Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
48 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
1 206 mg/m³
Explanation for the modification of the dose descriptor starting point:
The inhalation NOAEC of 2400 mg/m3 is corrected for exposure conditions (*6/8) and respiratory rate (*6.7/10)
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
no adjustment for allometry needed
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value (workers)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
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:
14 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
1 368 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The inhalation NOAEC of 2400 mg/m3 is converted (*0.38; *6h/8h) to a dermal NOAEL of 1368 mg/kg bw/d assuming dermal absorption of 50% and inhalation absorption of 100%
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
default value (rat study)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value (workers)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

A long-term systemic inhalation DNEL is derived from the NOAEC of 2400 mg/m3 in the 90 -day rat study. The inhalation NOAEC of 2400 mg/m3 is corrected for exposure conditions (*6/8) and respiratory rate (*6.7/10). Application of assessment factors of 2 (extrapolation from a sub-chronic study to chronic exposure), 2.5 (interspecies differences) and 5 (intraspecies differences) results in a DNEL value of 48 mg/m3.

A short-term systemic inhalation DNEL is not derived in the absence of any indication of an acute hazard.

Local inhalation DNELs are not derived in the absence of any identified hazard.

A long term systemic dermal inhalation DNEL is derived from the NOAEC of 2400 mg/m3 in the 90 -day rat study.  The inhalation NOAEC of 2400 mg/m3 is converted (*0.38; *6h/8h) to a dermal NOAEL of 1368 mg/kg bw/d assuming dermal absorption of 50% and inhalation absorption of 100%. Applying assessment factors of 2 (extrapolation from subchronic to chronic exposure, 4 (allometric scaling), 2.5 (other interspecies differences) and 5 (intraspecies differences) results in a DNEL of 14 mg/kg bw/d.

A short-term systemic dermal DNEL is not derived in the absence of any indication of an acute hazard.

Local dermal DNELs are not derived in the absence of any identified hazard.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Value:
600 mg/m³
Explanation for the modification of the dose descriptor starting point:
The inhalation NOAEC of 2400 mg/m3 is corrected for exposure conditions (*6/24)
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from a sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable (already accounted for)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 380 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The inhalation NOAEC of 2400 mg/m3 is converted (*1.15; *6h/24h) to a dermal NOAEL of 1380 mg/kg bw/d assuming dermal absorption of 50% and inhalation absorption of 100%
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
default value (rat study)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
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:
6.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 380 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The inhalation NOAEC of 2400 mg/m3 is converted (*1.15; *6h/24h) to an oral NOAEL of 1380 mg/kg bw/d assuming oral absorption of 50% and inhalation absorption of 100%
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
default (rat study)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
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

A long-term systemic inhalation DNEL is derived from the NOAEC of 2400 mg/m3 in the 90 -day rat study. The inhalation NOAEC of 2400 mg/m3 is corrected for exposure conditions (*6/24). Application of assessment factors of 2 (extrapolation from a sub-chronic study to chronic exposure), 2.5 (interspecies differences) and 10 (intraspecies differences) results in a DNEL value of 12 mg/m3.

A short-term systemic inhalation DNEL is not derived in the absence of any indication of an acute hazard.

Local inhalation DNELs are not derived in the absence of any identified hazard.

A long term systemic dermal inhalation DNEL is derived from the NOAEC of 2400 mg/m3 in the 90 -day rat study.  The inhalation NOAEC of 2400 mg/m3 is converted (*1.15; *6h/24h) to a dermal NOAEL of 1380 mg/kg bw/d assuming dermal absorption of 50% and inhalation absorption of 100%. Applying assessment factors of 2 (extrapolation from subchronic to chronic exposure, 4 (allometric scaling), 2.5 (other interspecies differences) and 10 (intraspecies differences) results in a DNEL of 6.9 mg/kg bw/d.

A long term systemic oral inhalation DNEL is derived from the NOAEC of 2400 mg/m3 in the 90 -day rat study.  The inhalation NOAEC of 2400 mg/m3 is converted (*1.15; *6h/24h) to an oral NOAEL of 1380 mg/kg bw/d assuming oral absorption of 50% and inhalation absorption of 100%. Applying assessment factors of 2 (extrapolation from subchronic to chronic exposure, 4 (allometric scaling), 2.5 (other interspecies differences) and 10 (intraspecies differences) results in a DNEL of 6.9 mg/kg bw/d.

A short-term systemic dermal DNEL is not derived in the absence of any indication of an acute hazard.

Local dermal DNELs are not derived in the absence of any identified hazard.