Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.06 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
1.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the inhalation route is derived on the NOAEL from the oral 90-day study in which the NOAEL was 0.8 mg/kg bw/day. Correction for respiratory rate and volume (rat to human worker): (6.7 m3/d/10 m3/d)*(1/0.38 m3/kg) (default). Therefore, the corrected NOAEC for repeated-dose systemic effects via the inhalation route is [0.8 mg/kg bw/day*(6.7 m3/d/10 m3/d)*(1/0.38 m3/kg)] = 1.4 mg/m3

AF for dose response relationship:
1
Justification:
The starting point is the oral NOAEL which was the low dose tested. There was a dose response in incidence and severity of effects.
AF for differences in duration of exposure:
2
Justification:
default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
not required for inhalation route
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
available studies are good quality
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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:
0.13 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):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
0.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the dermal route is derived on the NOAEL from the oral 90-day study in which the NOAEL was 0.8 mg/kg bw/day. No corrections were made to the NOAEL. Therefore, the NOAEL for repeated-dose systemic effects via the dermal route is = 0.8 mg/kg bw/day. Although dermal absorption of the parent substance was demonstrated to be <0.1% in vitro signs of systemic toxicity were recorded in acute and repeat dose toxicity studies conducted by the dermal route indicating systemic exposure of substance-related material had occurred. Therefore, no correction for dermal absorption is applied.

AF for dose response relationship:
1
Justification:
The starting point is the oral NOAEL which was the lowest dose tested. There was a dose response in incidence and severity of effects.
AF for differences in duration of exposure:
2
Justification:
default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
default (rat to human)
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
available studies are good quality
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Short-term high exposures are considered unlikely given the high levels of control in place at sites producing and using the substance. DNELs for long-term exposure are therefore adequate to protect against short-term exposures and no separate short-term DNELs are calculated.

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:
DNEL (Derived No Effect Level)
Value:
0.004 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):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
0.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the dermal route is derived on the NOAEL from the oral 90-day study in which the NOAEL was 0.8 mg/kg bw/day. No corrections were made to the NOAEL. Therefore, the NOAEL for repeated-dose systemic effects via the dermal route is = 0.8 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The starting point is the oral NOAEL which was the low dose tested. There was a dose response in incidence and severity of effects.
AF for differences in duration of exposure:
2
Justification:
default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
default (rat to human)
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
Justification:
available studies are good quality
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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