Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
68.34 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Dermal
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:
other: NOEL
Value:
125 mg/kg bw/day
Modified dose descriptor starting point:
other: NOEL
Value:
512.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point NOEL = 125 mg/kg (rat dermal developmental tox study); [1/0.43 {RVM}] x [1/0.38{ convert to inhal dose}] x [6.7/10 {adjustment for ligh exercise}] = 512 mg/m3

AF for dose response relationship:
1
Justification:
Not required: starting point was a NOEL
AF for differences in duration of exposure:
1
Justification:
Not required
AF for interspecies differences (allometric scaling):
1
Justification:
Not required
AF for other interspecies differences:
2.5
Justification:
Interspecies rat to human (R8 guidance)
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
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 288 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:
other: NOEC
Value:
6 000 mg/m³
Modified dose descriptor starting point:
other: NOEC
Value:
32 160 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point NOEC = 6,000 mg/m3 (rat acute study); 120 minutes/day, adjusted for duration of work [120/15 {minutes/day}] x [6.7/10 {light work ventilation rate}] = 32,160 mg/m3

AF for dose response relationship:
1
Justification:
Not required: Starting point was a NOEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required
AF for other interspecies differences:
2.5
Justification:
Interspecies rat to human (R8 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 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:
2.91 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 procedure but incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
24
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
69.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point NOAEL [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:
1
Justification:
Not required, starting point was a NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic (ECHA R.8 guidance)
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies rat to human (R8 guidance)
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:
low hazard (no threshold derived)

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:
DNEL (Derived No Effect Level)
Value:
20.22 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance procedure but incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
other: NOEL
Value:
125 mg/kg bw/day
Modified dose descriptor starting point:
other: NOEL
Value:
252.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point NOEL = 125 mg/kg (rat dermal development tox study); x [1/0.43 {for RVM}] x [1/1.15 {convert to inhal dose}] = 252 mg/m3

AF for dose response relationship:
1
Justification:
Not required, starting point was a NOEL
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 rat to human (R8 guidance)
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:
DNEL (Derived No Effect Level)
Value:
2 572.8 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):
12.5
Dose descriptor starting point:
other: NOEC
Value:
6 000 mg/m³
Modified dose descriptor starting point:
other: NOEC
Value:
32 160 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point NOEC = 6,000 mg/m3 (rat acute study); 120 minutes/day, adjusted for duration of work [120/15 {minutes/day}] x [6.7/10 {light work ventilation rate}] = 32,160 mg/m3

AF for dose response relationship:
1
Justification:
Not required: Starting point was a NOEC
AF for interspecies differences (allometric scaling):
1
Justification:
Not required
AF for other interspecies differences:
2.5
Justification:
Interspecies rat to human (R8 guidance)
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

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:
1.25 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 procedure but incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
49.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point NOAEL= 30 mg/Kg, (90 day dermal rat  study); 5 days/wk adjusted for duration of exposure [5/7{days/week} x 1/0.43 {animal absorption factor} = 49.9 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Not required: starting point was a NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic (ECHA R.8 guidance)
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies rat to human (R.8 guidance)
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:
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:
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:
1.25 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 procedure but incorporating ECETOC intraspecies AF
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
49.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point NOAEL= 30 mg/Kg, (90 day dermal rat  study); 5 days/wk adjusted for duration of exposure [5/7{days/week}] x [1/0.43 {animal absorption factor}] = 49.9 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Not required: starting point was a NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic (ECHA R.8 guidance)
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies rat to human (R.8 guidance)
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:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population