Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
245 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see justification and comments below.
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Value:
1 490 mg/m³
Explanation for the modification of the dose descriptor starting point:

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 NOEC=640mg/kgbw/day). This is converted to an inhalation dose by dividing by 0.38 (Example R-82 p65 of guidance) = 1684mg/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 2245mg/m3. Corrected for basal load (light exercise, x0.667) this is equivalent to a human concentration of 1490mg/m3.

Molecular weight correction was performed on the effect level used to determine the DNEL. The molecular weight used for this test material is based on a weighted average using the typical composition.  The molecular weight of the components were multiplied by their typical percentage and then added up. This resulted in the weighted molecular weight of 260.

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 the inhalation route where the units are in 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:
265 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see justification and comments below.
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Value:
6 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long term dermal systemic DNEL based on data from a structurally related substance by read across.. The estimated NOAEL is from a repeat dose study in rats (Dow (1990), molecular weight corrected NOEC=6400mg/kgbw/day). Dermal absorption is assumed to be 100%, which is likely to be exceptionally conservative.

Molecular weight correction was performed on the effect level used to determine the DNEL. The molecular weight used for this test material is based on a weighted average using the typical composition. The molecular weight of the components were multiplied by their typical percentage and then added up. This resulted in the weighted molecular weight of 260.

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

The evaluation in this section is based on the data fora significant and representative component of this substance: 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol. This component is expected to exhibit the highest level of toxicity (within an overall spectrum of very low toxicity) and therefore an evaluation based on this component alone will produce a conservative assessment for this UVCB/multicomponent substance.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
149 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see justification and comments below.
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
1 490 mg/m³
Explanation for the modification of the dose descriptor starting point:

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 NOEC=640mg/kgbw/day). This is converted to an inhalation dose by dividing by 0.38 (Example R-82 p65 of guidance) = 1684mg/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 2245mg/m3. Corrected for basal load (light exercise, x0.667) this is equivalent to a human concentration of 1490mg/m3.

Molecular weight correction was performed on the effect level used to determine the DNEL. The molecular weight used for this test material is based on a weighted average using the typical composition. The molecular weight of the components were multiplied by their typical percentage and then added up. This resulted in the weighted molecular weight of 260.

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 the inhalation route where the units are in 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:
160 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: See justification and comments below.
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
6 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long term dermal systemic DNEL based on data from a structurally related substance by read across.. The estimated NOAEL is from a repeat dose study in rats (Dow (1990), molecular weight corrected NOEC=6400mg/kgbw/day). Dermal absorption is assumed to be 100%, which is likely to be exceptionally conservative.

Molecular weight correction was performed on the effect level used to determine the DNEL. The molecular weight used for this test material is based on a weighted average using the typical composition. The molecular weight of the components were multiplied by their typical percentage and then added up. This resulted in the weighted molecular weight of 260.

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:
16 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: See justification and comments below
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
640 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:
medium hazard (no threshold derived)

Additional information - General Population

The evaluation in this section is based on the data for a significant and representative component of this substance: 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol. This component is expected to exhibit the highest level of toxicity (within an overall spectrum of very low toxicity) and therefore an evaluation based on this component alone will produce a conservative assessment for this UVCB/multicomponent substance.

There is no data that indicates long or short term local dermal effects.