * (ABS oral-rat / ABS dermal-human)

-- ABS derm-human = ca. 30% (from in vitro skin absorption study)

-- ABS oral-rat = ca. 90% (from different ADME studies in rats)

Corrected dose descriptor: corrected NOAEL = 30 mg/kg bw/d * (0.90/0.30) = 90 mg/kg bw/d

Assessment factors:

-- Allometric scaling (including "non-calorimetric differences"): 4 * 2,5 (ECHA default)

-- Intra-species differences: 5 (ECHA default for workers)

-- Duration of exposure: 2 (ECHA default for sub-chronic to chronic)

-- Dose-response relationship: 1 (ECHA default)

-- Quality of whole database: 1 (ECHA default)

Overall assessment factor: 100

DNEL: 90 mg/kg bw/d / 100 = 0.9 mg/kg bw/d

Systemic long-term DNEL for inhalation route:

Starting point: NOAEL from reprotox study with 90d exposure duration: NOAEL = 30 mg/kg bw/d.

Correcting of the starting point: convert NOAEL to NOAEC:

NOAEC = [NOAEL / 0.38 m3/kg bw] * [6.7 m3 / 10 m3] = 52.90 mg/m3

Corrected dose descriptor: corrected NOAEC = [NOAEL / 0.38 m3/kg bw] * [6.7 m3/ 10 m3] = 52.90 mg/m3

Assessment factors:

-- Oral-to-inhalation extrapolation: 1 (deviation from ECHA default due to the fact that in the toxicokinetics studies it is shown that oral absorption is high (> 90%) and fast).

-- Allometric scaling (only "non-calorimetric differences"): 2,5 (ECHA default)

-- Intra-species differences: 5 (ECHA default for workers)

-- Duration of exposure: 2 (ECHA default for sub-chronic to chronic)

-- Dose-response relationship: 1 (ECHA default)

-- Quality of whole database: 1 (ECHA default)

Overall assessment factor: 25

DNEL: 52.90 mg/m3 / 25 = 2.1 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/m³
Most sensitive endpoint:
effect on fertility
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.45 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Systemic long-term DNEL for dermal contact:

Starting point: NOAEL from reprotox study with 90d exposure duration: NOAEL = 30 mg/kg bw/d.

Correcting of the starting point: correct for difference in absorption between dermal and oral route and for difference between absorption through rat or human skin: corrected NOAEL = oral rat NOAEL * (ABS oral-rat / ABS dermal-human)

-- ABS derm-human = ca. 30% (from in vitro skin absorption study)

-- ABS oral-rat = ca. 90% (from different ADME studies in rats)

Corrected dose descriptor: corrected NOAEL = 30 mg/kg bw/d * (0.90/0.30) = 90 mg/kg bw/d

Assessment factors:

-- Allometric scaling (including "non-calorimetric differences"): 4 * 2,5 (ECHA default)

-- Intra-species differences: 10 (ECHA default for general population)

-- Duration of exposure: 2 (ECHA default for sub-chronic to chronic)

-- Dose-response relationship: 1 (ECHA default)

-- Quality of whole database: 1 (ECHA default)

Overall assessment factor: 200

DNEL: 90 mg/kg bw/d / 200 = 0.45 mg/kg bw/d

Systemic long-term DNEL for inhalation route:

Starting point: NOAEL from reprotox study with 90d exposure duration: NOAEL = 30 mg/kg bw/d.

Correcting of the starting point: convert NOAEL to NOAEC:

NOAEC = [NOAEL / 1.15 m3/kg bw] = 26.09 mg/m3

Corrected dose descriptor: corrected NOAEC = [NOAEL / 1.15 m3/kg bw] = 26.09 mg/m3

Assessment factors:

-- Oral-to-inhalation extrapolation: 1 (deviation from ECHA default due to the fact that in the toxicokinetics studies it is shown that oral absorption is high (> 90%) and fast)

-- Allometric scaling (only "non-calorimetric differences"): 2,5 (ECHA default)

-- Intra-species differences: 10 (ECHA default for general population)

-- Duration of exposure: 2 (ECHA default for sub-chronic to chronic)

-- Dose-response relationship: 1 (ECHA default)

-- Quality of whole database: 1 (ECHA default)

Overall assessment factor: 50

DNEL: 26.09 mg/m3 / 50 = 0.5 mg/m3

Systemic long-term DNEL for oral route:

Starting point: NOAEL from reprotox study with 90d exposure duration: NOAEL = 30 mg/kg bw/d.

Correcting of the starting point: not required

Assessment factors:

-- Allometric scaling (including "non-calorimetric differences"): 4 * 2,5 (ECHA default)

-- Intra-species differences: 10 (ECHA default for general population)

-- Duration of exposure: 2 (ECHA default for sub-chronic to chronic)

-- Dose-response relationship: 1 (ECHA default)

-- Quality of whole database: 1 (ECHA default)

Overall assessment factor: 200

DNEL: 30 mg/kg bw/d / 200 = 0.150 mg/kg bw/d