Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
950 mg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
DNEL derivation method:
other: see discussion below under 'explanation for hazard conclusion'.
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:
343 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see detailed description below
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
DNEL value:
8 238 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is no specific data for humans. The oral DNEL is used as the point of departure. NOAEL for repeat dose toxicity =1730mg/kg (male rats). No correction is necessary for bioavailability or exposure conditions.  Assuming a dermal absorption factor (worse case) of 21% (see IUCLID chapter 7.1.2) leads to a NOAEL dose descriptor starting point of 8238mg/kg for occlusive conditions. (Note that under non-occlusive conditions, the data available suggests that absorption is about 10% of that under occlusive conditions).

AF for dose response relationship:
1
Justification:
No additional factor required. Default is 1 without a clear need for such a factor.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation of sub-chronic to chronic duration.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for extrapolation from rats to humans.
AF for other interspecies differences:
1
Justification:
No additional factor required. Rats and humans show similar effects from exposure to ethanol. See separate justification attached to this record.
AF for intraspecies differences:
3
Justification:
A factor of 3 seems sufficient for differences between humans - see separate justification attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
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:
medium 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:
114 mg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
DNEL derivation method:
other: see discussion below under 'explanation for hazard conclusion'
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:
DNEL (Derived No Effect Level)
Value:
206 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see discussions below.
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 730 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is no specific data for humans. The oral DNEL is the point of departure. NOAEL for repeat dose toxicity =1730mg/kg (male rats). No correction is necessary for bioavailability or exposure conditions.  Assuming a dermal absorption factor (worse case) of 21% (see chapter 7.1.2) leads to a NOAEL dose descriptor starting point of 8238mg/kg for occlusive conditions. (Note that under non-occlusive conditions, the data available suggests that absorption is about 10% of that under occlusive conditions due to evaporation).

No further correction is necessary for bioavailability or exposure conditions.

AF for dose response relationship:
1
Justification:
No additional factor required. Default is 1 without a clear need for such a factor.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation of sub-chronic to chronic duration.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for extrapolation from rats to humans.
AF for other interspecies differences:
1
Justification:
No additional factor required. Rats and humans show similar effects from exposure to ethanol. See separate justification attached to this record.
AF for intraspecies differences:
5
Justification:
A factor of 5 seems sufficient for differences between humans - see separate justification attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
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:
87 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: see discussions below
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:

NOAEL for repeat dose toxicity =1730mg/kg (male rats). No further correction is necessary for bioavailability or exposure conditions.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population