Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.94 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):
30
Modified dose descriptor starting point:
NOAEC
DNEL value:
88.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
The original study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for other interspecies differences:
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
708.8 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
DNEL value:
3 543.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
The original study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for other interspecies differences:
1
Justification:
Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 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):
120
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The original study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.1 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 010 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The original study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

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:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

please refer to "justification and comments" of each hazard point

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.73 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):
60
Modified dose descriptor starting point:
NOAEC
DNEL value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
The original study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for other interspecies differences:
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
174.8 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 747.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
The original study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for other interspecies differences:
1
Justification:
Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.21 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):
240
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The original study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50.3 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 010 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The original study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

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:
low hazard (no threshold derived)
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:
0.21 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):
240
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
n.a.; most sensitive endpoint study is repeated dose oral toxicity study
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50.3 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 010 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
n.a.; most sensitive endpoint study is acute oral toxicity study
AF for dose response relationship:
1
Justification:
Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

please refer to "justification and comments" of each hazard point