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EC number: 278-169-7 | CAS number: 75277-39-3
- 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)
- Endpoint:
- basic toxicokinetics, other
- Type of information:
- other:
- Remarks:
- Expert statement
- Adequacy of study:
- key study
- Study period:
- not applicable
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Expert statement, no study available
- Objective of study:
- toxicokinetics
- Principles of method if other than guideline:
- Expert statement
- GLP compliance:
- no
- Details on absorption:
- Generally, oral absorption is favoured for molecular weights below 500 g/mol. The high water solubility of 758 g/L enables the test substance to dissolve in the gastrointestinal fluids. The substance is a zwitterion and therefore contains ionisable groups. It is generally thought that ionized substances do not readily diffuse across biological membranes. Furthermore, the hydrophilicity of the test substance as determined by its high water solubility and low octanol/water partition coefficient indicates a low potential for passive diffusion through cell membranes. Furthermore, the molecular weight of 260 g/mol shows that the passage through aqueous pores or through the epithelial barrier by the bulk passage of water is less likely. Taken together, the physiochemical properties indicate that the test substance becomes bioavailable following the oral route with a limited extent.
Due to the high melting point above 200 °C, no availability as a vapour under standard environmental conditions is expected for the test substance. Still the vapour pressure was determined and is very low for the test substance. It was calculated to be 2.5*10E-14 Pa at 25 °C. As the test substance appears as a powder, formation and inhalation of dust might occur. Generally, particles with an aerodynamic diameter below 100 μm have the potential to be inspired, below 50 μm may reach the thoracic region and those below 15 μm can pass into the alveolar region of the respiratory tract. With a D50 value of 5.6 and D90 of 15.6 μm a high proportion of particles smaller than 100 μm exist for the test substance. As demonstrated by the distribution of the particle size, the test substance’s particles might possess the ability to reach the alveolar region. Due to the high water solubility the deposited test substance may dissolve into the mucus lining but the potential to be absorbed directly across the respiratory tract epithelium is limited. In addition, the molecular weight shows that passage through aqueous pores or across membranes with the bulk passage of water is less likely and passive diffusion is also unlikely due to the low log Pow. Most of the test substance will be retained in the mucus and transported out of the respiratory tract. Only a very small amount may be taken up by phagocytosis and transported to the blood via the lymphatic system.
As a powder, the test substance is not readily taken up by the skin. However, once moistened on the skin surface, absorption is possible, due to the high water solubility determined. The molecular weight of the test substance neither favours nor excludes dermal uptake. Considering the low log Pow of below -3.8, the test substance is likely to be too lipophobic to cross the stratum corneum, resulting in low absorption. - Details on distribution in tissues:
- As mentioned above, the physicochemical properties of the test substance favour systemic absorption following oral, inhalative and dermal uptake to a certain extent.
Direct transport through aqueous pores in general will be favoured as an entry route to the systemic circulation due to the hydrophilic properties. Due to the molecule size, this entry route will be slightly limited. After being absorbed into the body, the test substance is most likely not distributed into the interior part of cells due to the hydrophilic properties (log Pow below -3.8) and in turn the extracellular concentration is expected to be higher than the intracellular concentration.
The test substance does not have a bioaccumulative potential. The log Pow indicates no bioaccumulation potential, as it is well below 3. - Details on excretion:
- A certain amount of the test substance will be excreted most likely in its unhydrolised but possibly metabolised form. However, based on data for the piperazine ring most of the substance will be excreted in non-metabolised form (DrugBank 2021; Human Metabolome Database 2021).
The most prominent excretion pathway is via urine, as the test substance has a molecular weight below 300 g/mol and a high water solubility prone for this pathway. - Metabolites identified:
- not specified
- Executive summary:
No study is available, in which the toxicokinetic properties (distribution, metabolism, elimination) of the test item were investigated.
The expected toxicokinetic behaviour is assessed in a qualitative manner based on the physicochemical properties and the results from the available toxicological studies following the instructions given in the ‘Guidance on information requirements and chemical safety assessment - Chapter R.7c: Endpoint specific guidance’ (Version 1.1).
Physico-chemical data
The test item is a zwitterionic organic chemical. It is a white crystalline powder with a molecular weight of 260 g/mol. It has a median particle size of 5.6 μm with a 10%-quantile of 15.6 μm. The test item is highly water soluble (758 g/L at 20 °C) and is considered to be hydrolytically stable at pH 4, 7 and 9 (at 50 °C). With an estimated log P of < -3.8, the test item is hydrophilic. It has a very low volatility, as its vapour pressure was estimated to be 2.5*10E-14 Pa at 25 °C. With a mean surface tension of 63.3 mN/m (at 20°C), the test item is not surface active.
Absorption
Generally, oral absorption is favoured for molecular weights below 500 g/mol. The high water solubility of 758 g/L enables the test substance to dissolve in the gastrointestinal fluids. The substance is a zwitterion and therefore contains ionisable groups. It is generally thought that ionized substances do not readily diffuse across biological membranes. Furthermore, the hydrophilicity of the test substance as determined by its high water solubility and low octanol/water partition coefficient indicates a low potential for passive diffusion through cell membranes. In addition, the molecular weight of 260 g/mol shows that the passage through aqueous pores or through the epithelial barrier by the bulk passage of water is less likely. Taken together, the physiochemical properties indicate that the test substance becomes bioavailable following the oral route to a limited extent.
Due to the high melting point above 200 °C, no availability as a vapour under standard environmental conditions is expected for the test substance. Still the vapour pressure was determined and is very low for the test substance. It was calculated to be 2.5*10E-14 Pa at 25 °C. As the test substance appears as a powder, formation and inhalation of dust might occur. Generally, particles with an aerodynamic diameter below 100 μm have the potential to be inspired, below 50 μm may reach the thoracic region and those below 15 μm can pass into the alveolar region of the respiratory tract. With a D50 value of 5.6 and D90 of 15.6 μm a high proportion of particles smaller than 100 μm exist for the test substance. As demonstrated by the distribution of the particle size, the test substance’s particles might possess the ability to reach the alveolar region. Due to the high water solubility the deposited test substance may dissolve into the mucus lining but the potential to be absorbed directly across the respiratory tract epithelium is limited. Furthermore, the molecular weight shows that passage through aqueous pores or across membranes with the bulk passage of water is less likely and passive diffusion is also unlikely due to the low log Pow. Most of the test substance will be retained in the mucus and transported out of the respiratory tract. Only a very small amount may be taken up by phagocytosis and transported to the blood via the lymphatic system.
As a powder, the test substance is not readily taken up by the skin. However, once moistened on the skin surface, absorption is possible, due to the high water solubility determined. The molecular weight of the test substance neither favours nor excludes dermal uptake. Considering the low log Pow of below -3.8, the test substance is likely to be too lipophobic to cross the stratum corneum, resulting in low absorption.
Distribution
As mentioned above, the physicochemical properties of the test substance favour systemic absorption following oral, inhalative and dermal uptake to a certain extent.
Direct transport through aqueous pores in general will be favoured as an entry route to the systemic circulation due to the hydrophilic properties. Due to the molecule size, this entry route will be slightly limited. After being absorbed into the body, the test substance is most likely not distributed into the interior part of cells due to the hydrophilic properties (log Pow below -3.8) and in turn the extracellular concentration is expected to be higher than the intracellular concentration.
The test substance does not have a bioaccumulative potential. The log Pow indicates no bioaccumulation potential, as it is well below 3.
Metabolism
The available genotoxicity study in bacteria indicates no remarkable differences in regard to genotoxicity and cytotoxicity in the presence or absence of metabolic activation systems. Thus, no metabolic activation is expected. Generally, it is likely that common protein interaction such as cytochrome P450 oxidases interaction during Phase I metabolism introduce a reactive or polar group in the substance. Oxidation is likely to be involved in metabolic changes in the piperazine ring, the most defining group of the test substance. The resulting compounds might be further processed into polar compounds during the metabolism in Phase II. Based on data for the piperazine ring group, the substance will only be metabolized in the liver to around 25 % (DrugBank 2021; Human Metabolome Database 2021).
Excretion
A certain amount of the test substance will be excreted most likely in its unhydrolised but possibly metabolised form. However, based on data for the piperazine ring most of the substance will be excreted in non-metabolised form (DrugBank 2021; Human Metabolome Database 2021).
The most prominent excretion pathway is via urine, as the test substance has a molecular weight below 300 g/mol and a high water solubility prone for this pathway.
References:
1. DrugBank (2021): https://go.drugbank.com/drugs/DB00592 (as of 2021-02-26)
2. Human Metabolome Database (2021): https://hmdb.ca/metabolites/HMDB0014730 (as of 2021-02-26)
Reference
Description of key information
In general, absorption via oral, inhalation and dermal route is expected for the test item. Since the substance is very hydrophilic, has a low log P, and is ionisable, diffusion through aqueous channels and pores is assumed and extracellular concentration might be higher than intracellular. Bioaccumulation in the lung, adipose tissue and stratum corneum is not expected. Metabolic activation is assumed to be unlikely. As the test item is very water soluble, excretion via urine can be assumed (reference 7.1.1-1).
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
No study is available, in which the toxicokinetic properties (distribution, metabolism, elimination) of the test item were investigated.
The expected toxicokinetic behaviour is assessed in a qualitative manner based on the physicochemical properties and the results from the available toxicological studies following the instructions given in the ‘Guidance on information requirements and chemical safety assessment - Chapter R.7c: Endpoint specific guidance’ (Version 1.1).
Physico-chemical data
The test item is a zwitterionic organic chemical. It is a white crystalline powder with a molecular weight of 260 g/mol. It has a median particle size of 5.6 μm with a 10%-quantile of 15.6 μm. The test item is highly water soluble (758 g/L at 20 °C) and is considered to be hydrolytically stable at pH 4, 7 and 9 (at 50 °C). With an estimated log P of < -3.8, the test item is hydrophilic. It has a very low volatility, as its vapour pressure was estimated to be 2.5*10E-14 Pa at 25 °C. With a mean surface tension of 63.3 mN/m (at 20°C), the test item is not surface active.
Absorption
Generally, oral absorption is favoured for molecular weights below 500 g/mol. The high water solubility of 758 g/L enables the test substance to dissolve in the gastrointestinal fluids. The substance is a zwitterion and therefore contains ionisable groups. It is generally thought that ionized substances do not readily diffuse across biological membranes. Furthermore, the hydrophilicity of the test substance as determined by its high water solubility and low octanol/water partition coefficient indicates a low potential for passive diffusion through cell membranes. In addition, the molecular weight of 260 g/mol shows that the passage through aqueous pores or through the epithelial barrier by the bulk passage of water is less likely. Taken together, the physiochemical properties indicate that the test substance becomes bioavailable following the oral route to a limited extent.
Due to the high melting point above 200 °C, no availability as a vapour under standard environmental conditions is expected for the test substance. Still the vapour pressure was determined and is very low for the test substance. It was calculated to be 2.5*10E-14 Pa at 25 °C. As the test substance appears as a powder, formation and inhalation of dust might occur. Generally, particles with an aerodynamic diameter below 100 μm have the potential to be inspired, below 50 μm may reach the thoracic region and those below 15 μm can pass into the alveolar region of the respiratory tract. With a D50 value of 5.6 and D90 of 15.6 μm a high proportion of particles smaller than 100 μm exist for the test substance. As demonstrated by the distribution of the particle size, the test substance’s particles might possess the ability to reach the alveolar region. Due to the high water solubility the deposited test substance may dissolve into the mucus lining but the potential to be absorbed directly across the respiratory tract epithelium is limited. Furthermore, the molecular weight shows that passage through aqueous pores or across membranes with the bulk passage of water is less likely and passive diffusion is also unlikely due to the low log Pow. Most of the test substance will be retained in the mucus and transported out of the respiratory tract. Only a very small amount may be taken up by phagocytosis and transported to the blood via the lymphatic system.
As a powder, the test substance is not readily taken up by the skin. However, once moistened on the skin surface, absorption is possible, due to the high water solubility determined. The molecular weight of the test substance neither favours nor excludes dermal uptake. Considering the low log Pow of below -3.8, the test substance is likely to be too lipophobic to cross the stratum corneum, resulting in low absorption.
Distribution
As mentioned above, the physicochemical properties of the test substance favour systemic absorption following oral, inhalative and dermal uptake to a certain extent.
Direct transport through aqueous pores in general will be favoured as an entry route to the systemic circulation due to the hydrophilic properties. Due to the molecule size, this entry route will be slightly limited. After being absorbed into the body, the test substance is most likely not distributed into the interior part of cells due to the hydrophilic properties (log Pow below -3.8) and in turn the extracellular concentration is expected to be higher than the intracellular concentration.
The test substance does not have a bioaccumulative potential. The log Pow indicates no bioaccumulation potential, as it is well below 3.
Metabolism
The available genotoxicity study in bacteria indicates no remarkable differences in regard to genotoxicity and cytotoxicity in the presence or absence of metabolic activation systems. Thus, no metabolic activation is expected. Generally, it is likely that common protein interaction such as cytochrome P450 oxidases interaction during Phase I metabolism introduce a reactive or polar group in the substance. Oxidation is likely to be involved in metabolic changes in the piperazine ring, the most defining group of the test substance. The resulting compounds might be further processed into polar compounds during the metabolism in Phase II. Based on data for the piperazine ring group, the substance will only be metabolized in the liver to around 25 % (DrugBank 2021; Human Metabolome Database 2021).
Excretion
A certain amount of the test substance will be excreted most likely in its unhydrolised but possibly metabolised form. However, based on data for the piperazine ring most of the substance will be excreted in non-metabolised form (DrugBank 2021; Human Metabolome Database 2021).
The most prominent excretion pathway is via urine, as the test substance has a molecular weight below 300 g/mol and a high water solubility prone for this pathway.
References:
1. DrugBank (2021): https://go.drugbank.com/drugs/DB00592 (as of 2021-02-26)
2. Human Metabolome Database (2021): https://hmdb.ca/metabolites/HMDB0014730 (as of 2021-02-26)
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