Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.28 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):
12.5
Dose descriptor starting point:
NOAEC
Value:
181 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
91 mg/m³
Explanation for the modification of the dose descriptor starting point:

A reliable repeated dose toxicity study with the analogue substance morpholine in rats is available.

181 mg/m³ * (6h/d / 8h/d) * (6.7 m3 (8h) / 10 m3 (8h)) = 91 mg/m³. For workers the resulting air concentration needs to be corrected for the differences between exposure duration and between basal caloric demand and caloric demand under light activity. Exposure duration for workers is typically a 8-hour period when for animals is a 6-hour period. Caloric demand correction factor derives from the inhaled volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity).

AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
1
Justification:
Chronic study (104 weeks of exposure, 5 days per week)
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for rats
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
As no dermal long-term study is available, route-to-route extrapolation has been performed. The absorption factor after both dermal and oral administration are assumed to be 50%, so no correction factor is applied.
AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
6
Justification:
Difference in duration subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for rats
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for rats
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.8 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
45.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
181 mg/m³ * (6h/d / 24h/d) = 45.3 mg/m³. For consumers the resulting air concentration needs to be corrected for differences between exposure durations in animal testing (6 hours) and consumers exposure (24 hours).
AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
1
Justification:
Chronic study (104 weeks of exposure, 5 days per week)
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for rats
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No reliable repeated dose toxicity study was available for DMDEE via the dermal route route of exposure. However, in a reliable oral combined repeated dose/reprotox toxicity test with DMDEE, a NOAEL of 300 mg/kg was determined. For route-to-route extrapolation (oral to dermal), no default factor (i.e. factor 1) should be applied as part of the overall assessment factor, as it is assumed that dermal absorption will not be higher than oral absorption.
AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
6
Justification:
Difference in duration subactue to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for rats
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for rats
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Difference in duration subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for rats
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for rats
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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