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EC number: 282-252-3 | CAS number: 84145-27-7
- 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
Toxicokinetic assessment of T001202
T001202 (CAS 84145-27-7) is a white crystalline powder with a moderate molecular weight (443.73 g/mol), a particle size of 22.666 µm (Mass Median Aerodynamic Diameter or MMAD), a high water solubility (28.6 g/L), a moderate partition coefficient (log Kow of 2.2 at neutral pH) and a low volatility (vapour pressure of 1.2 E-5 kPa at 25°C).
The backbone of T001202 is a 1,3-dioxolanylmethyl sulfonate group with 2 substituents at position 2 which are a 2,4-dichlorophenyl-group and a 1H-imidazolylmethyl-group. The substance is a hydrochloric salt, meaning that the nitrogen is positively charged leading to a higher water solubility.
Based on the physicochemical properties and the results of the toxicity studies (OECD 423, OECD 422), the oral absorption factor is set to 50%, the default for the oral route of exposure.
Based on the physicochemical properties, the respiratory absorption factor is set to 100%.
Based on the physicochemical properties and the results of the toxicity studies (OECD 404, OECD 402), the dermal absorption factor is set to 50%.
More information is provided below.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 50
- Absorption rate - inhalation (%):
- 100
Additional information
Toxicokinetic assessment of T001202
T001202 (CAS 84145-27-7) is a white crystalline powder with a moderate molecular weight (443.73 g/mol), a particle size of 22.666 µm (Mass Median Aerodynamic Diameter or MMAD), a high water solubility (28.6 g/L), a moderate partition coefficient (log Kow of 2.2 at neutral pH) and a low volatility (vapour pressure of 1.2 E-5 kPa at 25°C).
The backbone of T001202 is a 1,3-dioxolanylmethyl sulfonate group with 2 substituents at position 2 which are a 2,4-dichlorophenyl-group and a 1H-imidazolylmethyl-group. The substance is a hydrochloric salt, meaning that the nitrogen is positively charged leading to a higher water solubility.
No toxicokinetic data (animal or human studies) are available on this substance. The data present in this dossier are based on physicochemical and toxicological parameters and will allow a qualitative assessment of the toxicokinetic behaviour of T001202.
Absorption
Oral/GI absorption:
T001202 is considered favorable for absorption since its molecular weight is < 500 g/mol, its log Pow value is between -1 and 4 and its water solubility is high which leads to dissolution of the substance into the gastrointestinal fluids and absorption through passive diffusion. Since the substance is a hydrochloride salt, the presence of a charge makes the substance more soluble in water and may thus more readily dissolve in the gastrointestinal tract (predominantly in the small intestine) and be absorbed in the bloodstream more quickly.
In an acute oral toxicity study (OECD 423; Latour, 2015), T001202 was administered via oral gavage on a single occasion at dose levels 300 and 2000 mg eq/kg bodyweight. At the lowest dose level (300 mg eq/kg), no mortality occurred, but at the highest dose level (2000 mg eq/kg), two animals were found dead and one animal was sacrificed for humane reasons, on day 1. At 300 mg eq/kg bw, lethargy, hunched posture, uncoordinated movements, piloerection and/or ptosis were noted for the animals on days 1 and/or 2. At 2000 mg eq/kg bw, lethargy, flat- and hunched posture, uncoordinated movements, slow breathing, rales, shallow respiration, piloerection, watery discharge from the eyes, hypothermia and/or ptosis were noted for the animals on day 1. No abnormalities were observed in body weight or at macroscopic post-mortem examination. Therefore, T001202 was considered to be harmful if swallowed (LD50 cut-off of 500 mg/kg bodyweight).
A combined 28-day repeated dose oral toxicity study with the reproduction/developmental toxicity screening test (OECD 422; Peter, 2017) has been performed by gavage with T001202 on Wistar rats applying following doses: 0, 10, 30 and 100 mg eq/kg bodyweight/day. During the study period, no adverse test item-related morphologic alterations were observed up to 100 mg eq/kg bw/day. Non-adverse morphologic alterations were recorded in the thyroid gland (in males at 30 mg eq/kg bw/day and in females at 100 mg eq/kg bw/day) and in the liver at 100 mg eq/kg bodyweight/day. A test item-related increase in abnormal pregnancies/total litter loss was recorded at 30 and 100 mg eq/kg bw/day for females, resulting in changes in organ weights, macroscopic and microscopic findings (in thymus, liver, spleen, adrenal gland, uterus and ovaries). There were no morphological findings in the reproductive organs of both males and females which could explain the high incidence of reproductive failure observed at 30 and 100 mg eq/kg and which could be attributed to the test item. There was no test item-related mortality in the study. Three females at 100 mg eq/kg did not survive and their death is considered to be related to (test item related) affected pregnancies, so indirectly rather than directly caused by the test item. There were also no treatment-related changes in clinical signs, body weight and weight gain, food consumption and compound intake or behaviour. Changes in clinical pathology parameters and organ weights, linked to microscopic findings, were recorded mainly in females at 100 mg eq/kg and to a much lesser extent in females at 30 mg eq/kg bw/day and were considered to be related to the affected pregnancies. Females that did not deliver healthy pups showed microscopic findings which were considered to be related to the poor health condition of the females that had total litter loss (mostly at 30 mg eq/kg bw/day) or didn't deliver their pups after a normal pregnancy duration (mostly at 100 mg eq/kg bw/day). These observations were considered not to be directly related to test item treatment. No toxicologically significant changes were noted in the remaining parental parameters investigated: clinical appearance, functional observations, food consumption, serum concentration of the thyroid hormones (males only) and macroscopic examination.
Based on the physicochemical properties and the results of the toxicity studies, the oral absorption factor is set to 50%, the default for the oral route of exposure.
Respiratory absorption:
Given its low volatility, the availability of T001202 for inhalation as a vapour is limited. However, based on the fact that its aerodynamic diameter is smaller than 50 µm but larger than 15 µm, the solid particles have the potential to be inhaled and reach the thoracic region.
T001202 can diffuse/dissolve into the mucus lining the respiratory tract, since it is a highly water soluble powder. Its lipophilic character (logKow>0) implies that the product has the potential to be subsequently absorbed directly across the respiratory tract epithelium through passive diffusion.
Based on the physicochemical properties, the respiratory absorption factor is set to 100%.
Dermal absorption:
T001202 is a solid substance and therefore not readily taken up by the skin in comparison to liquid products. The product will have to dissolve into the surface moisture of the skin before uptake can take place. Based on its high water solubility (28.6 g/L), dermal uptake is expected to be high since the substance is sufficiently soluble in water to partition from the stratum corneum into the epidermis. The moderate logKow value of 2.2 indicates that the substance is lipophilic and therefore easily crosses the lipid rich environment of the stratum corneum leading to dermal uptake.
An acute dermal toxicity study (OECD 402; Latour, 2016) with Wistar rats to which a single dose of 2000 mg/kg was applied, showed no clinical signs related to the test material except for flat posture, ptosis, piloerection and/or chromodacryorrhoea on days 1 and/or 2 and local clinical effects at the treated skin area such as general erythema, scales and scabs. Abnormalities of the lungs (dark red discolouration) were noted for two male animals at macroscopic post mortem examination, but no abnormalities were found at macroscopic examination of the other animals. Based on an in vivo skin irritation test with New Zealand White rabbits (OECD 404; Sanders, 2004), T001202 was classified as non-irritant which implies that no enhanced penetration can be caused by damage to the skin
As a result, the dermal absorption factor is set to 50%.
Distribution
The high water solubility and moderate molecular weight predict that T001202 will probably distribute through the body due to diffusion through aqueous channels and pores. Since the substance is lipophilic (logKow>0), the substance is likely to distribute into cells leading to a higher intracellular concentration in comparison to the extracellular concentration particularly in fatty tissues.
Accumulation
Since T001202 has a Log Kow of 2.2, accumulation is considered unlikely.
Metabolism
Based on the structure, T001202 might undergo phase I biotransformation such as hydroxylation and oxidation followed by conjugation reactions (phase II) such as glucuronidation (by the enzyme glucuronosyltransferase) and sulfation (by the enzyme sulfotransferase). The Phase II conjugation reactions largely increase the hydrophilic character of the product. Metabolism mainly takes place in the liver, causing route specific presystemic (or first pass) effects, especially after oral intake. Other metabolic changes may take place in the gastrointestinal (GI) flora or within the GI tract epithelia (mainly in the small intestine), respiratory tract epithelia (in the nasal cavity, trachea-bronchial mucosa and alveoli and skin), etc.
Excretion
Given its high water solubility, a possible route of excretion of T001202 from the systemic circulation is the urine. In general, conjugated metabolites such as glucuronides and sulfates from Phase II biotransformation reactions are excreted in the urine. Most of them will have been filtered out from the blood by the kidneys, though a small amount can enter the urine directly by passive diffusion. There is also the potential for re-absorption into the systemic circulation across the tubular epithelium. Another route of excretion of T001202 can be the bile. Substances excreted in the bile generally have a higher molecular weight or may be conjugated (such as glucuronides). The excretion via the bile is highly influenced by hepatic function since metabolites formed in the liver may be excreted directly into the bile without entering the bloodstream. Products in the bile pass through the intestine before excretion in the faeces and can thus undergo enterohepatic recycling which will prolong their half-life.
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