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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.75 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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
881.58 mg/m³
Explanation for the modification of the dose descriptor starting point:

As a point of departure for the inhalation long term DNEL, the NOAEL of 1 000 mg/kg bw/day from the combined repeated dose toxicity with the reproduction/developmental toxicity screening test in rats was chosen. In the absence of any experimental absorption data for both the starting route (oral) and the end route (inhalation), the worst case assumption was made, assuming a limited absorption for the oral route, leading to a low (conservative) internal NOAEL. It is proposed, in the absence of route-specific information on the starting route, to include a default factor of 2 (50 % absorption is assumed for oral absorption, and 100 % for inhalation.) in accordance with ECHA guidance document R.8 (ECHA, 2012)[1].

[1]ECHA (2012) Guidance on information requirements and chemical safety assessment Guidance on information requirements and chemical safety assessment version: 2.1.

AF for dose response relationship:
1
Justification:
The starting point is a clear NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
No applicable for inhalation.
AF for other interspecies differences:
1
Justification:
Addressed by modification of starting point.
AF for intraspecies differences:
5
Justification:
Default value for workers.
AF for the quality of the whole database:
1
Justification:
Data available on the test substance appropriate for the tonnage band.
AF for remaining uncertainties:
2.5
Justification:
Default value.
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:
3.33 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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No hazard identified.

As a point of departure for the dermal long term DNEL, the NOAEL of 1 000 mg/kg bw/day from the combined repeated dose toxicity with the reproduction/developmental toxicity screening test in rats was chosen. A maximal absorption was already occurred by the oral route and no additional correction factor was introduced.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
1
Justification:
Addressed by modification of starting point.
AF for intraspecies differences:
5
Justification:
Default value for workers.
AF for the quality of the whole database:
1
Justification:
Data available on the test substance appropriate for the tonnage band.
AF for remaining uncertainties:
2.5
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No hazard identified.

No acute toxicity hazard (leading to C&L) has been identified for the registered substance following the oral, dermal and inhalation exposure. Therefore, according to ECHA R8 Guidance, no DNEL (acute) should be set.

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:
2.9 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):
150
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
434.78 mg/m³
Explanation for the modification of the dose descriptor starting point:

As a point of departure for the inhalation long term DNEL, the NOAEL of 1 000 mg/kg bw/day from the combined repeated dose toxicity with the reproduction/developmental toxicity screening test in rats was chosen. In the absence of any experimental absorption data for both the starting route (oral) and the end route (inhalation), the worst case assumption was made, assuming a limited absorption for the oral route, leading to a low (conservative) internal NOAEL. It is proposed, in the absence of route-specific information on the starting route, to include a default factor of 2 (50 % absorption is assumed for oral absorption, and 100 % for inhalation.) in accordance with ECHA guidance document R.8 (ECHA, 2012).

AF for dose response relationship:
1
Justification:
The starting point is a clear NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable for inhalation.
AF for other interspecies differences:
1
Justification:
Addressed by modification of starting point.
AF for intraspecies differences:
10
Justification:
Default value for general population.
AF for the quality of the whole database:
1
Justification:
Data available on the test substance appropriate for the tonnage band.
AF for remaining uncertainties:
2.5
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No hazard identified.

No acute toxicity hazard (leading to C&L) has been identified for the registered substance following the oral, dermal and inhalation exposure. Therefore, according to ECHA R8 Guidance, no DNEL (acute) should be set.

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:
1.67 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As a point of departure for the dermal long term DNEL, the NOAEL of 1 000 mg/kg bw/day from the combined repeated dose toxicity with the reproduction/developmental toxicity screening test in rats was chosen. A maximal absorption was already occurred by the oral route and no additional correction factor was introduced.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human.
AF for other interspecies differences:
1
Justification:
Addressed by modification of starting point.
AF for intraspecies differences:
10
Justification:
Default value for workers.
AF for the quality of the whole database:
1
Justification:
Data available on the test substance appropriate for the tonnage band.
AF for remaining uncertainties:
2.5
Justification:
Default value
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:
1.67 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The starting point is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human.
AF for other interspecies differences:
1
Justification:
Addressed by modification of starting point.
AF for intraspecies differences:
10
Justification:
Default value for workers.
AF for the quality of the whole database:
1
Justification:
Data available on the test substance appropriate for the tonnage band.
AF for remaining uncertainties:
2.5
Justification:
Default value
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