Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.88 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
18
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected inhalatory NOAEC = oral NOAEL (50 mg/kg bw/d) * 1/0.38 m3/kg/d * (ABS oral, rat/ABS inh,human = 100/100) * 6.7 m3/10 m3= 88 mg/m3.    

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Assuming chronic worker exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Included in the modification of the dose descriptor starting point.
AF for other interspecies differences:
1
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable study used
AF for remaining uncertainties:
1
Justification:
No reaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.69 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
72
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Corrected dermal NOAEL = oral NOAEL * ABSoral-rat/ABSderm-human = 50 * 100/100 = 50 mg/kg bw

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Assuming chronic worker exposure
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
3
AF for the quality of the whole database:
1
Justification:
Reliable study used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.17 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
3
Dose descriptor starting point:
other: 12.5 mg/cm2 (NOAEL)
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
Justification:
Local effect
AF for other interspecies differences:
1
Justification:
No other differences
AF for intraspecies differences:
3
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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:
1.45 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
30
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
43.55 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected inhalatory NOAEC = oral NOAEL (50 mg/kg bw/d) * 1/1.15 m3/kg/d * (ABS oral, rat/ABS inh,human = 100/100) =  43.5 mg/m3.

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:
Included in the modification of the dose descriptor starting point
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
Difference in sensitivity witin general population
AF for the quality of the whole database:
1
Justification:
Reliable study used.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
120
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Corrected dermal NOAEL = oral NOAEL * ABSoral-rat/ABSderm-human = 50 * 100/100 = 50 mg/kg bw

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: NOAEL of 12.5 mg/cm2
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
Justification:
Local effect
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
120
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification needed, oral study was used.

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):
4
AF for other interspecies differences:
1
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
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population