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EC number: 457-660-1 | CAS number: 104797-47-9
- 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
- Type of information:
- other: Compilation of available data
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Compilation of data and estimations.
Data source
Reference
- Reference Type:
- other: compilation and estimations
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
- Objective of study:
- other: Compilation of available data and estimations based on phys.-chem. properties.
Test guidelineopen allclose all
- Qualifier:
- no guideline available
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: ECHA Guidance on Information Requirement, R.7.12 Guidance on Toxicokinetics.
- Version / remarks:
- June 2017
- GLP compliance:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 457-660-1
- EC Name:
- -
- Cas Number:
- 104797-47-9
- Molecular formula:
- C14H10N4O3S3 (Hill formula) C14H10N4O3S3 (CAS Formula)
- IUPAC Name:
- (Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-(1,3-benzothiazol-2-ylsulfanyl)-2-oxoethylidene]amino acetate
- Details on test material:
- See the individual records on toxicological endpoints.
Constituent 1
Results and discussion
Main ADME results
- Type:
- absorption
- Results:
- Low.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Absorption, distribution:
Systemic effects were detected in the repeated oral dose study and the screening OECD 421 study. These effects indicate an absorption of the test substance in the gastrointestinal tract and a distribution in the body. No relevant systemic toxic effects were noted in the acute oral, the acute dermal and the acute inhalation toxicity studies.
Due to the positive result of the skin sensitisation study, some dermal uptake, but not necessarily a skin penetration must have occurred.
Based on the Section R.7.12.2.1 of the 'Guidance on information requirements and chemical safety assessment' some of the relevant physical-chemical properties for an oral absorption are:
- Molecular weights below 500 are favourable for absorption. The substance has a molecular weight of 378.
- The water solubility of T15-AE is very low and do not favour a dissolution of the solid T15-AE in the gastrointestinal fluids.
- The moderate log P of 3.1 is favourable for absorption by passive diffusion.
These data point to a low to moderate oral absorption - in agreement with the observed (non to low) toxic effects in the available oral toxicity studies.
Guidance for an inhalation absorption:
An acute inhalation toxicity study in rats with a MMAD of 3.3 µm did not show systemic toxic effects at the limit concentration of 5.03 mg/L, therefore no indication of an absorption was obtained. The relevant parameters for absorption at inhalation exposure are not very different to those for oral absorption, as described in the Section R.7.12.2.1 of the 'Guidance on information requirements and chemical safety assessment'.
Guidance for a dermal absorption:
For dermal absorption an even lesser absorption is predicted compared to the oral route, based on the following criteria:
- Molecular Weight: The molecular weight of 378.4 for T15-AE is in between favourable and unfavourable for dermal uptake.
- Water Solubility: The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore if the water solubility is below 1 mg/l, dermal uptake is likely to be low. The water solubility of T15-AE is 0.077 mg/L, i.e. <1 mg/L.
- n-octanol/water partition coefficient: Log P values between 1 and 4 would favour dermal absorption, but only if water solubility is high.
Based on the Section R.7.12.2.1 of the 'Guidance on information requirements and chemical safety assessment' some of the relevant physical-chemical properties for oral and inhalation absorption are:
- the substance is ionised at pH of the stomach, which does not favour an absorption in the stomach but the non-ionised form occurring in the intestine and also in the lungs will favour an absorption.
- the relatively low molecular mass of 378 ( favourable for absorption at <500),
- the very low water solubility of 0.08 mg/L (very hydrophobic substances will not be available for absorption),
- the n-octanol/water partition coefficient of log Pow = 3.1 is within the range of -1 to 4 that is favourable for absorption,
- the hydrolysis data point to a degradation within the time of passing the GIT, hence prediction on toxicokinetic data for the parent compound may be of limited relevance.
From these data it is concluded that a restricted oral absorption will occur, which is in agreement with the absorption observed in the repeated dose oral toxicity study.
More likely is an absorption after inhalation.
Dermal absorption:
- The molecular weight of 378 is neither favourable nor not favourable,
- from the low water solubility a low absorption is predicted,
- the n-octanol/water partition coefficient of log Pow = 3.1 is within the range of -1 to 4 that is favourable for absorption,
- the substance is not surface active which would enhance an absorption,
- the skin sensitising property points to some uptake in the skin.
A low dermal absorption is predicted. - Details on distribution in tissues:
- Distribution:
From the systemic effects observed in the repeated dose toxicity study it is concluded that some distribution occurs.
Transfer into organs
- Observation:
- other: No relevant data are available.
- Details on excretion:
- Excretion:
No relevant data are available, which provide evidence on the route of excretion.
Toxicokinetic parameters
- Toxicokinetic parameters:
- other: No relevant data are available.
Metabolite characterisation studies
- Details on metabolites:
- Metabolism:
No relevant differences occurred in the Ames-test with and without the addition of a metabolising system. A weak indication is obtained from the in vitro cytogenetic study that an external metabolism might render the substance less genotoxic. Therefore no strong indication of the importance of the metabolism of the test substance was obtained from the mutagenicity studies.
Any other information on results incl. tables
Bioaccumulation: No relevant accumulation is expected, based on the medium log Pow.
Applicant's summary and conclusion
- Executive summary:
Absorption, distribution:
Systemic effects were detected in the repeated oral dose study and the prescreening OECD 421 study. These effects indicate an absorption of the test substance in the gastrointestinal tract and a distribution in the body. No relevant systemic toxic effects were noted in the acute oral, the acute dermal and the acute inhalation toxicity studies.
Due to the positive result of the skin sensitisation study, some dermal uptake, but not necessarily a skin penetration must have occurred.
Based on the Section R.7.12.2.1 of the 'Guidance on information requirements and chemical safety assessment' some of the relevant physical-chemical properties for an oral absorption are:
- Molecular weights below 500 are favourable for absorption. The substance has a molecular weight of 378.
- The water solubility of T15-AE is very low and do not favour a dissolution of the solid T15-AE in the gastrointestinal fluids.
- The moderate log P of 3.1 is favourable for absorption by passive diffusion.
These data point to a low to moderate oral absorption - in agreement with the observed (non to low) toxic effects in the available oral toxicity studies.
Guidance for an inhalation absorption:
An acute inhalation toxicity study in rats with a MMAD of 3.3 µm did not show systemic toxic effects at the limit concentration of 5.03 mg/L, therefore no indication of an absorption was obtained. The relevant parameters for absorption at inhalation exposure are not very different to those for oral absorption, as described in the Section R.7.12.2.1 of the 'Guidance on information requirements and chemical safety assessment'.
Guidance for a dermal absorption:
For dermal absorption an even lesser absorption is predicted compared to the oral route, based on the following criteria:
- Molecular Weight: The molecular weight of 378.4 for T15-AE is in between favourable and unfavourable for dermal uptake.
- Water Solubility: The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore if the water solubility is below 1 mg/l, dermal uptake is likely to be low. The water solubility of T15-AE is 0.077 mg/L, i.e. <1 mg/L.
- n-octanol/water partition coefficient: Log P values between 1 and 4 would favour dermal absorption, but only if water solubility is high.
Excretion:
No relevant data are available, which provide evidence on the route of excretion.
Metabolism:
No relevant differences occurred in the Ames-test with and without the addition of a metabolising system. A weak indication is obtained from the in vitro cytogenetic study that an external metabolism might render the substance less genotoxic. Therefore no strong indication of the importance of the metabolism of the test substance was obtained from the mutagenicity studies.
Bioaccumulation: No relevant accumulation is expected, based on the medium log Pow.
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