Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.92 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
23 mg/m³
AF for dose response relationship:
1
Justification:
NOAEC is starting point for the DNEL description and the default assessment factor as standard procedure is 1
AF for differences in duration of exposure:
2
Justification:
The default AF (assessment factor) for differences in duration of exposure from sub-chronic exposure to chronic risk assessment is 2, according to Guidance Document R.8 (ECHA, 2012),
AF for interspecies differences (allometric scaling):
1
Justification:
The corrected NOAEC for workers 8h/day exposed is 23 mg/m³ and is covered with correction of dose-descriptor;
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences is 2.5.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies differences for workers is 5.
AF for the quality of the whole database:
1
Justification:
The database has a good quality and therefore the default factor of 1 applies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.322 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
other: LC 50
Value:
32.19 mg/m³
Explanation for the modification of the dose descriptor starting point:

A default AF of 100 is starting point, when deriving a DNELacute from LC50 according to Guidance Document R.8 (ECHA, 2012)

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.92 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor:
NOAEC
Value:
23 mg/m³
AF for dose response relationship:
1
Justification:
NOAEC is starting point for the DNEL description and the default assessment factor as standard procedure is 1
AF for differences in duration of exposure:
2
Justification:
The default AF (assessment factor) for differences in duration of exposure from sub-chronic exposure to chronic risk assessment is 2, according to Guidance Document R.8 (ECHA, 2012),
AF for interspecies differences (allometric scaling):
1
Justification:
The corrected NOAEC for workers 8h/day exposed is 23 mg/m³ and is covered with correction of dose-descriptor;
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences is 2.5.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies differences for workers is 5.
AF for the quality of the whole database:
1
Justification:
The database has a good quality and therefore the default factor of 1 applies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.322 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
other: LC50
Value:
32.19 mg/m³
Justification:
.

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.02 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
200.45 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:

The total AF for inter- and intraspecies variability (excluding allometry) of 12.5 for workers and of 25 for the general population, according to Guidance Document R.8 (ECHA, 2012)

AF for dose response relationship:
1
Justification:
NOAEL is starting point for the DNEL description and the default assessment factor as standard procedure is 1
AF for differences in duration of exposure:
2
Justification:
The default AF (assessment factor) for differences in duration of exposure from sub-chronic exposure to chronic risk assessment is 2, according to Guidance Document R.8 (ECHA, 2012),
AF for interspecies differences (allometric scaling):
1
Justification:
The corrected NOAEC for workers 8h/day exposed is 200.45 mg/kg bw and is covered with correction of dose-descriptor;
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences is 2.5.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies differences for workers is 5.
AF for the quality of the whole database:
1
Justification:
The database has a good quality and therefore the default factor of 1 applies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
other: LD50
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A default AF of 100 is starting point, when deriving a DNELacute from LD50 according to Guidance Document R.8 (ECHA, 2012),

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.758 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Justification:
The REACH TGD considers the availability of information on intraspecies variation of local effects very sparse and therefore proposes the same default AF as for systemic effects, i.e. 5 for workers and 10 for the general population.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.46 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
Value:
23 mg/m³
AF for dose response relationship:
1
Justification:
NOAEC is starting point for the DNEL description and the default assessment factor as standard procedure is 1
AF for differences in duration of exposure:
2
Justification:
The default AF (assessment factor) for differences in duration of exposure from sub-chronic exposure to chronic risk assessment is 2, according to Guidance Document R.8 (ECHA, 2012),
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences is 2.5.
AF for intraspecies differences:
10
Justification:
Default factor for intraspecies differences for general population is 10.
AF for the quality of the whole database:
1
Justification:
The database has a good quality and therefore the default factor of 1 applies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.322 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
other: LC50
Value:
32.19 mg/m³
Explanation for the modification of the dose descriptor starting point:

A default AF of 100 is starting point, when deriving a DNELacute from LC50 according to Guidance Document R.8 (ECHA, 2012),

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.46 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor:
NOAEC
Value:
23 mg/m³
AF for dose response relationship:
1
Justification:
NOAEC is starting point for the DNEL description and the default assessment factor as standard procedure is 1
AF for differences in duration of exposure:
2
Justification:
The default AF (assessment factor) for differences in duration of exposure from sub-chronic exposure to chronic risk assessment is 2, according to Guidance Document R.8 (ECHA, 2012),
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences is 2.5.
AF for intraspecies differences:
10
Justification:
Default factor for intraspecies differences for workers is 10
AF for the quality of the whole database:
1
Justification:
The database has a good quality and therefore the default factor of 1 applies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.322 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
other: LC50
Value:
32.19 mg/m³

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.01 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
200.45 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The total AF for inter- and intraspecies variability (excluding allometry) of 12.5 for workers and of 25 for the general population, according to Guidance Document R.8 (ECHA, 2012)

AF for dose response relationship:
1
Justification:
NOAEL is starting point for the DNEL description and the default assessment factor as standard procedure is 1
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
2
Justification:
Default factor for differences rat vs. human
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences is 2.5.
AF for intraspecies differences:
10
Justification:

Default factor for intraspecies differences for general population is10.
AF for the quality of the whole database:
1
Justification:
The database has a good quality and therefore the default factor of 1 applies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The total AF for inter- and intraspecies variability (excluding allometry) of 12.5 for workers and of 25 for the general population, according to Guidance Document R.8 (ECHA, 2012)

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.379 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Justification:
The REACH TGD considers the availability of information on intraspecies variation of local effects very sparse and therefore proposes the same default AF as for systemic effects, i.e. 5 for workers and 10 for the general population.
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:
3.85 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:
385 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL is starting point for the DNEL description and the default assessment factor as standard procedure is 1
AF for differences in duration of exposure:
1
Justification:
The data on mice and rats are available from oral sub-chronic and chronic studies demonstrating that toxicity is not depending on time of exposure.
The NOAEL in oral sub-chronic and chronic studies are similar.
Consequently, the factor of 1 used in this derivation can be considered conservative and appropriate.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for differences rat vs. human
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences is 2.5.
AF for intraspecies differences:
10
Justification:
Default factor for intraspecies differences for general population is10.
AF for the quality of the whole database:
1
Justification:
The database has a good quality and therefore the default factor of 1 applies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.9 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):
100
Dose descriptor starting point:
other: LD50
Value:
590 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A default AF of 100 is starting point, when deriving a DNELacute from LD50 according to Guidance Document R.8 (ECHA, 2012).

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population