Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.56 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
Dose descriptor starting point:
NOAEL
DNEL value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
264 mg/m³
Explanation for the modification of the dose descriptor starting point:

- Data available from an oral 90-days repeated dose toxicity study in rats shows a NOAEL of 150 mg/kg bw/day. This NOAEL being the lowest from the repeated dose studies available (90-days oral toxicity study, prenatal developmental study and two generation reproduction study) is used as a dose descriptor starting point. This NOAEL value of 150 mg/kg bw/day was also observed in a 28-days oral repeated dose toxicity study in rats.

- For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 150 mg/kg bw/day x 1/(0.38 m³/kg bw/d) x 6.7 m³/10 m³ x 1 = 264 mg/m³. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m3/kg for 8 hours exposure of workers). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). No correction for bioavailability via the inhalation route is made as for both the oral and the inhalatory route 100% absorption is assumed, following the assumptions of the existing risk assessment (16 -07 -2008) for this substance.

AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
assessment factor not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
default assessment factor for rats
AF for intraspecies differences:
5
Justification:
default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 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
Dose descriptor starting point:
NOAEL
DNEL value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

-Data available from an oral 90-days repeated dose toxicity study in rats shows a NOAEL of 150 mg/kg bw/day. This NOAEL being the lowest from the repeated dose studies available (90-days oral toxicity study, prenatal developmental study and two generation reproduction study) is used asa dose descriptor starting point. This NOAEL value of 150 mg/kg bw/day was also observed in a 28-days oral repeated dose toxicity study in rats.

- For the route-to-route extrapolation from oral to dermal, on the assumption that dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be applied as part of the overall assessment factor.

AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default assessment factor for rats
AF for other interspecies differences:
2.5
Justification:
default assessment factor for rats
AF for intraspecies differences:
5
Justification:
default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
high 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)
Value:
2.61 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):
50
Dose descriptor starting point:
NOAEL
DNEL value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
130.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

- Data available from an oral 90-days repeated dose toxicity study in rats shows a NOAEL of 150 mg/kg bw/day. This NOAEL being the lowest from the repeated dose studies available (90-days oral toxicity study, prenatal developmental study and two generation reproduction study) is used asa dose descriptor starting point.

- For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 150 mg/kg bw/day x 1/(1.15 m³/kg bw/d) = 130.4 mg/m³. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure of the general population). No correction for bioavailability via the inhalation route is made as for both the oral and the inhalatory route 100% absorption is assumed, following the assumptions of the existing risk assessment (16 -07 -2008) for this substance.

AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
assessment factor not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
default assessment factor for rats
AF for intraspecies differences:
10
Justification:
default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
0.75 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
Dose descriptor starting point:
NOAEL
DNEL value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

- Data available from an oral 90-days repeated dose toxicity study in rats shows a NOAEL of 150 mg/kg bw/day. This NOAEL being the lowest from the repeated dose studies available (90-days oral toxicity study, prenatal developmental study and two generation reproduction study) is used as a dose descriptor starting point.

- For extrapolation of the oral rat NOAEL into an oral NOAEL in humans no modification of the dose descriptor is needed.

AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default assessment factor for rats
AF for other interspecies differences:
2.5
Justification:
default assessment factor for rats
AF for intraspecies differences:
10
Justification:
default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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

For exposure of man via the environment, a long-term systemic DNEL for oral and inhalation exposure is calculated.