Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
173 µg/m³
Most sensitive endpoint:
carcinogenicity
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:
2.46 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
4.34 mg/m³
Explanation for the modification of the dose descriptor starting point:

=NOAEL *6.7/10/0.38 (see REACH guidance chapter R.8, 2012)

AF for dose response relationship:
1
Justification:
see REACH guidance R.8
AF for differences in duration of exposure:
1
Justification:
basis is chronic study
Justification:
see REACH guidance R.8, included in modified dose descriptor
AF for other interspecies differences:
2.5
Justification:
see REACH guidance R.8
AF for intraspecies differences:
5
Justification:
see REACH guidance R.8
AF for the quality of the whole database:
1
Justification:
Studies are complete, consistent and availble in good quality. Read across from hydrobromide to free base is considered not to add systemic uncertainty.
AF for remaining uncertainties:
2
Justification:
Use of scopolamine hydrobromid read across
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24.6 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
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:
2.46 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
0.615 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal absorption rate factor versus oral is taken as 1. Allometric scaling factor of 4 used in modified dose descriptor as per REACH guidance chapter R.8 (2012).

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
see REACH guidance R.8, included in modified dose descriptor
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high 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:
87 µg/m³
Most sensitive endpoint:
carcinogenicity
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:
2.46 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
4.34 mg/m³
Explanation for the modification of the dose descriptor starting point:

=NOAEL *6.7/10/0.38 (see REACH guidance chapter R.8, 2012)

AF for dose response relationship:
1
Justification:
see REACH guidance R.8
AF for differences in duration of exposure:
1
Justification:
chronic 2-year study
Justification:
see REACH guidance R.8, included in modified dose descriptor
AF for other interspecies differences:
2.5
Justification:
see REACH guidance R.8
AF for intraspecies differences:
10
Justification:
see REACH guidance R.8
AF for the quality of the whole database:
1
Justification:
Studies are complete, consistent and availble in good quality. Read across from hydrobromide to free base is considered not to add systemic uncertainty.
AF for remaining uncertainties:
2
Justification:
not applicable
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
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)
Value:
12.3 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
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:
2.46 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
0.615 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal absorption rate factor versus oral is taken as 1. Allometric scaling included in modified dose descriptor as per REACH guidance chapter R.8 (2012).

AF for dose response relationship:
1
Justification:
see REACH guidance R.8
AF for differences in duration of exposure:
1
Justification:
chronic 2-year study
Justification:
see REACH guidance R.8, included in modified dose descriptor
AF for other interspecies differences:
2.5
Justification:
see REACH guidance R.8
AF for intraspecies differences:
10
Justification:
see REACH guidance R.8
AF for the quality of the whole database:
1
Justification:
Studies are complete, consistent and availble in good quality. Read across from hydrobromide to free base is considered not to add systemic uncertainty.
AF for remaining uncertainties:
2
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.3 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
2.46 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
0.615 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Allometric scaling included in modified dose descriptor as per REACH guidance chapter R.8 (2012).

AF for dose response relationship:
1
Justification:
see REACH guidance R.8
AF for differences in duration of exposure:
1
Justification:
chronic 2-year study
Justification:
see REACH guidance R.8, included in modified dose descriptor
AF for other interspecies differences:
2.5
Justification:
see REACH guidance R.8
AF for intraspecies differences:
10
Justification:
see REACH guidance R.8
AF for the quality of the whole database:
1
Justification:
Studies are complete, consistent and availble in good quality. Read across from hydrobromide to free base is considered not to add systemic uncertainty.
AF for remaining uncertainties:
2
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population