Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
195 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see justification below.
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Value:
1 170 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL of 500mg/kg established for the oral route is converted to an inhalation dose by dividing by 0.38 (Example R-82 p65 of guidance) = 1316mg/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 1754mg/m3. Corrected for basal load for workers (light exercise, x0.667) this is equivalent to a human concentration of 1170mg/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:
No factor required for inhalation when expressed in units of mg/m3.
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:
208 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: see justification below
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Value:
5 000 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:
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Note that the derived DNEL exceeds the saturated vapour pressure for this substance so this is a theoretical value only.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
117 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see discussion below
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
1 170 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL of 500mg/kg established for the oral route is converted to an inhalation dose by dividing by 0.38 (Example R-82 p65 of guidance) = 1316mg/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 1754mg/m3. Corrected for basal load (light exercise, x0.667) this is equivalent to a human concentration of 1170mg/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:
No factor required for inhalation when expressed in units of mg/m3.
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:
125 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: see justification below
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
5 000 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 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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see justification below.
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
500 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 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

The inhalation DNEL would need to be corrected for duration for toxicity via the environment comparisons. Note also that this DNEL exceeds the saturated vapour pressure.

Note that the derived DNEL exceeds the saturated vapour pressure for this substance so this is a theoretical value only.