Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
64.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
DNEL value:
804 mg/m³
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:
1
Justification:
DNEL is based on an inhalation 1-year study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 354.6 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):
12.5
Modified dose descriptor starting point:
NOAEC
DNEL value:
16 932.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

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:
1.7 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal NOAEL=oral NOAEL*( ABSoral-rat/ABSdermal-human) = (250 mg/kg bw/day)*(1/0.5) = 500 mg/kg bw/day. It is assumed that the dermal absorption rate is 50% of that of the oral absorption (see Toxicokinetics). 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:
6
Justification:
DNEL is based on a 28-day 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
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:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
16 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
400 mg/m³
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:
1
Justification:
DNEL is based on an inhalation 1-year study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 016 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
25 398.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

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:
0.8 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal NOAEL=oral NOAEL*( ABSoral-rat/ABSdermal-human) = (250 mg/kg bw/day)*(1/0.5) = 500 mg/kg bw/day. It is assumed that the dermal absorption rate is 50% of that of the oral absorption (see Toxicokinetics). 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:
6
Justification:
DNEL is based on a 28-day 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
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:
low hazard (no threshold derived)
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:
DNEL (Derived No Effect Level)
Value:
0.4 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
250 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:
6
Justification:
DNEL is based on a 28-day 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
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