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Diss Factsheets
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EC number: 433-100-1 | CAS number: -
- 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
- Remarks:
- expert statement
- Type of information:
- other: expert statement
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: expert statement based on physical/chemical and toxicology properties, no study on toxicokinetics available
- Principles of method if other than guideline:
- Expert statement
- GLP compliance:
- no
- Details on species / strain selection:
- not applicable
- Details on test animals or test system and environmental conditions:
- not applicable
- Details on exposure:
- not applicable
- Duration and frequency of treatment / exposure:
- not applicable
- No. of animals per sex per dose / concentration:
- not applicable
- Positive control reference chemical:
- not applicable
- Details on study design:
- not applicable
- Details on dosing and sampling:
- not applicable
- Statistics:
- not applicable
- Details on absorption:
- Generally, oral absorption is favoured for molecular weights below 500 g/mol and only molecular weights above 1000 g/mol do no longer favour absorption. The moderate water solubility of 411 mg/L enables the substance to dissolve in the gastrointestinal fluids. In combination with the molecular weight range of 214 g/mol constituent a) might pass through aqueous pores or can be carried through the epithelial barrier by the bulk passage of water. Due to the larger molecular weights constituent b) (459 g/mol) and constituent c) (705 g/mol) favour the formation of micells and pinocytosis and thereby are absorbed into the lymphatic system. Those later mechanisms of uptake are also favoured by the high log Pow values of 6.3 for constituent b) and 18 for constituent c), as generally observed for lipophilic substances. Taken together, the physiochemical properties indicate that the test substance becomes bioavailable though different mechanisms following the oral route. This assumption is neither confirmed nor rebutted by the results of the acute toxicity study conducted with the test substance. Assuming that some compounds of test substance become bioavailable after oral uptake, data from an acute oral toxicity study demonstrated, that absorbed molecules are of low systemic toxicity (an LD50 > 2000 mg/kg bw was obtained).
Due to the low vapour pressure of the test substance it is very unlikely that the substance will be available as a vapour to a large extend. In case such an exposure might occur the diverse log Pow values indicate a limitation of absorption via inhalation route directly across the respiratory tract epithelium by passive diffusion to the main constituent, while the other constituents may be taken up by micellular solubilisation. As no formation of substance’s aerosol is expected during production and handling of the substance, the uptake via inhalation is very unlikely.
Dermal absorption might also take place, favoured by the water solubility of some compounds. The log Pow range indicates an uptake of the substance into the stratum corneum. In addition it shows a possible limitation of the penetration rate by the rate of transfer between the stratum corneum and the epidermis, thereby limiting the dermal absorption of the test substance up to a certain degree. As the test substance was found to be not skin irritating and not sensitising no direct conclusion from these endpoints can be made for dermal absorption. However, at least from the guinea pig assay, in which the skin barrier was artificially compromised (intradermal application), a bioavailability can be expected. Based on the results (no effects) it can therefore be concluded, that the substance if becoming bioavailable after skin contact, is not likely to cause any adverse effects. - Details on distribution in tissues:
- As mentioned above, the physicochemical properties of the test substance favour a limited systemic absorption following oral and dermal uptake, while via inhalation practical no systemic uptake is expected.
Dependent on the constituent of the substance direct transport through aqueous pores (constituent a)) is likely to be an entry route to the systemic circulation as well as the formation of micells and pinocytosis (constituents b) and c)). After being absorbed into the body, the constituents b) and c) are most likely distributed into the interior part of cells due to their lipophilic properties and in turn the intracellular concentration may be higher than extracellular concentration particularly in adipose tissues. Constituent a) might be highly distributed through the body fluids due to the low molecular weight (214 g/mol) and it hydrophilic properties (log Pow: -3.1), while the uptake into cells will limited to aqueous channels as diffusion through the lipid membrane layers will not occur.
The log Pow range of the test substance may indicate a possible bioaccumulation potential. Due to the lipophilic tendency, the test substance may be bioaccumulative in individuals that are frequently exposed. Especially the constituents b) and c) are considered for bioaccumulation, while the hydrophilic properties of constituent a) indicate an unlikely bioaccumulation for this constituent. Nevertheless, it is expected that the substance, including constituents b) and c), is metabolized in the human body leading to metabolites with lower log Pow and higher water solubility to facilitate excretion and consequently bioaccumulation is not considered critical. - Details on excretion:
- The excretion pathway of the test substance is likely to be via urine or bile/ faeces dependent on the constituent and the involvement of Phase II metabolism. Substances with a molecular weight below 300 g/mol are prone for excretion via urine and constituent a)’s molecular weight is 214 g/mol, therefore it is the likely pathway for the main constituents. As both other constituents, b) and c), have higher molecular weights and are more or less highly lipophilic, as indicated by the log Pows, they are likely to be excreted via bile and faeces.
- Details on metabolites:
- The genotoxicity studies indicated no remarkable differences in regard to genotoxicity and cytotoxicity in the presence or absence of metabolic activation systems. This lack of cytotoxicity in the presence and absence of S9 mix indicates, that the substance itself has no cytotoxic potential and that cytochrome P450 oxidases mediated processes (metabolism) is also not likely to form reactive molecules, potentially causing toxic effects. Based on the chemical structure it is likely that cytochrome P450 oxidases interaction during Phase I metabolism introduce a reactive or polar group in the test substance. Those might be further processed into polar compounds during the metabolism in Phase II.
- Conclusions:
- Bioaccumulation of the test substance is not considered critical based on an expert statement.
- Executive summary:
Based on physicochemical characteristics, particularly water solubility, molecular weight and octanol-water partition coefficient, limited absorption by the dermal and oral route is expected, while inhalation seems unlikely. Bioaccumulation of the test substance is not considered critical, as it is expected that the substance is metabolized in the human body leading to metabolites with lower log Pow and higher water solubility to facilitate excretion. Phase I and II metabolism within liver cells is likely and excretion will presumably occur after renal passage via urine for the main constituent while the other constituents are most likely execrated via bile and faeces.
Reference
Description of key information
Based on physicochemical characteristics, particularly water solubility, molecular weight and octanol-water partition coefficient, limited absorption by the dermal and oral route is expected, while inhalation seems unlikely. Bioaccumulation of the test substance is not considered critical, as it is expected that the substance is metabolized in the human body leading to metabolites with lower log Pow and higher water solubility to facilitate excretion. Phase I and II metabolism within liver cells is likely and excretion will presumably occur after renal passage via urine for the main constituent while the other constituents are most likely execrated via bile and faeces.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
Toxicokinetic assessment
The test substance is a white solid at room temperature with a molecular weight in the range of 214 to 705 g/mol. The substance is soluble in water (411 mg/L at 20 °C). The log Pow was determined to be in the range of -3.1 to 18 due to the three different constituents. The test substance has a very low vapour pressure of < 8E-08 Pa at 25 °C. The test substance is a multi-constituent substance consisting of constituent a) (ca. 49.2 % (w/w)), constituent b) (ca. 41.1 % (w/w)) and constituent c) (ca. 9.7 % (w/w)).
Absorption
Generally, oral absorption is favoured for molecular weights below 500 g/mol and only molecular weights above 1000 g/mol do no longer favour absorption. The moderate water solubility of 411 mg/L enables the substance to dissolve in the gastrointestinal fluids. In combination with the molecular weight range of 214 g/mol constituent a) might pass through aqueous pores or can be carried through the epithelial barrier by the bulk passage of water. Due to the larger molecular weights constituent b) (459 g/mol) and constituent c) (705 g/mol) favour the formation of micells and pinocytosis and thereby are absorbed into the lymphatic system. Those later mechanisms of uptake are also favoured by the high log Pow values of 6.3 for constituent b) and 18 for constituent c), as generally observed for lipophilic substances. Taken together, the physiochemical properties indicate that the test substance becomes bioavailable though different mechanisms following the oral route. This assumption is neither confirmed nor rebutted by the results of the acute toxicity study conducted with the test substance. Assuming that some compounds of the test substance become bioavailable after oral uptake, data from an acute oral toxicity study demonstrated, that absorbed molecules are of low systemic toxicity (an LD50 > 2000 mg/kg bw was obtained).
Due to the low vapour pressure of the test substance it is very unlikely that the substance will be available as a vapour to a large extend. In case such an exposure might occur the diverse log Pow values indicate a limitation of absorption via inhalation route directly across the respiratory tract epithelium by passive diffusion to the main constituent, while the other constituents may be taken up by micellular solubilisation. As no formation of substance’s aerosol is expected during production and handling of the substance, the uptake via inhalation is very unlikely.
Dermal absorption might also take place, favoured by the water solubility of some compounds. The log Pow range indicates an uptake of the substance into the stratum corneum. In addition it shows a possible limitation of the penetration rate by the rate of transfer between the stratum corneum and the epidermis, thereby limiting the dermal absorption of the test substance up to a certain degree. As the test substance was found to be not skin irritating and not sensitising no direct conclusion from these endpoints can be made for dermal absorption. However, at least from the guinea pig assay, in which the skin barrier was artificially compromised (intradermal application), a bioavailability can be expected. Based on the results (no effects) it can therefore be concluded, that the substance if becoming bioavailable after skin contact, is not likely to cause any adverse effects.
Distribution
As mentioned above, the physicochemical properties of the test substance favour a limited systemic absorption following oral and dermal uptake, while via inhalation practical no systemic uptake is expected.
Dependent on the constituent of the substance direct transport through aqueous pores (constituent a)) is likely to be an entry route to the systemic circulation as well as the formation of micells and pinocytosis (constituent b) and c)). After being absorbed into the body, the constituents b) and c) are most likely distributed into the interior part of cells due to their lipophilic properties and in turn the intracellular concentration may be higher than extracellular concentration particularly in adipose tissues. constituent a) might be highly distributed through the body fluids due to the low molecular weight (214 g/mol) and it hydrophilic properties (log Pow: -3.1), while the uptake into cells will limited to aqueous channels as diffusion through the lipid membrane layers will not occur.
The log Pow range of the test substance may indicate a possible bioaccumulation potential. Due to the lipophilic tendency, the test substance may be bioaccumulative in individuals that are frequently exposed. Especially the constituents b) and c) are considered for bioaccumulation, while the hydrophilic properties of constituent a) indicate an unlikely bioaccumulation for this constituent. Nevertheless, it is expected that the substance, including constituent b) and c), is metabolized in the human body leading to metabolites with lower log Pow and higher water solubility to facilitate excretion and consequently bioaccumulation is not considered critical.
Metabolism
The genotoxicity studies indicated no remarkable differences in regard to genotoxicity and cytotoxicity in the presence or absence of metabolic activation systems. This lack of cytotoxicity in the presence and absence of S9 mix indicates, that the substance itself has no cytotoxic potential and that cytochrome P450 oxidases mediated processes (metabolism) is also not likely to form reactive molecules, potentially causing toxic effects. Based on the chemical structure it is likely that cytochrome P450 oxidases interaction during Phase I metabolism introduce a reactive or polar group in the test substance. Those might be further processed into polar compounds during the metabolism in Phase II.
Excretion
The excretion pathway of the test substance is likely to be via urine or bile/ faeces dependent on the constituent and the involvement of Phase II metabolism. Substances with a molecular weight below 300 g/mol are prone for excretion via urine and constituent a)’s molecular weight is 214 g/mol, therefore it is the likely pathway for the main constituents. As both other constituents, constituent b) and c), have higher molecular weights and are more or less highly lipophilic, as indicated by the log Pows, they are likely to be excreted via bile and faeces.
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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