Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.72 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC method
Overall assessment factor (AF):
18
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
67 mg/m³
Explanation for the modification of the dose descriptor starting point:

75 mg/kg bw/day x (1/0.38) x (50% oral abs / 100% inhalation abs ) x (6.7/10)

AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirment and chemical safety assessment and in ECETOX Technical Report 110.
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with table R.8.5 of Chapter R.8 of Guiudance on information requirements and chemical safety assessment and in ECETOC Technical Report 110.
AF for interspecies differences (allometric scaling):
1
Justification:
Already taken into account during allometric scaling of the starting point
AF for other interspecies differences:
1
Justification:
All interspecies differences accounted for by allometric scaling. Default value in ECETOC Technical Report No. 110.
AF for intraspecies differences:
3
Justification:
Default value in ECETOC Technical Report No. 110
AF for the quality of the whole database:
1
Justification:
Database appropriate for tonnage
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No adverse effrects identified in acute oral toxicity study. LD50 is considered to be greater than 2000 mg/kg

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)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.04 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC Method
Overall assessment factor (AF):
72
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default value in line with section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment and in ECETOC TEchnical Report 110
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to subchronic exposure value in line with table R.8.5 of chapter R.8 of Guidance on information requirements and chemical safety assessment and in ECETOC Technical Report 110.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in ECETOC Technical Report 110
AF for other interspecies differences:
1
Justification:
Default value in ECETOC Technical Report No. 110.
AF for intraspecies differences:
3
Justification:
Default value in ECETOC Technical Report No. 110
AF for the quality of the whole database:
1
Justification:
database appropriate for tonnage
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:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The substance was not considered mutagenic in studies that were adequately conducted. In a reliable OECD 422 gavage study in the rat the NOAEL was established at the limit dose (75 mg/kg bw/day) with no adverse effects for either repeat dose or reproductive toxicity. No adverse effects were observed at the limit dose in the acute oral toxicity study.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC Method
Overall assessment factor (AF):
30
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
33 mg/m³
Explanation for the modification of the dose descriptor starting point:

75 x 1 / 1.15 x 0.5 = 32.6 mg/m3

AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8.5 of chapter R.8 of Guidance on information requirements and chemical safety assessment and in ECETOC Technical REport 110.
AF for interspecies differences (allometric scaling):
1
Justification:
Already taken into account during allometric scaling of the starting point
AF for other interspecies differences:
1
Justification:
All interspecies differences accounted for by allometric scaling. Default value in ECETOC TEchnical Report No.100
AF for intraspecies differences:
5
Justification:
Default value in ECETOC Technical Report No.100
AF for the quality of the whole database:
1
Justification:
Database appropriate for tonnage
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No adverse effects identified in acute oral (2000 mg/kg) toxicity study

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)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.625 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC MEthod
Overall assessment factor (AF):
120
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessements
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8.5 of chapter R.8 of Guidance on information requirements and chemical safety assessment and in ECETOC Technical REport 110.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in ECETOC Technical Report No. 110
AF for other interspecies differences:
1
Justification:
Default value in ECETOC Technical REport No. 110
AF for intraspecies differences:
5
Justification:
Default value in ECETOC Technical Report No. 110
AF for the quality of the whole database:
1
Justification:
Database appropriate for tonnage
AF for remaining uncertainties:
1
Justification:
No uncertianities remain
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
0.625 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC Method
Overall assessment factor (AF):
120
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of chapter R.8 of Guidance on information requirements and chemical safety assessments
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with table R.8.5 of chapter R.8 of Guidance on information requirements and chemical safety assessment and in ECETOC Technical Report 110.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in ECETOC Technical Report No. 110
AF for other interspecies differences:
1
Justification:
Default value in ECETOC Technical Report 110.
AF for intraspecies differences:
5
Justification:
Default value in ECETOC Technical Report 110
AF for the quality of the whole database:
1
Justification:
Database appropriate for tonnage
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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