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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

Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
There are no specific data on the absorption, distribution, metabolism and excretion of N-methyl piperazine CAS No 109 -01 -3. Some information is available on the related substances Aminoethyl piperazine CAS No 140 -31 -8 and piperazine CAS No 110 -85 -0 and information from the OECD Tool Box and other models.
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - oral (%):
- 89.6
- Absorption rate - dermal (%):
- 50
- Absorption rate - inhalation (%):
- 100
Additional information
Toxicokinetics
Molecular chemical profile and estimated properties:
|
1-methyl piperazine |
Aminoethyl piperazine |
Piperazine |
CAS |
109-01-3 |
140-31-8 |
110-85-0 |
Structure |
See attached |
See attached |
See attached |
Physical state |
Liquid |
Liquid |
Solid crystalline |
SMILES |
N1(CCNCC1)C |
N1(CCNCC1)CCN |
C1CNCCN1 |
Molecular formula |
C5H12N2 |
C6H15N3 |
C4H10N2 |
Molecular weight |
100.1622 |
129.2034 |
86.1356 |
Solubility: avgLogS (g/L) |
0.55 (355 g/L) |
0.45 (364 g/L) |
0.27 (160 g/L) |
Solubility (meas) |
Completely miscible |
Completely miscible (pH=12) |
150 g/L (pH =11) |
Density |
0.902 |
0.98 |
1.26 |
pKa: neutral 1+: 2+: 3+: |
pKa = 5.13 & 9.46 50% at pH 9.5 Max. 98.7% at pH 7.3 ≥99.9% at pH≤2.2 |
pKa = 3.11, 8.90 & 9.68 50% at pH 9.75 Max. 55.14% at pH 9.3 Max 99.74% at pH= 6.0 ≥99.0% at pH≤1.1 |
pKa = 5.18 & 9.56 50% at pH 9.6 Max. 98.7% at pH 7.4 ≥99.9% at pH≤2.2 |
logPow(ALOGPS 2.1) (KOWWIN v1.67) |
-0.40 (±0.29) -0.5878 |
-1.24 (±0.34) -1.5677 |
-0.85 (±0.37) -0.7990 |
logPow (meas) |
-0.57 |
-1.48 |
-1.24 |
logD (Chemaxon) |
pH logD 1,700 -6,798 4,600 -4,308 5,500 -3,743 7,400 -2,392 |
pH logD 1,700 -8,844 4,600 -7,405 5,500 -7,224 7,400 -4,886 |
pH logD 1,700 -7,013 4,600 -4,640 5,500 -4,078 7,400 -2,859 |
Mp (EPIWIN) |
19.4°C |
53.69°C |
7.3°C |
bp (EPIWIN) |
154.12°C |
228.04°C |
163.75°C |
Vp (EPIWIN) |
929 Pa |
17.5 Pa |
94.9 Pa |
Mp (meas) |
-5.57°C |
-19°C |
105°C |
bp (meas) |
136.66°C |
220.4°C |
147.7 °C |
Vp (meas) |
667 Pa @ 19.7°C |
5.15Pa @ 20°C |
39.2 Pa @ 22.5°C |
Reactivity |
DNA adducts via an SN1 mechanism (tert.aliphatic amine) |
DNA adducts via an SN1 mechanism (tert.aliphatic amine) |
Schiff base reactions resulting in DNA cross-linking.(Piperazine) |
HOMO LUMO (difference) |
-8.99 2.9 (11.89) |
-8.85 2.72 (11.57) |
-9.14 3.11 (12.25) |
Dermal penetration coefficient Kp (est) |
1.23E-4 cm/h |
3.06E-5 cm/h |
7.72E-5 cm/h |
Max. dermal absorption |
0.082348 mg/ cm²/hr |
0.057549 mg/ cm²/hr |
0.015092 mg/ cm²/hr |
Human Intestinal absorption (HIA) |
89.6% |
83.4% |
89.7% |
Molecular formula, molecular weight, pKa and logD were all calculated using ChemAxon MarvinSketch (v.5.4.0.1).
Melting point, boiling point, vapour pressure and logPow were estimated by EPI Suite (v4.1).
Solubility and logPow are estimated using ALOGPS 2.1 (VCCLAB, Virtual Computational Chemistry Laboratory,http://www.vcclab.org, 2005)
Reactivity: QSAR Toolbox v.3.0: profiling: DNA binding (OASIS v1.1; OECD); Protein binding (OASIS v1.1; OECD)
HOMO/LUMO Energy, [eV], quantum-chemical descriptor (the energy of the highest occupied resp. lowest unoccupied molecular orbital), calculated in OASIS software, based on MOPAC 7.
(a large difference between HOMO and LUMO energies implies high stability and thus low reactivity)
Absorption properties:
- dermal: EpiSuite v. 4.1; intestinal (water:0.0005 cm/hr):
- HIA: QSAR toolbox (version 3.1) (Human Intestinal Absorption)
Max. dermal absorption: IH Skin Perm v1.03 from AIHA
Absorption
Piperazine has been shown to be readily absorbed from the gastrointestinal tract, the REACH dossier suggest 100% absorption. Information in the REACH dossier for Aminoethyl piperazine also suggests high oral bioavailability. The information from the QSAR tool box above indicates similar high percentage of human intestinal absorption, for all three substances; therefore 1-methyl piperazine is expected to have high oral bioavailability. Also all three should be absorbed through the skin with 1 -methyl piperazine and aminoethyl piperazine having a similar and higher potential for dermal penetration based on the data from the model. The physicochemical properties both measured and calculated above, indicate more similarities between the aminoethyl piperazine and the 1-methyl piperazine which are both liquids at room temperature compared to piperazine which is a crystalline solid and both have higher water solubility.
Distribution
Based on related molecules such as diethylene triamine wide distribution in the tissues of the body would be expected for the 1-methyl piperazine, this is also expected for piperazine and aminoethyl piperazine, due to their basic nature and high water solubility/ low Log Pows. This would be followed by rapid elimination of the substances and their metabolites, mainly via the urine.
Metabolism
Metabolism data is not available for 1-methyl piperazine, piperazine or amino ethyl piperazine. The Rat liver S9 metabolism simulator and skin metabolism simulator in the OECD tool box, predict similar metabolites for piperazine and 1-methyl piperazine, with some similar metabolites for the aminoethyl piperazine based on the oxidation of the ethylamine group (see attached documents for details). Any piperazine formed will be metabolized to ethylene diamine by N-dealkylation of the piperazine ring. Other possible aldehydes which are possibly formed such as formaldehyde from the 1-methyl piperazine would be finally metabolized to CO2.
Excretion
Excretion of the 1-methy piperazine and its metabolites would be expected to be primarily in the urine with a small percentage in the faeces based on the available information on piperazine and related amines. Some of the products of the metabolism such as aldehydes would be fully metabolized and excreted as CO2.
References:
Dissemninated REACH dossier for Aminoethyl piperazine CAS No 140-31-8 2010
Dissemninated REACH dossier for Piperazine CAS No 110-85-0 2010
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.
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