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EC number: 200-861-4 | CAS number: 75-33-2
- 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)
Description of key information
Absorption
No studies on absorption and excretion of propane-1-thiol and propane-2-thiol are available. However, predictions based on physicochemical properties and evidence from acute toxicity studies suggest that the substances are absorbed following exposure. Given the high volatility, high water solubility and low log Kowof substances, most excretion is expected to be via the urine or in exhaled breath.
Oral route
Propane-1-thiol and propane-2-thiol have a molecular weight of 76.15, and molecular weights below 500 are favourable for oral absorption. The substances have a moderate water solubility (1.9/3.7 g/L) and a moderate logP (1.68/1.81) which is also favorable for absorption by passive diffusion. Mortalities and signs of systemic toxicity observed in the acute oral toxicity studies are also indicative of a significant oral absorption.
Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, high rates of absorption from the gastrointestinal tract were predicted propane-1-thiol and propane-2-thiol (Danish QSAR database).
Absorption from the gastrointestinal tract (%)
Dose |
Propane-1-thiol 107-03-9 |
Propane-2-thiol 75-33-2 |
1 mg |
90 |
90 |
1000 mg |
90 |
90 |
As well, high absorption rates were also predicted for both substances with the pkCSM method (ca. 90%) (Pires et al., 2015) and the ADMETlab platform (70-90%) (Dongsheng Cao et al., 2018).
Inhalation exposure
Based on the high vapour pressure of propane-1-thiol and propane-2-thiol, inhalation exposure is likely. With log P values of 1.81 and 1.68, respectively, propane-1-thiol and propane-2-thiol are expected to be absorbed directly across the respiratory tract epithelium by passive diffusion. The mortality and/or clinical signs observed in the acute inhalation toxicity studies give also the indication of a significant inhalation absorption.
Dermal absorption
The dermal absorption rates ofpropane-1-thiol and propane-2-thiolwere estimated with IH SkinPerm v2.04 model (AIHA, 2018). Compared toin vitrodata from OECD 428 studies, IH skinPerm allowed the estimation of the dermal absorption rate with a good confidence and a low frequency (ca. 2%) of underestimation for liquids (Arkema’s internal validation study, 2018). According to the data input, IH SkinPerm v2.04 model leads to the following results:
Fraction absorbed (%)* |
Instantaneous deposition |
Deposition over time |
Propane-1-thiol 107-03-9 |
0.55 |
1.08 |
Propane-2-thiol 75-33-2 |
0.36 |
0.59 |
*End time observation 8 hr
For both compounds, the skin absorption rates were similar and very low.
Distribution
When reaching the body,propane-1-thiol and propane-2-thiolmay be distributed into cells due to their lipophilic properties and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues.
The evaluation ofpropane-1-thiol and propane-2-thiolin the pkCSM method (Pireset al., 2015) for predicting small-molecule pharmacokinetic properties does not show any significant differences in the models related to distribution.
Model Name |
Predicted Value |
|
Propane-2-thiol |
Propane-1-thiol |
|
VDss (human) |
0.033 |
0.062 |
Fraction unbound (human) |
0.657 |
0.68 |
BBB permeability |
0.064 |
0.11 |
CNS permeability |
-2.08 |
-2.307 |
As well, similar parameters related to distribution were predicted forpropane-1-thiol and propane-2-thiolwith the ADMETlab platform (Dongsheng Caoet al., 2018).
Property |
Propane-1-thiol |
Propane-2-thiol |
Meaning & Preference |
PPB (Plasma Protein Binding) |
44.654 % |
47.832 % |
Significant with drugs that are highly protein-bound and have a low therapeutic index. |
VD (Volume Distribution) |
0.044 L/kg |
-0.156 L/kg |
Optimal: 0.04-20L/kg; Range: <0.07L/kg: Confined to blood, Bound to plasma protein or highly hydrophilic; 0.07-0.7L/kg: Evenly distributed; >0.7L/kg: Bound to tissue components (e.g., protein, lipid),highly lipophilic. |
BBB (Blood–Brain Barrier) |
+++ |
+++ |
BB ratio >=0.1: BBB+; BB ratio <0.1: BBB- These features tend to improve BBB permeation: H-bonds (total) < 8–10; MW < 400–500; No acids. |
Metabolism
Simple thiol flavouring agents have been assessed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2000). Metabolic pathways for thiols are described in detail in that document:
Simple aliphatic and aromatic thiols undergo S-methylation in mammals to produce the corresponding ethyl thioether or sulfide. Methylation is catalysed by thiopurine methyltransferase in the cytoplasm and thiol methyltransferase in microsomes, and both reactions require S-adenosyl-l- methionine as a methyl group donor. Thiopurine methyltransferase is present in human liver, kidney, and erythrocytes; preferential substrates for this enzyme include aromatic and heterocyclic thiols. S- Methylation of aliphatic thiols is catalysed by microsomal thiol methyltransferase, and the resulting methyl thioether (sulfide) metabolite would undergo S-oxidation to give the methyl sulfoxide and methyl sulfone analogues as urinary products.
Thiols may react with glutathione and other endogenous thiol substances to form mixed disulfides. Both microsomal and cytoplasmlic thioltransferases have been reported to catalyse the formation of mixed disulfides. The resulting mixed disulfides can undergo reduction back to thiols, oxidative desulfuration, or oxidation to a sulfonic acid via the intermediate thiosulfinate and sulfinic acids. The principal S-Glucuronidation of aromatic thiols has been reported, and this may be a pathway for the metabolism of aromatic thiols (thiophenols) (Nos 525 and 528-531) and simple aromatic disulfides (Nos 576 and 578; subgroup vii) after their reduction (see below). Glucuronyl transferases behave similarly towards hydroxyl and sulfydryl groups, and the two activities have the same subcellular location and optimal pH. Thiols may be oxidized to form sulfenic acids (RSOH), which are unstable and readily undergo further oxidation to sulfinic (RSO2H) and sulfonic (RSO3H) acids or combine with nucleophiles. The sulfonic acid group is a highly polar centre and makes molelcules highly soluble in water. In general, sulfonic acids are stable to metabolism.
Alkyl thiols of low relative molecular mass undergo oxidative desulfuration in vivo to yield CO2and SO4=. This reaction has been shown, for example, for methanethiol (methyl mercaptan). hereas the carbon atom from thiols may be used in the biosynthesis of amino acids, the sulfur atom is not used significantly in the synthesis of sulfur-containing amino acids.
The metabolism of di-n-propyl disulphide (DPDS), was investigatedin vivoin the rat (Germain et al., 2008). A single dose (200 mg/kg)) was administered by gastric intubation and the time courses of DPDS and its metabolites were followed over 48 h by gas chromatography coupled with mass spectrometry in the stomach, intestine, liver, and blood. DPDS was detected in the stomach where it was transformed into n-propyl mercaptan (propane-1-thiol), whereas the liver contained only traces of DPDS and none at all in the other examined organs. The metabolites methylpropyl sulphide, methylpropyl sulphoxide (MPSO), and methylpropyl sulphone (MPSO2) were sequentially formed in the liver from n-propyl mercaptan. The route of elimination from the liver seemed to be mainly via the blood. The bile also participated in the excretory process, but only for MPSO2. The pharmacokinetic parameters were determined for all of the above compounds. Whereas the bioavailability of DPDS was very low (0.008 h mM), the areas under the curve were higher for n-propyl mercaptan, i.e. 3.44 h mM and the S-oxidized metabolites MPSO and MPSO2, i.e. 9.64 and 24.15 h mM, respectively. The half-lives for DPDS and its metabolites varied between 2.0 and 8.25 h, except for MPSO2, which had a half-life of 29.6 h. MPSO2was the most abundant and persistent of these metabolites.
Propane-1-thiol and propane-2-thiolare therefore all expected to follow similar metabolic pathways.
Excretion
The evaluation of propane-1-thiol and propane-2-thiol in the pkCSM (Pires et al., 2015) and ADMETlab (Dongsheng Cao et al., 2018) platforms does not show any significant differences in the parameters related to excretion.
pkCSM model name |
Predicted Value |
|
Propane-2-thiol |
Propane-1-thiol |
|
Total Clearance (log ml/min/kg) |
0.281 |
0.232 |
Renal Organic Cation Transporter 2 (OCT2) substrate |
no |
no |
ADMETlab property |
Propane-1-thiol |
Propane-2-thiol |
Meaning & Preference |
T1/2(Half Life Time) |
1.483 h |
1.768 h |
Range: >8h: high; 3h< Cl < 8h: moderate; <3h: low |
CL (Clearance Rate) |
1.071 mL/min/kg |
1.011 mL/min/kg |
Range: >15 mL/min/kg: high; 5mL/min/kg< Cl < 15mL/min/kg: moderate; <5 mL/min/kg: low |
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 90
- Absorption rate - dermal (%):
- 10
- Absorption rate - inhalation (%):
- 100
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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