Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.4 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
Value:
1 230 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL is derived based on an OECD 422 study in rats via the oral route using default assessment factors.

AF for dose response relationship:
1
Justification:
Default AF used in the absence of effects
AF for differences in duration of exposure:
6
Justification:
Default AF for subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Covered by route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default value sufficient
AF for intraspecies differences:
5
Justification:
Default value sufficient
AF for the quality of the whole database:
1
Justification:
No additional AF necessary as the OECD 422 study used is of good quality and applicability
AF for remaining uncertainties:
1
Justification:
No further AF required.
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:
4.67 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
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The OECD 422 study is of good quality and applicability and no uncertainties are foreseen.

AF for dose response relationship:
1
Justification:
Default AF- no uncertainties related to reliability for dose response.
AF for differences in duration of exposure:
6
Justification:
Default AF for subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for allometric scaling from rat to human
AF for other interspecies differences:
2.5
Justification:
Default AF for interspecies fifferences
AF for intraspecies differences:
5
Justification:
Default for worker population
AF for the quality of the whole database:
1
Justification:
No gaps in the database
AF for remaining uncertainties:
1
Justification:
No further assessment factors necessary
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No DNEL is derived as no hazards to the skin or eye were identified nor effects seen via the dermal route and there are no acute effects seen via the oral route.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
2.9 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
Value:
435 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default modification factor used for the corresponding air concentration.

AF for dose response relationship:
1
Justification:
No uncertainties exist regarding the dose response relationship.
AF for differences in duration of exposure:
6
Justification:
Default factor for subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
Default value, covered by route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default for interspecies differences.
AF for intraspecies differences:
10
Justification:
Default for the general population
AF for the quality of the whole database:
1
Justification:
No additional AF necessary for the quality of the database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties requiring additional AFs necessary.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No studies via inhalation exposure are available. The substance is not classified for acute oral toxicity and so no acute effects via inhalation exposure are expected.

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:
1.67 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
AF for dose response relationship:
1
Justification:
Default AF used, no uncertainties regarding dose response relationship.
AF for differences in duration of exposure:
6
Justification:
Default subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rat to human scaling
AF for other interspecies differences:
2.5
Justification:
Default for interspecies differences
AF for intraspecies differences:
10
Justification:
Default for the general population
AF for the quality of the whole database:
1
Justification:
Default AF, no additional uncertainties regarding the database
AF for remaining uncertainties:
1
Justification:
No further AF required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not classified for local effects.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.67 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
AF for dose response relationship:
1
Justification:
Default- no additional uncertainties
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic exposure extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat to human scaling
AF for other interspecies differences:
2.5
Justification:
Default AF for interspecies differences
AF for intraspecies differences:
10
Justification:
Default AF for the general population
AF for the quality of the whole database:
1
Justification:
Default- no additional uncertainties related to the quality of the database
AF for remaining uncertainties:
1
Justification:
No additional AFs necessary
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

References:

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterization of dose [concentration]-response for human health. Version 2.1, November 2012

ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterization, Version 3.0, May 2016