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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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
Modified dose descriptor starting point:
NOAEC
Value:
264 mg/m³
Explanation for the modification of the dose descriptor starting point:

No specific toxicokinetic data available, thus according to ECHA guidance 50% oral absorption in rat is assumed as well as 100%  by inhalation

AF for dose response relationship:
1
Justification:
NOAEL was used as starting point
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
This factor describes the differences in metabolic rate between rats and humans.
AF for other interspecies differences:
2.5
Justification:
Default factor to accounts for remaining differences (e.g. toxicodynamics)
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
No further uncertainties, NOAEL is already based on worst case assumptions.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
83 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
Modified dose descriptor starting point:
NOAEL
Value:
25 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A NOAEL of 300 mg/kg bw/day was identified from an oral rat OECD 422 study.                                                                                                                                             The corrected dermal NOAEL = NOAEL (oral) x ABS (rat-oral)/ABS (derm - human) as given in ECHA guidance R8, example B.5.                                                         Assuming an oral absorption of 100% (rat) and using testing data (0.6%)  from an in vitro human dermal absorption study (see section 7.1.2)  the corrected dermal NOAEL is  NOAEL = 300 mg/kg bw/day x 100%/0.6% = 50000 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
NOAEL was used as starting point
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
This factor describes the differences in metabolic rate between rats and humans.
AF for other interspecies differences:
2.5
Justification:
Default factor to accounts for remaining differences (e.g. toxicodynamics)
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
No further uncertainties, NOAEL is already based on worst case assumptions.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The following DNEL values for workers have been considered:

DNEL (inhalation, long-term systemic effects): 3.5 mg/m3

DNEL (inhalation, long-term local effects effects): no adequate data aviallable

DNEL (dermal, long-term systemic effect): 83 mg/kg d

DNEL (dermal, long-term local effects): skin sensitiser/ irritant

DNEL (dermal, short term local effects): skin senstiser

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 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
Modified dose descriptor starting point:
NOAEC
Value:
130 mg/m³
Explanation for the modification of the dose descriptor starting point:

No specific toxicokinetic data available, thus according to ECHA guidance 50% oral absorption in rat is assumed as well as 100%  by inhalation

AF for dose response relationship:
1
Justification:
NOAEL was used as starting point
AF for differences in duration of exposure:
6
Justification:
No extrapolation needed
AF for interspecies differences (allometric scaling):
1
Justification:
This factor describes the differences in metabolic rate between rats and humans.
AF for other interspecies differences:
2.5
Justification:
Default factor to accounts for remaining differences (e.g. toxicodynamics)
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
No further uncertainties, NOAEL is already based on worst case assumptions.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
42 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
Modified dose descriptor starting point:
NOAEL
Value:
25 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A NOAEL of 300 mg/kg bw/day was identified from an oral rat OECD 422 study.                                                                                                                                             The corrected dermal NOAEL = NOAEL (oral) x ABS (rat-oral)/ABS (derm - human) as given in ECHA guidance R8, example B.5.                                                         Assuming an oral absorption of 100% (rat) and using testing data (0.6%)  from an in vitro human dermal absorption study (see section 7.1.2)  the corrected dermal NOAEL is  NOAEL = 300 mg/kg bw/day x 100%/0.6% = 50000 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
NOAEL was used as starting point
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
This factor describes the differences in metabolic rate between rats and humans.
AF for other interspecies differences:
2.5
Justification:
Default factor to accounts for remaining differences (e.g. toxicodynamics)
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
No further uncertainties, NOAEL is already based on worst case assumptions.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Assume same oral absorption rate in rat and human

AF for dose response relationship:
1
Justification:
NOAEL was used as starting point
AF for differences in duration of exposure:
6
Justification:
No extrapolation needed
AF for interspecies differences (allometric scaling):
4
Justification:
This factor describes the differences in metabolic rate between mice and humans.
AF for other interspecies differences:
2.5
Justification:
Default factor to accounts for remaining differences (e.g. toxicodynamics)
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
No further uncertainties, NOAEL is already based on worst case assumptions.
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

The following DNEL values for the general population have been considered:

DNEL (inhalation, long-term systemic effects): 0.87 mg/m3

DNEL (inhalation, long-term local effects effects): no adequate data aviallable

DNEL (dermal, long-term systemic effect): 42 mg/kg /d

DNEL (dermal, long-term local effects): skin sensitiser/ irritant

DNEL (dermal, short term local effects): skin senstiser

DNEL (oral, long-term, systemic effects): 0.5 mg/kg /d

DNEL (oral, short term local effects): No hazard identified