Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.176 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):
75
Dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
13.22 mg/m³
Explanation for the modification of the dose descriptor starting point:

Inhalatory NOAEC= 15 mg/kg bw/day*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.) =13.22 mg/m3

Differences in absorption Abs (oral-rat) / Abs (inhalation-human): 0.5  

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not used for inhalation
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Local 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:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.05 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:
NOAEL
DNEL value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL=15 mg/kg bw/day* (ABSoral/ABSdermal) = 15 mg/kg bw/day                                                                                                                                                     Differences in absorption Abs (oral-rat) / Abs (dermal-human): 1

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
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
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high 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:
DNEL (Derived No Effect Level)
Value:
0.043 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):
150
Dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
6.52 mg/m³
Explanation for the modification of the dose descriptor starting point:

Inhalation NOAEC = 15 mg/kg bw/day * (1/1.15m3/kg/d) * 0.5 = 6.52 mg/m3

Differences in absorption Abs (oral-rat) / Abs (inhalation-human): 0.5  

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not used for inhalation
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Local 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:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.025 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:
NOAEL
DNEL value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL=15 mg/kg bw/day*( ABSoral/ABSdermal) = 15 mg/kg bw/day                                                                                                                                            

Differences in absorption Abs (oral-rat) / Abs (dermal-human): 1                                                                                                                                                                      

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
4
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
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
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:
0.025 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:
NOAEL
DNEL value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
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
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population