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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
Value:
18 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
20 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point from an oral study (oral NOAEL) is modified taking into account activity levels (*6.7/10), breathing rate (*1/0.38), the extent of oral absorption (46%, measured) and the extent of inhalation absorption (100%, assumed), and differerences in exposure pattern (*7/5).  The modified starting point (inhalation NOAEC) is therefore 20 mg/m3.

AF for dose response relationship:
1
Justification:
An AF of 1 is used as the starting point is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
An AF of 1 is used as the starting point is from a chronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
An AF is not required as allometric factors have already been taken into account when deriving the modified starting point.
AF for other interspecies differences:
2.5
Justification:
A default AF of 2.5 is used, in line with ECHA guidance.
AF for intraspecies differences:
5
Justification:
A default AF of 5 is used, in line with ECHA guidance.
AF for the quality of the whole database:
1
Justification:
An AF of 1 is used as the database is of high quality.
AF for remaining uncertainties:
1
Justification:
An AF of 1 is used in the absence of 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:
116 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):
50
Dose descriptor starting point:
NOAEL
Value:
18 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
5 796 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point from an oral study (oral NOAEL) is modified taking into account the extent of oral absorption (46%, measured) and the extent of dermal absorption (0.2%, measured), and differerences in exposure pattern (*7/5).  The modified starting point (dermal NOAEL) is therefore 5796 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
An AF of 1 is used as the starting point is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
An AF of 1 is used as the starting point is from a chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
An AF of 4 is used as the starting point is from a rat study.
AF for other interspecies differences:
2.5
Justification:
A default AF of 2.5 is used, in line with ECHA guidance.
AF for intraspecies differences:
5
Justification:
A default AF of 5 is used, in line with ECHA guidance.
AF for the quality of the whole database:
1
Justification:
An AF of 1 is used as the database is of high quality.
AF for remaining uncertainties:
1
Justification:
An AF of 1 is used in the absence of 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

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:
0.3 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):
25
Dose descriptor starting point:
NOAEL
Value:
18 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
7.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point from an oral study (oral NOAEL) is modified taking into breathing rate (*1/1.15), the extent of oral absorption (46%, measured) and the extent of inhalation absorption (100%, assumed). The modified starting point (inhalation NOAEC) is therefore 7.2 mg/m3.

AF for dose response relationship:
1
Justification:
An AF of 1 is used as the starting point is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
An AF of 1 is used as the starting point is from a chronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
An AF is not required as allometric factors have already been taken into account when deriving the modified starting point.
AF for other interspecies differences:
2.5
Justification:
A default AF of 2.5 is used, in line with ECHA guidance.
AF for intraspecies differences:
10
Justification:
A default AF of 10 is used, in line with ECHA guidance.
AF for the quality of the whole database:
1
Justification:
An AF of 1 is used as the database is of high quality.
AF for remaining uncertainties:
1
Justification:
An AF of 1 is used in the absence of 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:
41 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):
100
Dose descriptor starting point:
NOAEL
Value:
18 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
4 140 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point from an oral study (oral NOAEL) is modified taking into account the extent of oral absorption (46%, measured) and the extent of dermal absorption (0.2%, measured). The modified starting point (dermal NOAEL) is therefore 4140 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
An AF of 1 is used as the starting point is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
An AF of 1 is used as the starting point is from a chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
An AF of 4 is used as the starting point is from a rat study.
AF for other interspecies differences:
2.5
Justification:
A default AF of 2.5 is used, in line with ECHA guidance.
AF for intraspecies differences:
10
Justification:
A default AF of 10 is used, in line with ECHA guidance.
AF for the quality of the whole database:
1
Justification:
An AF of 1 is used as the database is of high quality.
AF for remaining uncertainties:
1
Justification:
An AF of 1 is used in the absence of 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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.18 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):
100
Dose descriptor starting point:
NOAEL
Value:
18 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
18 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point is from an oral study and does not therefore require modification.

AF for dose response relationship:
1
Justification:
An AF of 1 is used as the starting point is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
An AF of 1 is used as the starting point is from a chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
An AF of 4 is used as the starting point is from a rat study.
AF for other interspecies differences:
2.5
Justification:
A default AF of 2.5 is used, in line with ECHA guidance.
AF for intraspecies differences:
10
Justification:
A default AF of 10 is used, in line with ECHA guidance.
AF for the quality of the whole database:
1
Justification:
An AF of 1 is used as the database is of high quality.
AF for remaining uncertainties:
1
Justification:
An AF of 1 is used in the absence of 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:
no hazard identified

Additional information - General Population