Registration Dossier

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:
NOAEL
DNEL value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
88.16 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 100 mg/kg/day in 28 -day repeated dose toxicity study (oral route, OECD 407; Braun, 2008) was used to derive a DNEL long-term, systemic effects via the inhalation route (most sensitive endpoint/lowest NOAEL). After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point NOAEC is 88.16 mg/m³ = 100 mg/kg/d x 1/0.38 m³/kg/d x 0.67 x 0.5. This correction factor is derived from the inhaled volumes in 8 hours under respective conditions (6.7 m³ for base level, 10m³ for light activity). An additional correction factor of 0.5 is used as it is assumed that the bioavailability after oral exposure is 50% while the bioavailability after inhalation is assumed to be 100%.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point
AF for differences in duration of exposure:
6
Justification:
difference in study duration subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
included in the route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
no need for further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for further 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
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:
NOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 100 mg/kg/day established in the 28 -day repeated dose toxicity study (oral route, OECD 407; Braun, 2008) was used to derive a DNEL long-term, systemic effects via dermal administration (most sensitive endpoint/lowest NOAEL). After route-to-route extrapolation (oral to dermal) the dose descriptor starting point is 100 mg/kg/d. No additional correction factor is applied as bioavailability after oral exposure as well as after dermal exposure is assumed to be 50%.

AF for dose response relationship:
1
Justification:
starting point NOAEL
AF for differences in duration of exposure:
6
Justification:
difference in duration subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
no need for further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for further 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:
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:
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:
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 for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

No DNEL is derived for general population as no consumer use is expected.