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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
6.61 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):
10
Dose descriptor starting point:
NOAEL
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
66.12 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:
2
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 "explanation for hazard conclusion")
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 "explanation for hazard conclusion")
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 adverse effects were observed in this study up to 75 mg/kg bw/day (females), the highest dose tested. Therefore the NOAEL of this study was >/= 75 mg/kg bw/day and no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor starting point:
NOAEC
559.5 mg/m³
Modified dose descriptor starting point:
other: LC50
1 670 mg/m³
Explanation for the modification of the dose descriptor starting point:

Since original study was via inhalation route no route-to-route extrapolation is mandatory

AF for dose response relationship:
1
Justification:
LC50 is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
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 "explanation for hazard conclusion")
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 "explanation for hazard conclusion")
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)
1.88 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):
40
Dose descriptor starting point:
NOAEL
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Since a dermal absoprtion of 100% was assumed the orally derived dose descriptor starting point does not need to be modified.

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:
2
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 adverse effects were observed in this study up to 75 mg/kg bw/day (females), the highest dose tested. Therefore the NOAEL of this study was >/= 75 mg/kg bw/day and no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor starting point:
other: LD50
2 800 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
2 800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Since a dermal absoprtion of 100% was assumed the orally derived dose descriptor starting point does not need to be modified.

AF for dose response relationship:
1
Justification:
LD50 is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
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:
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

please refer to "explanation for hazard conclusion" of each hazard point

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
1.63 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):
20
Dose descriptor starting point:
NOAEL
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
32.61 mg/m³
Explanation for the modification of the dose descriptor starting point:

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:
2
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 "explanation for hazard conclusion")
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 "explanation for hazard conclusion")
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 adverse effects were observed in this study up to 75 mg/kg bw/day (females), the highest dose tested. Therefore the NOAEL of this study was >/= 75 mg/kg bw/day and no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information
Explanation for the modification of the dose descriptor starting point:

.

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:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
0.94 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):
80
Dose descriptor starting point:
NOAEL
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Since a dermal absoprtion of 100% was assumed the orally derived dose descriptor starting point does not need to be modified.

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:
2
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 adverse effects were observed in this study up to 75 mg/kg bw/day (females), the highest dose tested. Therefore the NOAEL of this study was >/= 75 mg/kg bw/day and no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
0.94 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):
80
Dose descriptor starting point:
NOAEL
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of dose descriptor starting point needed since original study used oral route.

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:
2
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 adverse effects were observed in this study up to 75 mg/kg bw/day (females), the highest dose tested. Therefore the NOAEL of this study was >/= 75 mg/kg bw/day and no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

please refer to "explanation for hazard conclusion" of each hazard point