Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.73 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECHA R.8 guidance incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
45
Dose descriptor starting point:
LOAEL
DNEL value:
30 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
DNEL value:
123 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point LOAEL (dermal rat 13 week repeat dose studies); x [1/0.43 {Adjust the human dermal uptake to rat with adjustment factor of 0.43 to account for increased rat absorption}] x [6.7/10 {light work ventilation rate}] x [1/0.38{adjust for human inhalation rate from dermal}] = 123 mg/m3

AF for dose response relationship:
3
Justification:
LOAEL converted to a NOAEL (ECHA R.8 guidance)
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic (ECHA R.8 value)
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required
AF for other interspecies differences:
2.5
Justification:
Interspecies rat to human (ECHA R.8 value)
AF for intraspecies differences:
3
Justification:
ECETOC intraspecies AF
AF for the quality of the whole database:
1
Justification:
Reliable study available
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.58 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA R.8 guidance incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
45
Dose descriptor:
NOAEC
DNEL value:
251 mg/m³
AF for dose response relationship:
1
Justification:
Not required, starting point was a NOAEC
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic (ECHA R.8 guidance)
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required
AF for other interspecies differences:
2.5
Justification:
Interspecies rat to human (ECHA R.8 guidance)
AF for intraspecies differences:
3
Justification:
ECETOC intraspecies AF
AF for the quality of the whole database:
1
Justification:
Reliable study available
AF for remaining uncertainties:
1
Justification:
Not requried
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:
0.97 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECHA R.8 guidance incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
72
Dose descriptor starting point:
LOAEL
DNEL value:
30 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
69.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point LOAEL (dermal rat 13 week repeat dose study); x [1/0.43 {Adjust the human dermal uptake to rat with adjustment factor of 0.43 to account for increased rat absorption}] = 69 mg/kg/day

AF for dose response relationship:
3
Justification:
LOAEL converted to NOAEL (ECHA R.8 value)
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic (ECHA R.8 value)
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies rat to human (ECHA R8 value)
AF for other interspecies differences:
1
Justification:
Not required
AF for intraspecies differences:
3
Justification:
ECETOC intrapsecies AF
AF for the quality of the whole database:
1
Justification:
Reliable study available
AF for remaining uncertainties:
1
Justification:
Not required
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:
no hazard identified

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:
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

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:
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

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.74 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA R.8 guidance incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
120
Dose descriptor starting point:
LOAEL
DNEL value:
125 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
89.3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point LOAEL (oral rat 13 week repeat dose study); x 5 days per week adjusted [5/7 {5 days/7 days}] = 89.3 mg/kg/day

AF for dose response relationship:
3
Justification:
LOAEL converted to a NOAEL (ECHA R.8 guidance)
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic (ECHA R.8 value)
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies rat to man (ECHA R.8 value)
AF for other interspecies differences:
1
Justification:
Not required
AF for intraspecies differences:
5
Justification:
ECETOC intraspecies AF
AF for the quality of the whole database:
1
Justification:
Reliable study available
AF for remaining uncertainties:
1
Justification:
Not required
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 for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population