Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.48 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEC
Value:
40 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
50.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation used
AF for dose response relationship:
1
Justification:
NOAEC used
AF for differences in duration of exposure:
6
Justification:
Sub acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation
AF for other interspecies differences:
2.5
Justification:
No data are available on any remaining interspecies uncertainties; therefore, the default factor of 2.5 was applied.
AF for intraspecies differences:
5
Justification:
Standard default for workers
AF for the quality of the whole database:
1
Justification:
No additional assessment factor was assigned due to the close structural similarity between DMEE and 2-(2-aminoethoxy)ethanol, see section 13 Read Across Justification
AF for remaining uncertainties:
1
Justification:
N/A
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.07 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
Value:
5.33 mg/m³
AF for dose response relationship:
1
Justification:
NOAEC used
AF for differences in duration of exposure:
1
Justification:
Increasing the duration does not increase the severity as is the case for certain local effects in the respiratory tract. This is relevant when there is no substantial difference in the N(L)OAECs following acute and subacute exposure by inhalation. The effects can thus be considered concentration rather than dose-dependent (ECHA R8, pg 29).
AF for interspecies differences (allometric scaling):
1
Justification:
AFs not used for local or inhalation effects
AF for other interspecies differences:
1
Justification:
Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1). For the remaining uncertainties in kinetic (at a smaller extent) and in dynamic (at a larger extent) interspecies differences, consideration of the mechanism of toxicity is crucial, e.g. if the effect is a simple destruction of membranes due to the physicochemical properties (e.g. pH) of the chemical concerned as opposed to a mechanism involving local metabolism (see pg 26 of R8). The mechanism of action for DMEE is corrosion which is a simple destruction of membranes.
AF for intraspecies differences:
5
Justification:
Standard default for workers
AF for the quality of the whole database:
1
Justification:
No additional assessment factor was assigned due to the close structural similarity between DMEE and 2-(2-aminoethoxy)ethanol, see section 13 Read Across Justification
AF for remaining uncertainties:
1
Justification:
N/A
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
175 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
222.25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation used
AF for dose response relationship:
1
Justification:
NOAEL used
AF for differences in duration of exposure:
2
Justification:
90 day study used to calculate DNEL - sub-chronic to chronic AF of 2 is applied
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to humans AF of 4 is applied
AF for other interspecies differences:
2.5
Justification:
No data are available on any remaining interspecies uncertainties; therefore, the default factor of 2.5 was applied.
AF for intraspecies differences:
5
Justification:
Standard default for workers
AF for the quality of the whole database:
1
Justification:
No additional assessment factor was assigned due to the close structural similarity between DMEE and 2-(2-aminoethoxy)ethanol, see section 13 Read Across Justification
AF for remaining uncertainties:
1
Justification:
N/A
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Long term exposure dermal and inhalation DNELs have been calculated for workers as 2.33 mg/kg/day and 0.48 mg/m3, respectively. A long term inhalation DNEL for local effects has been calculated for workers as 1.07 mg/m3. Insufficient dose information was available to derive a definitive NOAEL from the 90-day dermal study on 2-(2-aminoethoxy)ethanol. Given the corrosive nature of DMEE (Skin Corrosion Category 1C), a medium hazard was assigned. Therefore, in accordance with ECHA guidance, a qualitative assessment will be performed for long-term local dermal effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.085 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEC
Value:
40 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
50.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation used
AF for dose response relationship:
1
Justification:
NOAEC used
AF for differences in duration of exposure:
6
Justification:
Sub acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
AFs not used for inhalation exposure
AF for other interspecies differences:
2.5
Justification:
No data are available on any remaining interspecies uncertainties; therefore, the default factor of 2.5 was applied.
AF for intraspecies differences:
10
Justification:
Standard default for general population
AF for the quality of the whole database:
1
Justification:
No additional assessment factor was assigned due to the close structural similarity between DMEE and 2-(2-aminoethoxy)ethanol, see section 13 Read Across Justification
AF for remaining uncertainties:
1
Justification:
N/A
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.127 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
NOAEC used
AF for differences in duration of exposure:
1
Justification:
Increasing the duration does not increase the severity as is the case for certain local effects in the respiratory tract. This is relevant when there is no substantial difference in the N(L)OAECs following acute and subacute exposure by inhalation. The effects can thus be considered concentration rather than dose-dependent (ECHA R8, pg 29).
AF for interspecies differences (allometric scaling):
1
Justification:
AFs not used for local or inhalation effects
AF for other interspecies differences:
1
Justification:
Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1). For the remaining uncertainties in kinetic (at a smaller extent) and in dynamic (at a larger extent) interspecies differences, consideration of the mechanism of toxicity is crucial, e.g. if the effect is a simple destruction of membranes due to the physicochemical properties (e.g. pH) of the chemical concerned as opposed to a mechanism involving local metabolism (see pg 26 of R8). The mechanism of action for DMEE is corrosion which is a simple destruction of membranes.
AF for intraspecies differences:
10
Justification:
Standard default for general population
AF for the quality of the whole database:
1
Justification:
No additional assessment factor was assigned due to the close structural similarity between DMEE and 2-(2-aminoethoxy)ethanol, see section 13 Read Across Justification
AF for remaining uncertainties:
1
Justification:
N/A
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:
0.28 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
Value:
175 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
222.25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation used
AF for dose response relationship:
1
Justification:
NOAEL used
AF for differences in duration of exposure:
2
Justification:
90 day study used to calculate DNEL - sub-chronic to chronic AF of 2 is applied
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to humans AF of 4 is applied
AF for other interspecies differences:
2.5
Justification:
No data are available on any remaining interspecies uncertainties; therefore, the default factor of 2.5 was applied.
AF for intraspecies differences:
10
Justification:
Standard default for general population
AF for the quality of the whole database:
1
Justification:
No additional assessment factor was assigned due to the close structural similarity between DMEE and 2-(2-aminoethoxy)ethanol, see section 13 Read Across Justification
AF for remaining uncertainties:
1
Justification:
N/A
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term

General Population - Hazard via oral route

Systemic 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 for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Long term exposure dermal and inhalation DNELs for systemic effects have been calculated for the general population as 0.28 mg/kg/day and 0.085 mg/m3, respectively. A long term exposure inhalation DNEL for local effects has been calculated as 0.085 mg/m3. Insufficient dose information was available to derive a definitive NOAEL from the 90-day dermal study on 2-(2-aminoethoxy)ethanol. Given the corrosive nature of DMEE (Skin Corrosion Category 1C), a high hazard was assigned. Therefore, in accordance with ECHA guidance, a qualitative assessment will be performed for long-term local dermal effects.