Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.82 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):
10
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:

As no long-term study on inhalation is available, route-to-route extrapolation has been performed.

The NOAEL observed in the 90-day repeated dose toxicity study via oral gavage was used to derive a DNEL long-term, systemic effects via the inhalation route. For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 100 mg/kg bw/day x 1/(0.38 m3/kg/day) x 6.7 m3/10 m3 x 0.5 = 88.16 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 basic caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under the respective conditions (6.7 m3 for base level, 10 m3 for light acivity). In addition, the NOAEL needs to be divided by 2 as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%.

AF for dose response relationship:
1
Justification:
default assessment factor, adequate data available
AF for differences in duration of exposure:
2
Justification:
Difference in duration, subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Covered by calculation for route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
rat to human, local effects
AF for intraspecies differences:
5
Justification:
worker 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:
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:
2.5 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):
40
Dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As no dermal long-term study is available, route to route extrapolation has been performed.

The NOAEL observed in the 90 -day repeated dose toxicity study via oral gavage was used to derive a DNEL long-term, systemic effects via the dermal route.

No additional correction factor should be applied as bioavailability after oral and dermal exposure is assumed to be 50%.

AF for dose response relationship:
1
Justification:
default assessment factor, adequate data available
AF for differences in duration of exposure:
2
Justification:
Difference in duration, subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
1
Justification:
rat to human, local effects
AF for intraspecies differences:
5
Justification:
worker 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:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
high 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:
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
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 consumer use is expected, therefore no hazard assessment for the general population is performed.