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Diss Factsheets
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EC number: 203-639-5 | CAS number: 109-01-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.08 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
- Dose descriptor starting point:
- NOAEC
- Value:
- 53.5 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 26.88 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Key toxic endpoint was in the rabbit OECD414 study, the NOAEL was 75mg/kg bodyweight.
Based on this the Long-Term Inhalation DNEL for workers would be:
75 /2 (extrapolation from oral to inhalation) /2.4 (adjustment for allometic scaling for a rabbit) *70 kg/10m3 (converting from NOEAL in rats to NOAEC in workers) *7/5 to convert from 7 day a week exposure in rabbits to 5 days a week for workers) = NOAEC of 153.125 mg/m3 this is then divided by the assessment factors 1* (interspecies already included) 2.5* (other interspecies) 5*intraspecies 1 (exposure duration as OECD414) *1 (quality of data base) = 12.5 so DNEL = 153.125/12.5 = 12.25
Alternatively, the Long-term Inhalation DNEL for workers could be based on NOAEL for systemic effects in the 90-day inhalation study for the read across substance Aminoethyl piperazine of 53.5 mg/m3
The NOAEC for workers is calculated taking into account that exposure in the 90-day study was 6 hours a day 5 days a week. 53.5 * 6h/8h = 40.125* 6.7m3/10m3 = 26.88 mg/m3
This is then divided by the assessment factors:
1 (interspecies already included) * 2.5 (other interspecies) * 5 (intraspecies) *2 (duration 90 day) * 1 (dose response) *1 (data quality) = 25 so DNEL = 26.88/25 = 1.08 mg/m3
As this gives a more protective lower DNEL this was the approach used.
- AF for dose response relationship:
- 1
- Justification:
- Effects show a clear dose response so factor of 1 used.
- AF for differences in duration of exposure:
- 5
- Justification:
- ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEC from a 90 day study are derived using an assessment factor of 2. The NOAEC used as a point of departure is from a modern 90 inhalation study therfore a factor of 2 was used.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is already included in the route to route extrapolation from the rat inhalation NOEC to the equivalent human inhalation NOAEC.
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA guidelines require a factor of 2.5 for other interspecies differences
- AF for intraspecies differences:
- 5
- Justification:
- ECHA guidance requires a factor of 5 for intraspecies differnces bewteen workers.
- AF for the quality of the whole database:
- 1
- Justification:
- This DNEL is based on a NOAEC from a high quality modern 90-day inhalation study with the read across substance Aminoethyl piperazine.so a a factor of 1 was used. While the DNEL is based on read across to aminoethyl piperazine, as the effects seen are local irritation resulting from the corrosive properties of the test substance, as n-methyl piperazine is also corrosive the database is considered high quality no additional factor for read across is considered necessary.
- AF for remaining uncertainties:
- 1
- Justification:
- All uncertainties are already included so a factor of 1 is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 15 µg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 10
- Dose descriptor:
- NOAEC
- Value:
- 0.15 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- There is a clear dose response in the 90 day inhalation study.
- AF for differences in duration of exposure:
- 2
- Justification:
- The ECHA guidelines provide a default assessment factor of 2 when extrapolating from a 90 day study to long term exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No assessment factor is required when extrapolating local concentration dependent effects in the respiratory tract in an inhalation study from rats to humans.
- AF for other interspecies differences:
- 1
- Justification:
- As the effects were local irritation in the nasal passages and the substance is corrosive a factor of 1 is selected for remaining interspecies differences.
- AF for intraspecies differences:
- 5
- Justification:
- The ECHA guideline give an assessment factor of 5 for intra species differences between workers.
- AF for the quality of the whole database:
- 1
- Justification:
- While the DNEL is based on read across to aminoethyl piperazine, as the effects seen are local irritation resulting from the corrosive properties of the test substance, as n-methyl piperazine is also corrosive the database is considered high quality and a factor of 1 is applied as no additional factor for read across is considered necessary.
- AF for remaining uncertainties:
- 1
- Justification:
- A factor of 1 is selected as there are no remaining uncertainties.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 80 µg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 5
- Dose descriptor starting point:
- NOAEC
- Value:
- 0.4 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- There is a clear dose response in the 14-day inhalation probe study.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- There is no ECHA assessment for duration for short term local exposure effects in the 14-day (2-week) inhalation probe study so a factor of 1 is used.
- AF for other interspecies differences:
- 1
- Justification:
- As the effects were local irritation in the nasal passages and the substance is corrosive a factor of 1 is selected for remaining interspecies differences
- AF for intraspecies differences:
- 5
- Justification:
- The ECHA guideline give an assessment factor of 5 for intra species differences between workers.
- AF for the quality of the whole database:
- 1
- Justification:
- While the DNEL is based on read across to aminoethyl piperazine, as the effects seen are local irritation resulting from the corrosive properties of the test substance, as n-methyl piperazine is also corrosive the database is considered high quality and a factor of 1 is applied as no additional factor for read across is considered necessary.
- AF for remaining uncertainties:
- 1
- Justification:
- A factor of 1 is selected as there are no remaining uncertainties.
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.89 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:
- 190 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 266 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
There are two possible ways to derive a long-term Dermal DNEL for workers.
Based on Rabbit OECD 414 NOAEL 75mg/kg bw/day which is modified to give the Point of Departure by a correction from the 7 day a week dosing in rabbits to the 5 days a week exposure for workers, Modified dose descriptor NOAEL = NOAEL OECD414 rabbit oral *7/5 = 75 mg/kg *7/5 = 105 mg/kg bw/day.
This is divided by the assessment factors. Allometric scaling for rabbits 2.4 x additional inter species factor 2.5 x intraspecies factor for workers of 5 x exposure duration 1 for an OECD414 study x 1 as there is clear dose response x data base quality of 1 = 30
This gives a Long-term DNEL of 105/30 = 3.5 mg/kg bw/day
If the DNEL is calculated based on the OECD422 study for N-methyl piperazine the NOAEL was 2500 ppm, which represented 190 mg/kg in the males. This is the lowest dose level for the 2500ppm in the drinking water. To give a point of departure a correction from the 7 day a week dosing in rats to the 5 days a week exposure for workers. Modified dose descriptor NOAEL = NOAEL OECD422 males oral *7/5 = 190 *7/5 = 266 mg/kg bw/day.
This is divided by the assessment factors. Allometric scaling for rats 4 x additional inter species factor 2.5 x intraspecies factor for workers of 5 x exposure duration 6 for an OECD422 study x 1 as there is clear dose response x data base quality of 1 = 300.
This gives a long-term Dermal DNEL of 266/300 = 0.89 mg/kg bw/day
Based on the two alternatives the DNEL will be calculated based on the NOAEL in males in the OECD422 study as this gives the lowest of the two possible DNELs.
- AF for dose response relationship:
- 1
- Justification:
- Effects show a clear dose response so factor of 1 used.
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 28 day study are derived using an assessment factor of 6 and with a 90 day study using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. This OECD422 study was 43 days for males and at least 43 days for females, therefore a factor of 6 has been selected.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- A factor of 4 is applied based on ECHA guidance for allometric scaling of data from rats to humans.
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor of 2.5 is applied based on ECHA guidance for the assessment factor for other inter species differences.
- AF for intraspecies differences:
- 5
- Justification:
- The ECHA guideline give an assessment factor of 5 for intra species differences between workers.
- AF for the quality of the whole database:
- 1
- Justification:
- This DNEL is based on a NOAEL from a high quality modern OECD422 study on 1-methyl piperazine, therefore we have used a factor of 1.
- AF for remaining uncertainties:
- 1
- Justification:
- All uncertainties are already included so a factor of 1 is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
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:
- 0.268 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):
- 50
- Dose descriptor starting point:
- NOAEC
- Value:
- 53.5 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 13.375 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The Key toxic endpoint for the aminoethyl piperazine the read across source was in the rabbit OECD414 study, the NOAEL was 75mg/kg bodyweight.
Based on this the Long-Term Inhalation DNEL for the general population would be:
75 *50/100 (extrapolation from oral to inhalation) /2.4 (allometric scaling converting from NOAEL in rabbits to NOAEC in the general population Exposure in rabbits was 7 days a week as would be the exposure of the general population via the environment = NOAEC of 46.875 mg/m3 this is then divided by the assessment factors 1* (interspecies already included) 2.5* (other interspecies) 10*intraspecies *1 (exposure duration as OECD414) *1 (quality of data base) = 25 so DNEL = 46.875/25 = 1.875 mg/m3
Alternatively, the Long-term Inhalation DNEL for workers could be based on NOAEL for systemic effects in the 90-day inhalation study for the read across substance Aminoethyl piperazine of 53.5 mg/m3
The NOAEC for the general population is calculated taking into account that exposure in the 90-day study was 6 hours a day, 5 days a week. 53.5 * 6h/24h = 13.375 mg/m3
This is then divided by the assessment factors:
1 (interspecies already included) * 2.5 (other interspecies) * 10 (intraspecies) *2 (duration 90 day) * 1 (dose response) *1 (data quality) = 50 so DNEL = 13.375/50 = 0.268 mg/m3
As this gives a more protective lower DNEL this was the approach used.
The basis for the DNEL calculation was selected as it gave the lowest DNEL based on the 90-day inhalation study which would also protect from the developmental toxicity seen in rabbits.
- AF for dose response relationship:
- 1
- Justification:
- There is a clear dose response in the 90-day inhalation study.
- AF for differences in duration of exposure:
- 2
- Justification:
- The ECHA guidelines provide a default assessment factor of 2 when extrapolating from a 90-day study to long term exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No assessment factor is required when extrapolating from inhalation NOECs in rats to NOECs in humans and the different breathing volume already takes allometric scaling into account.
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA guidance recommends a factor of 2.5 to cover any additional interspecies differences in addition to allometric scaling.
- AF for intraspecies differences:
- 10
- Justification:
- The ECHA guideline give an assessment factor of 10 for intra species differences between the general population.
- AF for the quality of the whole database:
- 1
- Justification:
- While the DNEL is based on read across to aminoethyl piperazine, as the effects seen are local irritation resulting from the corrosive properties of the test substance, as n-methyl piperazine is also corrosive the database is considered high quality and a factor of 1 is applied as no additional factor for read across is considered necessary.
- AF for remaining uncertainties:
- 1
- Justification:
- A factor of 1 is selected as there are no remaining uncertainties.
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)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.317 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:
- 190 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 190 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
There are two possible ways to derive a long-term Dermal DNEL for the general population.
Based on Rabbit OECD 414 oral NOAEL 75mg/kg bw/day which does not need to be modified to give the Point of Departure as both the rabbits and the general population were exposed 7 day as a week unlike workers. This is divided by the assessment factors. Allometric scaling for rabbits 2.4 x additional inter species factor 2.5 x intraspecies factor for the general population of 10 x exposure duration 1 for an OECD414 study x 1 as there is clear dose response x 1 for data base quality = 60
This gives a Long-term DNEL of 75/60 = 1.25 mg/kg bw/day
If the DNEL is calculated based on the oral OECD422 study for 1-methyl piperazine the NOAEL was 2500 ppm, which represented 190 mg/kg in the males. This is the lowest dose level for the 2500ppm in the drinking water. ECHA guidance indicates that oral NOAEL values can also be used for deriving dermal DNELs which is a conservative approach.
To give a point of departure no correction is needed for days of dosing as both the rats and general population are exposed 7 days a week.
The 190 mg/kg NOAEL is divided by the assessment factors. Allometric scaling for rats 4 x additional inter species factor 2.5 x intraspecies factor for the general population of 10 x exposure duration 6 for an OECD422 study x 1 as there is clear dose response x 1 for the data base quality = 600.
This gives a long-term Dermal DNEL of 190/600 = 0.317 mg/kg bw/day
Based on the two alternatives the DNEL will be calculated based on the NOAEL in males in the OECD422 study as this gives the lowest of the two possible DNELs which would also protect from the developmental effects seen in the rabbit study.
- AF for dose response relationship:
- 1
- Justification:
- There is a clear dose response in the OECD442 study.
- AF for differences in duration of exposure:
- 6
- Justification:
- The ECHA guidelines provide a default assessment factor of 6 when extrapolating from an OECD422 study to long term exposure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA guidelines recommend a factor of 4 for allometric scaling when extrapolating for rats to humans.
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA guidance recommends a factor of 2.5 to cover any additional interspecies differences in addition to allometric scaling.
- AF for intraspecies differences:
- 10
- Justification:
- The ECHA guideline give an assessment factor of 10 for intra species differences between the general population.
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on the NOAEL from a modern GLP compliant guideline OECD422 study on the 1-methyl piperazine. Therefore, the database is considered high quality and a factor of 1 is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- A factor of 1 is selected as there are no remaining uncertainties.
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:
- 0.317 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:
- 190 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 190 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
There are two possible ways to derive a long-term oral DNEL for the general population.
Based on Rabbit OECD 414 oral NOAEL 75mg/kg bw/day which does not need to be modified to give the Point of Departure as both the rabbits and the general population were exposed 7 days as a week unlike workers. This is divided by the assessment factors. Allometric scaling for rabbits 2.4 x additional inter species factor 2.5 x intraspecies factor for the general population of 10 x exposure duration 1 for an OECD414 study x 1 as there is clear dose response x 1 for data base quality = 60
This gives a Long-term DNEL of 75/60 = 1.25 mg/kg bw/day
If the DNEL is calculated based on the OECD422 study for N-methyl piperazine the NOAEL was 2500 ppm, which represented 190 mg/kg in the males. This is the lowest dose level for the 2500ppm in the drinking water.
To give a point of departure no correction is needed for days of dosing as both the rats and general population are exposed 7 days a week.
The 190 mg/kg NOAEL is divided by the assessment factors. Allometric scaling for rats 4 x additional inter species factor 2.5 x intraspecies factor for the general population of 10 x exposure duration 6 for an OECD422 study x 1 as there is clear dose response x 1 for the data base quality = 600.
This gives a long-term Oral DNEL of 190/600 = 0.317 mg/kg bw/day
Based on the two alternatives the DNEL will be calculated based on the NOAEL in males in the OECD422 study as this gives the lowest of the two possible DNELs which would also protect from the developmental effects seen in the rabbit study.
- AF for dose response relationship:
- 1
- Justification:
- There is a clear dose response in the OECD442 study so factor of 1 used.
- AF for differences in duration of exposure:
- 6
- Justification:
- The ECHA guidelines provide a default assessment factor of 6 when extrapolating from an OECD422 study to long term exposure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA guidelines recommend a factor of 4 for allometric scaling when extrapolating for rats to humans.
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA guidance recommends a factor of 2.5 to cover any additional interspecies differences in addition to allometric scaling.
- AF for intraspecies differences:
- 10
- Justification:
- The ECHA guideline give an assessment factor of 10 for intra species differences between the general population.The ECHA guideline give an assessment factor of 10 for intra species differences between the general population.
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on the NOAEL from a modern GLP compliant guideline OECD422 study on the 1-methyl piperazine. Therefore, the database is considered high quality and a factor of 1 is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- All uncertainties are already included so a factor of 1 is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - General Population
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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