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EC number: 226-827-9 | CAS number: 5495-84-1
- 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)
- Endpoint:
- dermal absorption, other
- Remarks:
- QSAR
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on QSARs R.6
- Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on IR&CSA, Chapter R.14, Occupational exposure assessment Update to change the scope of the guidance from exposure estimation to exposure assessment
- Principles of method if other than guideline:
- IH SkinPerm (v2.04) is a mathematical tool for estimating dermal absorption. The rate of mass build-up (or loss) on the skin comes from the deposition rate onto the skin minus the absorption rate into the Stratum Corneum (SC) and the amount evaporating from the skin to the air.
- Species:
- other: human
- Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Details on study design:
- DATA INPUT
Molecular weight: 254 g/mol
Temperature: 20 °C
Vapour Pressure: 0.00003 Pa
Water solubility: 0.34 mg/L
Log Kow: 5.59
Density: 732 mg/cm3
Melting point: 75°C
SCENARIO PARAMETERS
- Instantaneous deposition
Deposition dose*: 1000 mg
Affected skin area**: 1000 cm²
Maximum skin adherence***: 2 mg/cm²
Thickness of stagnant air****: 1 cm
Weight fraction: 1
Timing parameters
. Start deposition: 0 hr
. End time observation: 8 hr
Report parameters
. Calculation (intervals/hr): 10000
. Report (intervals/hr): 100
- Deposition over time
Affected skin area**: 1000 cm²
Maximum skin adherence***: 1 mg/cm²
Dermal deposition rate: 2 mg/cm²/hr
Thickness of stagnant air****: 1 cm
Weight fraction: 1
Timing parameters
. Start deposition: 0 hr
. Duration of deposition: 8hr
. End time observation*: 8 hr
Report parameters
. Calculation (intervals/hr): 10000
. Report (intervals/hr): 100
*Default value defined according to the internal validation study
**Estimated skin surface of two hands of an adult.
***The skin adherence field is greyed out and a default of -1 is indicated if the substance is a liquid at 25°C. Smart logic is built into IH SkinPerm; the program recognizes whether a substance is a solid or liquid at standard temperature (25°C) based on the physicochemical properties. For substances
that are solids at 25°C a maximum adherence value up to 2 mg/cm² is allowed based on studies of soil-on-skin adherence. If the deposition rate results in an increase above the input figure (0.2-2 mg/cm²), it is assumed that the surplus disappears just by removal from the skin.
*** 3 cm if clothing involved, 1 cm if bare skin involved - Time point:
- 8 h
- Dose:
- 1000 mg
- Parameter:
- percentage
- Absorption:
- 0.317 %
- Remarks on result:
- other: Instantaneous deposition
- Time point:
- 8 h
- Dose:
- 1 mg/cm²/h
- Parameter:
- percentage
- Absorption:
- 0.02 %
- Remarks on result:
- other: Deposition over time for 8 hr
- Conclusions:
- The dermal absorption of 2-Isopropylthioxanthone is estimated to be < 10%
- Executive summary:
The dermal absorption of 2-Isopropylthioxanthone leads to the following results, obtained using the SkinPerm v2.04 model according to the input data:
Instantaneous deposition
Deposition over time
End time observation 8 hr
Total deposition (mg) or deposition rate (mg/cm²/hr)
1000
16000
Fraction absorbed (%)
0.317
0.0198
Amount absorbed (mg)0.
3.17 3.17
Lag time stratum corneum (min)
6.26
Max. derm. abs. (mg/cm²/h)
0.000198
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- G.I. human passive absorption
- Type of information:
- calculation (if not (Q)SAR)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Objective of study:
- absorption
- Guideline:
- other: REACH Guidance on QSARs R.6
- Principles of method if other than guideline:
- Model to predict either high or low fraction absorbed for an orally administered, passively transported substance on the basis of a new absorption parameter. The model includes only two inputs: the octanol-water partition coefficient (Kow) and the dimensionless oversaturation number (OLumen). The latter is the ratio of the concentration of drug delivered to the gastro-intestinal (GI) fluid to the solubility of the compound in that environment.
- Specific details on test material used for the study:
- SMILES (used for QSAR prediction): c12C(=O)c3c(ccc(C(C)C)c3)Sc1cccc2
- Species:
- other: Human
- Route of administration:
- oral: unspecified
- Type:
- absorption
- Results:
- Absorption from gastrointestinal tract for 1 mg dose: 100%
- Type:
- absorption
- Results:
- Absorption from gastrointestinal tract for 1000 mg dose: 50%
- Conclusions:
- Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, the rates of absorption were 100% and 50% for a dose of 1 and 1000 mg respectively (Danish (Q)SAR Database).
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- in silico
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- See enclosed files
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on QSARs R.6
- Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on IR&CSA, Chapter R.14, Occupational exposure assessment Update to change the scope of the guidance from exposure estimation to exposure assessment
- Version / remarks:
- August 2016
- Principles of method if other than guideline:
- pkCSM uses graph-based signatures to develop predictive models of central ADME properties. pkCSM performs as well or better than current methods.
- Specific details on test material used for the study:
- SMILE : c12C(=O)c3c(ccc(C(C)C)c3)Sc1cccc2
- Type:
- absorption
- Results:
- Intestinal absorption (human): 96.12%
- Type:
- distribution
- Results:
- VDss (human) (log L/kg): 0.274
- Type:
- distribution
- Results:
- Fraction unbound (human) : 0.07
- Type:
- distribution
- Results:
- BBB permeability (log BB): 0.627
- Type:
- distribution
- Results:
- CNS permeability (log PS): -1.212
- Type:
- excretion
- Results:
- Renal OCT2 substrate: no
- Type:
- excretion
- Results:
- Total Clearance (log ml/min/kg): -0.044
- Details on absorption:
- According to the model "Intestinal absorption (human)", 96 % of the substance is absorbed after oral exposure.
- Details on distribution in tissues:
- According to the model "VDss (human)", the volume of distribution (VD, i.e. theoritical volume that the total dose of a drug would need to be uniformly distributed to give the same concentration as in blood plasma) is moderate (Log between -0.15 and 0.45).
According to the model "Fraction unbound (human)", 7% of the absorbed dose is unbound in the plasma.
According to the model "BBB permeability", the substance is cross readily the blood-brain barrier (log BB > 0.3).
According to the model "CNS permeability", the substance is considered to penetrate the Central Nervous System (CNS) (log PS > -2). - Details on excretion:
- According to the model "Renal OCT2 substrate", the substance is not a OCT2 substrate. The substance is not transported by this renal transporter.
According to the model "Total clearance" , the predicted total clearance (hepatic & renal clearance) is of 0.9 ml/min/kg (log(ml/min/kg) -0.044) corresponding to a very low clearance. - Metabolites identified:
- no
- Conclusions:
- According to the QSAR pkCSM, the substance is well absorbed by oral route, and well distributed into the body. Moreover, a very low total clearance is expected.
Referenceopen allclose all
Description of key information
No experimental studies of the absorption, distribution, metabolism or elimination on 2-Isopropylthioxanthone are available. However, the physical chemical properties, the QSAR prediction and the existing toxicology studies on the substance have been used to predict its potential toxicokinetics.
After oral exposure, a high absorption and a good distribution is expected for 2-Isopropylthioxanthone. However a low dermal absorption is expected.
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - oral (%):
- 100
- Absorption rate - dermal (%):
- 10
- Absorption rate - inhalation (%):
- 100
Additional information
No experimental studies of the absorption, distribution, metabolism or elimination on 2-Isopropylthioxanthone are available. However, the physical chemical properties, the QSAR prediction and the existing toxicology studies on the substance have been used to predict its potential toxicokinetics.
The substance 2-Isopropylthioxanthone is a mono-constituent substance. It is a cream to pale yellow powder, with a median particle size D50 of 369 µm, D10 of 106 µm and D90 of 829 µm. Its molecular weight (MW) is 254.347 g/mol. The substance is very poorly water-soluble (0.34 mg/L at 20 °C), and its partition coefficient (Log Kow/Log Pow) is 5.59. The vapour pressure was determined to be 3 x 10^-5 Pa at 20 °C.
Oral Absorption
The very low water-solubility and high Log Pow would limit the rate of absorption from the gut; the molecular weight slightly greater than 200 also indicates that passage through aqueous pores or transport through the epithelial barrier by the bulk passage of water are unlikely. However, micellar solubilisation may be of particular importance for absorption mainly in the small intestine.
Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, the rates of absorption were 100% and 50% for a dose of 1 and 1000 mg respectively (Danish (Q)SAR Database). According to the QSAR pkCSM, the substance is well absorbed by oral route (96%).
The results of the acute oral studies in rats, with the no mortality or clinical signs at 2000 mg/kg, confirm a limited absorption. However, under repeated oral dosing regimen, effects mainly on the liver were observed in the repeated dose toxicity studies in rats, confirming the oral absorption.
Based on this information, it is clear that significant oral absorption is likely : an oral absorption of 100% is taken into account for human health risk assessment purposes.
Dermal Absorption
Although 2-Isopropylthioxanthone is not an excessively large molecule, it is a solid, and the extremely low water solubility (0.34 mg/L at 20 °C) and high Log Pow (5.59) indicate that dermal uptake will be low, and the rate of transfer between the stratum corneum and the epidermis will be slow. This is supported by the acute dermal toxicity study in rats, where no mortality or clinical signs at 2 000 mg/kg. In addition, the substance is not irritating to the rabbit skin, and not skin sensitising in guinea pigs.
According to the IH SkinPerm prediction (QSAR), the dermal absorption of 2-Isopropylthioxanthone is estimated to be < 10%.
A dermal absorption of 10% is taken into account for human health risk assessment purposes.
Inhalation Absorption
Particle size distribution of 2-Isopropylthioxanthone indicates the substance is too large for reaching the respiratory system. In addition, the very low vapour pressure (6.1 x10-5Pa at 25 °C) indicates that the substance cannot generate an inhalable vapour. The extremely low water-solubility suggests that any inhaled particles reaching the upper respiratory tract could be coughed or sneezed out of the body or swallowed. In the absence of any quantitative data, and in accordance with ECHA guidance, for human health risk assessment purposes absorption by inhalation of 2-Isopropylthioxanthone is assumed to be 100 %.
Distribution
The available repeat-dose oral toxicity studies in rats identified the liver as the main target organ. The relatively low molecular weight of the substance would suggest wider distribution although this might be countered by the low water solubility. The Log Pow value suggests that the intracellular concentration may be higher than extracellular concentration.
According to the QSAR pkCSM, the substance is well distributed into the body, including in the central nervous system.
Metabolism
The two 28-day repeated dose toxicity studies in rats showed increases of liver weight accompanied by hepatocellular hypertrophy, suggesting hepatic enzyme induction and enhanced liver metabolism following oral administration of 2-Isopropylthioxanthone.
Excretion
The low molecular weight would suggest prevalence of urinary excretion in case conjugated metabolites are formed. No notable kidney weight changes were observed in the available 28-day repeated dose toxicity studies in rats; biliary excretion may well be another route of excretion for this poorly water-soluble substance.
According to the QSAR pkCSM, a very low total clearance is expected with 2-Isopropylthioxanthone.
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