Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.29 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
247 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL should be 200mg/kg/day as NOAEL because, in terms of sensitivity, the value from the reproductive toxicity screening study should be referred to.  The reason is because it is more reliable than 28d repeated toxicity data as the exposure duration is longer (over 60-day for female animals) and the lower LOAEL (600 mg/kg/day) was obtained.

AF for dose response relationship:
1
Justification:
The value of 1 is the default for dose descriptor NOAEL.
AF for differences in duration of exposure:
6
Justification:
The value of 6 is default for sub-acute study.
AF for interspecies differences (allometric scaling):
1
Justification:
The default value 4 for rat is not applicable as respiratory rates depend directly on caloric demand, hence value 1 is used.
AF for other interspecies differences:
2.5
Justification:
The value of 2.5 is default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
5
Justification:
The default value is 5 for works according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
AF for the quality of the whole database:
1
Justification:
The default value is 1 according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
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:
0.933 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
280 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL should be 200mg/kg/day as NOAEL because, in terms of sensitivity, the value from the reproductive toxicity screening study should be referred to.  The reason is because it is more reliable than 28d repeated toxicity data as the exposure duration is longer (over 60-day for female animals) and the lower LOAEL (600 mg/kg/day) was obtained.

AF for dose response relationship:
1
Justification:
The value of 1 is default for dose descriptor NOAEL.
AF for differences in duration of exposure:
6
Justification:
The value of 6 is default for sub-acute study.
AF for interspecies differences (allometric scaling):
4
Justification:
The default value is 4 for study animal rats.
AF for other interspecies differences:
2.5
Justification:
The value of 2.5 is default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
5
Justification:
The default value is 5 for works according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
AF for the quality of the whole database:
1
Justification:
The default value is 1 for quality of whole database according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
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:
0.58 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL should be 200mg/kg/day as NOAEL because, in terms of sensitivity, the value from the reproductive toxicity screening study should be referred to.  The reason is because it is more reliable than 28d repeated toxicity data as the exposure duration is longer (over 60-day for female animals) and the lower LOAEL (600 mg/kg/day) was obtained.

AF for dose response relationship:
1
Justification:
The value of 1 is default for dose descriptor NOAEL.
AF for differences in duration of exposure:
6
Justification:
The value of 6 is default for sub-acute study.
AF for interspecies differences (allometric scaling):
1
Justification:
The default value 4 for rat is not applicable as respiratory rates depend directly on caloric demand, hence value 1 is used.
AF for other interspecies differences:
2.5
Justification:
The value of 2.5 is default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
10
Justification:
The default value is 10 for general population according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
AF for the quality of the whole database:
1
Justification:
The default value is 1 for quality of whole database according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
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:
0.333 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL should be 200mg/kg/day as NOAEL because, in terms of sensitivity, the value from the reproductive toxicity screening study should be referred to.  The reason is because it is more reliable than 28d repeated toxicity data as the exposure duration is longer (over 60-day for female animals) and the lower LOAEL (600 mg/kg/day) was obtained.

AF for dose response relationship:
1
Justification:
The value of 1 is default for dose descriptor NOAEL.
AF for differences in duration of exposure:
6
Justification:
The value of 6 is default for sub-acute study.
AF for interspecies differences (allometric scaling):
4
Justification:
The default value is 4 for study animal rats.
AF for other interspecies differences:
2.5
Justification:
The value of 2.5 is default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
10
Justification:
The default value is 10 for general population according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
AF for the quality of the whole database:
1
Justification:
The default value is 1 for quality of whole database according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
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:
0.333 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL should be 200mg/kg/day as NOAEL because, in terms of sensitivity, the value from the reproductive toxicity screening study should be referred to.  The reason is because it is more reliable than 28d repeated toxicity data as the exposure duration is longer (over 60-day for female animals) and the lower LOAEL (600 mg/kg/day) was obtained.

AF for dose response relationship:
1
Justification:
The value of 1 is default for dose descriptor NOAEL.
AF for differences in duration of exposure:
6
Justification:
The value of 6 is default for sub-acute study.
AF for interspecies differences (allometric scaling):
4
Justification:
The default value is 4 for study animal rats.
AF for other interspecies differences:
2.5
Justification:
The value of 2.5 is default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
10
Justification:
The default value is 10 for general population according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
AF for the quality of the whole database:
1
Justification:
The default value is 1 for quality of whole database according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8.
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