Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
35.26 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor start point is modified from a NOAEL by oral administration in rats (mg/kg/day) to a No Observed Adverse Effect Concentration (NOAEC) in humans by inhalation exposure (mg/m3) before Adjustment Factors (AFs) can be applied to determine the DNEL. The conversion in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment Chapter R8 is as follows (in case of Workers exposed 8 hours/day):

NOAEC = oral NOAEL x 1/sRVrat x ABSoral rat / ABSinh human x sRVhuman / wRV

Where: sRV = Standard respiratory volume (0.38 m3 rat and 6.7 m3 human)

            ABS = Absorption

            wRV = Worker respiratory volume (10 m3)

Therefore: NOAEC = 1000 x 1/0.38 x 1/1 x 6.7/10

NOAEC = 1763 mg/m3

AF for dose response relationship:
1
Justification:
NOAEL taken as PoD for modification
AF for differences in duration of exposure:
2
Justification:
Sub-chronic (OECD 422) to chronic duration
AF for interspecies differences (allometric scaling):
1
Justification:
Not required since modification of oral NOAEL to inhalation NOAEC in humans has been made
AF for other interspecies differences:
2.5
Justification:
Default factor for toxicokinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Starting dose taken from a guideline, GLP study
AF for remaining uncertainties:
2
Justification:
Assessment factor of 2 applied as data is read across from N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] to 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
105.78 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
other: Systemic long term DNEL
Value:
35.26 mg/m³
Explanation for the modification of the dose descriptor starting point:

The inhalation systemic acute DNEL has been taken from the systemic inhalation long term DNEL. In the absence of reliable experimental data an acute DNEL can by default be set at 1-5 times the long term DNEL. Although there is no acute inhalation data available, acute dermal and acute oral toxicity studies were conducted in rats, with LD50 values of  >5000 mg/kg bodyweight and >2000 mg/kg bodyweight determined, respectively. Therefore, the extrapolation factor was set at 3.

    

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
Justification:
3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
200
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
other: No dose modification required
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL taken as Point of Departure
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic duration (OECD 421)
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for rats to humans
AF for other interspecies differences:
2.5
Justification:
Default factor for toxicokinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Starting dose taken from a guideline, GLP study
AF for remaining uncertainties:
2
Justification:
Assessment factor of 2 applied as data is read across from N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] to 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
other: Systemic long term DNEL
Value:
5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dermal systemic acute DNEL has been taken from the systemic dermal long term DNEL. An acute DNEL can by default be set at 1-5 times the long term DNEL. An acute dermal toxicity study was conducted with the test substance, with an LD50 value of >5000 mg/kg bodyweight. Additionally, a dermal toxicity study was conducted in rabbits with the test substamce, and no signs of erythema or oedema were observed in any animals. Therefore, it is considered appropriate to modify the systemic long-term DNEL of 5 mg/kg/day by a factor of 5.

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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:
8.7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
869.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor start point is modified from a NOAEL by oral administration in rats (mg/kg/day) to a No Observed Adverse Effect Concentration (NOAEC) in humans by inhalation exposure (mg/m3) before Adjustment Factors (AFs) can be applied to determine the DNEL. The conversion in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment Chapter R8 is as follows (in case of General Population exposed 24 hours/day):

NOAEC = oral NOAEL x 1/sRVrat x ABSoral rat / ABSinh human

Where: sRV = Standard respiratory volume (1.15 m3/kg/day)

            ABS = Absorption

NOAEC = 1000 x 1/1.15 x 1/1

NOAEC = 869.6 mg/m3

AF for dose response relationship:
1
Justification:
NOAEL taken as Point of Departure
AF for differences in duration of exposure:
2
Justification:
Sub-chronic (OECD 421) to chronic duration
AF for interspecies differences (allometric scaling):
1
Justification:
Not required since modification of oral NOAEL to inhalation NOAEC in humans has been made
AF for other interspecies differences:
2.5
Justification:
Default factor for toxicokinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Starting dose taken from a guideline, GLP study
AF for remaining uncertainties:
2
Justification:
Assessment factor of 2 applied as data is read across from N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] to 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
other: Systemic long-term DNEL
Value:
8.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The inhalation systemic acute DNEL has been taken from the systemic inhalation long term DNEL. In the absence of reliable experimental data an acute DNEL can by default be set at 1-5 times the long term DNEL. Although there is no acute inhalation data available, acute dermal and acute oral toxicity studies were conducted in rats, with LD50 values of  >5000 mg/kg bodyweight and >2000 mg/kg bodyweight determined, respectively. Therefore, the extrapolation factor was set at 3.

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
400
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
other: No dose modification required
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL taken as Point of Departure
AF for differences in duration of exposure:
2
Justification:
Sub-chronic (OECD 421) to chronic duration
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for rats to humans
AF for other interspecies differences:
2.5
Justification:
Default factor for toxicokinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Starting dose taken from a guideline, GLP study
AF for remaining uncertainties:
2
Justification:
Assessment factor of 2 applied as data is read across from N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] to 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
Acute/short 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:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
other: Systemic long-term DNEL
Value:
2.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dermal systemic acute DNEL has been taken from the systemic dermal long term DNEL. An acute DNEL can by default be set at 1-5 times the long term DNEL. An acute dermal toxicity study was conducted with the test substance, with an LD50 value of >5000 mg/kg bodyweight. Additionally, a dermal toxicity study was conducted in rabbits with the test substamce, and no signs of erythema or oedema were observed in any animals. Therefore, it is considered appropriate to modify the systemic long-term DNEL of 2.5 mg/kg/day by a factor of 5.

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
400
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
other: No dose modification required
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL taken as Point of Departure
AF for differences in duration of exposure:
2
Justification:
Sub-chronic (OECD 421) to chronic duration
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for rats to humans
AF for other interspecies differences:
2.5
Justification:
Default factor for toxicokinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Starting dose taken from a guideline, GLP study
AF for remaining uncertainties:
2
Justification:
Assessment factor of 2 applied as data is read across from N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] to 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
Acute/short 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:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEL
Value:
2.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral systemic acute DNEL has been taken from the systemic oral long term DNEL. An acute DNEL can by default be set at 1-5 times the long term DNEL. An acute oral toxicity study was conducted in rats with the test substance, with an LD50 value of >2000 mg/kg bodyweight. Therefore, it is considered appropriate to modify the systemic long-term DNEL of 5 mg/kg/day by a factor of 5.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population