Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
734 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: DNEL is based on IOELV and not derived by conventional assessment factors method.
Explanation for the modification of the dose descriptor starting point:

The long term local effects DNELs for inhalation are based on the IOEL 8 hr TWA set by the SCOEL in in 1997 (SEG/SUM1D) of 734mg/m3 (200ppm). This IOELV is also supported by national limits in the UK and Germany that are supported by criteria documents. The critical effect was sensory irritation. These studies are described in chapter 7.10.3. There is no new data that has become subsequently available that would render this conclusion invalid. This DNEL is also protective for long term systemic effects; both DNELS are set to the same value. The long term systemic effects DNEL is set the same as for the local effects DNEL on a conservative basis. There are no long term systemic effects seen in any of the studies seen at doses lower than those associated with local effects.

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 468 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: DNEL is based on IOELV and not derived by conventional assessment factors method.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
734 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: DNEL is based on IOELV and not derived by conventional assessment factors method.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 468 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
63 mg/kg bw/day
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: DNEL derived by route to route extrapolation from inhalation DNEL that is in turn based on an IOELV. DNEL not therefore derived by conventional assessment factors method.
Explanation for the modification of the dose descriptor starting point:

There is no repeat dose information available from the dermal route. A dermal DNEL is therefore derived by route to route extrapolation. The DNEL of 734mg/m3 for the inhalation route is equivalent to an uptake of 4400mg/day (assuming 60% uptake efficiency and a breathing rate of 10m3/day), which converts to 63mg/kg for a 70kg person. This can be considered conservative as the most sensitive end point (respiratory irritation) is based on an end point that is not relevant to the dermal route and can therefore be considered as a route to route extrapolation from the (conservative) systemic inhalation DNEL.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The guidance on dose/concentration response regarding human health (section R8.1.2.5 of chapter R.8 of the Guidance on Information Requirements and Chemical Safety Assessment) indicates that an acute DNEL does not need to be calculated for substances that are not classified for an acute toxicity hazard. As this substance is not classified for acute toxicity hazards, no acute DNEL needs to be calculated.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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:
367 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: DNEL is originally based on IOELV for workers as the starting point and not derived by conventional assessment factors method.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
734 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: DNEL is originally based on IOELV for workers as the starting point and not derived by conventional assessment factors method.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
367 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: DNEL is originally based on IOELV for workers as the starting point and not derived by conventional assessment factors method
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
734 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: DNEL is originally based on IOELV for workers as the starting point and not derived by conventional assessment factors method.

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
37 mg/kg bw/day
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: DNEL derived by route to route extrapolation from inhalation DNEL that is in turn based on an IOELV. DNEL not therefore derived by conventional assessment factors method.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
4.5 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):
200
Dose descriptor starting point:
NOAEL
Value:
900 mg/kg bw/day
AF for dose response relationship:
1
Justification:
No reason for deviating from default value as suggested in guidance.
AF for differences in duration of exposure:
2
Justification:
As recommended in guidance
AF for interspecies differences (allometric scaling):
4
Justification:
As recommended in guidance - rat to human.
AF for other interspecies differences:
2.5
Justification:
As recommended in guidance.
AF for intraspecies differences:
10
Justification:
As recommended in guidance.
AF for the quality of the whole database:
1
Justification:
No reason for deviating from default value as suggested in guidance
AF for remaining uncertainties:
1
Justification:
No reason for deviating from default value as suggested in guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population