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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.52 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: informed assessment factors
Overall assessment factor (AF):
5
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
17.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL for reproductive toxicity of 20 mg/kg bw/d

Modification of starting point involves conversion of rat oral exposure to human inhalation exposure using ECHA Ch R8, Fig. 8.3. Human NOAEC = Oral NOAEL X 1/0.38 m³/kg/d X 0.5 absn. Default X 6.7/10 = 17.6 mg/m³

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
No time extrapolation required, since the susceptible window is fully covered
AF for interspecies differences (allometric scaling):
1
Justification:
default corrections for respiratory rate and respiratory volume have been included in route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected.
AF for intraspecies differences:
5
Justification:
default AF for workers
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required.
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:
1 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: informed assessment factors
Overall assessment factor (AF):
20
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL for reproductive toxicity of 20 mg/kg bw/d

Modification of starting point involves conversion of rat oral exposure to human dermal exposure using ECHA Ch R8, Ex. B5, page 69. Human NOAEL = Oral NOAEL X 1 (Absorption factor for oral to dermal route =1; ECHA Ch R8. page 25.)

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
No time extrapolation required, since the susceptible window is fully covered
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected.
AF for intraspecies differences:
5
Justification:
default AF (workers)
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required.
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: informed assessment factors
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
8.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL for reproductive toxicity of 20 mg/kg bw/d

Modification of starting point involves conversion of rat oral exposure to human inhalation exposure using ECHA Ch R8, Fig. 8.3. Human NOAEC = Oral NOAEL X 1/1.15 m³/kg/d X 0.5 absn. = 8.7 mg/m³

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
No time extrapolation required, since the susceptible window is fully covered
AF for interspecies differences (allometric scaling):
1
Justification:
default corrections for respiratory rate and respiratory volume have been included in route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected.
AF for intraspecies differences:
10
Justification:
default AF (general population)
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required.
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: informed assessment factors
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL for reproductive toxicity of 20 mg/kg bw/d

Modification of starting point involves conversion of rat oral exposure to human dermal exposure using ECHA Ch R8, Ex. B5, page 69. Human NOAEC = Oral NOAEL X 1 (Absorption factor for oral to dermal route =1; ECHA Ch R8. page 25.)

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
No time extrapolation required, since the susceptible window is fully covered
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected.
AF for intraspecies differences:
10
Justification:
default AF (general population)
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: informed assessment factors
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

no route to route extrapolation required

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
No time extrapolation required, since the susceptible window is fully covered
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected
AF for intraspecies differences:
10
Justification:
default AF (general population)
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required
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

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