Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.18 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
88.16 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 LOAEL of 100 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with the analogue. 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’) November (2012); where: LOAELoral rat = 100 mg/kg bw/d; SRvrat = 0.38 m3/kg bw; SRvhuman = 6.7 m3; WSRvhuman = 10 m3; ABSoral-rat = 50%; ABSinh-human = 100%; =100 x 1/0.38 x 6.7/10 x 50/100 = 88.16 mg/m3.
AF for dose response relationship:
3
Justification:
Dose response (starting point is a LOAEL)
AF for differences in duration of exposure:
2
Justification:
Assessment factors for 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:
2.5
Justification:
Assessment factors for remaining non-metabolic differences
AF for intraspecies differences:
5
Justification:
Assessment factors for workers
AF for the quality of the whole database:
1
Justification:
Good quality study
AF for remaining uncertainties:
1
Justification:
No additional factors are required
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)
Value:
0.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
100 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 LOAEL of 100 mg/kg bw/day derived from a 90 -day repeated dose dietary toxicity study conducted with the analogue. 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’) November (2012); where: LOAELoral rat = 100 mg/kg bw/d; ABSoral-rat = 50%; ABSderm-human = 50%; = 100 x 50/50 = 100 mg/kg bw/day.
AF for dose response relationship:
3
Justification:
Dose-response (starting point is a LOAEL)
AF for differences in duration of exposure:
2
Justification:
For 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:
2.5
Justification:
Assessment factor for any remaining non-metabolic differences
AF for intraspecies differences:
5
Justification:
Assessment factor for workers
AF for the quality of the whole database:
1
Justification:
Good quality study
AF for remaining uncertainties:
1
Justification:
Not additional assessment factors are required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

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:
no hazard identified
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:
no hazard identified
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

General Population - Hazard via oral route

Systemic 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 for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population