Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 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:
100 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:

100 x 1/0.38 x 6.7/10 x 0.5 [50% oral absorption rat / 100% inhalation absorption human]

AF for dose response relationship:
1
Justification:
A clear NOAEL was derived
AF for differences in duration of exposure:
6
Justification:
default - subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
differences between rats and humans already taken into account when modifying the starting point
AF for other interspecies differences:
2.5
Justification:
default - any remaining difference
AF for intraspecies differences:
5
Justification:
default - workers
AF for the quality of the whole database:
1
Justification:
database complete for the tonnage band
AF for remaining uncertainties:
1
Justification:
DNEL based on experimental data on the substance. No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 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
Dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

100 x 2 [oral absorption rat 50%/dermal absorption human 25%]

AF for dose response relationship:
1
Justification:
A clear NOAEL was derived
AF for differences in duration of exposure:
6
Justification:
default - subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default - rat
AF for other interspecies differences:
2.5
Justification:
default - any remaining difference
AF for intraspecies differences:
5
Justification:
default - workers
AF for the quality of the whole database:
1
Justification:
database complete for the tonnage band
AF for remaining uncertainties:
1
Justification:
DNEL based on experimental data on the substance. There were no remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

The registered substance was not acutely toxic via the oral route of exposure, was demonstrated to to be non-genotoxic in a battery of genotoxicity studies appropriate to the tonnage, not developmentally toxic or toxic for reproduction in a reproductive screening study, and to possess a NOAEL of 100 mg/kg bw/day in a 28 day repeat dose toxicity study. This was the most critical NOAEL for deriving the risk assessment.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

100 x 1/1.15 x 0.5 [oral abosrption rat 50%/inhalation absorption human 100%]

AF for dose response relationship:
1
Justification:
A clear NOAEL was derived
AF for differences in duration of exposure:
6
Justification:
default - subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
differences between rats and humans already taken into account for modifying the starting point
AF for other interspecies differences:
2.5
Justification:
default - any remaining difference
AF for intraspecies differences:
10
Justification:
default - general population
AF for the quality of the whole database:
1
Justification:
database complete for the ton bandage
AF for remaining uncertainties:
1
Justification:
DNEL based on experimental data on the substance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

100 x 2 [oral absorption rat 50%/dermal absorption human 25%]

AF for dose response relationship:
1
Justification:
A clear NOAEL was derived
AF for differences in duration of exposure:
6
Justification:
default - subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default - rat
AF for other interspecies differences:
2.5
Justification:
any remaining difference
AF for intraspecies differences:
10
Justification:
default - general population
AF for the quality of the whole database:
1
Justification:
database complete for the ton bandage
AF for remaining uncertainties:
1
Justification:
DNEL based on experimental data on the substance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.2 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

oral absorption in rats = oral absorption in humans

AF for dose response relationship:
1
Justification:
Aclear NOAEL was derived
AF for differences in duration of exposure:
6
Justification:
default - subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default - rat
AF for other interspecies differences:
2.5
Justification:
any remaining difference
AF for intraspecies differences:
10
Justification:
default - general population
AF for the quality of the whole database:
1
Justification:
database complete for the ton bandage
AF for remaining uncertainties:
1
Justification:
DNEL based on experimental data for the substance.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

The registered substance was not acutely toxic via the oral route of exposure, was demonstrated to to be non-genotoxic in a battery of genotoxicity studies appropriate to the tonnage, not developmentally toxic or toxic for reproduction in a reproductive screening study, and to possess a NOAEL of 100 mg/kg bw/day in a 28 day repeat dose toxicity study. This was the most critical NOAEL for deriving the risk assessment.