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 and comments 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:

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=500mg/kgbw/day). This 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:
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:
208 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:
5 000 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=5000mg/kgbw/day). Dermal absorption is assumed to be 100%, which is likely to be exceptionally conservative.

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:
medium 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:
117 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:
1 170 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=500mg/kgbw/day). This 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:
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:
125 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:
5 000 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=5000mg/kgbw/day). Dermal absorption is assumed to be 100%, which is likely to be exceptionally conservative.

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:
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 and comments 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 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.