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EC number: 223-578-8 | CAS number: 3965-55-7
- 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
SIM-Ester is considered to be similarly absorbed by the oral and inhalation route.
Dermal penetration is assumed to be very low.
Metabolism is dominated by hydrolyses to the monomethylester and to 5-sulfoisophthalic acid.
Excretion occurs via urine.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 5
- Absorption rate - inhalation (%):
- 50
Additional information
In line with chapter R.7 c (ECHA, 2012) the main toxicokinetic properties of SIM-Ester (CAS-No. 3965-55-7) are assessed on the basis of its physico-chemical properties, the results of the standard toxicity studies performed with this substance and toxicokinetic data available on the structurally related compound dimethylterephthalic acid (DMT). In addition metabolism was elucidated in silico. Specific toxicokinetics or dermal absorption studies are not available for the substance.
1. Relevant physico-chemical properties of SIM-Ester
Molecular weight: 286.2 g/mol
Physical state: solid (RT)
logPow: -2.86
Water solubility: 32 g/L (20°C)
pKa: -1.34 +/- 0.30 (25°C)
Melting point: 374°C
Particle size distribution: D10: 0.8 +/- 0.1 µm, D50: 5.1 +/- 1.3 µm, D90: 44.7 +/- 29.9 µm
2. Absorption
Oral
Based on its low molecular weight of 286.2 g/mol SIM-Ester is likely to be absorbed in the GI tract since small molecules with a molecular weight below 500 g/mol do favour oral absorption. This assumption is supported by the results of the acute oral toxicity study (Haskell Laboratory for Toxicology and Industrial Medicine (a), 1959). In this study white precipitate in urine was seen at concentrations between 3400 and 11000 mg/kg bw indicating bioavailability after oral dosing. Due to the very good water solubility (32 g/L) and the negative pKa SIM-Ester will readily dissolve into the gastrointestinal fluids. However, absorption by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. This is also in the line with the log Pow value of -2.86 since absorption by passive diffusion generally requires a moderate log Pow value between -1 and 4.
Inhalation
Since the melting point of the test item is 374°C it is not expected that SIM-Ester is available for inhalation as vapour. The potential to be inhaled by humans is given if dust particles exhibit an aerodynamic diameter below 100 µm. Particles with an aerodynamic diameter below 50 µm may reach the thoracic region and those below 15 µm the alveolar region of the respiratory tract. Since the particle size distribution (Clariant Produkte (Deutschland) GmbH (d), 2011) of the test substance revealed a median particle size is 5.1 +/- 1.3 µm (D50) a deposition of the substance throughout the respiratory tract including the alveolar region tract can be expected when exposure to dust occurs. Absorption directly across the respiratory tract epithelium by passive diffusion may be likely but limited due to the high water solubility and negative pKa as mentioned above (GI absorption). The results obtained in the acute and subacute inhalation toxicity study (Haskell Laboratory for Toxicology and Industrial Medicine (c), 1959) do not allow a conclusion on inhalation absorption: In both studies rats were exposed to test item dust at the very high concentration of 32 mg/L +/- 20 % (75 % of the particles were≤3 µm). The observed clinical signs were not specific for systemic toxicity. Pathological changes were limited to the lung and most likely attributable to the dust overload phenomenon.
Based on the above information it is concluded that absorption of the substance is comparable after exposure via the oral and inhalation route. For risk assessment purposes an oral and inhalation absorption of 50% is assumed.
Dermal
Based on molecular weight (286.2 g/mol), log Pow (-2.86), pKa (-1.34) and water solubility (32 g/L), the dermal absorption of SIM-Ester is expected to be very low. The substance must be sufficiently soluble in water for partition from the stratum corneum into the epidermis. However, if water solubility is above 10 g/L and the low Pow value below 0 the substance is too hydrophilic to cross the lipid rich environment of the stratum corneum and dermal uptake of these substance will be low. The results of an acute dermal toxicity study in rats (Toxi-Coop Zrt. (b), 2012) do not provide any further information on dermal absorption as no systemic effects were observed at the limit dose of 2000 mg/kg bw. A dermal absorption of 10 % has been reported for dimethylterephthalate (DMT) (OECD, 2001a). In comparison to SIM-Ester DMT is not ionized, much less water soluble (19 mg/L) and has a much higher log Pow (2.25) which favors dermal absorption. This indicates that dermal absorption far below 10% can be expected for SIM-Ester and confirms the initial assumption that dermal penetration of SIM-Ester is very low. For risk assessment purposes the conservative dermal absorption value of 5% is assumed.
3. Distribution/Metabolism
In metabolism studies with the structurally related substance DMT the parent compound was basically quantitatively transformed to terephthalic acid in the rat, whereas in mice metabolism resulted in 70 % monomethyl terephthalic acid and 30 % terephthalic acid. The same hydrolytical reactions are expected for SIM-Ester leading to monomethyl-5 -sulfoisophthalate and 5 -sulfoisophthalic acid. This metabolic pathway has been confirmed in silico with the liver metabolism simulator integrated in the OECD QSAR Toolbox.
Due to the high water solubility and low log Pow of SIM-Ester distribution throughout the body via the extracellular aqueous compartment seems likely and a passage of the parent compound or its metabolites through the blood/brain barrier is unlikely.
4. Excretion
The log Pow of – 2.86, the good water solubility and the molecular weight below 300 g/mol indicated that SIM-Ester has no bioaccumulation potential and that urinary excretion subsequent to metabolism will be the most relevant route of excretion. This has been also show for the DMT which is primarily excreted by the kidney as the monomethylester and terephthalic acid (mouse) or solely as terephthalic acid (rat).
5. Generic absorption rates
Based on the above information and due to the fact that there are no specific toxicokinetic data available the generic values of 50 % for oral absorption and inhalation absorption of respirable particles as well as 5 % for dermal absorption were derived.
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