Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.24 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):
25
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
881.05 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL is taken from repeat dose oral toxicity studies in rats. It is assumed that oral absorption of the substance is half that of inhalation absorption.

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

= 1000 * 2.63 * 0.67 * 0.5

= 881.05 mg/m3

DNEL = PoD/AF

= 881.05/25

= 35.24 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:
2
Justification:
To account for using PoD taken from a subchronic 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:
2.5
Justification:
Default factor.
AF for intraspecies differences:
5
Justification:
To account for intraspecies differences in an occupational setting.
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:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
35.24 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):
25
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
881.05 mg/m³

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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):
100
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:

The NOAEL is taken from repeat dose oral toxicity studies in rats.

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

                = 1000 x (1/1)

DNEL = PoD/AF

= 1000/100

= 10 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:
2
Justification:
To account for using PoD taken from a subchronic 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:
2.5
Justification:
Default factor.
AF for intraspecies differences:
5
Justification:
To account for intraspecies differences in an occupational setting.
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:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
10 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):
100
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

Local effects

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

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:
8.69 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):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
434.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

In the absence of a repeated dose toxicity study conducted via the inhalation route of exposure the use of a PoD using the oral route of exposure has been employed.

The NOAEL is taken from repeat dose oral toxicity studies in rats. It is assumed that oral absorption of the substance is half that of inhalation absorption.

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

= 1000 * 0.869 * 0.5

= 434.5 mg/m3

DNEL = PoD/AF

= 434.5/50

= 8.69 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:
2
Justification:
To account for using PoD taken from a subchronic 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:
2.5
Justification:
Default factor.
AF for intraspecies differences:
10
Justification:
To account for intraspecies differences.
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:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
8.69 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):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
434.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

In the absence of a repeated dose toxicity study conducted via the inhalation route of exposure the use of a PoD using the oral route of exposure has been employed.

The NOAEL is taken from repeat dose oral toxicity studies in rats. It is assumed that oral absorption of the substance is half that of inhalation absorption.

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

= 1000 * 0.869 * 0.5

= 434.5 mg/m3

DNEL = PoD/AF

= 434.5/50

= 8.69 mg/m3

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:
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:
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:

NOAEL is taken from a repeat dose toxicity study via the oral route of exposure.

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

= 1000 * (1/1)

= 1000

DNEL = PoD/AF

= 1000/200

= 5 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:
2
Justification:
To account for using PoD taken from a subchronic 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:
2.5
Justification:
Default factor
AF for intraspecies differences:
10
Justification:
To account for intraspecies differences.
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:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
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:
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:

NOAEL is taken from a repeat dose toxicity study via the oral route of expsoure.

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

= 1000 * (1/1)

= 1000

DNEL = PoD/AF

= 1000/200

= 5 mg/kg bw/day

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
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:
1 000 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:
2
Justification:
To account for using PoD taken from a subchronic 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:
2.5
Justification:
Default factor
AF for intraspecies differences:
10
Justification:
To account for intraspecies differences.
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:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
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:
1 000 mg/kg bw/day

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population