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EC number: 448-060-0 | CAS number: 727678-39-9
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
There are no toxicokinetic studies available for 2-[2-(3-Butoxypropyl)-1, 1-dioxo-1,2, 4-benzothiadiazin-3-yl-5’-tert-butyl-2-(5, 5-dimethyl-2, 4-dioxo-1, 3-oxazolidin-3-yl)-2 ‘-[(2-ethylhexyl)thio]acetanilide (UY-330). Whenever possible, the toxicokinetic properties of the substance were assessed, taking into account the available information on physico-chemical and toxicological characteristics, according to ‘Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance’ (ECHA, 2012).
UY-330 is a white powder with a molecular weight of 757.02 g/mol (including crystallization water). The substance is insoluble in water (< 0.08 mg/L at 20 °C), has a low vapour pressure (0.0025 Pa at 20 °C) and a high partition coefficient (log Pow) of 8.8.
Absorption
Absorption is a function of the potential for a substance to diffuse across biological membranes. In addition to molecular weight the most useful parameters providing information on this potential are the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow provides information on the relative solubility of the substance in water and octanol and is a measure of lipophilicity (ECHA, 2012).
Oral
The smaller the molecule, the more easily it will be taken up. In general, molecular weights below 500 are favorable for oral absorption. Solids have to dissolve before they can be absorbed (ECHA, 2012).
Due to the molecular weight of 757.02 g/mol and the log Pow of 8.8 two rules of the “Lipinski Rule of Five” (Lipinski et al., 2001) are not fulfilled and therefore only marginal absorption of UY-330 is expected after oral intake.
Moreover, an acute oral toxicity study has been conducted in male and female rats (Hooiveld, 2003a). According to OECD 423, a LD50 value of 5000 mg/kg bw was determined since there was no mortality following administration of 2000 mg/kg bw in two separate steps. Besides the hunched posture observed in all animals on the first treatment day, no other clinical signs and no effects on the body weight were observed in any animal during the 14 d observation period. Macroscopic examinations at necropsy did not reveal any abnormalities.
In an oral repeated dose toxicity study, male and female rats were treated for 28 d with UY-330 via gavage according to OECD 407 (van Otterdijk, 2004). No mortality occurred during the study period. Since there were no adverse effects observed on gross pathology, organ weights and histopathology, the NOAEL is ≥ 1000 mg/kg bw/d for males and females in this study.
Taken together, based on the low water solubility of the substance and the Lipinski rule of five, bioavailability of UY-330 in the gastrointestinal tract is not expected.
Inhalation
UY-330 has a low vapor pressure (0.0025 Pa at 20 °C), thus indicating a low volatility. In humans, particles with aerodynamic diameters below 100 µm have the potential to be inhaled (ECHA, 2012). Since the mass median diameter of UY-330 is 21.69 µm, absorption of the test substance after inhalation is possible. However, UY-330 is not used in spray processes and due to the insolubility in water, most of the inhaled particles will remain in the upper airways and/or will be swallowed, with few or no particles reaching the pulmonary alveols.
Dermal
The smaller the molecule, the more easily it may be taken up. In general, a molecular weight below 100 favours dermal absorption, above 500 g/mol the molecule may be too large.Log Pow values between 1 and 4 favour dermal absorption particularly if water solubility is high(ECHA, 2012).
As UY-330 is an insoluble solid with a molecular weight of 757.02 g/mol and a log Pow of 8.8, dermal absorption of the substance is not likely.
In a standard acute dermal toxicity study performed in accordance with OECD 402, a dispersion of UY-330 in propylene glycol was tested at 2000 mg/kg bw under occlusive conditions (van Otterdijk, 2004). No mortality occurred during the 14 d observation period. Local effects like chromodacryorrhoea, white staining, scales, scabs and/or erythema on the treated skin sites were noted in all animals. Between days 1 and 3, a hunched posture was observed in all animals. On Day 2, shallow respiration was noted in 1 male and 1 female and a further female showed uncoordinated movements. No abnormal findings were noted at necropsy. The LD50 of the test substance was > 2000 mg/kg bw.
In the skin irritation and sensitization studies or following instillation of UY-330 in the eye sack no signs of systemic toxicity concerning behavior, body weight and food consumption were observed (Hooiveld, 2003b, 2003c, 2003d).
In summary, in the standard acute toxicity study, effects were observed which are likely to be treatment-related but not substance-related as UY-330 has a high molecular weight, a high log Pow and is insoluble in water. Based on the physico-chemical properties, dermal absorption of UY-330 is not expected.
Accumulation
Lipophilic substances tend in general to concentrate in adipose tissue and depending on the conditions of exposure may accumulate. Moreover, lipophilic substances that come into contact with the skin can readily penetrate the lipid rich stratum corneum but are not well absorbed systemically. Although there is no direct correlation between the lipophilicity of a substance and its biological half-life, it is generally the case that substances with high log Pow values have long biological half-lives (ECHA, 2012).
The high log Pow of 8.8 indicates that UY-330 may have the potential to accumulate in the fat tissue and in stratum corneum.
Distribution
Distribution within the body depends on the molecular weight, the lipophilic character and water solubility of a substance. In general, the smaller the molecule, the wider is the distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues (ECHA, 2012).
Distribution of the substance in the body is considered to be limited due to the insolubility in water and the molecular weight of 757.02 g/mol. The log Pow of 8.8 indicates a high lipophilicity of the test substance and therefore distribution particularly in fatty tissues is likely.
Metabolism
Based on the molecular weight of 757.08 g/mol, the log Pow of 8.8 and the insolubility in water, absorption of relevant amounts of UY-330 is not expected and therefore, metabolism under in vivo conditions is not expected.
Theoretically, in the gastro-intestinal tract, the central amide group may already undergo cleavage, resulting in more polar break-down products. However, because of the low solubility of UY-330 this is not anticipated. In the case absorption of UY-330 occurs, the unsaturated rings will undergo extensive hydroxylation, followed by rapid sulfation or glucuronidation. The resulting metabolites will be excreted via bile and/or urine. Also hydroxylation of the peripheral aliphatic groups may take place, with subsequent sulfation and glucuronidation. The resulting metabolites will also be excreted via bile and/or urine.
The results of the studies on genetic toxicity (Ames test,in vitrochromosome aberration test in mammalian cells, HPRT) were all negative with and without metabolic activation. Thus, they do not indicate that UY-330 is activated to reactive compounds underin vitrotest conditions (Buskens, 2003; Buskens, 2004; Lazová, 2013). Moreover, UY-330 did not reveal any test substance related effects in a sub-acute oral repeated dose toxicity study (van Otterdijk, 2004).No mortality and no adverse clinical signs were observed. Body weights, food consumption, haematology, clinical chemistry and investigations on neurobehaviour revealed no adverse effects. In addition, gross pathology, organ weight determination and histopathology were without any adverse finding.
Excretion
According to the molecular weight and the insolubility in water, UY-330 is expected to be excreted mainly via faeces and to a minor extent via urine. The portion of the substance which has penetrated the lipid rich stratum corneum after dermal application is considered to be sloughed off with the skin cells.
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