Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
169 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see justification, comments and discussion below.
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 015 mg/m³
Explanation for the modification of the dose descriptor starting point:
The substance is effectively non-volatile. Inhalation data cannot be derived directly. It is only possible to estimate a DNEL by route to route extrapolation from the oral data. This derivation is described as follows: The long term oral systemic NOAEL is based on weight of evidence from two structurally related substances by read across (interpolation). The estimated NOAEL is from a repeat dose study in rats (BRRC (1990), molecular weight corrected NOAEL=434mg/kgbw/day). This is converted to an inhalation dose by dividing by 0.38 (Example R-82 p65 of guidance) = 1142mg/m3. Assuming 75% uptake of inhaled substance (upper end of range normally seen with oxygenated solvents) this is equivalent to an inhaled concentration (external) of 1523mg/m3. Corrected for basal load (light exercise) this is equivalent to a human concentration of 1015mg/m3.
AF for dose response relationship:
1
Justification:
Based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic default factor.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation route of exposure
AF for other interspecies differences:
1
Justification:
No additional factor deemed necessary. See detailed justification in document attached to this record.
AF for intraspecies differences:
3
Justification:
Proposed factor for workers. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
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:
181 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: see justification, comments and discussion below.
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
DNEL value:
4 340 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic default factor.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human extrapolation.
AF for other interspecies differences:
1
Justification:
No additional factor deemed necessary. See detailed justification in document attached to this record.
AF for intraspecies differences:
3
Justification:
No additional factor deemed necessary. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
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:
114 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see justification, comments and discussion below.
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 142 mg/m³
Explanation for the modification of the dose descriptor starting point:
The substance is effectively non-volatile. Inhalation data cannot be derived directly. It is only possible to estimate a DNEL by route to route extrapolation from the oral data. This derivation is described below: Long term oral systemic DNEL is based on weight of evidence from two structurally related substances by read across (interpolation). The estimated NOAEL is from a repeat dose study in rats (BRRC (1990), molecular weight corrected NOAEL=434mg/kgbw/day). This is converted to an inhalation dose by dividing by 0.38 (Example R-82 p65 of guidance) = 1142mg/m3. Assuming 75% uptake of inhaled substance (upper end of range normally seen with oxygenated solvents) this is equivalent to an inhaled concentration (external) of 1523mg/m3. Corrected for basal load (light exercise) this is equivalent to a human concentration of 1015mg/m3.
AF for dose response relationship:
1
Justification:
Based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic default factor.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation exposure.
AF for other interspecies differences:
1
Justification:
No additional factor deemed necessary. See detailed justification in document attached to this record.
AF for intraspecies differences:
5
Justification:
Proposed factor for consumers. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
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:
85 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: see justification, comments and discussion below.
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
4 340 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic default factor.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human extrapolation.
AF for other interspecies differences:
1
Justification:
No additional factor deemed necessary. See detailed justification in document attached to this record.
AF for intraspecies differences:
5
Justification:
Proposed factor for workers. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
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:
8.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see justification, comments and discussion below.
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
434 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic default factor.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human extrapolation.
AF for other interspecies differences:
1
Justification:
No additional factor deemed necessary. See detailed justification in document attached to this record.
AF for intraspecies differences:
5
Justification:
Proposed factor for workers. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default.
AF for remaining uncertainties:
1
Justification:
default.
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