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EC number: 254-274-3 | CAS number: 39072-70-3
- 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
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- Transport and distribution
- Environmental data
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- 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
Based on its physicochemical properties and the results obtained from the comprehensive toxicological investigation, it is unlikely that considerable amounts ofN,N''-hexane-1,6-diylbis[N'-benzylurea]will become bioavailable following oral, dermal or inhalative exposure. As a result, no relevant amounts of the substance will be distributed or metabolised within the body. Following oral intake, it is expected that the substance will be readily excreted via the faeces. Based on the physicochemical properties and the calculated BCF value the chemical is not considered to be bioaccumulative.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
1 Physicochemical Data on N,N''-hexane-1,6-diylbis[N'-benzylurea]
The substance N,N''-hexane-1,6-diylbis[N'-benzylurea] appears as a white solid in granular form at standard ambient temperature and pressure.The molecular weight (Mw) of the substance is 382.4992 g/mol and the molecular formula is C22H30N4O2. At standard ambient pressure, the melting point is 219°C while the boiling point could not be determined due to limited stability of the substance.The chemical has a very low vapour pressure which can be regarded as negligible for the present assessment.The substance is not soluble in water as indicated by the low water solubility value of 0.057 mg/L. The logPow value for the chemical wasdetermined to be 2.4 at 23°C (HPLC method). The BCF (Bioconcentration factor) value was determined to be 17.8 L/kg (based on a calculation with EpiSuite (BCFBAF v3.01) and a measured LogKOW of 2.4).
2 Toxicokinetic Analysis of N,N''-hexane-1,6-diylbis[N'-benzylurea]
Absorption
Oral route:
Solely based on the substance’s molecular weight and logPow, absorption through the walls of the gastrointestinal (GI) tract via mechanisms of passive diffusion is possible. However, in order to be absorbable, the substance has to dissolve into the GI fluids and hence make contact with the mucosal surface. Taking the solid granular form and the extremely low water solubility of the substance into account, it is unlikely that considerable amounts will be absorbed into the systemic circulation following oral ingestion.
This assumption is further supported by the results obtained from the toxicological evaluation. More specifically, in an acute oral systemic toxicity study in rats (OECD 423), the LD50 value for N,N''-hexane-1,6-diylbis[N'-benzylurea]was determined to be higher than 2000 mg/kg bw (limit dose) with no local or systemic effects noted.
Furthermore, a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats (OECD 422) was conducted on the substance. No adverse effects were observed in the parental animals and the offspring. Thus, the NOAEL for general, reproductive and developmental toxicity was determined to be 1000 mg/kgbw/day (limit dose).
Overall,with regard to the physicochemical properties and the absence of systemic effects in the toxicological investigation, it is unlikely that relevant amounts of N,N''-hexane-1,6-diylbis[N'-benzylurea]will reach the systemic circulation. Even if certain amounts become bioavailable no systemic toxicity is expected.
Inhalation route:
Based on the very low vapour pressure and the fact that the substance appears in granular form, inhalation exposure, either to vapour or to dust particles, can be excluded.
Dermal route:
The physicochemical properties of N,N''-hexane-1,6-diylbis[N'-benzylurea] do not favour dermal absorption. As the chemical consists of granulates at room temperature, it has to dissolve into the surface moisture of the skin before systemic uptake can take place. This pre-requisite combined with the poor water solubility will drastically limit the amount of chemical bioavailable when placed in contact to the skin.
Again, the assumption that no dermal absorption occurs is further strengthened by the results achieved from the dermal toxicity testing. In an acute dermal toxicity study (OECD 402), the substance did not cause any local or systemic effects and the LD50 was determined to be greater than the limit dose (2000 mg/kg bw). Furthermore, no indication of systemic absorption was evident with respect to the results obtained from an LLNA assay conducted on mice. Here, no immunological response was triggered and no signs of systemic toxicity were present.
Overall, the physicochemical properties and the findings from the dermal toxicity study support that practically no absorption into the systemic circulation is expected after dermal application.
Distribution
With regards to the physicochemical properties and the results achieved from the comprehensive toxicity testing, it appears that the bioavailability ofN,N''-hexane-1,6-diylbis[N'-benzylurea]via the main entrance routes (i.e., oral, dermal and through inhalation) is rather limited, if taken place at all. Therefore, it is doubtful that toxicologically relevant amounts of the substance will enter the systemic circulation and in turn be further distributed inside the body. Even if some amounts become systemically available, the presented data clearly indicates that such amounts have very low toxicity.
Metabolism
Because the absorption ofN,N''-hexane-1,6-diylbis[N'-benzylurea]into the interior part of the body cells is considered to be negligible, considerable contact of the substance with intracellular metabolising enzymes is not expected and therefore the formation of potential metabolites (e.g. cleavage of the urea moiety or hydroxylation of the benzene ring) is rather unlikely.
Excretion
As mentioned before, it is expected that the bioavailability ofN,N''-hexane-1,6-diylbis[N'-benzylurea]following oral, dermal and inhalation exposure is most likely to be rather limited, if taken place at all. Thus, when ingested via the oral route the substance is expected to be readily excreted in its unchanged form via the faeces. However, if a certain amount of the substance is absorbed, it is highly unlikely that bioaccumulation within the body will occur according to the determined BCF (Bioconcentration factor) value of 17.8.
3 Summary
Based on its physicochemical properties and the results obtained from the comprehensive toxicological investigation, it is unlikely that considerable amounts ofN,N''-hexane-1,6-diylbis[N'-benzylurea]will become bioavailable following oral, dermal or inhalative exposure. As a result, no relevant amounts of the substance will be distributed or metabolised within the body. Following oral intake, it is expected that the substance will be readily excreted via the faeces. Based on the physicochemical properties and the calculated BCF value the chemical is not considered to be bioaccumulative.
4 References
Bonse G., Metzler M. (1978) Biotransformation organischer Fremdsubstanzen. Thieme Verlag, Stuttgart.
ECHA (2008) Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.
Marquardt H., Schäfer S. (2004) Toxicology.Academic Press,,, 2nd Edition 688-689.
Mutschler E., Schäfer-Korting M. (2001) Arzneimittelwirkungen. Lehrbuch der Pharmakologie und Toxikologie. Wissenschaftliche Verlagsgesellschaft, Stuttgart.
Renwick A.G. (1994) Toxicokinetics - pharmacokinetics in toxicology. In Hayes,A.W. (ed.)
Principles and Methods of Toxicology. Raven Press, New York, p 103.
Rozman K.K., Klaassen C.D. (1996) Absorption, Distribution, and Excretion of Toxicants. In Klaassen C.D. (ed.) Cassarett and Doull's Toxicology: The Basic Science of Poisons. McGraw-Hill, New York.
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