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Diss Factsheets
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EC number: 610-122-1 | CAS number: 433733-94-9
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics, other
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2001 - 2019
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
Data source
Reference
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
- Objective of study:
- absorption
- distribution
- toxicokinetics
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- This theoretical assessment was prepared, taking all currently available relevant information
into account, based on the REACH Guidance: Guidance on Information Requirements and
Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance. - GLP compliance:
- yes
Test material
- Reference substance name:
- [(2S,3R,5S)-3-acetoxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl acetate
- EC Number:
- 610-122-1
- Cas Number:
- 433733-94-9
- Molecular formula:
- C14H18N2O7
- IUPAC Name:
- [(2S,3R,5S)-3-acetoxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl acetate
Constituent 1
- Radiolabelling:
- no
Administration / exposure
- Details on study design:
- This theoretical assessment was prepared, taking all currently available relevant information
into account, based on the REACH Guidance: Guidance on Information Requirements and
Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance.
Results and discussion
- Preliminary studies:
- A substance can enter the body via the gastrointestinal tract, the lungs, or the skin, depending
on the exposure route. To determine the rate of absorption adequately, the different exposure
routes are assessed individually.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract (1). Diacetyl Thymidine (LDT600-C3) dissolves well in water (12.9 g/L at 20°C), therefore passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage of such molecules across membranes with the bulk passage of water) is expected. The molecular weight of Diacetyl Thymidine (LDT600-C3) (326.3) will not hamper fast absorption, as smaller molecules with a molecular weight below 500 are taken up easily. Similarly, the lipophilicity of the substance is moderate (resulting in a log Pow of 1), which allows penetration through lipid membranes by passive diffusion. Diacetyl Thymidine (LDT600-C3) does not have ionisable groups, implying that potential uptake will not be hampered by presence of charged groups. Finally, the hydrolysis data indicate that the substance is stable at lower pH at body temperature, therefore rapid breakdown in the gastro-intestinal tract is not expected.
Taken together, absorption of Diacetyl Thymidine (LDT600-C3) after oral exposure is to be expected due to its moderate lipophilicity and good water solubility. Furthermore, its size and the fact that the substance is not ionisable do not indicate hampering of uptake. For risk assessment purposes oral absorption of Diacetyl Thymidine (LDT600-C3) is therefore set at 100% The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.
Diacetyl Thymidine (LDT600-C3) has a very low vapour pressure (2.12*10-8 Pa at 20°C) and no boiling point. This implies that exposure via inhalation of vapour is not likely to occur. On the other hand, Diacetyl Thymidine (LDT600-C3) particles are small (D10 = 86.83 μm, D50 = 260.5 μm and D90 = 506.6 μm). In general, particles with aerodynamic diameters below 100 μm have the potential to be inhaled, which will be the case for a minor part of the substance. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm can enter the alveolar region of the respiratory tract (2). This indicates that during exposure to Diacetyl Thymidine (LDT600-C3) by inhalation some particles may reach both the nasopharyncheal region and the tracheo/bronchial/pulmonary region. Once Diacetyl Thymidine (LDT600-C3) reaches the lung tissue, it will dissolve within the mucus lining of the respiratory tract and will be taken up. Related to the very low vapour pressure and based on the fact that the inhalable part is expected to be less than 50% of the substance, for risk assessment purposes the inhalation absorption of Diacetyl Thymidine (LDT600-C3) is set at 50%.
Diacetyl Thymidine (LDT600-C3) is a powder, and in this state uptake through skin is expected to be very limited. In presence of fluid (e.g. skin moisture), it will dissolve which allows adsorption into the skin. The first layer of the skin, the stratum corneum, is a barrier for hydrophilic compounds. As Diacetyl Thymidine (LDT600-C3) is of moderate lipophilicity, some penetration by passive diffusion through lipid layers is to be expected. Furthermore, Diacetyl Thymidine (LDT600-C3) has a molecular weight below 500, which will not hamper fast absorption. The substance is expected not to be ionized, implying adsorption will not be negatively influenced by for example binding to skin components.
According to the criteria given in the REACH Guidance (2), 10% dermal absorption will be considered in case MW >500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. With regard to both parameters, Diacetyl Thymidine (LDT600-C3) does not fulfill the criteria (MW > 500). Based on these considerations, for risk assessment purposes dermal absorption is set at 100%. - Details on distribution in tissues:
- Once absorbed, wide distribution of the test substance throughout the body is expected based on its molecular weight (MW = 326.3) and water solubility (12.9 g/L at 20°C). Furthermore, related to the moderate lipophilicity of Diacetyl Thymidine (LDT600-C3) (log Pow = 1), the substance is not expected to accumulate in adipose tissue. Absorbed Diacetyl Thymidine (LDT600-C3) is most likely excreted via urine and/ or bile. In conclusion, Diacetyl Thymidine (LDT600-C3) is not expected to bio-accumulate significantly in the body upon exposure.
Metabolite characterisation studies
- Metabolites identified:
- not specified
Applicant's summary and conclusion
- Conclusions:
- A toxicokinetic assessment for Diacetyl Thymidine (LDT600-C3) was performed. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 100% (oral), 50% (inhalation) and 100% (dermal) for risk assessment purposes.
The bioaccumulation potential is expected to be low.
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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