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EC number: 276-763-0 | CAS number: 72676-55-2
- 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:
- 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:
- SMILES: S=C1NN=C(SSC2=NNC(=S)S2)S1
- Type:
- absorption
- Results:
- Intestinal absorption (human): 88.38%
- Type:
- distribution
- Results:
- VDss (human) (log L/kg): 0.044
- Type:
- distribution
- Results:
- Fraction unbound (human) : 0.634
- Type:
- distribution
- Results:
- BBB permeability (log BB): 0.242
- Type:
- distribution
- Results:
- CNS permeability (log PS): -3.911
- Type:
- excretion
- Results:
- Renal OCT2 substrate: no
- Type:
- excretion
- Results:
- Total Clearance (log ml/min/kg): -0.268
- Details on absorption:
- According to the model "Intestinal absorption (human)", 88.38% 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)", 63.4 % of the absorbed dose is unbound in the plasma.
According to the model "BBB permeability", the substance is moderately cross the blood-brain barrier (0.1 < Log BB < 0.3).
According to the model "CNS permeability",the substance is unable to penetrate the CNS (log PS <-3). - 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 0.54 ml/min/kg (log(ml/min/kg) -0.268) corresponding to the very low clearance (below 6 ml/min/kg). - Metabolites identified:
- no
- Conclusions:
- According to the QSAR pkCSM, the substance is well absorbed by oral route (88.38%), and well distributed into the body. Moreover, no hepatic and renal clearance is expected.
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- G.I. human passive absorption
- Type of information:
- calculation (if not (Q)SAR)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- accepted calculation method
- 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): S=C1NN=C(SSC2=NNC(=S)S2)S1
- Species:
- other: Human
- Route of administration:
- oral: unspecified
- Type:
- absorption
- Results:
- Absorption from gastrointestinal tract for 1 mg dose: 50%
- 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 of 5,5'-dithiodi-1,3,4-thiadiazole-2(3H)-thione were 50% for a dose of 1 or 1000 mg (Danish QSAR).
- 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: 142 g/mol
Temperature: 25 °C
Vapour Pressure: 12.6 Pa
Water solubility: 18.3 mg/L
Log Kow: 4.47
Density: 930 mg/cm3
Melting point: -94.8°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:
- 15.1 %
- Remarks on result:
- other: Instantaneous deposition
- Time point:
- 8 h
- Dose:
- 1 mg/cm²/h
- Parameter:
- percentage
- Absorption:
- 0.94 %
- Remarks on result:
- other: Deposition over time for 8 hr
- Conclusions:
- The dermal absorption of 5,5'-dithiodi-1,3,4-thiadiazole-2(3H)-thione is estimated to be moderate.
- Executive summary:
The dermal absorption of 5,5'-dithiodi-1,3,4-thiadiazole-2(3H)-thione 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 (%)
15.1
0.941
Amount absorbed (mg)
151 151
Lag time stratum corneum (min)
2.34
Max. derm. abs. (mg/cm²/h)
0.00941
Referenceopen allclose all
Property |
Model Name |
Predicted Value |
Unit |
Absorption |
Water solubility |
-3.55 |
Numeric (log mol/L) |
Absorption |
Caco2 permeability |
1.324 |
Numeric (log Papp in 10-6cm/s) |
Absorption |
Intestinal absorption (human) |
88.382 |
Numeric (% Absorbed) |
Absorption |
Skin Permeability |
-2.753 |
Numeric (log Kp) |
Absorption |
P-glycoprotein substrate |
No |
Categorical (Yes/No) |
Absorption |
P-glycoprotein I inhibitor |
No |
Categorical (Yes/No) |
Absorption |
P-glycoprotein II inhibitor |
No |
Categorical (Yes/No) |
Distribution |
VDss (human) |
0.044 |
Numeric (log L/kg) |
Distribution |
Fraction unbound (human) |
0.634 |
Numeric (Fu) |
Distribution |
BBB permeability |
0.242 |
Numeric (log BB) |
Distribution |
CNS permeability |
-3.911 |
Numeric (log PS) |
Metabolism |
CYP2D6 substrate |
No |
Categorical (Yes/No) |
Metabolism |
CYP3A4 substrate |
No |
Categorical (Yes/No) |
Metabolism |
CYP1A2 inhibitior |
YES |
Categorical (Yes/No) |
Metabolism |
CYP2C19 inhibitior |
No |
Categorical (Yes/No) |
Metabolism |
CYP2C9 inhibitior |
No |
Categorical (Yes/No) |
Metabolism |
CYP2D6 inhibitior |
No |
Categorical (Yes/No) |
Metabolism |
CYP3A4 inhibitior |
No |
Categorical (Yes/No) |
Excretion |
Total Clearance |
-0.268 |
Numeric (log ml/min/kg) |
Excretion |
Renal OCT2 substrate |
No |
Categorical (Yes/No) |
Description of key information
No experimental toxicokinetic study is available on 5,5’-Dithiodi-1,3,4-thiadiazole-2(3H)-thione.
However, as per REACH guidance document R7.C , information on absorption, distribution, metabolism and excretion may be deduced from the physical-chemical properties and QSAR predictions.
Based on the physical-chemical properties and QSAR predictions, the absorption of 5,5’-Dithiodi-1,3,4-thiadiazole-2(3H)-thione is expected to be high by oral route and inhalation, but moderate by dermal route. A good distribution and excretion of the substance are expected.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 100
- Absorption rate - dermal (%):
- 50
- Absorption rate - inhalation (%):
- 100
Additional information
The physical-chemical properties of 5,5’-Dithiodi-1,3,4-thiadiazole-2(3H)-thione (CAS RN 72676-55-2):
• Molecular weight (MW): 298.45 g/mol
• Water solubility: 167 mg/L
• N-octanol/water partition coefficient (log P): 1.46
• Vapour pressure: 0.000041 Pa
Oral Absorption
The physicochemical characteristics of 5,5’-Dithiodi-1,3,4-thiadiazole-2(3H)-thione (log Pow of 1.46 and water solubility of 167 mg/L) and the molecular mass are in a range suggestive of absorption from the gastro-intestinal tract subsequent to oral ingestion. It is also projected to be orally bioavailable based on Lipinski's Rule. This assumption of oral absorption is confirmed by the systemic effects observed in the studies involving repeated exposure via the oral route.
Using a model to predict either low or high fraction absorbed for an orally administered, passively transported substance, the rates of absorption of 5,5'-dithiodi-1,3,4-thiadiazole-2(3H)-thione were 50% for a dose of 1 or 1000 mg (Danish QSAR). According to the model "Intestinal absorption (human)" (pkCSM), 88.38% of the substance is absorbed after oral exposure.
For the risk assessment, an oral absorption of 100% is taken into account.
Dermal Absorption
N-octanol/water partition coefficient and molecular weight of 5,5’-Dithiodi-1,3,4-thiadiazole-2(3H) -thione are in ranges which favor dermal absorption. Dermal absorption is inferred based upon the positive result in the skin sensitisation study in which 5,5’-Dithiodi-1,3,4-thiadiazole-2(3H)-thione is considered to be a skin sensitizer (OECD TG 429).
According to the IH skin perm (QSAR), the dermal absorption of 5,5’-Dithiodi-1,3,4-thiadiazole-2(3H) -thione is between 1% and 15 %. Consequently, 50% of absorption is taken into account for the risk assessment.
Inhalation absorption
No absorption by inhalation is expected due to the low vapour pressure of 5,5’-Dithiodi-1,3,4-thiadiazole-2(3H) –thione.
However, 100% of absorption is taken into account for the risk assessment as a default value and in the absence of experimental data.
Distribution and Metabolism
As a small molecule (MW<500 g/mol), a wide distribution is expected. This assumption is confirmed by the test substance or its metabolites (brown/yellow pigment) observed in the renal tubular epithelial cells and the systemic effects shown in the animal studies involving a repeated exposure.
According to the QSAR pkCSM, the substance is well distributed into the body.
Elimination
The rapid hydrolytic degradation at all pH and the n-octanol/water partition coefficient (log Pow 1.46) of 5,5’-Dithiodi-1,3,4-thiadiazole-2(3H)-thione suggest that the potential for accumulation in fatty tissues is very limited after absorption. Based on the molecular structure excretion into urine is assumed to be a preferred route of elimination. This assumption is confirmed by the observation of the test substance or its metabolites (brown/yellow pigment) in the renal tubular epithelial cells in the combined repeated dose toxicity study. Elimination is assumed to be rapid. Therefore, no potential for bioaccumulation is expected.
According to the QSAR pkCSM, no hepatic and renal clearance is expected.
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