Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.79 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance and ECETOC (2010)
Overall assessment factor (AF):
3
Dose descriptor starting point:
NOAEL
Value:
32 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
56.39 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL is taken from a combined chronic/carcinogenicity feeding study in rats, resulting in a NOAEL of 32 mg/kg bw/day. The recommended factor of 2 when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs has not been applied here. Due to low vapour pressure, exposure is only possible as aerosol (use is without fine spraying, only larger droplets). Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

 

Inhalatory N(L)OAEC = oral N(L)OAEL*(1/0.38 m3/kg bw/d)*0.67

= 32 * 2.63 * 0.67

= 56.39 mg/m3

AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
1
Justification:
To account for using PoD taken from a chronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is usually not applied in the derivation of the inhalation DNEL.
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 would also be acceptable. In addition, as effects are local and related to the route of exposure, the already applied allometric scaling already represents a worst case.
AF for intraspecies differences:
3
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for workers is 3 and not 5. As the effects for which the risk assessment is made is based on a local response following a specific mechanism for irritation/corrosion with inherently relative low variation between individuals no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.79 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance and ECETOC (2010)
Overall assessment factor (AF):
3
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance and ECETOC (2010)
Overall assessment factor (AF):
12
Dose descriptor starting point:
NOAEL
Value:
32 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
32 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL is taken from a combined chronic/carcinogenicity feeding study in rats, resulting in a NOAEL of 32 mg/kg bw/day.

Dermal N(L)OAEL=oral (N(L)OAEL*( ABSoral/ABSdermal)

                = 32 x (1/1)

= 32 mg/kg bw/day

AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
1
Justification:
To account for using PoD taken from a chronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to account for differences in allometry in using the rat as a test model.
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 would also be acceptable. In addition, as effects are local and related to the route of exposure, the already applied allometric scaling already represents a worst case.
AF for intraspecies differences:
3
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for workers is 3 and not 5. As the effects for which the risk assessment is made is based on a local response following a specific mechanism for irritation/corrosion with inherently relative low variation between individuals no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

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:
7.36 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance and ECETOC (2010)
Overall assessment factor (AF):
5
Dose descriptor starting point:
NOAEL
Value:
32 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
36.82 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL is taken from a combined chronic/carcinogenicity feeding study in rats, resulting in a NOAEL of 32 mg/kg bw/day. The recommended factor of 2 when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs has not been applied here. Due to low vapour pressure, exposure is only possible as aerosol (use is without fine spraying, only larger droplets). Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

Inhalatory N(L)OAEC = oral N(L)OAEL*(1/1.15 m3/kg bw/d)

= 32 * 0.869

= 36.82 mg/m3

AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
1
Justification:
To account for using PoD taken from a chronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is usually not applied in the derivation of the inhalation DNEL.
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 would also be acceptable. In addition, as effects are local and related to the route of exposure, the already applied allometric scaling already represents a worst case.
AF for intraspecies differences:
5
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for workers is 5 and not 10. As the effects for which the risk assessment is made is based on a local response following a specific mechanism for irritation/corrosion with inherently relative low variation between individuals no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.36 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance and ECETOC (2010)
Overall assessment factor (AF):
5
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance and ECETOC (2010)
Overall assessment factor (AF):
20
Dose descriptor starting point:
NOAEL
Value:
32 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
32 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL is taken from a combined chronic/carcinogenicity feeding study in rats, resulting in a NOAEL of 32 mg/kg bw/day.

Dermal N(L)OAEL=oral (N(L)OAEL*( ABSoral/ABSdermal)

= 32 * (1/1)

= 32 mg/kg bw/day

AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
1
Justification:
To account for using PoD taken from a chronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to account for differences in allometry in using the rat as a test model.
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 would also be acceptable. In addition, as effects are local and related to the route of exposure, the already applied allometric scaling already represents a worst case.
AF for intraspecies differences:
5
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for workers is 5 and not 10. As the effects for which the risk assessment is made is based on a local response following a specific mechanism for irritation/corrosion with inherently relative low variation between individuals no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance and ECETOC (2010)
Overall assessment factor (AF):
20
Dose descriptor starting point:
NOAEL
Value:
32 mg/kg bw/day
AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
1
Justification:
To account for using PoD taken from a chronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to account for differences in allometry in using the rat as a test model.
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 would also be acceptable. In addition, as effects are local and related to the route of exposure, the already applied allometric scaling already represents a worst case.
AF for intraspecies differences:
5
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for workers is 5 and not 10. As the effects for which the risk assessment is made is based on a local response following a specific mechanism for irritation/corrosion with inherently relative low variation between individuals no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance and ECETOC (2010)
Overall assessment factor (AF):
20
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population