Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.82 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
DNEL value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
661.18 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation has been usesd to determine the inhalation NOAEC from a starting dose descriptor oral NOAEL, in accordance with the ECHA REACH guidance:

Inhalation NOAEC = oral NOAEL*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.)

AF for dose response relationship:
1
Justification:
A NOAEL of 750 mg/kg bw/d has been used as the starting point for DNEL derivation. Default AF used.
AF for differences in duration of exposure:
6
Justification:
The exposure duration of the test from which the dose descriptor is taken, subacute 28-d to chronic. Default AF used.
AF for interspecies differences (allometric scaling):
1
Justification:
In accordance with the ECHA REACH guidance, for inhalation, allometric scaling is usually not appplied.
AF for other interspecies differences:
2.5
Justification:
To take into account the interspecies differences an assessment factor for remaining differences should be used . Default AF used.
AF for intraspecies differences:
5
Justification:
To take into account intraspecies variations for DNELs for workers, the assessment factor is 5. Default AF used.
AF for the quality of the whole database:
1
Justification:
The subacute toxicity study via the oral route was conducted in accordance with GLP and OECD guideline 407, therefore has been assigned a reliability score of 1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.82 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor:
NOAEC
DNEL value:
661.18 mg/m³
AF for dose response relationship:
1
Justification:
A NOAEL of 750 mg/kg bw/d has been used as the starting point for DNEL derivation. Default AF used.
AF for differences in duration of exposure:
6
Justification:
The exposure duration of the test from which the dose descriptor is taken, subacute 28-d to chronic. Default AF used.
AF for interspecies differences (allometric scaling):
1
Justification:
In accordance with the ECHA REACH guidance, no allometric scaling default value is provided.
AF for other interspecies differences:
2.5
Justification:
To take into account the interspecies differences an assessment factor for remaining differences should be used . Default AF used.
AF for intraspecies differences:
5
Justification:
To take into account intraspecies variations for DNELs for workers, the assessment factor is 5. Default AF used.
AF for the quality of the whole database:
1
Justification:
The subacute toxicity study via the oral route was conducted in accordance with GLP and OECD guideline 407, therefore has been assigned a reliability score of 1.
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:
2.5 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):
300
Dose descriptor starting point:
NOAEL
DNEL value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation, oral to dermal, dermal NOAEC = oral NOAEL*(ABSoral/ ABSdermal). It has been assumed that the dermal adsorption is the same as the oral adsorption. Therefore, the dermal NOAEL is the same as the oral NOAEL, 750 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
A NOAEL of 750 mg/kg bw/d has been used as the starting point for DNEL derivation. Default AF used.
AF for differences in duration of exposure:
6
Justification:
The exposure duration of the test from which the dose descriptor is taken, subacute 28-d to chronic. Default AF used.
AF for interspecies differences (allometric scaling):
4
Justification:
The subacute toxicity study via the oral route was conducted using rats. Default AF used.
AF for other interspecies differences:
2.5
Justification:
To take into account the interspecies differences an assessment factor for remaining differences should be used . Default AF used.
AF for intraspecies differences:
5
Justification:
To take into account intraspecies variations for DNELs for workers, the assessment factor is 5. Default AF used.
AF for the quality of the whole database:
1
Justification:
The subacute toxicity study via the oral route was conducted in accordance with GLP and OECD guideline 407, therefore has been assigned a reliability score of 1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor:
NOAEC
DNEL value:
750 mg/m³
AF for dose response relationship:
1
Justification:
A NOAEL of 750 mg/kg bw/d has been used as the starting point for DNEL derivation. Default AF used.
AF for differences in duration of exposure:
6
Justification:
The exposure duration of the test from which the dose descriptor is taken, subacute 28-d to chronic. Default AF used.
AF for interspecies differences (allometric scaling):
1
Justification:
In accordance with the ECHA REACH guidance, no allometric scaling default value is provided.
AF for other interspecies differences:
2.5
Justification:
To take into account the interspecies differences an assessment factor for remaining differences should be used . Default AF used.
AF for intraspecies differences:
5
Justification:
To take into account intraspecies variations for DNELs for workers, the assessment factor is 5. Default AF used.
AF for the quality of the whole database:
1
Justification:
The subacute toxicity study via the oral route was conducted in accordance with GLP and OECD guideline 407, therefore has been assigned a reliability score of 1.
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:
2.17 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
DNEL value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
326.09 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation has been usesd to determine the inhalation NOAEC from a starting dose descriptor oral NOAEL, in accordance with the ECHA REACH guidance:

Inhalation NOAEC = oral NOAEL*(1/1.15 m3/kg/d)*(ABSoral/ABSinh.)

AF for dose response relationship:
1
Justification:
A NOAEL of 750 mg/kg bw/d has been used as the starting point for DNEL derivation. Default AF used.
AF for differences in duration of exposure:
6
Justification:
The exposure duration of the test from which the dose descriptor is taken, subacute 28-d to chronic. Default AF used.
AF for interspecies differences (allometric scaling):
1
Justification:
In accordance with the ECHA REACH guidance, for inhalation, allometric scaling is usually not appplied.
AF for other interspecies differences:
2.5
Justification:
To take into account the interspecies differences an assessment factor for remaining differences should be used . Default AF used.
AF for intraspecies differences:
10
Justification:
To take into account intraspecies variations for DNELs for the general population, the assessment factor is 10. Default AF used.
AF for the quality of the whole database:
1
Justification:
The subacute toxicity study via the oral route was conducted in accordance with GLP and OECD guideline 407, therefore has been assigned a reliability score of 1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.17 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor:
NOAEC
DNEL value:
326.09 mg/m³
AF for dose response relationship:
1
Justification:
A NOAEL of 750 mg/kg bw/d has been used as the starting point for DNEL derivation. Default AF used.
AF for differences in duration of exposure:
6
Justification:
The exposure duration of the test from which the dose descriptor is taken, subacute 28-d to chronic. Default AF used.
AF for interspecies differences (allometric scaling):
1
Justification:
In accordance with the ECHA REACH guidance, no allometric scaling default value is provided.
AF for other interspecies differences:
2.5
Justification:
To take into account the interspecies differences an assessment factor for remaining differences should be used . Default AF used.
AF for intraspecies differences:
10
Justification:
To take into account intraspecies variations for DNELs for the general population, the assessment factor is 10. Default AF used.
AF for the quality of the whole database:
1
Justification:
The subacute toxicity study via the oral route was conducted in accordance with GLP and OECD guideline 407, therefore has been assigned a reliability score of 1.
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:
1.25 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
DNEL value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation, oral to dermal, dermal NOAEC = oral NOAEL*(ABSoral/ ABSdermal). It has been assumed that the dermal adsorption is the same as the oral adsorption. Therefore, the dermal NOAEL is the same as the oral NOAEL, 750 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
A NOEAL of 750 mg/kg bw/d has been used as the starting point for DNEL derivation. Default AF used.
AF for differences in duration of exposure:
6
Justification:
The exposure duration of the test from which the dose descriptor is taken, subacute 28-d to chronic. Default AF used.
AF for interspecies differences (allometric scaling):
4
Justification:
The subacute toxicity study via the oral route was conducted using rats. Default AF used.
AF for other interspecies differences:
2.5
Justification:
To take into account the intersdpecies differences an assessment factor for remaining differences should be used . Default AF used.
AF for intraspecies differences:
10
Justification:
To take into account intraspecies variations for DNELs for the general population, the assessment factor is 10. Default AF used.
AF for the quality of the whole database:
1
Justification:
The subacute toxicity study via the oral route was conducted in accordance with GLP and OECD guideline 407, therefore has been assigned a reliability score of 1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor:
NOAEC
DNEL value:
750 mg/m³
AF for dose response relationship:
1
Justification:
A NOEAL of 750 mg/kg bw/d has been used as the starting point for DNEL derivation. Default AF used.
AF for differences in duration of exposure:
6
Justification:
The exposure duration of the test from which the dose descriptor is taken, subacute 28-d to chronic. Default AF used.
AF for interspecies differences (allometric scaling):
1
Justification:
In accordance with the ECHA REACH guidance, no allometric scaling default value is provided.
AF for other interspecies differences:
2.5
Justification:
To take into account the intersdpecies differences an assessment factor for remaining differences should be used . Default AF used.
AF for intraspecies differences:
10
Justification:
To take into account intraspecies variations for DNELs for the general population, the assessment factor is 10. Default AF used.
AF for the quality of the whole database:
1
Justification:
The subacute toxicity study via the oral route was conducted in accordance with GLP and OECD guideline 407, therefore has been assigned a reliability score of 1.
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:
1.25 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
DNEL value:
750 mg/kg bw/day
AF for dose response relationship:
1
Justification:
A NOEAL of 750 mg/kg bw/d has been used as the starting point for DNEL derivation. Default AF used.
AF for differences in duration of exposure:
6
Justification:
The exposure duration of the test from which the dose descriptor is taken, subacute 28-d to chronic. Default AF used.
AF for interspecies differences (allometric scaling):
4
Justification:
The subacute toxicity study via the oral route was conducted using rats. Default AF used.
AF for other interspecies differences:
2.5
Justification:
To take into account the intersdpecies differences an assessment factor for remaining differences should be used . Default AF used.
AF for intraspecies differences:
10
Justification:
To take into account intraspecies variations for DNELs for the general population, the assessment factor is 10. Default AF used.
AF for the quality of the whole database:
1
Justification:
The subacute toxicity study via the oral route was conducted in accordance with GLP and OECD guideline 407, therefore has been assigned a reliability score of 1.
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