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EC number: - | 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
- Type of information:
- other: Toxicokinetic asessment based on the physicochemical properties of the substance and on the results of various in vitro and in vivo study results, including an OECD422 repeat dose and reproductive toxicity screening study.
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Based on toxicological data of the substance itself and on the physicochemical characteristics determined for the substance.
- Qualifier:
- according to guideline
- Guideline:
- other: Expert statement
- Deviations:
- no
- GLP compliance:
- no
- Details on absorption:
- Oral Route
The physical chemical properties described above indicate that the substance has a molecular size at the upper end of the range that may be expected to be easily absorbed within the mammalian gastrointestinal tract, should that material be ingested. Being a mix of components with both lipophilic and hydrophilic properties the substance may be expected to cross gastrointestinal epithelial barriers, and the evidence from the repeated dose toxicity study indicates that absorption did occur because there were dose-related increases in liver organ weights. An acute oral gavage toxicity study identified no evidence of toxicity (LD50 >2000 mg/kg bw). The repeat dose and reproductive screening toxicology study using the oral route gave a NOAEL of 600 mg/kg bw/day, the upper dose level being limited by local irritation effects in the intestine. The absence of adverse findings following oral dosing is probably due to a low index of inherent toxicity for this substance, and/or its metabolite(s).
Dermal Route
Regarding the dermal absorption of the substance, its rate of uptake into the stratum corneum and its rate of transfer between the stratum corneum and the epidermis are likely to be slow considering both the high MW, the log Pow, and its low water solubility. These assumptions were supported by the absence of observed systemic effects following dermal application of the substance in the acute dermal toxicity study at up to 2000 mg/kg bw. However, the substance causes irritant effects after dermal exposure (although not classified for skin irritation) and this may facilitate absorption through the skin after prolonged exposure.
Inhalation Route
The potential for inhalation toxicity was not studied directly in a toxicology study using the inhalation route. However, the physical nature of the substance (semi-solid) and low vapour pressure of the substance indicate a very low propensity to enter atmospheric air in a respirable form. Thus, respiratory absorption under normal use and based on the life-cycle information of this substance, is expected to be inconsequential.
- Details on distribution in tissues:
- Systemic distribution of the substance can be predicted from the physical chemical properties of this substance. The relatively low LogPow and poor water solubility of the majority of the substance, suggests that this substance, upon systemic absorption, may be transported through the circulatory system both in the aqueous phase and in association with a carrier molecule such as a lipoprotein or other macromolecules. The major proportion of the substance will not readily traverse cellular barriers or distribute into fatty tissues. There is evidence of systemic exposure and histopathological changes in repeated dose studies, but not of cumulative toxicity, as would be manifested by an accumulation of the substance or metabolites in tissues.
The substance is a UVCB and like most xenobiotics, it may be expected to undergo phase I oxidation/reduction, esterase-catalyzed hydrolysis and subsequent Phase II conjugation. Acute and repeated-dose toxicity testing provided no evidence that the substance was metabolized into toxic metabolites. Data from bacterial mutagenicity and mammalian cell mutagenicity tests in mammalian cells, in which the substance was subjected to rat hepatic microsomal enzyme systems, did not show any evidence of genotoxic activity from the substance or its metabolites. Furthermore, the in vitro toxicity of the substance was slightly reduced in the presence of metabolic enzymes. This may indicate that the metabolites may be less toxic than the substance itself but more likely that the presence of protein may bind the substance, or protect the cells, such that the toxicity is reduced. - Details on excretion:
- The structural characteristics of the substance suggest that this molecule may undergo phase I and phase II metabolic transformation. The resulting metabolic by-products are expected to undergo routine renal and or biliary excretion.
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- other: Please see conclusion
- Conclusions:
Toxicokinetic assessment of the test substance
The toxicokinetic profile of the substance was predicted using the physical chemical properties of the substance, the data obtained from acute and repeated-dose toxicity studies, as well as information gained from genotoxicity assays.
Physico-chemical properties
The substance is a yellow, semi-solid UVCB and the molecular weight of the major components is in the range of 395.6 to 475.5 with the majority at the upper end of the range. The substance is water soluble but loading rate dependent, such that no single figure may be given. However, at a 10% loading rate the range for four of the major components is 4.14 x 10-2to 59.5 g/L, with an estimated octanol/water partition coefficient in the range of log Pow-9.88 x 10-2to 2.68, and a low vapour pressure (0.254 Pa @ 25oC). The surface tension of the substance was 40.0 mN/m at 21.8°C and the substance is considered to be surface active. The majority of the substance components are salts and considered to dissociate.
Absorption
Oral Route
The physical chemical properties described above indicate that the substance has a molecular size at the upper end of the range that may be expected to be easily absorbed within the mammalian gastrointestinal tract, should that material be ingested. Being a mix of components with both lipophilic and hydrophilic properties the substance may be expected to cross gastrointestinal epithelial barriers, and the evidence from the repeated dose toxicity study indicates that absorption did occur because there were dose-related increases in liver organ weights. An acute oral gavage toxicity study identified no evidence of toxicity (LD50 >2000 mg/kg bw). The repeat dose and reproductive screening toxicology study using the oral route gave a NOAEL of 600 mg/kg bw/day, the upper dose level being limited by local irritation effects in the intestine. The absence of adverse findings following oral dosing is probably due to a low index of inherent toxicity for this substance, and/or its metabolite(s).
Dermal Route
Regarding the dermal absorption of the substance, its rate of uptake into the stratum corneum and its rate of transfer between the stratum corneum and the epidermis are likely to be slow considering both the high MW, the log Pow, and its low water solubility. These assumptions were supported by the absence of observed systemic effects following dermal application of the substance in the acute dermal toxicity study at up to 2000 mg/kg bw. However, the substance causes irritant effects after dermal exposure (although not classified for skin irritation) and this may facilitate absorption through the skin after prolonged exposure.
Inhalation Route
The potential for inhalation toxicity was not studied directly in a toxicology study using the inhalation route. However, the physical nature of the substance (semi-solid) and low vapour pressure of the substance indicate a very low propensity to enter atmospheric air in a respirable form. Thus, respiratory absorption under normal use and based on the life-cycle information of this substance, is expected to be inconsequential.
Distribution
Systemic distribution of the substance can be predicted from the physical chemical properties of this substance. The relatively low LogPow and poor water solubility of the majority of the substance, suggests that this substance, upon systemic absorption, may be transported through the circulatory system both in the aqueous phase and in association with a carrier molecule such as a lipoprotein or other macromolecules. The major proportion of the substance will not readily traverse cellular barriers or distribute into fatty tissues. There is evidence of systemic exposure and histopathological changes in repeated dose studies, but not of cumulative toxicity, as would be manifested by an accumulation of the substance or metabolites in tissues.
Metabolism
The substance is a UVCB and like most xenobiotics, it may be expected to undergo phase I oxidation/reduction, esterase-catalyzed hydrolysis and subsequent Phase II conjugation. Acute and repeated-dose toxicity testing provided no evidence that the substance was metabolized into toxic metabolites. Data from bacterial mutagenicity and mammalian cell mutagenicity tests in mammalian cells, in which the substance was subjected to rat hepatic microsomal enzyme systems, did not show any evidence of genotoxic activity from the substance or its metabolites. Furthermore, the in vitro toxicity of the substance was slightly reduced in the presence of metabolic enzymes. This may indicate that the metabolites may be less toxic than the substance itself but more likely that the presence of protein may bind the substance, or protect the cells, such that the toxicity is reduced.
Excretion
The structural characteristics of the substance suggest that this molecule may undergo phase I and phase II metabolic transformation. The resulting metabolic by-products are expected to undergo routine renal and or biliary excretion.- Executive summary:
Toxicokinetic assessment of the test substance
The toxicokinetic profile of the substance was predicted using the physical chemical properties of the substance, the data obtained from acute and repeated-dose toxicity studies, as well as information gained from genotoxicity assays.
Physico-chemical properties
The substance is a yellow, semi-solid UVCB and the molecular weight of the major components is in the range of 395.6 to 475.5 with the majority at the upper end of the range. The substance is water soluble but loading rate dependent, such that no single figure may be given. However, at a 10% loading rate the range for four of the major components is 4.14 x 10E-2 to 59.5 g/L, with an estimated octanol/water partition coefficient in the range of log Pow-9.88 x 10E-2 to 2.68, and a low vapour pressure (0.254 Pa @ 25oC). The surface tension of the substance was 40.0 mN/m at 21.8°C and the substance is considered to be surface active. The majority of the substance components are salts and considered to dissociate.
Absorption
Oral Route
The physical chemical properties described above indicate that the substance has a molecular size at the upper end of the range that may be expected to be easily absorbed within the mammalian gastrointestinal tract, should that material be ingested. Being a mix of components with both lipophilic and hydrophilic properties the substance may be expected to cross gastrointestinal epithelial barriers, and the evidence from the repeated dose toxicity study indicates that absorption did occur because there were dose-related increases in liver organ weights. An acute oral gavage toxicity study identified no evidence of toxicity (LD50 >2000 mg/kg bw). The repeat dose and reproductive screening toxicology study using the oral route gave a NOAEL of 600 mg/kg bw/day, the upper dose level being limited by local irritation effects in the intestine. The absence of adverse findings following oral dosing is probably due to a low index of inherent toxicity for this substance, and/or its metabolite(s).
Dermal Route
Regarding the dermal absorption of the substance, its rate of uptake into the stratum corneum and its rate of transfer between the stratum corneum and the epidermis are likely to be slow considering both the high MW, the log Pow, and its low water solubility. These assumptions were supported by the absence of observed systemic effects following dermal application of the substance in the acute dermal toxicity study at up to 2000 mg/kg bw. However, the substance causes irritant effects after dermal exposure (although not classified for skin irritation) and this may facilitate absorption through the skin after prolonged exposure.
Inhalation Route
The potential for inhalation toxicity was not studied directly in a toxicology study using the inhalation route. However, the physical nature of the substance (semi-solid) and low vapour pressure of the substance indicate a very low propensity to enter atmospheric air in a respirable form. Thus, respiratory absorption under normal use and based on the life-cycle information of this substance, is expected to be inconsequential.
Distribution
Systemic distribution of the substance can be predicted from the physical chemical properties of this substance. The relatively low LogPow and poor water solubility of the majority of the substance, suggests that this substance, upon systemic absorption, may be transported through the circulatory system both in the aqueous phase and in association with a carrier molecule such as a lipoprotein or other macromolecules. The major proportion of the substance will not readily traverse cellular barriers or distribute into fatty tissues. There is evidence of systemic exposure and histopathological changes in repeated dose studies, but not of cumulative toxicity, as would be manifested by an accumulation of the substance or metabolites in tissues.
Metabolism
The substance is a UVCB and like most xenobiotics, it may be expected to undergo phase I oxidation/reduction, esterase-catalyzed hydrolysis and subsequent Phase II conjugation. Acute and repeated-dose toxicity testing provided no evidence that the substance was metabolized into toxic metabolites. Data from bacterial mutagenicity and mammalian cell mutagenicity tests in mammalian cells, in which the substance was subjected to rat hepatic microsomal enzyme systems, did not show any evidence of genotoxic activity from the substance or its metabolites. Furthermore, the in vitro toxicity of the substance was slightly reduced in the presence of metabolic enzymes. This may indicate that the metabolites may be less toxic than the substance itself but more likely that the presence of protein may bind the substance, or protect the cells, such that the toxicity is reduced.
Excretion
The structural characteristics of the substance suggest that this molecule may undergo phase I and phase II metabolic transformation. The resulting metabolic by-products are expected to undergo routine renal and or biliary excretion.
Reference
Description of key information
Toxicokinetic assessment of the test substance
The toxicokinetic profile of the substance was predicted using the physical chemical properties of the substance, the data obtained from acute and repeated-dose toxicity studies, as well as information gained from genotoxicity assays.
Physico-chemical properties
The substance is a yellow, semi-solid UVCB and the molecular weight of the major components is in the range of 395.6 to 475.5 with the majority at the upper end of the range. The substance is water soluble but loading rate dependent, such that no single figure may be given. However, at a 10% loading rate the range for four of the major components is 4.14 x 10-2to 59.5 g/L, with an estimated octanol/water partition coefficient in the range of log Pow-9.88 x 10-2to 2.68, and a low vapour pressure (0.254 Pa @ 25oC). The surface tension of the substance was 40.0 mN/m at 21.8°C and the substance is considered to be surface active. The majority of the substance components are salts and considered to dissociate.
Absorption
Oral Route
The physical chemical properties described above indicate that the substance has a molecular size at the upper end of the range that may be expected to be easily absorbed within the mammalian gastrointestinal tract, should that material be ingested. Being a mix of components with both lipophilic and hydrophilic properties the substance may be expected to cross gastrointestinal epithelial barriers, and the evidence from the repeated dose toxicity study indicates that absorption did occur because there were dose-related increases in liver organ weights. An acute oral gavage toxicity study identified no evidence of toxicity (LD50 >2000 mg/kg bw). The repeat dose and reproductive screening toxicology study using the oral route gave a NOAEL of 600 mg/kg bw/day, the upper dose level being limited by local irritation effects in the intestine. The absence of adverse findings following oral dosing is probably due to a low index of inherent toxicity for this substance, and/or its metabolite(s).
Dermal Route
Regarding the dermal absorption of the substance, its rate of uptake into the stratum corneum and its rate of transfer between the stratum corneum and the epidermis are likely to be slow considering both the high MW, the log Pow, and its low water solubility. These assumptions were supported by the absence of observed systemic effects following dermal application of the substance in the acute dermal toxicity study at up to 2000 mg/kg bw. However, the substance causes irritant effects after dermal exposure (although not classified for skin irritation) and this may facilitate absorption through the skin after prolonged exposure.
Inhalation Route
The potential for inhalation toxicity was not studied directly in a toxicology study using the inhalation route. However, the physical nature of the substance (semi-solid) and low vapour pressure of the substance indicate a very low propensity to enter atmospheric air in a respirable form. Thus, respiratory absorption under normal use and based on the life-cycle information of this substance, is expected to be inconsequential.
Distribution
Systemic distribution of the substance can be predicted from the physical chemical properties of this substance. The relatively low LogPow and poor water solubility of the majority of the substance, suggests that this substance, upon systemic absorption, may be transported through the circulatory system both in the aqueous phase and in association with a carrier molecule such as a lipoprotein or other macromolecules. The major proportion of the substance will not readily traverse cellular barriers or distribute into fatty tissues. There is evidence of systemic exposure and histopathological changes in repeated dose studies, but not of cumulative toxicity, as would be manifested by an accumulation of the substance or metabolites in tissues.
Metabolism
The substance is a UVCB and like most xenobiotics, it may be expected to undergo phase I oxidation/reduction, esterase-catalyzed hydrolysis and subsequent Phase II conjugation. Acute and repeated-dose toxicity testing provided no evidence that the substance was metabolized into toxic metabolites. Data from bacterial mutagenicity and mammalian cell mutagenicity tests in mammalian cells, in which the substance was subjected to rat hepatic microsomal enzyme systems, did not show any evidence of genotoxic activity from the substance or its metabolites. Furthermore, the in vitro toxicity of the substance was slightly reduced in the presence of metabolic enzymes. This may indicate that the metabolites may be less toxic than the substance itself but more likely that the presence of protein may bind the substance, or protect the cells, such that the toxicity is reduced.
Excretion
The structural characteristics of the substance suggest that this molecule may undergo phase I and phase II metabolic transformation. The resulting metabolic by-products are expected to undergo routine renal and or biliary excretion.
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
Additional information
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.