Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
3.32 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
19.92 mg/m³
Explanation for the modification of the dose descriptor starting point:
The relevant dose descriptor selected to derive the inhalation DNEL, was the oral rat NOAEL of 113 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with read-across substance C12-18 TMAC.This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat ÷ SRvrat x (SRvhuman ÷ WSRvhuman) x (ABSoral-rat/ABSinh-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral rat = 113 mg/kg bw/d; SRvrat = 0.38 m3/kg bw; SRvhuman = 6.7 m3; WSRvhuman = 10 m3; ; ABSoral-rat = 10%; ABSinh-human = 100%.
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub-chronic to chronic study)
AF for interspecies differences (allometric scaling):
1
Justification:
No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC
AF for other interspecies differences:
1
Justification:
Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
AF for intraspecies differences:
3
Justification:
Intraspecies variation (workers). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
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:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
4.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
113 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The relevant dose descriptor selected to derive the dermal DNEL, was the oral rat NOAEL of 113 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with the read-across substance C12-18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat x (ABSoral-rat/ABSderm-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral rat = 113 mg/kg bw/d; ABSoral-rat = 10%; ABSderm-human = 10%).
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
AF for other interspecies differences:
1
Justification:
Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
AF for intraspecies differences:
3
Justification:
Intraspecies variation (workers). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
0.11 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
6
Dose descriptor:
other: corrected NOAEL of 0.63 mg/cm2/day
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Assessment factor for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) not required since this is already accounted for when obtaining the corrected NOAEL
AF for other interspecies differences:
1
Justification:
Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
AF for intraspecies differences:
3
Justification:
Intraspecies variation (workers). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
0.98 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
9.83 mg/m³
Explanation for the modification of the dose descriptor starting point:
The relevant dose descriptor selected to derive the inhalation DNEL, was the oral rat NOAEL of 113 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with the read-across substance C12-18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat ÷ SRvrat x (ABSoral-rat/ABSinh-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral rat = 113 mg/kg bw/d; SRvrat = 1.15 m3/kg bw; ABSoral-rat = 10%; ABSinh-human = 100%.
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC
AF for other interspecies differences:
1
Justification:
Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
AF for intraspecies differences:
5
Justification:
Intraspecies variation (general population). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
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:
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)
2.83 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
113 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The relevant dose descriptor selected to derive the dermal DNEL, was the oral rat NOAEL of 113 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with the read-across substance C12-18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat x (ABSoral-rat/ABSderm-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral rat = 113 mg/kg bw/d; ABSoral-rat = 10%; ABSderm-human = 10%).
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub-chronic to chronic study)
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
AF for other interspecies differences:
1
Justification:
Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
AF for intraspecies differences:
5
Justification:
Intraspecies variation (general population). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
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)
0.06 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
10
Dose descriptor:
other: corrected NOAEL of 0.63 mg/cm2/day
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub-chronic to chronic study)
AF for interspecies differences (allometric scaling):
1
Justification:
Assessment factor for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) not required since this is already accounted for when obtaining the corrected NOAEL
AF for other interspecies differences:
1
Justification:
Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
AF for intraspecies differences:
5
Justification:
Intraspecies variation (general population). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
2.83 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
113 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation needed
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub-chronic to chronic study)
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
AF for other interspecies differences:
1
Justification:
Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
AF for intraspecies differences:
5
Justification:
Intraspecies variation (general population). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population