Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70.52 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 763.16 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr=NOAELoral*(1/0.38 m³/kg/d)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 1000 mg/kg/d*(1/0.38 m³/kg/d)*(1/1)*0.67 = 1763.16 mg/m³. ABSoral-rat=oral absorption rate in rats, ABSinh-human=inhalation absorption rate in humans.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on an oral subchronic (90-day) toxicity study
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling already included in ECHA starting point derivation method
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
for workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 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:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal NOAEL=NOAELoral*(ABSoral-rat/ABSdermal-human) = (1000 mg/kg bw/day)*(1/0.5) = 2000 mg/kg bw/day. Although the physicochemical properties (high molecular weight in combination with high log Pow and low water solubility) of the test substance do not suggest a significant absorption through the skin, the dermal absorption is assumed to be 50% compared to the oral route (factor: 1/0.5) in a worst-case approach and is considered as sufficiently conservative for hazard assessment. ABSoral-rat=oral absorption rate in rats, ABSdermal-human=dermal absorption rate in humans.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on an oral subchronic (90-day) toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
DNEL is based on a study in rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
for workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

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
Most sensitive endpoint:
skin irritation/corrosion

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:
17.39 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
869.56 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr=NOAELoral*(1/1.15 m³/kg/d)*(ABSoral-rat/ABSinh-human) = 1000 mg/kg/d*(1/1.15 m³/kg/d)*(1/1) = 869.56 mg/m³. ABSoral-rat=oral absorption rate in rats, ABSinh-human=inhalation absorption rate in humans
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on an oral 90-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling already included in ECHA starting point derivation method; no further factor required.
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
for general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal NOAEL=NOAELoral*(ABSoral-rat/ABSdermal-human) = (1000 mg/kg bw/day)*(1/0.5) = 2000 mg/kg bw/day. Although the physicochemical properties (high molecular weight in combination with high log Pow and low water solubility) of the test substance do not suggest a significant absorption through the skin, the dermal absorption is assumed to be 50% compared to the oral route (factor: 1/0.5) in a worst-case approach and is considered as sufficiently conservative for hazard assessment. ABSoral-rat=oral absorption rate in rats, ABSdermal-human=dermal absorption rate in humans.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on an oral subchronic (90-day) toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
DNEL is based on a study in rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
for general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

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
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on an oral subchronic (90-day) toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
DNEL is based on a study in rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
for general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population