Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.18 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance procedure but incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
22.5
Dose descriptor starting point:
LOAEL
DNEL value:
1 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
DNEL value:
4.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point LOAEL  (dermal teratology study): x [1/0.43 {Adjust the human dermal uptake to rat with adjustment factor of 0.43 to account for increased rat absorption}] x [1/0.38]{for route to route extrapolation}] x [6.7/10]{light activity rate}] = 4.5 mg/m3

AF for dose response relationship:
3
Justification:
LOAEL to NOAEL conversion
AF for differences in duration of exposure:
1
Justification:
Not required
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required
AF for other interspecies differences:
2.5
Justification:
Interspecies AF (ECHA R.8)
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:
DNEL (Derived No Effect Level)
Value:
4 716.8 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance procedure but incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
7.5
Dose descriptor starting point:
NOAEC
DNEL value:
3 300 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
35 376 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point NOAEC (acute rat LC50 inhalation study): x 4 hrs/day; adjusted for duration of work [4/0.25 {hrs/day}] x [6.7/10 {light work ventilation rate}]

AF for dose response relationship:
1
Justification:
Not required: starting point was a NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required
AF for other interspecies differences:
2.5
Justification:
Interspecies AF (ECHA R.8)
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

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:
0.065 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance procedure but incorporating CONCAWE intra/interspecies AF
Overall assessment factor (AF):
36
Dose descriptor starting point:
LOAEL
DNEL value:
1 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
2.3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point LOAEL (dermal teratology study): x [1/0.43 {Adjust the human dermal uptake to rat with adjustment factor of 0.43 to account for increased rat absorption}]

AF for dose response relationship:
3
Justification:
LOAEL to NOAEL
AF for differences in duration of exposure:
1
Justification:
Not required
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies rat to human
AF for other interspecies differences:
1
Justification:
Not required
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:
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:
0.015 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
DNEL value:
1.06 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
0.61 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point NOAEL (Subchronic dermal rat study): x [1/0.43 {Adjust the human dermal uptake to rat with adjustment factor of 0.43 to account for increased rat absorption}] x 8 hours per Day, 5 days per week [8/24{hours per day} {5/7{days per week}]

AF for dose response relationship:
1
Justification:
Not required: starting point a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic (ECHA R.8)
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies rat to human (ECHA R.8)
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