Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.3 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):
300
Modified dose descriptor starting point:
NOAEC
Value:
7 000 mg/m³
Explanation for the modification of the dose descriptor starting point:

No inhalation study undertaken.

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic default value
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value
AF for other interspecies differences:
2.5
Justification:
Correction for metabolic rate default value
AF for intraspecies differences:
5
Justification:
Worker default value
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
280 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
14 000 mg/m³
Explanation for the modification of the dose descriptor starting point:

No inhalation study avalaible

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value
AF for other interspecies differences:
2.5
Justification:
Correction for metabolic rate default value
AF for intraspecies differences:
5
Justification:
Worker default value
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic exposure default value.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value
AF for other interspecies differences:
2.5
Justification:
Correction for metabolic rate default value
AF for intraspecies differences:
5
Justification:
Worker default value
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
280 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value
AF for other interspecies differences:
2.5
Justification:
Correction for metabolic rate default value
AF for intraspecies differences:
5
Justification:
Worker default value
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No dermal study available.

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic exposure default value.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value
AF for other interspecies differences:
2.5
Justification:
Correction for metabolic rate default value
AF for intraspecies differences:
5
Justification:
Worker default value
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40 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):
50
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No dermal study available.

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value
AF for other interspecies differences:
2.5
Justification:
Correction for metabolic rate; default value
AF for intraspecies differences:
5
Justification:
Worker default value
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
120
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic exposure default value.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value
AF for other interspecies differences:
1
Justification:
No indication of irritation, therefore 1:1 extrapolation used.
AF for intraspecies differences:
5
Justification:
Worker default value
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor starting point:
other: NOAEL
AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value
AF for other interspecies differences:
1
Justification:
No indication of irritation, therefore 1:1 extrapolation used.
AF for intraspecies differences:
5
Justification:
Worker default value
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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:
11.7 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):
600
Modified dose descriptor starting point:
NOAEC
Value:
7 000 mg/m³
Explanation for the modification of the dose descriptor starting point:

No inhalation study available.

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic defualt value.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
2.5
Justification:
Default value for correction to metabolic rate value.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 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):
100
Modified dose descriptor starting point:
NOAEC
Value:
14 000 mg/m³
Explanation for the modification of the dose descriptor starting point:

no inhalation study available.

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
2.5
Justification:
Default value for correction to metabolic rate value.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic defualt value.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
2.5
Justification:
Default value for correction to metabolic rate value.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
140 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:
NOAEC
AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
2.5
Justification:
Default value for correction to metabolic rate value.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal study returned a negative result. Only oral study available.

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic default value.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
2.5
Justification:
Default value for correction to metabolic rate value.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal study returned a negative result. Only oral study available.

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
2.5
Justification:
Default value for correction to metabolic rate value.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
240
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for differences in duration of exposure:
6
Justification:
Sub-chronic to chronic default value.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
1
Justification:
Dermal toxicity study gave a negative reponse. Therefore a 1:1 extrapolation employed.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Dose descriptor starting point:
other: NOAEL
AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
1
Justification:
Dermal toxicity study gave a negative reponse. Therefore a 1:1 extrapolation employed.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal study returned a negative result. Only oral study available.

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for differences in duration of exposure:
6
Justification:
Sub acute to chronic default value.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
2.5
Justification:
Default value for correction to metabolic rate value.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal study returned a negative result. Only oral study available.

AF for dose response relationship:
1
Justification:
Dose response regarded as reliable
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human default value.
AF for other interspecies differences:
2.5
Justification:
Default value for correction to metabolic rate value.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value; database regarded as reliable.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population