Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23 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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:

There is no inhalation toxicity study available. The NOAEC is calculated as follows: oral NOAEL*(1/(0.38 m3/kg/d))*(ABSoral rat/ABSinh human)*(6.7 m3(8h)/10 m3(8h)) 

AF for dose response relationship:
1
Justification:
No assessment factor is needed as a NOAEL was used as starting dose descriptor.
AF for differences in duration of exposure:
6
Justification:
Standard factor for scaling of subacute to chronic duration of the study.
AF for interspecies differences (allometric scaling):
1
Justification:
This is taken into account in the calculation from NOAEL to NOAEC.
AF for other interspecies differences:
2.5
Justification:
Standard factor.
AF for intraspecies differences:
5
Justification:
Standard factor for worker.
AF for the quality of the whole database:
1
Justification:
DNEL is derived from a reliable repeated dose toxicity study
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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:
26 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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
7 874 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is no inhalation toxicity study available. The corrected dermal NOAEL is based on the available dermal absorption study and resulting skin absorption value of 12.7%.

AF for dose response relationship:
1
Justification:
No assessment factor is needed as a NOAEL was used as starting dose descriptor.
AF for differences in duration of exposure:
6
Justification:
Standard factor for scaling of subacute to chronic duration of the study.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor.
AF for other interspecies differences:
2.5
Justification:
Standard factor.
AF for intraspecies differences:
5
Justification:
Standard factor for worker.
AF for the quality of the whole database:
1
Justification:
DNEL is derived from a reliable repeated dose toxicity study.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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:
DNEL (Derived No Effect Level)
Value:
2 050 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
Justification:
No assessment factor is needed as a no effect concentration was used as starting dose descriptor.
AF for interspecies differences (allometric scaling):
1
Justification:
There are no interspecies differences as the study was performed in human.
AF for other interspecies differences:
1
Justification:
There are no interspecies differences as the study was performed in human.
AF for intraspecies differences:
10
Justification:
Standard factor for general population.
AF for the quality of the whole database:
1
Justification:
Threshold is derived from a reliable hRIPT.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.

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:
5.7 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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
869 mg/m³
Explanation for the modification of the dose descriptor starting point:

There is no inhalation toxicity study available. The NOAEC is calculated as follows: oral NOAEL*(1/(1.15 m3/kg/d))*(ABSoral rat/ABSinh human).

AF for dose response relationship:
1
Justification:
No assessment factor is needed as a NOAEL was used as starting dose descriptor.
AF for differences in duration of exposure:
6
Justification:
Standard factor for scaling of subacute to chronic duration of the study.
AF for interspecies differences (allometric scaling):
1
Justification:
This is taken into account in the calculation from NOAEL to NOAEC.
AF for other interspecies differences:
2.5
Justification:
Standard factor.
AF for intraspecies differences:
10
Justification:
Standard factor for general population.
AF for the quality of the whole database:
1
Justification:
DNEL is derived from a reliable repeated dose toxicity study
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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:
13 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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
7 874 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is no inhalation toxicity study available. The corrected dermal NOAEL is based on the available dermal absorption study and resulting skin absorption value of 12.7%.

AF for dose response relationship:
1
Justification:
No assessment factor is needed as a NOAEL was used as starting dose descriptor.
AF for differences in duration of exposure:
6
Justification:
Standard factor for scaling of subacute to chronic duration of the study.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor.
AF for other interspecies differences:
2.5
Justification:
Standard factor.
AF for intraspecies differences:
10
Justification:
Standard factor for general population.
AF for the quality of the whole database:
1
Justification:
DNEL is derived from a reliable repeated dose toxicity study.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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:
DNEL (Derived No Effect Level)
Value:
2 050 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
Justification:
No assessment factor is needed as a no effect concentration was used as starting dose descriptor.
AF for interspecies differences (allometric scaling):
1
Justification:
There are no interspecies differences as the study was performed in human.
AF for other interspecies differences:
1
Justification:
There are no interspecies differences as the study was performed in human.
AF for intraspecies differences:
10
Justification:
Standard factor for general population.
AF for the quality of the whole database:
1
Justification:
Threshold is derived from a reliable hRIPT.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.

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:
ECHA REACH Guidance
Overall assessment factor (AF):
600
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 most relevant NOAEL for oral DNELs is 1000 mg/kg bw/d determined in a combined 28-day repeated dose toxicity (OECD 422) study.

AF for dose response relationship:
1
Justification:
No assessment factor is needed as a NOAEL was used as starting dose descriptor.
AF for differences in duration of exposure:
6
Justification:
Standard factor for scaling of subacute to chronic duration of the study.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor.
AF for other interspecies differences:
2.5
Justification:
Standard factor.
AF for intraspecies differences:
10
Justification:
Standard factor for general population.
AF for the quality of the whole database:
1
Justification:
DNEL is derived from reliable repeated dose toxicity study.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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