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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.24 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:
414 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
243 mg/m³
Explanation for the modification of the dose descriptor starting point:

A NOAEC of 414 mg/m³ air was derived (NOAEC 100 ppm; Klimisch 2; key; equivalent to OECD 412; DiPasquale, 1979). DiPasquale (1979) investigated inhalation toxicity of the test substance after repeated whole body exposure for two weeks (1 or 7 hours per day, 5 days per week). Sprague Dawley male and female rats were exposed to 0 (control), 100 or 1000 ppm (eq. of 0, 414 or 4140 mg/m³; 15 males and 15 females/dose). The results of the current study suggest that gross signs of irritation, transient cloudiness of the eye, and possibly elevations in atypical lymphocyte differential counts were the only detectable manifestations of exposure of rats to the test substance vapors for five days per week for two weeks.


The dose descriptor starting point = 414 mg/m³ * (7h/d / 8h/d) * (6.7 m³ (8h) / 10 m³ (8h)) = 243 mg/m³ . For workers, the resulting air concentration needs to be corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). A correction factor for duration of activity (or exposure) is added (factor 7/8).

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):
1
Justification:
already included in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
rat to human
AF for intraspecies differences:
5
Justification:
worker 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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.67 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:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No reliable repeated dose toxicity study was available for the test substance via the dermal route of exposure. However, in a reliable oral repeated dose toxicity test of the read-across substance N-ethylmorpholine, a NOAEL of 200 mg/kg was determined. For the route-to-route extrapolation from oral to dermal, on the assumption that dermal absorption will not be higher than oral absorption, no default factor (i. e. factor 1) should be applied; bioavailability is assumed to be 50% after dermal and oral exposure. No additional factor is taken into account for the fact that the dose descriptor is taken from the read-across substance NEM. The available read-across data is sufficiently reliable and consistent.

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:
rat to human
AF for other interspecies differences:
2.5
Justification:
rat to human
AF for intraspecies differences:
5
Justification:
worker 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
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

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:
0.81 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:
414 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
121 mg/m³
Explanation for the modification of the dose descriptor starting point:

DiPasquale (1979) investigated inhalation toxicity of the test substance after repeated whole body exposure for 10 days (1 or 7 hours per day, 5 days per week). Sprague Dawley male and female rats were exposed to 0 (control), 100 or 1000 ppm (eq. to 0, 414 and 4140 mg/m³; 15 males and 15 females/dose). The results of the current study suggest that gross signs of irritation, transient cloudiness of the eye, and possibly elevations in atypical lymphocyte differential counts were the only detectable manifestations of exposure of rats to the test substance vapors. A NOAEC of 100 ppm or 414 mg/m³ air was derived. The dose descriptor starting point = 414 mg/m³ * (7h/d / 24h/d) = 121 mg/m³.

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):
1
Justification:
already included in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
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:
0.33 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:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In a reliable read-across information of N-ethylmorpholine repeated oral toxicity of the test substance was investigated in male/female Crj: CD(SD) IGS rats. A NOAEL of 200 mg/kg bw/d is proposed. No additional factor is taken into account for the fact that the dose descriptor is taken from the read-across substance NEM. The available read-across data is sufficiently reliable and consistent


For the route-to-route extrapolation from oral to dermal, on the assumption that dermal absorption will not be higher than oral absorption, no default factor (i. e. factor 1) should be applied as part of the overall assessment factor.

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:
rat to human
AF for other interspecies differences:
2.5
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
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:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 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:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In a reliable read-across information of N-ethylmorpholine repeated oral toxicity of the test substance was investigated in male/female Crj: CD(SD) IGS rats. A NOAEL of 200 mg/kg bw/d is proposed. No additional factor is taken into account for the fact that the dose descriptor is taken from the read-across substance NEM. The available read-across data is sufficiently reliable and consistent.

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):
2.5
Justification:
rat to human
AF for other interspecies differences:
4
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population