Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.1 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
Modified dose descriptor starting point:
NOAEC
Value:
52.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
Starting point is a 90-day study in rat by oral route which establishing a NOAEL of 30 mg/kg bw/day for systemic toxicity. Corrected inhalation NOAEC = oral NOAELrat (30 mg/kg) * 1/0.38 * 6.7/10 = 52.9 mg/m3. No factor 2 route extrapolation from oral to inhalation. Due to low vapour pressure (0.18 Pa at 20 °C), relevant exposure is only possible as aerosol (no fine spraying, only larger droplets). Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.
AF for dose response relationship:
1
Justification:
No specific concerns. Effects at LOAEL are not severe and mostly of local nature (irritation stomach)
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation since this is already accounted for when obtaining the corrected NOEC
AF for other interspecies differences:
2.5
Justification:
Default remaining factor
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
Based on good quality and consistent data.
AF for remaining uncertainties:
1
Justification:
No major remaining uncertainties. As based on basic data, the default AF have been applied in full.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Starting point is a 90-day study in rat by oral route which establishing a NOAEL of 30 mg/kg bw/day for systemic toxicity.
AF for dose response relationship:
1
Justification:
No specific concerns. Effects at LOAEL are not severe and mostly of local nature (irritation stomach)
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
Default remaining factor
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
Based on good quality and consistent data
AF for remaining uncertainties:
1
Justification:
No major remaining uncertainties. As based on basic data, the default AFs have been applied in full.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

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:
0.52 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
26.1 mg/m³
Explanation for the modification of the dose descriptor starting point:
Starting point is a 90-day study in rat by oral route which establishing a NOAEL of 30 mg/kg bw/day for systemic toxicity. Corrected inhalation NOAEC = oral NOAELrat (30 mg/kg) * 1/1.15 mg/m3 = 26.1 mg/m3. No factor 2 route extrapolation from oral to inhalation. Due to low vapour pressure (0.18 Pa at 20 °C), relevant exposure is only possible as aerosol (no fine spraying, only larger droplets). Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.
AF for dose response relationship:
1
Justification:
No specific concerns. Effects at LOAEL are not severe and mostly of local nature (irritation stomach)
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation since this is already accounted for when obtaining the corrected NOEC
AF for other interspecies differences:
2.5
Justification:
Default remaining factor
AF for intraspecies differences:
10
Justification:
Default for general public
AF for the quality of the whole database:
1
Justification:
Based on good quality and consistent data
AF for remaining uncertainties:
1
Justification:
No major remaining uncertainties. As based on basic data, the default AFs have been applied in full.
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:
0.15 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
30
Explanation for the modification of the dose descriptor starting point:
Starting point is a 90-day study in rat by oral route which establishing a NOAEL of 30 mg/kg bw/day for systemic toxicity.
AF for dose response relationship:
1
Justification:
No specific concerns. Effects at LOAEL are not severe and mostly of local nature (irritation stomach)
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
Default remaining factor
AF for intraspecies differences:
10
Justification:
Default for general public
AF for the quality of the whole database:
1
Justification:
Based on good quality and consistent data
AF for remaining uncertainties:
1
Justification:
No major remaining uncertainties. As based on basic data, the default AFs have been applied in full.
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:
0.15 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required
AF for dose response relationship:
1
Justification:
No specific concerns. Effects at LOAEL are not severe and mostly of local nature (irritation stomach)
AF for differences in duration of exposure:
2
Justification:
Default sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
Default remaining factor
AF for intraspecies differences:
10
Justification:
Default for general public
AF for the quality of the whole database:
1
Justification:
Based on good quality and consistent data
AF for remaining uncertainties:
1
Justification:
No major remaining uncertainties. As based on basic data, the default AFs have been applied in full.
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

The uses indicated in this dossier are limited to industrial and professional users and exposure of the general population is not to be expected.

Also assessment of indirect exposure is not needed as the tonnage is not above 1000 tpa, and the substance not is classified as CMR or toxic (R48 or STOT-RE).

However, to allow for evaluation from indirect exposures via the environment, DNELs have been derived for systemic toxicity from long term exposures via all routes.